FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Manini, AF McAfee, AT Noble, VE Bohan, JS AF Manini, A. F. McAfee, A. T. Noble, V. E. Bohan, J. S. TI Utility of acute cardiac ischemia time-insensitive predictive instrument in the chest pain observation unit SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Harvard Affiliated Emergency Med Residency, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 37 BP S12 EP S12 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400037 ER PT J AU Moussally, JS Pallin, D Goldstein, J Pelletier, A Camargo, C AF Moussally, J. S. Pallin, D. Goldstein, J. Pelletier, A. Camargo, C. TI National study of emergency department visits for seizure, 1993-2003 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 62 BP S19 EP S19 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400063 ER PT J AU Nagurney, JT Moselewski, F Pena, AJ Nichols, JH Parry, BA Butler, J Manini, AF Brown, DF Siebert, U Hoffmann, U AF Nagurney, J. T. Moselewski, F. Pena, A. J. Nichols, J. H. Parry, B. A. Butler, J. Manini, A. F. Brown, D. F. Siebert, U. Hoffmann, U. TI How often do emergency department patients with chest pain meet eligibility criteria for multi-detector computerized tomography of the coronary arteries? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 53 BP S17 EP S17 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400054 ER PT J AU Peacock, W Bhatt, D Diercks, D Amsterdam, E Chandra, A Ohman, EM Brown, D Januzzi, J AF Peacock, W. Bhatt, D. Diercks, D. Amsterdam, E. Chandra, A. Ohman, E. M. Brown, D. Januzzi, J. TI American College of Cardiology/American Heart Association guidelines for management of ST-Elevation Myocardial Infarction: Cardiologist and emergency physician opinions and knowledge SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Cleveland Clin, Cleveland, OH 44106 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Duke Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 93 BP S29 EP S29 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400094 ER PT J AU Pozner, CN Levine, M Listwa, T Barker, T Zane, R Pallin, D AF Pozner, C. N. Levine, M. Listwa, T. Barker, T. Zane, R. Pallin, D. TI Does the presence of physicians at professional football games reduce the number of patient transports? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 177 BP S55 EP S55 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400180 ER PT J AU Shewakramani, S Harrison, TH Gates, JD Thomas, SH AF Shewakramani, S. Harrison, T. H. Gates, J. D. Thomas, S. H. TI Interfacility helicopter transport of patients with leaking aortic aneurysms directly into the operating room SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 15-16, 2006 CL New Orleans, LA SP Amer Coll Emergency Physicians C1 Harvard Affiliated Emergency Med Residency, Boston, MA USA. Boston MedFlight, Bedford, MA USA. Brigham & Womens Hosp, Harvard Med Sch, Dept Surg, Boston, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Emergency Services, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2006 VL 48 IS 4 SU S MA 169 BP S53 EP S53 PG 1 WC Emergency Medicine SC Emergency Medicine GA 090NQ UT WOS:000240958400172 ER PT J AU Leleu, X Terriou, L Duhamel, A Moreau, AS Andrieux, J Dupire, S Coiteux, V Berthon, C Micol, JB Guieze, R Facon, T Bauters, F AF Leleu, Xavier Terriou, Louis Duhamel, Alain Moreau, Anne-Sophie Andrieux, Joris Dupire, Sophie Coiteux, Valerie Berthon, Celine Micol, Jean-Baptiste Guieze, Romain Facon, Thierry Bauters, Francis TI Long-term outcome in acquired aplastic anemia treated with an intensified dose schedule of horse antilymphocyte globulin in combination with androgens SO ANNALS OF HEMATOLOGY LA English DT Article DE aplastic anemia; horse antilymphocyte globulin; androgens; late clonal complications ID SAA WORKING PARTY; BONE-MARROW-TRANSPLANTATION; ANTITHYMOCYTE GLOBULIN; IMMUNOSUPPRESSIVE TREATMENT; CYTOGENETIC ABNORMALITIES; RANDOMIZED TRIAL; CYCLOSPORINE; MANAGEMENT AB Aplastic anemia (AA) is a rare hematopoietic stem cell disease, which can be treated with horse antilymphocyte globulin (ALG) for patients not eligible for bone marrow transplantation. ALG gives about 60% overall survival rate (OS) after 5 years, a 30% of persistent complete remission and a 20% early death rate related to failure. ALG has been incriminated in the emergence of 10 to 20% therapy-related AML/MDS (t-AML/MDS) with the usual doses. Questions remain whether higher doses of ALG could improve the response and OS rates and whether the combination with androgens is able to protect patients from t-AML/MDS. We have carried out a single institutional retrospective study of 87 AA treated with higher doses of ALG, twice the usual posology (140 mg/kg instead of 75 mg/kg), combined to androgens. The overall response rate was 77% and the OS rate at 5 years was 78%. Androgens in combination with ALG improved response and OS rates. At diagnosis, 6% of AA had an abnormal karyotype using conventional cytogenetic not related to any time-to-event. Two patients displayed a cytogenetic conversion related to the occurrence of secondary malignancies. The incidence of t-AML/MDS was 2.3% with an estimated 10-year cumulative incidence of 3.1. Our results show that higher doses of ALG combined to androgens are feasible and give results close to those recently describe with the immunosuppressive treatments including ALG associated to cyclosporine, with a low SMD/AML incidence rate. C1 Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CHU Lille, Lab Biostat & Biomath, Lille, France. CHU Lille, Lab Genet Med, Lille, France. CHU Lille, Hop Huriez, Serv Malad Sang, Lille, France. RP Leleu, X (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, 44 Binney St, Boston, MA 02115 USA. EM xavier_leleu@dfci.harvard.edu RI Duhamel, Alain/B-8624-2011; FACON, THIERRY/M-9736-2014; Duhamel, Alain/A-4899-2013 OI FACON, THIERRY/0000-0001-7705-8460; NR 21 TC 7 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD OCT PY 2006 VL 85 IS 10 BP 711 EP 716 DI 10.1007/s00277-006-0152-y PG 6 WC Hematology SC Hematology GA 075LH UT WOS:000239886000005 PM 16830141 ER PT J AU Kobler, JB Rosen, DI Burns, JA Akst, LM Broadhurst, MS Zeitels, SM Hillman, RE AF Kobler, James B. Rosen, David I. Burns, James A. Akst, Lee M. Broadhurst, Matthew S. Zeitels, Steven M. Hillman, Robert E. TI Comparison of a flexible laryngoscope with calibrated sizing function to intraoperative measurements SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 19-20, 2006 CL Chicago, IL SP Amer Laryngol Assoc DE calibration; endoscope; laryngology; laryngoscopy; optics; videostroboscopy; vocal fold AB Objectives: The objectives were to assess the clinical performance and accuracy of a prototype fiberoptic transnasal laryngeal endoscope with an auxiliary optical system that allows images to be spatially calibrated. Methods: A novel fiberoptic endoscope was developed that projects green laser beams across the field of view from a separate optical channel. According to the location of the spots in the field of view, the images can be calibrated with a software routine. To assess its performance, we compared measurements of 14 lesions imaged with the calibrated endoscope and during microlaryngoscopy, where a calibration instrument was placed next to the lesions. Four clinicians measured lesion length, width, and area from the collected images. Results: The calibrated endoscope performed as well as current flexible fiberoptic laryngoscopes in terms of image quality and patient comfort. For lesions with well-defined borders, the error ranged from 14% to 23% for length, from 20% to 30% for width, and from 33% to 50% for area across observers. Factors contributing to larger errors in some subjects were identified. Conclusions: The calibrated endoscope is capable of providing useful sizing information for laryngeal structures, and these measures correspond quite well to more direct measurements in the operating room. Objective sizing of laryngeal lesions is complicated by subjective judgments of lesion boundaries, which can be indistinct in many cases. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Phys Sci Inc, Andover, MA USA. RP Kobler, JB (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq 11th Floor, Boston, MA 02114 USA. FU NIDCD NIH HHS [1R43DC04533-01A1] NR 8 TC 10 Z9 10 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 2006 VL 115 IS 10 BP 733 EP 740 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 095XJ UT WOS:000241341300004 PM 17076094 ER PT J AU Boseley, ME Hartnick, CJ AF Boseley, Mark E. Hartnick, Christopher J. TI Development of the human true vocal fold: Depth of cell layers and quantifying cell types within the lamina propria SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 19-20, 2006 CL Chicago, IL SP Amer Laryngol Assoc DE development; lamina propria; larynx; phonosurgery ID HUMAN NEWBORN AB Objectives: We sought to further describe the development of the 3-layered human vocal fold in children and to quantify macrophage and myofibroblast concentrations in each layer. Methods: We used an optical analysis software package to examine 8 longitudinally sectioned human vocal folds that had been fixed in formalin (ages 2 days to 14 years). Results: The 2-day-old vocal fold contained only a monolayer of cells. This became a bilayer by 5 months, and a trilayer began to become evident by 7 years. The percent of total depth represented by the superficial layer of the lamina propria (SLP) gradually decreased with age. The SLP made up 22% of the total lamina propria by age 7 years; this percentage approximates that in the adult vocal fold. Macrophages and myofibroblasts were predominately found in the SLP, and began to be apparent by 11 months of age. Conclusions: These results help describe the development of human voice and may have implications as to when phonosurgical therapy can be considered for children. C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Hartnick, CJ (reprint author), 325 Cambridge St, Boston, MA 02115 USA. NR 14 TC 21 Z9 22 U1 0 U2 4 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 2006 VL 115 IS 10 BP 784 EP 788 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 095XJ UT WOS:000241341300012 PM 17076102 ER PT J AU Agus, MSD Javid, PJ Piper, HG Wypij, D Duggan, CP Ryan, DP Jaksic, T AF Agus, Michael S. D. Javid, Patrick J. Piper, Hannah G. Wypij, David Duggan, Christopher P. Ryan, Daniel P. Jaksic, Tom TI The effect of insulin infusion upon protein metabolism in neonates on extracorporeal life support SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 126th Annual Meeting of the American-Surgical-Association CY APR 20-22, 2006 CL Boston, MA SP Amer Surg Assoc ID BIRTH-WEIGHT INFANTS; CRITICALLY-ILL PATIENTS; HUMAN GROWTH-HORMONE; WHOLE-BODY; SKELETAL-MUSCLE; MEMBRANE-OXYGENATION; LEUCINE METABOLISM; ENERGY-EXPENDITURE; GLUCOSE-PRODUCTION; CONTROLLED TRIAL AB Objective: Critically ill neonates on extracorporeal life support (ECLS) demonstrate elevated rates of protein breakdown that, in turn, are associated with increased morbidity and mortality. This study sought to determine if the administration of the anabolic hormone insulin improved net protein balance in neonates on ECLS. Methods: Twelve parenterally fed neonates, on ECLS, were enrolled in a randomized, prospective, crossover trial. Subjects were administered a hyperinsulinemic euglycemic clamp and a control saline infusion. Protein metabolism was quantified using ring-D5-phenylyalanine and ring-D2-tyrosine stable isotopic infusions. Statistical comparisons were made by paired sample t tests (significance at P < 0.05). Results: Serum insulin concentration increased 20-fold during insulin infusion compared with saline infusion control (P < 0.0001). Protein breakdown was significantly decreased during insulin infusion compared with controls (7.98 +/- 1.82 vs. 6.89 +/- 1.03 g/kg per day; P < 0.05). Serum amino acid concentrations were significantly decreased by insulin infusion (28,450 +/- 9270 vs. 20,830 +/- 8110 mu mol/L; P < 0.02). Insulin administration tended to decrease protein synthesis (9.58 +/- 2.10 g/kg per day vs. 8.60 +/- 1.20; P = 0.05). For the whole cohort, insulin only slightly improved net protein balance (protein synthesis minus protein breakdown) (1.60 +/- 0.80 vs. 1.71 +/- 0.89 g/kg per day; P = 0.08). In neonates receiving :2 g/kg per day of dietary amino acids insulin significantly improved net protein balance (2.17 +/- 0.34 vs. 2.40 +/- 0.26 g/kg per day; P < 0.01). Conclusions: Insulin effectively decreases protein breakdown in critically ill neonates on ECLS. However, this is associated with a significant reduction in plasma amino acids and a trend toward decreased protein synthesis. Insulin administration significantly improves net protein balance only in those ECLS neonates in whom adequate dietary protein is provided. C1 Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Clin Res Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Jaksic, T (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM tom.jaksic@childrens.harvard.edu FU NCRR NIH HHS [M01 RR002172, M01-RR02172]; NICHD NIH HHS [R01 HD0415310]; NIDDK NIH HHS [P30 DK040561, P30 DK40561, P30 DK040561-11] NR 55 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 2006 VL 244 IS 4 BP 536 EP 544 DI 10.1097/01.sla.0000237758.93186.c8 PG 9 WC Surgery SC Surgery GA 094QU UT WOS:000241254900007 PM 16998362 ER PT J AU Ramlawi, B Rudolph, JL Mieno, S Khabbaz, K Sodha, NR Boodhwani, M Levkoff, SE Marcantonio, ER Sellke, FW AF Ramlawi, Basel Rudolph, James L. Mieno, Shigetoshi Khabbaz, Kamal Sodha, Neel R. Boodhwani, Munir Levkoff, Sue E. Marcantonio, Edward R. Sellke, Frank W. TI Serologic markers of brain injury and cognitive function after cardiopulmonary bypass SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 126th Annual Meeting of the American-Surgical-Association CY APR 20-22, 2006 CL Boston, MA SP Amer Surg Assoc ID CORONARY-ARTERY-BYPASS; NEURON-SPECIFIC ENOLASE; CARDIAC-SURGERY; INFLAMMATORY RESPONSE; S-100 PROTEIN; CEREBROSPINAL-FLUID; NEUROBIOCHEMICAL MARKERS; GRAFT-SURGERY; HEAD-INJURY; SERUM AB Objective: To examine the association between biochemical markers of brain injury (MBI) and the inflammatory response in relation to neurocognitive deficiency (NCD) after cardiopulmonary bypass (CPB). Summary Background Data: In cardiac surgery, NCD is a common but underdiagnosed complication with an unclear pathophysiology leading to significant morbidity. Despite extensive investigation, identification of a MBI for clinical use and clarifying the pathophysiology of NCD have not been achieved. Methods: Forty patients undergoing CABG and/or valve procedures using CPB were administered a validated neurocognitive battery preoperatively and postoperatively at day 4 and 3 months. S-100b, neuron specific enolase (NSE), and tau protein were assayed as MBIs preoperatively and postoperatively at 6 hours and day 4. C-reactive protein (CRP), interleukin (IL)-6, C3a, and total peroxide levels were also quantified from serum. Impact of cardiotomy suction and antifibrinolytics on markers of brain injury was assessed. Results: The incidence of early NCD was 40% (16 of 40). NSE and tau protein at the 6-hour time point were both significantly elevated in the presence of NCD (NCD group) compared with those without NCD (NORM group) (8.69 +/- 0.82 vs. 5.98 +/- 0.61; P = 0.018 and 68.8 vs. 29.2%; P = 0.015, respectively). S-100b increase was not different between the NCD and NORM groups. Cardiotomy suction significantly elevated S-100b levels, whereas NSE and tau were not significantly influenced. Aprotinin did not have an effect on NCD or levels of MBIs. Also, the NCD group had significantly elevated CRP and peroxide levels compared with the NORM group at postoperative day 4 while C3a was significantly elevated at 6 hours. Conclusion: NSE and tau are better associated with NCD and less influenced by cardiotomy suction compared with S-100 beta. Inflammatory and oxidative stress is associated with NCD post-CPB. C1 Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Primary Care Gen Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. RP Sellke, FW (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiothorac Surg, LMOB 2A,110 Francis St, Boston, MA 02215 USA. EM fsellke@caregroup.harvard.edu FU NHLBI NIH HHS [HL-46716, HL04095-06, K30 HL004095, R01 HL046716]; NIA NIH HHS [P60 AG008812, 5 K12 AG00294-18, 5 P60 AG08812-14, K12 AG000294] NR 41 TC 49 Z9 54 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 2006 VL 244 IS 4 BP 593 EP 601 DI 10.1097/01.sla.0000239087.00826.b4 PG 9 WC Surgery SC Surgery GA 094QU UT WOS:000241254900013 PM 16998368 ER PT J AU Bartlett, DL Berlin, J Lauwers, GY Messersmith, WA Petrelli, NJ Venook, AP AF Bartlett, David L. Berlin, Jordan Lauwers, Gregory Y. Messersmith, Wells A. Petrelli, Nicholas J. Venook, Alan P. TI Chemotherapy and regional therapy of hepatic colorectal metastases: Expert consensus statement SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Consensus Conference on Hepatic Colorectal Metastases CY JAN 25, 2006 CL San Francisco, CA SP Amer Hepato Pancreato Biliary Assoc, Soc Surg Alimentary Tract, Soc Surg Oncol DE colorectal metastases; unresectable metastases; adjuvant chemotherapy; liver resection; intra-arterial chemotherapy; drug-related hepatotoxicity; snusoidal injury; steatosis; steatohepatitis; nodular regeneration; biliary sclerosis ID PHASE-II TRIAL; ARTERIAL INFUSION CHEMOTHERAPY; FLUOROURACIL PLUS LEVAMISOLE; MULTICENTER RANDOMIZED-TRIAL; SURGICAL ADJUVANT BREAST; CANCER LIVER METASTASES; COLON-CANCER; FOLINIC ACID; SCLEROSING CHOLANGITIS; DUKES B C1 Helen F Graham Canc Ctr, Dept Surg, Newark, DE 19713 USA. Univ Pittsburgh, Div Surg Oncol, Pittsburgh, PA USA. Vanderbilt Ingram Canc Ctr, Div Internal Med & Med Oncol, Nashville, TN USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Gastrointestinal Oncol Program, Baltimore, MD USA. Helen F Graham Canc Ctr, Dept Surg, Newark, DE 19713 USA. Univ Calif San Francisco, Dept Clin Med, San Francisco, CA 94143 USA. RP Petrelli, NJ (reprint author), Helen F Graham Canc Ctr, Dept Surg, 4701 Ogleton Stanton Rd,Suite 1233, Newark, DE 19713 USA. EM npetrelli@christianacare.org NR 69 TC 26 Z9 26 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2006 VL 13 IS 10 BP 1284 EP 1292 DI 10.1245/s10434-006-9018-8 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 093LY UT WOS:000241171000006 PM 16955384 ER PT J AU Wright, CD AF Wright, Cameron D. TI Pleuropneumonectomy for the treatment of Masaoka stage IVA thymoma SO ANNALS OF THORACIC SURGERY LA English DT Article ID CLINICOPATHOLOGICAL FEATURES; RECURRENCE; TUMORS AB Background. The treatment of locally advanced Masaoka stage IVA thymoma is not standardized and is problematic. Methods. A single-institution retrospective study was made of 5 patients with World Health Organization B3 thymomas who underwent pleuropneumonectomy for locally advanced thymoma. Two patients had recurrent thymoma and 3 presented de novo with stage IVA disease. Patients had a variety of induction and adjuvant treatments. Results. There was no operative mortality, and only 1 patient had a major complication. Several patients had relatively prolonged disease-free survival. The median survival was 86 months, and the Kaplan-Meier survival was 75% (95% confidence interval: 53% to 97%) at 5 years and 50% (95% confidence interval: 25% to 75%) at 10 years. Conclusions. Pleuropneumonectomy can be performed safely in patients with advanced thymomas and may improve survival. Highly selected patients might be cured with this approach if a complete resection is performed. While the optimal multimodality strategy for these patients is unknown, induction chemotherapy followed by resection then chemoradiotherapy seems promising. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM cameron@mgh.harvard.edu NR 19 TC 40 Z9 43 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 OCT PY 2006 VL 82 IS 4 BP 1234 EP 1239 DI 10.1016/j.athoracsur.2006.05.028 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 086XQ UT WOS:000240706800011 PM 16996913 ER PT J AU Marty, FM Lowry, CM Lempitski, SJ Kubiak, DW Finkelman, MA Baden, LR AF Marty, Francisco M. Lowry, Colleen M. Lempitski, Steven J. Kubiak, David W. Finkelman, Malcolm A. Baden, Lindsey R. TI Reactivity of (1 -> 3)-beta-D-glucan assay with commonly used intravenous antimicrobials SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RECEIVING PIPERACILLIN-TAZOBACTAM; LIMULUS TEST; GALACTOMANNAN; (1->3)-BETA-D-GLUCAN; ANTIGENEMIA; PLASMA; GLUCAN AB Forty-four intravenous antimicrobials were tested for the presence of (1 -> 3)-beta-D-glucan (BG). Colistin, ertapenem, cefazolin, trimethoprim-sulfamethoxazole, cefotaxime, cefepime, and ampicillin-sulbactam tested positive for BG at reconstituted-vial concentrations but not when diluted to usual maximum plasma concentrations. False-positive BG assays may occur when some antimicrobials are administered; however, this needs to be confirmed. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Associates Cape Cod Inc, E Falmouth, MA USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM fmarty@partners.org NR 18 TC 62 Z9 68 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2006 VL 50 IS 10 BP 3450 EP 3453 DI 10.1128/AAC.00658-06 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 091IX UT WOS:000241021700032 PM 17005829 ER PT J AU Zhang, LH Bastepe, M Juppner, H Ruan, KH AF Zhang, Lihai Bastepe, Murat Juppner, Harald Ruan, Ke-He TI Characterization of the molecular mechanisms of the coupling between intracellular loops of prostacyclin receptor with the C-terminal domain of the G alpha s protein in human coronary artery smooth muscle cells SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE prostacyclin receptor; Gs protein; minigene; smooth muscle cells ID 2ND EXTRACELLULAR LOOP; PROSTANOID RECEPTORS; LIGAND-BINDING; CLONING; EXPRESSION; CDNA; SUBUNIT; SUBTYPE; ACTIVATION AB The C-terminal domain of the Gs protein alpha subunit (Gas Ct) and the first intracellular loop (iLP1) of prostacyclin receptor (IP) have been predicted to be involved in the receptor signaling mediated through the IP/Gs protein coupling by our previous NMR studies using synthetic peptides. To test whether the results of the peptide studies can be applied to the protein interaction between the IP receptor and the Gs protein in cells, a minigene technique was used to construct cDNAs that encoded either the amino acid residues of the Gas or that of the individual intracellular loops of the IP receptor. The effects of the minigene-expressed protein fragments on cAMP production mediated by the IP/Gs coupling were evaluated through experiments that co-expressed peptides either through the Gas Ct or the IP intracellular loops with the IP receptor in HEK293 cells. The first (iLP1) and third (iLP3) IP intracellular loops, as well as the Gas Ct, which are important to the IP/Gs coupling-mediated signaling, were identified by the significant reduction of cAMP production when the corresponding peptides were expressed in the cells. Furthermore, the cAMP productions were significantly impaired in Gas-knockout cells coexpressing the IP receptor with the Gas C-terminal mutants (E392A, L393A and L394A), compared with the Gas wild type. Blocking of the endogenous IP/Gs coupling by the minigene-expressed peptides of the Gets CT, iLP1 and iLP3 was further observed in the human coronary artery smooth muscle cells (SMCs). These results indicate that the three residues (E392-L394) of the Gas protein predicted from NMR peptide studies, and the IP iLP1 and iLP3 play important roles in the Gas-mediated IP receptor signaling in the cells, which may be a general binding site for the corresponding regions of the other prostanoid receptors that couple to Gs protein. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Internal Med, Vasc Biol Res Ctr, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Dept Internal Med, Div Hematol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ruan, KH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Internal Med, Vasc Biol Res Ctr, Houston, TX 77030 USA. EM Ke.H.Ruan@uth.tmc.edu FU NHLBI NIH HHS [R01 HL079389-05, HL79389, HL56712, R01 HL056712-12] NR 29 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 1 PY 2006 VL 454 IS 1 BP 80 EP 88 DI 10.1016/j.abb.2006.06.023 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 092EN UT WOS:000241079900010 PM 16942748 ER PT J AU Hernandez-Valencia, M Patti, ME AF Hernandez-Valencia, Marcelino Patti, Mary-Elizabeth TI A thin phenotype is protective for impaired glucose tolerance and related to low birth weight in mice SO ARCHIVES OF MEDICAL RESEARCH LA English DT Article DE low birth weight; diabetes; nutrition; thin phenotype ID CATCH-UP GROWTH; EXPRESSION; OBESITY AB Background. Low birth weight is an independent risk factor for impaired glucose tolerance (IGT) and diabetes in adult life. This risk extends to both preterm and term infants, a particularly important finding given the increased survival of low-birth-weight infants with improvements in neonatal care. One potential strategy for prevention of low-birth-weight- associated glucose intolerance is postnatal nutritional modification and prevention of early postnatal weight gain. To determine the efficacy of this approach, we utilized our mouse model of low birth weight related to maternal undernutrition during the third week of pregnancy. Methods. We studied three experimental groups of offspring mice: controls (C), undernutrition with low birth weight (UN) fed ad lib postnatally, and undernutrition with food restriction continued in postnatal life (UN-UN). Mean birth weight was significantly reduced in both groups of undernutrition offspring in utero (C: 1.86 +/- 0.03 vs. UN: 1.37 +/- 0.04 and UN-UN: 1.32 +/- 0.06, p < 0.001). As expected, and in accord with human data, differences in weight between C and UN mice disappeared by week 2 of life, indicating catch-up growth in the UN group. Results. Body weight was similar in all groups until 4 months of age, after which the UN-UN group had reduced body weight as compared with controls (p <0.05 at 6 months). Insulin tolerance test (1 U/kg), glucose tolerance test (2 g/kg) and glucose-stimulated insulin secretion test (3 g/kg) at 2 months of age were identical among C, UN, and UN-UN groups. By age 6 months, IGT had developed in the UN mice (p <0.05 vs. C). By contrast, UN offspring with caloric restriction postnatally (UN-UN) were protected from the development of glucose intolerance, with glucose levels identical to that of control mice. These differences appeared to be related to improved insulin sensitivity in the UN-UN mice as compared with UN mice, although data did not reach statistical significance. Conclusions. Our data suggest that alterations in early postnatal nutrition are associated with prevention of weight gain and the development of IGT in low-birth-weight mice. (C) 2006 IMSS. Published by Elsevier Inc. C1 Inst Mexicano Seguro Social, Endocrine Res Unit, Ctr Med Nacl Siglo XXI, Mexico City 06720, DF, Mexico. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hernandez-Valencia, M (reprint author), Inst Mexicano Seguro Social, Endocrine Res Unit, Ctr Med Nacl Siglo XXI, Av Cuauhtemoc 330,Col Doctores, Mexico City 06720, DF, Mexico. EM mhernandezvalencia@prodigy.net.mx NR 18 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0188-4409 J9 ARCH MED RES JI Arch. Med. Res. PD OCT PY 2006 VL 37 IS 7 BP 813 EP 817 DI 10.1016/j.arcmed.2006.03.003 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 089PZ UT WOS:000240894300001 PM 16971218 ER PT J AU Stavitsky, K Brickman, AM Scarmeas, N Torgan, RL Tang, MX Albert, M Brandt, J Blacker, D Stern, Y AF Stavitsky, Karina Brickman, Adam M. Scarmeas, Nikolaos Torgan, Rebecca L. Tang, Ming-Xin Albert, Marilyn Brandt, Jason Blacker, Deborah Stern, Yaakov TI The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; BODY VARIANT; EXTRAPYRAMIDAL SIGNS; PSYCHOPATHOLOGICAL FEATURES; DIAGNOSTIC-ACCURACY; CLINICAL-DIAGNOSIS; PATIENT DEPENDENCE; VASCULAR DEMENTIA; MOTOR SIGNS; PREDICTORS AB Background: Although dementia with Lewy bodies (DLB) may be one of most common forms of dementia, relatively little is known about its cognitive and functional course. Objective: To compare change over time in general cognitive status, memory test performance, psychiatric symptoms, neurological signs, and functional abilities in patients with probable DLB and probable Alzheimer disease (AD). Design: Twenty-eight patients who met diagnostic criteria for DLB were recruited into the study from 3 sites. Patients with AD (n=55) were selected from a larger cohort and matched 2 to 1 to the patients with DLB on age and baseline global cognitive status. Patients were followed up at 6-month intervals for an average of 6.2 visits and assessed at each visit with tests of global cognitive functioning and verbal learning and memory and measures of psychiatric, neurological, and functional status. Results: At the baseline evaluation, patients with DLB performed more poorly on a measure of constructional praxis and all measures of functional status. They also had more severe psychiatric symptoms and neurological signs than the AD group. Despite these initial differences, generalized estimating equations applied to regression analyses with repeated measures determined that the only difference between the 2 groups in change in cognitive test performance was on a measure of recognition memory; patients with AD declined, while patients with DLB remained relatively stable. Patients with DLB had relatively stable behavioral symptoms and visual illusions, whereas patients with AD had a significant increase in these symptoms over time. Neurological and functional changes over time were similar in the 2 groups. Conclusions: Both baseline and longitudinal differences between patients with DLB and patients with AD were noted; these have implications for clinical diagnosis and treatment. C1 Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10032 USA. Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Stern, Y (reprint author), Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, 18th Floor,630 W 168th St,P&S Box 16, New York, NY 10032 USA. EM ys11@columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370] NR 56 TC 46 Z9 46 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2006 VL 63 IS 10 BP 1450 EP 1456 DI 10.1001/archneur.63.10.1450 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 091VW UT WOS:000241057400015 PM 17030662 ER PT J AU Kezirian, EJ Weaver, EM Yueh, B Khuri, SF Daley, J Henderson, WG AF Kezirian, Eric J. Weaver, Edward M. Yueh, Bevan Khuri, Shukri F. Daley, Jennifer Henderson, William G. TI Risk factors for serious complication after uvulopalatopharyngoplasty SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 03-08, 2003 CL CHICAGO, IL SP Assoc Prof Sleep Soc ID OBSTRUCTIVE SLEEP-APNEA; PERIOPERATIVE COMPLICATIONS; CARDIOVASCULAR-DISEASE; MORTALITY; CARE; HYPERTENSION; ASSOCIATION; SURGERY; QUALITY AB Objective: To test the hypothesis that comorbidity, performance of concurrent sleep apnea procedures in addition to uvulopalatopharyngoplasty, body mass index, apnea-hypopnea index, and lowest oxygen saturation are risk factors for serious perioperative complications after uvulopalatopharyngoplasty. Design: Prospective cohort and nested case-control studies. Setting: United States Veterans Affairs medical centers. Patients: A prospective cohort of 3130 consecutive adult inpatients who underwent uvulopalatopharyngoplasty from 1991 to 2001 was retrospectively analyzed from the Veterans Affairs National Surgical Quality Improvement Program database to determine the relationship between perioperative complications and both concurrent procedures and medical comorbidity. A nested case-control analysis was conducted on 43 cases with complications and 212 controls without complications from the cohort. Controls were matched on age, sex, year of operation, and concurrent surgery; this case-control analysis enabled the study of body mass index, apnea-hypopnea index, and lowest oxygen saturation, which were not available in the cohort database. Multivariate logistic regression measured associations between risk factors and complications, adjusting or controlling for age, sex, race, smoking status, year of uvulopalatopharyngoplasty, and presence of any concurrent procedure. Main Outcome Measure: Sixteen specific serious perioperative complications, including 30-day mortality. Results: The cohort included 3130 veterans (97% were men aged 50 +/- 11 [ mean +/- SD] years). In the cohort study, comorbidity was associated with serious complication: the adjusted risk ratio was 1.96 (95% confidence interval, 1.16-3.18) for each increase in American Society of Anesthesiologists class. Concurrent nonnasal procedures increased the risk of complication compared with no concurrent procedures ( adjusted risk ratio, 4.94; 95% confidence interval, 2.34-10.4). In the case-control analyses, the apnea-hypopnea index, body mass index, and medical comorbidity were each associated with serious complication after adjustment for confounding variables, but this study had insufficient power to determine if these risk factors were independent of each other. Concurrent retrolingual procedures demonstrated an independent association with complication after adjustment for confounders. The lowest oxygen saturation was not associated with serious complication. Conclusions: Apnea-hypopnea index, body mass index, and medical comorbidity were each associated with serious complication; however, the low complication rate precluded demonstration of associations independent of each other. Concurrent retrolingual procedures were also associated with serious complication, but the cumulative risk of separate retrolingual procedures is unknown. C1 Univ Calif San Francisco, Sch Med, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. Brockton W Roxbury Vet Affairs Med Ctr, Dept Surg, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Tenet HealthCare, Dallas, TX USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. RP Weaver, EM (reprint author), Mail Stop 112-OTO,1660 S Columbian Way, Seattle, WA 98108 USA. EM eweaver@u.washington.edu OI Yueh, Bevan/0000-0003-1380-1053 FU NHLBI NIH HHS [K23 HL068849-04, HL068849, K23 HL068849]; NIDCD NIH HHS [T32 DC000018] NR 23 TC 17 Z9 24 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2006 VL 132 IS 10 BP 1091 EP 1098 DI 10.1001/archotol.132.10.1091 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 095DD UT WOS:000241287500011 PM 17043257 ER PT J AU Lewis, CM Resto, VA Wu, D Goguen, L AF Lewis, Carol M. Resto, Vicente A. Wu, David Goguen, Laura TI Pathology quiz case 2 - Diagnosis: Malakoplakia of the left tongue base SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID NECK C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Lewis, CM (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RI Resto, Vicente/D-9891-2014 NR 9 TC 1 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2006 VL 132 IS 10 BP 1157 EP + DI 10.1001/archotol.132.10.1157 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 095DD UT WOS:000241287500026 PM 17043272 ER PT J AU Misdraji, J Oliva, E Goldblum, JR Lauwers, CY Compton, CC AF Misdraji, Joseph Oliva, Esther Goldblum, John R. Lauwers, Cregory Y. Compton, Carolyn C. CA Coll Amer Pathologists TI Protocol for the examination of specimens from patients with invasive carcinomas of the appendix SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID DISSEMINATED PERITONEAL ADENOMUCINOSIS; INTRAPERITONEAL CHEMOTHERAPY; VERMIFORM APPENDIX; PSEUDOMYXOMA-PERITONEI; CYTOREDUCTIVE SURGERY; CLINICOPATHOLOGICAL ANALYSIS; MUCINOUS CARCINOMATOSIS; PRIMARY ADENOCARCINOMA; TUMORS; PROGNOSIS C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA. NCI, Off Director, Bethesda, MD 20892 USA. RP Misdraji, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg 105F, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 26 TC 2 Z9 2 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2006 VL 130 IS 10 BP 1433 EP 1439 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 091SS UT WOS:000241049200006 PM 17090183 ER PT J AU Jain, NB Brown, R Tun, CG Gagnon, D Garshick, E AF Jain, Nitin B. Brown, Robert Tun, Carlos G. Gagnon, David Garshick, Eric TI Determinants of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC in chronic spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Paraplegia-Society CY SEP 07-09, 2004 CL Las Vegas, NV SP Amer Paraplegia Soc DE pulmonary disease, chronic obstruction; pulmonary function tests; quadriplegia; rehabilitation; spinal cord injuries ID PULMONARY-FUNCTION; RESPIRATORY SYMPTOMS; LUNG-VOLUMES; ADULTS; HYPERRESPONSIVENESS; QUADRIPLEGIA; DYSFUNCTION; POPULATION; MECHANICS; STANDARDS AB Objective: To assess factors that influence pulmonary function, because respiratory system dysfunction is common in chronic spinal cord injury (SCI). Design: Cross-sectional cohort study. Setting: Veterans Affairs Boston SCI service and the community. Participants: Between 1994 and 2003, 339 white men with chronic SCI completed a respiratory questionnaire and underwent spirometry. Interventions: Not applicable. Main Outcome Measures: Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC. Results: Adjusting for SCI level and completeness, FEV1 (-21.0mL/y; 95% confidence interval [CI], -26.3 to -15.7 mL/y) and FVC (-17.2mL/y; 95% CI, -23.7 to -10.8mL/y) declined with age. Lifetime cigarette use was also associated with a decrease in FEV1 (-3.8mL/pack-year; 95% CI, -6.5 to -1.1 mL/pack-year), and persistent wheeze and elevated body mass index were associated with a lower FEV1/FVC. A greater maximal inspiratory pressure (MIP) was associated with a greater FEV1 and FVC. FEV1 significantly decreased with injury duration (-6. 1mL/y; 95% CI, -11.7 to -0.6mL/y), with the greatest decrement in the most neurologically impaired. The most neurologically impaired also had a greater FEV1/ FVC, and their FEV1 and FVC were less affected by age and smoking. Conclusions: Smoking, persistent wheeze, obesity, and MIP, in addition to SCI level and completeness, were significant determinants of pulmonary function. In SCI, FEV1, FVC, and FEV1/FVC may be less sensitive to factors associated with change in airway size and not reliably detect the severity of airflow obstruction. C1 VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, W Roxbury, MA 02132 USA. VA Boston Healthcare Syst, Res Serv, W Roxbury, MA 02132 USA. VA Boston Healthcare Syst, Phys Med & Rehabil Med Serv, W Roxbury, MA 02132 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM eric.garshick@med.va.gov OI Gagnon, David/0000-0002-6367-3179 FU NICHD NIH HHS [R01 HD042141, R01 HD42141] NR 41 TC 28 Z9 28 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2006 VL 87 IS 10 BP 1327 EP 1333 DI 10.1016/j.apmr.2006.06.015 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 095OA UT WOS:000241316000006 PM 17023241 ER PT J AU Zmitrewicz, RJ Neptune, RR Walden, JG Rogers, WE Bosker, GW AF Zmitrewicz, Robert J. Neptune, Richard R. Walden, Judith G. Rogers, William E. Bosker, Gordon W. TI The effect of foot and ankle prosthetic components on braking and propulsive impulses during transtibial amputee gait SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE amputees; rehabilitation; walking ID BELOW-KNEE AMPUTEES; SOUND LIMB; FLEX-FOOT; SACH FOOT; FEET; INDIVIDUALS; AMPUTATION; AMBULATION; SEATTLE AB Objective: To assess the influence of energy storage and return (ESAR) prosthetic feet and multi-axis ankles on ground reaction forces and loading asymmetry between lower limbs in transtibial amputees. Design: Subjects wore 2 different prosthetic feet with and without a multi-axis ankle and were analyzed using a blind repeated-measures multivariate analysis-of-variance design. Setting: Gait analysis laboratory. Participants: Fifteen healthy unilateral transtibial amputees (>55 y) who had an amputation at least 1 year before testing because of vascular disorders. Interventions: Not applicable. Main Outcome Measures: The anteroposterior ground reaction force impulse, peak ground reaction forces, and braking and propulsion impulse duration were analyzed as subjects walked at a self-selected speed while wearing each of the 4 foot-ankle prosthesis combinations. Statistical analyses were used to determine if there was a significant foot, ankle, or foot-ankle interaction effect on the outcome measures for each foot (P<.05). Results: Amputees generated a significantly greater propulsive impulse with the residual leg when wearing a multi-axis ankle with the ESAR and non-ESAR foot, which improved the propulsive symmetry between the residual and intact legs. There was no prosthetic foot effect on these measures. There were no significant differences in the peak residual-leg braking or propulsive ground reaction forces or the impulse durations due to the prosthetic foot, ankle, or foot-ankle interactions, although an increase in the propulsive impulse duration approached significance (P=.062) with a multi-axis ankle. Conclusions: These results suggest that amputee gait may improve with the prescription of multi-axis ankles that allow for greater propulsive impulses by the residual leg, which improve the loading symmetry between legs. C1 Univ Texas, Dept Mech Engn, Austin, TX 78712 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX USA. RP Neptune, RR (reprint author), Univ Texas, Dept Mech Engn, 1 Univ Stn C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu RI Rogers, Bill/F-7689-2010 NR 21 TC 45 Z9 46 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2006 VL 87 IS 10 BP 1334 EP 1339 DI 10.1016/j.apmr.2006.06.013 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 095OA UT WOS:000241316000007 PM 17023242 ER PT J AU Steere, AC Angelis, SM AF Steere, Allen C. Angelis, Sheryn M. TI Therapy for Lyme artritis - Strategies for the treatment of antibiotic-refractory arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Review ID BORRELIA-BURGDORFERI DNA; SURFACE PROTEIN-A; POLYMERASE-CHAIN-REACTION; HLA-DR MOLECULES; SYNOVIAL-FLUID; RHEUMATOID-ARTHRITIS; INFECTED MICE; JOINT FLUID; DISEASE; CEFTRIAXONE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Steere, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CNY 149-8301,55 Fruit St, Boston, MA 02114 USA. EM asteere@partners.org FU NIAMS NIH HHS [AR-20358] NR 48 TC 98 Z9 99 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2006 VL 54 IS 10 BP 3079 EP 3086 DI 10.1002/art.22131 PG 8 WC Rheumatology SC Rheumatology GA 094TB UT WOS:000241260800005 PM 17009226 ER PT J AU Behera, AK Hildebrand, E Szafranski, J Hung, HH Grodzinsky, AJ Lafyatis, R Koch, AE Kalish, R Perides, G Steere, AC Hu, LT AF Behera, Aruna K. Hildebrand, Ethan Szafranski, Jon Hung, Han-Hwa Grodzinsky, Alan J. Lafyatis, Robert Koch, Alisa E. Kalish, Robert Perides, George Steere, Allen C. Hu, Linden T. TI Role of aggrecanase 1 in Lyme arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ACTIVATED PROTEIN-KINASE; HUMAN SYNOVIAL-FLUID; INTERGLOBULAR DOMAIN; ARTICULAR-CARTILAGE; MATRIX METALLOPROTEINASES; BORRELIA-BURGDORFERI; CLEAVAGE SITE; PHASE-I; CATABOLISM; DEGRADATION AB Objective. Arthritis is one of the hallmarks of late-stage Lyme disease. Previous studies have shown that infection with Borrelia burgdorferi, the causative agent of Lyme disease, results in degradation of proteoglycans and collagen in cartilage. B burgdorferi do not appear to produce any exported proteases capable of digesting proteoglycans and collagen, but instead, induce and activate host proteases, such as matrix metalloproteinases (MMPs), which results in cartilage degradation. The role of aggrecanases in Lyme arthritis has not yet been determined. We therefore sought to delineate the contribution of aggrecanases to joint destruction in Lyme arthritis. Methods. We examined the expression patterns of aggrecanases 1 and 2 (ADAMTS 4 and 5, respectively) in B burgdorferi-infected primary human chondrocyte cell cultures, in synovial fluid samples from patients with active Lyme arthritis, and in the joints of mice by real-time quantitative reverse transcription-polymerase chain reaction and immunoblotting techniques. Bovine cartilage explants were used to determine the role of aggrecanases in B burgdorferi-induced cartilage degradation. Results. ADAMTS-4, but not ADAMTS-5, was induced in human chondrocytes infected with B burgdorferi. The active forms of ADAMTS-4 were increased in synovial fluid samples from patients with active Lyme arthritis and were elevated in the joints of mice infected with B burgdorferi. Using cartilage explant models of Lyme arthritis, it appeared that the cleavage of aggrecan was predominantly mediated by "aggrecanases" rather than MMPs. Conclusion. The induction of ADAMTS-4 by B burgdorferi results in the cleavage of aggrecan, which may be an important first step that leads to permanent degradation of cartilage. C1 Tufts Univ, Sch Med, Tupper Res Inst, Boston, MA 02111 USA. MIT, Cambridge, MA 02139 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Vet Affairs Healthcare Syst, Ann Arbor, MI USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hu, LT (reprint author), Tufts Univ New England Med Ctr, 750 Washington St,Box 41, Boston, MA 02111 USA. EM lhu@tufts-nemc.org RI Koch, Alisa/B-6894-2011; Hu, Linden/L-6314-2016 OI Hu, Linden/0000-0003-1659-5558 FU NIAID NIH HHS [R01 AI050043-03, R01 AI050043, R01 AI050043-01A1, R01 AI050043-02, R01 AI050043-04, R01 AI050043-05, R01-AI-40987, R01-AI-44240, R01-AI-50043, U01-AI-058266]; NIAMS NIH HHS [AR-20358, AR-45779, R01-AR-48267] NR 37 TC 25 Z9 26 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2006 VL 54 IS 10 BP 3319 EP 3329 DI 10.1002/art.22128 PG 11 WC Rheumatology SC Rheumatology GA 094TB UT WOS:000241260800033 PM 17009305 ER PT J AU Costouros, JG Clavert, P Warner, JJP AF Costouros, John G. Clavert, Philippe Warner, Jon J. P. TI Trans-cuff portal for arthroscopic posterior capsulorrhaphy SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE shoulder; arthroscopy; posterior instability; Bankart; beach chair position ID ANTERIOR SHOULDER INSTABILITY; BANKART REPAIR; FOLLOW-UP; SUBLUXATION; LESIONS; JOINT AB Arthroscopic repair of posterior shoulder instability is becoming an accepted method of treatment. Most surgeons perform this procedure with the patient in a lateral decubitus position to facilitate access to the posterior glenoid. We have developed an accessory portal placed through the midportion of the rotator cuff that allows easy and complete viewing of the posterior glenohumeral joint when the patient is in a beach chair position and does not require the use of traction. This portal provides a superior-to-inferior view of the posterior glenoid rim and capsule and allows use of anterior and posterior routine portals for posterior Bankart repair. In this study, the technique of posterior labral repair in the beach chair position with use of the trans-cuff portal is described, and preliminary results in 5 patients at an average follow-up of 24 months are presented. Through this approach, we were able to place 3 anchors, with the lowest tit the 7 o'clock position (for a right shoulder), in all patients. Mean American Shoulder Elbow Surgeons (ASES) score improved from 53 +/- 1.5 preoperatively to 87 +/- 8 postoperatively (P < .01). All patients had an excellent result with complete resolution of pain and instability. C1 Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Dept Orthopaed Surg,Yawkwy Ctr Outpatient Care, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Dept Orthopaed Surg,Yawkwy Ctr Outpatient Care, 55 Fruit St,Suite 3200, Boston, MA 02114 USA. EM jwarner@partners.org NR 14 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD OCT PY 2006 VL 22 IS 10 AR 1138.e1 DI 10.1016/j.arthro.2006.05.013 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 101ET UT WOS:000241722700021 ER PT J AU Li, GH Oparil, S Sanders, JM Zhang, L Dai, MR Chen, LB Conway, SJ McNamara, CA Sarembock, IJ AF Li, Guohong Oparil, Suzanne Sanders, John M. Zhang, Lin Dai, Meiru Chen, Lan Bo Conway, Simon J. McNamara, Coleen A. Sarembock, Ian J. TI Phosphatidylinositol-3-kinase signaling mediates vascular smooth muscle cell expression of periostin in vivo and in vitro SO ATHEROSCLEROSIS LA English DT Article DE periostin; PI-3-kinase; smooth muscle; migration ID ADVENTITIAL FIBROBLAST MIGRATION; OSTEOBLAST-SPECIFIC FACTOR; OSTEOPONTIN EXPRESSION; GROWTH; PROLIFERATION; INJURY; INHIBITION; 3-KINASE; PROTEIN; MOUSE AB Objective: Periostin is dramatically upregulated in rat carotid arteries after balloon injury. The objective of the present study was to understand mechanisms underlying periostin upregulation in balloon-injured rat carotid arteries and in cultured vascular smooth muscle cells (VSMCs). Methods and results: Periostin protein was strongly expressed at 3 days (in the medial SMCs) and 7 days (in the neointima) after injury. It was also abundantly expressed in the neointima in the late phase (at 14 and 28 days) after injury. Periostin upregulation was mediated through PI-3-kinase-dependent signaling pathway. In vivo, wortmannin, a PI-3-kinase inhibitor, inhibited balloon injury-induced Akt phosphorylation and periostin mRNA expression. In vitro, periostin mRNA expression in cultured VSMCs was stimulated by growth factors (transforming growth factor-beta 1 (TGF-beta 1), fibroblast growth factors (FGFs), PDGF-BB, and angiotensin 11). This stimulatory effect was inhibited by the PI-3-kinase inhibitor LY294002. Further, periostin protein was mostly located in the cytoplasma of VSMCs in culture and abundantly secreted into the culture medium (CM) after stimulation with FGF-2, which significantly promoted VSMC migration in vitro. Immunodepletion of periostin from the VSMC-CM or blockade of periostin function with an anti-periostin antibody significantly reduced VSMC migration. Conclusions: Upregulation of periostin expression in rat carotid arteries following balloon injury and in cultured VSMCs after stimulation by growth factors is mediated through PI-3-kinase-dependent signaling pathway. Periostin protein secreted by VSMCs plays a significant role in regulating VSMC migration in vitro. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Virginia Hlth Syst, Cardiovasc Div Internal Med, Charlottesville, VA USA. Univ Virginia Hlth Syst, Cardiovasc Res Ctr, Charlottesville, VA USA. Univ Alabama, Vasc Biol & Hypertens Program, Birmingham, AL USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. Indiana Univ, Sch Med, Wells Ctr Pediat Res, Indianapolis, IN USA. RP Li, GH (reprint author), Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27514 USA. EM ghli@med.unc.edu FU NHLBI NIH HHS [R01 HL062522, HL-062522, HL-66264, HL64614, R01 HL060714, R01 HL060714-09, R01 HL064614, R01 HL066264] NR 21 TC 51 Z9 58 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2006 VL 188 IS 2 BP 292 EP 300 DI 10.1016/j.atherosclerosis.2005.11.002 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 090EL UT WOS:000240933300009 PM 16325820 ER PT J AU Karameh, FN Dahleh, MA Brown, EN Massaquoi, SG AF Karameh, Fadi N. Dahleh, Munther A. Brown, Emery N. Massaquoi, Steve G. TI Modeling the contribution of lamina 5 neuronal and network dynamics to low frequency EEG phenomena SO BIOLOGICAL CYBERNETICS LA English DT Article ID DUAL INTRACELLULAR-RECORDINGS; NEOCORTICAL PYRAMIDAL NEURONS; PRIMARY SOMATOSENSORY CORTEX; SHORT-TERM PLASTICITY; RAT BARREL CORTEX; LAYER-V NEURONS; IN-VIVO; SYNCHRONIZED OSCILLATIONS; SPATIOTEMPORAL PROPERTIES; AUGMENTING RESPONSES AB The Electroencephalogram (EEG) is an important clinical and research tool in neurophysiology. With the advent of recording techniques, new evidence is emerging on the neuronal populations and wiring in the neocortex. A main challenge is to relate the EEG generation mechanisms to the underlying circuitry of the neocortex. In this paper, we look at the principal intrinsic properties of neocortical cells in layer 5 and their network behavior in simplified simulation models to explain the emergence of several important EEG phenomena such as the alpha rhythms, slow-wave sleep oscillations, and a form of cortical seizure. The models also predict the ability of layer 5 cells to produce a resonance-like neuronal recruitment known as the augmenting response. While previous models point to deeper brain structures, such as the thalamus, as the origin of many EEG rhythms (spindles), the current model suggests that the cortical circuitry itself has intrinsic oscillatory dynamics which could account for a wide variety of EEG phenomena. C1 Amer Univ Beirut, Dept Elect & Comp Engn, Beirut 11072020, Lebanon. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Karameh, FN (reprint author), Amer Univ Beirut, Dept Elect & Comp Engn, Beirut 11072020, Lebanon. EM fk14@aub.edu.lb FU NIDA NIH HHS [R01 DA015644]; NIMH NIH HHS [MH61637, MH59733] NR 75 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-1200 EI 1432-0770 J9 BIOL CYBERN JI Biol. Cybern. PD OCT PY 2006 VL 95 IS 4 BP 289 EP 310 DI 10.1007/s00422-006-0090-8 PG 22 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA 089QV UT WOS:000240896600001 PM 16897093 ER PT J AU Yehuda, R Tischler, L Golier, JA Grossman, R Brand, SR Kaufman, S Harvey, PD AF Yehuda, Rachel Tischler, Lisa Golier, Julia A. Grossman, Robert Brand, Sarah R. Kaufman, Shira Harvey, Philip D. TI Longitudinal assessment of cognitive performance in Holocaust survivors with and without PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Article DE aging; California Verbal Learning Test; memory; paired associate learning; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; VIVO HIPPOCAMPAL VOLUMETRICS; MEMORY PERFORMANCE; COMBAT VETERANS; CORTISOL-LEVELS; FOLLOW-UP; DYSFUNCTION; PRISONERS; DEFICITS; ATROPHY AB Background: There are currently no longitudinal studies of cognitive performance in older patients with Posttraumatic Stress Disorder (PTSD). It is therefore unclear whether relationships between memory and symptoms differ over time among older persons with and without PTSD. Methods: Twenty-eight Holocaust survivors and nineteen comparison subjects were evaluated 5 years after they had received a memory assessment including paired-associates learning and the California Verbal Learning Test (CVLT). Results: While Holocaust survivors with PTSD showed a diminution in symptom severity (t = 2.99, df = 12, p = .011), they still manifested a decline in paired associates learning, suggesting an acceleration in age-related memory impairment (related word pairs: t = 2.87. df = 13, p = .013; unrelated word pairs: t = 2.06 df = 13, p = .060). The survivors with PTSD showed improvements on several CVLT measures over time. These improvements correlated with symptom improvements, such that group differences at the follow-up were no longer detected. Conclusions: The discrepancy in the pattern of performance on these two tests of memory following symptom improvement suggests possible differentiation between of aspects of memory functions associated with aging and trauma exposure and those associated with the severity of PTSD symptoms. Performance on the CVLT appeared related to clinical symptom severity while paired associate learning worsened over time in Holocaust survivors with PTSD, consistent with earlier cross-sectional findings. C1 Bronx Vet Affairs, Mt Sinai Sch Med, Traumat Stress Studies Program, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Div Psychol, Dept Psychiat, New York, NY USA. James J Peters VA Med Ctr, VISN 3, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA. RP Yehuda, R (reprint author), Bronx VA OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov FU PHS HHS [NIMH R01-0-64675, NIMH R01-2-49555] NR 37 TC 44 Z9 44 U1 4 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2006 VL 60 IS 7 BP 714 EP 721 DI 10.1016/j.biopsych.2006.03.069 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 090TB UT WOS:000240973300008 PM 17008144 ER PT J AU Orr, SP Milad, MR Metzger, LJ Lasko, NB Gilbertson, MW Pitman, RK AF Orr, Scott P. Milad, Mohammed R. Metzger, Linda J. Lasko, Natasha B. Gilbertson, Mark W. Pitman, Roger K. TI Effects of beta blockade, PTSD diagnosis, and explicit threat on the extinction and retention of an aversively conditioned response SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE conditioning; extinction; retention; skin conductance; posttraumatic stress disorder; beta bluockade ID POSTTRAUMATIC-STRESS-DISORDER; HIPPOCAMPAL CA1 REGION; MEMORY RETRIEVAL; PSYCHOPHYSIOLOGICAL ASSESSMENT; FEAR MEMORY; PROPRANOLOL; AMYGDALA; RATS; ADRENOCEPTORS; ACQUISITION AB An aversively conditioned SC response was assessed in 18 males meeting DSM-IV criteria for chronic posttraumatic stress disorder (PTSD) and 10 trauma-exposed males who never developed PTSD. Effects of beta blockade on acquisition and retention of a conditioned response (CR) were examined by administering propranolol HCl before acquisition or following extinction trials. Retention of the CR was assessed I week following acquisition under conditions of non-threat and threat. Conditioned stimuli were colored circles and the unconditioned stimulus (UCS) was a "highly annoying" electrical stimulus. The propranolol failed to produce any measurable effects on acquisition or retention of the CR and there was no evidence of increased conditionability in individuals diagnosed with PTSD. One week following acquisition, the differential CR to the reinforced stimulus was evident only in the threat condition. This suggests that belief in the presence of a threat is necessary and sufficient for activating a previously established CR. (c) 2006 Elsevier B.V. All rights reserved. C1 Dept Vet Affairs Med Ctr, Res Serv, Manchester, NH 03104 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Orr, SP (reprint author), Dept Vet Affairs Med Ctr, Res Serv, 151,718 Smyth Rd, Manchester, NH 03104 USA. EM scott.orr@med.va.gov NR 40 TC 36 Z9 37 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD OCT PY 2006 VL 73 IS 3 BP 262 EP 271 DI 10.1016/j.biopsycho.2006.05.001 PG 10 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 112UX UT WOS:000242554000007 PM 16828533 ER PT J AU Alyea, EP Kim, HT Ho, V Cutler, C DeAngelo, DJ Stone, R Ritz, J Antin, JH Soiffer, RJ AF Alyea, Edwin P. Kim, Haesook T. Ho, Vincent Cutler, Corey DeAngelo, Daniel J. Stone, Richard Ritz, Jerome Antin, Joseph H. Soiffer, Robert J. TI Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodyspiastic syndrome SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE acute leukemia; myelodysplastic syndrome; allogeneic; graft versus leukemia ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; POSTREMISSION THERAPY; COMPETING RISK; PATIENTS OLDER; CHEMOTHERAPY; MORBIDITY; REMISSION; MORTALITY; DONORS AB We reviewed 136 patients with advanced acute myelogenous leukemia (AML) and myelodysplastic syndrome (AIDS) undergoing allogeneic transplantation to assess the impact of conditioning regimen intensity on outcome. Thirty-nine patients receiving nonmyeloablative stem cell transplantation (NST) were compared with 97 patients receiving myeloablative transplantation. Patients receiving NST were at high risk for treatment-related complications given that they were older, 57 vs 43 years (P < .001), and more likely had received previous or myeloablative transplantation (54% vs 2%; P < .0001). The cumulative risk of relapse was higher for patients after NST (61% vs 38%; P = .02). The 100-day mortality was less after NST (15% vs 32%) Overall survival (OS) at 2 years was 28% for NST and 34% for myeloablative transplantation (P = .89). Progression-free survival (PFS) at 2 years was 20% for NST and 31% for myeloablative transplantation (P = .31). Cox regression analysis showed that the intensity of the conditioning regimen had no effect on either OS or PFS. Despite the high-risk features of patients with advanced AML or MDS undergoing NST, OS and PFS in these patients was similar to those in patients receiving myeloablative transplantation. These results demonstrate that dose intensity plays a significant role in control of disease after transplantation, but that this benefit is negated by increasing treatment-related mortality. These results suggest that NST is a reasonable alternative for patients with advanced AML and MDS at high risk for complications after myeloablative transplantation. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Edwin_alyea@dfci.harvard.edu FU NHLBI NIH HHS [P01 HL070149] NR 23 TC 115 Z9 120 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2006 VL 12 IS 10 BP 1047 EP 1055 DI 10.1016/J.BBMT.2006.06.003 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 095KF UT WOS:000241305900006 PM 17067911 ER PT J AU Brown, JR T Kim, H Li, SL Stephans, K Fisher, DC Cutler, C Ho, V Lee, SJ Milford, EL Ritz, J Antin, JH Soiffer, RJ Gribben, JG Alyea, EP AF Brown, Jennifer R. T Kim, Haesook Li, Shuli Stephans, Katherine Fisher, David C. Cutler, Corey Ho, Vincent Lee, Stephanie J. Milford, Edgar L. Ritz, Jerome Antin, Joseph H. Soiffer, Robert J. Gribben, John G. Alyea, Edwin P. TI Predictors of improved progression-free survival after nonmyeloablative allogeneic stem cell transplantation for advanced chronic lymphocytic leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE CLL; NST; chimerism ID BONE-MARROW-TRANSPLANTATION; HEAVY-CHAIN GENE; PROGNOSTIC FACTORS; MATCHED ANALYSIS; POOR-PROGNOSIS; FLUDARABINE; RITUXIMAB; RISK; CLL; CHEMOIMMUNOTHERAPY AB Although chronic lymphocytic leukemia (CLL) remains an incurable disease with standard chemotherapy, the appropriate role and tinting of transplantation are unclear. In this analysis, we report the outcomes of 46 patients with advanced CLL who underwent nonmyeloablative stem cell transplantation (NST) from HLA-matched unrelated (67%) or related (33%) donors. Fludarabine (30 mg/m(2) x 4) and low-dose intravenous busulfan (0.8 mg/kg/day x 4) were used for conditioning. The 2-year overall survival (OS) and progression-free survival (PFS) rates in this refractory patient population were 54% and 34%, respectively, with a median follow-up of 20 months. The primary cause of treatment failure was relapse, with a 2-year cumulative incidence of 48%. High hematopoietic donor chimerism >= 75% at day +30 was a significant predictor of 2-year PFS (47% vs 11%; P = .03). In multivariate analysis, chemotherapy-refractory disease at transplantation was associated with a 3.2-fold risk of progression (P = .01) and a 4.6-fold risk of death (P = .02). Increasing number of previous therapies and increasing bone marrow involvement were also associated with decreased PFS and OS. These results suggest that NST using fludarabine and low-dose intravenous busulfan is a reasonable treatment option for patients with advanced CLL, but that NST earlier in the disease course will likely be needed to achieve long-term disease control in a high proportion of patients. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Edwin_alyea@dfci.harvard.edu FU NCI NIH HHS [K23 CA115682-01, P01 CA81538]; NHLBI NIH HHS [P01 HL070149]; PHS HHS [A129530] NR 29 TC 67 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2006 VL 12 IS 10 BP 1056 EP 1064 DI 10.1016/j.bbmt.2006.06.004 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 095KF UT WOS:000241305900007 PM 17084369 ER PT J AU Hahn, MS Teply, BA Stevens, MM Zeitels, SM Langer, R AF Hahn, MS Teply, BA Stevens, MM Zeitels, SM Langer, R TI Collagen composite hydrogels for vocal fold lamina propria restoration SO BIOMATERIALS LA English DT Article DE vocal fold; tissue engineering; augmentation; hydrogel; collagen; hyaluronan ID FIBROBLASTS; ALGINATE; CHONDROGENESIS; AUGMENTATION; CONTRACTION; BIOREACTOR; HYALURONAN; SYSTEM AB Chronic voice impairment due to scarring of the vocal fold (VF) lamina propria (LP) can be debilitating in terms of quality of life. Due to the dependence of normal VF vibration on proper VF geometry, an implant inserted to restore appropriate shape and pliability to scarred LP should ideally maintain its insertion-dimensions while being replaced by newly synthesized extracellular matrix (ECM). In the present study, collagen-alginate and collagen-hyaluronan (HA) composite hydrogels were investigated for their ability to support ECM synthesis by VF fibroblasts with limited hydrogel compaction and/or resorption. Collagen-HA composites showed significant mass loss over 28 days of culture, with little evidence of new matrix production. Collagen-alginate composites, in contrast, resisted scaffold compaction and mass loss for at least 42 days in culture while allowing for ECM synthesis. Collagen-alginate hydrogels appear to be promising materials for VF restoration, warranting further investigation. (c) 2005 Elsevier Ltd. All rights reserved. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Dept Mat Sci, Cambridge, MA 02139 USA. Univ London Imperial Coll Sci Technol & Med, Dept Mat, London SW7 2AZ, England. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rlanger@mit.edu RI Hahn, Mariah/G-3998-2014 OI Hahn, Mariah/0000-0001-8794-129X NR 17 TC 68 Z9 72 U1 1 U2 31 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 OCT PY 2006 VL 27 IS 7 BP 1104 EP 1109 DI 10.1016/j.biomaterials.2005.07.022 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 996BB UT WOS:000234148300019 PM 16154633 ER PT J AU Fukuda, J Khademhosseini, A Yeo, Y Yang, XY Yeh, J Eng, G Blumling, J Wang, CF Kohane, DS Langer, R AF Fukuda, Junji Khademhosseini, Ali Yeo, Yoon Yang, Xiaoyu Yeh, Judy Eng, George Blumling, James Wang, Chi-Fong Kohane, Daniel S. Langer, Robert TI Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures SO BIOMATERIALS LA English DT Article DE spheroid; chitosan; hydrogel; co-culture; hepatocyte; fibroblast ID ADULT-RAT HEPATOCYTES; HYBRID ARTIFICIAL LIVER; HIGH ALBUMIN PRODUCTION; IN-VITRO; MULTICELLULAR SPHEROIDS; CELL-INTERACTIONS; CULTURE; SCAFFOLD; BIOLOGY; REGENERATION AB Bioengineering approaches, such as co-cultures of multiple cell types, that aim to mimic the physiological microenvironment may be beneficial for optimizing cell function and for engineering tissues in vitro. This study describes a novel method for preparing a spheroid microarray on microfabricated hydrogels, alone or in co-cultures. Photocrosslinkable chitosan was synthesized and utilized for fabricating hydrogel microstructures through a micromolding process. The chitosan surface was initially cell repellent but became increasingly cell adhesive over time. By using this unique property of chitosan hydrogels, it was possible to generate patterned co-cultures of spheroids and support cells. In this scheme, cells were initially microarrayed within low shear stress regions of microwells. Human hepatoblastoma cells, Hep G2, seeded in these wells formed spheroids with controlled sizes and shapes and stably secreted albumin during the culture period. The change of cell adhesive properties in the chitosan surface facilitated the adhesion and growth of a second cell type, NIH-3T3 fibroblast, and therefore enabled co-cultures of hepatocyte spheroids and fibroblast monolayers. This co-culture system could be a useful platform for studying heterotypic cell-cell interactions, for drug screening, and for developing implantable bioartificial organs. (c) 2006 Elsevier Ltd. All rights reserved. C1 MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. RP Langer, R (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rlanger@mit.edu RI Khademhosseini, Ali/A-9435-2010; Fukuda, Junji/B-9257-2011; OI Khademhosseini, Ali/0000-0002-2692-1524; Fukuda, Junji/0000-0002-7194-8099; Khademhosseini, Ali/0000-0001-6322-8852 FU NHLBI NIH HHS [HL60435] NR 42 TC 174 Z9 178 U1 3 U2 68 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 OCT PY 2006 VL 27 IS 30 BP 5259 EP 5267 DI 10.1016/j.biomaterials.2006.05.044 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 084BK UT WOS:000240506400012 PM 16814859 ER PT J AU Bois, F Baldwin, RM Kula, NS Baldessarini, RJ Al Tikriti, M Innis, RB Tamagnan, GD AF Bois, Frederic Baldwin, Ronald M. Kula, Nora S. Baldessarini, Ross J. Al Tikriti, M. Innis, Robert B. Tamagnan, Gilles D. TI Synthesis and monoamine transporter affinity of 2 beta-carbomethoxy-3 beta-(4 '-p-substituted phenyl)-piperidine analogs of cocaine SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE SERT; monoamine transporter; SPECT; cocaine; imaging ID PIPERIDINE-BASED ANALOGS; SEROTONIN TRANSPORTERS; BETA-CIT; DOPAMINE; SAR AB A series of novel piperidine based analogs of cocaine was synthesized and evaluated in vitro against the three monoamine transporters to develop new potential selective SERT radiotracers. Modification of the phenyl substitution with five-membered heterocyclic groups resulted in a wide affinity and selectivity scale. Radiolabeling and mouse in vivo study was performed on the piperidine analog of ZIENT, which crossed the blood-brain barrier but failed to selectively accumulate in the regions of the brain rich in SERT. (c) 2006 Elsevier Ltd. All rights reserved. C1 Yale Univ, Sch Med, VA Connecticut HCS 116A2, West Haven, CT 06516 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat & Neurosci P, McLean Div,Mailman Res Ctr, Belmont, MA 02478 USA. RP Tamagnan, GD (reprint author), Yale Univ, Sch Med, VA Connecticut HCS 116A2, 950 Campbell Ave, West Haven, CT 06516 USA. EM gtamagnan@indd.org FU NIMH NIH HHS [MH-34006, MH-47370] NR 10 TC 2 Z9 2 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 1 PY 2006 VL 16 IS 19 BP 5222 EP 5225 DI 10.1016/j.bmcl.2006.07.013 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 085PG UT WOS:000240615400047 PM 16908151 ER PT J AU Marangell, LB Bauer, MS Dennehy, EB Wisniewski, SR Allen, MH Miklowitz, DJ Oquendo, MA Frank, E Perlis, RH Martinez, JM Fagiolini, A Otto, MW Chessick, CA Zboyan, HA Miyahara, S Sachs, G Thase, ME AF Marangell, Lauren B. Bauer, Mark S. Dennehy, Ellen B. Wisniewski, Stephen R. Allen, Michael H. Miklowitz, David J. Oquendo, Maria A. Frank, Ellen Perlis, Roy H. Martinez, James M. Fagiolini, Andrea Otto, Michael W. Chessick, Cheryl A. Zboyan, Holly A. Miyahara, Sachiko Sachs, Gary Thase, Michael E. TI Prospective predictors of suicide and suicide attempts in 1,556 patients with bipolar disorders followed for up to 2 years SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; prospective; risk factors; suicide; suicide attempts ID TREATMENT ENHANCEMENT PROGRAM; MAJOR DEPRESSIVE DISORDER; STEP-BD; CLINICAL PREDICTORS; COMPLETED SUICIDE; MOOD DISORDERS; RISK-FACTORS; BEHAVIOR; SCALE; ANTIDEPRESSANTS AB Objectives: Bipolar disorders are associated with high rates of suicide attempts (SAs) and completions. Several factors have been reported to be associated with suicide in persons with bipolar disorder, but most studies to date have been retrospective and have not utilized multivariate statistics to account for the redundant prediction among variables submitted for analysis. Methods: This study examined the association between baseline clinical and demographic variables and subsequent SAs and completions through 2 years of follow-up of participants in the Systematic Treatment Enhancement Program for Bipolar Disorder using a pattern-mixture model. Results: Of the sample with complete data (n = 1,556), 57 patients (3.66%) experienced an SA or completion (CS). Several variables predicted suicidality (SA + CS) in this data set when considered alone, but after controlling for redundant prediction from other baseline characteristics, only history of suicide [odds ratio (OR) = 4.52, p < 0.0001] and percent days depressed in the past year (OR = 1.16, p = 0.036) were significantly associated with SAs and completions. A secondary analysis included a greater number of variables but a smaller sample size (n = 1,014). In the secondary analyses, only prior SAs predicted prospective suicidality (OR = 3.87, p = 0.0029). Conclusions: These results indicate that patients with bipolar disorder who present with a history of SAs are over four times as likely to have a subsequent SA or completion. Further studies are needed to evaluate and prevent future attempts in this high-risk cohort. C1 Baylor Coll Med, Menninger Dept Psychiat, Mood Disorders Ctr, Houston, TX 77030 USA. Dept Vet Affairs, Houston, TX USA. Brown Univ, Dept Psychiat, Providence, RI 02912 USA. Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. Univ Pittsburgh, Dept Epidemiol & Psychiat, Pittsburgh, PA USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Marangell, LB (reprint author), Baylor Coll Med, Menninger Dept Psychiat, Mood Disorders Ctr, 6655 Travis St,Suite 560, Houston, TX 77030 USA. EM laurenm@bcm.tmc.edu RI Allen, Michael/A-8776-2011; OI FAGIOLINI, ANDREA/0000-0001-5827-0853; Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 48 TC 73 Z9 77 U1 2 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2006 VL 8 IS 5 BP 566 EP 575 DI 10.1111/j.1399-5618.2006.00369.x PN 2 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 095XW UT WOS:000241342600006 PM 17042830 ER PT J AU Gonzalez-Pinto, A Mosquera, F Alonso, M Lopez, P Ramirez, F Vieta, E Baldessarini, RJ AF Gonzalez-Pinto, Ana Mosquera, Fernando Alonso, Marta Lopez, Purificacion Ramirez, Fernando Vieta, Eduard Baldessarini, Ross J. TI Suicidal risk in bipolar I disorder patients and adherence to long-term lithium treatment SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; lithium; patient non-adherence; risk factors; suicide; therapeutics ID MAJOR AFFECTIVE-DISORDERS; ANTIDEPRESSANT TREATMENT; DOUBLE-BLIND; FOLLOW-UP; MAINTENANCE; MORTALITY; BEHAVIOR; MOOD; DISCONTINUATION; METAANALYSIS AB Objectives: Among the well-established treatments for bipolar disorder (BPD), lithium continues to offer an unusually broad spectrum of benefits that may include reduction of suicidal risk. Methods: We examined the association of suicidal acts with adherence to long-term lithium maintenance treatment and other potential risk factors in 72 BP I patients followed prospectively for up to 10 years at a Mood Disorders Research Center in Spain. Results: The observed rates of suicide were 0.143, and of attempts, 2.01%/year, with a 5.2-fold (95% CI: 1.5-18.6) greater risk among patients consistently rated poorly versus highly adherent to lithium prophylaxis (11.4/2.2 acts/100 person-years). Treatment non-adherence was associated with substance abuse, being unmarried, being male, and having more hypomanic-manic illness and hospitalizations. Suicidal risk was higher with prior attempts, more depression and hospitalization, familial mood disorders, and being single and younger, as well as treatment non-adherence, but with neither sex nor substance abuse. In multivariate analysis, suicidal risk was associated with previous suicidality > poor treatment adherence > more depressive episodes > younger age. Conclusions: The findings support growing evidence of lower risk of suicidal acts during closely monitored and highly adherent, long-term treatment with lithium and indicate that treatment adherence is a potentially modifiable factor contributing to antisuicidal benefits. C1 Stanley Inst Int Mood Disorders Res Ctr, Vitoria, Spain. Hosp Clin Barcelona, IDIBAPS, Stanley Inst Int Mood Disorders Res Ctr, Barcelona, Spain. Harvard Univ, Sch Med, Int Consortium Bipolar Disorders Res, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Boston, MA 02114 USA. RP Gonzalez-Pinto, A (reprint author), Univ Basque Country, Hosp Santiago Apostol, Stanley Int Mood Disorders Res Ctr, Olaguibel 29, Vitoria 01004, Spain. EM agonzalez@hsan.osakidetza.net RI Vieta, Eduard/I-6330-2013 OI Vieta, Eduard/0000-0002-0548-0053 NR 48 TC 86 Z9 87 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2006 VL 8 IS 5 BP 618 EP 624 DI 10.1111/j.1399-5618.2006.00368.x PN 2 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 095XW UT WOS:000241342600010 PM 17042834 ER PT J AU Baldessarini, RJ Tondo, L Davis, P Pompili, M Goodwin, FK Hennen, J AF Baldessarini, Ross J. Tondo, Leonardo Davis, Paula Pompili, Maurizio Goodwin, Frederick K. Hennen, John TI Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; lithium; major affective disorders; meta-analysis; suicide ID BIPOLAR-I DISORDER; MAJOR AFFECTIVE-DISORDERS; CONTROLLED 18-MONTH TRIAL; RECURRENT MOOD DISORDERS; MAINTENANCE TREATMENT; PROPHYLACTIC LITHIUM; CLINICAL-TRIALS; DOUBLE-BLIND; DEPRESSIVE-ILLNESS; MORTALITY AB Objectives: To update and extend comparisons of rates of suicides and suicide attempts among patients with major affective disorders with versus without long-term lithium treatment. Methods: Broad searching yielded 45 studies providing rates of suicidal acts during lithium treatment, including 34 also providing rates without lithium treatment. We scored study quality, tested between-study variance, and examined suicidal rates on versus off lithium by meta-analytic methods to determine risk ratios (RRs) and 95% confidence intervals (CI). Results: In 31 studies suitable for meta-analysis, involving a total of 85,229 person-years of risk-exposure, the overall risk of suicides and attempts was five times less among lithium-treated subjects than among those not treated with lithium (RR = 4.91, 95% CI 3.82-6.31, p < 0.0001). Similar effects were found with other meta-analytic methods, as well as for completed versus attempted suicide, and for bipolar versus major mood disorder patients. Studies with higher quality ratings, including randomized, controlled trials, involved shorter exposures with somewhat lesser lithium superiority. Omitting one very large study or those involving lithium-discontinuation had little effect on the results. The incidence-ratio of attempts-to-suicides increased 2.5 times with lithium-treatment, indicating reduced lethality of suicidal acts. There was no indication of bias toward reporting positive findings, nor were outcomes significantly influenced by publication-year or study size. Conclusions: Risks of completed and attempted suicide were consistently lower, by approximately 80%, during treatment of bipolar and other major affective disorder patients with lithium for an average of 18 months. These benefits were sustained in randomized as well as open clinical trials. C1 Harvard Univ, Sch Med, Dept Psychiat, Int Consortium Res Bipolar Disorders, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Belmont, MA USA. Univ Cagliari, Dept Psychol, Cagliari, Sardinia, Italy. Lucio Bini Mood Disorder Ctr, Cagliari, Sardinia, Italy. Univ Roma La Sapienza, SantAndrea Hosp, Dept Psychiat, Rome, Italy. George Washington Univ, Sch Med, Dept Psychiat, Washington, DC USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, 115 Mill St, Belmont, MA 02178 USA. EM rjb@mclean.org OI Pompili, Maurizio/0000-0003-1886-4977 NR 88 TC 237 Z9 241 U1 3 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2006 VL 8 IS 5 BP 625 EP 639 DI 10.1111/j.1399-5618.2006.00344.x PN 2 PG 15 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 095XW UT WOS:000241342600011 PM 17042835 ER PT J AU Ritz, J AF Ritz, Jerome TI Trans-presentation of IL-15 SO BLOOD LA English DT Editorial Material ID IL-15R-ALPHA; EXPRESSION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2006 VL 108 IS 7 BP 2135 EP 2136 DI 10.1182/blood-2006-07-035246 PG 2 WC Hematology SC Hematology GA 088ZD UT WOS:000240848700004 ER PT J AU Rowe, PSN Matsumoto, N Jo, OD Shih, RNJ Oconnor, J Roudier, MP Bain, S Liu, SG Harrison, J Yanagawa, N AF Rowe, Peter S. N. Matsumoto, Naoko Jo, Oak D. Shih, Remi N. J. Oconnor, Jeannine Roudier, Martine P. Bain, Steve Liu, Shiguang Harrison, Jody Yanagawa, Norimoto TI Correction of the mineralization defect in hyp mice treated with protease inhibitors CA074 and pepstatin SO BONE LA English DT Article DE MEPE; rickets; osteomalacia; PHEX; mineralization; FGF23 ID LINKED HYPOPHOSPHATEMIC RICKETS; MOUSE BONE-CELLS; MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; TUMOR-INDUCED OSTEOMALACIA; RENAL PHOSPHATE-TRANSPORT; ABNORMAL PHEX EXPRESSION; HUMAN OSTEOBLAST CELLS; VITAMIN-D METABOLISM; IN-VIVO; SKELETAL ABNORMALITIES AB Increased expression of several osteoblastic proteases and MEPE (a bone matrix protein) occurs in X-linked hypophosphatemic rickets (hyp). This is associated with an increased release of a protease-resistant MEPE peptide (ASARM peptide), a potent inhibitor of mineralization. Cathepsin B cleaves MEPE releasing ASARM peptide and hyp osteoblast/osteocyte cells hypersecrete cathepsin D, an activator of cathepsin B. Our aims were to determine whether cathepsin inhibitors correct the mineralization defect in vivo and whether hyp-bone ASARM peptide levels are reduced after protease treatment. Normal littermates and hyp mice (n = 6) were injected intraperitoneally once a day for 4 weeks with pepstatin, CAO74 or vehicle. Animals were then sacrificed and bones plus serum removed for comprehensive analysis. All hyp mice groups (treated and untreated) remained hypophosphatemic with serum 1,25 vitamin D3 inappropriately normal. Serum PTH was significantly elevated in all hyp mice groups relative to normal mice (P = 0.0017). Untreated hyp mice had six-fold elevated levels of serum alkaline-phosphatase and two-fold elevated levels of ASARM peptides relative to normal mice (P < 0.001). In contrast, serum alkaline phosphatase and serum ASARM peptides were significantly reduced (normalized) in hyp mice treated with CA074 or pepstatin. Serum FGF23 levels remained high in all hyp animal groups (P < 0.0001). Hyp mice treated with protease inhibitors showed dramatic reductions in unmineralized osteoid (femurs) compared to control hyp mice (Goldner staining). Also, hyp animals treated with protease inhibitors showed marked and significant improvements in growth plate width (42%), osteoid thickness (40%) and cortical area (40%) (P < 0.002). The mineralization apposition rate, bone formation rate and mineralization surface were normalized by protease-treatment. High-resolution pQCT mineral histomorphometry measurements and uCT also confirmed a marked mineralization improvement. Finally, the growth plate and cortical bone of hyp femurs contained a massive accumulation of osteoblast-derived ASARM peptide(s) that was reduced in hyp animals treated with CA074 or pepstatin. This study confirms in vivo administration of cathepsin inhibitors improves bone mineralization in hyp mice. This may be due to a protease inhibitor mediated decrease in proteolytic degradation of the extracellular matrix and a reduced release of ASARM peptides (potent mineralization inhibitors). (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Kansas, Med Ctr, Dept Internal Med, Kidney Inst, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Div Nephrol, Kansas City, KS 66160 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Med & Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Periodont, San Antonio, TX 78229 USA. SkeleTech Inc, Bothell, WA 98021 USA. RP Rowe, PSN (reprint author), Univ Kansas, Med Ctr, Dept Internal Med, Kidney Inst, 3901 Rainbow Blvd,6020B Wahl Hall E, Kansas City, KS 66160 USA. EM prowe@kumc.edu FU NCRR NIH HHS [M01 RR000865, 5P20RR017708-03, MO1-RR00865, P20 RR017708]; NIAMS NIH HHS [2 RO1-AR045955-07, P30 AR058886, R0-1 AR51598-01, R0-1 DK-AR58886, R01 AR045955, R01 AR051598]; NIDCR NIH HHS [1R03DE015900-01, R03 DE015900] NR 88 TC 37 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD OCT PY 2006 VL 39 IS 4 BP 773 EP 786 DI 10.1016/j.bone.2006.04.012 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088DW UT WOS:000240792700011 PM 16762607 ER PT J AU Kurland, J Naeser, MA Doron, K Bogdan, A Baker, E Martin, P Kim, DS AF Kurland, J. Naeser, M. A. Doron, K. Bogdan, A. Baker, E. Martin, P. Kim, D. S. TI Nonverbal semantic decisions with actions in chronic, moderate-to-severe nonfluent aphasia: An fMRI investigation SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID KNOWLEDGE C1 Univ Colorado, Boulder, CO 80309 USA. Harold Goodglass Boston Univ, Aphasia Res Ctr, VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Ctr Biomed Imaging, Boston, MA 02215 USA. EM kurlandj@colorado.edu NR 5 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD OCT-NOV PY 2006 VL 99 IS 1-2 BP 191 EP 192 DI 10.1016/j.bandl.2006.06.104 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 107VK UT WOS:000242198900091 ER PT J AU Zipse, L Kearns, K Marantz, A AF Zipse, Lauryn Kearns, Kevin Marantz, Alec TI Identity priming of the m350 response: A single-trial analysis approach SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 MIT, HST SHBT, Boston, MA 02129 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02129 USA. MIT, KIT MEG Lab, Cambridge, MA 02139 USA. EM kkearns@mghihp.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD OCT-NOV PY 2006 VL 99 IS 1-2 BP 208 EP 209 DI 10.1016/j.bandl.2006.06.112 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 107VK UT WOS:000242198900099 ER PT J AU Cosenza-Nashat, MA Kim, MO Zhao, ML Suh, HS Lee, SC AF Cosenza-Nashat, Melissa A. Kim, Mee-Ohk Zhao, Meng-Liang Suh, Hyeon-Sook Lee, Sunhee C. TI CD45 isoform expression in microglia and inflammatory cells in HIV-1 encephalitis SO BRAIN PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SEVERE COMBINED IMMUNODEFICIENCY; CATALYZED REPORTER DEPOSITION; LEUKOCYTE COMMON ANTIGEN; HCK TYROSINE KINASE; CD8(+) T-CELLS; SIGNAL AMPLIFICATION; ALZHEIMERS-DISEASE; NEUROLOGICAL DISEASE; PROTEIN-KINASE AB CD45 is a membrane tyrosine phosphatase that modulates the function of the hematopoietic cells. In vitro, agonist antibodies to CD45RO or CD45RB isoforms have been shown to suppress microglial activation, but whether microglia in vivo express these isoforms in HIV encephalitis (HIVE) is unknown. Brain sections from control and HIVE were immunostained for CD45 isoforms using exon-specific antibodies (RA, RB, RC and RO). RA and RC were limited to rare lymphocytes, while RB expression was robust in microglia and inflammatory cells. RO was low in control microglia, but increased in HIVE. RO was also localized to macrophages and CD8+ T cells. Targeting CD45 in vivo with isoform-specific antibodies remains a therapeutic option for neuroinflammatory diseases. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. CUNY, BMCC, Dept Sci, New York, NY 10021 USA. RP Lee, SC (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, 1300 Morris Pk Ave,F718S, Bronx, NY 10461 USA. EM slee@aecom.yu.edu FU NIAID NIH HHS [AI051519, P30 AI051519]; NIMH NIH HHS [R24 MH059724, R01 MH055477, R01 MH55477, R24MH59724]; NINDS NIH HHS [NS 07098, T32 NS007098] NR 58 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 2006 VL 16 IS 4 BP 256 EP 265 DI 10.1111/j.1750-3639.2006.00027.x PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 106OT UT WOS:000242111100002 PM 17107594 ER PT J AU Lycette, JL Luoh, SW Beer, TM Deloughery, TG AF Lycette, Jennifer L. Luoh, Shiuh-Wen Beer, Tomasz M. Deloughery, Thomas G. TI Acute bilateral pulmonary emboli occurring while on adjuvant aromatase inhibitor therapy with anastrozole: case report and review of the literature SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE anastrozole; aromatase inhibitors; breast cancer; pulmonary embolus; venous thromboembolism ID EARLY BREAST-CANCER; HORMONE REPLACEMENT THERAPY; DEEP-VEIN THROMBOSIS; POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; RANDOMIZED-TRIAL; VENOUS THROMBOEMBOLISM; RISK-FACTORS; HEALTHY WOMEN; LETROZOLE AB Hormonal therapy is the mainstay of adjuvant treatment for women with early-stage estrogen receptor-positive breast cancer. Recently, the aromatase inhibitors have moved to the forefront of adjuvant hormonal therapy,. however, the adverse effects of these agents are not yet fully understood. It is generally accepted that tamoxifen, but not the aromatase inhibitors, is associated with an increased risk of thrombosis in women with breast cancer. Studies comparing aromatase inhibitors to tamoxifen in the adjuvant setting have reported a lower rate of venous thromboembolism with the aromatase inhibitors, yet the incidence of venous thromboembolism with these new agents is higher than that expected in the general population. Here we report a case of acute bilateral pulmonary emboli occurring while on adjuvant aromatase inhibitor therapy with anastrozole, and review the literature on the incidence of venous thromboembolism during the use of aromatase, inhibitors in the adjuvant setting. C1 Oregon Hlth Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Lycette, JL (reprint author), Oregon Hlth Sci Univ, Div Hematol & Med Oncol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM lycettej@ohsu.edu NR 41 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2006 VL 99 IS 3 BP 249 EP 255 DI 10.1007/s10549-006-9212-1 PG 7 WC Oncology SC Oncology GA 093UD UT WOS:000241194900002 PM 16752073 ER PT J AU Ingle, JN Tu, DS Pater, JL Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Shepherd, LE Pritchards, KI Livingston, RB Davidsonlo, NE Norton, L Perez, EA Abrams, JS Cameron, DA Palmer, MJ Goss, PE AF Ingle, James N. Tu, Dongsheng Pater, Joseph L. Martino, Silvana Robert, Nicholas J. Muss, Hyman B. Piccart, Martine J. Castiglione, Monica Shepherd, Lois E. Pritchards, Kathleen I. Livingston, Robert B. Davidsonlo, Nancy E. Norton, Larry Perez, Edith A. Abrams, Jeffrey S. Cameron, David A. Palmer, Michael J. Goss, Paul E. TI Duration of letrozole treatment and outcomes in the placebo-controlled NCICCTG MA.17 extended adjuvant therapy trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE adjuvant hormonal therapy; early breast cancer ID BREAST-CANCER; RANDOMIZED-TRIAL; UPDATED FINDINGS; TAMOXIFEN AB Purpose. MA. 17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes. Methods. The final MA. 17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS),. distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate. Results. Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole. with the trend being significant (p < 0.0001 and p = 0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p = 0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p = 0.027) whereas the HRs for DDFS and OS showed no significant change over time. Conclusion. These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting. C1 Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. Angeles Clin & Res Inst, Santa Monica, CA USA. Inova Fairfax Hosp, Falls Church, VA USA. Univ Vermont, Burlington, VT USA. Inst Jules Bordet, B-1000 Brussels, Belgium. IBCSG Coordinating Ctr, Bern, Switzerland. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Univ Washington, Seattle, WA 98195 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Jacksonville, FL 32224 USA. NCI, Clin Invest Branch, Rockville, MD USA. Western Gen Hosp, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ingle, JN (reprint author), Mayo Clin, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM ingle.james@mayo.edu OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA25224, CA21115, CA31946, CA32102, CA38926] NR 8 TC 61 Z9 65 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2006 VL 99 IS 3 BP 295 EP 300 DI 10.1007/s10549-006-9207-y PG 6 WC Oncology SC Oncology GA 093UD UT WOS:000241194900007 PM 16541302 ER PT J AU Raje, N Kumar, S Hideshima, T Ishitsuka, K Yasui, H Chhetri, S Vallet, S Vonescu, E Shiraishi, N Kiziltepe, T Elford, HL Munshi, NC Anderson, KC AF Raje, N. Kumar, S. Hideshima, T. Ishitsuka, K. Yasui, H. Chhetri, S. Vallet, S. Vonescu, E. Shiraishi, N. Kiziltepe, T. Elford, H. L. Munshi, N. C. Anderson, K. C. TI Didox, a ribonucleotide reductase inhibitor, induces apoptosis and inhibits DNA repair in multiple myeloma cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE DNA synthesis; myeloma; apoptosis; ribonucleotide reductase inhibitors ID NF-KAPPA-B; GROWTH-FACTOR; DRUG-RESISTANCE; COMBINATION; ACTIVATION; TRIMIDOX; BORTEZOMIB; ADHESION; DISEASE; IDENTIFICATION AB Ribonucleotide reductase (RR) is the enzyme that catalyses the rate-limiting step in DNA synthesis, the production of deoxynucleotides. RR activity is markedly elevated in tumour tissue and is crucial for cell division. It is therefore an excellent target for cancer chemotherapy. This study examined the anti-myeloma activity of Didox (3,4-Dihydroxybenzohydroxamic acid), a novel RR inhibitor (RRI). Our data showed that Didox induced caspase-dependent multiple myeloma (MM) cell apoptosis. Didox, unlike other RRIs that mainly target the pyrimidine metabolism pathway, targets both purine and pyrimidine metabolism pathways in MM, as demonstrated by transcriptional profiling using the Affymetrix U133A 2.0 gene chip. Specifically, a >= 2-fold downregulation of genes in these anabolic pathways was shown as early as 12 h after exposure to Didox. Furthermore, apoptosis was accompanied by downregulation of bcl family proteins including bcl-2, bcl(xl), and XIAP. Importantly, RR M1 component transcript was also downregulated, associated with decreased protein expression. Genes involved in DNA repair mechanisms, specifically RAD 51 homologue, were also downregulated. As Didox acts on MM cells by inhibiting DNA synthesis and repair, combination studies with melphalan, an agent commonly used in MM, were performed. A strong in vitro synergism was shown, with combination indices of < 0.7 as determined by the Chou-Talalay method. These studies therefore provide the preclinical rationale for evaluation of Didox, alone and in combination with DNA-damaging agents, to improve patient outcome in MM. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02114 USA. Mayo Clin, Div Hematol, Rochester, MN USA. Mol Hlth Inc, Richmond, VA USA. RP Raje, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cox 813,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 FU NCI NIH HHS [IP50 CA10070-01, R0-1 CA 50947]; PHS HHS [P0-1 78378] NR 49 TC 11 Z9 11 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2006 VL 135 IS 1 BP 52 EP 61 DI 10.1111/j.1365-2141.2006.06261.x PG 10 WC Hematology SC Hematology GA 080ZV UT WOS:000240287900006 PM 16925573 ER PT J AU Gazda, HT Sieff, CA AF Gazda, Hanna T. Sieff, Colin A. TI Recent insights into the pathogenesis of Diamond-Blackfan anaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE Diamond-Blackfan anaemia; erythropoiesis; RPS19; ribosomal protein; ribosomal RNA processing ID RIBOSOMAL-PROTEIN S19; CONGENITAL HYPOPLASTIC-ANEMIA; IN-VITRO RESPONSE; GENETIC-HETEROGENEITY; ERYTHROID PROGENITORS; WILLIAMS-SYNDROME; MAMMALIAN-CELLS; RAT-LIVER; MUTATIONS; EXPRESSION AB Diamond-Blackfan anaemia (DBA) is a congenital anaemia and broad developmental disease that develops soon after birth. The anaemia is due to failure of erythropoiesis, with normal platelet and myeloid lineages, and it can be managed with steroids, blood transfusions, or stem cell transplantation. Normal erythropoiesis after transplantation shows that the defect is intrinsic to an erythroid precursor. DBA is inherited in about 10-20% of cases, and genetic studies have identified mutations in a ribosomal protein gene, RPS19, in 25% of cases; there is evidence for involvement of at least two other genes. In yeast, RPS19 deletion leads to a block in ribosomal RNA biogenesis. The critical question is how mutations in RPS19 lead to the failure of proliferation and differentiation of erythroid progenitors. While this question has not yet been answered, understanding the biology of DBA may provide insight not only into the defect in erythropoisis, but also into the other developmental abnormalities that are present in about 40% of patients, and into the cancer predisposition that is inherent to DBA. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Program Genom, Boston, MA 02115 USA. Childrens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sieff, CA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM sieff@wi.mit.edu NR 77 TC 33 Z9 35 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2006 VL 135 IS 2 BP 149 EP 157 DI 10.1111/j.1365-2141.2006.06268.x PG 9 WC Hematology SC Hematology GA 084WZ UT WOS:000240566400001 PM 16942586 ER PT J AU Barlogie, B Tricot, GJ van Rhee, F Angtuaco, E Walker, R Epstein, J Shaughnessy, JD Jagannath, S Bolejack, V Gurley, J Hoering, A Vesole, D Desikan, R Siegel, D Mehta, J Singhal, S Munshi, NC Dhodapkar, M Jenkins, B Attal, M Harousseau, JL Crowley, J AF Barlogie, Bart Tricot, Guido J. van Rhee, Frits Angtuaco, Edguardo Walker, Ron Epstein, Joshua Shaughnessy, John D. Jagannath, Sundar Bolejack, Vanessa Gurley, Jennifer Hoering, Antje Vesole, David Desikan, Raman Siegel, David Mehta, Jayesh Singhal, Seema Munshi, Nikhil C. Dhodapkar, Madhav Jenkins, Bonnie Attal, Michel Harousseau, Jean-Luc Crowley, John TI Long-term outcome results of the first tandem autotransplant trial for multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myeloma; high-dose melphalan; prognosis ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CHEMORADIOTHERAPY; AUTOLOGOUS TRANSPLANTATION; COMBINATION CHEMOTHERAPY; MELPHALAN; THALIDOMIDE; ABNORMALITIES; CHROMOSOME-13; THERAPY AB Total Therapy 1, the first tandem autotransplant trial for newly diagnosed patients with multiple myeloma, was designed to increase the frequency of complete response (CR) and thereby extend survival. With a median follow-up of 12 years, 62 of 231 initially enrolled patients are alive (17% at 15 years); 31 remain event free (7% at 15 years) including 16 of 94 (41%) that initially achieved CR. Currently alive patients less frequently had cytogenetic abnormalities (CAs) at baseline (P = 0.002), postenrolment (P < 0.001) and at relapse (P = 0.004); elevations of serum C-reactive protein (CRP) (P = 0.003) and lactate dehydrogenase (P = 0.029), anaemia (P = 0.029) and they more often completed two transplants within 12 months (P = 0.019). Postenrolment overall survival (OS) and event-free survival (EFS) were superior in the absence of CA of the hypodiploidy or deletion 13 variety (P < 0.001 and 0.037 respectively) and in the presence of low CRP at baseline (P = 0.001 and 0.017 respectively). Postrelapse survival was longer in the absence of CA at relapse (P < 0.001), IgA isotype (P = 0.002), International Staging System stage 3 (P = 0.014), and when patients had two protocol transplants prior to relapse (P = 0.038). Ten-year EFS and OS could be accomplished in 15% and 33% of patients, respectively, when all agents available in 1989, especially high-dose melphalan, were applied together upfront for the management of myeloma. C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Canc Res & Biostat, Seattle, WA USA. Arkansas Oncol Assoc, Little Rock, AR USA. Hackensack Univ, Ctr Med, Hackensack, NJ USA. Northwestern Univ, Myeloma Program, Chicago, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rockefeller Univ, New York, NY 10021 USA. Hop Purpan, Toulouse, France. CHU Hotel Dieu, Hematol Clin, Nantes, France. RP Barlogie, B (reprint author), 4301 W Markham,816, Little Rock, AR 72205 USA. EM BarlogieBart@uams.edu FU NCI NIH HHS [CA55819] NR 28 TC 106 Z9 110 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2006 VL 135 IS 2 BP 158 EP 164 DI 10.1111/j.1365-2141.2006.06271.x PG 7 WC Hematology SC Hematology GA 084WZ UT WOS:000240566400002 PM 16939489 ER PT J AU Appelbaum, FR Kopecky, KJ Tallman, MS Slovak, ML Gundacker, HM Kim, HT Dewald, GW Kantarjian, HM Pierce, SR Estey, EH AF Appelbaum, Frederick R. Kopecky, Kenneth J. Tallman, Martin S. Slovak, Marilyn L. Gundacker, Holly M. Kim, Haesook T. Dewald, Gordon W. Kantarjian, Hagop M. Pierce, Sherry R. Estey, Elihu H. TI The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE acute myeloid leukaemia; core binding factor leukaemia; cytogenetics of leukaemia; leukaemia treatment; adult leukaemia ID COOPERATIVE-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; HIGH-DOSE CYTARABINE; FRENCH AML INTERGROUP; INDUCTION CHEMOTHERAPY; REPETITIVE CYCLES; PROGNOSTIC FACTOR; 1ST REMISSION; GROUP-B; TRIAL AB To better understand the spectrum of adult acute myeloid leukaemia (AML) associated with core binding factor (CBF) translocations, 370 patients with newly diagnosed CBF-associated AML were analysed. Patients' age ranged from 16-83 years (median 39 years) with a slight male predominance (55%); 53% had inv(16); 47% had t(8;21). Patients with t(8;21) tended to be younger (P = 0.056), have lower peripheral blood white cell counts (P < 0.0001) and were more likely to have additional cytogenetic abnormalities (P < 0.0001). Loss of sex chromosome, del(9q) and complex abnormalities were more common among patients with t(8;21), while +22 and +21 were more common with inv(16). Overall, 87% [95% confidence interval (CI) 83-90%] of patients achieved complete response (CR) with no difference between t(8;21) and inv(16); however, the CR rate was lower in older patients due to increased resistant disease and early deaths. Ten-year overall survival (OS) was 44% (95% CI 39-50%) and, in multivariate analysis, was shorter with increasing age (P < 0.0001), increased peripheral blast percentage (P = 0.0006), in patients with complex cytogenetic abnormalities in addition to the CBF translocation (P = 0.021), and in patients with t(8;21) (P = 0.025). OS was superior in patients who received regimens with high-dose cytarabine, a combination of fludarabine and intermediate-dose cytarabine, or haematopoietic cell transplantation. C1 SW Oncol Grp, Ctr Stat, Seattle, WA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Appelbaum, FR (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-310,POB 19024, Seattle, WA 98109 USA. EM fappelb@fhcrc.org FU NCI NIH HHS [CA21115, CA23318, CA17145, CA32102, CA38926, CA66636] NR 32 TC 110 Z9 118 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2006 VL 135 IS 2 BP 165 EP 173 DI 10.1111/j.1365-2141.2006.06276.x PG 9 WC Hematology SC Hematology GA 084WZ UT WOS:000240566400003 PM 16939487 ER PT J AU Panek, J Karcz, D Pieton, R Zasada, J Tusinski, M Dolecki, M Winiarski, M AF Panek, Jozefa Karcz, Danuta Pieton, Richard Zasada, Jakub Tusinski, Marcin Dolecki, Miroslaw Winiarski, Marek TI Blood serum levels of proinflammatory cytokines in patients with different degrees of biliary pancreatitis SO CANADIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE acute biliary pancreatitis; interleukins ID CLASSIFICATION-SYSTEM; ORGAN DYSFUNCTION; INTERLEUKIN-6; SEVERITY AB BACKGROUND: Proinflammatory cytokines play a fundamental role in the local and systemic inflammatory responses in the initial stages of acute biliary pancreatitis (ABP) and in the development of severe forms of the disease. OBJECTIVES: The aim of the present study was to assess the systemic release of proinflammatory cytokines and to characterize differences between patients with mild ABP (MABP) and severe ABP (SABP) PATIENTS AND METHODS: In the current study, 54 patients with MABP were compared with 14 patients with SABP. Serum levels of turnout necrosis)actor-alpha, interleukin (IL)-1 beta, IL-6, IL-8 and IL-12p40 were measured every second day after admission for one week. RESULTS: The turnout necrosis factor-alpha level was similar in all days of analysis in patients with MABP but was lower compared with SABP patients. The level of IL-1 beta was higher at admission in patients with MABP. The level of IL-6 peaked on admission day in both groups, but in patients with SABP, the obtained values were higher. The level of IL-8 on admission day was slightly higher in patients with MABP and systematically decreased when measured on the following days (the third, fifth and seventh days of the study). An increased level of IL-8 during the third, fifth and seventh days of the investigation was seen in SABP patients. The level of IL-12p40 was slightly higher in patients with MABP on the day of admission. CONCLUSIONS: The levels of some proinflammatory cytokines are higher in patients with SABP than in patients with MABP. The most consistent difference between the two groups was that the levels of IL-6 were significantly higher in patients with SABP throughout the study. Serum concentration of IL-6 may be helpful as a marker of severity and outcome of ABP. C1 Jagiellonian Univ, Coll Med, Dept Surg 2, PL-31501 Krakow, Poland. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Panek, J (reprint author), Jagiellonian Univ, Coll Med, Dept Surg 2, Ul Kopernika 21, PL-31501 Krakow, Poland. EM mspanek@cyf-kr.edu.pl NR 23 TC 10 Z9 14 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0835-7900 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. PD OCT PY 2006 VL 20 IS 10 BP 645 EP 648 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 097IP UT WOS:000241441000006 PM 17066155 ER PT J AU Papakostas, GI Fava, M AF Papakostas, George I. Fava, Maurizio TI A metaanalysis of clinical trials comparing moclobemide with selective serotonin reuptake inhibitors for the treatment of major depressive disorder SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Review DE moclobemide; selective serotonin reuptake inhibitor; monoamine oxidase inhibitor; major depressive disorder ID DOUBLE-BLIND TRIAL; RATING-SCALE; ATYPICAL DEPRESSION; GENERAL-PRACTICE; FLUOXETINE; MULTICENTER; CITALOPRAM; EFFICACY; ESCITALOPRAM; OUTPATIENTS AB Objective: To compare response rates among patients with major depressive disorder (MDD) treated with either moclobemide, an antidepressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or selective serotonin reuptake inhibitors (SSRIs). Methods: Using a random-effects model, we combined 12 trials involving 1207 outpatients with MDD. Results: Patients treated with moclobemide were as likely to experience clinical response as those treated with SSRIs (risk ratio 1.08; 95% confidence interval, 0.92 to 1.26; P = 0.314). Simply pooling response rates for the 2 agents resulted in a 62.1% response rate for moclobemide and a 57.5% response rate for the SSRIs. A metaregression did not reveal a statistically significant relation between the mean moclobemide dosage for each study and the risk ratio for response rates. Further, we found no difference between the 2 treatments in overall discontinuation rates, discontinuation rates due to adverse events, or discontinuation rates due to lack of efficacy. Also, rates of fatigue or somnolence and of insomnia were similar between the 2 treatment groups. However, SSRI treatment was associated with higher rates of nausea, headaches, and treatment-emergent anxiety than was treatment with moclobemide. Conclusions: These results suggest that moclobemide and the SSRIs do differ with respect to their side effect profiles but not in their overall efficacy in the treatment of MDD. C1 Harvard Univ, Dept Psychiat, Depress Clin & Res Program, Med Sch,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Dept Psychiat, Depress Clin & Res Program, Med Sch,Massachusetts Gen Hosp, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 41 TC 26 Z9 26 U1 1 U2 6 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD OCT PY 2006 VL 51 IS 12 BP 783 EP 790 PG 8 WC Psychiatry SC Psychiatry GA 105CQ UT WOS:000242007300008 PM 17168253 ER PT J AU Horwitz, EM Levy, LB Thames, HD Kupelian, PA Martinez, AA Michalski, JM Pisansky, TM Sandler, HM Shipley, WU Zelefsky, MJ Zietman, AL Kuban, DA AF Horwitz, Eric M. Levy, Lawrence B. Thames, Howard D. Kupelian, Patrick A. Martinez, Alvaro A. Michalski, Jeffrey M. Pisansky, Thomas M. Sandler, Howard M. Shipley, William U. Zelefsky, Michael J. Zietman, Anthony L. Kuban, Deborah A. TI Biochemical and clinical significance of the posttreatment prostate-specific antigen bounce for prostate cancer patients treated with external beam radiation therapy alone - A multiinstitutional pooled analysis SO CANCER LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE prostatic neoplasms; prostate-specific antigen; PSA bounce; radiation therapy; biochemical control ID SEED IMPLANTATION; BRACHYTHERAPY; RADIOTHERAPY; DEFINITIONS; FAILURE AB BACKGROUND. The posttreatment prostate-specific antigen (PSA) bounce phenomenon has been recognized in at least 20% of all patients treated with radiation. The purpose of the current report was to determine if there was a difference in biochemical and clinical control between the bounce and nonbounce (NB) patients using pooled data on 4839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions between 1986 and 1995. METHODS. The median follow-up was 6.3 years. A posttreatment PSA bounce was defined by a minimal rise of 0.4 ng/mL over a 6-month follow-up period, followed by a drop in PSA level of any magnitude. Endpoints included no biochemical evidence of disease (bNED) failure (BF) (ASTRO definition), distant failure (DF), cause-specific failure (CSF), and overall survival (OS). Patients were stratified by pretreatment PSA, Gleason score, T stage, age, dose, and risk group. RESULTS. In all, 978 (20%) patients experienced at least 1 posttreatment PSA bounce. Within 3 subgroups (risk group, pretreatment PSA, and age), statistically significant differences of remaining bounce-free were observed on univariate analysis. Patients < 70 years had a 72% chance of remaining bounce-free at 5 years compared with 75% for older patients (P = .04). The NB patients had 72% bNED control at 10 years compared with 58% for the bounce patients. The effect of a bounce remained statistically significant on multivariate analysis (P < .0001). No statistically significant difference in DE CSF, or OS was observed. CONCLUSIONS. Patients treated with external beam radiation therapy alone who experience a posttreatment PSA bounce have increased risk of BE However, this did not translate into a difference in clinical failure with the available follow-up in the current study. C1 Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI USA. Mallinckrodt Inst Radiol, Dept Radiat Oncol, 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. Univ Texas, MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. RP Horwitz, EM (reprint author), Fox Chase Canc Ctr, Dept Radiat Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM eric.horwitz@fccc.edu NR 14 TC 39 Z9 40 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 2006 VL 107 IS 7 BP 1496 EP 1502 DI 10.1002/cncr.22183 PG 7 WC Oncology SC Oncology GA 089VL UT WOS:000240909400011 PM 16944536 ER PT J AU Miller, DR Asomaning, K Liu, G Wain, JC Lynch, TJ Neuberg, D Su, L Christiani, DC AF Miller, David R. Asomaning, Kofi Liu, Geoffrey Wain, John C. Lynch, Thomas J. Neuberg, Donna Su, Li Christiani, David C. TI An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma SO CANCER LA English DT Article DE GSTP1; early age onset lung carcinoma; case control; logistic regression; interaction ID MICROSOMAL EPOXIDE HYDROLASE; CANCER-RISK; AFRICAN-AMERICANS; TOBACCO-SMOKE; DNA-DAMAGE; SUSCEPTIBILITY; CYP1A1; POPULATION; GENOTYPES; GSTM1 AB BACKGROUND. Among the genes that encode the glutathione S-transferase (GST) superfamily of Phase 2 metabolizing enzymes, GSTP1 has the highest expression in the lung. The polymorphic GSTP1 gene encodes glutathione S-transferase pi, which is an enzyme that detoxifies cigarette carcinogens, such as benzo-[a]-pyrene. The variant GSTP1 GG genotype is associated with lower enzymatic activity and higher DNA adduct levels in human lymphocytes compared with the AA genotype. METHODS. The authors evaluated the association of GSTP1 genotypes with lung cancer in 1921 cases. and 1343 controls of Caucasian descent by using polymerase chain reaction-restriction fragment length polymorphism techniques. The results were analyzed with multiple logistic regression adjusting for age, gender, smoking status, and pack-years. To investigate specifically the subset of younger lung cancer patients and controls, the effect of age (either as a dichotomous or continuous variable in separate models) was analyzed as a modifying factor of the association between the GSTP1 polymorphism and lung cancer. RESULTS. The GSTP1 GG genotype was not associated with an overall increased risk of lung cancer (adjusted odds ratio, 1.02; 95% confidence interval [95% CI], 0.78-1.34) compared with the GSTP1 AA genotype. In both models that evaluated the gene-age interaction, an overall statistically significant interaction (P <.01) was observed between age and the GG genotype. However, for the model that included age as a dichotomous variable, the odds ratio of lung cancer risk with the GG genotype compared with the AA among individuals age <= 50 years was 2.67 (95% CI, 1.36-5.22); in older individuals, the risk was 0.87 (95% CI, 0.65-1.2). CONCLUSIONS. The GSTP1 GG genotype was associated with increased lung cancer susceptibility among younger study participants. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Oncol Unit, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulmonary & Crit Care Unit, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA 74386, ES/CA06409]; NIEHS NIH HHS [ES00002] NR 39 TC 22 Z9 24 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 2006 VL 107 IS 7 BP 1570 EP 1577 DI 10.1002/cncr.22124 PG 8 WC Oncology SC Oncology GA 089VL UT WOS:000240909400020 PM 16933328 ER PT J AU Hieronymus, H Lamb, J Ross, KN Peng, XP Clement, C Rodina, A Nieto, M Du, JY Stegmaier, K Raj, SM Maloney, KN Clardy, J Hahn, WC Chiosis, G Golub, TR AF Hieronymus, Haley Lamb, Justin Ross, Kenneth N. Peng, Xiao P. Clement, Cristina Rodina, Anna Nieto, Maria Du, Jinyan Stegmaier, Kimberly Raj, Srilakshmi M. Maloney, Katherine N. Clardy, Jon Hahn, William C. Chiosis, Gabriela Golub, Todd R. TI Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators SO CANCER CELL LA English DT Article ID MOLECULAR CHAPERONE HSP90; ANDROGEN RECEPTOR GENE; HUMAN PROSTATE-CANCER; ANTIMALARIAL ACTIVITY; RESPONSIVE GENES; HORMONAL-THERAPY; TUMOR-CELLS; INHIBITORS; PROTEIN; HEAT-SHOCK-PROTEIN-90 AB Although androgen receptor (AR)-mediated signaling is central to prostate cancer, the ability to modulate AIR signaling states is limited. Here we establish a chemical genomic approach for discovery and target prediction of modulators of cancer phenotypes, as exemplified by AIR signaling. We first identify AIR activation inhibitors, including a group of structurally related compounds comprising celastrol, gedunin, and derivatives. To develop an in silico approach for target pathway identification, we apply a gene expression-based analysis that classifies HSP90 inhibitors as having similar activity to celastrol and gedunin. Validating this prediction, we demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR. Broadly, this work identifies new modes of HSP90 modulation through a gene expression-based strategy. C1 Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Chem, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Golub, TR (reprint author), Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. EM golub@broad.harvard.edu NR 47 TC 271 Z9 281 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD OCT PY 2006 VL 10 IS 4 BP 321 EP 330 DI 10.1016/j.ccr.2006.09.005 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 101BR UT WOS:000241714400008 PM 17010675 ER PT J AU Wei, G Twomey, D Lamb, J Schlis, K Agarwal, J Stam, RW Opferman, JT Sallan, SE den Boer, ML Pieters, R Golub, TR Armstrong, SA AF Wei, Guo Twomey, David Lamb, Justin Schlis, Krysta Agarwal, Jyoti Stam, Ronald W. Opferman, Joseph T. Sallan, Stephen E. den Boer, Monique L. Pieters, Rob Golub, Todd R. Armstrong, Scott A. TI Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance SO CANCER CELL LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CELLULAR-DRUG RESISTANCE; HEMATOPOIETIC STEM-CELLS; INHIBITS MULTIPLE FORMS; BH3-ONLY PROTEINS PUMA; BCL-2 FAMILY-MEMBERS; INDUCED APOPTOSIS; TRANSGENIC MICE; BREAST-CANCER; SURVIVAL AB Drug resistance remains a major obstacle to successful cancer treatment. A database of drug-associated gene expression profiles was screened for molecules whose profile overlapped with a gene expression signature of glucocorticoid (GC) sensitivity/resistance in acute lymphoblastic leukemia (ALL) cells. The screen indicated that the mTOR inhibitor rapamycin profile matched the signature of GC sensitivity. We tested the hypothesis that rapamycin would induce GC sensitivity in lymphoid malignancy cells and found that it sensitized to GC-induced apoptosis via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an important regulator of GC-induced apoptosis and that the combination of rapamycin and glucocorticoids has potential utility in lymphoid malignancies. Furthermore, this approach represents a strategy for identification of promising combination therapies for cancer. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Erasmus Univ, Sophia Childrens Hosp, Med Ctr, Div Pediat Hematol Oncol, NL-3015 GE Rotterdam, Netherlands. St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM scott.armstrong@childrens.harvard.edu FU NCI NIH HHS [K08 CA92551, P01 CA068484] NR 61 TC 268 Z9 279 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD OCT PY 2006 VL 10 IS 4 BP 331 EP 342 DI 10.1016/j.ccr.2006.09.006 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 101BR UT WOS:000241714400009 PM 17010674 ER PT J AU Haile, RW Thomas, DC McGuire, V Felberg, A John, EM Milne, RL Hopper, JL Jenkins, MA Levine, AJ Daly, MM Buys, SS Senie, RT Andrulis, IL Knight, JA Godwin, AK Southey, M McCredie, MRE Giles, GG Andrews, L Tucker, K Miron, A Apicella, C Tesoriero, A Bane, A Pike, MC Whittemore, AS AF Haile, Robert W. Thomas, Duncan C. McGuire, Valerie Felberg, Anna John, Esther M. Milne, Roger L. Hopper, John L. Jenkins, Mark A. Levine, A. Joan Daly, Mary M. Buys, Saundra S. Senie, Ruby T. Andrulis, Irene L. Knight, Julia A. Godwin, Andrew K. Southey, Melissa McCredie, Margaret R. E. Giles, Graham G. Andrews, Lesley Tucker, Katherine Miron, Alexander Apicella, Carmel Tesoriero, Andrea Bane, Anita Pike, Malcolm C. Whittemore, Alice S. CA kConFab Investigators Ontario Canc Genetics Network Inve TI BRCA1 and BRCA2 mutation carriers, oral contraceptive use, and breast cancer before age 50 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID OVARIAN-CANCER; RISK; WOMEN; GENE; NONCARRIERS; EPIDEMIOLOGY; REGISTRY; HISTORY; PCR AB Background: Understanding the effect of oral contraceptives on risk of breast cancer in BRCA1 or BRCA2 mutation carriers is important because oral contraceptive use is a common, modifiable practice. Methods: We studied 497 BRCA1 and 307 BRCA2 mutation carriers, of whom 195 and 128, respectively, had been diagnosed with breast cancer. Case-control analyses were conducted using unconditional logistic regression with adjustments for family history and familial relationships and were restricted to subjects with a reference age under 50 years. Results: For BRCA1 mutation carriers, there was no significant association between risk of breast cancer and use of oral contraceptives for at least 1 year [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.53-1.12] or duration of oral contraceptive use (P-trend = 0.62). For BRCA2 mutation carriers, there was no association with use of oral contraceptives for at least 1 year (OR, 1.62; 95% CI, 0.90-2.92); however, there was an association of elevated risk with oral contraceptive use for at least 5 years (OR, 2.06; 95% CI, 1.08-3.94) and with duration of use (ORtrend per year of use, 1.08; P = 0.008). Similar results were obtained when we considered only use of oral contraceptives that first started in 1975 or later. Conclusions: We found no evidence overall that use of oral contraceptives for at least 1 year is associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers before age 50. For BRCA2 mutation carriers, use of oral contraceptives may be associated with an increased risk of breast cancer among women who use them for at least 5 years. Further studies reporting results separately for BRCA1 and BRCA2 mutation carriers are needed to resolve this important issue. C1 Univ So Calif, Dept Prevent Med, Calif Keck Sch Med, Los Angeles, CA 90089 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. No Calif Canc Ctr, Fremont, CA USA. Early Detect Lab, Melbourne, Vic, Australia. Univ Melbourne, Melbourne, Vic, Australia. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Utah, Dept Hematol Oncol, Salt Lake City, UT USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Mt Sinai Hosp, Canc Care Ontario, Toronto, ON M5G 1X5, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Otago, Dunedin, New Zealand. Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia. Prince Wales Univ, Hereditary Canc Clin, Sydney, NSW, Australia. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. RP Haile, RW (reprint author), Univ So Calif, Dept Prevent Med, Calif Keck Sch Med, 1441 Eastlake Ave,MS 9175, Los Angeles, CA 90089 USA. EM haile@usc.edu RI Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013; Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Giles, Graham/0000-0003-4946-9099 FU NCI NIH HHS [CA-95-003, U01 CA069417, U01 CA069417-10] NR 26 TC 58 Z9 60 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2006 VL 15 IS 10 BP 1863 EP 1870 DI 10.1158/1055-9965.EPI-06-0258 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800019 PM 17021353 ER PT J AU Levy, AG Shea, J Williams, SV Quistberg, A Armstrong, K AF Levy, Andrea Gurmankin Shea, Judy Williams, Sankey V. Quistberg, Alex Armstrong, Katrina TI Measuring perceptions of breast cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SMOKING CESSATION PROGRAM; SELF-PROTECTIVE BEHAVIOR; RANDOMIZED TRIAL; FIELD EXPERIMENT; FAMILY-HISTORY; PROBABILITY; WOMEN; MAMMOGRAPHY; SUSCEPTIBILITY; MOOD AB Background: Accurate measurement of people's risk perceptions is important for numerous bodies of research and in clinical practice, but there is no consensus about the best measure. Objective: This study evaluated three measures of women's breast cancer risk perception by assessing their psychometric and test characteristics. Design: A cross-sectional mailed survey to women from a primary care population asked participants to rate their chance of developing breast cancer in their lifetime on a 0% to 100% numerical scale and a verbal scale with five descriptive categories, and to compare their risk to others (seven categories). Six hundred three of 956 women returned the survey (63.1%), and we analyzed surveys from the 566 women without a self-reported personal history of breast or ovarian cancer. Results: Scores on the numeric, verbal, and comparative measures were correlated with each other (r > 0.50), worry (r > 0.51), the Gail estimate (r > 0.26), and family history (r > 0.25). The numerical scale had the strongest correlation with annual mammogram (r = 0.19), and its correlation with the Gail estimate was unassociated with participants' sociodemographics. The numerical and comparative measures had the highest sensitivity (0.89-0.90) and specificity (0.99) for identifying women with very high risk perception. The numerical and comparative scale also did well in identifying women with very low risk perception, although the numerical scale had the highest specificity (0.96), whereas the comparative scale had the highest sensitivity (0.89). Conclusion: Different measures of women's perceptions about breast cancer risk have different strengths and weaknesses. Although the numerical measure did best overall, the optimal measure depends on the goals of the measure (i.e., avoidance of false positives or false negatives). C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Levy, AG (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,Smith 253, Boston, MA 02115 USA. EM andrea_gurmankin@dfci.harvard.edu RI Quistberg, D Alex/C-7953-2009 OI Quistberg, D Alex/0000-0001-9730-2686 NR 51 TC 24 Z9 24 U1 4 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2006 VL 15 IS 10 BP 1893 EP 1898 DI 10.1158/1055-9965.EPI-05-0482 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800023 ER PT J AU Cheng, I Penney, KL Stram, DO Le Marchand, L Giorgi, E Haiman, CA Kolonel, LN Pike, M Hirschhorn, J Henderson, BE Freedman, ML AF Cheng, Iona Penney, Kathryn L. Stram, Daniel O. Le Marchand, Loic Giorgi, Elena Haiman, Christopher A. Kolonel, Laurence N. Pike, Malcolm Hirschhorn, Joel Henderson, Brian E. Freedman, Matthew L. TI Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast cancer risk: The multiethnic cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FACTOR-BINDING PROTEIN-3; GROWTH-FACTOR-I; GENETIC-VARIATION; CIRCULATING LEVELS; SERUM-LEVELS; LOS-ANGELES; POLYMORPHISMS; IGF1; HAWAII; SAMPLE AB Collective evidence suggests that the insulin-like growth factor (IGF) system plays a role in prostate and breast cancer risk. IGF-binding proteins (IGFBP) are the principal regulatory molecules that modulate IGF-I bioavailability in the circulation and tissues. To examine whether inherited differences in the IGFBP1 and IGFBP3 genes influence prostate and breast cancer susceptibility, we conducted two large population-based association studies of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites. To thoroughly assess the genetic variation across the two loci, we (a) sequenced the IGFBP1 and IGFBP3 exons in 95 aggressive prostate and 95 advanced breast cancer cases to ensure that we had identified all common missense variants and (b) characterized the linkage disequilibrium patterns and common haplotypes by genotyping 36 single nucleotide polymorphisms (SNP) spanning 71 kb across the loci (similar to 20 kb upstream and similar to 40 kb downstream, respectively) in a panel of 349 control subjects of the five racial/ethnic groups. No new missense SNPs were found. We identified three regions of strong linkage disequilibrium and selected a subset of 23 tagging SNPs that could accurately predict both the common IGFBP1 and IGFBP3 haplotypes and the remaining 13 SNPs. We tested the association between IGFBP1 and IGFBP3 genotypes and haplotypes for their associations with prostate and breast cancer risk in two large case-control studies nested within the Multiethnic Cohort [prostate cases/controls = 2,320/2,290; breast cases (largely postmenopausal)/controls = 1,615/1,962]. We observed no strong associations between IGFBP1 and IGFBP3 genotypes or haplotypes with either prostate or breast cancer risk. Our results suggest that common genetic variation in the IGFBP1 and IGFBP3 genes do not substantially influence prostate and breast cancer susceptibility. C1 Dana Farber Canc Inst, Program Med & Populat Genet, Dept Pediat, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Human Genet, San Francisco, CA 94143 USA. Harvard Univ, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. Univ So Calif, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Hawaii, Canc Epidemiol Program, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Program Med & Populat Genet, Dept Pediat, Boston, MA 02115 USA. EM freedman@broad.mit.edu FU NCI NIH HHS [CA 54281, CA 63464] NR 26 TC 34 Z9 34 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 OCT PY 2006 VL 15 IS 10 BP 1993 EP 1997 DI 10.1158/1055-9965.EPI-06-0361 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800038 PM 17035411 ER PT J AU Takahashi, C Ewen, ME AF Takahashi, Chiaki Ewen, Mark E. TI Genetic interaction between Rb and N-ras: Differentiation control and metastasis SO CANCER RESEARCH LA English DT Review ID ONCOGENE INDUCES DIFFERENTIATION; RETINOBLASTOMA PROTEIN; ADIPOCYTE DIFFERENTIATION; RHO-GTPASES; K-RAS; TUMOR; ACTIVATION; CANCER; MOUSE; CELLS AB The retinoblastoma tumor suppressor gene, Rb, and the ras proto-oncogenes regulate various cellular processes, including differentiation and proliferation. Rb and ras genetically interact to positively influence differentiation in the mouse. This genetic interaction between Rb and ras also affects tumor development, either positively or negatively depending on cell type. Loss of one or two N-ras alleles allows medullary thyroid (C cell) adenomas occurring in Rb heterozygous mice to progress to metastatic carcinomas, an event associated with C cells displaying a less-differentiated phenotype. Here, we discuss the genetic interaction between Rb and ras and the development of a mouse model of medullary thyroid carcinoma. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, 21st Century Ctr, Excellence Program,Dept Mol Oncol, Kyoto, Japan. RP Ewen, ME (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM mark_ewen@dfci.harvard.edu FU NCI NIH HHS [R01 CA065842] NR 35 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2006 VL 66 IS 19 BP 9345 EP 9348 DI 10.1158/0008-5472.CAN-06-1250 PG 4 WC Oncology SC Oncology GA 091GE UT WOS:000241014200001 PM 17018584 ER PT J AU DeYoung, MP Johannessen, CM Leong, CO Faquin, W Rocco, JW Ellisen, LW AF DeYoung, Maurice Phillip Johannessen, Cory M. Leong, Chee-Onn Faquin, William Rocco, James W. Ellisen, Leif W. TI Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma SO CANCER RESEARCH LA English DT Article ID P53 HOMOLOG; DIFFERENTIATION; SUPPRESSION; EXPRESSION; APOPTOSIS; SURVIVAL; PROGRAM; HEAD; LIMB AB p63 is essential for normal epithelial development and is overexpressed in the vast majority of squamous cell carcinomas (SCC). Recent work had shown that ANp63eL is essential for survival of SCC cells, raising the possibility that the p63 pathway may be an attractive therapeutic target in these tumors. Nevertheless, it is unknown whether a therapeutic window exists for inhibiting p63 in tumor cells versus normal epithelia. Here, we show that SCC cells are uniquely dependent on Delta Np63 alpha for survival, unlike normal p63-expressing epithelial cells, and that dependence is mediated through tumor-specific up-regulation of the related protein p73. In normal primary human keratinocytes, we find that inhibition of endogenous p63 by RNA interference (RNAi) induces p21(CIP1) expression, inhibits cell cycle progression, and ultimately promotes cellular senescence. In contrast, p63 inhibition in SCC cells induces proapoptotic bcl-2 family members and rapidly triggers apoptosis. Expression of p73 is low in uncultured basal keratinocytes but is markedly up-regulated in both SCC cell lines and primary tumors in vivo. Whereas p21(CIP1) induction following loss of p63 in normal cells is independent of p53 and p73, both proapoptotic gene induction and cell death following p63 RNAi in tumor cells are p73 dependent. Finally, ectopic p73 expression in primary keratinocytes does not affect baseline cell proliferation but is sufficient to trigger cell death following loss of p63. Together, these findings define a specific molecular mechanism of p63 dependence through p73 up-regulation, and they provide a rationale for targeting the p63 pathway as a therapeutic strategy in SCCs. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ 904,55 Fruit St, Boston, MA 02114 USA. EM lellisen@partners.org FU NIDCR NIH HHS [R01 DE015945, R01 DE15945] NR 20 TC 71 Z9 73 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2006 VL 66 IS 19 BP 9362 EP 9368 DI 10.1158/0008-5472.CAN-06-1619 PG 7 WC Oncology SC Oncology GA 091GE UT WOS:000241014200005 PM 17018588 ER PT J AU Balsitis, S Dick, F Dyson, N Lambert, PF AF Balsitis, Scott Dick, Fred Dyson, Nicholas Lambert, Paul F. TI Critical roles for non-pRb targets of human papillomavirus type 16 E7 in cervical carcinogenesis SO CANCER RESEARCH LA English DT Article ID RETINOBLASTOMA TUMOR-SUPPRESSOR; CELL-CYCLE ARREST; IN-VIVO; HUMAN KERATINOCYTES; GROWTH ARREST; GENE-PRODUCT; G(1) CONTROL; ONCOPROTEIN; PROTEIN; DNA AB High-risk human papillomaviruses (HPV) encode two oncogenes, E6 and E7, expressed in nearly all cervical cancers. In vivo, HPAF-16 E7 has been shown to induce multiple phenotypes in the context of transgenic mice, including cervical cancer. E7 is a multifunctional protein known best for its ability to inactivate the tumor suppressor pRb. To determine the importance of pRb inactivation by E7 in cervical cancer, we pursued studies with genetically engineered mice. E7 expression in estrogen-treated murine cervix induced dysplasia and invasive cancers as reported previously,. p but targeted Rb inactivation in cervical epithelium was not sufficient to induce any cervical dysplasia or neoplasia. Furthermore, E7 induced cervical cancer formation even when the E7-pRb interaction was disrupted by the use of a knock-in mouse carrying an E7-resistant mutant Rb allele. pRb inactivation was necessary but not sufficient for E7 to overcome differentiation-induced or DNA damage-induced cell cycle arrest, and expression patterns of the E2F-responsive genes Mcm7 and cyclin E indicate that other E2F regulators besides pRb are important targets of E7. Together, these data indicate that non-pRb targets of E7 play critical roles in cervical carcinogenesis. C1 Univ Wisconsin, Sch Med, McArdle Lab Canc Res, Madison, WI 53706 USA. Univ Western Ontario, Dept Biochem, London, ON, Canada. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Lambert, PF (reprint author), Univ Wisconsin, Sch Med, McArdle Lab Canc Res, 1400 Univ Ave, Madison, WI 53706 USA. EM lambert@oncology.wisc.edu FU NCI NIH HHS [P01 CA022443-310006, CA098428, CA22443, CA64402, P01 CA022443, P30 CA014520, R01 CA064402, R01 CA098428, R01 CA098428-05, R01 CA098428-06]; NIGMS NIH HHS [T32 GM00721] NR 48 TC 40 Z9 40 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2006 VL 66 IS 19 BP 9393 EP 9400 DI 10.1158/0008.CAN-06-0984 PG 8 WC Oncology SC Oncology GA 091GE UT WOS:000241014200010 PM 17018593 ER PT J AU Mantena, SK Sharma, SD Katiyar, SK AF Mantena, Sudheer K. Sharma, Som D. Katiyar, Santosh K. TI Berberine inhibits growth, induces G(1) arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP SO CARCINOGENESIS LA English DT Article ID DEPENDENT KINASE INHIBITORS; CYTOCHROME-C; BCL-2 FAMILY; CANCER; DEATH; INDUCTION; PROTEIN; NEOPLASIA; HEALTH; DRUGS AB Chemotherapeutic approach using non-toxic botanicals may be one of the strategies for the management of the skin cancers. Here we report that in vitro treatment of human epidermoid carcinoma A431 cells with berberine, a naturally occurring isoquinoline alkaloid, decreased cell viability (3-77%, P < 0.05-0.001) and induced cell death (3-51%, P < 0.01-0.001) in a dose (5-75 mu M)- and time (12-72 h)-dependent manner, which was associated with an increase in G(1) arrest. G(0)/G(1) phase of the cell cycle is known to be controlled by cyclin dependent kinases (Cdk), cyclin kinase inhibitors (Cdki) and cyclins. Our western blot analysis showed that berberine-induced G(1) cell cycle arrest was mediated through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27), a simultaneous decrease in Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and enhanced binding of Cdki-Cdk. In additional studies, treatment of A431 cells with berberine (15-75 mu M) for 72 h resulted in a significant dose-dependent increase in apoptosis (31-60%, P < 0.05-0.001) than non-berberine-treated control (11.7%), which was associated with an increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspases 9, 3 and poly (ADP-ribose) polymerase. Pretreatment of A431 cells with the pan-caspase inhibitor (z-VAD-fmk) significantly blocked the berberine-induced apoptosis in A431 cells confirmed that berberine-induced apoptosis is mediated through activation of caspase 3-dependent pathway. Together, this study for the first time identified berberine as a chemotherapeutic agent against human epidermoid carcinoma A431 cells in vitro, further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the management of non-melanoma skin cancers. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670,Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NIAMS NIH HHS [AR050948-01] NR 42 TC 126 Z9 135 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2006 VL 27 IS 10 BP 2018 EP 2027 DI 10.1093/carcin/bgl043 PG 10 WC Oncology SC Oncology GA 090CF UT WOS:000240927500010 PM 16621886 ER PT J AU Nagy, N Goldstein, AM AF Nagy, Nandor Goldstein, Allan M. TI Intestinal coelomic transplants: a novel method for studying enteric nervous system development SO CELL AND TISSUE RESEARCH LA English DT Article DE enteric nervous system; coelomic graft; hindgut; quail-chick chimera; mouse-chick chimera ID NEURAL CREST CELLS; ENDOTHELIN RECEPTOR-B; MICE LACKING GDNF; NADPH-DIAPHORASE ACTIVITY; FETAL-RAT GUT; IN-VITRO; HIRSCHSPRUNG-DISEASE; NEURONAL DEVELOPMENT; DIGESTIVE-TRACT; ORGAN-CULTURE AB Normal development of the enteric nervous system (ENS) requires the coordinated activity of multiple proteins to regulate the migration, proliferation, and differentiation of enteric neural crest cells. Much of our current knowledge of the molecular regulation of ENS development has been gained from transgenic mouse models and cultured neural crest cells. We have developed a method for studying the molecular basis of ENS formation complementing these techniques. Aneural quail or mouse hindgut, isolated prior to the arrival of neural crest cells, was transplanted into the coelomic cavity of a host chick embryo. Neural crest cells from the chick host migrated to and colonized the grafted hindgut. Thorough characterization of the resulting intestinal chimeras was performed by using immunohistochemistry and vital dye labeling to determine the origin of the host-derived cells, their pattern of migration, and their capacity to differentiate. The formation of the ENS in the intestinal chimeras was found to recapitulate many aspects of normal ENS development. The host-derived cells arose from the vagal neural crest and populated the graft in a rostral-to-caudal wave of migration, with the submucosal plexus being colonized first. These crest-derived cells differentiated into neurons and glial cells, forming ganglionated plexuses grossly indistinguishable from normal ENS. The resulting plexuses were specific to the grafted hindgut, with quail grafts developing two ganglionated plexuses, but mouse grafts developing only a single myenteric plexus. We discuss the advantages of intestinal coelomic transplants for studying ENS development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1085 Budapest, Hungary. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. EM agoldstein@partners.org FU NICHD NIH HHS [K08HD46655] NR 68 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X EI 1432-0878 J9 CELL TISSUE RES JI Cell Tissue Res. PD OCT PY 2006 VL 326 IS 1 BP 43 EP 55 DI 10.1007/s00441-006-0207-3 PG 13 WC Cell Biology SC Cell Biology GA 090GU UT WOS:000240939700004 PM 16736197 ER PT J AU Wuest, T Farber, J Luster, A Carr, DJJ AF Wuest, Todd Farber, Joshua Luster, Andrew Carr, Daniel J. J. TI CD4(+) T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection SO CELLULAR IMMUNOLOGY LA English DT Article DE HSV-1; chemokines; CXCL9; CXCL10; knockout mice; cornea; T lymphocyte ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INDUCED STROMAL KERATITIS; NATURAL-KILLER-CELLS; IFN-GAMMA; INDUCIBLE PROTEIN-10; INTERFERON-GAMMA; TRIGEMINAL GANGLION; CYTOKINE PRODUCTION; CHEMOKINE LIGAND-9 AB The role of CXCL9 and CXCL10 in the ocular immune response to herpes simplex virus type I (HSV-1) infection was investigated using mice deficient in either CXCL9 or CXCL10. CXCL10 but not CXCL9 deficient mice showed an increase in sensitivity to ocular virus infection as measured by an elevation in virus titer recovered in the tear film and corneal tissue. The increase in virus was associated with an increase in the expression of the chemokine CCL2 but no significant change in the infiltration of CD4(+) T cells or NK cells into the corneal stroma. In contrast, a significant reduction in CD4(+) T cell infiltration into the cornea was found in CXCL9 deficient mice following HSV-1 infection consistent with the absence of CXCL9 expression and reduction in expression of other chemokines including CCL3, CCL5, CXCL1, and CXCL10. Collectively, the results suggest a non-redundant role for CXCL9 and CXCL10 in response to ocular HSV-1 infection in terms of controlling virus replication and recruitment of CD4(+) T cells into the cornea. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. Natl Inst Allergy & Infect Dis, Lab Clin Invest, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA. RP Carr, DJJ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. EM dan-carr@oulisc.edu FU NEI NIH HHS [EY12190, EY015566, P30 EY012190, R21 EY015566] NR 43 TC 30 Z9 30 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT PY 2006 VL 243 IS 2 BP 83 EP 89 DI 10.1016/j.cellimm.2007.01.001 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 152VV UT WOS:000245391000003 PM 17296171 ER PT J AU Ishiguro, K Avruch, J Landry, A Qin, S Ando, T Goto, H Xavier, R AF Ishiguro, Kazuhiro Avruch, Joe Landry, Aimee Qin, Shan Ando, Takafumi Goto, Hidemi Xavier, Ramnik TI Nore1B regulates TCR signaling via Ras and Carma1 SO CELLULAR SIGNALLING LA English DT Article DE T-lymphocytes; NF-kappa B; Ras proteins; MAGUK proteins; lymphocyte activation ID NF-KAPPA-B; T-CELL-RECEPTOR; LYMPHOCYTE-ACTIVATION; TUMOR-SUPPRESSOR; KINASE; IDENTIFICATION; EFFECTOR; CARD11; PROLIFERATION; REQUIREMENT AB Nore1A was originally identified as a potential Ras effector, and Nore1B is an alternatively spliced isoform. Both share a Ras/Rap association domain (RA domain) but only Nore1A contains sequence motifs that predict SH3 domain binding and diacylglycerol/phorbol ester binding in the amino-terminal region. Here we report that Carma1 binds to Nore1A and Nore1B through the RA domain and that Carma1 interacts with active Ras in the presence of Note1B. RNA interference against Nore1B attenuates NF-kappa B activation induced by T cell receptor (TCR) ligation, but not NF-kappa B activation induced by TNF alpha or lipoteichoic acid. In addition, Nore1B is also required for KiRas GV12-mediated ERK1 activation and Elk1 reporter activity in T cells. We also provide evidence that knockdown of Nore1B also impairs polarized redistribution of Ras at the B cell-T cell immune interface. Together, these findings suggest that endogenous Nore1B recruits active Ras to the APC-T cell interface and mediates the interaction between Ras and Carma1. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Nagoya Univ, Sch Med, Showa Ku, Nagoya, Aichi 4668550, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Xavier, R (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM Xavier@molbio.mgh.harvard.edu OI Ishiguro, Kazuhiro/0000-0003-1776-2805 FU NIDDK NIH HHS [DK43351, P30 DK040561-11, P30 DK040561, P30 DK043351] NR 38 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD OCT PY 2006 VL 18 IS 10 BP 1647 EP 1654 DI 10.1016/j.cellsig.2006.01.015 PG 8 WC Cell Biology SC Cell Biology GA 082MQ UT WOS:000240391300011 PM 16520020 ER PT J AU Peck, R AF Peck, R. TI Ophthalmoplegic migraine presenting in infancy: a self-reported case SO CEPHALALGIA LA English DT Editorial Material ID OCULOMOTOR NERVE C1 Massachusetts Gen Hosp, Dept Med & Pediat, Boston, MA 02114 USA. RP Peck, R (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM rpeck@partners.org NR 10 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD OCT PY 2006 VL 26 IS 10 BP 1242 EP 1244 DI 10.1111/j.1468-2982.2006.01181.x PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 082DE UT WOS:000240366100013 PM 16961794 ER PT J AU Murphey, RD Stern, HM Straub, CT Zon, LI AF Murphey, Ryan D. Stern, Howard M. Straub, Christian T. Zon, Leonard I. TI A chemical genetic screen for cell cycle inhibitors in zebrafish embryos SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE zebrafish; chemical genetics; cell cycle; small molecule; screen ID SMALL MOLECULES; DRUG DISCOVERY; IDENTIFICATION; ACTIVATION; CHECKPOINT; APOPTOSIS; CHEMISTRY; MITOSIS; MUTANT AB Chemical genetic screening is an effective strategy to identify compounds that alter a specific biological phenotype. As a complement to cell line screens, multicellular organism screens may reveal additional compounds. The zebrafish embryo is ideal for small molecule studies because of its small size and the ease of waterborne treatment. We first examined a broad range of known cell cycle compounds in embryos using the mitotic marker phospho-histone H3. The majority of the known compounds exhibited the predicted cell cycle effect in embryos. To determine whether we could identify novel compounds, we screened a 16 320-compound library for alterations of pH3. This screen revealed 14 compounds that had not been previously identified as having cell cycle activity despite numerous mitotic screens of the same library with mammalian cell lines. With six of the novel compounds, sensitivity was greater in embryos than cell lines, but activity was still detected in cell lines at higher doses. One compound had activity in zebrafish embryos and cell lines but not in mammalian cell lines. The remaining compounds exhibited activity only in embryos. These findings demonstrate that small molecule screens in zebrafish can identify compounds with novel activity and thus may be useful tools for chemical genetics and drug discovery. C1 Childrens Hosp, Dana Farber Canc Inst, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Howard Hughes Med Inst, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, Dana Farber Canc Inst, Howard Hughes Med Inst, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NICHD NIH HHS [1R01 HD044930]; NIDDK NIH HHS [1R01 DK55381] NR 17 TC 80 Z9 84 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD OCT PY 2006 VL 68 IS 4 BP 213 EP 219 DI 10.1111/j.1747-0285.2006.00439.x PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 115HS UT WOS:000242726000004 PM 17105485 ER PT J AU Lanuti, M Digumarthy, SR Sharma, A Martino, J Shepard, JAO Mathisen, DJ AF Lanuti, Michael Digumarthy, Subba R. Sharma, Amita Martino, Joanne Shepard, Jo-Anne O. Mathisen, Douglas J. TI Radiofrequency ablation for cure of inoperable lung cancer: A single institution experience SO CHEST LA English DT Meeting Abstract CT CHEST 2006 Conference CY OCT 21-26, 2006 CL Salt Lake City, UT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 OCT PY 2006 VL 130 IS 4 SU S BP 132S EP 132S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 095DI UT WOS:000241288000172 ER PT J AU Mortensen, E Restrepo, M Copeland, L Anzueto, A Pugh, J Pugh, MJ AF Mortensen, Eric Restrepo, Marcos Copeland, Laurel Anzueto, Antonio Pugh, Jacqueline Pugh, Mary Jo TI Impact of statin and angiotensin II receptor blocker use on mortality for patients hospitalized with sepsis SO CHEST LA English DT Meeting Abstract CT CHEST 2006 Conference CY OCT 21-26, 2006 CL Salt Lake City, UT C1 S Texas Vet Healthcare Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2006 VL 130 IS 4 SU S BP 135S EP 135S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 095DI UT WOS:000241288000182 ER PT J AU Adams, SG Simpson, T Allan, PF Lee, S Vipraio, G Smith, PK Anzueto, A Pugh, JA Kearney, L AF Adams, Sandra G. Simpson, Tamara Allan, Patrick F. Lee, Shuko Vipraio, Gilbert Smith, Paulla K. Anzueto, Antonio Pugh, Jacqueline A. Kearney, Lisa TI Cognitive behavioral group therapy improves quality of life more than general health education for anxiety in severe chronic obstructive pulmonary disease SO CHEST LA English DT Meeting Abstract CT CHEST 2006 Conference CY OCT 21-26, 2006 CL Salt Lake City, UT C1 UTHSCSA, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 1 U2 7 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2006 VL 130 IS 4 SU S BP 180S EP 180S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 095DI UT WOS:000241288000338 ER PT J AU Schmidt, SA Waxman, A AF Schmidt, Sarah A. Waxman, Aaron TI Preoperative intravenous epoprostenol prior to surgical repair of a ventricular septal defect in an adult with Eisenmenger Syndrome SO CHEST LA English DT Meeting Abstract CT CHEST 2006 Conference CY OCT 21-26, 2006 CL Salt Lake City, UT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2006 VL 130 IS 4 SU S BP 305S EP 305S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 095DI UT WOS:000241288001418 ER PT J AU Gorse, GJ O'Connor, TZ Young, SL Habib, MP Wittes, J Neuzil, KM Nichol, KL AF Gorse, Geoffrey J. O'Connor, Theresa Z. Young, Stephen L. Habib, Michael P. Wittes, Janet Neuzil, Kathleen M. Nichol, Kristin L. TI Impact of a winter respiratory virus season on patients with COPD and association with influenza vaccination SO CHEST LA English DT Article DE COPD; health-related quality of life; influenza virus; pulmonary function; vaccine ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC LUNG-DISEASE; VIRAL-INFECTIONS; ELDERLY PERSONS; UNDERLYING CONDITIONS; ACUTE EXACERBATIONS; CHRONIC-BRONCHITIS; SYNCYTIAL VIRUS; A INFECTIONS; MORTALITY AB Background: We assessed the effects of an influenza season on patients with COPD. Data from 2,215 veterans in a multicenter, randomized, double-blind influenza vaccine efficacy study were analyzed for changes in spirometric and functional status, comparing patients with laboratory-documented influenza (LDI)-caused illness, non-LDI-caused respiratory illness, or no illness, and for association with influenza vaccination. Methods: Patients received either IM trivalent inactivated influenza virus vaccine (TIV) plus intranasal trivalent, live attenuated, cold-adapted influenza virus vaccine (TC) or TIV plus intranasal placebo (TP). We performed spirometry, measured the chronic lung disease severity index (CLDSI) score to assess functional status and well-being, and tested for influenza virus infection. Results: Worsening in FEV1, percentage of predicted FEV, and CLDSI score (p < 0.001) was associated with acute respiratory illness in 585 illnesses including 94 LDI-caused illnesses. LDI-caused illness was more likely to be associated with worsening in FEV, and CLDSI score acutely than non-LDI-caused illness (p < 0.01). Logistic regression showed acute respiratory illness (odds ratio [OR], 1.78; 95% confidence limit [CL], 1.40 to 2.26) to be associated with worsening in CLDSI score, and receipt of TC (OR, 1.39; 95% CL, 1.10 to 1.74) and no illness (OR, 0.70; 95% CL, 0.53 to 0.91 for acute respiratory illness) to be associated with better CLDSI score at the end of the study. Hospitalization was more frequent in patients with acute respiratory illness (p < 0.0001). Conclusions: Acute respiratory illness was associated with increased health-care utilization and obstruction to airflow, and worse functional status and well-being. At the end of the study, receipt of TC was associated with improvement and acute respiratory illness was associated with worsening in functional status and well-being. C1 St Louis Univ, Hlth Sci Ctr, Div Infect Dis & Immunol, St Louis, MO 63110 USA. Dept Vet Affairs Med Ctr, St Louis, MO USA. Cooperat Studies Program, Coordinating Ctr, Dept Vet Affairs, West Haven, CT USA. Dept Vet Affairs Med Ctr, Durham, NC USA. Dept Vet Affairs Med Ctr, Tucson, AZ USA. Stat Collaborat, Washington, DC USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Minnesota, Minneapolis, MN USA. Dept Vet Affairs Med Ctr, Minneapolis, MN USA. RP Gorse, GJ (reprint author), St Louis Univ, Hlth Sci Ctr, Div Infect Dis & Immunol, 3635 Vista Ave FDT-8N, St Louis, MO 63110 USA. EM gorsegj@slu.edu NR 45 TC 20 Z9 23 U1 0 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2006 VL 130 IS 4 BP 1109 EP 1116 DI 10.1378/chest.130.4.1109 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 094UX UT WOS:000241265700029 PM 17035445 ER PT J AU Mercer, JL Boninger, M KoontZ, A Ren, DX Dyson-Hudson, T Cooper, R AF Mercer, Jennifer L. Boninger, Michael KoontZ, Alicia Ren, Dianxu Dyson-Hudson, Trevor Cooper, Rory TI Shoulder joint kinetics and pathology in manual wheelchair users SO CLINICAL BIOMECHANICS LA English DT Article DE shoulder; joint kinetics; spinal cord injury; biomechanics; pathology; inverse dynamics ID SPINAL-CORD-INJURY; REPETITIVE WORK; ROTATOR CUFF; IMAGING ABNORMALITIES; PUSHRIM BIOMECHANICS; NECK/SHOULDER PAIN; UPPER EXTREMITY; RISK-FACTORS; PROPULSION; WEIGHT AB Background. Manual wheelchair users rely heavily on their upper limbs for independent mobility which likely leads to a high prevalence of shoulder pain and injury. The goal of this study was to examine the relationship between shoulder forces and moments experienced during wheelchair propulsion and shoulder pathology. Methods. Kinetic and kinematic data was recorded from 33 subjects with paraplegia as they propelled their wheelchairs at two speeds (0.9 and 1.8 m/s). Shoulder joint forces and moments were calculated using inverse dynamic methods and shoulder pathology was evaluated using a physical exam and magnetic resonance imaging scan. Findings. Subjects who experienced higher posterior force (Odds Ratio (OR) = 1.29, P = 0.03), lateral force (OR = 1.35, P = 0.047), or extension moment (OR = 1.35, P = 0.09) during propulsion were more likely to exhibit coracoacromial ligament edema. Individuals who displayed larger lateral forces (OR = 4.35, P = 0.045) or abduction moments (OR = 1.58, P = 0.06) were more likely to have coracoacromial ligament thickening. Higher superior forces (OR = 1.05, P = 0.09) and internal rotation moments (OR = 1.61 P = 0.02) at the shoulder were associated with increased signs of shoulder pathology during the physical exam. Interpretation. Specific joint forces and moments were related to measures of shoulder pathology. This may indicate a need to reduce the overall force required to propel a wheelchair in order to preserve upper limb integrity. Potential interventions include changes to wheelchair setup, propulsion training, or alternative means of mobility. (c) 2006 Elsevier Ltd. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Spinal Cord Injury Rehabil Res, Kessler Med Rehabil Res & Educ Corp, W Orange, NJ USA. Univ Med & Dent New Jersey, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. RP Boninger, M (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, 7180 Highland Dr,151R1-H, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU PHS HHS [H133A011107] NR 40 TC 106 Z9 108 U1 2 U2 20 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD OCT PY 2006 VL 21 IS 8 BP 781 EP 789 DI 10.1016/j.clinbiomech.2006.04.010 PG 9 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 082LE UT WOS:000240387500003 PM 16808992 ER PT J AU Moreau, LA McGrady, P London, WB Shimada, H Cohn, SL Maris, JM Diller, L Look, AT George, RE AF Moreau, Lisa A. McGrady, Patrick London, Wendy B. Shimada, Hiroyuki Cohn, Susan L. Maris, John M. Diller, Lisa Look, A. Thomas George, Rani E. TI Does MYCN amplification manifested as homogeneously staining regions at diagnosis predict a worse outcome in children with neuroblastoma? A Children's Oncology Group study SO CLINICAL CANCER RESEARCH LA English DT Article ID DOUBLE-MINUTE CHROMOSOMES; GENE AMPLIFICATION; N-MYC; TUMOR-CELLS; DNA; PROGRESSION; ONCOGENE; COPIES; TUMORIGENICITY; ASSOCIATION AB Purpose: MYCN amplification in neuroblastoma tumor cells is manifested primarily as double minutes (dmins), whereas in cell lines it often appears in the form of homogeneously staining regions (HSR), suggesting that HSRs are associated with a more aggressive tumor phenotype and worse clinical outcome. The aim of this study was to determine whether children with neuroblastoma in which MYCN oncogene amplification is manifested as HSRs at diagnosis have a worse prognosis than those whose tumors exhibit dmins. Experimental Design: A retrospective analysis of primary neuroblastomas analyzed for MYCN amplification by the Children's Oncology Group between 1993 and 2004 was done. Tumors with MYCN amplification were defined as having dmins, HSRs, or both (dmins + HSRs), and associations with currently used risk group stratification variables and patient outcome were assessed. Results: Of the 4,102 tumor samples analyzed, 800 (19.5%) had MYCN amplification. Among the 677 tumors for which the pattern of amplification was known, 629 (92.9%) had dmins, 40 (5.9%) had HSRs, and 8 (0.1%) had dmins + HSRs. Although MYCN amplification is associated with older age, higher stage, and unfavorable histology, whether the amplification occurred as dmins or HSRs did not significantly affect these risk factors. There were no differences in the event-free survival (EFS) or overall survival in patients with MYCN amplification manifested as either dmins or HSRs (5-year EFS, 35 +/- 3% versus 38 +/- 15%; P = 0.59). Although the eight patients with dmins + HSRs fared worse than either of the individual subgroups (EFS, 18 +/- 16% versus 35 +/- 3% for dmins and 38 +/- 15% for HSRs), these differences were not significant. Conclusions: MYCN amplification in any form (HSRs or dmins) is associated with a poor outcome. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Florida, Natl Ctr Pediat Canc Genet, Childrens Oncol Grp, Gainesville, FL USA. Univ Florida, Stat & Data Ctr, Childrens Oncol Grp, Gainesville, FL USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP George, RE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 322,44 Binney St, Boston, MA 02115 USA. EM rani_george@dfci.harvard.edu OI Cohn, Susan/0000-0001-5749-7650 FU NCI NIH HHS [CA 25408, CA 30969, CA 98543, U10 CA 29139]; NINDS NIH HHS [K08 NS 047983] NR 32 TC 19 Z9 22 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2006 VL 12 IS 19 BP 5693 EP 5697 DI 10.1158/1078-0432.CCR-06-1500 PG 5 WC Oncology SC Oncology GA 092LL UT WOS:000241098100014 PM 17020972 ER PT J AU Hideshima, T Neri, P Tassone, P Yasui, H Ishitsuka, K Raje, N Chauhan, D Podarl, K Mitsiades, C Dang, L Munshi, N Richardson, P Schenkein, D Anderson, KC AF Hideshima, Teru Neri, Paola Tassone, Pierfranchesco Yasui, Hiroshi Ishitsuka, Kenji Raje, Noopur Chauhan, Dharminder Podarl, Klaus Mitsiades, Constantine Dang, Lenny Munshi, Nikhil Richardson, Paul Schenkein, David Anderson, Kenneth C. TI MLN120B, a novel I kappa B kinase beta inhibitor, blocks multiple myeloma cell growth in vitro and in vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; MARROW STROMAL CELLS; RESISTANCE CAM-DR; BONE-MARROW; THERAPEUTIC IMPLICATIONS; MULTIDRUG-RESISTANCE; BIOLOGIC SEQUELAE; INDUCED APOPTOSIS; PLASMA-CELLS; INTERLEUKIN-6 AB Purpose: The purpose of this study is to delineate the biological significance of I kappa B kinase (IKK) beta inhibition in multiple myeloma cells in the context of bone marrow stromal cells (BMSC) using a novel IKK beta inhibitor MLN120B. Experimental Design: Growth-inhibitory effect of MLN120B in multiple myeloma cells in the presence of cytokines [interleukin-6 (IL-6) and insulin-like growth factor-I (IGF-1)], conventional agents (dexamethasone, melphalan, and doxorubicin), or BMSC was assessed in vitro. In vivo anti-multiple myeloma activity of MLN120B was evaluated in severe combined immunodeficient (SCID) - hu model. Results: MLN120B inhibits both baseline and tumor necrosis factor- alpha -induced nuclear factor-kappa B activation, associated with down-regulation of I kappa B alpha and p65 nuclear factor-kappa B phosphorylation. MLN120B triggers 25% to 90% growth inhibition in a dose-dependent fashion in multiple myeloma cell lines and significantly augments tumor necrosis factor-alpha- induced cytotoxicity in MM.1S cells. MLN120B augments growth inhibition triggered by doxorubicin and melphalan in both RPMI 8226 and IL-6-dependent INA6 cell lines. Neither IL-6 nor IGF-1 overcomes the growth-inhibitory effect of MLN120B. MLN120B inhibits constitutive IL-6 secretion by BMSCs by 70% to 80% without affecting viability. Importantly, MLN120B almost completely blocks stimulation of MM.1S, U266, and INA6 cell growth, as well as IL-6 secretion from BMSCs, induced by multiple myeloma cell adherence to BMSCs. MLN120B overcomes the protective effect of BMSCs against conventional (dexamethasone) therapy. Conclusions: Our data show that the novel IKK beta inhibitor MLN120B induces growth inhibition of multiple myeloma cells in SCID-hu mouse model. These studies provide the framework for clinical evaluation of MLN120B, alone and in combined therapies, trials of these novel agents to improve patient outcome in multiple myeloma. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [1P50 CA 10070, R01 CA 50947]; PHS HHS [P01 78378] NR 42 TC 95 Z9 98 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 OCT 1 PY 2006 VL 12 IS 19 BP 5887 EP 5894 DI 10.1158/1078-0432.CCR-05-2501 PG 8 WC Oncology SC Oncology GA 092LL UT WOS:000241098100039 PM 17020997 ER PT J AU Amicarelli, G Adlerstein, D Shehi, E Wang, FF Makrigiorgos, GM AF Amicarelli, Giulia Adlerstein, Daniel Shehi, Erlet Wang, Fengfei Makrigiorgos, G. Mike TI Genotype-specific signal generation based on digestion of 3-way DNA junctions: Application to KRAS variation detection SO CLINICAL CHEMISTRY LA English DT Article ID FACTOR-V-LEIDEN; CELL LUNG-CANCER; POLYMERASE-CHAIN-REACTION; GROWTH-FACTOR RECEPTOR; SINGLE-NUCLEOTIDE POLYMORPHISMS; CHRONIC MYELOID-LEUKEMIA; RAS CODON-12 MUTATIONS; REAL-TIME PCR; CLINICAL RESISTANCE; SOMATIC MUTATIONS AB Background: Genotyping methods that reveal single-nucleotide differences are useful for a wide range of applications. We used digestion of 3-way DNA junctions in a novel technology, OneCutEventAmplificatioN (OCEAN) that allows sequence-specific signal generation and amplification. We combined OCEAN with peptide-nucleic-acid (PNA)-based variant enrichment to detect and simultaneously genotype v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) codon 12 sequence variants in human tissue specimens. Materials and Methods: We analyzed KRAS codon 12 sequence variants in 106 lung cancer surgical specimens. We conducted a PNA-PCR reaction that suppresses wild-type KRAS amplification and genotyped the product with a set of OCEAN reactions carried out in fluorescence microplate format. The isothermal OCEAN assay enabled a 3-way DNA junction to form between the specific target nucleic acid, a fluorescently labeled "amplifier", and an "anchor". The amplifier-anchor contact contains the recognition site for a restriction enzyme. Digestion produces a cleaved amplifier and generation of a fluorescent signal. The cleaved amplifier dissociates from the 3-way DNA junction, allowing a new amplifier to bind and propagate the reaction. Results: The system detected and genotyped KRAS sequence variants down to similar to 0.3% variant-to-wild-type alleles. PNA-PCR/OCEAN had a concordance rate with PNA-PCR/sequencing of 93% to 98%, depending on the exact implementation. Concordance rate with restriction endonuclease-mediated selective-PCR/sequencing was 89%. Conclusion: OCEAN is a practical and low-cost novel technology for sequence-specific signal generation. Reliable analysis of KRAS sequence alterations in human specimens circumvents the requirement for sequencing. Application is expected in genotyping KRAS codon 12 sequence variants in surgical specimens or in bodily fluids, as well as single-base variations and sequence. alterations in other genes. (c) 2006 American Association for Clinical Chemistry. C1 DiaSorin SpA, Saluggia, VC, Italy. Univ Milano Bicocca, Dept Biosci & Biotechnol, Milan, Italy. Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RP Adlerstein, D (reprint author), Diasorin SpA, Piazza Sci 4, I-20126 Milan, Italy. EM daniel.adlerstein@diasorin.it NR 46 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 2006 VL 52 IS 10 BP 1855 EP 1863 DI 10.1373/clinchem.2006.068817 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 089CP UT WOS:000240858000005 PM 16916990 ER PT J AU Yang, ZP Harris, LE Palmer-Toy, DE Hancock, WS AF Yang, Ziping Harris, Lyndsay E. Palmer-Toy, Darryl E. Hancock, William S. TI Multilectin affinity chromatography for characterization of multiple glycoprotein biomarker candidates in serum from breast cancer patients SO CLINICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HUMAN PLASMA PROTEOME; COMPREHENSIVE ANALYSIS; EPITHELIAL-CELLS; SURVIVAL FACTOR; ALPHA-1-ANTICHYMOTRYPSIN; GLYCOSYLATION; EXPRESSION; INHIBITOR; PROGNOSIS AB Background: Glycoproteins are often associated with cancer and are important in serum studies, for which glycosylation is a common posttranslational modification. Methods: We used multilectin affinity chromatography (M-LAC) to isolate glycoproteins from the sera of breast cancer patients and controls. The proteins were identified by HPLC-tandem mass spectrometry, (MS/MS) analysis of the corresponding tryptic digests. We used the FuncAssociate Gene Ontology program for association analysis of the identified proteins. Biomarker candidates in these groups were comparatively quantitated by use of peak area measurements, with inclusion of an internal standard. We analyzed data for concordance within the ontology association groups for vector of change with the development of breast cancer. Results: Detection of the known low-concentration biomarker HER-2 (8-24 mu g/L) enabled us to establish a dynamic range of 10(6), relative to the amount of albumin, for the depletion step. We then used ELISA to confirm this range. Proteins associated with lipid transport and metabolism, cell growth and maintenance, ion homeostasis, and protease inhibition were found to be differentially regulated in serum from women with breast cancer compared with serum from women without breast cancer. Conclusions: M-LAC for isolation of the serum glyco-proteome, coupled with liquid chromatography-MS/MS and the use of gene ontology associations, can be used to characterize large panels of candidate markers, which can then be evaluated in a particular patient population. (c) 2006 American Association for Clinical Chemistry. C1 Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. Northeastern Univ, Dept Chem & Biol Chem, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Renal Unit, Cambridge, MA 02138 USA. RP Hancock, WS (reprint author), Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. EM wi.hancock@neu.edu NR 48 TC 102 Z9 103 U1 4 U2 21 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 2006 VL 52 IS 10 BP 1897 EP 1905 DI 10.1373/clinchem.2005.065862 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 089CP UT WOS:000240858000010 PM 16916992 ER PT J AU Corey, KE Ross, AS Wurcel, A Wiesch, JSZ Kim, AY Lauer, GM Chung, RT AF Corey, Kathleen E. Ross, Andrew S. Wurcel, Alysse Wiesch, Julian Schulze Zur Kim, Arthur Y. Lauer, Georg M. Chung, Raymond T. TI Outcomes and treatment of acute hepatitis C virus infection in a United States population SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID VIRAL CLEARANCE AB Back-ground & Aims: Acute hepatitis C infection progresses to chronic infection in up to 80% of infected persons. Reports from Europe indicate that early treatment of acute hepatitis C infection produces sustained virologic response rates as high as 80%-98%. However, the outcome of acute hepatitis C infection in United States cohorts is not well-characterized. Methods: We describe the clinical course of 28 episodes of acute hepatitis C infection in 24 persons at our institution. Results: Of the 28 infections, 7 episodes resolved spontaneously. Of the remaining 21 episodes, 16 were treated, and 5 did not receive treatment. Of the 16 treated episodes, 4 received interferon and ribavirin, 11 received pegylated interferon and ribavirin, and 1 was treated initially with interferon monotherapy followed by pegylated interferon monotherapy. Among those episodes treated with interferon, 3 of 4 experienced sustained virologic response. Among those episodes treated with pegylated interferon, all 12 achieved SVR. In total, 15 of 16 treated patients (94%) experienced SVR. In all, 18 of the 24 patients (75%) experienced spontaneous or treatment-induced sustained virologic clearance. Conclusions: Our experience with treated and untreated acute HCV infection is comparable to that observed in Europe. Patients treated with antiviral therapy had an excellent response. Randomized trials to investigate immediate versus delayed treatment of acute hepatitis C infection are warranted. In view of these strongly positive outcomes, increased vigilance for acute hepatitis C becomes essential. C1 Harvard Univ, Gastroenterol Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Med Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Chung, RT (reprint author), Harvard Univ, Gastroenterol Unit, Massachusetts Gen Hosp, Sch Med, GRJ-825, Boston, MA 02114 USA. EM rtchung@partners.org FU NIAID NIH HHS [U19 AI066345, R01 AI069939] NR 9 TC 34 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2006 VL 4 IS 10 BP 1278 EP 1282 DI 10.1016/j.cgh.2006.06.026 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 097KZ UT WOS:000241447700019 PM 16931171 ER PT J AU Bhattacharyya, T Blyler, C Shenaq, D AF Bhattacharyya, Timothy Blyler, Ciantel Shenaq, Deana TI The natural history of new orthopaedic devices SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PERCUTANEOUS VERTEBROPLASTY; FRACTURES; COMPLICATIONS AB Each year, hundreds of new devices and implants are introduced for orthopaedic surgeons. However, the proportion of new devices which ultimately will be successful is unknown. We investigated the natural history of new devices introduced to the orthopaedic market. From a list of all devices approved for use by the Food & Drug Administration 5 and 10 years before, a cohort of 100 devices was randomly selected using a random number list. Companies were contacted regarding the safety record and current availability of these devices. The company response rate was 93%. Forty-seven percent of devices approved 10 years ago and 25% of devices approved 5 years ago no longer were on the market. Of the 55 companies studied, 18 (33%) were out of business and their devices no longer were available. Devices approved 10 years ago were more likely to be unavailable than devices approved 5 years ago. Devices introduced by smaller companies were more likely to be unavailable. The majority of unavailable devices were discontinued not for clinical problems, but for poor market performance. Only 2% of devices studied had safety problems. Approximately 50% of devices approved for introduction to the orthopaedic marketplace no longer are available 10 years later. However, major device-related problems seem uncommon. C1 Brigham & Womens Hosp, Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. RP Bhattacharyya, T (reprint author), Brigham & Womens Hosp, Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, 55 Fruit St,Yawkey 3600, Boston, MA 02114 USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2006 IS 451 BP 263 EP 266 DI 10.1097/01.blo.0000229312.13137.2f PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119OI UT WOS:000243021200047 ER PT J AU Franko, DL Keel, PK AF Franko, Debra L. Keel, Pamela K. TI Suicidality in eating disorders: Occurrence, correlates, and clinical implications SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article DE suicide; suicidality; anorexia nervosa; bulimia nervosa; eating disorders; mortality; death ID BORDERLINE PERSONALITY-DISORDER; DIALECTICAL BEHAVIOR-THERAPY; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; LONG-TERM; PSYCHIATRIC COMORBIDITY; FOLLOW-UP; MORTALITY; RECOVERY; RELAPSE AB This review summarizes the published studies on suicide and suicide attempts in individuals with eating disorders, highlighting rates of occurrence, clinical correlates, and implications for practitioners. Multiple studies find high rates of suicide in patients with anorexia nervosa (AN) [Standardized Mortality Ratio (SMR) for suicide range from 1.0 to 5.3], whereas suicide rates do not appear to be elevated in bulimia nervosa (BN). In contrast, suicide attempts occur in approximately 3-20% of patients with anorexia nervosa and in 25-35% of patients with bulimia nervosa. Clinical correlates of suicidality in eating disorders include purging behaviors, depression, substance abuse, and a history of childhood physical and/or sexual abuse. Patients with eating disorders, particularly those with comorbid disorders, should be assessed routinely for suicidal ideation, regardless of the severity of eating disorder or depressive symptoms. (c) 2006 Published by Elsevier Ltd. C1 Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. RP Franko, DL (reprint author), Northeastern Univ, Dept Counseling & Appl Educ Psychol, 203 Lake Hall, Boston, MA 02115 USA. EM d.franko@neu.edu NR 63 TC 94 Z9 95 U1 1 U2 10 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 OCT PY 2006 VL 26 IS 6 BP 769 EP 782 DI 10.1016/j.cpr.2006.04.001 PG 14 WC Psychology, Clinical SC Psychology GA 087TQ UT WOS:000240765700006 PM 16875766 ER PT J AU Cusack, KJ Grubaugh, AL Knapp, RG Frueh, BC AF Cusack, Karen J. Grubaugh, Anouk L. Knapp, Rebecca G. Frueh, B. Christopher TI Unrecognized trauma and PTSD among public mental health consumers with chronic and severe mental illness SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE community mental health; severe mental illness; traumatic events; posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOMETRIC PROPERTIES; CIVILIAN VERSION; WOMEN; PREVALENCE; CHECKLIST; COMMUNITY; COMORBIDITY; SERVICES; HISTORY AB Lifetime prevalence of traumatic events and current PTSD was assessed among 142 mental health consumers with serious mental illness served by a psychosocial. rehabilitation day program. Lifetime exposure to trauma was high (87%). The rate of PTSD based on the PTSD Checklist (PCL) was also high (19-30% depending on different scoring criteria). Overall, the PCL had strong internal reliability for this sample. Documentation of trauma and PTSD was exceptionally low in medical records. Results suggest that trauma and PTSD are significantly overlooked in the public mental health system. Improved recognition of trauma and PTSD are needed in order to provide meaningful services to this highly vulnerable population. C1 Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27515 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Cusack, KJ (reprint author), Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, 725 Martin Luther King, Chapel Hill, NC 27515 USA. EM kcusack@schsr.unc.edu NR 42 TC 35 Z9 35 U1 6 U2 10 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD OCT PY 2006 VL 42 IS 5 BP 487 EP 500 DI 10.1007/s10597-006-9049-4 PG 14 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 101CO UT WOS:000241716700005 PM 16868841 ER PT J AU Behnam, K Murray, SS Brochmann, EJ AF Behnam, Keyvan Murray, Samuel S. Brochmann, Elsa J. TI BMP stimulation of alkaline phosphatase activity in pluripotent mouse C2C12 cells is inhibited by dermatopontin, one of the most abundant low molecular weight proteins in demineralized bone matrix SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE bone morphogenetic protein; demineralized bone matrix; dermatopontin; proteomics; TGF-beta ID GROWTH-FACTOR-BETA; OSTEOBLAST-LIKE CELLS; EXTRACELLULAR-MATRIX; MORPHOGENETIC PROTEINS; TARGETED DISRUPTION; BOVINE BONE; IN-VITRO; EXPRESSION; COLLAGEN; IDENTIFICATION AB Demineralized bone matrix (DBM) is a complex mixture of osteoinductive bone morphogenetic proteins (BMPs), as well as BMP-binding proteins that regulate BMP bioactivity and localization. Our aim was to use modern proteomic methods to identify additional BMP-binding proteins in DBM, with initial emphasis on the most abundant. Relatively large, water-soluble noncollagenous proteins (NCPs) were preferentially extracted from DBM with alkalinized urea. The insoluble residue, which contained the BMP activity, was extracted with GuHCl/CaCl2, dialyzed versus citrate, defatted, resuspended in GuHCl, dialyzed sequentially against Triton X-100 and water, pelleted, and lyophilized. The proteins in this pellet were fractionated by hydroxyapatite affinity chromatography. Proteins that copurified with BMP bioactivity were separated by SDS-PAGE. Distinct bands were excised, and the proteins in them were reduced and alkylated, digested with trypsin, eluted, and subjected to MALDI/ToF MS (matrix-assisted laser-desorption ionization time-of-flight mass spectrometry). Computer-assisted peptide fingerprint analysis of the MS profiles was used to identify C-terminal lysine-6-oxidase; dermatopontin (DPT); histones H2A2, H2A3, and H2B; and trace amounts of gamma-actin. DPT is a 22-kDa, tyrosine-rich acidic matrix protein not previously recognized to be among the most abundant small proteins to copurify with BMP bioactivity in DBM. We tested the effects of DPT on BMP-2 stimulation of alkaline phosphatase (ALP) activity in C2C12 cells. BMP-2 stimulated ALP activity in C2C12 cells by 6.2-fold above basal levels. DPT alone had no effect on ALP activity in C2C12 cells. When added with BMP-2, DPT blocked 40% of the stimulatory effect of BMP-2 on ALP activity in C2C12 cells. DPT is an abundant protein in DBM, and it can inhibit the stimulatory effects of BMP-2 on ALP activity in C2C12 cells. C1 VA Great Los Angeles Healthcare Syst, GRECC, Sepulveda, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Murray, SS (reprint author), VA Med Ctr, GRECC, 11-E,16111 Plummer St, Sepulveda, CA 91343 USA. EM Samuel.Murray@med.va.gov NR 26 TC 10 Z9 10 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PD OCT-DEC PY 2006 VL 47 IS 5 BP 271 EP 277 DI 10.1080/03008200600995908 PG 7 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 107ZQ UT WOS:000242209900004 PM 17118749 ER PT J AU Mattison, MLP Rudolph, JL Kiely, DK Marcantonio, ER AF Mattison, Melissa L. P. Rudolph, James L. Kiely, Dan K. Marcantonio, Edward R. TI Nursing home patients in the intensive care unit: Risk factors for mortality SO CRITICAL CARE MEDICINE LA English DT Article DE mortality; function; intensive care; activities of daily living; aged; nursing home ID MEDICARE BENEFICIARIES; HOSPITALIZED ADULTS; OLDER PATIENTS; SERIOUSLY ILL; HEALTH-CARE; AGE; RESIDENTS; ERRORS; COSTS; LIFE AB Objective. To determine intensive care unit (ICU) admission characteristics predictive of mortality among older nursing home residents. Design: Retrospective cohort study. Setting. A 725-bed teaching nursing home and two teaching-hospital ICUs. Patients: One hundred twenty-three nursing home residents >= 75 yrs admitted to the ICU between July 1, 1999, and September 30,2003. Interventions: None. Measurements and Main Results. Characteristics of nursing home residents admitted to the ICU were identified by medical record review at the nursing home and the hospital. Additionally, the minimum data set was used to calculate preadmission functional status using the Activities of Daily Living-Long Form (ADL-L) and cognitive status with the Cognitive Performance Scale (CPS). Our primary outcomes were hospital mortality and mortality within 90 days of ICU admission. The nursing home residents admitted to the ICU were old (87.7 +/- 5.4 yrs) with impaired cognition (CPS 2.8 +/- 1.7, range 0-6, where 6 = most impaired) and moderately dependent function (ADL-L 14.5 +/- 9.4, range 0-28, where 28 = total dependence). Of the 123 patients, 33 (27%) died in the hospital, whereas 90 (73%) survived to hospital discharge. Acute Physiology and Chronic Health Evaluation (APACHE) III score was independently associated with significantly increased odds of hospital mortality (adjusted odds ratio 1.04; 95% confidence interval 1.02, 1.07). Among the 90 patients who survived to return to the nursing home, 34 (37.8%) died within 90 days. Cox regression demonstrated that higher APACHE III score (adjusted risk ratio 1.02; 95% confidence interval 1.01, 1.04) and increasing functional dependency before ICU admission (adjusted risk ratio 1.6; 95% confidence interval 1.05, 2.57, per ADL-L quartile) were independently associated with increased mortality rate within 90 days. Conclusions: Among vulnerable elderly nursing home residents, higher APACHE III score is independently associated with increased hospital mortality rate and mortality within 90 days. Among hospital survivors, impaired functional status is independently associated with increased mortality rate within 90 days. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Hebrew Senior Life, Inst Aging Res, Boston, MA USA. Beth Israel Deaconess Med Ctr, Hebrew Rehabil Ctr, Boston, MA 02215 USA. Faulkner Hosp, Boston, MA USA. RP Mattison, MLP (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. FU NIA NIH HHS [5K12 AG00294] NR 28 TC 9 Z9 9 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2006 VL 34 IS 10 BP 2583 EP 2587 DI 10.1097/01.CCM.0000239112.49567.BD PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 088EZ UT WOS:000240795700010 PM 16915114 ER PT J AU Mitsiades, CS Mitsiades, N Hideshima, T Richardson, PG Anderson, KC AF Mitsiades, Constantine S. Mitsiades, Nicholas Hideshima, Teru Richardson, Paul G. Anderson, Kenneth C. TI Proteasome inhibition as a new therapeutic principle in hematological malignancies SO CURRENT DRUG TARGETS LA English DT Review DE proteasome; PS-341; bortezomib; multiple myeloma; apoptosis; combination therapies ID MULTIPLE-MYELOMA CELLS; NF-KAPPA-B; PHASE-I TRIAL; APOPTOTIC DEATH ACTIVATION; UNFOLDED PROTEIN RESPONSE; NON-HODGKINS-LYMPHOMA; PROSTATE-CANCER; CHEMOTHERAPEUTIC-AGENTS; INCREASED SENSITIVITY; CLINICAL-EXPERIENCE AB The intracellular concentration of proteins in both normal and tumor cells are regulated by the balance between the rates of protein synthesis vs. degradation. The ubiquitin-proteasome pathway is the main intracellular cascade for controlled degradation of proteins and has attracted in recent years major interest not only because of its biochemical complexity and the intricate regulation of its function, but also because diverse cell cycle regulators and modulators of apoptosis are subject to regulation by proteasome function, and can therefore be significantly affected by small molecule inhibitors of the proteolytic activity of the proteasome. In fact, bortezomib, the prototypic member of this class of agents, was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma patients. This review article focuses on the exciting recent progress in the use of proteasome inhibitors, with emphasis on the bench-to-bedside research effort which provided the foundation for clinical development of bortezomib for the treatment of multiple myeloma, as well as other hematologic malignancies, such as mantle cell lymphoma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM Constantine_Mitsiades@dfci.harvard.edu FU PHS HHS [R0-1 50947, P0-1 78378] NR 96 TC 32 Z9 33 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD OCT PY 2006 VL 7 IS 10 BP 1341 EP 1347 DI 10.2174/138945006778559247 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 083MX UT WOS:000240461200014 PM 17073596 ER PT J AU Horowitz, SH AF Horowitz, Steven H. TI Recent clinical advances in diabetic polyneuropathy SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Article DE diabetic polyneuropathy; impaired glucose tolerance; neuropathic pain AB Purpose of review Recent dramatic increases in the incidence and prevalence of diabetes make an understanding of chronic symmetric sensorimotor diabetic polyneuropathy, the most common and problematic of chronic diabetic complications, essential for a wide range of medical practitioners. Recent findings The demonstration of neuropathic dysfunction in patients with prediabetes or impaired glucose tolerance emphasizes the susceptibility of peripheral nerve fibers, especially small A delta fibers and C fibers, to relatively mild, short-duration hyperglycemia. New testing can reveal peripheral nerve dysfunction prior to clinical neuropathic symptoms and signs. In the absence of effective medications to halt or reverse nerve damage or promote nerve regeneration, early diagnosis of diabetic polyneuropathy, followed by tight glycemic control with diet and exercise, offers the best opportunity to prevent progressive symptoms of sensory loss, pain, autonomic dysfunction, ulcerations, and amputations. Some patients with impaired glucose tolerance have a reversal of neuropathic features with tight glycemic control. Nonpharmacologic therapies for neuropathic pain in diabetic polyneuropathy appear promising. Summary Tight glycemic control, especially early in diabetes, is the best approach to minimizing the prevalence and severity of diabetic polyneuropathy and makes research into the deleterious effects of even mild hyperglycemia imperative. C1 [Horowitz, Steven H.] Massachusetts Gen Hosp, Dept Neurol, WACC 835,55 Fruit St, Boston, MA 02114 USA. RP Horowitz, SH (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC 835,55 Fruit St, Boston, MA 02114 USA. EM shhorowitz@partners.org NR 62 TC 14 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD OCT PY 2006 VL 19 IS 5 BP 573 EP 578 DI 10.1097/01.aco.0000245287.37905.c5 PG 6 WC Anesthesiology SC Anesthesiology GA V42RZ UT WOS:000209632200018 PM 16960494 ER PT J AU Luo, BH Springer, TA AF Luo, Bing-Hao Springer, Timothy A. TI Integrin structures and conformational signaling SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID ALPHA(L)BETA(2) HYBRID DOMAIN; INSIDE-OUT ACTIVATION; LOW-AFFINITY STATE; BETA-A DOMAIN; I-LIKE DOMAIN; CRYSTAL-STRUCTURE; EXTRACELLULAR SEGMENT; TRANSMEMBRANE HELICES; CYTOPLASMIC FACE; SUBUNIT AB Integrins are cell adhesion molecules that play critical roles in development, wound healing, hemostasis, immunity and cancer. Advances in the past two years have shed light on the structural basis for integrin regulation and signaling, especially on how global conformational changes between bent and extended conformations relate to the inter-domain and intra-domain shape shifting that regulates affinity for ligand. The downward movements of the C-terminal helices of the alpha 1 and beta 1 domains and the swing-out of the hybrid domain play pivotal roles in integrin conformational signaling. Experiments have also shown that integrins transmit bidirectional signals across the plasma membrane by coupling extracellular conformational change with an unclasping and separation of the alpha and beta transmembrane and cytoplasmic domains. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM SpringerOffice@cbr.med.harvard.edu FU NCI NIH HHS [R01 CA031799, CA31798, R01 CA031798, R37 CA031798]; NHLBI NIH HHS [HL48675, P01 HL048675]; NIAID NIH HHS [AI72765, R01 AI072765] NR 52 TC 143 Z9 150 U1 4 U2 15 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2006 VL 18 IS 5 BP 579 EP 586 DI 10.1016/j.ceb.2006.08.005 PG 8 WC Cell Biology SC Cell Biology GA 090HY UT WOS:000240943000016 PM 16904883 ER PT J AU Watt, FM Lo Celso, C Silva-Vargas, V AF Watt, Fiona M. Lo Celso, Cristina Silva-Vargas, Violeta TI Epidermal stem cells: an update SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID TRANSIT-AMPLIFYING CELLS; HAIR FOLLICLE; BETA-CATENIN; DIFFERENTIATION; SKIN; EXPRESSION; PROLIFERATION; RENEWAL; TUMORS; GROWTH AB The mammalian epidermis is a highly accessible tissue in which to study the properties of adult stem cells. Global gene expression profiling has revealed new markers and regulators of the stem cell compartment. Although stem cells have the potential to differentiate into multiple lineages, their progeny follow a more restricted number of lineages in undamaged epidermis as a result of local microenvironmental cues. The response of the epidermis to a particular signal depends on signal strength and duration. Recent advances in the field have led to elucidation of the mechanisms by which stem cells are maintained and the pathways that interact with Wnt signalling to specify lineage choice as cells leave the stem cell compartment. This work has also yielded new insights into skin tumour development. C1 Canc Res UK London Res Inst, London WC2A 3PX, England. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Watt, FM (reprint author), Canc Res UK London Res Inst, 44 Lincolns Inn Fields, London WC2A 3PX, England. EM fiona.watt@cancer.org.uk OI Lo Celso, Cristina/0000-0002-1163-4207; Watt, Fiona/0000-0001-9151-5154 NR 42 TC 124 Z9 136 U1 0 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD OCT PY 2006 VL 16 IS 5 BP 518 EP 524 DI 10.1016/j.gde.2006.08.006 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 095PP UT WOS:000241320300013 PM 16919447 ER PT J AU Ivers, LC Ryan, ET AF Ivers, Louise C. Ryan, Edward T. TI Infectious diseases of severe weather-related and flood-related natural disasters SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE cyclone; flood; hurricane; monsoon; tsunami; typhoon ID NINO-SOUTHERN-OSCILLATION; DENGUE HEMORRHAGIC-FEVER; TSUNAMI SURVIVORS; WOUND INFECTIONS; UNITED-STATES; SRI-LANKA; CUTANEOUS MELIOIDOSIS; CLIMATE VARIABILITY; YUCATAN PENINSULA; POTENTIAL IMPACTS AB Purpose of review The present review will focus on some of the possible infectious disease consequences of disastrous natural phenomena and severe weather, with a particular emphasis on infections associated with floods and the destruction of infrastructure. Recent findings The risk of infectious diseases after weather or flood-related natural disasters is often specific to the event itself and is dependent on a number of factors, including the endemicity of specific pathogens in the affected region before the disaster, the type of disaster itself, the impact of the disaster on water and sanitation systems, the availability of shelter, the congregating of displaced persons, the functionality of the surviving public health infrastructure, the availability of healthcare services, and the rapidity, extent, and sustainability of the response after the disaster. Weather events and floods may also impact disease vectors and animal hosts in a complex system. Summary Weather or flood-related natural disasters may be associated with an increased risk of soft tissue, respiratory, diarrheal, and vector-borne infectious diseases among survivors and responders. C1 Massachusetts Gen Hosp, Div Infect Dis, Trop & Geog Med Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Trop & Geog Med Ctr, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM etryan@partners.org NR 89 TC 62 Z9 65 U1 8 U2 56 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD OCT PY 2006 VL 19 IS 5 BP 408 EP 414 DI 10.1097/01.qco.0000244044.85393.9e PG 7 WC Infectious Diseases SC Infectious Diseases GA 089RP UT WOS:000240898600002 PM 16940862 ER PT J AU Howlett, GJ Moore, KJ AF Howlett, Geoffrey J. Moore, Kathryn J. TI Untangling the role of amyloid in atherosclerosis SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE amyloid; apolipoproteins; atherosclerosis; macrophages; scavenger receptors ID LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-C-II; B SCAVENGER RECEPTOR; ALZHEIMERS-DISEASE; BETA PEPTIDE; MACROPHAGE ACTIVATION; PLATELET PHAGOCYTOSIS; HUMAN MONOCYTES; A-I; CD36 AB Purpose of review Amyloid deposits are a defining feature of several age-related and debilitating diseases. Their widespread presence in atherosclerotic plaques suggests a potential role in lesion development. This review discusses the proteins known to accumulate in atheroma and examines the evidence that amyloid-like structures activate macrophage signaling pathways linked to inflammation and prothrombotic potential. Recent findings Numerous proteins that accumulate in atherosclerotic plaques form amyloid fibrils in vivo, including apolipoproteins, beta-amyloid, and alpha(1)-antitrypsin. In addition, oxidation or enzymatic modification of low-density lipoproteins induces a structural reorganization of the particle, including the acquisition of amyloid-like properties. Similarly, glycation of serum albumin, as observed in diabetes, is accompanied by the formation of aggregates with ail the hallmarks of amyloid. Several receptors implicated in atherogenesis modulate the fate of amyloid fibrils by mediating their clearance (scavenger receptors A and B-I), activating inflammatory signaling cascades (receptor for advanced glycation endproducts), or both (CD36). Finally, recent studies indicate that amyloid deposition accelerates diet-induced atherosclerosis in mice. Summary Given the substantial evidence that amyloid fibrils or preamyloidogenic species are cytotoxic, the aberrant deposition of amyloid in the intima may be pathologically important in vascular inflammation and the promotion of atherosclerosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit,Dept Med, Boston, MA 02114 USA. Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic, Australia. RP Moore, KJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit,Dept Med, GRJ1328,55 Fruit St, Boston, MA 02114 USA. EM kmoore@molbio.mgh.harvard.edu FU NIA NIH HHS [AG 020255] NR 53 TC 44 Z9 45 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD OCT PY 2006 VL 17 IS 5 BP 541 EP 547 DI 10.1097/01.mol.0000245260.63505.4f PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 092CR UT WOS:000241075100007 PM 16960503 ER PT J AU John, JF AF John, Joseph F., Jr. TI Drug evaluation: Tefibazumab - a monoclonal antibody against staphylococcal infection SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article ID CLUMPING FACTOR-A; AUREUS BACTEREMIA; EVOLUTION; SAFETY AB Inhibitex Inc is investigating tefibazumab, a humanized monoclonal antibody specific for the fibrin-binding surface epitope clumping factor A protein ( expressed on the surface of most Staphylococcus aureus strains), for the potential intravenous prevention and/or treatment of S aureus infections. In June 2006, Inhibitex was seeking to outlicense certain development rights to the drug. Pending the outcome of partnering discussions, Inhibitex suspended the initiation of any additional clinical trials of tefibazumab. Preclinical in vivo studies were ongoing at that time. C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29401 USA. RP John, JF (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. EM joseph.john2@med.va.gov NR 24 TC 7 Z9 7 U1 0 U2 1 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD OCT PY 2006 VL 8 IS 5 BP 455 EP 460 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 088NC UT WOS:000240817400011 PM 17078388 ER PT J AU Ramasubbu, K Bozkurt, B Mann, DL AF Ramasubbu, Kumudha Bozkurt, Biykem Mann, Douglas L. TI Mechanisms of idiopathic dilated cardiomyopathies SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE dilated cardiomyopathy; familial dilated cardiomyopathy; pathomechanisms; viral cardiomyopathy ID LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; BLACK-WHITE DIFFERENCES; ENDOMYOCARDIAL BIOPSY; MUSCULAR-DYSTROPHY; CLINICAL-FEATURES; RANDOMIZED-TRIAL; NATURAL-HISTORY; SKELETAL-MUSCLE; CARDIAC-MUSCLE AB Purpose of review Dilated cardiomyopathy is a disease of the heart muscle, characterized by ventricular dilation and depressed myocardial contractility in the absence of abnormal loading conditions or ischemic heart disease. Dilated cardiomyopathy may be viewed as a progressive disorder that is initiated after an 'index event' damages the heart muscle, thereby preventing the heart from contracting normally. This review will discuss the mechanisms of dilated cardiomyopathy, with special focus on familial dilated cardiomyopathy and virus-induced dilated cardiomyopathy. Recent findings In the past few years, discoveries in molecular genetics and virology have offered insights into the pathomechanisms of dilated cardiomyopathy. Summary The increasing knowledge of a potential causal link between genetic mutations and viral infections and the development of dilated cardiomyopathy may lead to a breakthrough in the treatment of the disease. In particular, the development of gene therapy to treat familial cardiomyopathy and the development of antiviral agents to treat persistent viral infections in virus-induced cardiomyopathy could greatly enhance the treatment of dilated cardiomyopathy. C1 Baylor Coll Med, Dept Cardiol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Cardiol Sect, Houston, TX USA. St Lukes Episcopal Hosp, Houston, TX 77030 USA. Texas Heart Inst, Winters Ctr Heart Failure Res, Houston, TX 77025 USA. RP Mann, DL (reprint author), St Lukes Episcopal Hosp, Baylor Coll Med, Dept Cardiol, 1709 Dryden,Suite 900, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 NR 81 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD OCT PY 2006 VL 11 IS 5 BP 553 EP 559 DI 10.1097/01.mot.0000244643.62599.9e PG 7 WC Transplantation SC Transplantation GA 097LC UT WOS:000241448000014 ER PT J AU Yasui, H Hideshima, T Richardson, PG Anderson, KC AF Yasui, Hiroshi Hideshima, Teru Richardson, Paul G. Anderson, Kenneth C. TI Recent advances in the treatment of multiple myeloma SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review ID NF-KAPPA-B; PROTEASOME INHIBITOR PS-341; OVERCOMES DRUG-RESISTANCE; BONE-MARROW MICROENVIRONMENT; HISTONE DEACETYLASE INHIBITOR; FIBROBLAST-GROWTH-FACTOR; NEWLY-DIAGNOSED MYELOMA; CELL-GROWTH; IN-VIVO; HEMATOLOGIC MALIGNANCIES AB Multiple Myeloma (MM) remains an incurable plasma cell malignancy in the bone marrow (BM) despite conventional therapies as well as high-dose therapies with stem cell support. Therefore novel biologically-based therapeutic approaches are required. Recently, intensive laboratory and preclinical studies have identified and validated therapeutic molecular targets in MM. In particular, recognition of the biologic significance of the BM microenvironment in MM pathogenesis and as a potential target for novel therapeutics has derived several promising approaches. Novel FDA approved agents including thatidomide/thalomid (R), its immunomodulatory derivatives lenalidomide/Revlimid (R), and proteasome inhibitor bortezomib/Velcade (R) are directed at molecular targets not only in MM cells but also in its BM milieu, and have already achieved promising results in clinical studies. Here we discuss the mechanisms of action of these novel drugs and their clinical application, alone or combined with conventional or novel drugs. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. RP Hideshima, T (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM teru_hideshima@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [R0-1 CA 50947, IP50 CA10070]; PHS HHS [P0-178378] NR 136 TC 11 Z9 13 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD OCT PY 2006 VL 7 IS 5 BP 381 EP 393 DI 10.2174/138920106778521569 PG 13 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 086JO UT WOS:000240669800008 PM 17076653 ER PT J AU Gritman, K Van Winkle, DM Lorentz, CU Pennica, D Habecker, BA AF Gritman, Kurt Van Winkle, Donna M. Lorentz, Christina U. Pennica, Diane Habecker, Beth A. TI The lack of cardiotrophin-1 alters expression of interleukin-6 and leukemia inhibitory factor mRNA but does not impair cardiac injury response SO CYTOKINE LA English DT Article DE gp130; cardiac protection; leukemia inhibitory factor; cardiotrophin-1; interleukin-6 ID EXPERIMENTAL MYOCARDIAL-INFARCTION; SYMPATHETIC-NERVE ACTIVITY; FACTOR-RECEPTOR; TARGETED DISRUPTION; MYOCYTE HYPERTROPHY; CELL HYPERTROPHY; GP130; CYTOKINE; SURVIVAL; HEART AB Cardiotrophin-1 (CT-1) was identified as a growth factor for cardiac myocytes and CT-1 protects myocytes from cell death. Adult CT-1(-/-) mice exhibit neural deficits including the loss of preganglionic sympathetic neurons, but their autonomic and cardiac parameters have not been examined. We used these mice to determine if the absence of CT-1 or loss of preganglionic sympathetic input altered heart rate, left ventricular pressure, cardiac contractility (dP/dt), or cell death following ischemia-reperfusion. Basal heart rate was increased in CT-1(-/-) mice, and this difference was abolished by ganglionic block. Left ventricular pressure and dP/dt were unchanged. Dobutamine stimulated similar increases in heart rate and dP/dt in both genotypes, but ventricular pressure was significantly lower in CT-1 nulls. Cardiac expression of interleukin-6 (IL-6) mRNA was increased significantly in CT-1 null mice, while leukemia inhibitory factor (LIF) mRNA was unchanged. Infarct size normalized to area at risk was no different in CT-1(-/-) mice (33.8 +/- 1.0% vs. 37.7 +/- 3.2% WT) 24 h after ischemia-reperfusion. Induction of IL-6 mRNA after infarct was significantly abrogated in CT-1 null mice compared to wild-type mice, but LIF mRNA-induction remained significant in CT-1 null mice and might contribute to cardiac protection in the absence of CT-1. (c) 2006 Elsevier Ltd. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Anesthesiol, Portland, OR 97239 USA. Portland VA Med Ctr, Anesthesiol Serv, Portland, OR 97239 USA. Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. RP Habecker, BA (reprint author), Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. EM habecker@ohsu.edu OI Habecker, Beth/0000-0002-4658-8730 FU NHLBI NIH HHS [HL68231, R01 HL068231] NR 46 TC 16 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2006 VL 36 IS 1-2 BP 9 EP 16 DI 10.1016/j.cyto.2006.10.004 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 130PA UT WOS:000243810300002 PM 17150369 ER PT J AU Tolland, JP Brenn, T Guldbakke, KK Schanbacher, CF AF Tolland, Julia P. Brenn, Thomas Guldbakke, Kjetil K. Schanbacher, Carl F. TI Mohs micrographic surgery, sentinel lymph node mapping, and estrogen receptor analysis for the treatment of malignant nodular hidradenoma SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID SWEAT GLAND CARCINOMA; ECCRINE SPIRADENOMA; BREAST-CANCER; HIDRADENOCARCINOMA; ACROSPIROMA; BIOPSY; ADENOCARCINOMA; NECK; IMMUNOHISTOCHEMISTRY; NEOPLASMS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Dermatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Royal Hosp Trust, Dept Dermatol, Belfast, Antrim, North Ireland. RP Tolland, JP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Dermatol, 44 Binney St, Boston, MA 02115 USA. EM Carl_Schanbacher@dfci.harvard.edu NR 46 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 2006 VL 32 IS 10 BP 1294 EP 1301 DI 10.1111/j.1524-4725.2006.32295.x PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 093XB UT WOS:000241202500015 PM 17034384 ER PT J AU Mikkola, HKA Orkin, SH AF Mikkola, Hanna K. A. Orkin, Stuart H. TI The journey of developing hematopoietic stem cells SO DEVELOPMENT LA English DT Review ID FETAL LIVER HEMATOPOIESIS; BLOOD-ISLAND FORMATION; SLAM FAMILY RECEPTORS; SAC-EMBRYO CHIMERAS; ALPHA-IIB-INTEGRIN; EX-VIVO EXPANSION; ADULT BONE-MARROW; MURINE YOLK-SAC; LONG-TERM; MOUSE EMBRYO AB Hematopoietic stem cells (HSCs) develop during embryogenesis in a complex process that involves multiple anatomical sites. Once HSC precursors have been specified from mesoderm, they have to mature into functional HSCs and undergo self-renewing divisions to generate a pool of HSCs. During this process, developing HSCs migrate through various embryonic niches, which provide signals for their establishment and the conservation of their self-renewal ability. These processes have to be recapitulated to generate HSCs from embryonic stem cells. Elucidating the interactions between developing HSCs and their niches should facilitate the generation and expansion of HSCs in vitro to exploit their clinical potential. C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Inst Stem Cell Biol & Med, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst,Harvard Stem Cell Inst, Childrens Hosp,Dept Pediat Oncol, Boston, MA 02115 USA. RP Mikkola, HKA (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Inst Stem Cell Biol & Med, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. EM hmikkola@mcdb.ucla.edu NR 132 TC 210 Z9 215 U1 2 U2 31 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT 1 PY 2006 VL 133 IS 19 BP 3733 EP 3744 DI 10.1242/dev.02568 PG 12 WC Developmental Biology SC Developmental Biology GA 083LR UT WOS:000240457900001 PM 16968814 ER PT J AU Soccio, T Zhang, YY Bacci, S Mlynarski, W Placha, G Raggio, G Di Paola, R Marucci, A Johnstone, MT Gervino, EV Abumrad, NA Klein, S Trischitta, V Doria, A AF Soccio, Teresa Zhang, Yuan-Yuan Bacci, Simonetta Mlynarski, Wojciech Placha, Grzegorz Raggio, Greer Di Paola, Rosa Marucci, Antonella Johnstone, Michael T. Gervino, Ernest V. Abumrad, Nada A. Klein, Samuel Trischitta, Vincenzo Doria, Alessandro TI Common haplotypes at the adiponectin receptor 1 (ADIPOR1) locus are associated with increased risk of coronary artery disease in type 2 diabetes SO DIABETES LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; PLASMA-PROTEIN ADIPONECTIN; INSULIN-RESISTANCE; MYOCARDIAL-INFARCTION; ENCODING ADIPONECTIN; GENETIC-VARIATION; FAMILY-HISTORY; DEFICIENT MICE; HUMAN GENOME; APM1 GENE AB Adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects. This study investigated whether common polymorphisms in the adiponectin receptor 1 (ADIPOR1) gene mediating these effects influence the risk of coronary artery disease (CAD) in type 2 diabetes. Linkage disequilibrium. analysis of 28 single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR1 locus revealed two haplotype blocks that could be tagged by six SNPs. These six markers were typed in two populations of CAD-positive and -negative subjects with type 2 diabetes, one from Boston (n = 411) and the other from Italy (n = 533). In the Boston population, the three tags of the more 3' block were all significantly associated with CAD (P = 0.001-0.01). A similar trend, although not significant, was found in Italian subjects. Haplotype analysis of the combined populations revealed different haplotype distributions in case and control subjects (P = 0.0002), with one common haplotype being associated in homozygotes with a greater than threefold increase in cardiovascular risk (odds ratio 3.6 [95% CI 1.8-7.2]). Some of the genotypes associated with increased cardiovascular risk were associated with 30-40% lower ADIPOR1 mRNA levels in blood mononuclear cells (n = 60) and adipose tissue biopsies (n = 28) (P = 0.001-0.014). Our findings point to genetic variability at the ADIPOR1 locus as a strong determinant of CAD susceptibility in type 2 diabetes. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. IRCCS Casa Sollievo Sofferenza, Endocrine Unit, San Giovanni Rotondo, Italy. Warsaw Univ, Dept Hypertens, Warsaw, Poland. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Washington Univ, Sch Med, Dept Med, Div Nutr Sci, St Louis, MO USA. Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu RI Di Paola, Rosa/G-7813-2011; Trischitta, Vincenzo/K-1487-2016; marucci, antonella/B-8722-2017 OI Di Paola, Rosa/0000-0001-5837-9111; Trischitta, Vincenzo/0000-0003-1174-127X; marucci, antonella/0000-0001-8131-8317 FU NHLBI NIH HHS [HL71981, HL73168, R01 HL073168, R01 HL073168-03]; NIDDK NIH HHS [DK56341, DK36836, DK60837, P30 DK056341, P30 DK056341-05S2, P30 DK056341-06] NR 36 TC 29 Z9 35 U1 1 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2006 VL 55 IS 10 BP 2763 EP 2770 DI 10.2337/db06-0613 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089VU UT WOS:000240910400012 PM 17003341 ER PT J AU Yao-Borengasser, A Rasouli, N Varma, V Miles, LM Phanavanh, B Starks, TN Phan, J Spencer, HJ McGehee, RE Reue, K Kern, PA AF Yao-Borengasser, Aiwei Rasouli, Neda Varma, Vijayalakshmi Miles, Leslie M. Phanavanh, Bounleut Starks, Tasha N. Phan, Jack Spencer, Horace J., III McGehee, Robert E., Jr. Reue, Karen Kern, Philip A. TI Lipin expression is attenuated in adipose tissue of insulin-resistant human subjects and increases with peroxisome proliferator-activated receptor gamma activation SO DIABETES LA English DT Article ID TREATMENT PANEL-III; NONDIABETIC SUBJECTS; WEIGHT-LOSS; IN-VIVO; SENSITIVITY; GLUCOSE; OBESITY; FAT; LIPODYSTROPHY; REDUCTION AB Lipin-alpha and -beta are the alternatively spliced gene products of the Lpin1 gene, whose product lipin is required for adipocyte differentiation. Lipin deficiency causes lipodystrophy, fatty liver, and insulin resistance in mice, whereas adipose tissue lipin overexpression results in increased adiposity but improved insulin sensitivity. To assess lipin expression and its relation to insulin resistance in humans, we examined lipin-alpha and -beta mRNA levels in subjects with normal or impaired glucose tolerance. We found higher expression levels of both lipin isoforms in lean, insulin-sensitive subjects. When compared with normal glucose-tolerant subjects, individuals with impaired glucose tolerance were more insulin resistant, demonstrated higher levels of intramyocellular lipids (IMCLs), and expressed similar to 50% lower levels of lipin-alpha and -beta. In addition, there was a strong inverse correlation between adipose tissue lipin expression and muscle IMCLs but no evidence for an increase in muscle lipid oxidation. After treatment of the impaired glucose-tolerant subjects with insulin sensitizers for 10 weeks, pioglitazone (but not metformin) resulted in a 60% increase in the insulin sensitivity index (Si) and a 32% decrease in IMCLs (both P < 0.01), along with an increase in lipin-beta (but not lipin-alpha) expression by 200% (P < 0.005). Lipin expression in skeletal muscle, however, was not related to obesity or insulin resistance. Hence, high adipose tissue lipin expression is found in insulin-sensitive subjects, and lipin-beta expression increases following treatment with pioglitazone. These results suggest that increased adipogenesis and/or lipogenesis in subcutaneous fat, mediated by the LPIN1 gene, may prevent lipotoxicity in muscle, leading to improved insulin sensitivity. C1 Univ Arkansas Med Sci, Dept Med, Div Endocrinol, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Human Genet, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. RP Kern, PA (reprint author), Univ Arkansas Med Sci, Dept Med, Div Endocrinol, Cent Arkansas Vet Healthcare Syst, 598-151 LR,4300 W 7th St, Little Rock, AR 72205 USA. EM kernphilipa@uams.edu FU NCRR NIH HHS [M01RR14288]; NHLBI NIH HHS [HL 24841]; NIDDK NIH HHS [DK 71346, DK 39176, DK 71277] NR 36 TC 71 Z9 75 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 OCT PY 2006 VL 55 IS 10 BP 2811 EP 2818 DI 10.2337/db05-1688 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089VU UT WOS:000240910400018 PM 17003347 ER PT J AU Saxena, R Gianniny, L Burtt, NP Lyssenko, V Giuducci, C Sjogren, M Florez, JC Almgren, P Isomaa, B Orho-Melander, M Lindblad, U Daly, MJ Tuomi, T Hirschhorn, JN Ardlie, KG Groop, LC Altshuler, D AF Saxena, Richa Gianniny, Lauren Burtt, Noel P. Lyssenko, Valeriya Giuducci, Candace Sjogren, Marketa Florez, Jose C. Almgren, Peter Isomaa, Bo Orho-Melander, Marju Lindblad, Ulf Daly, Mark J. Tuomi, Tiinamaija Hirschhorn, Joel N. Ardlie, Kristin G. Groop, Leif C. Altshuler, David TI Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals SO DIABETES LA English DT Article ID LARGE-SCALE ASSOCIATION; GENE REGION; HAPLOTYPE STRUCTURE; E23K VARIANT; 7,883 PEOPLE; BETA-CELL; RISK; CHANNEL; DISEASES; RECEPTOR AB Recently, common noncoding variants in the TCF7L2 gene were strongly associated with increased risk of type 2 diabetes in samples from Iceland, Denmark, and the U.S. We genotyped 13 single nucleotide polymorphisms (SNPs) across TCF7L2 in 8,310 individuals in family-based and case-control designs from Scandinavia, Poland, and the U.S. We convincingly confirmed the previous association of TCF7L2 SNPs with the risk of type 2 diabetes (rs7903146T odds ratio 1.40 [95% CI 1.30-1.50], P = 6.74 x 10(-20)). In nondiabetic individuals, the risk genotypes were associated with a substantial reduction in the insulinogenic index derived from an oral glucose tolerance test (risk allele homozygotes have half the insulin response to glucose of noncarriers, P = 0.003) but not with increased insulin resistance. These results suggest that TCF7L2 variants may act through insulin secretion to increase the risk of type 2 diabetes. C1 MIT, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Helsinki, Cent Hosp, Dept Med, Folkhalsan Inst Genet,Folkhalsan Res Ctr, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Skaraborg Inst, Skovde, Sweden. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Gen Collaborat, Cambridge, MA USA. RP Altshuler, D (reprint author), Dept Mol Biol Endocrinol, Simches Res Bldg,175 Cambridge St,CPZN-6818, Boston, MA 02114 USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NIDDK NIH HHS [1 K23 DK65978-03] NR 26 TC 244 Z9 252 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2006 VL 55 IS 10 BP 2890 EP 2895 DI 10.2337/db06-0381 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089VU UT WOS:000240910400029 PM 17003358 ER PT J AU Ahmed, J Ward, TP Bursell, SE Aiello, LM Cavallerano, JD Vigersky, RA AF Ahmed, Jehanara Ward, Thomas P. Bursell, Sven-Eric Aiello, Lloyd M. Cavallerano, Jerry D. Vigersky, Robert A. TI The sensitivity and specificity of nonmydriatic digital stereoscopic retinal imaging in detecting diabetic retinopathy SO DIABETES CARE LA English DT Article ID MACULAR EDEMA; UNITED-STATES; PREVALENCE; CARE; TELEMEDICINE; PROGRAM; CAMERA AB OBJECTIVE - The objective of this study was to determine the sensitivity and specificity of Joslin Vision Network nonmydriatic digital stereoscopic retinal imaging (NMDSRI) as a screening tool in detecting diabetic retinopathy. RESEARCH DESIGN AND METHODS - We reviewed the records of 244 patients with diabetes who had a dilated funduscopic examination (DFE) and NMDSRI done within I year of each other at four locations in the metropolitan Washington, DC, area. The images were transmitted through a local area network to a central reading location where they were graded by a single retinal specialist. RESULTS - Images of 482 eyes from 243 patients were included in the study. Four images did not transmit, and 35% of the images were not gradable. Of the remaining 311 eyes, there was 86% agreement in the grading between NMDSRI and DFE: 227 eyes with no diabetic retinopathy and 40 eyes with diabetic retinopathy. In 46 eyes (15%) there was a disagreement between gradings made by the two techniques. NMDSRI detected diabetic retinopathy in 35 eyes reported as normal by DFE, and in the remaining II eyes, the DFE grade was one grade higher than the NMDSRI grade. Adjudicated nonconcordant examinations were within one grade. In the 76 eyes with diabetic retinopathy, retinal thickness could not be assessed in 17 (21%) eyes. When the NMDSRI result was gradable, the overall sensitivity of NMDSRI was 98% and the specificity was 100% for retinopathy within one grade of the DFE. In the limited number of eyes that had diabetic retinopathy with macular edema (six), agreement with the clinical examination was 100%. CONCLUSIONS - NMDSRI is a sensitive and specific method for the screening and diagnosis of diabetic retinopathy, which may help improve compliance with the standards of eye care for patients with diabetes. C1 Walter Reed Army Med Ctr, Serv Endocrinol, Washington, DC 20307 USA. Howard Univ Hosp, Div Endocrinol & Metab, Washington, DC USA. Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA. Harvard Univ, Sch Med, Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Vigersky, RA (reprint author), Walter Reed Army Med Ctr, Serv Endocrinol, 6900 Georgia Ave NW, Washington, DC 20307 USA. EM robert.vigersky@na.amedd.army.mil NR 21 TC 71 Z9 73 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2006 VL 29 IS 10 BP 2205 EP 2209 DI 10.2337/dc06-0295 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 091FZ UT WOS:000241013600004 PM 17003294 ER PT J AU Grant, RW Wald, JS Poon, EG Schnipper, JL Gandhi, TK Volk, LA Middleton, B AF Grant, Richard W. Wald, Jonathan S. Poon, Eric G. Schnipper, Jeffrey L. Gandhi, Tejal K. Volk, Lynn A. Middleton, Blackford TI Design and implementation of a web-based patient portal linked to an ambulatory care electronic health record: Patient gateway for diabetes collaborative care SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID SELF-MANAGEMENT PROGRAMS; RISK-FACTORS; HYPERTENSIVE POPULATION; RANDOMIZED-TRIAL; CLINICAL INERTIA; CHRONIC ILLNESS; UNITED-STATES; QUALITY; DISEASE; ADULTS AB Background: Despite the availability of expert guidelines and widespread diabetes quality improvement efforts, care of patients with diabetes remains suboptimal. Two key barriers to care that may be amenable to informatics-based interventions include (1) lack of patient engagement with therapeutic care plans and (2) lack of medication adjustment by physicians ("clinical inertia") during clinical encounters. Methods: The authors describe the conceptual framework, design, implementation, and analysis plan for a diabetes patient web-portal linked directly to the electronic health record (EHR) of a large academic medical center via secure Internet access designed to overcome barriers to effective diabetes care. Results: Partners HealthCare System (Boston, MA), a multi-hospital health care network comprising several thousand physicians caring for over 1 million individual patients, has developed a comprehensive patient web-portal called Patient Gateway that allows patients to interact directly with their EHR via secure Internet access. Using this portal, a specific diabetes interface was designed to maximize patient engagement by importing the patient's current clinical data in an educational format, providing patient-tailored decision support, and enabling the patient to author a "Diabetes Care Plan." The physician view of the patient's Diabetes Care Plan was designed to be concise and to fit into typical EHR clinical workflow. Conclusions: We successfully designed and implemented a Diabetes Patient portal that allows direct interaction with our system's EHR. We are assessing the impact of this advanced informatics tool for collaborative diabetes care in a clinic-randomized controlled trial among 14 primary care practices within our integrated health care system. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Partners Informat Syst, Clin Informat Res & Dev, Wellesley, MA USA. Partners Informat Syst, Clin & Qual Anal, Wellesley, MA USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50-9 Staniford St, Boston, MA 02114 USA. EM Rgrant@partners.org OI Middleton, Blackford/0000-0002-1819-1234; Grant, Richard/0000-0002-6164-8025 FU AHRQ HHS [R01 HS013660-02]; NIDDK NIH HHS [K23 DK067452, K23 DK067452-02] NR 43 TC 31 Z9 32 U1 1 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD OCT PY 2006 VL 8 IS 5 BP 576 EP 586 DI 10.1089/dia.2006.8.576 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112NB UT WOS:000242531700007 PM 17037972 ER PT J AU Kotton, CN Lankowski, AJ Hohmann, EL AF Kotton, Camille N. Lankowski, Alexander J. Hohmann, Elizabeth L. TI Comparison of rectal swabs with fecal cultures for detection of Salmonella typhimurium in adult volunteers SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Salmonella; swab; culture ID INFECTIONS; CARRIAGE; DURATION; VACCINE; SYSTEM AB Rectal swabs are generally considered less sensitive than fecal culture, but there are no data directly comparing human rectal swabs with fecal samples for detection of Salmonella. A phase I clinical study of a live oral attenuated Salmonella typhimurium, vaccine strain in volunteers receiving a large known inoculum provided the opportunity to compare concurrent rectal swab and fecal cultures. Of 155 paired samples from 9 volunteers, 65 (42%) were culture positive: 35 (54%) by both methods, 20 (31%) by fecal culture only, and 10 (15%) by swab only. When compared with fecal culture, rectal swabs were 64% sensitive and 90% specific. Rectal swabs are of moderate diagnostic utility for detection of Salmonella and may be useful when collection of fecal samples is impractical. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. EM ckotton@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIAID NIH HHS [K08 AI001701]; PHS HHS [R01 51206] NR 19 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 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD OCT PY 2006 VL 56 IS 2 BP 123 EP 126 DI 10.1016/j.diagmicrobio.2006.04.003 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 097JV UT WOS:000241444400003 PM 16725299 ER PT J AU Quivy, JP Guenatri, M Roche, D Bailly, D Maison, C Kirschner, D Tagami, H Nakatani, Y Almouzni, G AF Quivy, J. P. Guenatri, M. Roche, D. Bailly, D. Maison, C. Kirschner, D. Tagami, H. Nakatani, Y. Almouzni, G. TI Propagation of epigenetic states at the level of chromatin assembly SO DIFFERENTIATION LA English DT Meeting Abstract C1 Inst Curie Rech, CNRS, UMR 218, Paris, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Pasteur, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD OCT PY 2006 VL 74 IS 8 MA O7 BP 450 EP 451 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 085KN UT WOS:000240603100010 ER PT J AU Upton, MP Nishioka, NS Ransil, BJ Rosenberg, SJ Puricelli, WP Zwas, FR Shields, HM AF Upton, Melissa P. Nishioka, Norman S. Ransil, Bernard J. Rosenberg, Stanley J. Puricelli, William P. Zwas, Felice R. Shields, Helen M. TI Multilayered epithelium may be found in patients with Barrett's epithelium and dysplasia or adenocarcinoma SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE multilayered epithelium; Barrett's epithelium; dysplasia; adenocarcinoma; photodynamic therapy ID COLUMNAR-LINED ESOPHAGUS; GASTROESOPHAGEAL REFLUX DISEASE; RESERVE CELL HYPERPLASIA; PHOTODYNAMIC THERAPY; ESOPHAGOGASTRIC JUNCTION; ACID SUPPRESSION; INTESTINAL METAPLASIA; CANCER-RISK; BILE REFLUX; SURVEILLANCE AB To determine if multilayered epithelium (MLE) is a useful prognostic indicator for a benign natural history of Barrett's epithelium, we evaluated endoscopic biopsies from patients with Barrett's epithelium without and with dysplasia and/or adenocarcinoma and from non-Barrett's controls for the presence of MLE. MLE was found in 6% of non-Barrett's controls, 30% of Barrett's patients with no dysplasia, and 14% of Barrett's patients with dysplasia and/or adenocarcinoma. MLE was significantly associated with shorter lengths of Barrett's epithelium in both Barrett's groups. Three of 5 photodynamic therapy patients were noted to develop MLE after therapy. MLE may be found in patients with dysplasia and/or adenocarcinoma and after photodynamic therapy; its presence is not useful as a prognostic indicator for a more benign course of Barrett's. This study confirms that MLE is significantly associated with shorter lengths of Barrett's epithelium. C1 Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT USA. Greenwich Hosp, Dept Med, Greenwich, England. RP Shields, HM (reprint author), Beth Israel Deaconess Med Ctr, Div Gastroenterol, 330 Brookline Ave, Boston, MA 02215 USA. EM hshields@bidmc.harvard.edu NR 58 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2006 VL 51 IS 10 BP 1783 EP 1790 DI 10.1007/s10620-006-9243-9 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099XY UT WOS:000241632300021 PM 16967312 ER PT J AU Gross, RD Horne, RS Atwood, CW AF Gross, Roxann D. Horne, R. S. Atwood, C. W. TI Novel computer program that quantifies pharyngeal residue SO DYSPHAGIA LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Visualizat Software LLC, Stanford, CA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD OCT PY 2006 VL 21 IS 4 BP 292 EP 292 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA 128IJ UT WOS:000243651100022 ER PT J AU Nunn, D Gaissert, H Zeitels, S AF Nunn, Danny Gaissert, H. Zeitels, S. TI Successful revision of laryngeal/tracheal diversion: Case study SO DYSPHAGIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD OCT PY 2006 VL 21 IS 4 BP 311 EP 311 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA 128IJ UT WOS:000243651100056 ER PT J AU Nunn, D Gaissert, H AF Nunn, Danny Gaissert, H. TI Swallowing after pharyngeal colonic interposition-review of 6 cases SO DYSPHAGIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD OCT PY 2006 VL 21 IS 4 BP 323 EP 323 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA 128IJ UT WOS:000243651100080 ER PT J AU Kammer, R Baillies, A Gill, G Hind, J Hewitt, A Robbins, J AF Kammer, Rachael Baillies, A. Gill, G. Hind, J. Hewitt, A. Robbins, J. TI Comparison of commercial thickeners for achieving diagnostic and treatment congruence SO DYSPHAGIA LA English DT Meeting Abstract C1 Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Univ Wisconsin, Sch Med, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD OCT PY 2006 VL 21 IS 4 BP 328 EP 328 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA 128IJ UT WOS:000243651100091 ER PT J AU Ashland, J Hartnick, C Haver, K Chien, W Hardy, S AF Ashland, Jean Hartnick, C. Haver, K. Chien, W. Hardy, S. TI Laryngeal cleft in children: Dysphagia assessment and outcomes SO DYSPHAGIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD OCT PY 2006 VL 21 IS 4 BP 329 EP 329 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA 128IJ UT WOS:000243651100093 ER PT J AU Baskin, DG AF Baskin, Denis G. TI Single-minded view of melanocortin signaling in energy homeostasis SO ENDOCRINOLOGY LA English DT Editorial Material ID CAUDAL BRAIN-STEM; CENTRAL-NERVOUS-SYSTEM; FOOD-INTAKE; SIM1 GENE; PARAVENTRICULAR NUCLEUS; RECEPTOR STIMULATION; EXPRESSION PATTERNS; OBESITY; NEURONS; PROTEIN C1 Univ Washington, Sch Med, Div Endocrinol Metab, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Baskin, DG (reprint author), Univ Washington, Sch Med, Div Endocrinol Metab, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 32 TC 7 Z9 7 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2006 VL 147 IS 10 BP 4539 EP 4541 DI 10.1210/en.2006-0807 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 087IW UT WOS:000240737100001 PM 16980439 ER PT J AU Bounoutas, GS Tawfeek, H Frohlich, LF Chung, UI Abou-Samra, AB AF Bounoutas, George S. Tawfeek, Hesham Frohlich, Leopold F. Chung, Ung-il Abou-Samra, Abdul B. TI Impact of impaired receptor internalization on calcium homeostasis in knock-in mice expressing a phosphorylation-deficient parathyroid hormone (PTH)/PTH-related peptide receptor SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; ABNORMAL SKELETAL RESPONSE; KIDNEY-CELLS; DOWN-REGULATION; PTH/PTHRP RECEPTOR; ADENYLATE-CYCLASE; CHRONIC UREMIA; KINASE-C; DESENSITIZATION; BETA AB Internalization of G protein-coupled receptors ( GPCRs) and desensitization of the hormonal responses are well characterized in vitro for several hormonal systems. The physiological role of internalization for a GPCR receptor involved in homeostatic functions has not been established, although it has been assumed based on in vitro data. We have previously shown that phosphorylation of the PTH/PTHrP receptor is required for its internalization and for the desensitization of the responsiveness to PTH and PTHrP in vitro; the internalization and desensitization response is impaired in a PTH/PTHrP receptor mutant bearing serine to alanine mutations in the phosphate acceptor sites. To understand the physiological role of receptor internalization on calcium homeostasis, we have knocked-in the internalization-impaired PTH/PTHrP receptor mutant using homologous recombination technology. The genetically modified animals exhibited calcium levels no different from control animals, but PTH levels were one third of those in control animals indicating that homeostasis could be maintained only by 3-fold suppression of PTH secretion. We also analyzed the calcemic response to PTH in vivo. Here we show that mice expressing the internalization-impaired PTH/PTHrP receptor mutant have dramatically exaggerated cAMP and calcemic responses to sc PTH administration when compared with control animals given the same dose. These data show for the first time the role of G protein receptor phosphorylation and internalization per se in the regulatory function of an endocrine system controlled by a GPCR. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [R01 DK062285, P01 DK45485] NR 35 TC 18 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2006 VL 147 IS 10 BP 4674 EP 4679 DI 10.1210/en.2006-0301 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 087IW UT WOS:000240737100018 PM 16840548 ER PT J AU Bird, TD AF Bird, Thomas D. TI Invited comments on the Shostak and Ottman review SO EPILEPSIA LA English DT Editorial Material ID HUNTINGTON-DISEASE; ALZHEIMERS-DISEASE; SUICIDE; IMPACT; RISK C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Bird, TD (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM tomnroz@u.washington.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2006 VL 47 IS 10 BP 1748 EP 1749 DI 10.1111/j.1528-1167.2006.00885_3.x PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 093TB UT WOS:000241191100024 PM 17054702 ER PT J AU Cavusoglu, E Ruwende, C Chopra, V Yanamadala, S Eng, C Clark, LT Pinsky, DJ Marmur, JD AF Cavusoglu, Erdal Ruwende, Cyril Chopra, Vineet Yanamadala, Sunitha Eng, Calvin Clark, Luther T. Pinsky, David J. Marmur, Jonathan D. TI Adiponectin is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction in patients presenting with chest pain SO EUROPEAN HEART JOURNAL LA English DT Article DE inflammation; adiponectin; prognosis; body mass index; TIMP-1; biomarker; IL-10 ID CHRONIC HEART-FAILURE; ADIPOSE-SPECIFIC PROTEIN; TISSUE INHIBITOR; PLASMA ADIPONECTIN; CARDIOVASCULAR-DISEASE; FAT DISTRIBUTION; RAT MODEL; EXPRESSION; OBESITY; RISK AB Aims To determine the prognostic value of baseline plasma adiponectin levels in patients with known or suspected coronary artery disease referred for coronary angiography. Methods and results Adiponectin was measured in 325 male patients with stable angina, troponin-negative unstable angina, and non-ST-segment elevation myocardial infarction (MI) undergoing coronary angiography at a Veterans Administration Medical Center. The patients were then followed prospectively for the occurrence of all-cause mortality, cardiac mortality, and MI. Follow-up data at 24 months were available for 97% of the patients. Adiponectin was the only biomarker to independently predict the individual endpoints of all-cause mortality, cardiac mortality, and MI. The 24-month survival rates for patients in the lower (<= 4.431 mg/L), middle (> 4.431 and <= 8.008 mg/L), and upper (> 8.008 mg/L) tertiles of plasma adiponectin values were 95.0, 90.4, and 83.5%, respectively (P=0.0232 by log-rank test). Furthermore, when patients with chest pain were risk-stratified into those with and without a non-ST-segment elevation acute coronary syndrome (NSTEACS), adiponectin remained an independent predictor of both all-cause mortality and cardiac mortality in the NSTEACS subgroup. Conclusion In a cohort of male patients undergoing coronary angiography, a single baseline determination of plasma adiponectin is independently predictive of the subsequent risk of death and MI. C1 Suny Downstate Med Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. Bronx Vet Affairs Med Ctr, Dept Med, Div Cardiol, Bronx, NY USA. Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Marmur, JD (reprint author), Suny Downstate Med Ctr, Dept Med, Div Cardiol, 450 Clarkson Ave,Box 1257, Brooklyn, NY 11203 USA. EM jonathan@marmur.com NR 31 TC 137 Z9 145 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2006 VL 27 IS 19 BP 2300 EP 2309 DI 10.1093/eurheartj/ehl153 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086TZ UT WOS:000240697200010 PM 16864609 ER PT J AU Ray, KK Bach, RG Cannon, CP Cairns, R Kirtane, AJ Wiviott, SD McCabe, CH Braunwald, E Gibson, CM AF Ray, Kausik K. Bach, Richard G. Cannon, Christopher P. Cairns, Richard Kirtane, Ajay J. Wiviott, Stephen D. McCabe, Carolyn H. Braunwald, Eugene Gibson, C. Michael CA PROVE IT TIMI 22 Investigators TI Benefits of achieving the NCEP optional LDL-C goal among elderly patients with ACS SO EUROPEAN HEART JOURNAL LA English DT Article DE elderly; NCEP; LDL-C; clinical events; statins ID ACUTE CORONARY SYNDROMES; LIPID-LOWERING THERAPY; MYOCARDIAL-INFARCTION; HEART-DISEASE; CARDIOVASCULAR EVENTS; CONTROLLED TRIAL; OLDER PATIENTS; CHOLESTEROL; PRAVASTATIN; REGISTRY AB Aims To assess the efficacy and safety of the achievement of the NCEP goal of LDL-C < 1.8 mmol/L in elderly patients with ACS. Methods and results The relationship between LDL-C at 30 days after ACS and subsequent clinical outcomes were compared among elderly patients (aged >= 70 years) vs. younger counterparts in the PROVE IT-TIMI 22 trial, using the composite endpoint of death, myocardial infarction, or unstable angina. Among 634 elderly patients, the achievement of the NCEP goal was associated with an 8% absolute and a 40% relative lower risk of events [Hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.41-0.87, P=0.008] vs. corresponding benefits of 2.3 and 26% in 3150 younger patients (HR 0.74, 95% CI 0.59-0.94, P=0.013). The estimated number of events preventable among the elderly by the achievement of these goals was 80 events at 2 years for every 1000 patients at goal vs. those not at goal, compared with 23 events potentially prevented in younger patients. The incidence of major side effects among the elderly was similar to that in younger patients and did not differ with the intensity of the statin regimen. Conclusion Among elderly ACS patients, achieving the new NCEP LDL-C optional goal as part of a secondary prevention strategy can be both as safe and effective as in younger patients. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Washington Univ, Sch Med, Div Cardiovasc, St Louis, MO 63110 USA. Nottingham Clin Res Ltd, Isaac Newton Ctr, Nottingham Sci & Technol Pk, Nottingham N67 2RH, England. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Ray, KK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Dept Med, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM koshray@gmail.com NR 19 TC 39 Z9 41 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2006 VL 27 IS 19 BP 2310 EP 2316 DI 10.1093/eurheartj/ehl180 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086TZ UT WOS:000240697200011 PM 16887854 ER PT J AU Ahmed, S Cannon, CP Murphy, SA Braunwald, E AF Ahmed, Shaheeda Cannon, Christopher P. Murphy, Sabina A. Braunwald, Eugene TI Acute coronary syndromes and diabetes: is intensive lipid lowering beneficial? Results of the PROVE IT-TIMI 22 trial SO EUROPEAN HEART JOURNAL LA English DT Article DE diabetes mellitus; acute coronary syndromes; lipid lowering; inflammation ID SCANDINAVIAN-SIMVASTATIN-SURVIVAL; HIGH-DOSE ATORVASTATIN; C-REACTIVE PROTEIN; IMPAIRED FASTING GLUCOSE; MRC/BHF HEART PROTECTION; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR EVENTS; CHOLESTEROL LEVELS; SUBGROUP-ANALYSES; STATIN THERAPY AB Aims The impact of intensive lipid lowering therapy with statins in acute coronary syndrome (ACS) patients with diabetes mellitus (DM) is not well characterized. Methods and results We explored this question in data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) TIMI 22 trial, which tested standard (pravastatin 40 mg) vs. intensive (atorvastatin 80 mg) statin therapy among patients treated early in the post-ACS period. We compared outcomes between patients with DM (identified by history, fasting plasma glucose >= 126 mg/dL or haemoglobin A1C > 7%; n=978) against those without DM (n=3184). The rate of acute cardiac events (death, myocardial infarction, and unstable angina requiring rehospitalization) was much higher in patients with DM, but was reduced with intensive vs. standard therapy similarly in diabetic (21.1 vs. 26.6%, HR=0.75, P=0.03) and non-diabetic patients (14.0 vs. 18.0%, HR=0.76, P=0.002); P-interaction=0.97. Despite intensive therapy, the majority of diabetics (62%) did not reach the dual goal of LDL-C < 70 mg/dL and high-sensitivity C-reactive protein < 2 mg/L. Conclusion In ACS patients with DM, intensive statin therapy reduces acute cardiac events as it does in those without DM, with 55 vs. 40 events prevented per 1000 patients treated. However, our data highlight the need for additional strategies in this high-risk group. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org NR 37 TC 46 Z9 47 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2006 VL 27 IS 19 BP 2323 EP 2329 DI 10.1093/eurheartj/ehl220 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086TZ UT WOS:000240697200013 PM 16954134 ER PT J AU Raffel, OC Jang, IK AF Raffel, Owen Christopher Jang, Ik-Kyung TI Incidental finding of a ruptured thin-cap fibroatheroma by optical coherence tomography SO EUROPEAN HEART JOURNAL LA English DT Article C1 Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Dept Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org NR 0 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2006 VL 27 IS 20 BP 2393 EP 2393 DI 10.1093/eurheartj/ehi870 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 092JE UT WOS:000241092000010 PM 16613934 ER PT J AU Sabatine, MS AF Sabatine, Marc S. TI Clopidogrel in ST-elevation myocardial infarction SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article DE clopidogrel; fibrinolysis; ST-elevation myocardial infarction ID PERCUTANEOUS CORONARY INTERVENTION; PLACEBO-CONTROLLED TRIAL; FIBRINOLYTIC THERAPY; SEGMENT ELEVATION; REPERFUSION THERAPY; RANDOMIZED TRIAL; ASPIRIN; CLARITY-TIMI-28; PATENCY AB Platelet adhesion, activation, and aggregation are central to the pathophysiology of the acute coronary syndromes (ACS). Clopidogrel, an oral thienopyridine derivative, is a platelet adenosine diphosphate (ADP)-receptor antagonist capable of inhibiting platelet activation. The benefits of clopidogrel in patients with stable coronary artery disease undergoing elective percutaneous coronary interventions (PCI) and in patients presenting with non-ST-elevation ACS are well established. This article will review the results of recent clinical trials in which the utility of clopidogrel in patients with ST-elevation myocardial infarction was evaluated. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Thrombolysis Myocardial Infarct TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org NR 21 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD OCT PY 2006 VL 8 IS G BP G31 EP G34 DI 10.1093/eurheartj/sul052 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 105TD UT WOS:000242054300007 ER PT J AU Yuan, Q Campanella, GS Colvin, RA Hamilos, DL Jones, KJ Mathew, A Means, TK Luster, AD AF Yuan, Qian Campanella, Gabriele S. Colvin, Richard A. Hamilos, Daniel L. Jones, Krister J. Mathew, Anuja Means, Terry K. Luster, Andrew D. TI Membrane-bound eotaxin-3 mediates eosinophil transepithelial migration in IL-4-stimulated epithelial cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE chemokines; chemotaxis; eosinophils; human ID CHEMOATTRACTANT PROTEIN (MCP)-4; DEVELOP AIRWAY EOSINOPHILIA; CC-CHEMOKINE RECEPTOR-3; ENDOTHELIAL-CELLS; GENE-EXPRESSION; TISSUE EOSINOPHILIA; MOLECULAR-CLONING; PERIPHERAL-BLOOD; HEPARIN-BINDING; TH2 CELLS AB Epithelial cells play an important role in orchestrating mucosal immune responses. In allergic-type inflammation, epithelial cells control the recruitment of eosinophils into the mucosa. Th2-type cytokine-driven release of eosinophil-active chemokines from epithelial cells directs eosinophil migration into the mucosal epithelium. CCR3, the main eosinophil chemokine receptor, regulates this process; however, the respective contribution of individual CCR3 ligands in eosinophil transepithelial migration is less well understood. Using an in vitro transepithelial chemotaxis system, we found that eotaxin-3 produced by IL-4-stimulated airway epithelial cells and CCR3 on eosinophils exclusively mediate eosinophil transepithelial migration. Eotaxin-3 protein levels were also increased in the nasal mucosal epithelium recovered from allergic patients as compared to non-allergic patients. Surprisingly, eotaxin-3 in IL-4-stimulated airway epithelial cells was predominantly cell surface bound, and the cell surface form was critical for eosinophil transepithelial migration. Eotaxin-3 cell surface association was partially glycosaminoglycan (GAG) dependent, but was completely protein dependent, suggesting that eotaxin-3 associates with both GAG and cell surface proteins. We thus provide evidence that cell surface-associated eotaxin-3 is the critical IL-4-dependent chemotactic signal mediating eosinophil transepithelial migration in the setting of allergic inflammation. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat, Div Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, 8th Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu FU NIAID NIH HHS [R01-AI40618]; NIDDK NIH HHS [K08-DK68085] NR 44 TC 24 Z9 24 U1 0 U2 0 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 OCT PY 2006 VL 36 IS 10 BP 2700 EP 2714 DI 10.1002/eji.200636112 PG 15 WC Immunology SC Immunology GA 097RJ UT WOS:000241465700015 PM 16983721 ER PT J AU Barton, JJS Goff, DC Manoach, DS AF Barton, Jason J. S. Goff, Donald C. Manoach, Dara S. TI The inter-trial effects of stimulus and saccadic direction on prosaccades and antisaccades, in controls and schizophrenia patients SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE saccades; plasticity; inhibition of return; antisaccades; alternation advantage ID ATTENTIONAL ASYMMETRY; EYE-MOVEMENT; DEFICIENT INHIBITION; BLUNTED INHIBITION; ANTI-SACCADES; PRO-SACCADES; RETURN; TASK; PLASTICITY; VOLUNTARY AB We investigated the influence of the direction of preceding saccadic trials on the latency of current prosaccades and antisaccades, in healthy subjects and patients with schizophrenia. When prosaccades and antisaccades were performed in separate, single-task blocks, we found that only prosaccades were delayed if the saccade in the prior trial was in the same direction, consistent with the expected directional effect from an 'inhibition of return'-like alternation advantage. However, both types of saccades were executed more quickly when the saccade in the penultimate trial was in the same direction, consistent with previous demonstrations of directional plasticity in monkeys. In blocks of randomly mixed prosaccades and antisaccades, the directional effects in healthy subjects were greatest when a prosaccade was preceded by an antisaccade, consistent with a summation of effects of alternation advantage (from the prior stimulus) and directional plasticity (from the prior saccade). Schizophrenic patients showed an additional phenomenon, a directionally specific inhibition of upcoming saccades by preceding antisaccades. These results suggest that saccades in humans are modulated by inter-trial effects attributable to both an 'inhibition of return'-like alternation advantage and directional plasticity. C1 Univ British Columbia, Vancouver Gen Hosp, Eye Care Ctr,Dept Ophthalmol & Visual Sci, Neuroophthamol Sect D,Div Neurol, Vancouver, BC V5Z 3N9, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. Univ British Columbia, Dept Psychol, Vancouver, BC, Canada. RP Barton, JJS (reprint author), Univ British Columbia, Vancouver Gen Hosp, Eye Care Ctr,Dept Ophthalmol & Visual Sci, Neuroophthamol Sect D,Div Neurol, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada. EM jasonbarton@shaw.ca RI Barton, Jason/A-6362-2012 FU NIMH NIH HHS [R01 MH67720] NR 38 TC 19 Z9 19 U1 5 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 2006 VL 174 IS 3 BP 487 EP 498 DI 10.1007/s00221-006-0492-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 087BM UT WOS:000240717300010 PM 16642313 ER PT J AU Ishijima, M Ezura, Y Tsuji, K Rittling, SR Kurosawa, H Denhardt, DT Emi, M Nifuji, A Noda, M AF Ishijima, Muneaki Ezura, Yoichi Tsuji, Kunikazu Rittling, Susan R. Kurosawa, Hisashi Denhardt, David T. Emi, Mitsuru Nifuji, Akira Noda, Masaki TI Osteopontin is associated with nuclear factor kappa B gene expression during tail-suspension-induced bone loss SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE osteopontin; mechanical loading; rodent; array; stromal cell ID ENDOTHELIAL-CELL SURVIVAL; OSTEOBLAST-LIKE CELLS; MECHANICAL-STRESS; DEFICIENT MICE; SIGNALING PATHWAYS; SHEAR-STRESS; CANCER CELLS; ACTIVATION; EGR-1; RESORPTION AB Osteoporosis due to unloading-induced bone loss is a critical issue in the modem aging society. Although the mechanisms underlying this phenomenon are largely unknown, osteopontin (OPN) is one of the critical mediators required for unloading-induced bone loss [M. Ishijima, S.R. Rittling, T. Yamashita, K. Tsuji, H. Kurosawa, A. Nifuji, D.T. Denhardt, and M. Noda, Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin, J Exp Med, 193 (2001) 399-404]. To clarify the molecular bases for OPN actions, we carried out microarray analyses on the genes expressed in the femoral bone marrow cells in wild type and OPN-/- mice. The removal of the mechanical load induced bone loss in wild type, but not in OPN-/- mice, as previously reported. Expression analysis of 9586 cDNAs on a microarray system revealed that OPN deficiency blocked tail-suspension-induced expression of ten genes (group A). This observation was confirmed based on semi-quantitative RT-PCR analyses. On the other hand, expression of four genes (group B) was not altered by tail suspension in wild type but was enhanced in OPN-deficient mice. NF-kappa B p105 subunit gene (Nfkb1) was found in group A and Bax in group B. p53 gene expression was upregulated by tail suspension in wild type mice, but it was no longer observed in OPN-/- mice. These data indicate that OPN acts to mediate mechanical stress signaling upstream to the genes encoding apoptosis-related molecules, and its action is associated with alteration of the genes. (c) 2006 Elsevier Inc. All rights reserved. C1 Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 1010062, Japan. Rutgers State Univ, Nelson Labs, Piscataway, NJ 08854 USA. Forsyth Inst, Boston, MA 02115 USA. Nippon Med Coll, Inst Gerontol, Dept Mol Biol, Kawasaki, Kanagawa, Japan. Juntendo Univ, Sch Med, Dept Orthopaed, Tokyo 1138421, Japan. Tokyo Med & Dent Univ, 21st Century Ctr Excellence COE, Program Mol Destruct & Reconstruct Tooth & Bone, Tokyo 1010062, Japan. Tokyo Med & Dent Univ, Japan Soc Promot Sci, Core Core Program Adv Bone & Joint Sci, Tokyo 1010062, Japan. Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Tokyo 1010062, Japan. RP Ezura, Y (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, 3-10 Kanda Surugadai 2 Chome, Tokyo 1010062, Japan. EM ezura.mph@mril.tmd.ac.jp; noda.mph@mri.tmd.ac.jp RI Ezura, Yoichi/L-9485-2016 FU NCI NIH HHS [CA72740]; NIAMS NIH HHS [AR44434]; NIEHS NIH HHS [ES06897] NR 40 TC 29 Z9 35 U1 0 U2 6 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 1 PY 2006 VL 312 IS 16 BP 3075 EP 3083 DI 10.1016/j.yexcr.2006.06.003 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 085EV UT WOS:000240587200009 PM 16889770 ER PT J AU Nakuci, E Mahner, S DiRenzo, J ElShamy, WM AF Nakuci, Enkeleda Mahner, Sven DiRenzo, James ElShamy, Wad M. TI BRCA1-IRIS regulates cyclin D1 expression in breast cancer cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE BRCA1-IRIS; SRC1; SRC3; c-Jun; JNK; cyclin D1 ID STEROID-RECEPTOR COACTIVATOR-1; ESTROGEN-RESPONSIVE ELEMENT; CATHEPSIN-D GENE; C-JUN; MEDIATED TRANSACTIVATIONS; HISTONE ACETYLTRANSFERASE; TRANSCRIPTION FACTOR; ACTIVATION; AMPLIFICATION; INHIBITION AB The regulator of cell cycle progression, cyclin D1, is up-regulated in breast cancer cells; its expression is, in part, dependent on ER alpha signaling. However, many ER alpha-negative tumors and tumor cell lines (e.g., SKBR3) also show over-expression of cyclin D1. This suggests that, in addition to ER alpha signaling, cyclin D1 expression is under the control of other signaling pathways; these pathways may even be over-expressed in the ER alpha-negative cells. We previously noticed that both ER alpha-positive and -negative cell lines over-express BRCA1-IRIS mRNA and protein. Furthermore, the level of over-expression of BRCA1-IRIS in ER alpha-negative cell lines even exceeded its over-expression level in ER alpha-positive cell lines. In this study, we show that: (1) BRCA1-IRIS forms complex with two of the nuclear receptor co-activators, namely, SRC1 and SRC3 (AIB1) in an ER alpha-independent manner. (2) BRCA1-IRIS alone, or in connection with co-activators, is recruited to the cyclin D1 promoter through its binding to c-Jun/AP1 complex; this binding activates the cyclin D1 expression. (3) Over-expression of BRCA1-IRIS in breast cells over-activates JNK/c-Jun; this leads to the induction of cyclin D1 expression and cellular proliferation. (4) BRCA1-IRIS activation of JNK/c-Jun/AP1 appears to account for this, because in cells that were depleted from BRCA1-IRIS, JNK remained inactive. However, depletion of SRC1 or SRC3 instead reduced c-Jun expression. Our data suggest that this novel signaling pathway links BRCA1-IRIS to cellular proliferation through c-Jun/AP1 nuclear pathway; finally, this culminates in the increased expression of the cyclin D1 gene. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP ElShamy, WM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM wael_elshamy@dfci.harvard.edu RI Mahner, Sven/F-3560-2014 NR 38 TC 16 Z9 19 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 1 PY 2006 VL 312 IS 16 BP 3120 EP 3131 DI 10.1016/j.yexcr.2006.06.021 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 085EV UT WOS:000240587200013 PM 16860316 ER PT J AU Aggarwal, R Ghobrial, IA Roodman, GD AF Aggarwal, Rohit Ghobrial, Irene A. Roodman, G. David TI Chemokines in multiple myeloma SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID MACROPHAGE-INFLAMMATORY PROTEIN-1-ALPHA; CELL-DERIVED FACTOR-1-ALPHA; MARROW STROMAL CELLS; BONE-MARROW; PERIPHERAL-BLOOD; RECEPTOR CXCR3; LYMPHOCYTE CHEMOATTRACTANT; PROTEIN (MIP)-1-ALPHA; CHEMOTACTIC CYTOKINES; ENDOTHELIAL-CELLS AB Objective. In this article we focus on the role that chemokines and chemokine receptors play in the pathogenesis of multiple myeloma and the associated bone destructive process, and consider their utility as novel therapeutic targets for treating this devastating disease. Methods. Current research on the role that chemokine and chemokine receptors play in the pathogenesis of myeloma is reviewed. Results. The chemokines, MIP-1 alpha, MCP-1, IL-8, and SDF-1, and their receptors play important roles in homing of MM cells, tumor growth, and bone destruction in myeloma. They are attractive therapeutic targets for treating myeloma patients. Conclusion. Addition of chemokine antagonists to current treatment regimens for myeloma should result in better therapeutic responses because of the loss of both the protective effect of the marrow microenvironment on the MM cells and the induction of osteoclast activity. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Div Hematol, Pittsburgh, PA 15260 USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, Res & Dev 151U, Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu FU NCI NIH HHS [R01 CA133799, R01 CA133799-01A1] NR 76 TC 70 Z9 73 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 2006 VL 34 IS 10 BP 1289 EP 1295 DI 10.1016/j.exphem.2006.06.017 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 092YV UT WOS:000241134700001 PM 16982321 ER PT J AU Gordon, LK AF Gordon, L. K. TI Orbital inflammatory disease: a diagnostic and therapeutic challenge SO EYE LA English DT Review DE inflammation; orbit; myositis; pseudotumour ID TOLOSA-HUNT-SYNDROME; ERDHEIM-CHESTER-DISEASE; IDIOPATHIC SCLEROSING INFLAMMATION; SUPERIOR OBLIQUE MUSCLE; CHURG-STRAUSS-SYNDROME; GIANT-CELL ARTERITIS; RHEUMATOID-ARTHRITIS; WEGENERS-GRANULOMATOSIS; EYE DISEASE; MYCOPHENOLATE-MOFETIL AB The spectrum of orbital inflammatory disease (OID) ranges broadly from specific disease diagnoses, for example, Wegener's granulomatosis or sarcoidosis, to nonspecific inflammation which may involve one or multiple structures of the orbit. Mimics of idiopathic OID must be considered in a comprehensive differential diagnosis and include malignancies, congenital mass lesions, infectious diseases, and occult or distant trauma. Idiopathic OID may be secondary to an underlying systemic inflammatory disease, which must be diagnosed in order to develop a comprehensive therapeutic plan, or may represent localized pathologic processes without systemic involvement. Evaluation of the patient with suspected OID must include a careful history, physical examination, directed laboratory, and radiologic studies, and may sometimes require tissue for diagnostic studies. Therapeutic options for inflammatory diseases are expanding as biologically targeted agents become available that act on specific segments of the inflammatory cascades. The purpose of this paper is to provide a framework for the evaluation and management of patients with the spectrum of diseases known as OID and to discuss some of the new advances in immunologic monitoring and targeted immune therapies that will likely play an increasingly important role in the care of these patients. C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. EM lgordon@ucla.edu NR 123 TC 68 Z9 70 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD OCT PY 2006 VL 20 IS 10 BP 1196 EP 1206 DI 10.1038/sj.eye.6702383 PG 11 WC Ophthalmology SC Ophthalmology GA 092EG UT WOS:000241079200010 PM 17019419 ER PT J AU Probst, JC Laditka, SB Moore, CG Harun, N Powell, MP Baxley, EG AF Probst, Janice C. Laditka, Sarah B. Moore, Charity G. Harun, Nusrat Powell, M. Paige Baxley, Elizabeth G. TI Rural-urban differences in depression prevalence: Implications for family medicine SO FAMILY MEDICINE LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; MENTAL-HEALTH-SERVICES; MAJOR DEPRESSION; UNITED-STATES; SURVEY REPLICATION; RACIAL/ETHNIC DIFFERENCES; OLDER-ADULTS; DISORDERS; CARE; POLICY AB Background and Objectives: Rural populations experience more adverse living circumstances than urban populations, but the evidence regarding the prevalence of mental health disorders in rural areas is contradictory. We examined the prevalence of depression in rural versus urban areas. Methods: We performed a cross-sectional study using the 1999 National Health Interview Survey (NHIS). In face-to-face interviews, the NHIS administered the Composite International Diagnostic Interview Short Form (CIDI-SF) depression scale to a nationally representative sample of 30,801 adults, ages 18 and suffer from depression. The unadjusted prevalence over. Results: An estimated 2.6 million rural adults suffer from depression. was significantly higher among rural than urban populations (6.1% versus 5.2%). After adjusting for rural/urban population characteristics, however, the odds of depression did not differ by residence. Depression risk was higher among persons likely to be encountered in a primary care setting: those with fair or poor se self-reported health, hypertension, with limitations in daily activities, or whose health status changed during the previous year. Conclusions: The prevalence of depression is slightly but significantly higher in residents of rural areas compared to urban areas, possibly due to differing population characteristics. C1 Univ S Carolina, S Carolina Rural Hlth Res Ctr, Columbia, SC 29210 USA. Univ S Carolina, Dept Family & Prevent Med, Columbia, SC 29210 USA. Univ N Carolina, Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27515 USA. Univ Alabama, Dept Hlth Serv Adm, Birmingham, AL USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. RP Probst, JC (reprint author), Univ S Carolina, S Carolina Rural Hlth Res Ctr, 220 Stoneridge Dr,Suite 204, Columbia, SC 29210 USA. EM jprobst@gwm.se.edu NR 37 TC 65 Z9 65 U1 9 U2 16 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 J9 FAM MED JI Fam. Med. PD OCT PY 2006 VL 38 IS 9 BP 653 EP 660 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 186SQ UT WOS:000247798900010 PM 17009190 ER PT J AU Klucken, J Outeiro, TF Nguyen, P McLean, PJ Hyman, BT AF Klucken, Jochen Outeiro, Tiago F. Nguyen, Paul McLean, Pamela J. Hyman, Bradley T. TI Detection of novel intracellular alpha-synuclein oligomeric species by fluorescence lifetime imaging SO FASEB JOURNAL LA English DT Article DE Parkinson's disease; Lewy body disease; chaperone; protein aggregation ID PARKINSONS-DISEASE; IN-VITRO; DROSOPHILA MODEL; FIBRIL FORMATION; AGGREGATION; PROTEIN; TOXICITY; DYNAMICS; CONFORMATION; SUPPRESSION AB Oligomerization and aggregation of alpha-synuclein molecules are believed to play a major role in neuronal dysfunction and loss in Parkinson's disease (PD) and dementia with Lewy bodies. However, alpha-synuclein oligomerization and aggregation have been detected only indirectly in cells using detergent extraction methods. Here, we show for the first time intracellular alpha-synuclein oligomerization using fluorescence lifetime imaging (FLIM). Two forms of alpha-synuclein homomeric interactions were detected: an antiparallel amino terminus-carboxyl terminus interaction between alpha-synuclein molecules, and a close amino terminus-carboxy terminus interaction within single alpha-synuclein molecules. Coexpression of the chaperone protein Hsp70, which can block alpha-synuclein toxicity in several systems, causes alpha-synuclein to adopt a different, open conformation, but Hsp70 does not alter alpha-synuclein-alpha-synuclein interactions. Thus, the neuroprotective effect of Hsp70 can be explained by its chaperone activity on alpha-synuclein molecules, rather than alteration of alpha-synuclein-alpha-synuclein interactions. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. Univ Regensburg, Dept Neurol, D-8400 Regensburg, Germany. RP McLean, PJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimers Dis Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM pmclean@partners.org RI Outeiro, Tiago/C-1067-2008 OI Outeiro, Tiago/0000-0003-1679-1727 FU NINDS NIH HHS [5P50 NS38372A-06] NR 47 TC 53 Z9 56 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2006 VL 20 IS 12 BP 2050 EP 2057 DI 10.1096/fj.05-5422com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 093GS UT WOS:000241156900013 PM 17012257 ER PT J AU Yamagata, M Rook, SL Sassa, Y Ma, RC Geraldes, P Goddard, L Clermont, A Gao, B Salti, H Gundel, R White, M Feener, EP Aiello, LP King, GL AF Yamagata, Michiko Rook, Susan L. Sassa, Yukio Ma, Ronald C. Geraldes, Pedro Goddard, Lucy Clermont, Allen Gao, Benbo Salti, Haytham Gundel, Robert White, Mark Feener, Edward P. Aiello, Lloyd Paul King, George L. TI Bactericidal/permeability-increasing protein's signaling pathways and its retinal trophic and anti-angiogenic effects SO FASEB JOURNAL LA English DT Article DE ERK; Akt; diabetic retinopathy; age-related macular degeneration; glypican 4 ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY; CELL-SURVIVAL; IN-VIVO; NEOVASCULARIZATION; BPI; CAPILLARIES; RETINOPATHY; ACTIVATION; EXPRESSION AB Bactericidal/permeability-increasing protein (BPI) was originally identified as a lipopolysaccharide (LPS) binding protein with Gram-negative bactericidal activity in the leukocytes. In this study, we characterized the previously unknown effects of BPI in the eye and the molecular mechanisms involved in its action. BPI mRNA was detected in bovine retina; retinal pigment epithelium; and primary cultures of bovine retinal pigment epithelial cells (RPE), pericytes (RPC), and endothelial cells (REC); while BPI protein was measured in human vitreous and plasma. BPI, but not control protein thaumatin, activated extracellular regulated kinase (ERK) and AKT, and increased DNA synthesis in RPE and RPC but not in REC. A human recombinant 21 kDa modified amino-terminal fragment of BPI (rBPI(21)) reduced H2O2-induced apoptosis in RPE and inhibited vascular endothelial growth factor (VEGF)-stimulated ERK phosphorylation in REC when preincubated with VEGF. Intraperitoneal (i.p.)-injected rBPI21 reduced ischemia-induced retinal neovascularization and diabetes-induced retinal permeability. Since BPI has unusual dual properties of promoting RPC and RPE growth while suppressing VEGF-induced REC growth and vascular permeability, the mechanistic understanding of BPI's action may provide novel therapeutic opportunities for diabetic retinopathy and age-related macular degeneration. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. XOMA US LLC, Dept Preclin Res & Cellular, Berkeley, CA USA. XOMA US LLC, Dept Analyt Dev, Berkeley, CA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu RI Sassa, Yukio/H-6339-2012; Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X FU NIDDK NIH HHS [P30 DK036836, P30 DK36836] NR 32 TC 14 Z9 21 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2006 VL 20 IS 12 BP 2058 EP 2067 DI 10.1096/05-5662com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 093GS UT WOS:000241156900014 PM 17012258 ER PT J AU Spruill, LS McDermott, PJ AF Spruill, Laura S. McDermott, Paul J. TI Regulation of c-jun mRNA expression in adult cardiocytes by MAP kinase interacting kinase-1 (MNK1) SO FASEB JOURNAL LA English DT Article DE cardiac hypertrophy; translation; eIF4E; protein synthesis; mRNA stability ID INITIATION-FACTOR 4E; ACTIVATED PROTEIN-KINASES; MYOCYTE ENHANCER FACTOR-2; TRANSLATION INITIATION; CARDIAC-HYPERTROPHY; GENE-EXPRESSION; SYNTHESIS RATES; OVERLOAD HYPERTROPHY; FELINE CARDIOCYTES; FACTOR EIF-4E AB Hypertrophic growth of adult myocardium is associated with increased expression of the early response gene c-jun. The purpose of this study was to determine whether eukaryotic initiation factor (elF) 4E (eIF4E) regulates translational efficiency of c-jun mRNA as measured by flux into polysomes. Adult feline cardiomyocytes in primary culture were treated with 0.2 mu M 12-O-tetradecanoylphorbol 13-acetate (TPA), and c-jun mRNA was quantified in total, monosome, and polysome fractions by real-time polymerase chain reaction. After 1 h, TPA increased total c-jun mRNA by 10.5-fold. The corresponding flux into polysomes was significantly lower (5-fold). Adenoviral-mediated overexpression of either eIF4E or a nonphosphorylatable mutant (S209/A) did not affect total c-jun mRNA or its flux between monosomes and polysomes. Similar results were obtained following overexpression of the eIF4E kinase Mnk1. Thus, translational efficiency of c-jun mRNA was not affected by changes in activity or amount of eIF4E. In contrast, a kinase-deficient Mnk1 mutant significantly reduced total c-jun mRNA from 9.8-fold to 6.0-fold while flux between monosomes and polysomes remained constant. The decrease in total c-jun mRNA resulted from increased decay of c-jun mRNA incorporated into the polysomes. We conclude that Mnk1 activity stabilizes c-jun mRNA in polysomes independent of eIF4E phosphorylation. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Charleston, SC 29403 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP McDermott, PJ (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Strom Thurmond Biomed Res Bldg,Rm 303,114 Dohty, Charleston, SC 29403 USA. EM mcdermp@musc.edu FU NHLBI NIH HHS [P01 HL-48788] NR 48 TC 7 Z9 7 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2006 VL 20 IS 12 BP 2133 EP + DI 10.1096/fj.06-6245fje PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 093GS UT WOS:000241156900033 PM 16940435 ER PT J AU Montoya, A Price, BH Lepage, M AF Montoya, Alonso Price, Bruce H. Lepage, Martin TI Neural correlates of 'functional' symptoms in neurology SO FUNCTIONAL NEUROLOGY LA English DT Review DE functional neuroimaging; functional symptoms; hysteria; neural correlates; neuroimaging ID PSYCHOGENIC PARKINSONISM; DISEASE; CONVERSION; DISORDERS; MOVEMENT; HYSTERIA AB Functional symptoms are neurological deficits that are not explained by organic lesions in the nervous system, but usually associated with emotional "psychogenic" disturbances. These symptoms are common and can affect any aspect of elementary neurological function, presenting clinicians with difficulties in definition, diagnosis, and treatment. Although current concepts explain functional symptoms in the context of "psychogenic" stress, the exact nature of these symptoms remains largely unknown. Recent functional neuroimaging studies have shifted understanding of these deficits from a psychological and psychodynamic model to a neurobiological model. This review highlights the advances made using functional neuroimaging techniques in patients suffering from two conditions: unilateral loss of motor function and psychogenic parkinsonism. The evidence suggests that areas including the prefrontal and parietal cortices, anterior cingulate cortex, thalamus, and basal ganglia may be implicated. Future studies, assessing patients at different phases of their illness and using newer techniques such as functional MRI, are needed to extend current findings on functional symptoms. C1 McGill Univ, Douglas Hosp, Res Ctr, Brain Imaging Grp, Montreal, PQ H3A 2T5, Canada. Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Montoya, A (reprint author), McGill Univ, Douglas Hosp, Res Ctr, Brain Imaging Grp, Montreal, PQ H3A 2T5, Canada. EM montoya_alonso@lilly.com NR 29 TC 12 Z9 12 U1 0 U2 1 PU C I C-EDIZIONI INTERNAZIONALI SRL PI ROME PA CORSO TRIESTE, 42, 00198 ROME, ITALY SN 0393-5264 J9 FUNCT NEUROL JI Funct. Neurol. PD OCT-DEC PY 2006 VL 21 IS 4 BP 193 EP 197 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 162HQ UT WOS:000246078000004 PM 17367578 ER PT J AU Lin, OS Kozarek, RA Schembre, DB Ayub, K Gluck, M Cantone, N Soon, MS Dominitz, JA AF Lin, Otto S. Kozarek, Richard A. Schembre, Drew B. Ayub, Kamran Gluck, Michael Cantone, Nico Soon, Maw-Soan Dominitz, Jason A. TI Risk stratification for colon neoplasia: Screening strategies using colonoscopy and computerized tomographic colonography SO GASTROENTEROLOGY LA English DT Article ID COLORECTAL-CANCER; CT COLONOGRAPHY; AVERAGE-RISK; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; CONVENTIONAL COLONOSCOPY; ENDOSCOPIC CAPACITY; ADENOMATOUS POLYPS; PROXIMAL NEOPLASIA; FAMILY-HISTORY AB Background & Aims: We developed a risk index to identify low-risk patients who may be screened for colorectal cancer with computerized tomographic colonography (CTC) instead of colonoscopy. Methods: Asymptomatic persons aged 50 years or older who had undergone screening colonoscopy were randomized retrospectively to derivation (n = 1512) and validation (n = 1493) subgroups. We developed a risk index (based on age, sex, and family history) from the derivation group. The expected results of 3 screening strategies-universal colonoscopy, universal CTC, and a stratified strategy of colonoscopy for high-risk and CTC for low-risk patients-were then compared. outcomes for the 3 strategies were extrapolated from the known colonic findings in each patient, using sensitivity/specificity values for CTC from the medical literature. Results were validated in the validation subgroup. Results: In the derivation subgroup, universal colonoscopy detected 94% of advanced neoplasia and universal CTC detected only 70% and resulted in the largest total number of procedures and number of patients undergoing both procedures. The stratified strategy detected 92% of advanced neoplasia, requiring colonoscopy in 68% and CTC in 36% of patients, with only 4% having to undergo both procedures. In the validation subgroup, universal colonoscopy detected 94% and universal CTC detected 71% of advanced neoplasia, whereas the stratified strategy detected 89%, requiring colonoscopy in 64% and CTC in 40%. Unlike universal CTC, the stratified strategy was independent of assumptions for CTC sensitivity, specificity, and threshold for colonoscopy. Conclusions: The stratified strategy based on our risk index may optimize the yield of colonoscopic resources and reduce the number of patients undergoing colonoscopy. C1 Virginia Mason Med Ctr, Gastroenterol Sect, Seattle, WA 98101 USA. ChangHua Christian Med Ctr, Div Gastroenterol, Changhua, Taiwan. VA Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Lin, OS (reprint author), Virginia Mason Med Ctr, Gastroenterol Sect, 1100 9th Ave, Seattle, WA 98101 USA. EM Otto.Lin@vmmc.org OI Dominitz, Jason/0000-0002-8070-7086 NR 39 TC 32 Z9 34 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2006 VL 131 IS 4 BP 1011 EP 1019 DI 10.1053/j.gastro.2006.08.015 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 094NS UT WOS:000241246800011 PM 17030171 ER PT J AU Matthes, K Bounds, BC Collier, K Gutierrez, A Brugge, WR AF Matthes, Kai Bounds, Brenna C. Collier, Kerry Gutierrez, Alexandra Brugge, William R. TI EUS staging of upper GI malignancies: results of a prospective randomized trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/106th Annual Meeting of the American-Gastroenterological-Association CY MAY 14-19, 2005 CL Chicago, IL SP Amer Gastroenterol Assoc ID EARLY GASTRIC-CANCER; RADIAL-SCANNING ECHOENDOSCOPE; ENDOSCOPIC MUCOSAL RESECTION; LYMPH-NODE METASTASES; ESOPHAGEAL CANCER; ESOPHAGOGASTRIC JUNCTION; ULTRASONOGRAPHY; ULTRASOUND; CARCINOMA; TUMORS AB Background: Electronic 2700 transverse-array EUS (TA-EUS) provides high-quality cross-sectional images but cannot guide FNA. Linear EUS (L-EUS) provides longitudinal images of malignancies and the ability to guide FNA. Objective: We conducted a prospective randomized comparison of TA-EUS and L-EUS for the staging of upper-GI (UGI) malignancies. Design: Forty-three patients underwent L-EUS immediately followed by TA-EUS (N = 27, 63%) or TA-EUS immediately followed by L-EUS (N = 16, 37%). Patients: Forty-three subjects (mean age, 64 years; 37 men) with an UGI malignancy (4 stomach and 38 esophageal) were evaluated with both TA-EUS and L-EUS. Interventions: Abnormal lymph nodes were sampled by FNA for cytology. Results: There was agreement on the T stage by linear and radial techniques in 38 of 43 subjects (88%). Twenty-seven of 43 patients (63%) had abnormal lymph nodes by linear or transverse-array imaging. L-EUS demonstrated 66 abnormal lymph nodes in 27 subjects (average of 2.4 nodes/subject). TA-EUS demonstrated 90 abnormal lymph nodes in 27 subjects (average of 3.3 nodes/subject, P = .009, compared with L-EUS). In 16 of the 27 subjects, an FNA was performed, which was positive in 13 cases (81%) and negative in 3 cases (10%) for malignancy. Conclusions: TA-EUS and L-EUS provide similar results of T staging of UGI malignancies. However, the number of abnormal lymph nodes detected by TA-EUS was more than by L-EUS. These findings suggest that radial or transverse-array EUS imaging should be the primary method for staging of UGI malignancies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. RP Brugge, WR (reprint author), 55 Fruit St,Blake 4, Boston, MA 02114 USA. NR 37 TC 23 Z9 23 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2006 VL 64 IS 4 BP 496 EP 502 DI 10.1016/j.gie.2006.01.023 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 092ZE UT WOS:000241135800005 PM 16996338 ER PT J AU Lieberman, D AF Lieberman, David TI Home repair and colonoscopy: quality counts SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID COMPUTED TOMOGRAPHIC COLONOGRAPHY C1 Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97201 USA. RP Lieberman, D (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol, Portland VA Med Ctr, Portland, OR 97201 USA. NR 7 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 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2006 VL 64 IS 4 BP 563 EP 564 DI 10.1016/j.gie.2006.04.024 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 092ZE UT WOS:000241135800017 PM 16996350 ER PT J AU Matthes, K Cohen, J AF Matthes, Kai Cohen, Jonathan TI The Neo-Papilla: a new modification of porcine ex vivo simulators for ERCP training (with videos) SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/106th Annual Meeting of the American-Gastroenterological-Association CY MAY 14-19, 2005 CL Chicago, IL SP Amer Gastroenterol Assoc ID GASTROINTESTINAL ENDOSCOPY; GASTROENTEROLOGY FELLOWS; COLONOSCOPY SIMULATOR; GI ENDOSCOPY; EXPERIENCE; MODEL AB Background: Computer simulators, live pigs, and ex vivo porcine simulators are used for training in ERCP The location of the porcine biliary orifice in the proximal duodenum is dissimilar to human anatomy, making the endoscopy experience less realistic. In addition, in native porcine anatomy, the pancreatic duct enters the duodenum distal to the biliary orifice, limiting the teaching of pancreatic techniques and selective duct cannulation. Objective: To overcome these limitations, we aimed to construct a Neo-Papilla that could be incorporated into an ex vivo model. Design: We attached chicken heart tissue to the porcine duodenum, with integrated porcine arteries that resembled an artificial common bile duct and a pancreatic duct. Setting: The simulator was presented and evaluated at 2 major GI endoscopy conferences. Main Outcome Measurements: The feasibility and the realism of this prototype was tested by 9 recognized ERCP experts who rated this model in comparison to other teaching models for ERCP by recollection of prior experience. Results: The Neo-Papilla was more prominent and more distally located than the native porcine papilla. The experts rated this modification superior to existing models in its usefulness as an educational tool. Limitations: Pilot study. Conclusions: We demonstrated the technical feasibility of a real-tissue Neo-Papilla modification of porcine ex vivo simulators, more closely approximating the natural anatomy This new model should facilitate ERCP training. Formal validation studies are warranted. C1 NYU, Div Gastroenterol, Sch Med, New York, NY 10016 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. RP Cohen, J (reprint author), NYU, Div Gastroenterol, Sch Med, 232 E 30th St, New York, NY 10016 USA. NR 23 TC 22 Z9 23 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2006 VL 64 IS 4 BP 570 EP 576 DI 10.1016/j.gie.2006.02.046 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 092ZE UT WOS:000241135800019 PM 16996352 ER PT J AU Funovics, MA Alencar, H Montet, X Weissleder, R Mahmood, U AF Funovics, Martin A. Alencar, Herlen Montet, Xavier Weissleder, Ralph Mahmood, Umar TI Simultaneous fluorescence imaging of protease expression and vascularity during murine colonoscopy for colonic lesion characterization SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID LIGHT-SCATTERING SPECTROSCOPY; IN-VIVO; COLORECTAL-CANCER; MOUSE MODEL; BARRETTS-ESOPHAGUS; INTESTINAL TUMORS; GENE-EXPRESSION; ENZYME-ACTIVITY; BETA-CATENIN; MISS RATES AB Background: Molecularly targeted fluorescent probes are currently being developed to improve the endo- scopic detection of intestinal pathologic conditions. Objective: We report on the development and testing of a novel multichannel microendoscope capable of quantitatively reporting such probes simultaneously at different wavelengths in real time. We assessed the feasibility of detecting and quantifying beacons that can be activated by protease and correlating imaging with disease state. Design: The microendoscope consisted of a 20-gauge fiberoptic catheter and dichroic beam splitters that simultaneously display visible light, 700 nm and 800 nm near infrared (NIR) fluorescent light. NIR interchannel separation was tested on in vitro phantoms. Two mouse models were used (Apcmin(+/-) mice for colonic adenomas and CT26 murine colon cancer). A perfusion probe and one activated by protease at a separate wavelength were injected before endoscopic evaluation. Results: The microendoscope fluorochrome detection limit was approximately 10 fmol; ratio imaging in the NIR was accurate (+/- 8% of true probe concentration between 0.3 to 100 mu g/ml of a protease sensor). Both colonic adenomas and adenocarcinomas were clearly visible in the NIR channel on protease probe administration in live mice. Ratio imaging of protease activity/perfusion increased from healthy colon to adenomas to adenocarcinomas. Limitations: Evaluation across additional spontaneous tumor models may provide more data on the translation of these findings. Conclusions: Our data show the feasibility of multichannel microendoscopic imaging of molecular targets in vivo and that ratio imaging may provide a novel means for characterizing colonic lesions. When scaled up clinically, this could aid in increasing lesion detection and quantitative assessment of distinct molecular markers. RP Mahmood, U (reprint author), Harvard Univ, CMIR, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Med Sch, 149 13th St,5408, Charlestown, MA 02129 USA. OI Montet, Xavier/0000-0003-2442-5866 FU NIBIB NIH HHS [EB001872]; PHS HHS [P50 C 86355] NR 49 TC 37 Z9 37 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2006 VL 64 IS 4 BP 589 EP 597 DI 10.1016/j.gie.2006.02.048 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 092ZE UT WOS:000241135800022 PM 16996355 ER PT J AU Lee, HS Li, W Lee, A Rodine, P Graham, RR Ortmann, WA Batliwalla, F Lee, KW Bae, SC Behrens, TW Gregersen, PK AF Lee, H-S Li, W. Lee, A. Rodine, P. Graham, R. R. Ortmann, W. A. Batliwalla, F. Lee, K. W. Bae, S. C. Behrens, T. W. Gregersen, P. K. TI Microsatellite typing for DRB1 alleles: application to the analysis of HLA associations with rheumatoid arthritis SO GENES AND IMMUNITY LA English DT Article DE microsatellite typing; HLA-DRBI; rheumatoid arthritis ID HAPLOTYPE RECONSTRUCTION; SUSCEPTIBILITY; POPULATION; GENETICS; DISEASE; SEVERITY; HLA-DRB1; FREQUENCIES; GENOTYPE; GENES AB The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for DRB1 genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 RA patients and 374 controls) and 1364 Korean individuals (744 RA patients and 620 controls), all of whom were previously genotyped for DRB1. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value > 0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of DRB1* 09 and DRB1* 10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with rheumatoid arthritis, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility. C1 N Shore LIJ Hlth Syst, Robert S Boas Ctr Genom & Human Genet, Feinstein Inst Med Res, Manhasset, NY 11030 USA. Univ Minnesota, Sch Med, Dept Med, Div Rheumat & Autoimmune Dis, Minneapolis, MN 55455 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Human Genet Res & Mol Biol, Boston, MA 02114 USA. Hallym Univ, Sacred Heart Hosp, Hallym Inst Genom Applicat, Anyang, South Korea. Hanyang Univ, Coll Med, Hosp Rheumat Dis, Seoul 133791, South Korea. RP Gregersen, PK (reprint author), N Shore LIJ Hlth Syst, Robert S Boas Ctr Genom & Human Genet, Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA. EM peterg@nshs.edu OI Li, Wentian/0000-0003-1155-110X FU NIAMS NIH HHS [N01-AR-2-2263, R01-AR44222] NR 25 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT-NOV PY 2006 VL 7 IS 7 BP 533 EP 543 DI 10.1038/sj.gene.6364325 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 098XK UT WOS:000241556200001 PM 16855621 ER PT J AU Bilbao, JR Calvo, B Aransay, AM Martin-Pagola, A de Nanclares, GP Aly, TA Rica, I Vitoria, JC Gaztambide, S Noble, J Fain, PR Awdeh, ZL Alper, CA Castano, L AF Bilbao, J. R. Calvo, B. Aransay, A. M. Martin-Pagola, A. de Nanclares, G. Perez Aly, T. A. Rica, I. Vitoria, J. C. Gaztambide, S. Noble, J. Fain, P. R. Awdeh, Z. L. Alper, C. A. Castano, L. TI Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients with type 1 diabetes mellitus and celiac disease SO GENES AND IMMUNITY LA English DT Article DE conserved extended haplotypes; type 1 diabetes mellitus; celiac disease; HLA-DR3; single nucleotide polymorphism; Basque ID LINKAGE DISEQUILIBRIUM; HLA; COMPLEX; REGION; SUSCEPTIBILITY; HLA-DRB1; GENETICS; DISTINCT; ALLELES; IDDM1 AB The major susceptibility locus for type 1 diabetes mellitus (T1D) maps to the human lymphocyte antigen ( HLA) class II region in the major histocompatibility complex on chromosome 6p21. In southern European populations, like the Basques, the greatest risk to T1D is associated with DR3 homo- and heterozygosity and is comparable to that of DR3/DR4, the highest risk genotype in northern European populations. Celiac disease (CD) is another DR3-associated autoimmune disorder showing certain overlap with T1D that has been explained by the involvement of common genetic determinants, a situation more frequent in DR3-rich populations, like the Basques. As both T1D- and CD-associated HLA alleles are part of conserved extended haplotypes (CEH), we compared DR3-homozygous T1D and CD patients to determine whether CEHs were equally distributed between both disorders or there was a differential contribution of different haplotypes. We observed a very pronounced distribution bias (P < 10(-5)) of the two major DR3 CEHs, with DR3-B18 predominating in T1D and DR3-B8 in CD. Additionally, high-density single nucleotide polymorphism (SNP) analysis of the complete CEH [A*30-B*18-MICA*4-F1C30-DRB1*0301-DQB1*0201-DPB1*0202] revealed extraordinary conservation throughout the 4.9 Mbp analyzed supporting the existence of additional diabetogenic variants (other than HLA-DRB1*0301-DQB1*0201), conserved within the DR3-B18 CEH (but not in other DR3 haplotypes) that could explain its enhanced diabetogenicity. C1 Hosp Cruces, Endocrinol & Diabet Res Grp, E-48903 Bizkaia, Spain. Univ Basque Country, Dept Nursing, Bilbao, Spain. CIC Biogune Res Ctr, Derio, Bizkaia, Spain. Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. Univ Basque Country, Dept Pediat, Bilbao, Spain. Univ Basque Country, Dept Med, Bilbao, Spain. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Inst Biomed Res, CBR, Boston, MA USA. RP Castano, L (reprint author), Hosp Cruces, Endocrinol & Diabet Res Grp, E-48903 Bizkaia, Spain. EM lcastano@hcru.osakidetza.net RI Bilbao, Jose Ramon/A-9177-2008; Vitoria, Juan Carlos/B-8914-2009; Castano, Luis/C-3084-2009; Gaztambide, Sonia/E-1760-2012; Rica, Itxaso /E-7645-2012; Aransay, Ana/F-8086-2011 OI Castano, Luis/0000-0003-0437-9401; Bilbao, Jose Ramon/0000-0002-3176-501X; Vitoria, Juan Carlos/0000-0002-8741-8666; Aransay, Ana/0000-0002-8271-612X FU NHLBI NIH HHS [HL-29583]; NIDDK NIH HHS [R01 DK061722] NR 26 TC 29 Z9 30 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT-NOV PY 2006 VL 7 IS 7 BP 550 EP 554 DI 10.1038/sj.gene.6364328 PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 098XK UT WOS:000241556200003 PM 16929349 ER PT J AU Nimura, K Ishida, C Koriyama, H Hata, K Yamanaka, S Li, E Ura, K Kaneda, Y AF Nimura, Keisuke Ishida, Chisaki Koriyama, Hiroshi Hata, Kenichiro Yamanaka, Shinya Li, En Ura, Kiyoe Kaneda, Yasufumi TI Dnmt3a2 targets endogenous Dnmt3L to ES cell chromatin and induces regional DNA methylation SO GENES TO CELLS LA English DT Article ID DE-NOVO METHYLATION; MAMMALIAN DEVELOPMENT; GERM-CELLS; STEM-CELLS; METHYLTRANSFERASES; FAMILY; GENE; ESTABLISHMENT; IMPRINTS; PROTEIN AB DNA methylation is involved in fundamental cellular processes such as silencing of genes and transposable elements, but the underlying mechanism of regulation of DNA methylation is largely unknown. DNA methyltransferase 3-like protein (Dnmt3L), a member of the Dnmt3 family of proteins, is required during the establishment of DNA methylation patterns in germ cells. Dnmt3L does not possess enzymatic activity. Rather, in vitro analysis indicates that Dnmt3L stimulates DNA methylation by both Dnmt3a and Dnmt3b through direct binding to these proteins. In the current study, we demonstrated that in vivo, Dnmt3L physically and functionally interacted with the Dnmt3 isoform Dnmt3a2. In wild-type embryonic stem (ES) cells, but not in cells lacking Dnmt3a, endogenous Dnmt3L was concentrated in chromatin foci. In ES cells deficient in both Dnmt3a and Dnmt3b, Dnmt3L was distributed diffusely throughout the nucleus and cytoplasm, and ectopic expression of Dnmt3a2, but not Dnmt3a or Dnmt3b, restored wild-type Dnmt3L localization. We showed that endogenous Dnmt3L physically interacted with Dnmt3a2, but not Dnmt3a or Dnmt3b, in ES cells and embryonic testes. We also found that specific CpG sites were demethylated upon depletion of either Dnmt3a or Dnmt3L, but not Dnmt3b, in ES cells. These results provide evidence for a physical and functional interaction between Dnmt3L and Dnmt3a2 in the nucleus. We propose that Dnmt3a2 recruits Dnmt3L to chromatin, and induces regional DNA methylation in germ cells. C1 Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Suita, Osaka 5650871, Japan. ROIS, Div Human Genet, Dept Integrated Genet, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan. Kyoto Univ, Dept Stem Cell Biol, Inst Frontier Med Sci, Kyoto 6068507, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. RP Ura, K (reprint author), Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. EM kiyoeura@gts.med.osaka-u.ac.jp NR 28 TC 36 Z9 39 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1356-9597 J9 GENES CELLS JI Genes Cells PD OCT PY 2006 VL 11 IS 10 BP 1225 EP 1237 DI 10.1111/j.1365-2443.2006.001012.x PG 13 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 086OW UT WOS:000240683900008 PM 16999741 ER PT J AU Hood, KK Johnson, SB Baughcum, AE She, JX Schatz, DA AF Hood, Korey K. Bennett Johnson, Suzanne Baughcum, Amy E. She, Jin-Xiong Schatz, Desmond A. TI Maternal understanding of infant diabetes risk: Differential effects of maternal anxiety and depression SO GENETICS IN MEDICINE LA English DT Article ID AT-RISK; CHILDREN; AUTOIMMUNITY; INFORMATION; CHILDHOOD; NEWBORNS; MELLITUS; PARENTS; IMPACT AB Purpose: This study describes maternal understanding of infant risk associated with newborn genetic screening for type 1 diabetes. Methods: Mothers of at-risk infants (n = 195), identified through the Prospective Assessment of Newborns for Diabetes Autoimmunity study, were notified of risk status by standardized script. Mothers participated in structured telephone interviews 1 and 3.5 months after notification that assessed understanding of infant risk and psychologic response to the news. Results: Most mothers (78.5%) were accurate in their understanding of infant risk at the initial interview, with a slight decline at the follow-up interview (73%). There was a significant increase in underestimation of risk from the initial (12%) to the follow-up interview (19%) (chi(2) (1) = 6.0, P =.01). Mothers with less education, those from ethnic minority backgrounds, and those who were not married tended to be less accurate. Further, mothers who experienced more anxiety and fewer depressive symptoms in response to the news were more likely to be accurate. Likewise, underestimation of risk was associated with fewer anxiety and more depressive symptoms. Conclusion: This study highlights the complex picture of factors promoting maternal understanding of infant diabetes risk in a sample of mothers whose newborns had been identified as at increased risk for type 1 diabetes. C1 Harvard Univ, Pediat & Adolescent Unit, Sch Med,Behav Res & Mental Hlth Sect, Joslin Diabet Ctr,Genet & Epidemiol Sect, Boston, MA 02215 USA. Florida State Univ, Coll Med, Dept Med Humanities & Social Sci, Tallahassee, FL 32306 USA. Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. RP Hood, KK (reprint author), Harvard Univ, Pediat & Adolescent Unit, Sch Med,Behav Res & Mental Hlth Sect, Joslin Diabet Ctr,Genet & Epidemiol Sect, 1 Joslin Pl, Boston, MA 02215 USA. FU NCRR NIH HHS [RR00082]; NICHD NIH HHS [R01-HD-37800, K04-HD-00686]; NIDDK NIH HHS [K23 DK-073340, P01-DK-39079] NR 23 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2006 VL 8 IS 10 BP 665 EP 670 DI 10.1097/01.gim.0000237794.24543.4d PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 102NJ UT WOS:000241818600009 PM 17079884 ER PT J AU Matulonis, UA Campos, S Duska, L Krasner, CN Atkinson, T Penson, RT Seiden, MV Verrill, C Fuller, AF Goodman, A AF Matulonis, U. A. Campos, S. Duska, L. Krasner, C. N. Atkinson, T. Penson, R. T. Seiden, M. V. Verrill, C. Fuller, A. F. Goodman, A. CA Gynecologic Canc Program Dana Far TI Phase I/II dose finding study of combination cisplatin and gemcitabine in patients with recurrent cervix cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cervical cancer; gemcitabine; cisplatin; combination chemotherapy ID GYNECOLOGIC-ONCOLOGY-GROUP; SQUAMOUS-CELL CARCINOMA; III TRIAL; PERSISTENT; TOPOTECAN AB Objectives. To evaluate the toxicity and efficacy of cisplatin and gemcitabine in women with recurrent cervical cancer. Methods. A multi-institutional phase I/II dose finding study of cisplatin and gemcitabine delivered, to women with recurrent previously radiated cervical carcinoma. Results. Twenty eight patients were enrolled. The mean and median age of patients was 51 years (age range 35 to 70 years). Chemotherapy was given on a 28-day cycle; cisplatin was administered at a fixed dose of 50 mg/m(2), day I and gemcitabine, days 1, 8, and 15. Gemcitabine doses started at 600 mg/m(2) (dose level 1) and were escalated by 100 mg/m(2)/dose level until 1000 mg/m(2) (dose level 5). Twenty seven patients were evaluable for toxicity and disease response, and 75 cycles of chemotherapy were administered. Toxicities were predominantly hematological; 18% of patients experienced grade 3 anemia, 37% grade 3 and 11% grade 4 leukopenia, 41% grade 3 neutropenia, and 26% grade 3 thrombocytopenia. The maximally tolerated dose (MTD) was not reached. One patient experienced a dose-limiting toxicity on dose level 2 (febrile neutropenia). One patient had a CR and 3 patients had a PR to therapy (15% response rate), 41% of patients had SD, and 44% had progression of cancer. Median survival was 11.9 months. Conclusion. Although this 28-day gemcitabine and cisplatin regimen in recurrent cervix cancer has tolerable toxicity, 21-day regimens are recommended because of improved practicality, higher dose intensity, and higher response rates. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02129 USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Div Med Oncol, 44 Binney St, Boston, MA 02114 USA. EM umatulonis@partners.org NR 20 TC 9 Z9 9 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 OCT PY 2006 VL 103 IS 1 BP 160 EP 164 DI 10.1016/j.ygyno.2006.02.017 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 089NJ UT WOS:000240887100030 PM 16566993 ER PT J AU Misdraji, J Vaidya, A Tambouret, RH Duska, L Bell, DA AF Misdraji, Joseph Vaidya, Ami Tambouret, Rosemary H. Duska, Linda Bell, Debra A. TI Psammoma bodies in cervicovaginal cytology specimens: A clinicopathological analysis of 31 cases SO GYNECOLOGIC ONCOLOGY LA English DT Article DE psammoma body; Papanicolaou smear; cervical cytology; ovarian carcinoma; endometrial carcinoma ID ENDOMETRIAL SMEARS; VAGINAL SMEAR; INTRAUTERINE-DEVICE; OVARIAN CARCINOMA; ENDOSALPINGIOSIS; ASSOCIATION; CELLS; TUMOR AB Background. Psammoma bodies in cervicovaginal cytology specimens are associated with malignant and benign conditions. Few studies have evaluated which features distinguish patients with underlying malignancy from those with benign conditions. Methods. Pathology files were searched for cervicovaginal specimens having psammoma bodies. The cytology specimen was assessed for the background, glandular atypia, squamous atypia, and presence of non-psammomatous calcifications. Clinical data was obtained from chart review. Results. Nineteen women (mean age 42.7 years) had benign outcomes. None had signs or symptoms suggesting malignancy. None had highly atypical or malignant appearing glandular cells. Twelve women had malignant neoplasms (mean age 56 years), including 6 with recurrent disease. Four women without prior malignancy had worrisome signs including bleeding or mass. All six women with prior malignancy had signs of recurrent disease. All specimens contained highly atypical or malignant glandular cells. Conclusions. The only cytologic feature predictive of outcome was the presence of highly atypical gladular cells in the specimen (P = 0.001), but these cells may be few. Women with underlying malignancy were older than those with benign outcome (P = 0.014) and more likely to be postmenopausal (P = 0.05). Women with malignancy had signs that warranted additional investigation whereas those with benign outcome were usually asymptomic (P = 0.001). (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cytopathol Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gynecol, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 37 TC 6 Z9 6 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 OCT PY 2006 VL 103 IS 1 BP 238 EP 246 DI 10.1016/j.ygyno.2006.02.035 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 089NJ UT WOS:000240887100044 PM 16624389 ER PT J AU Davis, GE Bryson, CL Yueh, B McDonell, MB Micek, MA Fihn, SD AF Davis, Greg E. Bryson, Chris L. Yueh, Bevan McDonell, Mary B. Micek, Mark A. Fihn, Stephan D. TI Treatment delay associated with alternative medicine use among veterans with head and neck cancer SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE complementary medicine; alternative medicine; head and neck cancer; delay of treatment; veterans ID UNITED-STATES; COMPLEMENTARY/ALTERNATIVE MEDICINE; PREVALENCE; HEALTH; DISTRESS; BREAST; COSTS AB Background. Use of complementary and alternative medicine (CAM) is increasing in the United States. This study investigates whether the use of alternative medicine is associated with a delay of treatment in head and neck cancer. Methods. This study used the records obtained from a large trial involving ambulatory care US veterans. Subjects completed a CAM utilization questionnaire. The primary outcome variable was the time duration from cancer diagnosis to the time of cancer treatment. Results. Of veterans with head and neck cancer, 51% reported using some form of CAM, whereas 23% reported using a therapy classified as alternative medicine. Patients who used alternative medicine significantly delayed cancer treatment by 22 days compared with those who did not use alternative medicine (p = .05, 95% confidence interval [CI] = 0-44 days). Conclusions. CAM use is common in veterans with head and neck cancer. Use of alternative medicine was associated with a significant delay in cancer treatment. (c) 2006 Wiley Periodicals, Inc. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Davis, GE (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. EM gedavis@u.washington.edu OI Yueh, Bevan/0000-0003-1380-1053 FU NIDCD NIH HHS [DC 00018] NR 17 TC 15 Z9 15 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2006 VL 28 IS 10 BP 926 EP 931 DI 10.1002/hed.20420 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 088ZL UT WOS:000240849500009 PM 16755583 ER PT J AU Nevzorova, YA Sicinski, P Trautwein, C Liedtke, C AF Nevzorova, Yulia A. Sicinski, Peter Trautwein, Christian Liedtke, Christian TI Ablation of cyclin E1 or cyclin E2 modifies the kinetics of liver regeneration in mice SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Hosp Aachen, Dept Med 111, Aachen, Germany. Rhein Westfal TH Aachen, Aachen, Germany. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 143 BP 242A EP 242A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300144 ER PT J AU Currie, S Tracy, D Ryan, J Belaye, T Kim, M Monto, A AF Currie, Sue Tracy, Daniel Ryan, James Belaye, Tigist Kim, Michael Monto, Alexander TI Injection drug users who resolve the HCV virus appear to be protected from reinfection SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, Div GI, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 167 BP 251A EP 251A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300168 ER PT J AU Delgado, A Liu, YSS Jordan, SH Agrawal, S Hui, Z Deborah, C Chung, RT AF Delgado, Aymin Liu, Yun-Sheen S. Jordan, Sergio H. Agrawal, Saurabh Hui, Zhang Deborah, Casson Chung, Raymond T. TI HCV infection is associated with progressive insulin resistance in liver transplant recipients SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 229 BP 275A EP 275A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300230 ER PT J AU Matthews, AM Huckans, MS Blackwell, AD Hauser, P AF Matthews, Annette M. Huckans, Marilyn S. Blackwell, Aaron D. Hauser, Peter TI Hepatitis C testing, infection, and treatment rates in bipolar patients with and without comorbid substance use disorders SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, JENS Lab, Portland, OR USA. Univ Oregon, Eugene, OR 97403 USA. RI Blackwell, Aaron/B-5258-2008 OI Blackwell, Aaron/0000-0002-5871-9865 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 241 BP 280A EP 280A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300242 ER PT J AU Lin, WY Kim, SS Kamegaya, Y Kim, KA Holtzman, MJ Chung, RT AF Lin, Wenyu Kim, Sun Suk Kamegaya, Yoshitaka Kim, Kyung Ah Holtzman, Michael J. Chung, Raymond T. TI HCV core protein interaction with the STAT1 SH2 domain is associated with impairment of STAT1 phosphorylation and IFN signaling SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastroenterol Unit, Boston, MA USA. Washington Univ, Sch Med, Dept Med & Cell Biol, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 287 BP 297A EP 297A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300288 ER PT J AU Nakamoto, N Ebinuma, H Li, Y Kwok, WW Price, D Levine, B Chang, KM AF Nakamoto, Nobuhiro Ebinuma, Hirotoshi Li, Yun Kwok, William W. Price, David Levine, Bruce Chang, Kyong-Mi TI In-vitro expansion of HCV-specific FoxP3+CD4+CD25+Treg cells SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Benaroya Res Inst, Seattle, WA USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RI Levine, Bruce/D-1688-2009; Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 299 BP 301A EP 301A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300300 ER PT J AU Barakat, F Carlson, MD Oliver, DL Edwards, K Karlen, N Hilsabeck, R Perry, W Hassanein, TI AF Barakat, Fatma Carlson, Meghan D. Oliver, Deanna L. Edwards, Kimberly Karlen, Naomi Hilsabeck, Robin Perry, William Hassanein, Tarek I. TI Fatigue in patients with hepatitis C and nonviral chronic liver disease SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif San Diego, San Diego, CA 92103 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 347 BP 319A EP 320A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300348 ER PT J AU Morasco, BJ Rifai, MA Loftis, JM Indest, DW Kizer, EE Moles, JK Hauser, P AF Morasco, Benjamin J. Rifai, Muhamad A. Loftis, Jennifer M. Indest, David W. Kizer, Emily E. Moles, James K. Hauser, Peter TI A randomized double-blind placebo-controlled trial of paroxetine to prevent interferon-ainduced depression in patients with hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. Salem VA Med Ctr, Salem, VA USA. NW Hepatitis C Resource Ctr, Portland, OR USA. Univ Virginia, Sch Med, Roanoke Salem, VA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 379 BP 332A EP 332A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300380 ER PT J AU Lin, WY Kim, SS Kim, KA Chung, RT AF Lin, Wenyu Kim, Sun Suk Kim, Kyung Ah Chung, Raymond T. TI HIV gp120 protein increases HCV replication in cell culture models SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastroenterol Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 431 BP 351A EP 351A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362300432 ER PT J AU Freudenberg, FU Yu, BB Biddinger, SB Leonard, MR Carey, MC AF Freudenberg, Folke U. Yu, Bian B. Biddinger, Sudha B. Leonard, Monika R. Carey, Martin C. TI Biliary lipid and bile salt molecular changes contributing to liver disease in a cystic fibrosis (CF) mouse model SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Joslin Diabet Ctr, Harvard Med Sch, Dept Med, Div Res, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 663 BP 435A EP 435A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301204 ER PT J AU Kanwal, F Spiegel, BM Bolus, R Hays, RD Kim, SJ Gralnek, IM AF Kanwal, Fasiha Spiegel, Brennan M. Bolus, Roger Hays, Ron D. Kim, Sun J. Gralnek, Ian M. TI Validation of the short form of liver disease quality of life (LDQOL) instrument SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 St Louis VA Med Ctr, St Louis, MO USA. St Louis Univ, St Louis, MO 63103 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ San Diego, San Diego, CA 92110 USA. Rambam Med Ctr, Haifa, Israel. RI Hays, Ronald/D-5629-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 689 BP 445A EP 445A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301230 ER PT J AU O'Leary, JG Elias, N Hertl, M Pratt, DS Cosimi, AB Chung, RT AF O'Leary, Jacqueline G. Elias, Nahel Hertl, Martin Pratt, Daniel S. Cosimi, Anthony B. Chung, Raymond T. TI Early HCV RNA levels and "super-recurrence" predict advanced allograft fibrosis at 1-year in patients undergoing liver transplant for HCV SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 775 BP 477A EP 477A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301316 ER PT J AU Carter, E Pitman, J Jung, W Fischman, AJ Tompkins, R AF Carter, Edward Pitman, Justin Jung, Walter Fischman, Alan J. Tompkins, Ronald TI Increased hepatic uptake of I125FIAU and Tc99m annexin in CCl4 treated mice SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 801 BP 487A EP 487A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301342 ER PT J AU Lieber, CS Cao, Q DeCarli, L Leo, MA Mak, KM Ponomarenko, A Ren, C Wang, XL AF Lieber, Charles S. Cao, Qi DeCarli, Leonore Leo, Maria A. Mak, Ki M. Ponomarenko, Anatoly Ren, Chaoling Wang, Xiaolei TI Role of medium-chain triglycerides (MCT) in the alcohol-mediated CYP2E1 induction of mitochondria SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Mt Sinai Sch Med, James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 895 BP 521A EP 521A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362301436 ER PT J AU Kim, SS Peng, LF Lin, WY Choe, WH Kim, KA Sakamoto, N Schreiber, SL Chung, RT AF Kim, Sun Suk Peng, Lee F. Lin, Wenyu Choe, Won Hyeok Kim, Kyung-Ah Sakamoto, Naoya Schreiber, Stuart L. Chung, Raymond T. TI An efficient cell-based high-throughput method for screening small molecules to identify regulators of hepatitis C virus (HCV) replication SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Tokyo Med & Dent Univ, Bunkyo Ku, Dept Gastroenterol & Hepatol, Tokyo, Japan. Harvard Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. RI Sakamoto, Naoya/G-2734-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 926 BP 532A EP 532A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302021 ER PT J AU Goessling, W North, T Zon, L AF Goessling, Wolfram North, Trista Zon, Leonard TI Wnt signaling mediates early liver growth and endodermal fate decisions SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1076 BP 589A EP 589A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302170 ER PT J AU Biddinger, S Yu, BB Kahn, CR Carey, MC AF Biddinger, Sudha Yu, Bian B. Kahn, C. Ronald Carey, Martin C. TI Hepatic insulin resistance promotes cholesterol gallstone formation in a mouse model of the metabolic syndrome SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1105 BP 599A EP 599A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302199 ER PT J AU Moriguchi, H Uemura, T Sato, C Chung, RT AF Moriguchi, Hisashi Uemura, Takamoto Sato, Chifumi Chung, Raymond T. TI Tumor ablation plus interferon therapy can reduce the risk of death for patients with hepatitis B virus or hepatitis C virus-related resectable hepatocellular carcinoma - A meta-analysis of randomized controlled trials - SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Tokyo, Lab Syst Biol & Med, Tokyo 106, Japan. Kyorin Univ, Sch Med, Mitaka, Tokyo, Japan. Tokyo Med & Dent Univ, Analyt Hlth Sci, Tokyo 113, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1135 BP 611A EP 611A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302229 ER PT J AU Kanwal, F Hoang, T Spiegel, BM Goetz, M Gralnek, IM Dominitz, JA Di Bisceglie, A Asch, S AF Kanwal, Fasiha Hoang, Tuyen Spiegel, Brennan M. Goetz, Mathew Gralnek, Ian M. Dominitz, Jason A. Di Bisceglie, Adrian Asch, Steve TI Quality of care in chronic hepatitis C virus (HCV) infection SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 VA Med Ctr, St Louis, MO USA. St Louis Univ, St Louis, MO 63103 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Portland VA Med Ctr, Portland, OR USA. Rambam Med Ctr, Haifa, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1296 BP 672A EP 673A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302390 ER PT J AU Fix, OK Andersen, J Koziel, MJ Sherman, KE Chung, RT Steiner, L Apple, R Peters, MG AF Fix, Oren K. Andersen, Janet Koziel, Margaret J. Sherman, Kenneth E. Chung, Raymond T. Steiner, Lori Apple, Raymond Peters, Marion G. TI The impact of polymorphisms in inflammation-related genes on the severity of liver disease and response to therapy in patients co-infected with HIV and hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Univ Cincinnati, Div Digest Dis, Cincinnati, OH USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Roche Mol Syst, Alameda, CA USA. RI apple, raymond/I-4506-2012 OI apple, raymond/0000-0002-8007-0345 NR 0 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1302 BP 675A EP 675A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302396 ER PT J AU Yee, HS Currie, SL Chapko, MK Monto, A AF Yee, Helen S. Currie, Sue L. Chapko, Michael K. Monto, Alexander TI Is hepatitis A and B screening and vaccination in chronic hepatitis C patients effective? SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA 1307 BP 676A EP 677A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302401 ER PT J AU Everson, GT Tong, MJ Jacobson, IM Jensen, DM Haller, AA Lauer, GM Parker, J Ferraro, J Cruickshank, SE Duke, RC Apelian, D Rodell, TC Schiff, ER AF Everson, Gregory T. Tong, Myron J. Jacobson, Ira M. Jensen, Donald M. Haller, Aurelia A. Lauer, Georg M. Parker, Joanne Ferraro, John Cruickshank, Scott E. Duke, Richard C. Apelian, David Rodell, Timothy C. Schiff, Eugene R. TI Interim results from a randomized, double-blind, placebo-controlled phase 1b study in subjects with chronic HCV after treatment with GI-5005, a yeast-based HCV immunotherapy targeting NS3 and core proteins SO HEPATOLOGY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 27-31, 2006 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Colorado, Sch Med, Denver, CO USA. Huntington Med Res Inst, Pasadena, CA USA. Cornell Univ, Coll Med, New York, NY USA. Univ Chicago Hosp, Chicago, IL 60637 USA. GlobeImmune Inc, Louisville, CO USA. Massachusetts Gen Hosp, Cambridge, MA USA. Harvard Med Sch, Boston, MA USA. Univ Miami, Sch Med, Miami, FL USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2006 VL 44 IS 4 SU 1 MA LB17 BP 697A EP 698A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 096FF UT WOS:000241362302456 ER PT J AU Yigitbas, E Dong, LS Wei-Zi, D Coruh, S Goren, G Uner, A Dicle, G Chen, DF Kansu, E Fraser, PA AF Yigitbas, Emre Dong, Lingsheng Wei-Zi, Ding Coruh, Serra Goren, Gozde Uner, Aysegul Dicle, Guc Chen, Donfeng Kansu, Emin Fraser, Patricia A. TI High resolution MHC class-I related chain a (MICA) genotyping and analysis of HLA-B - MICA haplotypes in a Turkish population sample SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 16-20, 2006 CL San Diego, CA SP Amer Soc Histocompatibil & Immunogenet C1 Hacettepe Univ, Inst Oncol, Ankara, Turkey. Harvard Univ, CBR, Biomed Res Ctr, Boston, MA 02115 USA. Duke Univ, Med Ctr, Clin Transplantat Immunol Lab, Durham, NC USA. RI Uner, Aysegul /A-9028-2011; zhang, jun/D-7782-2015 OI Uner, Aysegul /0000-0002-2522-1606; NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 2006 VL 67 IS 10 SU 1 BP S158 EP S158 DI 10.1016/j.humimm.2006.08.249 PG 1 WC Immunology SC Immunology GA 101OZ UT WOS:000241751400230 ER PT J AU Dechend, R Wolf, M Markovic, N Herse, F Wallukat, G Hubel, CA AF Dechend, Ralf Wolf, Myles Markovic, Nina Herse, Florian Wallukat, Gerd Hubel, Carl A. TI Presence of activating autoantibodies against the AT1-receptor in women with a history of preeclampsia SO HYPERTENSION LA English DT Meeting Abstract CT 11th Annual Meeting of the European-Council- for Cardiovascular Reseach CY SEP 29-OCT 01, 2006 CL Nice, FRANCE SP European Council Cardiovasc Res C1 Franz Volhard Klin, Berlin, Germany. Massachusetts Gen Hosp, Renal Unit, Boston, MA USA. Magee Womens Res Inst, Dept Obstet Gynecol, Pittsburgh, PA USA. Max Delbruck Med, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2006 VL 48 IS 4 BP E47 EP E47 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127FR UT WOS:000243571200293 ER PT J AU Nyby, MD Douglas, K Albedi, K Makino, H Tuck, ML AF Nyby, Michael D. Douglas, Kyle Albedi, Karolin Makino, Hirofumi Tuck, Michael L. TI Telmisartan and insulin affect angiotensin II type 1 and type 2 receptor expression in vascular smooth muscle and vascular endothelial cells SO HYPERTENSION LA English DT Meeting Abstract CT 11th Annual Meeting of the European-Council- for Cardiovascular Reseach CY SEP 29-OCT 01, 2006 CL Nice, FRANCE SP European Council Cardiovasc Res C1 VA Greater Los Angeles Healtcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healtcare Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2006 VL 48 IS 4 BP E89 EP E89 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127FR UT WOS:000243571200512 ER PT J AU Haidar, H Bouix, S Levitt, JJ McCarley, RW Shenton, ME Soul, JS AF Haidar, Haissam Bouix, Sylvain Levitt, James J. McCarley, Robert W. Shenton, Martha E. Soul, Janet S. TI Characterizing the shape of anatomical structures with Poisson's equation SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE brain morphometry; caudate nucleus; Poisson's equation; shape analysis ID SCHIZOTYPAL PERSONALITY-DISORDER; VOXEL-BASED MORPHOMETRY; PREMATURE-INFANT; CAUDATE-NUCLEUS; BRAIN; VOLUME; HIPPOCAMPAL; SCHIZOPHRENIA; ABNORMALITIES; THICKNESS AB Poisson's equation, a fundamental partial differential equation in classical physics, has a number of properties that are interesting for shape analysis. In particular, the equipotential sets of the solution graph become smoother as the potential increases. We use the displacement map, the length of the streamlines formed by the gradient field of the solution, to measure the "complexity" (or smoothness) of the equipotential sets, and study its behavior as the potential increases. We believe that this function complexity = f (potential), which we call the shape characteristic, is a very natural way to express shape. Robust algorithms are presented to compute the solution to Poisson's equation, the displacement map, and the shape characteristic. We first illustrate our technique on two-dimensional synthetic examples and natural silhouettes. We then perform two shape analysis studies on three-dimensional neuroanatomical data extracted from magnetic resonance (MR) images of the brain. In the first study, we investigate changes in the caudate nucleus in Schizotypal Personality Disorder (SPD) and confirm previously published results on this structure [1]. In the second study, we present a data set of caudate nuclei of premature infants with asymmetric white matter injury. Our method shows structural shape differences that volumetric measurements were unable to detect. C1 Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02114 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat,Brockton Div, Boston VA Healthcare Syst,Lab Neurosci,Clin Neuro, Boston, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat,Brockton Div, Boston VA Healthcare Syst,Lab Neurosci,Clin Neuro, Boston, MA 02215 USA. RP Bouix, S (reprint author), Brigham & Womens Hosp, Dept Psychiat, Psychiat Neuroimaging Lab, Boston, MA 02114 USA. EM sylvain@bwh.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Bouix, Sylvain/0000-0003-1326-6054 FU NIBIB NIH HHS [U54 EB005149, U54 EB005149-050012, U54-EB005149]; NICHD NIH HHS [P30 HD018655, P30-HD18655]; NIMH NIH HHS [K05 MH070047, K05 MH070047-06, K05-MH070047, R01 MH040799, R01 MH052807, R01-MH052807, R01-MH40799, R01-MH50747]; NINDS NIH HHS [P01 NS038475, P01-NS38475] NR 39 TC 10 Z9 10 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD OCT PY 2006 VL 25 IS 10 BP 1249 EP 1257 DI 10.1109/TMI.2006.881378 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 090OI UT WOS:000240960200001 PM 17024829 ER PT J AU Nishida, N Xie, C Shimaoka, M Cheng, YF Walz, T Springer, TA AF Nishida, Noritaka Xie, Can Shimaoka, Motomu Cheng, Yifan Walz, Thomas Springer, Timothy A. TI Activation of leukocyte beta(2) integrins by conversion from bent to extended conformations SO IMMUNITY LA English DT Article ID I-LIKE DOMAIN; FUNCTION-ASSOCIATED ANTIGEN-1; CRYSTAL-STRUCTURE; A-DOMAIN; INTEGRIN-BETA(2) SUBUNIT; CR3-DEPENDENT ADHESION; EXTRACELLULAR SEGMENT; ELECTRON-MICROSCOPY; ALPHA-SUBUNIT; HYBRID DOMAIN AB We used negative stain electron microscopy (EM) to examine the conformational changes in the ectodomains required for activation of the leukocyte integrins alpha(X)beta(2) and alpha(L)beta(2). They transitioned between a bent conformation and two extended conformations in which the headpiece was in either a closed or an open state. Extended integrins exhibited marked flexibility at the alpha subunit genu and between integrin epidermal growth factor-like (I-EGF) domains 1 and 2. A clasp to mimic juxtamembrane association between the integrin alpha and beta subunits stabilized the bent conformation strongly for alpha(X)beta(2) and less so for alpha(L)beta(2). A small molecule allosteric antagonist induced the extended, open headpiece conformation. A Fab known to activate beta(2) integrins on leukocytes induced extension, and a Fab reporter of activation bound only after extension had been induced. The results establish an intimate relationship between extension of beta(2) integrins and their activation in immune responses and leukocyte trafficking. C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR, Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Nishida, Noritaka/E-7087-2010 FU NIAID NIH HHS [AI63421, AI72765]; NIGMS NIH HHS [GM62580] NR 48 TC 136 Z9 139 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2006 VL 25 IS 4 BP 583 EP 594 DI 10.1016/j.immuni.2006.07.016 PG 12 WC Immunology SC Immunology GA 097WZ UT WOS:000241481500010 PM 17045822 ER PT J AU Iweala, OI Nagler, CR AF Iweala, Onyinye I. Nagler, Cathryn R. TI Immune privilege in the gut: the establishment and maintenance of non-responsiveness to dietary antigens and commensal flora SO IMMUNOLOGICAL REVIEWS LA English DT Review DE oral tolerance; commensal flora; regulatory T cells; food allergy; inflammatory bowel disease ID REGULATORY T-CELLS; INFLAMMATORY-BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; ORAL TOLERANCE INDUCTION; PROINFLAMMATORY GENE-EXPRESSION; PLASMACYTOID DENDRITIC CELLS; MESENTERIC LYMPH-NODES; MUCOSAL IGA RESPONSES; TOLL-LIKE RECEPTOR-4; MURINE PEYERS PATCH AB Immune privilege in the gut is the result of a complex interplay between the gut microbiome, gut luminal antigens, and the intestinal epithelial barrier. Composed of both physical and immunochemical components, the intestinal barrier secretes immunoregulatory mediators that promote the generation of tolerogenic antigen-presenting cells, phagocytic innate immune cells characterized by 'inflammatory anergy', and regulatory cells of the adaptive immune system. Innate immune cells mediate controlled transepithelial transport of luminal antigens as far as the mesenteric lymph nodes, where the intestinal and peripheral immune systems intersect. This promotes the generation of adaptive regulatory lymphocytes that actively suppress effector cell responses against gut luminal antigens and flora. The net result is the generation of tolerance to dietary antigens and the maintenance of gut homeostasis. Dysregulation of this complex immunoregulatory network leads to diseases such as food allergy and inflammatory bowel disease. Future therapies for these diseases will likely involve the functional restoration of the barrier and regulatory cell functions at the epithelial/luminal interface. C1 Massachusetts Gen Hosp, Mucosal Immun Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Nagler, CR (reprint author), Massachusetts Gen Hosp, Mucosal Immun Lab, Bldg 114,16th St 114-3503, Charlestown, MA 02129 USA. EM cnagleranderson@partners.org FU NIAID NIH HHS [5F31AI054229-04]; NIDDK NIH HHS [DK43551, DK55678] NR 190 TC 55 Z9 58 U1 1 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 2006 VL 213 BP 82 EP 100 DI 10.1111/j.1600-065X.2006.00431.x PG 19 WC Immunology SC Immunology GA 084VJ UT WOS:000240562200007 PM 16972898 ER PT J AU Macchia, I Gauduin, MC Kaur, A Johnson, RP AF Macchia, Iole Gauduin, Marie-Claire Kaur, Amitinder Johnson, R. Paul TI Expression of CD8 alpha identifies a distinct subset of effector memory CD4(+) T lymphocytes SO IMMUNOLOGY LA English DT Article DE animal models/studies : primates; helper T cells (Th cells, Th0, Th1, Th2, Th3); memory cells; simian immunodeficiency virus ID SIMIAN-IMMUNODEFICIENCY VIRUS; PERIPHERAL-BLOOD; CORECEPTOR FUNCTION; RHESUS-MACAQUES; THYMIC FUNCTION; PERSISTENT EXPANSIONS; PHENOTYPIC ANALYSIS; CD8(+) LYMPHOCYTES; CYNOMOLGUS MONKEYS; CYTOTOXIC ACTIVITY AB Circulating CD4(+) CD8(+) T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4(+) CD8(+) T cells in rhesus macaques. Two distinct populations of CD4(+) CD8(+) T cells were identified: the dominant one was CD4(hi) CD8(lo) and expressed the CD8 alpha alpha homodimer, while the minor population was CD4(lo) CD8(hi) and expressed the CD8 alpha beta heterodimer. The majority of CD4(hi) CD8 alpha(lo) T cells exhibited an activated effector/memory phenotype (CCR5(lo) CD7(-) CD28(-) HLA-DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4(hi) CD8 alpha(lo) T cells compared to single-positive CD4(+) T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4(hi) CD8 alpha(lo) T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4(hi) CD8 alpha(lo) lymphocytes only in a subset of animals. Taken together, these data suggest that CD4(+) T cells expressing CD8 alpha represent an effector/memory subset of CD4(+) T cells and that this cell population can be depleted during the course of SIV infection. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Immunol, Southborough, MA 01772 USA. Ist Super Sanita, I-00161 Rome, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Charlestown, MA USA. RP Johnson, RP (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Immunol, Southborough, MA 01772 USA. EM pjohnson@hms.harvard.edu FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168]; NIAID NIH HHS [AI43890, R01 AI062412, AI45314, AI62412, R01 AI043890] NR 68 TC 15 Z9 15 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD OCT PY 2006 VL 119 IS 2 BP 232 EP 242 DI 10.1111/j.1365-2567.2006.02428.x PG 11 WC Immunology SC Immunology GA 084XN UT WOS:000240567800010 PM 16836648 ER PT J AU Rollenhagen, JE Kalsy, A Cerda, F John, M Harris, JB LaRocque, RC Qadri, F Calderwood, SB Taylor, RK Ryan, ET AF Rollenhagen, Julianne E. Kalsy, Anuj Cerda, Francisca John, Manohar Harris, Jason B. LaRocque, Regina C. Qadri, Firdausi Calderwood, Stephen B. Taylor, Ronald K. Ryan, Edward T. TI Transcutaneous immunization with toxin-coregulated pilin A induces protective immunity against Vibrio cholerae O1 El Tor challenge in mice SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROTOXIGENIC ESCHERICHIA-COLI; MANNOSE-SENSITIVE HEMAGGLUTININ; ADP-RIBOSYLATING EXOTOXINS; HEAT-LABILE ENTEROTOXIN; COLONIZATION FACTOR; HUMAN INFECTION; VECTOR STRAINS; VACCINE; PILUS; MUCOSAL AB Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mu g of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], 50 mu g) on days 0, 19, and 40. Mice immunized with TcpA alone did not develop anti-TcpA responses. Mice that received transcutaneously applied TcpA and CT developed prominent anti-TepA immunoglobulin G (IgG) serum responses but minimal anti-TcpA IgA. Transcutaneous immunization with CT induced prominent IgG and IgA anti-CT serum responses. In an infant mouse model, offspring born to dams transcutaneously immunized either with TcpA and CT or with CT alone were challenged with 10(6) CFU (one 50% lethal dose) wild-type V. cholerae O1 Ell Tor strain N16961. At 48 h, mice born to females transcutaneously immunized with CT alone had 36% +/- 10% (mean +/- standard error of the mean) survival, while mice born to females transcutaneously immunized with TcpA and CT had 69% +/- 6% survival (P < 0.001). Our results suggest that transcutaneous immunization with TcpA and an immunoadjuvant induces protective anti-TcpA immune responses. Anti-TcpA responses may contribute to an optimal cholera vaccine. C1 Massachusetts Gen Hosp, Trop & Geog Med Ctr, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dartmouth Med Sch, Hanover, NH USA. B Ctr Hlth & Populat Studies, ICDDR B, Dhaka, Bangladesh. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Trop & Geog Med Ctr, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM etryan@partners.org FU FIC NIH HHS [K01 TW007144, K01 TW007409, K01TW07144, K01TW07409]; NIAID NIH HHS [R03 AI063079, AI058935, AI063079, AI40725, R01 AI025096, R01 AI040725, R01AI25096, R56 AI106878, T32 AI007061, U01 AI058935]; NICHD NIH HHS [K12 HD000850, K12HD00850] NR 44 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2006 VL 74 IS 10 BP 5834 EP 5839 DI 10.1128/IAI.00438-06 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 090RF UT WOS:000240967900046 PM 16988262 ER PT J AU Lo, M Bulach, DM Powell, DR Haake, DA Matsunaga, J Paustian, ML Zuerner, RL Adler, B AF Lo, Miranda Bulach, Dieter M. Powell, David R. Haake, David A. Matsunaga, James Paustian, Michael L. Zuerner, Richard L. Adler, Ben TI Effects of temperature on gene expression patterns in Leptospira interrogans serovar Lai as assessed by whole-genome microarrays SO INFECTION AND IMMUNITY LA English DT Article ID BORRELIA-BURGDORFERI; ESCHERICHIA-COLI; OUTER-MEMBRANE; SIGMA-FACTOR; MOLECULAR CHARACTERIZATION; GLOBAL ANALYSIS; PROTEINS; GROWTH; COPENHAGENI; SURVIVAL AB Leptospirosis is an important zoonosis of worldwide distribution. Humans become infected via exposure to pathogenic Leptospira spp. from infected animals or contaminated water or soil. The availability of genome sequences for Leptospira interrogans, serovars Lai and Copenhageni, has opened up opportunities to examine global transcription profiles using microarray technology. Temperature is a key environmental factor known to affect leptospiral protein expression. Leptospira spp. can grow in artificial media at a range of temperatures reflecting conditions found in the environment and the mammalian host. Therefore, transcriptional changes were compared between cultures grown at 20 degrees C, 30 degrees C, 37 degrees C, and 39 degrees C to represent ambient temperatures in the environment, growth under laboratory conditions, and temperatures in healthy and febrile hosts. Data from direct pairwise comparisons of the four temperatures were consolidated to examine transcriptional changes at two generalized biological conditions representing mammalian physiological temperatures (37 degrees C and 39 degrees C) versus environmental temperatures (20 degrees C and 30 degrees C). Additionally, cultures grown at 30 degrees C then shifted overnight to 37 degrees C were compared with those grown long-term at 30 degrees C and 37 degrees C to identify genes potentially expressed in the early stages of infection. Comparison of data sets from physiological versus environmental experiments with upshift experiments provided novel insights into possible transcriptional changes at different stages of infection. Changes included differential expression of chemotaxis and motility genes, signal transduction systems, and genes encoding proteins involved in alteration of the outer membrane. These findings indicate that temperature is an important factor regulating expression of proteins that facilitate invasion and establishment of disease. C1 Monash Univ, Dept Microbiol, Victorian Bioinformat Consortium, Clayton, Vic 3800, Australia. Monash Univ, Australian Bacterial Pathogenesis Program, Clayton, Vic 3800, Australia. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. USDA ARS, Bacterial Dis Livestock Res Unit, Natl Anim Dis Ctr, Ames, IA 50010 USA. Monash Univ, Australian Res Council, Ctr Excellence Struct & Funct Microbial Genom, Clayton, Vic 3800, Australia. RP Adler, B (reprint author), Monash Univ, Dept Microbiol, Victorian Bioinformat Consortium, Clayton, Vic 3800, Australia. EM Ben.Adler@med.monash.edu.au RI Bulach, Dieter/D-5793-2011 OI Bulach, Dieter/0000-0001-9823-6078 FU NIAID NIH HHS [R01 AI034431, AI-34431, R01 AI034431-09, R21 AI034431, R29 AI034431] NR 47 TC 66 Z9 67 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 OCT PY 2006 VL 74 IS 10 BP 5848 EP 5859 DI 10.1128/IAI.00755-06 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 090RF UT WOS:000240967900048 PM 16988264 ER PT J AU Petzold, EW Himmelreich, U Mylonakis, E Rude, T Toffaletti, D Cox, GM Miller, JL Perfect, JR AF Petzold, Elizabeth Wills Himmelreich, Uwe Mylonakis, Eleftherios Rude, Thomas Toffaletti, Dena Cox, Gary M. Miller, Jackie L. Perfect, John R. TI Characterization and regulation of the trehalose synthesis pathway and its importance in the pathogenicity of Cryptococcus neoformans SO INFECTION AND IMMUNITY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TREHALOSE-6-PHOSPHATE PHOSPHATASE; DECREASES INFECTIVITY; SCHIZOSACCHAROMYCES-POMBE; CARBOHYDRATE-METABOLISM; RESERVE CARBOHYDRATE; NEUTRAL TREHALASE; VIRULENCE FACTOR; ACID TREHALASE; YEAST GENE AB The disaccharide trehalose has been found to play diverse roles, from energy source to stress protectant, and this sugar is found in organisms as diverse as bacteria, fungi, plants, and invertebrates but not in mammals. Recent studies in the pathobiology of Cryptococcus neoformans identified the presence of a functioning trehalose pathway during infection and suggested its importance for C neoformans survival in the host. Therefore, in C neoformans we created null mutants of the trehalose-6-phosphate (T6P) synthase (TPS1), trehalose-6-phophate phosphatase (TPS2), and neutral trehalase (NTH1) genes. We found that both TPS1 and TPS2 are required for high-temperature (37 degrees C) growth and glycolysis but that the block at TPS2 results in the apparent toxic accumulation of T6P, which makes this enzyme a fungicidal target. Sorbitol suppresses the growth defect in the tps1 and tps2 mutants at 37 degrees C, which supports the hypothesis that these sugars (trehalose and sorbitol) act primarily as stress protectants for proteins and membranes during exposure to high temperatures in C neoformans. The essential nature of this pathway for disease was confirmed when a tps1 mutant strain was found to be avirulent in both rabbits and mice. Furthermore, in the system of the invertebrate C. elegans, in which high in vivo temperature is no longer an environmental factor, attenuation in virulence was still noted with the tps1 mutant, and this supports the hypothesis that the trehalose pathway in C. neoformans is involved in more host survival mechanisms than simply high-temperature stresses and glycolysis. These studies in C. neoformans and previous studies in other pathogenic fungi support the view of the trehalose pathway as a selective fungicidal target for use in antifungal development. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Univ Sydney, Ctr Infect Dis & Microbiol, Sydney, NSW 2006, Australia. Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Perfect, JR (reprint author), Duke Univ, Med Ctr, Dept Med, POB 3353, Durham, NC 27710 USA. EM perfe001@mc.duke.edu FU NIAID NIH HHS [AI28388, R01 AI028388, R56 AI028388] NR 60 TC 66 Z9 71 U1 0 U2 8 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 OCT PY 2006 VL 74 IS 10 BP 5877 EP 5887 DI 10.1128/IAI.00624-06 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 090RF UT WOS:000240967900051 PM 16988267 ER PT J AU Gonzalez, BE Rueda, AM Shelburne, SA Musher, DM Hamill, RJ Hulten, KG AF Gonzalez, Blanca E. Rueda, Adriana M. Shelburne, Samuel A., III Musher, Daniel M. Hamill, Richard J. Hulten, Kristina G. TI Community-associated strains of methicillin-resistant Staphylococccus aureus as the cause of healthcare-associated infection SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID PANTON-VALENTINE LEUKOCIDIN; FIELD GEL-ELECTROPHORESIS; UNITED-STATES; EMERGENCE; CHILDREN; CLONE; DEFINITIONS; CASSETTE; SEPSIS; GENOME AB OBJECTIVE. Methicillin-resistant Staphylococcus aureus ( MRSA) isolates from patients with community-associated infection have been described as strains genetically distinct from the strains isolated from patients with healthcare-associated infection. This study examines the hypothesis that community-associated MRSA ( CA-MRSA) strains now cause serious infections in hospitalized patients. METHODS. Thirty-seven clinical MRSA isolates were randomly selected from blood isolates obtained from July 2003 through June 2004. Strains were tested for staphylococcal chromosomal cassette mec ( SCCmec) type, pulsed-field gel electrophoresis ( PFGE) type, and presence of Panton-Valentine leukocidin ( PVL) genes. Medical records review and epidemiologic classification was performed by an investigator blinded to the results of the bacterial strain analysis. Episodes of bloodstream infection were independently classified as either community-associated or healthcare-associated infections, and bacterial isolates were independently classified as either CA-MRSA strains or healthcare-associated MRSA ( HA-MRSA) strains, according to established definitions. SETTING. A tertiary care Veterans Affairs Medical Center. RESULTS. Twenty-four ( 65%) of 37 MRSA isolates were SCCmec type IV, a genetic type characteristic of CA-MRSA strains; 22 of these 24 isolates belonged to the CA-MRSA clone USA300 and carried PVL genes. Thirteen ( 35%) of the 37 strains were SCCmec type II, of which 12 were USA100-ST5 and 12 lacked PVL genes. Thirty patients ( 81%) had healthcare-associated infections; 18 ( 60%) of these 30 were infected with isolates carrying markers of CA-MRSA strains. Of 7 patients with CA- MRSA infections, 6 were infected with isolates belonging to the USA300 clone. Patients with healthcare-associated bloodstream infections were as likely to be infected with a CA-MRSA strain as patients with a community-associated infection (P=.38). CONCLUSIONS. MRSA strains with molecular characteristics of CA- MRSA strains have emerged as an important cause of serious healthcare-associated infection in our hospital. C1 Baylor Coll Med, Infect Dis Sect, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Dept Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Hulten, KG (reprint author), Texas Childrens Hosp, Mail Code 3-2371,6621 Fannin St, Houston, TX 77030 USA. EM khulten@bcm.tmc.edu OI Hulten, Kristina/0000-0001-7446-157X FU NCRR NIH HHS [K12 RR 17665-04] NR 34 TC 112 Z9 115 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2006 VL 27 IS 10 BP 1051 EP 1056 DI 10.1086/507923 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 205AF UT WOS:000249084400008 PM 17006811 ER PT J AU Sonnenberg, A Collins, JF AF Sonnenberg, Amnon Collins, Judith F. TI Vicious circles in inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE complications of IBD; Crohn's disease; decision analysis; health service research; influence diagram; simulation; surgery of IBD ID ULCERATIVE-COLITIS; CROHNS-DISEASE; HEPARIN AB Background: Inflammatory bowel disease can present with a bewildering array of disease manifestations whose overall impact on patient health is difficult to disentangle. The multitude of disease complications and therapeutic side effects result in conflicting ideas on how to best manage a patient. The aim of the study is to test the usefulness of influence diagrams in resolving conflicts centered on managing complex disease processes. Methods: The influences of a disease process and the ensuing medical interventions on the health of a patient with inflammatory bowel disease are modeled by an influence diagram. Patient health is the focal point of multiple influences affecting its overall strength. Any downstream influence represents the focal point of other preceding upstream influences. The mathematics underlying the influence diagram is similar to that of a decision tree. Its formalism allows one to consider additive and inhibitory influences and include in the same analysis qualitatively different types of parameters, such as diagnoses, complications, side effects, and therapeutic outcomes. Results: Three exemplary cases are presented to illustrate the potential use of influence diagrams. In all three case scenarios, Crohn's disease resulted in disease manifestations that seemingly interfered with its own therapy. The presence of negative feedback loops rendered the management of each case particularly challenging. The analyses by influence diagrams revealed subtle interactions among the multiple influences and their joint contributions to the patient's overall health that would have been difficult to appreciate by verbal reasoning alone. Conclusion: influence diagrams represent a decision too] that is particularly suited to improve decision-making in inflammatory bowel disease. They highlight key factors of a complex disease process and help to assess their quantitative interactions. C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3G1, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 18 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2006 VL 12 IS 10 BP 944 EP 949 DI 10.1097/01.mib.0000231577.19301.95 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 092WP UT WOS:000241128300004 PM 17012965 ER PT J AU Nagler, C AF Nagler, Cathryn TI The hygiene hypothesis and the aberrant immune response: Mechanistic links SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT Inflammatory Bowel Disease Summit CY OCT 04-07, 2006 CL Cleveland, OH C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Immunol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2006 VL 12 SU 3 BP S2 EP S2 DI 10.1097/00054725-200610003-00003 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 109YN UT WOS:000242345600004 ER PT J AU Sands, BE AF Sands, Bruce E. TI Infliximab, adalimumab and certolizumab: Beneficial and adverse effects (present) SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT Inflammatory Bowel Disease Summit CY OCT 04-07, 2006 CL Cleveland, OH C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Mgh Crohns & Colitis Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2006 VL 12 SU 3 BP S6 EP S7 DI 10.1097/00054725-200610003-00014 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 109YN UT WOS:000242345600015 ER PT J AU Zeka, A Sullivan, JR Vokonas, PS Sparrow, D Schwartz, J AF Zeka, Ariana Sullivan, James R. Vokonas, Pantel S. Sparrow, David Schwartz, Joel TI Inflammatory markers and particulate air pollution: characterizing the pathway to disease SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE air pollution; C-reactive protein; blood sedimentation; fibrinogen; inflammation; sulphates; white blood cells ID C-REACTIVE PROTEIN; HEALTHY-HUMAN VOLUNTEERS; CORONARY-HEART-DISEASE; RISK-FACTORS; CARDIOVASCULAR RISK; RATE-VARIABILITY; ELDERLY SUBJECTS; DIESEL EXHAUST; BLOOD MARKERS; PARTICLES AB Background Increased concentrations of particles in air have been related to changes in inflammatory markers that in turn are hypothesized in mediating the particle effects on cardiovascular disease. The present work examined this association in an elderly cohort in the Greater Boston area and addresses the relative role of particles from different sources. Methods The study included 710 subjects, active members of the VA Normative Aging Study cohort with measurements of blood markers. Concentrations of particle number (PN), black carbon (BC), fine particulate matter (PM2.5), and sulphates were measured at a central site near the examination site. Results Positive associations were found between traffic-related particles (PN and BC) and inflammatory markers, but only suggestive associations were found with exposures to PM2.5 and sulphates. The particle effect on the inflammatory markers was greater among subjects older than 78 years and among obese. A suggestion for a greater effect of particles on inflammatory markers among GSTM1-null subjects and non-users of statin drugs was also seen. Conclusions The findings of the study support the hypothesis that particles can induce cardiovascular disease through inflammatory pathways, suggestive of a greater toxicity of traffic-related particles. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Zeka, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, 401 Pk Dr,Suite 415 W,POB 15677, Boston, MA 02115 USA. EM azeka@hsph.harvard.edu OI Zeka, Ariana/0000-0002-9570-8831 NR 65 TC 90 Z9 100 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 2006 VL 35 IS 5 BP 1347 EP 1354 DI 10.1093/ije/dyl132 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097EI UT WOS:000241429200044 PM 16844771 ER PT J AU Shapiro, EL Ginzberg, R AF Shapiro, Elizabeth L. Ginzberg, Rachel TI Buried treasure: Money, ethics, and countertransference in group therapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID PSYCHODYNAMIC GROUP-PSYCHOTHERAPY AB Exploring money in the context of group therapy highlights the powerful way that groups can magnify the most intimate and charged aspects of our patients as well as ourselves. A thorough self-examination that includes an ethical framework for decision-making about money matters can safeguard against problems resulting from therapists' and patients' unconscious relationship to money. This paper addresses the setting and raising of fees, pre-group evaluations, third-party payers, handling of payments and statements, as well as combined treatment. Special attention is paid to countertransference with an exploration of the particular difficulties inherent in reconciling one's identity as a healer with the business of clinical practice. C1 Massachusetts Gen Hosp, Dept Psychiat, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Shapiro, EL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Psychoanalyt Studies, ACC 805,15 Parkman St, Boston, MA 02114 USA. EM shapiropowers@rcn.com NR 16 TC 7 Z9 8 U1 1 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD OCT PY 2006 VL 56 IS 4 BP 477 EP 494 DI 10.1521/ijgp.2006.56.4.477 PG 18 WC Psychology, Clinical SC Psychology GA 094DZ UT WOS:000241221000005 PM 17040184 ER PT J AU McCluggage, WG Bissonnette, JP Young, RH AF McCluggage, W. Glenn Bissonnette, John P. Young, Robert H. TI Primary malignant melanoma of the ovary: A report of 9 definite or probable cases with emphasis on their morphologic diversity and mimicry of other primary and secondary ovarian neoplasms SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; malignant melanoma; teratoma; immunohistochemistry; differential diagnosis. ID SMALL-CELL CARCINOMA; CYSTIC TERATOMA; DERMOID CYST; CLINICOPATHOLOGICAL ANALYSIS; DIFFERENTIAL-DIAGNOSIS; HYPERCALCEMIC TYPE; TUMORS; INHIBIN; CALRETININ; NEVUS AB Most malignant melanomas encountered in the ovary are metastatic, and the recent literature has focused on such neoplasms. Primary tumors are rare with most reports being only of single cases. When the tumor is associated with teratomatous elements from which it arises, not only is the diagnosis of melanoma much more likely to be made but also is a primary nature proven. However, although all the primary tumors likely are of teratomatous origin, evidence of such an origin may be effaced resulting in problems both in identifying the tumor as melanoma and in determining if it is primary or not. In this report, we describe 9 primary or probably primary ovarian melanomas and explore the varied problems the cases posed. The patients ranged from 18 to 72 years. The tumors, all of which were unilateral, ranged from 4 to 23 cm; only 2 were black. In 6 cases, there was an associated dermoid cyst or monodermal teratoma (struma ovarii), 5 in the ipsilateral and 1 in the contralateral ovary. The tumors were variously composed of large epithelioid cells with eosinophilic cytoplasm, small cells, spindle-shaped cells, or a combination, and in 5 cases, melanin pigment (Masson Fontana positive) was identified. In all cases, most of the tumor cells had prominent nucleoli. All neoplasms had a predominantly diffuse growth pattern with a focal nested architecture in 3 cases. Other noteworthy morphological features were tumor giant cells with wreath-like nuclei (4 cases), signet ring cells (1 case), clear cells (1 case), intranuclear pseudoinclusions (2 cases), a focally myxoid stroma (2 cases), a pseudopapillary appearance caused by degeneration (2 cases), and follicle-like structures (3 cases). In 1 case in a 21-year-old, there was associated hypercalcemia, and focally, the neoplasm, which contained follicle-like structures, resembled small cell carcinoma of the hypercalcemic type. All cases tested by immunohistochemistry were positive with I or more melanocytic markers, and electron microscopy performed in 3 cases revealed intracytoplasmic melanosomes or premelanosomes. The wide differential potentially includes neoplasms within most of the categories of primary ovarian neoplasia, as well as metastatic melanoma, and is facilitated by thorough sampling to identify teratomatous elements, by awareness of the spectrum of melanoma in the ovary, and by positivity with melanocytic markers. This is an area where electron microscopy can still also contribute useful information. C1 Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BL, Antrim, North Ireland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BL, Antrim, North Ireland. EM glenn.mccluggage@bll.n-i.nhs.uk NR 50 TC 34 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2006 VL 25 IS 4 BP 321 EP 329 DI 10.1097/01.PGP.0000215301.39900.07 PG 9 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 087YA UT WOS:000240777500002 PM 16990706 ER PT J AU Rabban, JT Dal Cin, P Oliva, E AF Rabban, Joseph T. Dal Cin, Paola Oliva, Esther TI HMGA2 rearrangement in a case of vulvar aggressive angiomyxoma SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE vulva; aggressive angiomyxoma; cytogenetics; HMGA2 ID SOFT-TISSUE TUMORS; MESENCHYMAL TUMORS; PROTEIN GENE; EXPRESSION; LIPOMAS; CHROMOSOME; PERINEUM; REGION; 12Q15 AB The histogenesis of aggressive angiomyxoma, an uncommon mesenchymal neoplasm of the vulvar, pelvic, and perineal soft tissues, is poorly understood, although the neoplastic cells exhibit a myofibroblastic phenotype. Cytogenetic studies of aggressive angiomyxoma are scarce; however, a nonrandom involvement of the 12q 15 region where the high mobility group (HMG) protein HMGA2, an architectural transcription factor expressed primarily during embryogenesis, is located has been suggested. HMGA2 involvement has also been described in a variety of benign gynecologic mesenchymal neoplasms. We report an additional case of HMGA2 rearrangement in vulvar aggressive angiomyxoma, using fluorescence in situ hybridization. C1 Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94193 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rabban, JT (reprint author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94193 USA. EM joseph.rabban@ucsf.edu NR 25 TC 14 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2006 VL 25 IS 4 BP 403 EP 407 DI 10.1097/01.pgp.0000209572.54457.7b PG 5 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 087YA UT WOS:000240777500016 PM 16990720 ER PT J AU Luck, J Peabody, JW Lewis, BL AF Luck, J. Peabody, J. W. Lewis, B. L. TI An automated scoring algorithm for computerized clinical vignettes: Evaluating physician performance against explicit quality criteria SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE quality measurement; quality improvement; vignettes; informatics; primary care ID INFORMATION-TECHNOLOGY; STANDARDIZED PATIENTS; CHART ABSTRACTION; CARE; TERMINOLOGY; VALIDATION; DEPRESSION AB Objective: To evaluate the accuracy of an automated algorithm for scoring physicians' responses to open-ended clinical vignettes against explicit, evidence-based quality criteria. Methods: One hundred sixteen physicians completed a total of 915 computerized clinical vignettes at 4 sites. Each vignette simulated an outpatient primary care visit for one of 8 different clinical cases. The automated algorithm scored disease-specific quality criterion as done or not done by recognizing the presence or absence of predefined patterns in the physician's text response to the vignette. Scores generated by the automated algorithm for each criterion were compared to scores generated by trained human abstractors. Vignette responses were divided into development and test sets. Percentage agreement between automated and manual scores was computed separately for the development and test sets. Sensitivity and specificity were calculated. Costs of automated and manual scoring were compared. Results: Accuracy of the algorithm exceeds 90% for both the development and test sets, and is high for care items that were deemed either necessary or unnecessary, across diverse clinical cases, and for all domains of the outpatient clinical encounter. The sensitivity of the automated scoring algorithm is 89.0%, and specificity is 93.5%. Automated scoring is approximately 84% less expensive than manual scoring. Conclusion: Automated scoring of computerized vignettes appears feasible and accurate. Computerized vignettes incorporating accurate automated scoring offer the promise of a highly standardized but relatively inexpensive measurement tool for a wide range of quality assessments within and across health systems. Published by Elsevier Ireland Ltd. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Global Hlth, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RAND, Santa Monica, CA USA. Analyt Solut, Spokane, WA USA. RP Luck, J (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. EM jluck@ucla.edu NR 28 TC 6 Z9 6 U1 4 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD OCT-NOV PY 2006 VL 75 IS 10-11 BP 701 EP 707 DI 10.1016/j.ijmedinf.2005.10.005 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 100EE UT WOS:000241649800002 PM 16324882 ER PT J AU Horner, MD Bedwell, JS Duong, A AF Horner, Michael David Bedwell, Jeffrey S. Duong, Anna TI Abbreviated form of the Test of Memory Malingering SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the International-Neuropsychological-Society CY FEB 04-07, 2004 CL Baltimore, MD SP Int Neuropsychol Soc DE assessment; effort; malingering; measurement; memory; neuro-psychology ID TOMM AB The Test of Memory Malingering (TOMM) is a neuropsychological effort test in which scores below 45 on Trial 2 or Retention Trial indicate insufficient effort on testing, but Trial 1 score is not used. This study attempted to identify Trial 1 cut points above and below which further trials need not be administered. Data were analyzed from 114 patients referred for clinical neuropsychological evaluation. Sensitivity, specificity, and positive and negative predictive value for identifying failure on TOMM were calculated. Trial 1 scores >= 36 indicated 99% likelihood that TOMM would be passed; Trial 1 scores <= 27 indicated 100% likelihood of failure. C1 Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Horner, MD (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv, 116,109 Bee St, Charleston, SC 29401 USA. EM hornermd@musc.edu NR 6 TC 14 Z9 14 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PD OCT PY 2006 VL 116 IS 10 BP 1181 EP 1186 DI 10.1080/00207450500514029 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 075YG UT WOS:000239922900005 PM 16923686 ER PT J AU Ju, YJ Park, JE Juhn, KM Jeong, J Yun, M Park, MJ Park, GH Choi, KY Cho, MH Wong, KK Park, WB Lee, KH AF Ju, Yeun-Jin Park, Jeong Eun Juhn, Kyoung Mi Jeong, Jaemin Yun, Miyong Park, Myung-Jin Park, Gil-Hong Choi, Kang-Yell Cho, Myung-Haeng Wong, Kwok-Kin Park, Won-Bong Lee, Kee-Ho TI Chromosomal end fusion resulting from telomere erosion increases susceptibility to radiation via multinucleation: Effect of p53 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE chromosome; fusion; p53; radiosensitivity; telomerase ID HUMAN CELLULAR SENESCENCE; HUMAN CANCER; TUMOR-CELLS; IONIZING-RADIATION; HUMAN FIBROBLASTS; DNA-REPAIR; DYSFUNCTION; APOPTOSIS; MOUSE; DEATH AB Loss of p53 tumor suppressor facilitates acquisition of telomerase activity. In fact, both p53 inactivation and telomerase activation are frequently found in human cancers. p53 inactivation, however, eliminates or attenuates the biological responses to telomerase inhibition and the eventual telomere erosion. We show that telomere erosion can increase the susceptibility to radiation, irrespective of p53 status. Both telomerase inhibition and critically shortened telomere with significant change of chromosomal end-to-end fusion were essential for the enhancement of radiosensitivity. The enhancement was correlated with greater formation of multinucleated cells. p53 inactivation did not eliminate the observed generation of chromosomal fusion and multi-nucleation, and the resulting increased susceptibility to radiation, as opposed to the previously proved role of p53 in mediating cellular responses to telomere dysfunction. The present findings suggest the importance of chromosomal end fusion in modulating radiosensitivity rather than p53 DNA damage signaling. Thus, the suggested anticancer radiotherapeutic strategy combined with telomerase inhibition could clinically be applicable to cancers, irrespective of p53 status. C1 Korea Inst Radiol & Med Sci, Mol Oncol Lab, Seoul 139706, South Korea. Korea Univ, Coll Med, Dept Biochem, Seoul 136701, South Korea. Yonsei Univ, Coll Engn, Dept Biotechnol, Seoul 120749, South Korea. Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Seoul 151742, South Korea. Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151742, South Korea. Seoul Womens Univ, Div Nat Sci, Seoul 139744, South Korea. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Lee, KH (reprint author), Korea Inst Radiol & Med Sci, Mol Oncol Lab, 215-4 Gongneung Dong, Seoul 139706, South Korea. EM khlee@kcch.re.kr NR 40 TC 5 Z9 5 U1 0 U2 1 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 OCT PY 2006 VL 29 IS 4 BP 753 EP 763 PG 11 WC Oncology SC Oncology GA 088HX UT WOS:000240803900002 PM 16964373 ER PT J AU Floyd, SR Buchholz, TA Haffty, BG Goldberg, S Niemierko, A Raad, RA Oswald, MJ Sullivan, T Strom, EA Powell, SN Katz, A Taghian, AG AF Floyd, Scott R. Buchholz, Thomas A. Haffty, Bruce G. Goldberg, Saveli Niemierko, Andrzei Raad, Rita Abi Oswald, Mary J. Sullivan, Timothy Strom, Eric A. Powell, Simon N. Katz, Angela Taghian, Alphonse G. TI Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger 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 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE breast cancer; >= 5 cm; negative lymph node; mastectomy; no radiation therapy ID RECEIVING ADJUVANT CHEMOTHERAPY; POSTOPERATIVE RADIOTHERAPY; LOCOREGIONAL RECURRENCE; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; MASTECTOMY; FAILURE; TAMOXIFEN; PATTERNS; IRRADIATION AB Purpose: To assess the need for adjuvant radiotherapy following mastectomy for patients with node-negative breast tumors 5 cm or larger. Methods and Materials: Between 1981 and 2002, a total of 70 patients with node-negative breast cancer and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic therapies but without radiotherapy at three institutions. We retrospectively assessed rates and risk factors for locoregional failure (LRF), overall survival (OS), and disease-free survival (DFS) in these patients. Results: With a median follow-up of 85 months, the 5-year actuarial LRF rate was 7.6% (95% confidence interval, 3%-16%). LRF was primarily in the chest wall (415 local failures), and lymphatic-vascular invasion (LVI) was statistically significantly associated with LRF risk by the log-rank test (p = 0.017) and in Cox proportional hazards analysis (p = 0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was also significantly associated with OS and DFS in both univariate and multivariate analysis. Conclusions: This series demonstrates a low LRF rate of 7.6% among breast cancer patients with node-negative tumors 5 cm and larger after mastectomy and adjuvant systemic therapy. Our data indicate that further adjuvant radiation therapy to increase local control may not be indicated by tumor size alone in the absence of positive lymph nodes. LVI was significantly associated with LRF in our series, indicating that patients with this risk factor require careful consideration with regard to further local therapy. (c) 2006 Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. RP Taghian, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org NR 23 TC 30 Z9 30 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 OCT 1 PY 2006 VL 66 IS 2 BP 358 EP 364 DI 10.1016/j.ijrobp.2006.05.001 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 086UW UT WOS:000240699500009 PM 16887288 ER PT J AU Beard, C Schultz, D Loffredo, M Cote, K Renshaw, AA Hurwitz, MD D'Amico, AV AF Beard, Clair Schultz, Delray Loffredo, Marian Cote, Kerri Renshaw, Andrew A. Hurwitz, Mark D. D'Amico, Anthony V. TI Perineural invasion associated with increased cancer-specific mortality after external beam radiation therapy for men with low- and intermediate-risk prostate cancer 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 17-20, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE perineural invasion; prostate cancer; conformal radiation; mortality ID SURROGATE END-POINT; RADICAL PROSTATECTOMY; NEEDLE-BIOPSY; SCREENING POPULATION; PATHOLOGICAL STAGE; INCREASED FAILURE; PREDICTION; RADIOTHERAPY; RELAPSE AB Purpose: To identify an association between perineural invasion (PNI) and cancer-specific survival in patients With prostate cancer after standard-dose external beam radiation therapy (RT). Methods and Materials: A total of 517 consecutive patients who underwent RT (median dose, 70.5 Gy) between 1989 and 2003 for low-risk or intermediate-risk prostate cancer were studied. A genitourinary pathologist (AAR) scored presence or absence of PNI on all prostate needle-biopsy specimens. A Cox regression multivariable analysis was performed to assess whether the presence of PNI was associated with risk of prostate cancer-specific mortality after RT when the recognized risk-group variables were factored into the model. Estimates of cancer-specific mortality were made using a cumulative incidence method. Comparisons of survival were made using a two-tailed log-rank test. Results: At a median follow-up of 4.5 years, 84 patients (16%) have died, 15 of 84 (18%) from prostate cancer. PNI was the only significant predictor of prostate cancer-specific mortality after RT (p = 0.012). The estimated prostate cancer-specific mortality was 14% at 8 years for PNI + patients vs. 5% for PNI- patients (p = 0.0008). Conclusions: Patients with low- or intermediate-risk prostate cancer who have PNI on prostate needle biopsy have a significantly higher rate of prostate cancer-specific mortality after standard-dose radiation therapy than patients without PNI. Although this analysis is retrospective, this association argues for consideration of the use of more aggressive therapy, such as hormonal therapy with RT or dose escalation, in these select patients. (c) 2006 Elsevier Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Stat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Beard, C (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM cbeard@lroc.harvard.edu NR 30 TC 27 Z9 28 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 OCT 1 PY 2006 VL 66 IS 2 BP 403 EP 407 DI 10.1016/j.ijrobp.2006.03.033 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 086UW UT WOS:000240699500016 PM 16765530 ER PT J AU Hohmuth, BA Yamanija, JC Dayal, AS Nardell, E Salazar, JJ Fawzi, MCS AF Hohmuth, B. A. Yamanija, J. C. Dayal, A. S. Nardell, E. Salazar, J. J. Fawzi, M. C. Smith TI Latent tuberculosis infection: risks to health care students at a hospital in Lima, Peru SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculosis; transmission; nosocomial; Peru ID PULMONARY TUBERCULOSIS AB SETTING: University hospital and university campus in Lima, Peru. OBJECTIVE: To demonstrate the risk of latent tuberculosis infection (LTBI) in the hospital relative to the community. DESIGN: Prospective cohort study of university students measuring prevalence, boosting, and conversion of tuberculin skin tests (TSTs) among health care students (HCS) and non-health care students (NHCS). RESULTS: Among the HCS relative to NHCS, prevalence of initial positive TST was 20.9% vs. 12.2% (P < 0.001), and conversion rate was 1.1% vs. 0% (P = 0.423) at the 10 mm cut-off and 11.8% vs. 0% at the 6 mm cutoff (P = 0.00005). Multivariate analysis showed that the HCS group had a higher risk of baseline positive TST compared with the NHCS group after controlling for confounding factors (OR 1.7, 95% CI 1.1-2.6). CONCLUSION: HCS are at greater risk than NHCS for having positive baseline TSTs and for TST conversion at the 6 mm cut-off. We conclude that the hospital we studied in Lima, Peru, poses a greater risk than the surrounding community for tuberculosis infection, and greater attention to hospital infection control measures is warranted. A higher rate of skin test boosting among the HCS cohort suggests the possibility of transient, non-progressive LTBI, which merits further study. C1 Harvard Univ, Sch Med, Program Infect Dis & Social Change, Dept Social Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Partners Hlth, Boston, MA USA. Harvard Vanguard Med Associates, Boston, MA USA. Socios Salud, Lima, Peru. Massachusetts Gen Hosp Hlth Care Ctr, Revere, MA USA. RP Fawzi, MCS (reprint author), Harvard Univ, Sch Med, Program Infect Dis & Social Change, Dept Social Med, 641 Huntington Ave,1st Floor, Boston, MA 02115 USA. EM mksfawzi@msn.com NR 15 TC 10 Z9 12 U1 0 U2 1 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD OCT PY 2006 VL 10 IS 10 BP 1146 EP 1151 PG 6 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 088XJ UT WOS:000240844100013 PM 17044209 ER PT J AU Corless, IB Nicholas, PK Wantland, D McInerney, P Ncama, B Bhengu, B McGibbon, C Davis, S AF Corless, I. B. Nicholas, P. K. Wantland, D. McInerney, P. Ncama, B. Bhengu, B. McGibbon, C. Davis, S. TI The impact of meaning in life and life goals on adherence to a tuberculosis medication regimen in South Africa SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculosis; adherence; South Africa; meaning in life; life goals ID SELF-REPORTED ADHERENCE; ANTIRETROVIRAL THERAPY; COHERENCE; SENSE; ESTEEM; ADULTS AB SETTING: Out-patient tuberculosis (TB) clinics in Durban, South Africa. OBJECTIVE: Healthcare provider concerns about persons with active TB defaulting on medications led to a study of adherence among persons receiving anti-tuberculosis therapy and, specifically, the relationships between meaning in life, life goals, sense of coherence, social support, symptom presence and intensity, and adherence in individuals diagnosed with TB. DESIGN: A cross-sectional, descriptive design was used to gather self-reported data from TB-infected individuals who were enrolled in out-patient clinics. Data were collected from 159 Zulu and/or English-speaking persons who agreed to participate in the study. RESULTS: A significant relationship was found between higher life goals and adherence to TB treatment (P = 0.027). Analysis of variance revealed that higher meaning in life ratings were significantly associated with older age (P = 0.007). Having children and children living in the same household were significantly associated with low meaning in life ratings (P = 0.006 and P <= 0.001, respectively), indicating that these individuals were more concerned about basic matters of home and sustenance. CONCLUSIONS: The results of this study indicate that meaning in life and life goals may be useful for identifying individuals who will require additional support in adhering to anti-tuberculosis treatment. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02129 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ KwaZulu Natal, Durban, South Africa. Univ New Brunswick, Fredericton, NB, Canada. RP Corless, IB (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, CNY 36 1st Ave, Boston, MA 02129 USA. EM Icorless@mghihp.edu OI Corless, Inge/0000-0003-0438-2037 NR 33 TC 4 Z9 4 U1 1 U2 4 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD OCT PY 2006 VL 10 IS 10 BP 1159 EP 1165 PG 7 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 088XJ UT WOS:000240844100015 PM 17044211 ER PT J AU Fautsch, MP Johnson, DH AF Fautsch, Michael P. Johnson, Douglas H. CA Second ARVOPfizer Res Inst Working TI Aqueous humor outflow: What do we know? Where will it lead us? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; INNER-WALL ENDOTHELIUM; HUMAN TRABECULAR MESHWORK; SCHLEMMS CANAL CELLS; INTRAOCULAR-PRESSURE; HUMAN EYES; FLUORESCENCE MICROSCOPY; CHONDROITINASE ABC; ANTERIOR SEGMENTS; INCREASED LEVEL C1 Mayo Clin & Mayo Fdn, Dept Ophthalmol, Coll Med, Rochester, MN 55905 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Tokyo, Tokyo, Japan. Univ Miami, Miami, FL 33152 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Univ Penn, Philadelphia, PA 19104 USA. Alcon Res Inc, Ft Worth, TX USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Duke Univ, Ctr Eye, Durham, NC USA. Univ Toronto, Toronto, ON, Canada. Boston Univ, Sch Med, Boston, MA 02118 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Northwestern Univ, Evanston, IL USA. Univ Wisconsin, Madison, WI USA. Univ Erlangen Nurnberg, Erlangen, Germany. NEI, NIH, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ USA. Univ Regensburg, D-8400 Regensburg, Germany. Univ Washington, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19104 USA. Weizmann Inst Sci, IL-76100 Rehovot, Israel. Univ Vienna, Vienna, Austria. NCI, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Queens Univ Belfast, Belfast, Antrim, North Ireland. Texas A&M Univ, Syst Hlth Sci Ctr, College Stn, TX USA. Pfizer Ophthalm, New York, NY USA. Aerie Pharmaceut, Res Triangle Pk, NC USA. Tufts Univ, Sch Med, Boston, MA USA. Univ Louisville, Louisville, KY 40292 USA. Harvard Univ, Cambridge, MA 02138 USA. Lexicon Genet, The Woodlands, TX USA. Indiana Univ, Sch Med, Indianapolis, IN USA. RP Fautsch, MP (reprint author), Mayo Clin & Mayo Fdn, Dept Ophthalmol, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM fautsch@mayo.edu FU NEI NIH HHS [R01 EY015736, R01 EY015736-01A1] NR 77 TC 39 Z9 41 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2006 VL 47 IS 10 BP 4181 EP 4187 DI 10.1167/iovs.06-0830 PG 7 WC Ophthalmology SC Ophthalmology GA 088AU UT WOS:000240784700001 PM 17003404 ER PT J AU Primack, BA Gold, MA Land, SR Fine, MJ AF Primack, Brian A. Gold, Melanie A. Land, Stephanie R. Fine, Michael J. TI Association of cigarette smoking and media literacy about smoking among adolescents SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE smoking; tobacco; media; advertising; television; media messages; movies; media literacy; media education; adolescence; aubstance abuse; education; school-based ID TOBACCO USE; PROMOTION; CHILDREN; SUSCEPTIBILITY; VALIDATION; PREVENTION; INDUSTRY; ALCOHOL; PROGRAM; TRIAL AB Purpose: To determine whether media literacy concerning tobacco use is independently associated with two clinically relevant outcome measures in adolescents: current smoking and susceptibility to smoking. Methods: We asked high school students aged 14-18 years to complete a survey that included a validated 18-item smoking media literacy (SML) scale, items assessing current smoking and susceptibility to future smoking, and covariates shown to be related to smoking. We used logistic regression to assess independent associations between the two outcome measures and SML. Results: Of the 1211 students who completed the survey, 19% reported current smoking. Controlling for all potential confounders of smoking, we found that an increase of one point (out of 10) in SML was independently associated with an odds ratio for smoking of.84 (95% confidence interval [CI].71-99). Compared with students below the median score on the SML scale, students above the median had an odds ratio for smoking of.57 (95% CI.37-87). Of the students who were nonsmokers, 40% were classified as susceptible to future smoking. Controlling for all potential confounders of smoking, we found that an increase of one point (out of 10) was independently associated with and an odds ratio for smoking susceptibility of .68 (95% CI.58-79). Compared with students below the median SML, students above the median SML had an odds ratio for smoking susceptibility of .49 (95% CI .35-68). Conclusions: In this sample of high school students, higher SML is independently associated with reduced current smoking and reduced susceptibility to future smoking. (c) 2006 Society for Adolescent Medicine. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Primack, BA (reprint author), Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU NCI NIH HHS [K07 CA114315, K07 CA114315-01A1]; NIAID NIH HHS [K24 AI001769, 5K24 AI01769] NR 40 TC 33 Z9 35 U1 5 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD OCT PY 2006 VL 39 IS 4 BP 465 EP 472 DI 10.1016/j.jadohealth.2006.05.011 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 090QR UT WOS:000240966400003 PM 16982379 ER PT J AU Dienes, KA Hammen, C Henry, RM Cohen, AN Daley, SE AF Dienes, Kimberly A. Hammen, Constance Henry, Risha M. Cohen, Amy N. Daley, Shannon E. TI The stress sensitization hypothesis: Understanding the course of bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; stress; kindling; behavioral sensitization; stress sensitization ID LIFE EVENTS; KINDLING HYPOTHESIS; DEPRESSION; NEUROBIOLOGY; RECURRENCE; REACTIVITY; WOMEN; ABUSE AB Background: The influence of psychosocial stress on the course of bipolar disorder has been increasingly recognized. The authors tested hypotheses about both stress and early adversity "sensitization" on the course of bipolar disorder over a one-year period. Methods: The participants were 58 adults (29 male and 29 female) with a diagnosis of bipolar I disorder. They were evaluated every three months for one year. Stressful life events and the presence of early adversity were assessed by structured interview. Results: There was no significant interaction between stress and episode number in the prediction of bipolar recurrence. The interaction of early adversity severity and stressful life events significantly predicted recurrence in a manner consistent with the sensitization hypothesis. Participants with early adversity reported lower levels of stress prior to recurrence than those without early adversity. Individuals with early adversity also had a significantly younger age of bipolar onset. Limitations: The sample size was small and the number of past episodes was determined retrospectively, mainly through self-report. Conclusions: Severe early adversity may result in a greater effect of stress on bipolar recurrence and earlier onset of bipolar disorder, suggesting the need for further studies of stress mechanisms in bipolar disorder and of treatments designed to intervene early among those at risk. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. MIRECC, Los Angeles, CA USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. RP Dienes, KA (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,POB 951563,405 Hilgard Ave, Los Angeles, CA 90095 USA. EM kdienes@ucla.edu OI Dienes, Kimberly/0000-0002-6119-7025 FU NIMH NIH HHS [MH-14584, MH52239] NR 19 TC 60 Z9 62 U1 5 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2006 VL 95 IS 1-3 BP 43 EP 49 DI 10.1016/j.jad.2006.04.009 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 097VQ UT WOS:000241477700006 PM 16837055 ER PT J AU Rodriguez, KL Young, AJ AF Rodriguez, Keri L. Young, Amanda J. TI Elderly veterans' beliefs concerning life-sustaining treatment and the control of their end-of-life health and health care SO JOURNAL OF AGING AND HEALTH LA English DT Article DE veterans; advance care planning; geriatrics; health locus of control; qualitative research ID PERCEIVED CONTROL; EXTERNAL CONTROL; MHLC SCALES; LOCUS; DEPRESSION; DISEASES AB Objective: This study used qualitative methods to explore patients' beliefs about control of their end-of-life health and health care. Method: The authors recruited 30 elderly patients from a large, urban Veterans Administration medical center in the United States and engaged them in semistructured interviews about end-of-life care concepts. Using grounded theory methods, they coded, categorized, and compared responses. Results: The authors discovered that patients' decisions about using life-sustaining treatment were interconnected with their beliefs about their degree of control over circumstances and the role of external factors, including a higher power; institutions and individuals; medical interventions; medical conditions; and luck, chance, or fate. Discussion: The results shed light on why patients do or do not take active roles in advance decisions concerning the use of life-sustaining treatment. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Univ Memphis, Memphis, TN 38152 USA. RP Rodriguez, KL (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. NR 52 TC 6 Z9 6 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD OCT PY 2006 VL 18 IS 5 BP 686 EP 706 DI 10.1177/08982643063293258 PG 21 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 088TC UT WOS:000240833000003 PM 16980635 ER PT J AU He, XM Fowler, A Toner, M AF He, Xiaoming Fowler, Alex Toner, Mehmet TI Water activity and mobility in solutions of glycerol and small molecular weight sugars: Implication for cryo- and lyopreservation SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID POLYMER-SOLVENT SYSTEMS; MUTUAL DIFFUSION-COEFFICIENTS; AMORPHOUS PHARMACEUTICAL SOLIDS; GLASS-TRANSITION BEHAVIOR; FREE-VOLUME THEORY; PRESERVING DRY BIOMATERIALS; SELF-DIFFUSION; VAPOR ABSORPTION; REPLACEMENT HYPOTHESIS; TEMPERATURE-DEPENDENCE AB In this study, the free volume models, originally developed for large molecular weight polymer-solvent systems, were used to study the water activity and mobility in solutions of four small molecular weight cryo-/lyoprotectants, viz., glycerol, a monosaccharide (fructose), and two disaccharides (sucrose and trehalose). The free volume model parameters were determined by fitting the models to available experimental data using a nonlinear optimization procedure. It was found that free volume models could accurately predict the available experimental data, which suggests that the free volume models might be generally applicable to aqueous solutions of small molecular weight cryo-/lyoprotectants. Furthermore, several models for estimating the mutual diffusion coefficient were tested using available experimental data for aqueous solutions of glycerol and a better method to estimate the mutual diffusion coefficient was proposed. Free volume models were used to predict and analyze the water activity and mobility in solutions of four cryo-/lyoprotectants under conditions frequently encountered in cryo-/lyopreservation applications. It was found that the water mobility in the glassy state of the above four solutions is essentially negligible in the case of cryopreservation with storage temperature lower than -110 degrees C. However, the water mobility in a glass at higher temperature (>-80 degrees C) may be significant. As a result, a subcooling of up to 50 degrees C may be necessary for the long-term cryo-/lyopreservation of biomaterials depending on the water content and the type of cryo-/lyoprotectants. It was further shown that trehalose might be the best of the four protectants studied for lyopreservation (water mass fraction <= 0.1) when the storage temperature is above the room temperature. The results from this study might be useful for the development of more effective protocols for both cryopreservation and lyopreservation of living cells and other biomaterials. (c) 2006 American Institute of Physics. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu RI He, Xiaoming/C-5499-2008 OI He, Xiaoming/0000-0003-0125-6086 NR 82 TC 50 Z9 51 U1 1 U2 25 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD OCT 1 PY 2006 VL 100 IS 7 AR 074702 DI 10.1063/1.2336304 PG 11 WC Physics, Applied SC Physics GA 094OE UT WOS:000241248000103 ER PT J AU Reddy, ST Berk, DA Jain, RK Swartz, MA AF Reddy, Sai T. Berk, David A. Jain, Rakesh K. Swartz, Melody A. TI A sensitive in vivo model for quantifying interstitial convective transport of injected macromolecules and nanoparticles SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE drug delivery; size exclusion; lymphatic uptake; extracellular matrix; subcutaneous ID HINDERED CONVECTION; MATHEMATICAL-MODEL; AGAROSE GELS; FLUID; LYMPH; MOLECULES; PLASMA; TUMORS; EXCHANGE; PROTEINS AB A sensitive in vivo model for quantifying interstitial convective transport of injected macromolecules and nanoparticles. J Appl Physiol 101: 1162-1169, 2006. First published June 8, 2006; doi:10.1152/japplphysiol.00389.2006.-Effective interstitial transport of particles is necessary for injected drug/diagnostic agents to reach the intended target; however, quantitative methods to estimate such transport parameters are lacking. In this study, we develop an in vivo model for evaluating interstitial convection of injected macromolecules and nanoparticles. Fluorescently labeled macromolecules and particles are coinfused with a reference solute at constant infusion pressure intradermally into the mouse tail tip, and their relative convection coefficients are determined from spatial and temporal interstitial concentration profiles. Quantifying relative solute velocity with a coinfused reference solute eliminates the need to estimate interstitial fluid velocity profiles, greatly reducing experimental variability. To demonstrate sensitivity and usefulness of this model, we compare the effects of size (dextrans of 3, 40, 71, and 2,000 kDa and 40-nm diameter particles), shape (linear dextran 71 kDa vs. 69 kDa globular protein albumin), and charge (anionic vs. neutral dextran 3 kDa) on interstitial convection. We find significant differences in interstitial transport rates between each of these molecules and confirm expected transport phenomena, testifying to sensitivity of the model in comparing solutes of different size, shape, and charge. Our data show that size exclusion (within a specific size range) dominates molecular convection, while mechanical hindrance slows larger molecules and nanoparticles; proteins convect slower than linear molecules of equal molecular mass, and negative surface charges increase convection through matrix repulsion. Our in vivo model is presumably a sensitive and reliable tool for evaluating and optimizing potential drug/diagnostic vehicles that utilize interstitial and lymphatic delivery routes. C1 Ecole Polytech Fed Lausanne, Inst Bioengn, Lab Mechanobiol & Morphogenesis, Stn 15, CH-1015 Lausanne, Switzerland. Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester, Lancs, England. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Swartz, MA (reprint author), Ecole Polytech Fed Lausanne, Inst Bioengn, Lab Mechanobiol & Morphogenesis, Stn 15, CH-1015 Lausanne, Switzerland. EM melody.swartz@epfl.ch RI Swartz, Melody/B-7633-2009; Reddy, Sai/B-4190-2012; Swartz, Melody/F-9563-2011; Berk, David/A-4863-2012 OI Reddy, Sai/0000-0002-9177-0857; Berk, David/0000-0002-3855-6886 FU NCI NIH HHS [CA-85140, CA-80124, CA-89018-01] NR 26 TC 45 Z9 49 U1 1 U2 12 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 OCT PY 2006 VL 101 IS 4 BP 1162 EP 1169 DI 10.1152/japplphysiol.00389.2006 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 084CS UT WOS:000240510000022 PM 16763103 ER PT J AU Bragdon, CR Barrett, S Martell, JM Greene, ME Malchau, H Harris, WH AF Bragdon, Charles R. Barrett, Susan Martell, John M. Greene, Meridith E. Malchau, Henrik Harris, William H. TI Steady-state penetration rates of electron beam-irradiated, highly cross-linked polyethylene at an average 45-month follow-up SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip replacement; cross-linked polyethylene; wear; hip; arthroplasty ID TOTAL HIP-ARTHROPLASTY; MOLECULAR-WEIGHT POLYETHYLENE; WEAR; PERFORMANCE; SOCKETS; LINERS AB Steady-state penetration rates were determined on 53 total hip arthroplasties with a minimum 3-year follow-up using electron beam highly cross-linked melted polyethylene by determining the femoral head penetration occurring after the first year in vivo. These data were compared with that of a matched control group. The average steady-state penetration rate of the control group was 144 +/- 191 mu m/y, significantly higher than that of the highly crosslinked polyethylene group, 25 +/- 99 mu m/y (P = .0001). Linear regression analysis indicated that the magnitude of femoral head penetration did not increase with time in the cross-linked groups. Also, no significant difference existed between the steady-state wear rates of the highly cross-linked groups with two head sizes (28 vs 32 mm, P = .39). C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Chicago, Sect Orthopaed, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Jackson 1126, Boston, MA 02114 USA. NR 21 TC 36 Z9 36 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2006 VL 21 IS 7 BP 935 EP 943 DI 10.1016/j.arth.2006.01.006 PG 9 WC Orthopedics SC Orthopedics GA 101DC UT WOS:000241718100002 PM 17027534 ER PT J AU Wannomae, KK Bhattacharyya, S Freiberg, BA Estok, D Harris, WH Muratoglu, O AF Wannomae, Keith K. Bhattacharyya, Shayan Freiberg, Bs. Andrew Estok, Daniel Harris, William H. Muratoglu, Orhun TI Vivo oxidation of retrieved cross-linked ultra-high-molecular-weight polyethylene acetabular components with residual free radicals SO JOURNAL OF ARTHROPLASTY LA English DT Article DE highly cross-linked polyethylene; wear; oxidation; free radical; acetabular component ID WEAR-RESISTANCE; HIP; STERILIZATION; CUPS AB Wear of ultra-high-molecular-weight polyethylene (UHMWPE) contributes to debris that can lead to periprosthetic osteolysis in total hip arthroplasty. Irradiation not only decreases wear of UHMWPE but also generates residual free radicals that can oxidize the UHMWPE in the long term. Melting or annealing is used to quench the free radicals. Melting is more effective than annealing. We hypothesized that the postirradiation annealed UHMWPE components would oxidize in vivo and that postirradiation melted ones would not. We analyzed surgical explants of UHMWPE acetabular liners. The irradiated and annealed explants showed embrittlement, oxidation, and an increase in crystallinity. The irradiated and melted UHMWPE explants showed no oxidation, no increase in crystallinity, and no embrittlement. To prevent long-term chemical changes in highly cross-linked UHMWPE components, the residual free radicals must be stabilized after irradiation, preferably by melting and not annealing. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Muratoglu, O (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. NR 14 TC 58 Z9 59 U1 2 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2006 VL 21 IS 7 BP 1005 EP 1011 DI 10.1016/j.arth.2005.07.019 PG 7 WC Orthopedics SC Orthopedics GA 101DC UT WOS:000241718100011 PM 17027543 ER PT J AU Duffy, GP Lozynsky, AJ Harris, WH AF Duffy, Gavan P. Lozynsky, Andrew J. Harris, William H. TI Polished vs rough femoral components in grade A and grade C-2 cement mantles SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; cemented femoral component; surface finish; cement technique ID TOTAL HIP-ARTHROPLASTY; FOLLOW-UP; PROSTHESIS; CHARNLEY; FAILURE; SURFACE; STEMS AB The ideal surface for cemented femoral components remains controversial. Six polished stems were compared with 6 rough stems both with good cement mantle and also with poor cement mantles in a stair-climbing model. With good cement mantles, both the polished and the rough stems were loose by 6 million cycles. However, none were loose by radiographic criteria. With the poor cement mantle, both stems became loose earlier and developed more micromotion, the polished stems having significantly higher and earlier motion than the rough. Radiographic evidence of debonding was not visible until the stems had motion of more than 2000 mu m. In the presence of a good cement mantle in this laboratory model there was no significant difference in the development of micromotion under fatigue stair-climbing conditions between a polished or grit-blasted femoral component. However, in the presence of a poor cement mantle, the polished components had earlier and higher micromotion. This study reinforces the importance of centralization and cement technique, particularly if using a polished surface finish. C1 Mayo Clin, Dept Orthoped, Jacksonville, FL 32224 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. RP Duffy, GP (reprint author), Mayo Clin, Dept Orthoped, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. NR 25 TC 0 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2006 VL 21 IS 7 BP 1054 EP 1063 DI 10.1016/j.arth.2005.07.018 PG 10 WC Orthopedics SC Orthopedics GA 101DC UT WOS:000241718100019 PM 17027551 ER PT J AU Trief, PM Ouimette, P Wade, M Shanahan, P Weinstock, RS AF Trief, Paula M. Ouimette, Paige Wade, Michael Shanahan, Paul Weinstock, Ruth S. TI Post-traumatic stress disorder and diabetes: Co-morbidity and outcomes in a male veterans sample SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE diabetes mellitus; post-traumatic stress disorder; glycemic control; veterans ID CORONARY-HEART-DISEASE; POOR GLYCEMIC CONTROL; GULF-WAR VETERANS; HEALTH-STATUS; DEPRESSION; ILLNESS; ADULTS; CARE; ANXIETY; PREVALENCE AB The purpose of this study was to assess the prevalence and correlates of comorbid diabetes and Post-Traumatic Stress disorder(PTSD)and potential relationships between PTSD and diabetes outcomes. Male patients enrolled in a VA primary care database (N = 73,270) were classified as having diabetes from pharmacy records (N = 14,438) and grouped into those with diagnoses of PTSD with depression (N = 649), PTSD-only (N = 480), Depression-only (N = 1696), Other psychiatric diagnosis (N = 736), or No psychiatric diagnosis (N = 10,877) based on the Purpose of Visit diagnoses in the medical record. Outcomes included glycemic control (HbA1c), cholesterol and tryglycerides. Correlates were age, substance use disorder, other psychiatric diagnosis, number of primary care encounters, and medications. The prevalence of comorbid diabetes and PTSD was 8% (n = 1129). Of these, 57% (n = 649) had comorbid depression. Patients with PTSD and depression had higher rates of substance use disorder and higher cholesterol and LDL. Patients with depression had poorer glycemic control. Patients with PTSD and depression weighed more and had higher BMI than patients with neither diagnosis. Thus, male diabetes patients with PTSD and depression may be vulnerable to substance use disorders and to weight/lipid problems that can affect health. Depression is a likely contributor to poor glycemic control. Careful screening for mental health comorbidities is needed for diabetes patients. C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA. Vet Affairs Med Ctr, Ctr Integrated Healthcare, Syracuse, NY USA. Vet Affairs Med Ctr, Dept Med, Syracuse, NY USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. RP Trief, PM (reprint author), SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. NR 36 TC 52 Z9 54 U1 2 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD OCT PY 2006 VL 29 IS 5 BP 411 EP 418 DI 10.1007/s10865-006-9067-2 PG 8 WC Psychology, Clinical SC Psychology GA 082BZ UT WOS:000240362800002 PM 16865552 ER PT J AU Broom, WJ Auwarter, KE Ni, J Russel, DE Yeh, LA Maxwell, MM Glicksman, M Kazantsev, AG Brown, RH AF Broom, Wendy J. Auwarter, Kristen E. Ni, Jake Russel, Deborah E. Yeh, Li-An Maxwell, Michele M. Glicksman, Marcie Kazantsev, Aleksey G. Brown, Robert H., Jr. TI Two approaches to drug discovery in SODI-mediated ALS SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE cell-based assay; high-throughput screening; superoxide dismutase 1; amyotrophic lateral sclerosis; stable cell lines ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE GENE; MOTOR-NEURON DISEASE; HUNTINGTONS-DISEASE; MUTATIONS; MODEL; MICE; NEURODEGENERATION; PROTEIN AB Familial amyotrophic lateral sclerosis (ALS) accounts for 10% of all ALS cases; approximately 25% of these cases are due to mutations in the Cu/Zn superoxide dismutase gene (SOD1). To date, 105 different mutations spanning all 5 exons have been identified in the SOD1 gene. Mutant SOD1-associated ALS is caused by a toxic gain of function of the mutated protein. Therefore, regardless of the specific mechanism whereby mutant SOD1 initiates motor neuron death, the authors hypothesize that measures that decrease levels of mutant SOD1 protein should ameliorate the phenotype in transgenic mice and potentially in patients with SOD1-mediated disease. They have designed 2 cell-based screening assays to identify small, brain-permeant molecules that inactivate expression of the SOD1 gene or increase the degradation of the SOD I protein. Here they describe the development and optimization of these assays and the results of high-throughput screening using a variety of compound libraries, including a total of more than 116,000 compounds. The majority of the hit compounds identified that down-regulated SODI were shown to be toxic in a cell-based viability assay or were nonselective transcription inhibitors, but work is continuing on a number of nonspecific inhibitors of SOD1 expression. Ultimately, the authors believe that these 2 cell-based assays will provide powerful strategies to identify novel therapies for the treatment of inherited SOD1-associated forms of ALS. C1 Massachusetts Gen Hosp, Day Neuromuscular Res Lab, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, Lab Drug Discovery & Neurodegenert, Ctr Neurodegenerat & Repair, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, High Throughput Screening Lab, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Broom, WJ (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Res Lab, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM wbroom@partners.org NR 17 TC 16 Z9 17 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD OCT PY 2006 VL 11 IS 7 BP 729 EP 735 DI 10.1177/1087057106290937 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 095TN UT WOS:000241331300001 PM 16928982 ER PT J AU Green, DM Noble, PC Bocell, JR Ahuero, JS Poteet, BA Birdsall, HH AF Green, D. M. Noble, P. C. Bocell, J. R., Jr. Ahuero, J. S. Poteet, B. A. Birdsall, H. H. TI Effect of early full weight-bearing after joint injury on inflammation and cartilage degradation SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TUMOR-NECROSIS-FACTOR; DETECTED BONE BRUISES; ARTICULAR-CARTILAGE; CHONDROCYTE DEATH; FACTOR-ALPHA; IMPACT LOAD; TNF-ALPHA; EXPRESSION; MATRIX; INTERLEUKIN-10 AB Background: Early full weight-bearing after an acute osteochondral injury avoids problems associated with immobility but may also be harmful by amplifying the inflammatory response. To investigate these effects, we developed an in vivo model of subchondral trauma. Methods: After an impact injury to the femoral condyle, fourteen dogs were randomized to immediate full weight-bearing or to four weeks of minimal weight-bearing before full weight-bearing. Synovial fluid was sampled by aspiration at one, two, four, eight, twelve, sixteen, twenty, and twenty-four weeks. Neutrophils, monocytes, and lymphocytes were enumerated, and the concentrations of tumor necrosis factor-alpha, interleukin-10, nitric oxide, matrix metalloproteinases, and glycosaminoglycans were measured. Results: Compared with the findings for uninjured joints, the synovial fluid from the impacted joints of full-weight-bearing dogs had significantly higher peak concentrations of neutrophils (p = 0.0006 at one week), mononuclear leukocytes (p = 0.001 at four weeks), tumor necrosis factor-alpha (p = 0.001 at one week), nitric oxide (p = 0.001 at one week), matrix metalloproteinases (p = 0.008 at one week), and glycosaminoglycans (p = 0.002 at four weeks and p = 0.001 at six months). The size of the bone bruise correlated with the peak concentrations of tumor necrosis factor-alpha (r(2) = 0.89, p = 0.007; Spearman rank test), matrix metalloproteinases (r(2) = 0.96, p = 0.0004), and glycosaminoglycans (r(2) = 0.96, p = 0.0004). However, restriction to minimal weight-bearing for four weeks after the injury led to a significant reduction in the synovial fluid concentrations of neutrophils (p = 0.007 at one week and p = 0.01 at two weeks), tumor necrosis factor-alpha (p = 0.0006 to 0.02 during the first four weeks), nitric oxide (p = 0.001 to 0.04 during the first four weeks), and matrix metalloproteinases (p = 0.007 to 0.01 from the second week to the eighth week). In contrast, interleukin-10 concentrations were significantly higher (p = 0.002 at one week) and glycosaminoglycan levels remained at normal levels in animals that were restricted from immediate full weight-bearing after the injury. Conclusions: The magnitude of the inflammatory response is proportional to the size of the bone bruise. Restriction to minimal weight-bearing for four weeks reduces the magnitude of the inflammatory response and the cartilage degradation following articular cartilage impact injury. Clinical Relevance: Strategies to minimize mechanical stress during the early postinjury period may help to preserve cartilage integrity and forestall the development of osteoarthritis. C1 Michael E DeBakey Vet Affairs Med Ctr, Res Off, Houston, TX 77030 USA. Baylor Coll Med, Dept Orthoped Surg, Houston, TX 77030 USA. RP Green, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Res Off, MS 151,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgreen@bcm.tmc.edu NR 40 TC 19 Z9 24 U1 0 U2 0 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 OCT PY 2006 VL 88A IS 10 BP 2201 EP 2209 DI 10.2106/JBJS.E.00812 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 096YI UT WOS:000241412400012 PM 17015597 ER PT J AU Doornberg, JN Ring, DC AF Doornberg, Job N. Ring, David C. TI Fracture of the anteromedial facet of the coronoid process SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID RADIAL HEAD; ELBOW; DISLOCATION; ULNA; OLECRANON AB Background: Fracture of the anteromedial facet of the coronoid was recently recognized as a distinct type of coronoid fracture resulting from a varus posteromedial rotational injury force. Very few reports are available to help guide the management of these injuries. Methods: Eighteen patients with a fracture of the anteromedial facet of the coronoid process were treated over a six-year period. Twelve patients were treated for the acute fracture, and six were managed after initial treatment elsewhere. All but three patients (two with concomitant fracture of the olecranon and one with a second fracture at the base of the coronoid) had avulsion of the origin of the lateral collateral ligament complex from the lateral epicondyle. The initial treatment was operative in fifteen patients and nonoperative in three. The coronoid fracture was secured with a plate applied to the medial surface of the coronoid in nine patients, a screw in one patient, and sutures in one patient. It was not repaired in the remaining seven patients. Results: At the final evaluation, an average of twenty-six months after the injury, six patients had malalignment of the anteromedial facet of the coronoid with varus subluxation of the elbow, which was due to the fact that the fracture had not been specifically treated in four patients and to loss of fracture fixation in two patients. All six had development of arthrosis and a fair or poor result according to the system of Broberg and Morrey. The remaining twelve patients had good or excellent elbow function. Conclusions: Anteromedial fractures of the coronoid are associated with either subluxation or complete dislocation of the elbow in most patients. Secure fixation of the coronoid fracture usually restores good elbow function. Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Doornberg, JN (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 19 TC 57 Z9 66 U1 0 U2 3 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 OCT PY 2006 VL 88A IS 10 BP 2216 EP 2224 DI 10.2106/JBJS.E.01127 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 096YI UT WOS:000241412400014 PM 17015599 ER PT J AU Hendricks, KJ Harris, WH AF Hendricks, Kelly J. Harris, William H. TI High placement of noncemented acetabular components in revision total hip arthroplasty - A concise follow-up, at a minimum of fifteen years, of a previous report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID REPLACEMENT; CEMENT AB We previously reported the average ten-year results associated with the use of porous-coated noncemented acetabular shells that were placed at a high hip center at the time of revision total hip arthroplasty in thirty-four patients (thirty-six hips) with severe acetabular bone loss. We now report the average 16.8-year results for twenty-one patients (twenty-three hips). Of the original cohort of forty-four patients (forty-six hips), thirty-nine patients (forty-one hips; 89%) retained the shell. Two shells (4.3%) were revised because of aseptic loosening, and three (6.5%) were revised because of infection. Six femoral components were revised because of femoral osteolysis, and seven were revised because of aseptic loosening without osteolysis. On the basis of our results after an average duration of follow-up of 16.8 years, we believe that the placement of an uncemented acetabular component at a high hip center continues to be an excellent technique for revision total hip arthroplasty in selected patients with severe acetabular bone loss. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Hendricks, KJ (reprint author), Univ Kansas, Med Ctr, Dept Orthopaed Surg, MS 3017,3905 Rainbow Blvd, Overland Pk, KS 66210 USA. EM kchendri2002@yahoo.com; wharris.obbl@partners.org NR 14 TC 31 Z9 36 U1 0 U2 0 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 OCT PY 2006 VL 88A IS 10 BP 2231 EP 2236 DI 10.2106/JBJS.E.00247 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 096YI UT WOS:000241412400016 PM 17015601 ER PT J AU Rao, HW Lu, GW Kajiya, H Garcia-Palacios, V Kurihara, N Anderson, J Patrene, K Sheppard, D Blair, HC Windle, JJ Choi, SJ Roodman, GD AF Rao, Honowei Lu, Ganwei Kajiya, Hiroshi Garcia-Palacios, Veronica Kurihara, Noriyoshi Anderson, Judy Patrene, Ken Sheppard, Dean Blair, Harry C. Windle, Jolene J. Choi, Sun Jin Roodman, G. David TI alpha(9)beta(1): A novel osteoclast integrin that regulates osteoclast formation and function SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE alpha(9)beta(1) integrin; osteoclast; ADAM8; alpha(9) knockout mice ID STIMULATING FACTOR; MICE LACKING; CELL; BONE; EXPRESSION; IDENTIFICATION; OSTEOPONTIN; MIGRATION; ADHESION; FAMILY AB We identified a previously unknown integrin, alpha(9)beta(1), on OCLs and their precursors. Antibody to alpha(9) inhibited OCL formation in human marrow cultures, and OCLs from alpha(9) knockout mice had a defect in actin ring reorganization and an impaired bone resorption capacity. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA USA. Fukuoka Dent Coll, Sawara Ku, Fukuoka, Japan. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, R&D 151C-U,Room 2E-113,Univ Dr, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu OI Windle, Jolene/0000-0001-6690-385X FU NIA NIH HHS [R01 AG012951-07, AG12951, R01 AG012951]; NIAMS NIH HHS [AR47700, R01 AR041336, R01 AR041336-15, R01 AR047700, R01 AR047700-05, R01-AR41336] NR 28 TC 49 Z9 53 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2006 VL 21 IS 10 BP 1657 EP 1665 DI 10.1359/JBMR.060718 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088KG UT WOS:000240810000018 PM 16995821 ER PT J AU Henderson, BA Ali, R Kim, JY Ament, CS AF Henderson, Bonnie An Ali, Rasha Kim, Jae Yong Ament, Christine Shortsleeve TI Using endoscopy to teach cataract surgery SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID MICROENDOSCOPIC OCULAR SURGERY; INTRAOCULAR-LENS IMPLANTATION; TRANSSCLERAL SUTURE FIXATION; THERAPEUTIC STRATEGY; GLAUCOMA MANAGEMENT; RESIDENT EDUCATION; SYSTEM; PHACOEMULSIFICATION; OPHTHALMOLOGY; COMPETENCES AB Current methods of teaching cataract surgery include lectures, wet-lab sessions, and participation in real surgery. We describe a new method using a microendoscopic cyclophotocoagulation device during phacoemulsification cataract extraction and posterior chamber intraocular lens (IOL) implantation in 4 eyes of 4 patients. Endoscopic visualization during surgery aided in construction of the corneal incision, location of the capsulorhexis edge, and estimation of the lens groove depth. It also demonstrated clinical findings not observable with the surgical microscope such as misplaced IOL haptics and residual lens cortex. Use of the endoscope enhanced the educational value of the surgery and the final surgical outcome. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Univ Illinois, Coll Med, Chicago, IL USA. RP Henderson, BA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM bhenderson@meei.harvard.edu NR 33 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD OCT PY 2006 VL 32 IS 10 BP 1606 EP 1610 DI 10.1016/j.jcrs.2006.04.034 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 091PY UT WOS:000241042000012 PM 17010854 ER PT J AU Wu, JD Haugk, K Woodke, L Nelson, P Coleman, I Plymate, SR AF Wu, Jennifer D. Haugk, Kathy Woodke, Libby Nelson, Peter Coleman, Ilsa Plymate, Stephen R. TI Interaction of IGF signaling and the androgen receptor in prostate cancer progression SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE insulin-like growth factor type I receptor (IGF-IR); androgen receptor (AR); androgen-independent (AI); prostate cancer; AR co-regulators ID GROWTH-FACTOR-I; INSULIN-DEGRADING ENZYME; MALIGNANT PHENOTYPE; EPITHELIAL-CELLS; TUMOR-CELLS; EXPRESSION; APOPTOSIS; PROTEIN; INDEPENDENCE; ACTIVATION AB The insulin-like growth factor type I receptor (IGF-IR) has been suggested to play an important role in prostate cancer progression and possibly in the progression to androgen-independent (AI) disease. The term AI may not be entirely correct, in that recent data suggest that expression of androgen receptor (AR) and androgen-regulated genes is the primary association with prostate cancer progression after hormone ablation. Therefore, signaling through other growth factors has been thought to play a role in AR-mediated prostate cancer progression to AI disease in the absence of androgen ligand. However, existing data on how IGF-IR signaling interacts with AR activation in prostate cancer are conflicting. In this Prospect article, we review some of the published data on the mechanisms of IGF-IR/AR interaction and present new evidence that IGF-IR signaling may modulate AR compartmentation and thus alter AR activity in prostate cancer cells. Inhibition of IGF-IR signaling can result in cytoplasmic AR retention and a significant change in androgen-regulated gene expression. Translocation of AR from the cytoplasm to the nucleus may be associated with IGF-induced dephosphorylation. Since fully humanized antibodies targeting the IGF-IR are now in clinical trials, the current review is intended to reveal the mechanisms of potential therapeutic effects of these antibodies on AI prostate cancers. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Plymate, SR (reprint author), 325 9th Ave,Box 359625, Seattle, WA 98104 USA. EM splymate@u.washington.edu FU NCI NIH HHS [P01-CA85859, 1K01CA116002-01] NR 45 TC 100 Z9 105 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT 1 PY 2006 VL 99 IS 2 BP 392 EP 401 DI 10.1002/jcb.20929 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087RA UT WOS:000240758600007 PM 16639715 ER PT J AU Wierman, ME Basson, R Davis, SR Khosla, S Miller, KK Rosner, W Santoro, N AF Wierman, Margaret E. Basson, Rosemary Davis, Susan R. Khosla, Sundeep Miller, Karen K. Rosner, William Santoro, Nanette TI Androgen therapy in women: An endocrine society clinical practice guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID HORMONE-BINDING GLOBULIN; SURGICALLY MENOPAUSAL WOMEN; HYPOACTIVE SEXUAL DESIRE; HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MINERAL DENSITY; PLACEBO-CONTROLLED TRIAL; CHROMATOGRAPHY-MASS SPECTROMETRY; POSTMENOPAUSAL WOMEN; TESTOSTERONE THERAPY; BODY-COMPOSITION AB Objective: The objective was to provide guidelines for the therapeutic use of androgens in women. Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Evidence: The Task Force used systematic reviews of available evidence to inform its key recommendations. The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation ( GRADE) group. The strength of a recommendation is indicated by the number 1 ( strong recommendation, associated with the phrase "we recommend") or 2 ( weak recommendation, associated with the phrase "we suggest"). The quality of the evidence is indicated by cross-filled circles, such that +OOO denotes very-low-quality evidence, ++OO low quality, +++O moderate quality, and ++++-high quality. Each recommendation is followed by a description of the evidence. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and e-mail communications. The drafts prepared by the task force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Committee (CAC), and Executive Committee. The version approved by the CGS and CAC was placed on The Endocrine Society's web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. Conclusions: We recommend against making a diagnosis of androgen deficiency in women at present because of the lack of a well-defined clinical syndrome and normative data on total or free testosterone levels across the lifespan that can be used to define the disorder. Although there is evidence for short-term efficacy of testosterone in selected populations, such as surgically menopausal women, we recommend against the generalized use of testosterone by women because the indications are inadequate and evidence of safety in long-term studies is lacking. A review of the data currently available is presented, and areas of future research are outlined. To formulate clinical guidelines for use of testosterone in women, additional information will be necessary. This includes defining conditions that, when not treated with androgens, have adverse health consequences to women; defining clinical and laboratory parameters that distinguish those with these conditions; and assessing the efficacy and long-term safety of androgen administration on outcomes that are important to women diagnosed with these conditions. This necessary clinical research cannot occur until the biological, physiological, and psychological underpinnings of the role of androgens in women and candidate disorders are further elucidated. C1 Univ Colorado Denver & Hlth Sci Ctr, Aurora, CO 80010 USA. Univ British Columbia, Vancouver, BC V6T 1Z4, Canada. Monash Univ, Alfred Hosp, Melbourne, Vic 3181, Australia. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Lukes Roosevelt Hosp, New York, NY 10019 USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. RP Wierman, ME (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. RI Davis, Susan/A-3111-2009 NR 149 TC 157 Z9 163 U1 3 U2 14 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2006 VL 91 IS 10 BP 3697 EP 3710 DI 10.1210/jc.2006-1121 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092ML UT WOS:000241100900001 PM 17018650 ER PT J AU Page, ST Lin, DW Mostaghel, EA Hess, DL True, LD Amory, JK Nelson, PS Matsumoto, AM Bremner, WJ AF Page, Stephanie T. Lin, Daniel W. Mostaghel, Elahe A. Hess, David L. True, Lawrence D. Amory, John K. Nelson, Peter S. Matsumoto, Alvin M. Bremner, William J. TI Persistent intraprostatic androgen concentrations after medical castration in healthy men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; DUAL 5-ALPHA-REDUCTASE INHIBITOR; DEPRIVATION THERAPY; HORMONE ANTAGONIST; 3-MONTH TREATMENT; TISSUE; CANCER; DIHYDROTESTOSTERONE; TESTOSTERONE; EXPRESSION AB Context: The impact of serum androgen manipulation on prostate tissue hormone levels in normal men is unknown. Studies of men with prostate cancer have suggested that prostatic androgens are preserved in the setting of castration. Tissue androgens might stimulate prostate growth, producing adverse clinical consequences. Objective: The objective of the study was to determine the effect of serum androgen manipulation on intraprostatic androgens in normal men. Design: Thirteen male volunteers ages 35-55 yr (prostate-specific antigen < 2.0 ng/ml; normal transrectal ultrasound) were randomly assigned to: 1) a long-acting GnRH-antagonist, acyline, every 2 wk; 2) acyline plus testosterone ( T) gel ( 10 mg/d); or 3) placebo for 28 d. Serum hormones were assessed weekly. Prostate biopsies were obtained on d 28. Extracted androgens were measured by RIA, and immunohistochemistry for androgen-regulated proteins was performed. Results: The mean decrease in serum T was 94%, whereas prostatic T and dihydrotestosterone levels were 70 and 80% lower, respectively, in subjects receiving acyline alone compared with controls ( P < 0.05). Despite this decrease in prostate androgens, there were no detectable differences in prostate epithelial proliferation, apoptosis, prostate-specific antigen, and androgen receptor expression. Conclusion: In this small study of healthy subjects, despite a 94% decrease in serum T with medical castration, intraprostatic T and dihydrotestosterone levels remained 20-30% of control values, and prostate cell proliferation, apoptosis, and androgen-regulated protein expression were unaffected. Our data highlight the importance of assessing tissue hormone levels. The source of persistent prostate androgens associated with medical castration and their potential role in supporting prostate metabolism deserves further study. C1 Univ Washington, Sch Med, Med Ctr, Dept Med,Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Oregon Hlth Sci Univ, Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. RP Page, ST (reprint author), Univ Washington, Sch Med, Med Ctr, Dept Med,Div Metab Endocrinol & Nutr, Box 357138,1959 NE Pacific, Seattle, WA 98195 USA. EM page@u.washington.edu FU NCI NIH HHS [CA 97186]; NCRR NIH HHS [RR 00163]; NIA NIH HHS [K23 AG027238, K23 AG027238-03]; NICHD NIH HHS [U54 HD 42454, U54 HD 12629]; NIDDK NIH HHS [DK 65083, DK 65204] NR 41 TC 122 Z9 123 U1 2 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2006 VL 91 IS 10 BP 3850 EP 3856 DI 10.1210/jc.2006-0968 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092ML UT WOS:000241100900024 PM 16882745 ER PT J AU Murphy, MK Hall, JE Adams, JM Lee, H Welt, CK AF Murphy, M. K. Hall, J. E. Adams, J. M. Lee, H. Welt, C. K. TI Polycystic ovarian morphology in normal women does not predict the development of polycystic ovary syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; AGE-RELATED-CHANGES; AGING WOMEN; ROTTERDAM CRITERIA; INSULIN RESISTANCE; ENDOCRINE FEATURES; MENSTRUAL-CYCLE; FOLLICLE COHORT; OVULATORY WOMEN; POPULATION AB Context: Polycystic ovarian morphology (PCOM) is present in 25% of normal women in the absence of polycystic ovary syndrome ( PCOS); however, the natural history of PCOM is unknown. Objective: We hypothesized that the presence of PCOM predisposes the development of PCOS. Design: The study was a longitudinal follow-up study over 8.2 +/- 5.2 yr (mean +/- SD; range 1.7-17.5 yr). Setting: The study took place in an outpatient setting. Subjects: Women who took part in a previous study as a normal control and had an ultrasound examination (n = 40) participated. Intervention: Subjects underwent an interval menstrual history, physical exam, blood sampling, and repeat ultrasound in the follicular phase. Main Outcome Measure: Development of PCOS was diagnosed by irregular menses and hyperandrogenism, in the absence of other disorders. Changes in ovarian morphology over time were evaluated. Results: At the baseline visit, 23 women (57.5%) had PCOM and 17 (42.5%) had normal ovarian morphology. One subject with PCOM developed irregular menses and presumptive PCOS. Eleven subjects with PCOM no longer met the criteria for PCOM at follow-up. There was no factor that predicted the change to normal ovarian morphology at the follow-up visit. Conclusions: These data suggest that PCOM in women with regular ovulatory cycles does not commonly predispose the development of PCOS. Although it is unusual to develop PCOM if the ovaries are normal on first assessment, ovaries in women with PCOM no longer meet the criteria for PCOM in approximately half of cases over time. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01 RR 01066]; NICHD NIH HHS [U01 HD 4417] NR 40 TC 34 Z9 35 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2006 VL 91 IS 10 BP 3878 EP 3884 DI 10.1210/jc.2006-1085 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092ML UT WOS:000241100900028 PM 16882750 ER PT J AU Mitsiades, CS McMillin, D Kotoula, V Poulaki, V McMullan, C Negri, J Fanourakis, G Tseleni-Balafouta, S Ain, KB Mitsiades, N AF Mitsiades, Constantine S. McMillin, Douglas Kotoula, Vassiliki Poulaki, Vassiliki McMullan, Ciaran Negri, Joseph Fanourakis, Galinos Tseleni-Balafouta, Sophia Ain, Kenneth B. Mitsiades, Nicholas TI Antitumor effects of the proteasome inhibitor bortezomib in medullary and anaplastic thyroid carcinoma cells in vitro SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MULTIPLE-MYELOMA CELLS; FACTOR-KAPPA-B; THERAPEUTIC APPLICATIONS; HEMATOLOGIC MALIGNANCIES; MEDIATED APOPTOSIS; SOLID TUMORS; CANCER; TRIAL; ACTIVATION; RESISTANCE AB Context: The ubiquitin-proteasome pathway is a major pathway for degradation of intracellular proteins. Proteasome inhibitors constitute a novel class of antitumor agents with preclinical and clinical evidence of activity against hematological malignancies and solid tumors. The proteasome inhibitor bortezomib (PS-341, Velcade) has been approved by the Food and Drug Administration for the treatment of multiple myeloma and is being studied intensely in several other malignancies. Its mechanism of action is complex but appears to include the inhibition of inhibitory-kappa B degradation, which leads to inactivation of the transcriptional factor nuclear factor-kappa B (NF-kappa B). NF-kappa B has been implicated in the pathophysiology of the most aggressive forms of thyroid carcinoma, i.e. medullary and anaplastic. Objective and Methods: We evaluated the effect of bortezomib on a panel of thyroid carcinoma cell lines, originating from papillary, follicular, anaplastic, and medullary carcinomas. Results: Bortezomib induced apoptosis in medullary and anaplastic cell lines with IC(50) values well within the range of clinically achievable concentrations and much lower than respective IC50 values for other solid malignancies. Bortezomib inhibited NF-kappa B activity; increased p53, p21, and jun expression; and induced caspase-dependent apoptosis. Sensitivity of thyroid carcinoma cells to bortezomib was partially decreased by overexpression of Bcl-2 or treatment with IGF-I, whereas the combination of bortezomib with chemotherapy ( doxorubicin) was synergistic. Conclusions: These data provide both insights into the molecular mechanisms of antitumor activity of proteasome inhibitors and the rationale for future clinical trials of bortezomib, alone or in combination with conventional chemotherapy, to improve patient outcome in medullary and anaplastic thyroid carcinomas. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Aristotle Univ Thessaloniki, Sch Med, Dept Pathol, Thessaloniki 54621, Greece. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Univ Athens, Dept Pathol, Athens 11527, Greece. Vet Affairs Med Ctr, Thyroid Canc Res Lab, Lexington, KY 40511 USA. Univ Kentucky, Dept Internal Med, Div Hematol Oncol, Thyroid Oncol Program, Lexington, KY 40536 USA. RP Mitsiades, CS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer Bldg,Room M555,44 Binney St, Boston, MA 02115 USA. EM constantine_mitsiades@dfci.harvard.edu OI Ain, Kenneth/0000-0002-2668-934X NR 26 TC 80 Z9 85 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2006 VL 91 IS 10 BP 4013 EP 4021 DI 10.1210/jc.2005-2472 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092ML UT WOS:000241100900049 PM 16849420 ER PT J AU Engelman, JA Mukohara, T Zejnullahu, K Lifshits, E Borras, AM Gale, CM Naumov, GN Yeap, BY Jarrell, E Sun, J Tracy, S Zhao, XJ Heymach, JV Johnson, BE Cantley, LC Janne, PA AF Engelman, Jeffrey A. Mukohara, Toru Zejnullahu, Kreshnik Lifshits, Eugene Borras, Ana M. Gale, Christopher-Michael Naumov, George N. Yeap, Beow Y. Jarrell, Emily Sun, Jason Tracy, Sean Zhao, Xiaojun Heymach, John V. Johnson, Bruce E. Cantley, Lewis C. Janne, Pasi A. TI Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR RECEPTOR; GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE; ACQUIRED-RESISTANCE; PHOSPHATIDYLINOSITOL 3-KINASE; GEFITINIB SENSITIVITY; PROLONGED SURVIVAL; IMATINIB MESYLATE; GENE-MUTATIONS; BREAST-CANCER AB EGFR is frequently mutated and amplified in lung adenocarcinomas sensitive to EGFR inhibitors gefitinib and erlotinib. A secondary mutation, T790M, has been associated with acquired resistance but has not been shown to be sufficient to render EGFR mutant/amplified lung cancers resistant to EGFR inhibitors. We created a model for studying acquired resistance to gefitinib by prolonged exposure of a gefitinib-sensitive lung carcinoma cell line (H3255; EGFR mutated and amplified) to gefitinib in vitro. The resulting resistant cell line acquired a T790M mutation in a small fraction of the amplified alleles that was undetected by direct sequencing and identified only by a highly sensitive HPLC-based technique. In gefitinib-sensitive lung cancer cells with EGFR mutations and amplifications, exogenous introduction of EGFR T790M effectively conferred resistance to gefitinib and continued ErbB-3/PI3K/Akt signaling when in cis to an activating mutation. Moreover, continued activation of PI3K signaling by the PIK3CA oncogenic mutant, p 110 alpha E545K, was sufficient to abrogate gefitinib-induced apoptosis. These findings suggest that allelic dilution of biologically significant resistance mutations may go undetected by direct sequencing in cancers with amplified oncogenes and that restoration of PI3K activation via either a T790M mutation or other mechanisms can provide resistance to gefitinib. C1 Harvard Univ, Sch Med, Inst Med, Dept Syst Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Signal Transduct, Boston, MA 02215 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Translat Res Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Oncol, Houston, TX 77030 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Inst Med, Dept Syst Biol, 77 Ave Louis Pasteur,Room 1022, 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 [K08CA120060-01, 1K12CA87723-01, 1R01CA114465-01, K08 CA120060, K12 CA087723, P01 CA089021, P20 CA090578, P20CA90578-02, R01 CA114465]; NIGMS NIH HHS [GM41890, R01 GM041890, R37 GM041890] NR 55 TC 270 Z9 289 U1 1 U2 13 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 OCT PY 2006 VL 116 IS 10 BP 2695 EP 2706 DI 10.1172/JCI28656 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 090QK UT WOS:000240965700019 PM 16906227 ER PT J AU Souayah, N Chong, PST Cros, D AF Souayah, Nizar Chong, Peter Siao Tick Cros, Didier TI Acute sensory neuronopathy as the presenting symptom of Sjogren's syndrome SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE neuronopathy; Sjogren's syndrome; ataxia; sensory neuropathy; acute ganglionitis ID PERIPHERAL NEUROPATHY; ATAXIC NEUROPATHY; NERVOUS-SYSTEM; IMMUNOGLOBULIN; INVOLVEMENT; INFECTION; FEATURES AB Sensory neuronopathy associated with Sjogren's syndrome (SS) usually has a subacute or chronic onset. We report the case of a 37year-old woman who presented with an unusual hyperacute form of SS ganglionopathy. She initially developed paresthesias of her fingertips and rapidly became severely ataxic. Nerve conduction studies revealed abnormal sensory but normal motor functions. Lip biopsy showed findings consistent with SS. Sural nerve biopsy showed severe axonal loss. The patient showed modest improvement with immunosuppressive therapies. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol, Newark, NJ 07101 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neurophysiol Lab, Boston, MA 02115 USA. RP Souayah, N (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol, 90 Bergen St,Suite 8100, Newark, NJ 07101 USA. EM souayani@umdnj.edu NR 29 TC 4 Z9 4 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD OCT PY 2006 VL 13 IS 8 BP 862 EP 865 DI 10.1016/j.jocn.2005.12.029 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 099LR UT WOS:000241596700014 PM 16935510 ER PT J AU Ma, XJ Hilsenbeck, SG Wang, W Ding, L Sgroi, DC Bender, RA Osborne, CK Allred, DC Erlander, MG AF Ma, Xiao-Jun Hilsenbeck, Susan G. Wang, Wilson Ding, Li Sgroi, Dennis C. Bender, Richard A. Osborne, C. Kent Allred, D. Craig Erlander, Mark G. TI The HOXB13 : IL7BR expression index is a prognostic factor in early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 28th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2005 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas, San Antonio, Hlth Sci Ctr ID ADJUVANT ENDOCRINE THERAPY; POLYMERASE CHAIN-REACTION; ESTROGEN-RECEPTOR STATUS; GENE-EXPRESSION; PROGESTERONE-RECEPTOR; HOX GENES; MICROARRAY DATA; TAMOXIFEN; RECURRENCE; SURVIVAL AB Purpose We previously identified three genes, HOXB13, IL17BR and CHDH, and the HOXB13:IL17BR ratio index in particular, that strongly predicted clinical outcome in breast cancer patients receiving tamoxifen monotherapy. Confirmation in larger independent patient cohorts was needed to fully validate their clinical utility. Patients and Methods Expression of HOXB13, IL17BR, CHDH, estrogen receptor (ER) and progesterone receptor (PR) were quantified by real-time polymerase chain reaction in 852 formalin-fixed, paraffin-embedded primary breast cancers from 566 untreated and 286 tamoxifen-treated breast cancer patients. Gene expression and clinical variables were analyzed for association with relapse-free survival (RFS) by Cox proportional hazards regression models. Results ER and PR mRNA measurements were in close agreement with immunohistochemistry. In the entire cohort, expression of HOXB 13 was associated with shorter RFS (P =.008), and expression of IL17BR and CHDH was associated with longer RFS (P <.0001 for IL17BR and P =.0002 for CHDH. In ER+ patients, the HOXB13:1L17BR index predicted clinical outcome independently of treatment, but more strongly in node-negative patients. In multivariate analysis of the ER+ node-negative subgroup including age, PR status, tumor size, S phase fraction, and tamoxifen treatment, the two-gene index remained a significant predictor of RFS (hazard ratio = 3.9; 95% Cl, 1.5 to 10.3; P =.007). Conclusion This tumor bank study demonstrated HOXB13:IL17BR index is a strong independent prognostic factor for ER+ node-negative patients irrespective of tamoxifen therapy. C1 AviaraDx Inc, Carlsbad, CA USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Mol Pathol Res Unit, Boston, MA USA. Nichols Inst, Quest Diagnost, Dept Hematol Oncol, San Juan Capistrano, CA USA. RP Erlander, MG (reprint author), 2715 Loker Ave W, Carlsbad, CA 92008 USA. EM merlander@aviaradx.com FU NCI NIH HHS [5P01CA030195, 5P50CA058183, R01-1CA112021-01] NR 39 TC 167 Z9 171 U1 0 U2 4 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 OCT 1 PY 2006 VL 24 IS 28 BP 4611 EP 4619 DI 10.1200/JCO.2006.06.6944 PG 9 WC Oncology SC Oncology GA 090QG UT WOS:000240965300017 PM 17008703 ER PT J AU Robert, S Hamner, MB Ulmer, HG Lorberbaum, JP Durkalski, VL AF Robert, Sophie Hamner, Mark B. Ulmer, Helen G. Lorberbaum, Jeffrey P. Durkalski, Valerie L. TI Open-label trial of escitalopram in the treatment of posttraumatic stress disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 06-09, 2005 CL Boca Raton, FL SP NIMH, New Clin Drug Evaluat Unit ID SLEEP QUALITY INDEX; RATING SCALE; DOUBLE-BLIND; CITALOPRAM; PLACEBO; MULTICENTER; PAROXETINE; VETERANS; PTSD AB Background: Posttraumatic stress disorder (PTSD) is a highly prevalent, disabling illness. Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication treatment, with sertraline, paroxetine, and fluoxetine being the most studied. More limited but favorable data suggest that citalopram, an SSRI, may also have a role in the treatment of PTSD. Its S-enantiomer escitalopram, which may have faster onset and greater magnitude of effect than citalopram in other conditions, has not yet been investigated in PTSD. Objective: To assess the efficacy, safety, and tolerability of escitalopram in the treatment of PTSD. Method: A 12-week, prospective, open-label trial of escitalopram was conducted from January 2003 through August 2004 in military veterans with PTSD. Escitalopram was initiated at 10 mg daily for 4 weeks, then increased to 20 mg daily for the remainder of the study. Concomitant psychiatric medications were discontinued at least 2 weeks prior to enrollment. The primary outcome variable was the change from baseline to endpoint in global Clinician-Administered PTSD Scale-Symptom version (CAPS-SX) score. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, the Hamilton Rating Scale for Depression (HAM-D), and the Davidson Trauma Scale (DTS). Posttraumatic stress disorder and comorbid diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Results: Twenty-four of 25 patients were evaluated for efficacy. The mean global CAPS-SX score decreased from 79.4 (SD = 15.7) at baseline to 61.2 (SD = 24.7) at the end of the study (p = .0002). The CAPS-C avoidance/numbing and CAPS-D hyper-arousal subscale scores decreased significantly from baseline to endpoint (CAPS-C, p = .0171; CAPS-D, p = .0001), with trend-level reductions observed in CAPS-B reexperiencing subscale scores (p = .0593). Forty-five percent of patients (9/20) were much or very much improved at the end of the study (CGI-I of I or 2). The HAM-D and DTS also significantly improved (p = .0063 and p = .0004, respectively). Mild to moderate gastrointestinal disturbances were the most common side effects. Only 4 patients discontinued early because of adverse effects. Conclusions: This preliminary open-label study suggests that escitalopram is both efficacious and well tolerated in PTSD patients. However, randomized controlled studies are needed to confirm these results and to further define its potential role in the treatment of PTSD. C1 Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Psychiat, Hershey, PA 17033 USA. RP Robert, S (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv, 109 Bee St 116, Charleston, SC 29401 USA. EM robertso@musc.edu NR 29 TC 25 Z9 25 U1 5 U2 5 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 OCT PY 2006 VL 67 IS 10 BP 1522 EP 1526 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 104NE UT WOS:000241964300005 PM 17107242 ER PT J AU Altshuler, LL Post, RM Black, DO Keck, PE Nolen, WA Frye, MA Suppes, T Grunze, H Kupka, RW Leverich, GS McElroy, SL Walden, J Mintz, J AF Altshuler, Lori L. Post, Robert M. Black, David O. Keck, Paul E., Jr. Nolen, Willem A. Frye, Mark A. Suppes, Trisha Grunze, Heinz Kupka, Ralph W. Leverich, Gabriele S. McElroy, Susan L. Walden, Joerg Mintz, Jim TI Subsyndromal depressive symptoms are associated with functional impairment in patients with bipolar disorder: Results of a large, multisite study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID QUALITY-OF-LIFE; PROSPECTIVE FOLLOW-UP; SOCIAL-ADJUSTMENT; MAJOR DEPRESSION; SUBCLINICAL SYMPTOMS; GENERAL-POPULATION; SYMPTOMATOLOGY IDS; MEDICAL OUTCOMES; NATURAL-HISTORY; MOOD DISORDERS AB Objective: Studies of patients with unipolar depression have demonstrated a relationship between subthreshold depressive symptoms and impairment in role functioning. Research examining this relationship in persons with bipolar disorder is rare. This study sought to evaluate the association between subsyndromal depressive symptoms and role functioning in subjects with bipolar disorder. Method: 759 adult outpatients with a DSM-IV diagnosis of bipolar disorder were entered into this study at 7 different sites in the Stanley Foundation Bipolar Network (SFBN) beginning in March 1996 and ending in November 2002 and were followed longitudinally for assessment of their course of illness. Subsyndromal depression was operationalized using cutoff scores on the Inventory for Depressive Symptomatology-Clinician Rated (IDS-C), and patients were divided into 3 groups: not depressed (IDS-C score < 13), subsyndromally depressed (IDS-C score 13 to 27), and syndromally depressed (IDS-C score >= 28). Groups were compared using a series Of chi(2) analyses on degree of role function impairment across 4 role domains (work, home duties, family life, and friendships) from the Life Functioning Questionnaire. Logistic regression was used to estimate the probability of any impairment in life functioning based on severity of depressive symptoms. Results: Subsyndromally depressed patients were significantly more likely than those not depressed to report impairment in their work and home functioning roles, as well as impairment in relations with family and friends (p < .001). Across all domains of role function, the proportion of patients impaired in the subsyndromally depressed group was more similar to the syndromally depressed group than to the not depressed group. Conclusions: These findings clearly demonstrate the public health significance of subsyndromal depression in the bipolar population. The most appropriate interventions for subsyndromal depressive symptoms in patients with bipolar disorder remain to be determined. C1 Univ Calif Los Angeles, Dept Psychiat, VA Greater Los Angeles Heathcare Syst, W Los Angeles Healthcare, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Vet Affairs Med Ctr, Mental Hlth Care Line & Gen Clin Res Ctr, Cincinnati, OH 45267 USA. Univ Groningen, Med Ctr, Dept Psychiat, Groningen, Netherlands. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Ludwig Maximilians Univ Munchen, Dept Psychiat, Munich, Germany. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Freiburg, Dept Psychiat, Freiburg, Germany. Univ Munster, Dept Psychiat, Munster, Germany. RP Altshuler, LL (reprint author), 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Nolen, Willem/E-9006-2014 NR 67 TC 114 Z9 119 U1 2 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2006 VL 67 IS 10 BP 1551 EP 1560 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 104NE UT WOS:000241964300009 PM 17107246 ER PT J AU Monson, CM Schnurr, PP Resick, PA Friedman, MJ Young-Xu, Y Stevens, SP AF Monson, Candice M. Schnurr, Paula P. Resick, Patricia A. Friedman, Matthew J. Young-Xu, Yinong Stevens, Susan P. TI Cognitive processing therapy for veterans with military-related posttraumatic stress disorder SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; treatment; cognitive-behavioral therapy; disability; combat ID ADMINISTERED PTSD SCALE; CONFIRMATORY FACTOR-ANALYSIS; FEMALE RAPE VICTIMS; COMPENSATION-SEEKING; DISABILITY COMPENSATION; PSYCHOMETRIC PROPERTIES; COMPARATIVE EFFICACY; PROLONGED EXPOSURE; ASSAULT VICTIMS; PSYCHOTHERAPY AB Sixty veterans (54 men, 6 women) with chronic military-related posttraumatic stress disorder (PTSD) participated in a wait-list controlled trial of cognitive processing therapy (CPT). The overall dropout rate was 16.6% (20% from CPT, 13% from waiting list). Random regression analyses of the intention-to-treat sample revealed significant improvements in PTSD and comorbid symptoms in the CPT condition compared with the wait-list condition. Forty percent of the intention-to-treat sample receiving CPT did not meet criteria for a PTSD diagnosis, and 50% had a reliable change in their PTSD symptoms at posttreatment assessment. There was no relationship between PTSD disability status and outcomes. This trial provides some of the most encouraging results of PTSD treatment for veterans with chronic PTSD and supports increased use of cognitive-behavioral treatments in this population. C1 Vet Affairs Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA 02130 USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Boston Univ, Boston, MA 02215 USA. RP Monson, CM (reprint author), Vet Affairs Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM Candice.Monson@va.gov NR 54 TC 310 Z9 310 U1 9 U2 56 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2006 VL 74 IS 5 BP 898 EP 907 DI 10.1037/0022-006X.74.5.898 PG 10 WC Psychology, Clinical SC Psychology GA 097GO UT WOS:000241435400011 PM 17032094 ER PT J AU Bartlett, JD Ball, RL Kawai, T Tye, CE Tsuchiya, M Simmer, JP AF Bartlett, J. D. Ball, R. L. Kawai, T. Tye, C. E. Tsuchiya, M. Simmer, J. P. TI Origin, splicing, and expression of rodent amelogenin exon 8 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamelysin; enamel; amelogenin ID DEVELOPING DENTAL ENAMEL; MESSENGER-RNA; RAT INCISOR; IMPERFECTA; GENE; IDENTIFICATION; PROTEIN; CHROMOSOMES; TRANSCRIPT; PHENOTYPE AB Amelogenin RNA transcripts undergo extensive alternative splicing, and MMP-20 processes the isoforms following their secretion. Since amelogenins have been ascribed cell-signaling activities, we asked if a lack of proteolytic processing by MMP-20 affects amelogenin signaling and consequently alters amelogenin splice site selection. RT-PCR analyses of amelogenin mRNA between control and Mmp20(-/)-mice revealed no differences in the splicing pattern. We characterized 3 previously unidentified amelogenin alternatively spliced transcripts and demonstrated that exon-8-encoded amelogenin isoforms are processed by MMP-20. Transcripts with exon 8 were expressed approximately five-fold less than those with exon 7. Analyses of the mouse and rat amelogenin gene structures confirmed that exon 8 arose in a duplication of exons 4 through 5, with translocation of the copy downstream of exon 7. No downstream genomic sequences homologous to exons 4-5 were present in the bovine or human amelogenin genes, suggesting that this translocation occurred only in rodents. C1 Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Immunol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Tohoku Univ, Div Aging & Geriatr Dent, Grad Sch Dent, Sendai, Miyagi 9808578, Japan. Michigan Dent Res Lab, Ann Arbor, MI 48108 USA. RP Bartlett, JD (reprint author), Harvard Univ, Sch Dent Med, Dept Cytokine Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM jbartlett@forsyth.org OI Tsuchiya, Masahiro/0000-0002-7000-4547 FU NIDCR NIH HHS [DE 14084, R01 DE014084, R01 DE014084-01A1, R01 DE016276] NR 30 TC 14 Z9 15 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2006 VL 85 IS 10 BP 894 EP 899 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 086PJ UT WOS:000240685200004 PM 16998127 ER PT J AU Biederman, J Boellner, SW Childress, A Lopez, FA Krishnan, S Mandler, H AF Biederman, Joseph Boellner, Samuel W. Childress, Ann Lopez, Frank A. Krishnan, Suma Mandler, Hilary TI Improvements in symptoms of attention-deficit/hyperactivity disorder in school-aged children with lisdexamfetamine dimesylate [LDX; NRP104] and mixed amphetamine salts extended-release vs. placebo SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program Pediat Psychopharmacol, Boston, MA USA. Clin Study Ctr, Little Rock, AR USA. Ctr Psychiat & Behav Med, Las Vegas, NV USA. Childrens Dev Ctr, Maitland, FL USA. New River Pharmaceut Inc, Blacksburg, VA USA. Shire Dev Inc, Wayne, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2006 VL 27 IS 5 BP 442 EP 442 DI 10.1097/00004703-200610000-00056 PG 1 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 100CK UT WOS:000241644600054 ER PT J AU Biederman, J Mandler, H Krishnan, S Findling, RL AF Biederman, Joseph Mandler, Hilary Krishnan, Suma Findling, Robert L. TI Efficacy and safety of lisdexamfetamine dimesylate [LDX; NRP104] in children aged 6 to 12 years with attention-deficit/hyperactivity disorder SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program Pediat Psychopharmacol, Boston, MA USA. Shire Dev Inc, Wayne, PA USA. New River Pharmaceut Inc, Blacksburg, VA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2006 VL 27 IS 5 BP 443 EP 443 DI 10.1097/00004703-200610000-00057 PG 1 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 100CK UT WOS:000241644600055 ER PT J AU McCann, DJ Nadel, ES Barclay, D Listwa, T Miller, R Peak, D McNamara, M White, B Brown, DFM AF McCann, David J. Nadel, Eric S. Barclay, Derek Listwa, Todd Miller, Robert Peak, David McNamara, Mariah White, Benjamin Brown, David F. M. TI Rash and fever SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID STEVENS-JOHNSON SYNDROME; RECURRENT ERYTHEMA MULTIFORME; TOXIC EPIDERMAL NECROLYSIS; ACYCLOVIR; THERAPY; CHILDREN C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 19 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2006 VL 31 IS 3 BP 293 EP 297 DI 10.1016/j.jemermed.2006.07.001 PG 5 WC Emergency Medicine SC Emergency Medicine GA 090BG UT WOS:000240925000012 PM 16982364 ER PT J AU Soukos, NS Chen, PSY Morris, JT Ruggiero, K Abernethy, AD Som, S Foschi, F Doucette, S Bammann, LL Fontana, CR Doukas, AG Stashenko, PP AF Soukos, Nikolaos S. Chen, Peter Shih-Yao Morris, Jason T. Ruggiero, Karriann Abernethy, Abraham D. Som, Sovanda Foschi, Federico Doucette, Stephanie Bammann, Lili Luschke Fontana, Carla Raquel Doukas, Apostolos G. Stashenko, Philip P. TI Photodynamic therapy for endodontic disinfection SO JOURNAL OF ENDODONTICS LA English DT Article DE biofilms; endodontic bacteria; Enterococcus faecalis; methylene blue; photodynamic therapy; root canals ID ENTEROCOCCUS-FAECALIS; APICAL PERIODONTITIS; LETHAL PHOTOSENSITIZATION; DENTINAL TUBULES; TOLUIDINE BLUE; ROOT CANALS; IN-VITRO; BACTERIA; LIGHT; POPULATION AB The aims of this study were to investigate the effects of photodynamic therapy (PDT) on endodontic pathogens in planktonic phase as well as on Enterococcus faecalis biofilms in experimentally infected root canals of extracted teeth. Strains of microorganisms were sensitized with methylene blue (25 mu g/ml) for 5 minutes followed by exposure to red light of 665 nm with an energy fluence of 30 J/cm(2). Methylene blue fully eliminated all bacterial species with the exception of E. faecalis (53% killing). The same concentration of methylene blue in combination with red light (222 J/cm(2)) was able to eliminate 97% of E. faecalis biofilm bacteria in root canals using an optical fiber with multiple cylindrical diffusers that uniformly distributed light at 360 degrees. We conclude that PDT may be developed as an adjunctive procedure to kill residual bacteria in the root canal system after standard endodontic treatment. C1 Forsyth Inst, Appl Mol Photomed Lab, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Soukos, NS (reprint author), Forsyth Inst, Appl Mol Photomed Lab, 140 Fenway, Boston, MA 02115 USA. EM nsoukos@forsyth.org RI Foschi, Federico /E-7531-2012; Fontana, Carla/C-2033-2012; OI Fontana, Carla/0000-0002-9135-3690; Foschi, Federico/0000-0001-6901-0280 FU NIDCR NIH HHS [R01-DE-14360, R01-DE-16922] NR 39 TC 103 Z9 112 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD OCT PY 2006 VL 32 IS 10 BP 979 EP 984 DI 10.1016/j.joen.2006.04.007 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 090QP UT WOS:000240966200015 PM 16982278 ER PT J AU Macrae, F Jones, IT Pizzey, C Bertagnolli, M Hawk, E Eagle, C AF Macrae, F. Jones, I. T. Pizzey, C. Bertagnolli, M. Hawk, E. Eagle, C. CA A P C Trial Investigators TI Celecoxib reduces formation of sporadic adenomas: results from the adenoma prevention with celecoxib (APC) trial SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Meeting Abstract C1 Royal Melbourne Hosp, Dept Colorectal Med, Melbourne, Vic, Australia. Royal Melbourne Hosp, Dept Genet, Melbourne, Vic, Australia. Royal Melbourne Hosp, Dept Colorectal Surg, Melbourne, Vic, Australia. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2006 VL 21 SU 4 BP A264 EP A264 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 179WI UT WOS:000247320600035 ER PT J AU Gukovskaya, AS Mareninova, OA Odinokova, IV Sung, KF Lugea, A Fischer, L Wang, YL Gukovsky, I Pandol, SJ AF Gukovskaya, Anna S. Mareninova, Olga A. Odinokova, Irina V. Sung, Kai-Feng Lugea, Aurelia Fischer, Lars Wang, Yan-Ling Gukovsky, Ilya Pandol, Stephen J. TI Cell death in pancreatitis: Effects of alcohol SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE alcoholic pancreatitis; caspases; cytochrome c release; RIP; XIAP ID RECEPTOR-INTERACTING PROTEIN; INDUCED LIVER APOPTOSIS; ACINAR-CELLS; INFLAMMATORY MEDIATORS; AKT PHOSPHORYLATION; SIGNALING PATHWAYS; APAF-1 APOPTOSOME; NECROSIS; SEVERITY; XIAP AB Pancreatitis is a severe and frequently lethal disorder, a major cause of which is alcohol abuse. Parenchymal cell death is a major complication of pancreatitis. In experimental models of (non-alcoholic) acute pancreatitis, acinar cells have been shown to die through both necrosis and apoptosis, the two principal pathways of cell death. The severity of experimental acute pancreatitis correlates directly with the extent of necrosis and inversely with apoptosis. Thus, understanding the regulation of apoptosis and necrosis, and whether it is possible to manipulate the pattern of death responses, is becoming exceedingly important in investigations of the pathogenesis and treatment of pancreatitis. The effects of alcohol on cell death responses of pancreatitis, and the mechanisms that may mediate these effects, are just starting to be explored. This paper reviews the signaling pathways mediating the balance between apoptosis and necrosis in acute pancreatitis, and alcohol's effects on cell death responses in pancreatitis. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,VAGLAHS,W Los Angeles VA Healthcare Ctr, USC UCLA Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90073 USA. RP Gukovskaya, AS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,VAGLAHS,W Los Angeles VA Healthcare Ctr, USC UCLA Res Ctr Alcohol Liver & Pancreat Dis, 11301 Wilshire Blvd,Bldg 258,Room 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NIDDK NIH HHS [DK 59936]; PHS HHS [P50-A11999] NR 52 TC 23 Z9 25 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2006 VL 21 SU 3 BP S10 EP S13 DI 10.1111/j.1440-1746.2006.04571.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 075XC UT WOS:000239919600005 PM 16958657 ER PT J AU Pandol, SJ Tsukamoto, H AF Pandol, Steve J. Tsukamoto, Hide TI Action plan for enhancing global collaboration on alcoholic liver and pancreatic diseases: White paper SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article C1 Univ Calif Los Angeles, VA Greater LA Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90073 USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. RP Pandol, SJ (reprint author), Univ Calif Los Angeles, VA Greater LA Healthcare Syst, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM stephen.pandol@med.va.gov 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 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD OCT PY 2006 VL 21 SU 3 BP S109 EP S110 DI 10.1111/j.1440-1746.2006.04598.x PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 075XC UT WOS:000239919600029 PM 16958661 ER PT J AU Rubenstein, LV Meredith, LS Parker, LE Gordon, NP Hickey, SC Oken, C Lee, ML AF Rubenstein, Lisa V. Meredith, Lisa S. Parker, Louise E. Gordon, Nancy P. Hickey, Scot C. Oken, Carole Lee, Martin L. TI Impacts of evidence-based quality improvement on depression in primary care: A randomized experiment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality improvement; depression; continuous quality management; social function ID MANAGED PRIMARY-CARE; CONTROLLED-TRIAL; COLLABORATIVE CARE; COST-EFFECTIVENESS; HEALTH-CARE; CLINICAL-PRACTICE; MAJOR DEPRESSION; GUIDELINES; OUTCOMES; ORGANIZATIONS AB CONTEXT: Previous studies testing continuous quality improvement (CQI) for depression showed no effects. Methods for practices to self-improve depression care performance are needed. We assessed the impacts of evidence-based quality improvement (EBQI), a modification of CQI, as carried out by 2 different health care systems, and collected qualitative data on the design and implementation process. OBJECTIVE: Evaluate impacts of EBQI on practice-wide depression care and outcomes. DESIGN: Practice-level randomized experiment comparing EBQI with usual care. SETTING: Six Kaiser Permanente of Northern California and 3 Veterans Administration primary care practices randomly assigned to EBQI teams (6 practices) or usual care (3 practices). Practices included 245 primary care clinicians and 250,000 patients. INTERVENTION: Researchers assisted system senior leaders to identify priorities for EBQI teams; initiated the manual-based EBQI process; and provided references and tools. EVALUATION PARTICIPANTS: Five hundred and sixty-seven representative patients with major depression. MAIN OUTCOME MEASURES: Appropriate treatment, depression, functional status, and satisfaction. RESULTS: Depressed patients in EBQI practices showed a trend toward more appropriate treatment compared with those in usual care (46.0% vs 39.9% at 6 months, P=.07), but no significant improvement in 12-month depression symptom outcomes (27.0% vs 36.1% poor depression outcome, P=.18). Social functioning improved significantly (mean score 65.0 vs 56.8 at 12 months, P=.02); physical functioning did not. CONCLUSION: Evidence-based quality improvement had perceptible, but modest, effects on practice performance for patients with depression. The modest improvements, along with qualitative data, identify potential future directions for improving CQI research and practice. C1 VA Greater Los Angeles, North Hills, CA 91343 USA. RAND Hlth Program, Santa Monica, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Rubenstein, LV (reprint author), VA Greater Los Angeles, 16111 Plummer 152, North Hills, CA 91343 USA. EM lisa_rubenstein@rand.org NR 66 TC 42 Z9 42 U1 2 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 OCT PY 2006 VL 21 IS 10 BP 1027 EP 1035 DI 10.1111/j.1525-1497.2006.00549.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 081BH UT WOS:000240291700003 PM 16836631 ER PT J AU Kinder, LS Katon, WJ Ludman, E Russo, J Simon, G Lin, EHB Ciechanowski, P Von Korff, M Young, B AF Kinder, Leslie S. Katon, Wayne J. Ludman, Evette Russo, Joan Simon, Greg Lin, Elizabeth H. B. Ciechanowski, Paul Von Korff, Michael Young, Bessie TI Improving depression care in patients with diabetes and multiple complications SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE depression; diabetes mellitus; primary care ID COMORBID MEDICAL ILLNESS; COLLABORATIVE CARE; COMPETING DEMANDS; MAJOR DEPRESSION; CONTROLLED-TRIAL; SELF-CARE; MANAGEMENT; OUTCOMES; METAANALYSIS; MELLITUS AB BACKGROUND: Depression is common in patients with diabetes, but it is often inadequately treated within primary care. Competing clinical demands and treatment resistance may make it especially difficult to improve depressive symptoms in patients with diabetes who have multiple complications. OBJECTIVE: To determine whether a collaborative care intervention for depression would be as effective in patients with diabetes who had 2 or more complications as in patients with diabetes who had fewer complications. DESIGN: The Pathways Study was a randomized control trial comparing collaborative care case management for depression and usual primary care. This secondary analysis compared outcomes in patients with 2 or more complications to patients with fewer complications. PATIENTS: Three hundred and twenty-nine patients with diabetes and comorbid depression were recruited through primary care clinics of a large prepaid health plan. MEASUREMENTS: Depression was assessed at baseline, 3, 6, and 12 months with the 20-item depression scale from the Hopkins Symptom Checklist. Diabetes complications were determined from automated patient records. RESULTS: The Pathways collaborative care intervention was significantly more successful at reducing depressive symptoms than usual primary care in patients with diabetes who had 2 or more complications. Patients with fewer than 2 complications experienced similar reductions in depressive symptoms in both intervention and usual care. CONCLUSIONS: Patients with depression and diabetes who have multiple complications may benefit most from collaborative care for depression. These findings suggest that with appropriate intervention depression can be successfully treated in patients with diabetes who have the highest severity of medical problems. C1 Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98101 USA. RP Kinder, LS (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lskinder@stanfordalumni.org FU NIMH NIH HHS [R01 MH073686, MH073686, MH01643, MH4-1739] NR 36 TC 36 Z9 37 U1 2 U2 6 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 OCT PY 2006 VL 21 IS 10 BP 1036 EP 1041 DI 10.1111/j.1525-1497.2006.00552.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 081BH UT WOS:000240291700004 PM 16836628 ER PT J AU Bean-Mayberry, B Chang, CC Scholle, SH AF Bean-Mayberry, Bevanne Chang, Chung-Chou Scholle, Sarah Hudson TI Brief report: Lack of a race effect in primary care ratings among women veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient satisfaction; primary care; race; veterans; women ID HEALTH-CARE; PATIENT SATISFACTION; SERVICES; RACE/ETHNICITY; ASSESSMENTS; ATTRIBUTES; QUALITY; SYSTEM AB OBJECTIVE: To explore the effect of race on primary care quality and satisfaction among women in the Department of Veterans Affairs (VA). METHODS: We used a mail survey to measure primary care quality and satisfaction. We focused on 4 primary care domains: patient preference for provider, interpersonal communication, accumulated knowledge, and coordination. We performed univariate analyses to compare variables by race and multiple logistic regression analysis to examine the effect of race on the probability of reporting a perfect score on each domain, while adjusting for patient characteristics and site. RESULTS: Black women were younger, unmarried, educated, of higher income, and reported female providers and gynecological care in VA more often. In regression analysis, race was not significantly associated with any primary care domain or satisfaction. Gynecological care from VA provider was associated with perfect ratings on patient preference for provider (odds ratio [OR] 2.0, 95% confidence intervals [CI] 1.3, 3.1), and satisfaction (OR 1.6, 95% CI 1.2, 2.3), while female provider was associated with interpersonal communication (OR 1.9, 95% CI 1.4, 2.6). CONCLUSIONS: While demographics and health experiences vary by race among veterans, race had no effect on primary care ratings. Future studies need to determine whether this racial equity persists in health outcomes among women veterans. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Natl Comm Qual Assurance, Res & Anal Div, Washington, DC USA. RP Bean-Mayberry, B (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 151C-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM bevanne.bean-mayberry@va.gov NR 18 TC 5 Z9 5 U1 1 U2 2 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 OCT PY 2006 VL 21 IS 10 BP 1105 EP 1108 DI 10.1111/j.1525-1497.2006.00517.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 081BH UT WOS:000240291700016 PM 16970560 ER PT J AU He, QH Alexeev, D Estevez, ME McCabe, SL Calvert, PD Ong, DE Cornwall, MC Zimmerman, AL Makino, CL AF He, Quanhua Alexeev, Dmitriy Estevez, Maureen E. McCabe, Sarah L. Calvert, Peter D. Ong, David E. Cornwall, M. Carter Zimmerman, Anita L. Makino, Clint L. TI Cyclic nucleotide-gated ion channels in rod photoreceptors are protected from retinoid inhibition SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID GMP-SENSITIVE CONDUCTANCE; OUTER SEGMENT; VITAMIN-A; VISUAL PIGMENT; SALAMANDER RODS; DARK-ADAPTATION; SPECTRAL SENSITIVITY; CONE PHOTORECEPTORS; ACTIVATED CHANNEL; TIGER SALAMANDER AB In vertebrate rods, photoisomerization of the 11-cis retinal chromophore of rhodopsin to the all-trans conformation initiates a biochemical cascade that closes cGMP-gated channels and hyperpolarizes the cell. All-trans retinal is reduced to retinol and then removed to the pigment epithelium. The pigment epithelium supplies fresh 11-cis retinal to regenerate rhodopsin. The recent discovery that tens of nanomolar retinal inhibits cloned cGMP-gated channels at low [cGMP] raised the question of whether retinoid traffic across the plasma membrane of the rod might participate in the signaling of light. Native channels in excised patches from rods were very sensitive to retinoid inhibition. Perfusion of intact rods with exogenous 9-or 11-cis retinal closed cGMP-gated channels but required higher than expected concentrations. Channels reopened after perfusing the rod with cellular retinoid binding protein II. PDE activity, flash response kinetics, and relative sensitivity were unchanged, ruling out pharmacological activation of the phototransduction cascade. Bleaching of rhodopsin to create all-trans retinal and retinol inside the rod did not produce any measurable channel inhibition. Exposure of a bleached rod to 9-or 11-cis retinal did not elicit channel inhibition during the period of rhodopsin regeneration. Microspectrophotometric measurements showed that exogenous 9-or 11-cis retinal rapidly cross the plasma membrane of bleached rods and regenerate their rhodopsin. Although dark-adapted rods could also take up large quantities of 9-cis retinal, which they converted to retinol, the time course was slow. Apparently cGMP-gated channels in intact rods are protected from the inhibitory effects of retinoids that cross the plasma membrane by a large-capacity buffer. Opsin, with its chromophore binding pocket occupied ( rhodopsin) or vacant, may be an important component. Exceptionally high retinoid levels, e. g., associated with some retinal degenerations, could overcome the buffer, however, and impair sensitivity or delay the recovery after exposure to bright light. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. RP Makino, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM cmakino@meei.harvard.edu OI Cornwall, M./0000-0002-0847-939X; Makino, Clint/0000-0002-6005-9069 FU NEI NIH HHS [R01 EY012944, EY014104, EY012944, R01 EY007774, EY01157, EY07774, P30 EY014104, R01 EY001157]; NIDDK NIH HHS [R01 DK032642, DK32642] NR 73 TC 6 Z9 6 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD OCT PY 2006 VL 128 IS 4 BP 473 EP 485 DI 10.1085/jgp.200609619 PG 13 WC Physiology SC Physiology GA 093HT UT WOS:000241159800008 PM 17001087 ER PT J AU Hauser, MA Sena, DF Flor, J Walter, J Auguste, J LaRocque-Abramson, K Graham, F DelBono, E Haines, JL Pericak-Vance, MA Allingham, RR Wiggs, JL AF Hauser, Michael A. Sena, Dayse Figueiredo Flor, Jason Walter, Jeff Auguste, Josette LaRocque-Abramson, Karen Graham, Felicia DelBono, Elizabeth Haines, Jonathan L. Pericak-Vance, Margaret A. Allingham, R. Rand Wiggs, Janey L. TI Distribution of Optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United States SO JOURNAL OF GLAUCOMA LA English DT Article DE low-tension glaucoma; genetic study; optineurin; genotype-phenotype correlation ID OPEN-ANGLE GLAUCOMA; CLINICAL-FEATURES; JAPANESE PATIENTS; GENE; ADULT; MUTATIONS; LOCUS; ASSOCIATION; REGION; LOCALIZATION AB Purpose: Previous studies have suggested that Optineurin (OPTN) sequence variants contribute to low-tension glaucoma (LTG) in ethnically homogeneous populations. The purpose of this study is to evaluate the prevalence of OPTN sequence variants in an ethnically diverse population of LTG patients from the United States, and to describe the phenotype of patients with OPTN sequence variants preferentially found in LTG patients. Methods: Genomic DNA purified from 67 LTG patients was screened for DNA sequence variants located in the exons and flanking introns of the OPTN gene using high-performance liquid chromatography analysis and direct genomic DNA sequencing. Eighty-six primary open-angle glaucoma probands and 100 control patients were also analyzed. Results: Nine OPTN DNA sequence variants were identified in this patient population including the 2 previously identified heterozygous nonsynonymous single-nucleotide polymorphisms in exons 4 and 5. Four LTG patients with severe disease and positive family history of glaucoma, were found to have DNA sequence changes not found in primary open-angle glaucoma probands or control individuals including the previously reported E50K variation. Conclusions: The results of this study support the rare association of OPTN sequence variants with familial forms of LTG. The E50K mutation seems to be associated with a severe form of LTG, and although rare, the identification of this sequence variant in patients at risk may help direct appropriate therapy. C1 Harvard Univ, Dept Ophthalmol, Sch Med, Cambridge, MA 02138 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [P30EY14104, R01EY10886] NR 27 TC 44 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD OCT PY 2006 VL 15 IS 5 BP 358 EP 363 DI 10.1097/01.ijg.0000212255.17950.42 PG 6 WC Ophthalmology SC Ophthalmology GA 094VG UT WOS:000241266600003 PM 16988596 ER PT J AU Etter, JR Affel, EL Rhee, DJ AF Etter, Jonathan R. Affel, Elizabeth L. Rhee, Douglas J. TI High prevalence of plateau iris configuration in family members of patients with plateau iris syndrome SO JOURNAL OF GLAUCOMA LA English DT Article DE plateau iris syndrome; angle-closure glaucoma; narrow angles; family history ID ULTRASOUND BIOMICROSCOPY AB Purpose: The purpose of the study was to ascertain the prevalence of plateau iris syndrome in the first-degree relatives of those patients affected with plateau iris syndrome. Methods: All patients seen with plateau iris syndrome over a 5-year period were identified. These patients were approached for participation and first-degree family members above 18 years of age were screened. All people identified with plateau iris configuration underwent ultrasound biomicroscopy to document and confirm the angle configuration and subsequent gonioscopy after laser iridotomies. Results: Sixteen patients were identified; 3 refused to participate, 2 were unable to be contacted, and I withdrew after initially consenting to participate. In this case, the patient agreed to participate, but all her living first-degree family members refused to be screened. Among the 10 patients whose living first-degree relatives were screened, we found 5 families with at least I additional first-degree family member having plateau iris syndrome. Conclusions: Some families have more than I member with plateau iris syndrome. The pattern of inheritance resembles an autosomal dominant pattern with incomplete penetrance. C1 Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. Thomas Jefferson Univ, Wills Eye Hosp, William & Anna Goldberg Glaucoma Serv, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Wills Eye Hosp, Visual Physiol Dept, Philadelphia, PA 19107 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM DougRhee@aol.com FU NEI NIH HHS [EY 13997] NR 10 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD OCT PY 2006 VL 15 IS 5 BP 394 EP 398 DI 10.1097/01.ijg.0000212253.79831.7a PG 5 WC Ophthalmology SC Ophthalmology GA 094VG UT WOS:000241266600008 PM 16988601 ER PT J AU Gieser, DK Williams, RT O'Connell, W Pasquale, LR Rosenthal, BP Walt, JG Katz, LM Siegartel, LR Wang, LJ Rosenblatt, LC Stern, LS Doyle, JJ AF Gieser, David K. Williams, R. Tracy O'Connell, William Pasquale, Louis R. Rosenthal, Bruce P. Walt, John G. Katz, Laura M. Siegartel, Lisa R. Wang, Lujing Rosenblatt, Lisa C. Stern, Lee S. Doyle, John J. TI Costs and utilization of end-stage glaucoma patients receiving visual rehabilitation care: A US multisite retrospective study SO JOURNAL OF GLAUCOMA LA English DT Article DE end-stage primary open-angle glaucoma; visual rehabilitation care; blindness; resource use; direct costs ID OPEN-ANGLE GLAUCOMA; LOW-VISION SERVICES; FIELD LOSS; UNITED-STATES; INTRAOCULAR-PRESSURE; LONG-TERM; PROGRESSION; PREVALENCE; IMPAIRMENT; SEVERITY AB Purpose: Glaucoma is a prevalent ophthalmologic disease and leading cause of blindness. A retrospective analysis was conducted to evaluate resources and costs for end-stage glaucoma patients receiving visual rehabilitation care (VRC). Materials and Methods: A chart review was conducted in 3 United States VRC centers. Charts of patients with primary open-angle glaucoma as the primary cause of vision loss (1998 to 2003) were selected, yielding 81 records. Data were collected from patient-level billing and reimbursement records (ophthalmologist/optometrist visits, glaucoma medications, procedures, and specialized low-vision and glaucoma-related services). Visual rehabilitation services included utilization of low-vision devices, assessment of daily functioning, orientation and mobility training, and patient counseling. Results: Mean age at baseline was 72.7 years [standard deviation (SD) = 17.2, range: 29 to 95]. Of those with known sex (n = 77), 55.8% were women. Medicare was the payer type for most patients (59.3%), whereas 20% had Medicaid. Mean number of visits was 7.1 (SD = 6.1) in year 1 and 3.7 (SD = 4.2) in year 2, for an annual mean of 5.4 (SD = 5.0) visits overall. Total mean cost per patient in year I was greater than year 2 [$2170 (SD = $2252) vs. $1202 (SD = $1080), respectively]; of the total 2-year costs, 15% were VRC, 37% ophthalmology care, and 48% pharmacy. Analysis of nonpharmacy costs revealed that VRC accounted for 28% and ophthalmology for 72%. Conclusions: End-stage glaucoma is associated with appreciable resource utilization and costs, because of both vision rehabilitation and ophthalmology care. Advanced primary open-angle glaucoma has a substantial cost-of-illness, warranting improved management in early stages of disease. C1 Allergan Pharmaceut Inc, Irvine, CA 92715 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Analyt Int, New York, NY USA. Lighthouse Int, New York, NY USA. SUNY Coll Optometry, New York, NY 10010 USA. Wheaton Eye Clin, Wheaton, IL USA. Deicke Ctr Visual Rehabil, Wheaton, IL USA. RP Walt, JG (reprint author), 2525 Dupont Dr,POB 19534, Irvine, CA 92634 USA. EM Walt_John@Allergan.com NR 23 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD OCT PY 2006 VL 15 IS 5 BP 419 EP 425 DI 10.1097/01.ijg.0000212250.95078.6f PG 7 WC Ophthalmology SC Ophthalmology GA 094VG UT WOS:000241266600012 PM 16988605 ER PT J AU Ring, D Adey, L Zurakowski, D Jupiter, JB AF Ring, David Adey, Lauren Zurakowski, David Jupiter, Jesse B. TI Elbow capsulectomy for posttraumatic elbow stiffness SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article ID ANTERIOR CAPSULOTOMY; FLEXION CONTRACTURE; OPERATIVE TREATMENT; LATERAL APPROACH; ARTHROPLASTY; FRACTURE; RELEASE; HEAD AB Purpose: To determine factors associated with diminished elbow function and upper-extremity-specific health status after elbow capsulectomy for posttraumatic stiffness. Methods: Forty-six adult patients with posttraumatic elbow stiffness were evaluated an average of 48 months after open capsular excision. A second capsular excision was performed in 9 patients (29%). Stepwise multiple linear regression analysis was used to identify predictors of the American Shoulder and Elbow Surgeons Elbow Score, the Mayo Elbow Performance Index, and the Disabilities of the Arm, Shoulder, and Hand scores after all procedures. Results: The average improvement in ulnohumeral motion after the index surgery for capsular release was 53 degrees. (The average flexion was 98 degrees.) The 9 patients who had subsequent repeat elbow contracture release gained an additional 24 degrees, leading to a final average flexion arc for the entire cohort of 103 degrees. Multiple linear regression identified the American Shoulder and Elbow Surgeons pain score, persistent ulnar nerve dysfunction, and duration of follow-up evaluation after the initial capsular release as independent predictors of a higher Disabilities of the Arm, Shoulder, and Hand questionnaire score, flexion arc and pain score as independent predictors of the Mayo Elbow Performance Index; and flexion arc, forearm arc, pain score, and persistent ulnar neuropathy as independent predictors of the American Shoulder and Elbow Surgeons score. Conclusions: Open elbow capsulectomy for posttraumatic elbow stiffness restores a near-100 degrees flexion arc on average. Second elbow releases provide limited additional motion in most patients. Final motion influences physician-based rating scales but not patient-specific health status (Disabilities of the. Arm, Shoulder, and Hand questionnaire), which is dominated by pain and persistent ulnar neuropathy. C1 Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 22 TC 27 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2006 VL 31A IS 8 BP 1264 EP 1271 DI 10.1016/j.jhsa.2006.06.009 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 100DO UT WOS:000241647900002 PM 17027785 ER PT J AU Mallette, P Ring, D AF Mallette, Paige Ring, David TI Attitudes of hand surgeons, hand surgery patients, and the general public regarding psychologic influences on illness SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE hand pain; illness behavior; psycholosocial influences ID FUNCTIONAL SOMATIC SYNDROMES; IDIOPATHIC ARM PAIN; HYPOCHONDRIASIS; SYMPTOMS; CARE AB Purpose: Psychologic influences on illness are well recognized but infrequently addressed in the interactions of hand surgeons and patients. This study assessed the attitudes of hand surgery patients and hand surgeons regarding psychologic influences on illness and compared their attitudes with those of the general population. Methods: An 8-question survey regarding participant's attitudes toward psychologic influences on illness was given to the general public (people waiting in an airport), patients presenting to a hand surgery practice, and members of the American Society for Surgery of the Hand. Results: A total of 474 surgeons, 85 patients, and 42 public participants completed the survey. There were no notable differences between patients and the general public, but the surgeons' attitudes were markedly different from both patients and the general public with respect to 4 items: the surgeons underestimated the openness of patients and the general public to discussing psychologic influences and willingness to see a psychologist or psychiatrist; and they were more supportive than the general public or patients regarding the opinion that the placebo effect reflects the strong influence of psychologic factors in healing and that psychologic stress often is expressed as a physical complaint. The distribution of patient responses showed 2 subgroups with respect to the idea that psychologic stress often is expressed as a physical complaint and with regard to willingness to see a mental heath professional, reflecting that a subset of patients with a hand illness may be resistant to these concepts. Conclusions: Hand surgery patients and the general public are not as aware of the psychologic influences on illness as are hand surgeons, but they are more willing to consider and discuss psychologic factors-and even psychologic treatment-than their surgeons realize. Surgeons' views may be colored by a few negative interactions with challenging patients, but a dialogue with our patients regarding the influence of psychologic issues on illness will be well received by most patients and may facilitate recovery. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 16 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2006 VL 31A IS 8 BP 1362 EP 1366 DI 10.1016/j.jhsa.2006.06.002 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 100DO UT WOS:000241647900017 PM 17027800 ER PT J AU Prager, LM Wain, JC Roberts, DH Ginns, LC AF Prager, Laura M. Wain, John C. Roberts, David H. Ginns, Leo C. TI Medical and psychologic outcome of living lobar lung transplant donors SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID QUALITY-OF-LIFE; PRIMARY PULMONARY-HYPERTENSION; CYSTIC-FIBROSIS; KIDNEY DONORS; SHORT-FORM; DEPRESSION INVENTORY; EXPERIENCE; LOBECTOMY; ISSUES AB Background: Living donor lobar lung transplantation is a viable therapy for carefully selected patients with end-stage pulmonary,disease. Its success is largely dependent upon donor outcome, including both physical and emotional factors. To date, there has been little focus on psychosocial outcomes of lobar lung donors. Methods: Retrospective evaluation of 15 of 20 living lobar lung transplant donors was performed. Donors underwent evaluation of pulmonary function after recovery from donor lobectomy. Participants completed two self-report questionnaires, the SF-36 Health Survey (SF-36) and the Beck Depression Inventory (BDI), as well as an open-ended psychiatric interview. Results: After lobar donation, mean forced expiratory volume in 1 second (FEV1) decreased by 21 +/- 2%, forced vital capacity (FVC) decreased by 16 +/- 3%, total lung capacity (TLC) decreased by 15 +/- 3%, and single-breath diffusing capacity (DLCO) decreased by 14 +/- 4%. All subjects scored higher than the national average on both the physical and mental health components of the SF-36. The BDI scores showed no evidence of clinical depression. However, the subjective interviews elicited two common complaints: (1) a decline in exercise performance, not accounted for by resting lung function measurements; and (2) a dissatisfaction with the degree of acknowledgment of their donation. Conclusions: Living lobar lung transplant donors enjoy generally satisfactory physical and emotional health. Donors report positive feelings about donation, but wish to be recognized and valued by the transplant team and by the recipient. Despite preservation of lung function within the normal range, some donors also experience a subjective decline in exercise tolerance. Long-term medical and psychologic follow-up appears warranted to monitor symptoms of exercise impairment and to enhance the donor experience. C1 Massachusetts Gen Hosp, Lung Transplant Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ginns, LC (reprint author), Pulm Associates, 55 Fruit St,White 907, Boston, MA 02114 USA. EM lginns@partners.org NR 28 TC 17 Z9 18 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 OCT PY 2006 VL 25 IS 10 BP 1206 EP 1212 DI 10.1016/j.healun.2006.06.014 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 099DT UT WOS:000241573400005 PM 17045933 ER PT J AU Leslie, A Price, DA Mkhize, P Bishop, K Rathod, A Day, C Crawford, H Honeyborne, I Asher, TE Luzzi, G Edwards, A Rosseau, CM Mullins, JI Tudor-Williams, G Novelli, V Brander, C Douek, DC Kiepiela, P Walker, BD Goulder, PJR AF Leslie, Alasdair Price, David A. Mkhize, Pamela Bishop, Karen Rathod, Almas Day, Cheryl Crawford, Hayley Honeyborne, Isobella Asher, Tedi E. Luzzi, Graz Edwards, Anne Rosseau, Christine M. Mullins, James I. Tudor-Williams, Gareth Novelli, Vas Brander, Christian Douek, Daniel C. Kiepiela, Photini Walker, Bruce D. Goulder, Philip J. R. TI Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; IMMUNODEFICIENCY-VIRUS TYPE-1; CELL RESPONSES; TRANSGENIC MICE; ESCAPE; RECOGNITION; IMMUNODOMINANCE; INFECTION; POLYMORPHISM; SPECIFICITY AB HLA diversity is seen as a major challenge to CTL vaccines against HIV. One current approach focuses on "promiscuous" epitopes, presented by multiple HLA alleles from within the same HLA supertype. However, the effectiveness of such supertype vaccines depends upon the functional equivalence of CTL targeting a particular epitope, irrespective of the restricting HLA. In this study, we describe the promiscuous HIV-specific CTL epitopes presented by alleles within the B7 supertype. Substantial differences were observed in the ability of CTL to select for escape mutation when targeting the same epitope but restricted by different HLA. This observation was common to all six promiscuous B7 epitopes identified. Moreover, with one exception, there were no significant differences in the frequency, magnitude, or immunodominance of the CTL responses restricted by different HLA alleles to explain these discrepancies. This suggests that the unique peptide/MHC complexes generated by even closely related HLA induce CTL responses that are qualitatively different. This hypothesis is supported by additional differences observed between CTL targeting identical epitopes but restricted by different HLA: first, the occurrence of distinct, HLA-specific escape mutation; second, the recruitment of distinct TCR repertoires by particular peptide/MHC complexes; and, third, significant differences in the functional avidity of CTL. Taken together, these data indicate that significant functional differences exist between CTL targeting identical epitopes but restricted by different, albeit closely related HLA. These findings are of relevance to vaccine approaches that seek to exploit HLA supertypes to overcome the problem of HLA diversity. C1 Nuffield Dept Med, Dept Paediat, Oxford, England. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, ZA-4001 Durban, South Africa. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. High Wycombe Gen Hosp, Dept Genitourinary Med, High Wycombe, Bucks, England. Radcliffe Infirm Hosp, Harrison Clin, Oxford, England. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. St Marys Hosp, Imperial Coll Sch Med, London, England. Great Ormond St Hosp Children, London WC1N 3JH, England. RP Leslie, A (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg,S Parks Rd, Oxford OX1 3SY, England. EM alleslie8@yahoo.co.uk RI Price, David/C-7876-2013; Day, Cheryl/J-9844-2012; OI Price, David/0000-0001-9416-2737; Bishop, Karen/0000-0003-4935-7708 FU Medical Research Council [G108/441]; NIAID NIH HHS [2R01 AI 46995-06, N01 AI 15422]; Wellcome Trust NR 49 TC 60 Z9 61 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 OCT 1 PY 2006 VL 177 IS 7 BP 4699 EP 4708 PG 10 WC Immunology SC Immunology GA 088BV UT WOS:000240787400058 PM 16982909 ER PT J AU Zhang, M Takahashi, K Alicot, EM Vorup-Jensen, T Kessler, B Thiel, S Jensenius, JC Ezekowitz, RAB Moore, FD Carroll, MC AF Zhang, Ming Takahashi, Kazue Alicot, Elisabeth M. Vorup-Jensen, Thomas Kessler, Benedikt Thiel, Steffen Jensenius, Jens Christian Ezekowitz, R. Alan B. Moore, Francis D. Carroll, Michael C. TI Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MANNOSE-BINDING LECTIN; ISCHEMIA-REPERFUSION INJURY; RAT SMALL-INTESTINE; SERINE PROTEASES MASPS; REMOTE ORGAN INJURY; LOW-FLOW STATES; COMPLEMENT-PATHWAY; TISSUE-INJURY; MYOCARDIAL-ISCHEMIA; CEREBRAL-ISCHEMIA AB Reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement, which is activated by circulating natural IgM specific to self-Ags exposed by ischemia. Recent reports demonstrating a role for the lectin pathway raise a question regarding the initial events in complement activation. To dissect the individual roles of natural IgM and lectin in activation of complement, mice bearing genetic deficiency in early complement, IgM, or mannan-binding lectin were characterized in a mesenteric model of ischemia reperfusion injury. The results reveal that IgM binds initially to ischemic Ag providing a binding site for mannan-binding lectin which subsequently leads to activation of complement and injury. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. DecImmune Therapeut, Boston, MA 02115 USA. Univ Aarhus, Dept Med Microbiol & Immunol, Aarhus, Denmark. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbrinstitute.org OI Vorup-Jensen, Thomas/0000-0002-4140-6563; Kessler, Benedikt/0000-0002-8160-2446 FU NIGMS NIH HHS [P50 GM 52585] NR 68 TC 86 Z9 86 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 OCT 1 PY 2006 VL 177 IS 7 BP 4727 EP 4734 PG 8 WC Immunology SC Immunology GA 088BV UT WOS:000240787400061 PM 16982912 ER PT J AU Hunt, PW Harrigan, PR Huang, W Bates, M Williamson, DW McCune, JM Price, RW Spudich, SS Lampiris, H Hoh, R Leigler, T Martin, JN Deeks, SG AF Hunt, Peter W. Harrigan, P. Richard Huang, Wei Bates, Michael Williamson, David W. McCune, Joseph M. Price, Richard W. Spudich, Serena S. Lampiris, Harry Hoh, Rebecca Leigler, Teri Martin, Jeffrey N. Deeks, Steven G. TI Prevalence of CXCR4 tropism among antiretroviral-treated HIV-1 - Infected patients with detectable viremia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 13th Conference on Retroviruses and Opportunistic Infections CY FEB 05-09, 2006 CL Denver, CO ID IMMUNODEFICIENCY-VIRUS TYPE-1; BIOLOGICAL PHENOTYPE; INDIVIDUALS; PROGRESSION; CORECEPTOR; THERAPY; DISEASE AB Although CXCR4-tropic viruses are relatively uncommon among untreated human immunodeficiency virus (HIV) infected individuals except during advanced immunodeficiency, the prevalence of CXCR4-tropic viruses among treated patients with detectable viremia is unknown. To address this issue, viral coreceptor usage was measured with a single-cycle recombinant-virus phenotypic entry assay in treatment-naive and treated HIV-infected participants with detectable viremia sampled from 2 clinic-based cohorts. Of 182 treated participants, 75 (41%) harbored dual/ mixed or X4-tropic viruses, compared with 178 (18%) of the 976 treatment-naive participants (P < .001). This difference remained significant after adjustment for CD4(+) T cell count and CCR5 Delta 32 genotype. Enrichment for dual/mixed/X4-tropic viruses among treated participants was largely but incompletely explained by lower pretreatment nadir CD4(+) T cell counts. CCR5 inhibitors may thus be best strategically used before salvage therapy and before significant CD4(+) T cell depletion. C1 Univ San Francisco, Posit Hlth Program, San Francisco Gen Hosp, San Francisco, CA 94110 USA. Univ San Francisco, Dept Neurol, San Francisco Gen Hosp, San Francisco, CA 94110 USA. Univ San Francisco, Grad Program Biol & Med Informat, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94110 USA. Univ San Francisco, Dept Internal Med, San Francisco Vet Affairs Med Ctr, Div Expt Med, San Francisco, CA 94110 USA. Univ San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. Gladstone Inst Virol & Immunol, San Francisco, CA USA. Monogram Biosci Inc, San Francisco, CA USA. Univ British Columbia, Fac Med, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Fac Med, Vancouver, BC V5Z 1M9, Canada. RP Hunt, PW (reprint author), Univ San Francisco, Posit Hlth Program, San Francisco Gen Hosp, Bldg 80,Ward 84,995 Potrero Ave, San Francisco, CA 94110 USA. EM phunt@php.ucsf.edu FU NCRR NIH HHS [5-M01-RR00083-37]; NIAID NIH HHS [K23 AI65244, P30 AI27763, R01 AI52745, R37 AI40312]; NIH HHS [DPI OD00329]; NIMH NIH HHS [P30 MH59037, P30 MH62246]; NINDS NIH HHS [NS 37660] NR 15 TC 109 Z9 110 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2006 VL 194 IS 7 BP 926 EP 930 DI 10.1086/507312 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 081LE UT WOS:000240318300009 PM 16960780 ER PT J AU Heist, EK Chevalier, J Holmvang, G Singh, JP Ellinor, PT Milan, DJ D'Avila, A Mela, T Ruskin, JN Mansour, M AF Heist, E. Kevin Chevalier, Jianping Holmvang, Godtfred Singh, Jagmeet P. Ellinor, Patrick T. Milan, David J. D'Avila, Andre Mela, Theofanie Ruskin, Jeremy N. Mansour, Moussa TI Factors affecting error in integration of electroanatomic mapping with CT and MR imaging during catheter ablation of atrial fibrillation SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; image integration; electroanatomic mapping ID COMPUTED TOMOGRAPHIC-IMAGES; MAGNETIC NAVIGATION; SYSTEM; ANATOMY AB Objective Integration of 3-D electroanatomic mapping with Computed Tomographic (CT) and Magnetic Resonance (MR) imaging is gaining acceptance to facilitate catheter ablation of atrial fibrillation. This is critically dependent on accurate integration of electroanatomic maps with CT or MR images. We sought to examine the effect of patient- and technique-related factors on integration accuracy of electroanatomic mapping with CT and MR imaging of the left atrium. Materials and methods Sixty-one patients undergoing catheter-based atrial fibrillation (AF) ablation procedures were included. All patients underwent cardiac CT (n = 11) or MR (n = 50) imaging, and image integration with real-time electroanatomic mapping of the aorta and left atrium (LA). CARTO-Merge software (Biosense-Webster) was used to calculate the overall average accuracy of integration of electroanatomic points with the CT and MR-derived reconstructions of the LA and aorta. Results There was a significant correlation between LA size assessed by electroanatomic mapping (112 +/- 31 ml) and average integration error (1.9 +/- 0.6 mm) (r = 0.46, p = 0.0003). There was also greater integration error for patients with LA volume >= 110 ml (n = 31) < 10 ml (n = 31) (p = 0.004). In contrast, there was no significant association between average integration error and paroxysmal versus persistent AF, left ventricular ejection fraction, days from imaging to electroanatomic mapping, or images derived from CT versus MR. Conclusions Patients with larger LA volume may be prone to greater error during integration of electroanatomic mapping with CT and MR imaging. Strategies to reduce integration error may therefore be especially useful in patients with large LA volume. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 NR 17 TC 33 Z9 34 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD OCT PY 2006 VL 17 IS 1 BP 21 EP 27 DI 10.1007/s10840-006-9060-2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 136BU UT WOS:000244198400003 PM 17252200 ER PT J AU Singh, JP Heist, EK Ruskin, JN Harthorne, JW AF Singh, Jagmeet P. Heist, E. Kevin Ruskin, Jeremy N. Harthorne, J. Warren TI "Dialing-in" cardiac resynchronization therapy: Overcoming constraints of the coronary venous anatomy SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Review DE cardiac resynchronization therapy; biventricular pacing; left ventricular lead; right ventricular lead; heart failure; electrical activation ID LEFT-VENTRICULAR ACTIVATION; CONGESTIVE-HEART-FAILURE; BUNDLE-BRANCH BLOCK; STIMULATION SITE; LEAD PLACEMENT; QRS DURATION; CONDUCTION; IMPACT AB Several reports have indicated that left ventricular (LV) lead placement at an optimal anatomic pacing site is a critical determinant of outcome of cardiac resynchronization therapy (CRT). Selecting the 'right' patient for CRT but stimulating the 'wrong' site remains an important cause for the high incidence of non-responders to CRT. This technical report (a) recognizes the variance in the coronary venous anatomy and its impact on the final LV lead position, (b) emphasizes the importance of the ventricular electrical activation pattern and its alteration with RV and LV pacing and (c) proposes a novel method to "dial-in" the site for right ventricular (RV) pacing to maximize the electrical separation from the left ventricular lead, rather than taking the first acceptable RV site in the apex or the apico-septal region. This electrical distancing of the leads will potentially improve the mechanics of ventricular contraction and the flexibility of RV-LV optimization. C1 Harvard Univ, Cardiac Resynchronizat Therapy Program, Sch Med, Massachusetts Gen Hosp,Heart Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Cardiac Resynchronizat Therapy Program, Sch Med, Massachusetts Gen Hosp,Heart Ctr, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 23 TC 15 Z9 16 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD OCT PY 2006 VL 17 IS 1 BP 51 EP 58 DI 10.1007/s10840-006-9050-4 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 136BU UT WOS:000244198400008 PM 17252201 ER PT J AU Maguen, S Vogt, DS King, LA King, DW Litz, BT AF Maguen, Shira Vogt, Dawne S. King, Lynda A. King, Daniel W. Litz, Brett T. TI Posttraumatic growth among Gulf War I veterans: The predictive role of deployment-related experiences and background characteristics SO JOURNAL OF LOSS & TRAUMA LA English DT Article ID MALE VIETNAM VETERANS; STRESS-DISORDER; COMBAT EXPOSURE; NATIONAL SAMPLE; SEXUAL ASSAULT; TRAUMA; FEMALE; ZONE; RESILIENCE; ADULTHOOD AB In this study, we identified deployment-related and demographic predictors of several factors of posttraumatic growth in a sample of combat-exposed Gulf War I veterans. Participants were obtained via a Veterans Administration registry of Gulf War I veterans and were mailed a survey containing a number of scales assessing predeployment, deployment, and postdeployment factors from the Deployment Risk and Resilience Inventory and the Posttraumatic Growth Inventory. Military status and perceived threat were significant predictors of appreciation of life. Relating to others, personal strength, and posttraumatic growth as a whole were best predicted by the postdeployment variable of social support. Minority status was the only significant predictor of new possibilities, with ethnic minorities reporting more new possibilities postdeployment. Limitations and suggestions for future research are discussed. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program, 4150 Clement St, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov NR 30 TC 44 Z9 46 U1 0 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1532-5024 J9 J LOSS TRAUMA JI J. Loss Trauma PD OCT-DEC PY 2006 VL 11 IS 5 BP 373 EP 388 DI 10.1080/15325020600672004 PG 16 WC Psychology, Social SC Psychology GA 071AQ UT WOS:000239569500002 ER PT J AU Rumsfeld, JS AF Rumsfeld, John S. TI Introduction: Managing patients with chronic angina: Emerging therapeutic options for improving clinical efficacy and outcomes SO JOURNAL OF MANAGED CARE PHARMACY LA English DT Editorial Material ID QUALITY-OF-LIFE; ACUTE CORONARY SYNDROMES; STABLE ANGINA; MEDICAL-TREATMENT; PECTORIS; DISEASE C1 Denver VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM john.rumsfeld@va.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU ACADEMY MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 1083-4087 J9 J MANAG CARE PHARM JI J. Manag. Care Pharm. PD OCT PY 2006 VL 12 IS 8 SU S BP S2 EP S3 PG 2 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 109ZP UT WOS:000242348400001 PM 23577421 ER PT J AU Balasubramanian, S Mani, S Shiraishi, H Johnston, RK Yamane, K Willey, CD Cooper, G Tuxworth, WJ Kuppuswamy, D AF Balasubramanian, Sundaravadivel Mani, Santhoshkumar Shiraishi, Hirokazu Johnston, Rebecca K. Yamane, Kentaro Willey, Christopher D. Cooper, George Tuxworth, William J. Kuppuswamy, Dhandapani TI Enhanced ubiquitination of cytoskeletal proteins in pressure overloaded myocardium. is accompanied by changes in specific E3 ligases SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE ubiquitination; E3 ligases; Cbl; cardiac hypertrophy ID FOCAL COMPLEX-FORMATION; NF-KAPPA-B; C-CBL; CARDIAC-HYPERTROPHY; PROTEASOME SYSTEM; INSULIN-RECEPTOR; TYROSINE KINASE; GENE-EXPRESSION; MUSCLE-CELLS; DEGRADATION AB Ubiquitin conjugation of proteins is critical for cell homeostasis and contributes to both cell survival and death. Here we studied ubiquitination of proteins in pressure overloaded (PO) myocardium in the context of cardiomyocyte survival. Analysis using a feline right ventricular pressure overload (RVPO) model revealed a robust and transient increase in ubiquitination of proteins present in the Triton X-100-insoluble fraction in 24 to 48 h PO myocardium, and confocal micrographs indicate this increase in ubiquitination occurs subsarcolemmaly near the intercalated disc area of cardiomyocytes. The ubiquitination was accompanied by changes in E3 ligases including Cbl, E6AP, Mdm2 and cIAP in the same period of PO, although atrophy-related E3 ligases, MuRF1 and MuRF3 were unaltered. Furthermore, Cbl displayed a substantial increase in both levels of expression and tyrosine phosphorylation in 48 It PO myocardium. Confocal studies revealed enrichment of Cbl at the intercalated discs of 48 h PO cardiomyocytes, as evidenced by its colocalization with N-cadherin. Although apoptosis was observed in 48 It PO myocardium by TUNEL staining, cardiomyocytes showing ubiquitin staining were not positive for TUNEL staining. Furthennore, 48 It PO resulted in the phosphorylation of inhibitor of nuclear factor kappa B (I kappa B), suggesting its ubiquitin-mediated degradation and the nuclear localization of NF kappa B for the expression of specific cell survival factors such as cIAPs. Together these data indicate that increased levels of E3 ligases that regulate cell homeostasis and promote cell survival could ubiquitinate multiple cytoskeletal protein targets and that these events that occur during the early phase of PO may contribute to both cardiomyocyte survival and hypertrophy. (c) 2006 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, 114 Doughty St, Charleston, SC 29425 USA. EM kuppusd@musc.edu OI Willey, Christopher/0000-0001-9953-0279 FU NHLBI NIH HHS [HL-48788]; NIGMS NIH HHS [GM08716] NR 61 TC 29 Z9 31 U1 0 U2 0 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 OCT PY 2006 VL 41 IS 4 BP 669 EP 679 DI 10.1016/j.yjmcc.2006.04.022 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 096VC UT WOS:000241403900012 PM 16928382 ER PT J AU Fontana, A Rosenheck, R Ruzek, J McFall, M AF Fontana, Alan Rosenheck, Robert Ruzek, Josef McFall, Miles TI Specificity of patients' satisfaction with the delivery and outcome of treatment SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE satisfaction with treatment; delivery of care; clinical outcomes; veterans; posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; CONSUMER SATISFACTION; PSYCHIATRIC-CARE; ISSUES AB This study investigated the hypotheses that the gener disposition to be satisfied is more influential than the nature of service delivery in determining satisfaction with treatment, and that there is a specificity to satisfaction with the delivery of care and with clinical outcome of care that makes their ratings distinct. Data were obtained by questionnaire at intake into treatment and 4 months later from 154 male veterans. There were statistically significant relationships between the general disposition to be satisfied and satisfaction with treatment, but they had only a trivial effect on the relationships between treatment satisfaction and other variables. There was, however, a specificity to satisfaction ratings such that a major feature of the delivery of care, the experience of friendliness and caring from staff, was related more highly to satisfaction with care than to satisfaction with outcome, while measures of clinical outcome were related more highly to satisfaction with outcome than to satisfaction with care. A general disposition to be satisfied, therefore, appears not to have a major biasing effect on satisfaction with treatment. Further, patients appear to make valid differentiations between satisfaction with the delivery of care and the clinical outcome of care when their attention is focused specifically on satisfaction with these features. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. VA Natl Ctr PTSD, Evaluat Div, West Haven, CT USA. VA Natl Ctr PTSD, Educ Div, Menlo Pk, CA USA. VA Puget Sound Healthcare Syst, NW Network Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Fontana, A (reprint author), VA Connecticut Healthcare Syst, W Haven Campus,950 Campbell Ave,NEPEC 182, West Haven, CT 06516 USA. NR 21 TC 4 Z9 5 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 2006 VL 194 IS 10 BP 780 EP 784 DI 10.1097/01.nmd.0000240036.45462.e6 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 096FZ UT WOS:000241364300009 PM 17041291 ER PT J AU Wang, YP Mou, DL Song, JF Rao, ZR Li, D Ju, G AF Wang, Ying-Peng Mou, Dan-Lei Song, Jun-Feng Rao, Zhi-Ren Li, Duan Ju, Gong TI Aberrant activation of CDK5 is involved in the pathogenesis of OPIDN SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cyclin-dependent kinase 5; electron microscopy; horseradish peroxidase-tetramethylbenzidine; organophosphate-induced delayed neuropathy; triorthocresyl phosphate; western blot ID INDUCED DELAYED NEUROTOXICITY; CYCLIN-DEPENDENT KINASE-5; ANTEROGRADE AXONAL-TRANSPORT; NEUROPATHY TARGET ESTERASE; DIISOPROPYL PHOSPHOROFLUORIDATE; SCIATIC-NERVE; NEURODEGENERATION; DEGENERATION; PROTEIN; P35 AB Exposure to triorthocresyl phosphate (TOCP) may result in a late neurological complication, i.e. organophosphate-induced delayed neuropathy (OPIDN). The aim of this study was to examine changes in levels of cyclin-dependent kinase 5 (CDK5) and of its activator, p35/p25, in the spinal cord of hens treated by TOCP. After exposure to a single dose of TOCP, groups of adult hens were examined in 3, 5, 7, 9, 14, and 18 days after exposure. CDK5, p35/p25 expression and distribution in the lumbar spinal cord were evaluated by immunohistochemistry and Western blotting. The hens showed signs of OPIDN around day 9 after exposure. The number of p (phosphorylated) -CDK5 and p35 positive cells increased significantly. Co-localization and mislocalization of p-CDK5 and p35/p25 was identified and became evident in neurons around the 9th day. Meanwhile, CDK5, p-CDK5, p35, p25 protein levels and p25/p35 ratio were increased, and peaked around the 9th day, then decreased. Some hens' unilateral common peroneal was treated by roscovitine 3 days after TOCP exposure. Axonal transport of these nerves was faster than of their opposite side and of those simply treated by TOCP. These findings indicate aberrant activation of CDK5 may be involved in the pathogenesis of OPIDN. C1 Fourth Mil Med Univ, Inst Neurosci, Xian 710032, Peoples R China. Xian Jiaotong Univ, Coll Med, Xian 710049, Peoples R China. Xian Gaoxin Hosp, Dept Neurol, Xian, Peoples R China. Fourth Mil Med Univ, Dept Infect Dis, Tangdu Hosp, Xian, Peoples R China. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Northwestern Polytech Univ, Fac Life Sci, Xian 710072, Peoples R China. RP Wang, YP (reprint author), Fourth Mil Med Univ, Inst Neurosci, 17 Changle Xilu Rd, Xian 710032, Peoples R China. EM yingpwang@163.com NR 35 TC 9 Z9 10 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 OCT PY 2006 VL 99 IS 1 BP 186 EP 197 DI 10.1111/j.1471-4159.2006.04027.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 084IW UT WOS:000240527600017 PM 16987246 ER PT J AU Martuza, RL AF Martuza, Robert L. TI Editorial - Vestibular schwannoma SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Martuza, RL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2006 VL 105 IS 4 BP 526 EP 526 DI 10.3171/jns.2006.105.4.526 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 092AZ UT WOS:000241070700004 PM 17044552 ER PT J AU Wilde, EA Chu, ZL Bigler, ED Hunter, JV Fearing, MA Hanten, G Newsome, MR Scheibel, RSQ Li, X Levin, HS AF Wilde, Elisabeth A. Chu, Zili Bigler, Erin D. Hunter, Jill V. Fearing, Michael A. Hanten, Gerri Newsome, Mary R. Scheibel, Randall S. Li, Xiaoqi Levin, Harvey S. TI Diffusion tensor imaging in the corpus callosum in children after moderate to severe traumatic brain injury SO JOURNAL OF NEUROTRAUMA LA English DT Article; Proceedings Paper CT 14th Annual Conference on Traumatic Brain Injury - From Molecule to Family Systems CY 2004 CL Rotman Res Inst, Toronto, CANADA HO Rotman Res Inst DE child; corpus callosum; diffuse axonal injury; diffusion tensor imaging; fiber tracking; morphometry; traumatic brain injury ID CLOSED-HEAD-INJURY; AXONAL INJURY; MAGNETIC-RESONANCE; WHITE-MATTER; FIBER TRACKING; FRACTIONAL ANISOTROPY; CLINICAL-FEATURES; PRACTICAL SCALE; MRI; LESIONS AB Diffusion tensor imaging (DTI) is a recent imaging technique that assesses the microstructure of the cerebral white matter (WM) based on anisotropic diffusion (i.e., water molecules move faster in parallel to nerve fibers than perpendicular to them). Fractional anisotropy (FA), which ranges from 0 to 1.0, increases with myelination of WM tracts and is sensitive to diffuse axonal injury (DAI) in adults with traumatic brain injury (TBI). However, previous DTI studies of pediatric TBI were case reports without detailed outcome measures. Using mean FA derived from DTI fiber tractography, we compared DTI findings of the corpus callosum for 16 children who were at least 1 year (mean 3.1 years) post-severe TBI and individually matched, uninjured children. Interexaminer and intraexaminer reliability in measuring FA was satisfactory. FA was significantly lower in the patients for the genu, body, and splenium of the corpus callosum. Higher FA was related to increased cognitive processing speed and faster interference resolution on an inhibition task. In the TBI patients, higher FA was related to better functional outcome as measured by the dichotomized Glasgow Outcome Scale (GOS). FA also increased as a function of the area of specific regions of the corpus callosum such as the genu and splenium, and FA in the splenium was reduced with greater volume of lesions in this region. DTI may be useful in identifying biomarkers related to DAI and outcome of TBI in children. C1 Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Texas Childrens Hosp, Dept Diagnost Imaging, Houston, TX 77030 USA. Brigham Young Univ, Dept Psychol, Provo, UT USA. Brigham Young Univ, Dept Neurosci, Provo, UT USA. Univ Utah, Dept Radiol, Salt Lake City, UT USA. Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Levin, HS (reprint author), Cognit Neurosci Lab, 1709 Dryden Rd,Ste 725, Houston, TX 77030 USA. EM hlevin@bcm.tmc.edu FU NICHD NIH HHS [U19 HD035476]; NINDS NIH HHS [NS-21889] NR 73 TC 141 Z9 149 U1 0 U2 13 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 OCT PY 2006 VL 23 IS 10 BP 1412 EP 1426 DI 10.1089/neu.2006.23.1412 PG 15 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 093XL UT WOS:000241203500004 PM 17020479 ER PT J AU Sharp, ND Greiner, GT Li, YF Mitchell, PH Sochalski, JA Cournoyer, PR Sales, AE AF Sharp, Nancy D. Greiner, Gwendolyn T. Li, Yu-Fang Mitchell, Pamela H. Sochalski, Julie A. Cournoyer, Paulette R. Sales, Anne E. TI Nurse executive and staff nurse perceptions of the effects of reorganization in veterans health administration hospitals SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID QUALITY-OF-CARE; PATIENT; IMPACT; LEADERSHIP; MORTALITY; OUTCOMES; SYSTEM; WORK AB Objective: To examine nurse executive perceptions of effects of service line reorganization on nurse executive roles, nursing staff and patient care, and compare nurse executive responses to staff nurse reports of job satisfaction and quality of care in the same types of Veterans Health Administration facilities. Background: Although a growing body of research focuses on the association between nurse staffing structures, nurse satisfaction, and patient outcomes, relatively little attention has been paid to the effects of hospital restructuring on nursing management and nursing staff. Methods: Data on hospital and nursing service organization and nurse executive perceptions were collected through structured interviews with 125 nurse executives conducted from December 2002 through May 2003. Staff nurse data were derived from a survey of Veterans Health Administration nursing staff conducted from February through June 2003 at the same facilities. Results: Nurse executives in Veterans Health Administration described significant changes in the nurse executive role, and new challenges for managing nursing practice and achieving consistent quality of nursing care. Although nursing management perceived differences in the overall effects of restructuring on nursing staff depending on the type of reorganization, staff nurses reported significant differences in perceived quality of patient care across organization types. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, Seattle, WA 98101 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Dept Vet Affairs, Off Nursing Serv, Washington, DC USA. RP Sharp, ND (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM nancy.sharp@med.va.gov RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 26 TC 5 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD OCT PY 2006 VL 36 IS 10 BP 471 EP 478 DI 10.1097/00005110-200610000-00008 PG 8 WC Nursing SC Nursing GA 098UF UT WOS:000241547600008 PM 17035882 ER PT J AU Wang, H Khaoustov, VI Krishnan, B Cai, W Stoll, B Burrin, DG Yoffe, B AF Wang, Hui Khaoustov, Vladimir I. Krishnan, Buvaneswari Cai, Wei Stoll, Barbara Burrin, Douglas G. Yoffe, Boris TI Total parenteral nutrition induces liver steatosis and apoptosis in neonatal piglets SO JOURNAL OF NUTRITION LA English DT Article ID INDUCED HEPATOBILIARY DYSFUNCTION; NF-KAPPA-B; HEPATOCYTE APOPTOSIS; NONALCOHOLIC STEATOHEPATITIS; FATTY LIVER; CELL-DEATH; PATHOGENESIS; ACTIVATION; NECROSIS; INJURY AB Total parenteral nutrition (TPN) induces a high rate of liver disease in infants, yet the pathogenesis remains elusive. We used neonatal piglets as an animal model to assess early events leading to TPN-mediated liver injury. Newborn piglets (n = 7) were nourished for 7 d on TPN or enteral nutrition (EN) and the liver tissue and isolated hepatocytes were subjected to morphologic and molecular analysis. Histological analysis revealed prominent steatosis (grade > 2) in 6 of 7 TPN pigs, whereas minimal steatosis (grade : 1) was observed in only 2 EN pigs. Abundant cytosolic cytochrome C and DNA fragmentation were observed in hepatocytes from TPN compared with EN piglets. Markers of mitochondrial and Fas-mediated apoptosis were altered in TPN liver tissue, as indicated by a lower ATP concentration (P < 0.05), accumulation of ubiquitin, 9.9-fold activation of caspase-3 activity (P < 0.01), and increased cleavage of poly-(ADP-ribose) polymerase, caspase-8, -9, and -7 when compared with EN livers. Bcl-2 and proliferating cell nuclear antigen expression was downregulated, whereas Fas and Bax were upregulated in TPN livers. However, levels of caspase-12 and Bip/GRP78, both markers of endoplasmic reticulum-mediated apoptosis, did not differ between the groups. Short-term TPN induces steatosis and oxidative stress, which results in apoptosis mediated by the mitochondrial and Fas pathways. Thus, TPN-induced steatosis in newborn piglets may serve as a novel animal model to assess the pathogenesis of fatty liver and apoptosis-mediated liver injury in infants. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Univ, USDA ARS, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Yoffe, B (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. EM byoffe@bcm.tmc.edu FU NICHD NIH HHS [HD33920]; NIDDK NIH HHS [P30 DK56338] NR 36 TC 33 Z9 35 U1 1 U2 4 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 2006 VL 136 IS 10 BP 2547 EP 2552 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 089OH UT WOS:000240889600016 PM 16988124 ER PT J AU Gao, X Martin, A Lin, H Bermudez, OI Tucker, KL AF Gao, Xiang Martin, Antonio Lin, Hai Bermudez, Odilia I. Tucker, Katherine L. TI alpha-tocopherol intake and plasma concentration of Hispanic and non-Hispanic white elders is associated with dietary intake pattern SO JOURNAL OF NUTRITION LA English DT Article ID CARDIOVASCULAR-DISEASE RISK; VITAMIN-E STATUS; US ADULTS; DIABETES-MELLITUS; MAXIMAL AMOUNT; BETA-CAROTENE; WOMEN; CANCER; CONSUMPTION; SMOKERS AB alpha-Tocopherol from foods has been associated with protection against several chronic diseases and maintenance of immune function. However, most people do not meet current recommendations for intake. We examined alpha-tocopherol intake and plasma concentration in a representative sample of Puerto Rican and Dominican older adults (n = 447) and in neighborhood-matched non-Hispanic whites (n = 155). A validated food frequency questionnaire was used to assess dietary intake. Mean dietary intakes of alpha-tocopherol were 6 mg in both ethnicities. Only 4.7% of women and 7.9% of men met the estimated average requirement (12 mg/d) for vitamin E from food alone. Top sources of alpha-tocopherol for Hispanics included oils and milk, and for non-Hispanic whites they were ready-to-eat breakfast cereal and sweet baked products. Mean plasma alpha-tocopherol concentrations were 24.5 mu mol/L for Hispanics and 25.8 mu mol/L for non-Hispanic whites (P > 0.05). Plasma alpha-tocopherol was positively associated with alpha-tocopherol intake (P= 0.003), and significance remained after adjusting covariates and after exclusion of supplement users (P for trend = 0.008). We identified the following 5 dietary patterns by cluster analysis: 1) fruit and breakfast cereal, 2) starchy vegetables, 3) rice, 4) milk and milk products, and 5) sweets. Those following the sweets pattern had the lowest plasma alpha-tocopherol relative to those following the fruit and breakfast cereal or milk patterns (P < 0.05 for all), although they had similar intakes. A large proportion of these elders > 90%) have inadequate intake of alpha-tocopherol, and plasma concentrations were associated with intake patterns. C1 Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr, Medford, MA 02155 USA. Boston VA Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. RP Tucker, KL (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr, Medford, MA 02155 USA. EM katherine.tucker@tufts.edu RI Tucker, Katherine/A-4545-2010 FU NIA NIH HHS [AG10425, AG023394] NR 53 TC 24 Z9 24 U1 0 U2 0 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 2006 VL 136 IS 10 BP 2574 EP 2579 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 089OH UT WOS:000240889600021 PM 16988129 ER PT J AU Long, KZ Santos, JI Garcia, TE Haas, M Firestone, M Bhagwat, J DuPont, HL Hertzmark, E Rosado, JL Nanthakumar, NN AF Long, Kurt Z. Ignacio Santos, Jose Estrada Garcia, Teresa Haas, Meredith Firestone, Mathew Bhagwat, Jui DuPont, Herbert L. Hertzmark, Ellen Rosado, Jorge L. Nanthakumar, Nanda N. TI Vitamin A supplementation reduces the monocyte chemoattractant protein-1 intestinal immune response of Mexican children SO JOURNAL OF NUTRITION LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; NF-KAPPA-B; EPITHELIAL-CELLS; LYMPHOCYTE-ACTIVATION; CAMPYLOBACTER-JEJUNI; CC-CHEMOKINE; EXPRESSION; MCP-1; INFECTION; BACTERIAL AB The impact of vitamin A supplementation on childhood diarrhea may be determined by the regulatory effect supplementation has on the mucosal immune response in the gut. Previous studies have not addressed the impact of vitamin A supplementation on the production of monocyte chemoattractant protein 1 (MCP-1), an essential chemokine involved in pathogen-specific mucosal immune response. Fecal MCP-1 concentrations, determined by an enzyme-linked immune absorption assay, were compared among 127 Mexican children 5-15 mo of age randomized to receive a vitamin A supplement (< 12 mo of age, 20,000 IU of retinol; 12 mo, 45,000 (IU)) every 2 mo or a placebo as part of a larger vitamin A supplementation trial. Stools collected during the summer months were screened for MCP-1 and gastrointestinal pathogens. Values of MCP-1 were categorized into 3 levels (nondetectable, < median, >= median). Multinomial logistic regression models were used to determine whether vitamin A-supplemented children had different categorical values of MCP-1 compared with children in the placebo group. Differences in categorical values were also analyzed stratified by gastrointestinal pathogen infections and by diarrheal symptoms. Overall, children who received the vitamin A supplement had reduced fecal concentrations of MCP-1 compared with children in the placebo group (median pg/mg protein +/- interquartile range: 284.88 +/- 885.35 vs. 403.39 +/- 913.16; odds ratio 0.64, 95% Cl 0.42-97, P = 0.03). Vitamin A supplemented children infected with enteropathogenic Escherichia coli (EPEC) had reduced MCP-1 levels (odds ratio = 0.38, 95% Cl 0.18-0.80) compared with children in the placebo group. Among children not infected with Ascaris lumbricoides vitamin A supplemented children had reduced MCP-1 levels (OR = 0.62, 95% Cl 0.41-0.94). These findings suggest that vitamin A has an anti-inflammatory effect in the gastrointestinal tract by reducing MCP-1 concentrations. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. CINVESTAV, Dept Mol Biomed, Mexico City 14000, DF, Mexico. DePauw Univ, Greencastle, IN USA. Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Univ Autonoma Queretaro, Queretaro, Mexico. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Pediat GI & Nutr Unit, Boston, MA 02114 USA. RP Long, KZ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. EM klong@hsph.harvard.edu FU NIDDK NIH HHS [K01 DK06142-02] NR 41 TC 9 Z9 9 U1 0 U2 1 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 2006 VL 136 IS 10 BP 2600 EP 2605 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 089OH UT WOS:000240889600025 PM 16988133 ER PT J AU Reinold, MM AF Reinold, Michael M. TI Articular defects in the knee: Recent advances and future optimism SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Editorial Material ID AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; ARTHROSCOPIC REPAIR; AVASCULAR ZONE; CARTILAGE; REGENERATION; AGE C1 Massachusetts Gen Hosp, Ctr Sports Med, Boston, MA 02114 USA. Boston Red Sox Baseball Club, Boston, MA USA. Northeastern Univ, Boston, MA 02115 USA. RP Reinold, MM (reprint author), Massachusetts Gen Hosp, Ctr Sports Med, Boston, MA 02114 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU J O S P T, PI ALEXANDRIA PA 1111 NORTH FAIRFAX ST, STE 100, ALEXANDRIA, VA 22314-1436 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD OCT PY 2006 VL 36 IS 10 BP 715 EP 716 DI 10.2519/jospt.2006.0111 PG 2 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 091ZC UT WOS:000241065800001 PM 17063833 ER PT J AU Gill, TJ Asnis, PD Berkson, EM AF Gill, Thomas J. Asnis, Peter D. Berkson, Eric M. TI The treatment of articular cartilage defects using the microfracture technique SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Article DE bone; knee; patellofemoral joint; tibiofemoral joint ID CONTINUOUS PASSIVE MOTION; FREE PERIOSTEAL GRAFTS; MEDIAL FEMORAL CONDYLE; SUBCHONDRAL BONE; DEGENERATIVE ARTHRITIS; CHONDRAL DEFECTS; JOINT MOTION; REPAIR; KNEE; RABBIT AB Chondral defects of the articular surface pose a challenging problem to the orthopedic surgeon. The goal of surgery is to alleviate pain, maximize function, and prevent degenerative changes in the future. A number of techniques have been described to treat these lesions. When considering the treatment options for chondral defects, the surgeon must consider the size, depth, location, and chronicity of the lesion. In addition, the overall alignment of the joint must be evaluated. Prior to treating chondral defects, it is important to understand the indications and contraindications for the microfracture technique. When indicated, the microfracture technique has many advantages over other surgical options. This technique is relatively easy to perform, cost effective, and has low patient morbidity. in addition, the microfracture technique does not burn any long-term bridges, enabling the surgeon to choose a different procedure to revise the chondral defect if the microfracture fails. it is important to understand the mechanism of healing by microfracture, including the effects of the local environment. The postoperative protocol used after the procedure may be as important as the surgery itself. Understanding the science behind the microfracture procedure will lead to better surgical technique and improved outcomes. C1 Massachusetts Gen Hosp, Sports Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gill, TJ (reprint author), Massachusetts Gen Hosp, Sports Med Serv, 55 Fruit St,Yaekey 3G, Boston, MA 02114 USA. EM tgill@partners.org NR 53 TC 27 Z9 30 U1 0 U2 6 PU J O S P T, PI ALEXANDRIA PA 1111 NORTH FAIRFAX ST, STE 100, ALEXANDRIA, VA 22314-1436 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD OCT PY 2006 VL 36 IS 10 BP 728 EP 738 DI 10.2519/jospt.2006.2444 PG 11 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 091ZC UT WOS:000241065800003 PM 17063835 ER PT J AU Gillogly, SD Myers, TH Reinold, MM AF Gillogly, Scott D. Myers, Thomas H. Reinold, Michael M. TI Treatment of full-thickness chondral defects in the knee with autologous chondrocyte implantation SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Article DE cartilage; cartilage transplantation; chondrocyte transplantation; tibiofemoral joint ID ARTICULAR-CARTILAGE; TIBIAL OSTEOTOMY; TRANSPLANTATION; REPAIR; ALLOGRAFT; LESIONS; TRIAL AB Autologous chondrocyte implantation (ACI) has now been performed for over a decade in the United States. ACI has been demonstrated as a reproducible treatment option for large, full-thickness, symptomatic chondral injuries of the knee. As clinical experience has expanded and indications broadened to more complex cartilage defects, it has become evident that aggressive treatment of coexisting knee pathology is essential for optimal results. This includes management of malalignment, ligamentous, and/or meniscal deficiency, and subchondral bone loss to make the intra-articular environment as ideal as possible for successful cartilage restoration. Additionally, refinements in the rehabilitation necessary for biologic cartilage repair have been made, based on better understanding of the maturation process of the repair cartilage, allowing for earlier initiation of knee range of motion, strengthening exercises, and weight bearing. These changes have enhanced the recovery for the patient and decreased the risk of motion deficits. This article will discuss patient selection for ACI, review ACI surgical technique, including management of coexisting knee pathology, present postoperative ACI rehabilitation guidelines, and summarize clinical outcomes after ACI. C1 Atlanta Sports Med & Orthoped Ctr, Atlanta, GA USA. Atlanta Thrashers Hockey Club, Atlanta, GA USA. Atlanta Faclons Football Team, Atlanta, GA USA. Massachusetts Gen Hosp, Sports Ctr, Boston, MA 02114 USA. Northeastern Univ, Boston, MA 02115 USA. Boston Red Sox Baseball Club, Boston, MA USA. RP Gillogly, SD (reprint author), 3200 Downwood Circle,Suite 500, Atlanta, GA 30327 USA. EM sdg14@mindspring.com NR 36 TC 29 Z9 30 U1 0 U2 1 PU J O S P T, PI ALEXANDRIA PA 1111 NORTH FAIRFAX ST, STE 100, ALEXANDRIA, VA 22314-1436 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD OCT PY 2006 VL 36 IS 10 BP 751 EP 764 PG 14 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 091ZC UT WOS:000241065800005 PM 17063837 ER PT J AU Reinold, MM Wilk, KE Macrina, LC Dugas, JR Cain, EL AF Reinold, Michael M. Wilk, Kevin E. Macrina, Leonard C. Dugas, Jeffrey R. Cain, E. Lyle TI Current concepts in the rehabilitation following articular cartilage repair procedures in the knee SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Article DE autologous chondrocyte implantation; chondroplasty; microfracture; osteochondral autograft transplantation ID AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; ANTERIOR CRUCIATE LIGAMENT; CONTINUOUS PASSIVE MOTION; ELECTRICAL-STIMULATION; TIBIOFEMORAL MOVEMENT; PATELLOFEMORAL JOINT; SUBCHONDRAL BONE; CHONDRAL DEFECTS; IN-VITRO; RABBIT AB Postoperative rehabilitation programs following articular cartilage repair procedures will vary greatly among patients and need to be individualized based on the nature of the lesion, the unique characteristics of the patient, and the type and detail of each surgical procedure. These programs are based on knowledge of the basic science, anatomy, and biomechanics of articular cartilage as well as the biological course of healing following surgery. The goal is to restore full function in each patient as quickly as possible by facilitating a healing response without overloading the healing articular cartilage. The purpose of this paper is to overview the principles of rehabilitation following articular cartilage repair procedures. Furthermore, specific rehabilitation guidelines for debridement, abrasion chondroplasty, microfracture, osteochondral autograft transplantation, and autologous chondrocyte implantation will be presented based upon our current understanding of the biological healing response postoperatively. C1 Boston Red Sox Baseball Club, Boston, MA 02215 USA. Massachusetts Gen Hosp, Sports Ctr, Boston, MA 02114 USA. Champ Sports Med, Birmingham, AL USA. Alabama Sports Med & Orthoped Ctr, Birmingham, AL USA. RP Reinold, MM (reprint author), Boston Red Sox Baseball Club, Fenway Pk,4 Yawkey Way, Boston, MA 02215 USA. EM mreinold@redsox.com NR 63 TC 48 Z9 49 U1 1 U2 15 PU J O S P T, PI ALEXANDRIA PA 1111 NORTH FAIRFAX ST, STE 100, ALEXANDRIA, VA 22314-1436 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD OCT PY 2006 VL 36 IS 10 BP 774 EP 794 PG 21 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 091ZC UT WOS:000241065800007 PM 17063839 ER PT J AU Wilk, KE Briem, K Reinold, MM Devine, KM Dugas, J Andrews, JR AF Wilk, Kevin E. Briem, Kristin Reinold, Michael M. Devine, Kathleen M. Dugas, Jeffrey Andrews, James R. TI Rehabilitation of articular lesions in the Athlete's knee SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Article DE chondral lesion; exercise; nonoperative treatment; nutrition; tibiofemoral joint ID CRUCIATE LIGAMENT TEARS; STATIC PRESSURE DISTRIBUTION; TIBIAL PLATEAU FRACTURES; BONE-MINERAL DENSITY; TERM FOLLOW-UP; GLUCOSAMINE SULFATE; CHONDROITIN SULFATE; OSTEO-ARTHRITIS; CARTILAGE DEFECTS; DOUBLE-BLIND AB Articular cartilage lesions of the knee joint are common in patients of varying ages. Some articular cartilage lesions are focal lesions located on one aspect of the tibiofemoral or patellofemoral joint. Other lesions can be extremely large or involve multiple compartments of the knee joint and these are often referred to as osteoarthritis. There are numerous potential causes for the development of articular cartilage lesions: joint injury (trauma), biomechanics, genetics, activities, and biochemistry. Numerous factors also contribute to symptomatic episodes resulting from lesions to the articular cartilage: activities (sports and work), joint alignment, joint laxity, muscular weakness, genetics, dietary intake, and body mass index. Athletes appear to be more susceptible to developing articular cartilage lesions than other individuals. This is especially true with specific sports and subsequent to specific types of knee injuries. Injuries to the anterior cruciate ligament and/or menisci may increase the risk of developing an articular cartilage lesion. The treatment for an athletic patient with articular cartilage lesions is often difficult and met with limited success. In this article we will discuss several types of knee articular cartilage injuries such as focal lesions, advanced full-thickness lesions, and bone bruises. We will also discuss the risk factors for developing full-thickness articular cartilage lesions and osteoarthritis, and describe the clinical evaluation and nonoperative treatment strategies for these types of lesions in athletes. C1 Champ Sports Med, Birmingham, AL 35205 USA. Amer Sports Med Inst, Birmingham, AL USA. Univ Delaware, Newark, DE USA. Massachusetts Gen Hosp, Ctr Sports Med, Boston, MA 02114 USA. Boston Red Sox Baseball Club, Boston, MA USA. Northeastern Univ, Boston, MA 02115 USA. Adv Hlth Syst, Sarasota, FL USA. Ablabama Orthopaed & Sports Med, Birmingham, AL USA. Amer Sports Med Inst, Birmingham, AL USA. RP Wilk, KE (reprint author), Champ Sports Med, 806 St Vincents Dr,Suite 620, Birmingham, AL 35205 USA. EM KWilkpt@hotmail.com OI Briem, Kristin/0000-0002-0606-991X NR 99 TC 16 Z9 19 U1 4 U2 16 PU J O S P T, PI ALEXANDRIA PA 1111 NORTH FAIRFAX ST, STE 100, ALEXANDRIA, VA 22314-1436 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD OCT PY 2006 VL 36 IS 10 BP 815 EP 827 DI 10.2519/jospt.2006.2303 PG 13 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 091ZC UT WOS:000241065800009 PM 17063841 ER PT J AU Rutgers, M Ring, D AF Rutgers, Marijn Ring, David TI Treatment of diaphyseal fractures of the humerus using a functional brace SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE diaphyseal humerus fracture; functional brace ID SHAFT FRACTURES; DISTAL 3RD AB Objective: To determine humeral diaphyseal fractures at risk for nonunion with functional brace treatment. Design: Retrospective case series. Setting: A single surgeon's practice. Patients: Forty-nine of 52 consecutive patients treated non-operatively for an isolated diaphyseal fracture of the humerus during a 6-year period were followed until either union and full or near-full restoration of shoulder and elbow motion, or until 6 months had passed, or until a reconstructive surgery was performed (average follow-up 14 months; range 2 to 50 months). Intervention: Functional fracture brace. Main Outcome Measurements: Radiographic and clinical union. Results: Union was achieved in 44 of 49 patients (90%) with no more than 15-degree loss of shoulder or elbow motion in any patient. Four of 14 proximal-third fractures (29%), one of 22 middle-third fractures (4%), and none of the 13 distal-third fractures failed to heal. Conclusions: Proximal-third long oblique fractures may be at greater than average risk for nonunion after functional fracture bracing. Level of evidence: Level IV (case series). C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Unit, Boston, MA 02114 USA. RP Ring, D (reprint author), Yawkey Ctr, Orthopaed Hand & Upper Extrem Unit, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 16 TC 35 Z9 39 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD OCT PY 2006 VL 20 IS 9 BP 597 EP 601 DI 10.1097/01.bot.0000249423.48074.82 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 104NR UT WOS:000241965600002 PM 17088660 ER PT J AU Tripp, DA Nickel, JC Wang, Y Litwin, MS McNaughton-Collins, M Landis, JR Alexander, RB Schaeffer, AJ O'Leary, MP Pontari, MA Fowler, JE Nyberg, LM Kusek, JW AF Tripp, Dean A. Nickel, J. Curtis Wang, Yanlin Litwin, Mark S. McNaughton-Collins, Mary Landis, J. Richard Alexander, Richard B. Schaeffer, Anthony J. O'Leary, Michael P. Pontari, Michel A. Fowler, Jackson E., Jr. Nyberg, Leroy M. Kusek, John W. CA NIH-CPCRN grp TI Catastrophizing and pain-contingent rest predict patient adjustment in men with chronic prostatitis/chronic pelvic pain syndrome SO JOURNAL OF PAIN LA English DT Article DE chronic prostatitis; adjustment; catastrophizing; pain-contingent resting ID QUALITY-OF-LIFE; PHANTOM LIMB PAIN; LOW-BACK-PAIN; COPING STRATEGIES; RHEUMATOID-ARTHRITIS; PSYCHOLOGICAL DISTRESS; DISABILITY INDEX; SOCIAL SUPPORT; SYMPTOM INDEX; PRIMARY-CARE AB Cognitive/behavioral and environmental variables are significant predictors of patient adjustment in chronic pain. Using a biopsychosocial template and selecting several pain-relevant constructs from physical, cognitive/behavioral, and environmental predictors, outcomes of pain and disability in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were explored. Men (n = 253) from a North American multi-institutional NIH-funded Chronic Prostatitis Cohort Study in 6 US and 1 Canadian centers participated in a survey examining pain and disability. Measures included demographics, urinary symptoms, depression, pain, disability, catastrophizing, control over pain, pain-contingent rest, social support, and solicitous responses from a significant other. Regressions showed that urinary symptoms (beta = .20), depression (beta = .24), and helplessness catastrophizing (beta = .29) predicted overall pain. Further, affective pain was predicted by depression (beta = .39) and helplessness catastrophizing (beta = .44), whereas sensory pain was predicted by urinary symptoms (beta = .25) and helplessness catastrophizing (beta = .37). With regard to disability, urinary symptoms (beta = .17), pain (beta = .21), and pain-contingent rest (beta = .33) were the predictors. These results suggest cognitive/behavioral variables (ie, catastrophizing, pain-contingent rest) may have significant impact on patient adjustment in CP/CPPS. Findings support the need for greater research of such pain-related variables in CP/CPPS. Perspective: This article explores predictors of patient adjustment in chronic prostatitislchronk pelvic pain syndrome (CP/CPPS). Cognitive/behavioral variables of catastrophizing and pain-contingent rest respectively predicted greater pain and disability. Catastrophic helplessness was a prominent pain predictor. These findings inform clinicians and researchers on several new variables in CP/CPPS outcomes and suggest future research. (c) 2006 by the American Pain Society C1 Queens Univ, Dept Psychol, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Anesthesiol, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Urol, Kingston, ON K7L 3N6, Canada. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hlth Serv, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Vet Adm Maryland Hlth Care Syst, Baltimore, MD USA. Northwestern Univ, Chicago, IL 60611 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Mississippi, Oxford, MS USA. RP Tripp, DA (reprint author), Queens Univ, Dept Psychol, Humphrey Hall,62 Arch St, Kingston, ON K7L 3N6, Canada. EM dean.tripp@queensu.ca RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK NIH HHS [U01 DK53730, U01 DK53572, U01 DK53732, U01 DK53734, U01 DK53736, U01 DK53738, U01 DK53746] NR 98 TC 61 Z9 65 U1 4 U2 10 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 OCT PY 2006 VL 7 IS 10 BP 697 EP 708 DI 10.1016/j.jpain.2006.03.006 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 097FD UT WOS:000241431500003 PM 17018330 ER PT J AU Wu, SM Compton, P Bolus, R Schieffer, B Pham, Q Baria, A Van Vort, W Davis, F Shekelle, P Naliboff, BD AF Wu, Stephen M. Compton, Peggy Bolus, Roger Schieffer, Beatrix Pham, Quynh Baria, Ariel Van Vort, Walter Davis, Frederick Shekelle, Paul Naliboff, Bruce D. TI The Addiction Behaviors Checklist: Validation of a new clinician-based measure of inappropriate opioid use in chronic pain SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE chronic noncancer pain; opioid medications; substance abuse; addiction; medication misuse ID MEDICATION MISUSE; ASSESSMENT-TOOL; OPIATE ABUSE; PSEUDOADDICTION; THERAPY; ISSUES AB This study introduces the Addiction Behaviors Checklist (ABC), which is a brief (20-item) instrument designed to track behaviors characteristic of addiction related to prescription opioid medications in chronic pain populations. Items are focused on observable behaviors noted both during and between clinic visits. One hundred thirty-six consecutive veterans in a multidisciplinary Veterans Affairs Chronic Pain Clinic who were receiving long-term opioid medication treatment were included in this study. This study represents one of the first to follow a sample of chronic pain patients on opioid therapy over time, using a structured assessment tool to evaluate and track behaviors suggestive of addiction. Interrater reliability and concurrent validity data are presented, as well as a cut-Off scare for use in determining inappropriate medication use. The psychometric findings support the ABC as a viable assessment tool that can increase a provider's confidence in determinations of appropriate vs. inappropriate opioid use. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Acute Care Sect, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Naliboff, BD (reprint author), VAGLAHS, Ctr Neurovisceral Sci & Womens Hlth, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu NR 22 TC 74 Z9 75 U1 0 U2 4 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 OCT PY 2006 VL 32 IS 4 BP 342 EP 351 DI 10.1016/j.jpainsymman.2006.05.010 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 094BZ UT WOS:000241215600007 PM 17000351 ER PT J AU Hebert, RS Prigerson, HG Schulz, R Arnold, RM AF Hebert, Randy S. Prigerson, Holly G. Schulz, Richard Arnold, Robert M. TI Preparing Caregivers for the death of a loved one: A theoretical framework and suggestions for future research SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; PALLIATIVE CARE; PERCEIVED UNCERTAINTY; COMMUNICATION-SKILLS; HOSPICE ENROLLMENT; FAMILY CAREGIVERS; CANCER-PATIENTS; FOLLOW-UP; END; HEALTH AB Caring for a terminally ill loved one and the death of that person are two of the most stressful human experiences. Recent research suggests that a substantial number of caregivers are unprepared for the death and that these caregivers may be at greater risk of psychological distress. The literature on preparedness and mental health, however, is in its infancy. The purpose of this paper, therefore, is to summarize the literature in order to stimulate discussion and research on preparedness. It is our view that preparedness for the death of a loved one is an important contributor to caregiver well-being and bereavement outcomes and that more work in this area is needed in order to improve the care provided to caregivers of seriously or terminally ill patients. We briefly review the literature on preparedness, present a theoretical model delineating the relationships between preparedness, caregiver-health care provider communication, and caregiver well-being, and provide suggestions for future research. C1 Univ Pittsburgh, Sch Med, Div Gen Internal Med, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Sociol, Pittsburgh, PA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. RP Hebert, RS (reprint author), Div Gen Med, Sect Palliat Care & Med Eth, MUH 933W,200 Lothrop St, Pittsburgh, PA 15213 USA. EM hebertrs@upmc.edu FU NIMH NIH HHS [1K23 MH074963-01] NR 64 TC 41 Z9 41 U1 2 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2006 VL 9 IS 5 BP 1164 EP 1171 DI 10.1089/jpm.2006.9.1164 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 101QH UT WOS:000241755000020 PM 17040154 ER PT J AU Zhang, BH El-Jawahri, A Prigerson, HG AF Zhang, Baohui El-Jawahri, Areej Prigerson, Holly G. TI Update on bereavement research: Evidence-based guidelines for the diagnosis and treatment of complicated bereavement SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID TRAUMATIC GRIEF; CONJUGAL BEREAVEMENT; PRELIMINARY EXPLORATIONS; DEPRESSIVE EPISODES; SUICIDAL IDEATION; SOCIAL SUPPORT; HEALTH-CARE; LATER LIFE; RISK; NORTRIPTYLINE AB The past decade has witnessed considerable growth in the evidence-base from which clinical recommendations for bereavement care can be made. Research now provides guidance to assist clinicians in: a) recognizing differences between complicated and uncomplicated bereavement reactions, b) identifying risk factors that may make certain individuals more vulnerable to bereavement-related complications, c) appreciating and monitoring for potential adverse outcomes associated with bereavement and d) taking actions to prevent or minimize maladjustment to the loss. In this article we distinguish between the course of normal grief and abnormally prolonged, or complicated grief; clarify distinctions between Complicated Grief Disorder and other mental disorders secondary to bereavement; review outcomes associated with Complicated Grief Disorder; describe research on resilience in bereavement; present findings on stigmatization and the use of mental health services among recently bereaved persons; and summarize where the field is with respect to establishing the efficacy and effectiveness of bereavement interventions. Promising new psychotherapies for Complicated Grief Disorder have shown clinical efficacy. Nevertheless, further research is needed to enhance the detection of vulnerable bereaved persons, to promote resilience following significant interpersonal loss, and to tailor interventions to address the attachment issues that lie at the heart of this disorder. C1 Harvard Univ, Sch Med, Ctr Palliat Care,Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Psychiat, Boston, MA USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 440 Shields Warren,44 Binney St, Boston, MA 02115 USA. EM Holly_Prigerson@dfci.harvard.edu NR 75 TC 97 Z9 101 U1 10 U2 29 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD OCT PY 2006 VL 9 IS 5 BP 1188 EP 1203 DI 10.1089/jpm.2006.9.1188 PG 16 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 101QH UT WOS:000241755000023 PM 17040157 ER PT J AU Ogino, S Kawasaki, T Kirkner, GJ Ogawa, A Dorfman, I Loda, M Fuchs, CS AF Ogino, S. Kawasaki, T. Kirkner, G. J. Ogawa, A. Dorfman, I. Loda, M. Fuchs, C. S. TI Down-regulation of p21 (CDKNIA/CIP1) is inversely associated with microsatellite instability and CpG island methylator phenotype (CIMP) in colorectal cancer SO JOURNAL OF PATHOLOGY LA English DT Article DE DNA methylation; colon cancer; MethyLight; p21; p53; MSI; CIMP; BRAF; WAF1; KRAS ID ABERRANT CRYPT FOCI; DNA METHYLATION; BRAF MUTATION; COLON-CANCER; GENE; P53; CARCINOMA; TUMORS; CELLS; FIELD AB p2l (CDKN1A/CIP1/WAF1), one of the cyclin-dependent kinase inhibitors, plays a key role in regulating the cell cycle and is transcriptionally regulated by p53. Down-regulation of p21 is caused by TP53 mutations in colorectal cancer. CpG island methylator phenotype (CIMP) appears to be a distinct subtype of colorectal cancer with concordant methylation of multiple gene promoters and is associated with a high degree of microsatellite instability (NISI-H) and BKAF mutations. However, no study to date has evaluated the relationship between p21 expression and CIMP in colorectal cancer. The purpose of this study was to examine the inter-relationships between p21, p53, CIMP, MSI and KRAS/BRAF status in colorectal cancer. We utilized 737 relatively unbiased samples of colorectal cancers from two large prospective cohort studies. Using quantitative real-time PCR (MethyLight), we measured DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16/INK4A), CPABP1, MLH1 and NEUROG1]. CIMP-high (>= 415 methylated promoters) was diagnosed in 118 (16%) of the 737 tumours. We also assessed expression of p21 and p53 by immunohistochemistry. Among the 737 tumours, 371 (50%) showed p21 loss. Both p21 loss and p53 positivity were inversely associated with CIMP-high, MSI-H and BPAF mutations. The associations of p21 with these molecular features were still present after tumours were stratified by p53 status. In contrast, the associations of p53 positivity with the molecular features were no longer present after tumours were stratified by p21 status. When CIMP-high and non-CIMP-high tumours were stratified by MSI or KPAS/BRAF status, CIMP-high and MSI-H (but not BPAF mutations) were still inversely associated with p21 loss. In conclusion, down-regulation of p21 is inversely correlated with CIMP-high and MSI-H in colorectal cancer, independent of TP53 and BRAF status. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. 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. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA87969-03, P01 CA55075-13] NR 48 TC 48 Z9 49 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD OCT PY 2006 VL 210 IS 2 BP 147 EP 154 DI 10.1002/path.2030 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 091FN UT WOS:000241012300003 PM 16850502 ER PT J AU Cooper, NP Guinan, JJ AF Cooper, N. P. Guinan, J. J., Jr. TI Efferent-mediated control of basilar membrane motion SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID OUTER HAIR-CELLS; CROSSED OLIVOCOCHLEAR BUNDLE; AUDITORY-NERVE FIBERS; GUINEA-PIG COCHLEA; ELECTRICAL-STIMULATION; ACETYLCHOLINE; CAT; INHIBITION; RESPONSES; AMPLIFIER AB Medial olivocochlear efferent (MOCE) neurotics innervate the outer hair cells (OHCs) of the mammalian cochlea, and convey signals that are capable of controlling the sensitivity of the peripheral auditory system in a frequency-specific manner. Recent methodological developments have allowed the effects of the MOCE system to be observed in vivo at the level of the basilar membrane (BM). These observations have confirmed earlier theories that at least some of the MOCE's effects are mediated via the cochlea's mechanics,with the OHCs acting as the mechanical effectors. However, the new observations have also provided some unexpected twists: apparently, the MOCEs can enhance the BM's responses to some sounds while inhibiting its responses to others, and they can alter the BM's response to a single sound using at least two separate mechanisms. Such observations put new constraints on the way in which the cochlea's mechanics, and the OHCs in particular, are thought to operate. C1 Univ Keele, Sch Life Sci, Keele ST5 5BG, Staffs, England. Harvard Univ, Sch Med, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Cooper, NP (reprint author), Univ Keele, Sch Life Sci, Keele ST5 5BG, Staffs, England. EM n.p.cooper@keele.ac.uk FU NIDCD NIH HHS [R01 DC000235, R01 DC00235] NR 44 TC 69 Z9 70 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 1 PY 2006 VL 576 IS 1 BP 49 EP 54 DI 10.1113/jphysiol.2006.114991 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 093IU UT WOS:000241162800009 PM 16901947 ER PT J AU Jung, SR Kim, K Hille, B Nguyen, TD Koh, DS AF Jung, Seung-Ryoung Kim, Kyungjin Hille, Bertil Nguyen, Toan D. Koh, Duk-Su TI Pattern of Ca2+ increase determines the type of secretory mechanism activated in dog pancreatic duct epithelial cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID INTERMEDIATE CONDUCTANCE; CALCIUM OSCILLATIONS; CYSTIC-FIBROSIS; MATHEMATICAL-MODEL; POTASSIUM CHANNELS; GANGLION NEURONS; GENE-EXPRESSION; HCO3-TRANSPORT; CL-SECRETION; ATP RELEASE AB Intracellular calcium concentration ([Ca2+](i)) is a key factor controlling secretion from various cell types. We investigated how different patterns of [Ca2+](i) signals evoke salt secretion via ion transport mechanisms and mucin secretion via exocytosis in dog pancreatic duct epithelial cells (PDEC). Activation of epithelial P2Y(2) receptors by UTP generated two patterns of [Ca2+](i) change: 2-10 mu M UTP induced [Ca2+](i) oscillations, whereas 100 mu M UTP induced a sustained [Ca2+](i) increase, both in the micromolar range. As monitored by carbon-fibre amperometry, the sustained [Ca2+](i) increase stimulated a larger increase in exocytosis than [Ca2+](i) oscillations, despite their similar amplitude. In contrast, patch-clamp recordings revealed that [Ca2+](i) oscillations synchronously activated a K+ current as efficiently as the sustained [Ca2+](i) increase. This K+ current was mediated by intermediate-conductance Ca2+-activated K+ channels (32 pS at -100 mV) which were sensitive to charybdotoxin and resistant to TEA. Activation of these Ca2+-dependent K+ channels hyperpolarized the plasma membrane from a resting potential of - 40 mV to - 90 mV, as monitored in perforated whole-cell configuration, in turn enhancing Na+-independent, Cl--dependent and DIDS-sensitive HCO3-secretion, as monitored through changes in intracellular pH. PDEC therefore encode concentrations of purinergic agonists as different patterns of [Ca2+](i) changes, which differentially stimulate K+ channels, the Cl--HCO3- exchanger, and exocytosis. Thus, in addition to amplitude, the temporal pattern of [Ca2+](i) increases is an important mechanism for transducing extracellular stimuli into different physiological effects. C1 Univ Washington, Dept Physiol & Biophys, Sch Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Sch Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Pohang Univ Sci & Technol, Dept Phys, Pohang, South Korea. Seoul Natl Univ, Dept Life Sci, Seoul, South Korea. RP Koh, DS (reprint author), Univ Washington, Dept Physiol & Biophys, Sch Med, Hlth Sci Bldg, Seattle, WA 98195 USA. EM koh@u.washington.edu FU NIAMS NIH HHS [R01 AR017803, AR17803]; NIDDK NIH HHS [R01 DK055885, DK55885] NR 53 TC 17 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 1 PY 2006 VL 576 IS 1 BP 163 EP 178 DI 10.1113/jphysiol.2006.114876 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 093IU UT WOS:000241162800018 PM 16857709 ER PT J AU Roumanas, ED Garrett, N Blackwell, KE Freymiller, E Abemayor, E Wong, WK Reumer, J Fueki, K Fueki, W Kapur, KK AF Roumanas, Eleni D. Garrett, Neal Blackwell, Keith E. Freymiller, Earl Abemayor, Elliot Wong, Weng Kee Reumer, John, III Fueki, Kenji Fueki, Warawan Kapur, Krishan K. TI Masticatory and swallowing threshold performances with conventional and implant-supported prostheses after mandibular fibula free-flap reconstruction SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the Academy-of-Prosthodontics CY MAY, 2005 CL Scottsdale, AZ SP Acad Prosthodont ID MASSETER MUSCLE-ACTIVITY; OSSEOINTEGRATED IMPLANTS; OROMANDIBULAR RECONSTRUCTION; NATURAL DENTITION; DENTURE WEARERS; FUNCTIONAL-EVALUATION; CANCER PATIENT; BONE-GRAFTS; NECK-CANCER; HEAD AB Statement of problem. Significant strides in rnicrovascular surgical techniques allow predictable restoration of bony and soft tissue orofacial defects. In combination with prosthetic rehabilitation, varying degrees of improvement in esthetics, speech intelligibility, and swallowing have been noted; however, the relative impact of conventional and implant-supported prostheses on restoration of masticatory function arc not known. Purpose. The purpose of this study was to determine whether conventional or implant-supported dental prostheses and current surgical reconstructive procedures restore patients' masticatory function to presurgical levels. Material and methods. Of the 46 subjects enrolled in this study, 23 (7 edentulous and 16 partially dentate) completed conventional prosthesis (CP) treatment and masticatory evaluation, and of these, 15 (3 edentulous and 12 partially dentate) completed treatment and evaluation with an implant-supported prosthesis (IP). Standardized masticatory performance tests with peanuts and carrots as the test food were made on the defect and nondefect sides. Tests of swallowing threshold performance were made with carrots as the test food. Statistical analysis included repeated-measures analysis of variance (ANOVA) with post hoc Tukey HSD tests (alpha=.05). Results. Masticatory function at entry was markedly compromised. Further performance declines were noted following surgery (PS) on both the defect and nondefect sides. Restoration with CP and IP produced improvements (significant for defect side only, P<.05) in performance over the PS interval and were not significantly different from performances at entry prior to surgery. In addition, the performance on the defect side with the IP was significantly greater than the performance with the CP (P<.001). Conclusion. impairment in masticatory ability remains following free-flap reconstruction prior to prosthetic rehabilitation. Both CP and IP may provide improved masticatory ability, permitting patients to regain the functional level they possessed prior to surgical intervention. The IP may contribute to greater support and stability of the prosthesis, resulting in increased use for mastication and superior performance on the defect side compared to the CP. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Dent Res Lab, Los Angeles, CA USA. Tokyo Med & Dent Univ, Dept Removeable Prosthodont, Tokyo, Japan. Univ Calif Los Angeles, Sch Dent, Div Diagnost & Surg Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Dent, Sect Oral & Maxillofacial Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Dent, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90095 USA. RP Roumanas, ED (reprint author), Univ Calif Los Angeles, Sch Dent, Jane & Jerry Weintraub Ctr Reconstruct Biotechnol, Div Adv Prosthodont Biomat & Hosp Dent, 10833 Le Conte Ave,B3-087 CHS, Los Angeles, CA 90095 USA. EM eroumana@ucla.edu RI Fueki, Kenji/A-9909-2008 OI Fueki, Kenji/0000-0002-5885-2447 FU NCRR NIH HHS [C06 RR-14529-01]; NIDCR NIH HHS [1R01DE11255] NR 42 TC 35 Z9 35 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD OCT PY 2006 VL 96 IS 4 BP 289 EP 297 DI 10.1016/j.prosdent.2006.08.015 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 099CF UT WOS:000241569400010 PM 17052474 ER PT J AU Wynn, JK Breitmeyer, B Nuechterlein, KH Green, MF AF Wynn, Jonathan K. Breitmeyer, Bruno Nuechterlein, Keith H. Green, Michael F. TI Exploring the short term visual store in schizophrenia using the attentional blink SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat DE schizophrenia; visual processing; attentional blink; short term visual memory ID WORKING-MEMORY CONSOLIDATION; BACKWARD-MASKING; SUPPRESSION; DEFICITS; TASK; PERCEPTION; TRANSIENT; CHANNELS; MODEL AB Schizophrenia patients exhibit numerous deficits on visual processing tasks, ranging from very early stages of visual processing (e.g., backward masking) to the later working memory stages (e.g., delayed match-to-sample, N-back). However, little is known about deficits in an inter-mediate stage of visual information processing, namely short term visual memory (STVM). The attentional blink (AB) paradigm is considered to be a valid way to assess the STVM, and recent studies have reported AB deficits in schizophrenia. However, it is not clear whether the reported AB deficit in schizophrenia patients is due to their increased susceptibility to backward masking or increased vulnerability in the STVM. In this study we first found poorer performance in the AB task in 37 schizophrenia patients compared to 26 normal controls. To examine the effects of increasing and decreasing mask strength on AB performance in patients and controls, we next systematically varied the masking effect by varying the length of the distracters immediately following the targets. The manipulation had relatively little effect on the patient - control differences and patients continued to show an enhanced AB effect across conditions. The findings suggest that the enhanced AB effect in schizophrenia reflects an abnormality in their short term visual memory, as opposed to their enhanced susceptibility to visual masking. (c) 2006 Elsevier Ltd. All rights reserved. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Wynn, JK (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 210, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [MH-43292, MH-65707, MH14584] NR 34 TC 17 Z9 17 U1 1 U2 2 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 OCT PY 2006 VL 40 IS 7 BP 599 EP 605 DI 10.1016/j.jpsychires.2006.06.002 PG 7 WC Psychiatry SC Psychiatry GA 093AU UT WOS:000241140300004 PM 16890242 ER PT J AU Berkowitz, RS Kohorn, EI Goldstein, DP Fisher, RA AF Berkowitz, Ross S. Kohorn, Ernest I. Goldstein, Donald P. Fisher, Rosemary A. TI Advances in the management of gestational trophoblastic disease - Presentations from the XIIIth World Congress on Gestational Trophoblastic Disease SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Editorial Material DE gestational trophoblastic neoplasms; placental-site trophoblastic tumors; chemotherapy C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,MD Trophoblast Tumor Regist, Dana Farber Canc Inst,New England Trophoblast Dis, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Gynecol, New Haven, CT USA. Univ London Imperial Coll Sci Technol & Med, Div Surg Oncol Reprod Biol & Anaesthet, London, England. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,MD Trophoblast Tumor Regist, Dana Farber Canc Inst,New England Trophoblast Dis, 75 Francis St, Boston, MA 02115 USA. EM ross_berkowitz@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD OCT PY 2006 VL 51 IS 10 BP 759 EP 759 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095XM UT WOS:000241341600002 ER PT J AU Szigetvari, I Szepesi, J Vegh, G Batorfi, J Arato, G Gati, I Berkowitz, RS Fulop, V AF Szigetvari, Ivan Szepesi, Janos Vegh, Gyorgy Batorfi, Jozsef Arato, Gabriella Gati, Istvan Berkowitz, Ross S. Fulop, Vilmos TI 25 Years' experience in the treatment of gestational trophoblastic neoplasia in Hungary SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 19-20, 2006 CL Chicago, IL SP Amer Laryngol Assoc DE gestational trophoblastic neoplasms; anatomical stages; prognostic score; chemotherapy ID ACTINOMYCIN-D; PROPHYLACTIC CHEMOTHERAPY; MOLAR PREGNANCY; DISEASE; CHORIOCARCINOMA; METHOTREXATE; TUMORS; MANAGEMENT; ETOPOSIDE; DIAGNOSIS AB OBJECTIVE: To review our clinical experience in the treatment of gestational trophoblastic neoplasia (GTN) over the past 25 years in our national trophoblastic disease center. STUDY DESIGN. Between January 1, 1977, and December 31, 2001, we treated 355 patients with GTN. The patients were between 14 and 53 years of age, with an average of 28.3. Primary chemotherapy was selected based on the patient's stage of gestational trophoblastic tumor (GTT) and prognostic score. RESULTS: We found metastases in 49.3% (175 of 355) of our patients. Of 173 patients, 162 (93.2%) achieved remission as a result of methotrexate therapy. In 11 patients (6.8%) complete remission was achieved by combination chemotherapy, in some cases assisted by operation. Of 68 patients, 63 (92.6%) achieved remission as a result of actinomycin D therapy, and 5 (7.4%) achieved complete remission by combination chemotherapy. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% successful, therapy in cases of nonmetastatic and low-risk metastatic disease. CONCLUSION: According to our experience, methotrexatelfolinic acid or actinomycin D should be the primary treatment in patients with nonmetastatic or low-risk metastatic GTN. Patients with resistance to single-agent chemotherapy regularly achieve remission with combination chemotherapy. C1 Natl Hlth Ctr, Dept Obstet & Gynecol, H-1135 Budapest, Hungary. Natl Hlth Ctr, Dept Pathol, H-1135 Budapest, Hungary. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Trophoblast Dis Ctr,Div Gyn, Boston, MA 02115 USA. RP Fulop, V (reprint author), Natl Hlth Ctr, Dept Obstet & Gynecol, 35 Szabolcs St, H-1135 Budapest, Hungary. EM fulopvilmos@freemail.hu NR 20 TC 4 Z9 6 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD OCT PY 2006 VL 51 IS 10 BP 841 EP 848 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095XM UT WOS:000241341600015 PM 17086814 ER PT J AU Conrad, MF Albadawi, H Stone, DH Crawford, RS Entabi, F Watkins, MT AF Conrad, Mark F. Albadawi, Hassan Stone, David H. Crawford, Robert S. Entabi, Fateh Watkins, Michael T. TI Local administration of the poly ADP-ribose polymerase (PARP) inhibitor, PJ34 during hindlimb ischemia modulates skeletal muscle reperfusion injury SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 1st Annual Academic Surgical Congress of the Association-for-Academic-Surgery CY FEB 07-11, 2006 CL San Diego, CA SP Assoc Acad Surg DE PJ34; ischemia; reperfusion; murine; hindlimb; cytokines; myeloperoxidase ID NITRIC-OXIDE SYNTHASE; MURINE MODEL; CHEMOKINES; CYTOKINES; CELLS AB Background. PARP stabilizes DNA and modulates inflammation in murine models of sepsis, stroke, and myocardial infarction. Previous studies have shown that systemic PARP inhibition before hindlimb ischemia preserves tissue viability and modulates cytokine synthesis during reperfusion. The purpose of this study was to determine whether intra-muscular (IM) administration of PJ34, a potent inhibitor of PARP, after the onset of acute hindlimb ischemia (post hoc) modulates the local production of inflammatory mediators during ischemia/reperfusion (I/R). Materials and methods. The control tension tourniquet was used to establish unilateral hindlimb ischemia in mice for 3 h followed by 48 h I/R. The treatment group (PJ) received IM PJ34 (10 mg/kg) in the affected hindlimb 90 min into ischemia whereas the control group (UN) received IM saline (150 uL) at the same time point. Skeletal muscle viability (MTT mitochondrial activity), local neutrophil chemoattractant protein (KC), Interleukin 6 (IL-6), Interleukin 1 beta (IL-1 beta), and Myeloperoxidase (MPO) levels were measured in protein extracts after the reperfusion period. Results. Muscle viability (102% +/- 10 PJ, 78% +/- 4 UN, P = 0.04), IL-B (21.1 +/- 1.3 PJ, 15.5 +/- 1.0 UN, P = 0.02), and IL-6 levels (16.3 +/- 1.2 PJ, 10.9 +/- 1.4 UN, P = 0.04) after 48 I/R were significantly higher in PJ. KC and MPO levels were higher in PJ but neither reached statistical significance. Conclusions. Post hoc PJ34 therapy appears to protect skeletal muscle from I/R injury despite increased levels of local cytokines. These initial findings support the role of local post hoc therapy in the treatment of acute limb threatening ischemia suggesting that further study of this novel therapy is warranted. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Div Vasc & Endovasc Surg, Dept Surg, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Watkins, MT (reprint author), Harvard Univ, Div Vasc & Endovasc Surg, Dept Surg, Massachusetts Gen Hosp,Med Sch, 15 Parkman St,WAC 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 23 TC 10 Z9 12 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2006 VL 135 IS 2 BP 233 EP 237 DI 10.1016/j.jss.2006.04.027 PG 5 WC Surgery SC Surgery GA 094XV UT WOS:000241273500005 PM 16872633 ER PT J AU Biller, CK Antonacci, AC Pelletier, S Homel, P Spann, C Cunningham, MJ Eavey, RD AF Biller, C. Katarina Antonacci, Anthony C. Pelletier, Stephen Homel, Peter Spann, Cyril Cunningham, Michael J. Eavey, Roland D. TI The 80-hour work guidelines and resident survey perceptions of quality SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE 80 hour workweek; surgical residents; ACGME work guidelines; quality; medical error; continuity of care; miscommunication; cross coverage; work hour reduction ID PATIENT SAFETY; CARE; IMPACT AB Objective. We hypothesized that resident fatigue error should improve, related to well-rested trainees as a direct cause/effect benefit. However, patient hospital care quality is multifactorial, so impact on patient care quality by changing only one variable for a single caregiver group was unknown. Design and participants. Convenience samples of 156 residents from three surgical specialties were administered a questionnaire in early 2004 addressing perceptions of patient care quality before and after the 80-h workweek. Additionally, residents recently under work-hour restrictions (Newly Restricted, NR) were compared to New York state trainees already regulated by work-hour restrictions (Previously Restricted, PR). Setting. Surgical residency training venues. Main outcome measure. Survey results; the level of significance for all tests was 0.05. Results. The participation response rate was 94.5%. Eighty-eight percent of respondents indicated by survey subjective impression, that patient care quality was either unchanged (63%) or worse (26%) due to work-hour restrictions (P = 0.003). PR residents were more likely than NR residents to report unchanged or worse quality of care (P = 0.015). Residents overall did perceive improvement in some types of error with fewer fatigue-related errors (P < 0.001), e.g., medication (P < 0.001), judgment (P = 0.001), and dexterity (P = 0.013), subsequent to work-hour restrictions. However, more errors were perceived related to con-tinuity of care (P < 0.001), miscommunication (P 0.001), and cross-coverage availability (P = 0.001). Conclusions. Despite an expected perception of improvement in fatigue-related errors, most participants (particularly PR residents) reported impressions that patient care quality had remained unchanged or had declined under the work-hour restrictions. Unresolved challenges with continuity of care, miscommunication, and cross-coverage availability are possible explanations. Mere work-hour reduction does not appear to improve patient care quality automatically nor to decrease the possibility for some types of error. Process interventions that specifically target trainee sign-out coverage constraints as part of a global reassessment will be important for future attempts to enhance quality hospital patient care. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Dept Otolaryngol, Pediat Otolaryngol Serv,Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Med Sch, Boston, MA 02114 USA. Beth Israel Med Ctr, Dept Surg, New York, NY 10003 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Harvard Univ, Sch Med, Dept Educ Dev, Boston, MA 02115 USA. Beth Israel Med Ctr, Dept Pain Management & Palliat Care, New York, NY 10003 USA. Emory Univ, Sch Med, Dept Obstet & Gynecol, Crawford Long Med Ctr, Atlanta, GA 30322 USA. RP Eavey, RD (reprint author), Harvard Univ, Dept Otolaryngol, Pediat Otolaryngol Serv,Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Med Sch, 243 Charles St, Boston, MA 02114 USA. EM roland_eavey@meei.harvard.edu NR 16 TC 19 Z9 19 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2006 VL 135 IS 2 BP 275 EP 281 DI 10.1016/j.jss.2006.04.010 PG 7 WC Surgery SC Surgery GA 094XV UT WOS:000241273500012 PM 16934295 ER PT J AU Yoon, SS Segal, NH Park, PJ Detwiller, KY Fernando, NT Ryeom, SW Brennan, MF Singer, S AF Yoon, Sam S. Segal, Neil H. Park, Peter J. Detwiller, Kara Y. Fernando, Namali T. Ryeom, Sandra W. Brennan, Murray F. Singer, Samuel TI Angiogenic profile of soft tissue sarcomas based on analysis of circulating factors and microarray gene expression SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE soft tissue sarcoma; angiogenesis; vascular endothelial growth factor; basic fibroblast growth factor; angiopoietin 2; leptin ID ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; IN-VIVO; PREDICTION; PATTERNS; CANCER; SWITCH; CLASSIFICATION; TUMORIGENESIS; SIGNATURE AB Background. Broader understanding of diverse angiogenic pathways in a particular cancer can lead to better utilization of anti-angiogenic therapies. The aim of this study was to develop profiles of angiogenesis-related gene and protein expression for various histologic subtypes of soft tissue sarcomas (STS) growing in different sites. Materials and methods. Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin 2 (Ang2), and leptin were determined in 108 patients with primary STS. Gene expression patterns were analyzed in 38 STS samples and 13 normal tissues using oligonucleotide microarrays. Results. VEGF and bFGF plasma levels were elevated 10-13 fold in STS patients compared to controls. VEGF levels were broadly elevated while bFGF levels were higher in patients with fibrosarcomas and leiomyosarcomas. Ang2 levels correlated with tumor size and were most elevated for tumors located in the trunk, while leptin levels were highest in patients with liposarcomas. Hierarchical clustering of microarray data based on angiogenesis-related gene expression demonstrated that histologic subtypes of STS often shared similar expression patterns, and these patterns were distinctly different from those of normal tissues. Matrix metalloproteinase 2, platelet-derived growth factor receptor, a and Notch 4 were among several genes that were up-regulated at least 7-fold in STS. Conclusions. STS demonstrate significant heterogeneity in their angiogenic profiles based on size, histologic subtype, and location of tumor growth, which may have implications for anti-angiogenic strategies. Comparison of STS to normal tissues reveals a panel of upregulated genes that may be targets for future therapies. (c) 2006 Elsevier Inc. All rights reserved. C1 Mem Sloan Kettering Canc Ctr, Dept Surg, Sarcoma Dis Management Team, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, Sarcoma Dis Management Team, New York, NY 10021 USA. Harvard Univ, Sch Med, Div Surg Oncol, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston Childrens Hosp, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston Childrens Hosp, Div Vasc Biol, Boston, MA 02115 USA. RP Singer, S (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Sarcoma Dis Management Team, 1275 York Ave, New York, NY 10021 USA. EM singers@mskcc.org OI Brennan, Murray/0000-0003-2358-4371 NR 40 TC 40 Z9 43 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2006 VL 135 IS 2 BP 282 EP 290 DI 10.1016/j.jss.2006.01.023 PG 9 WC Surgery SC Surgery GA 094XV UT WOS:000241273500013 PM 16603191 ER PT J AU Biederman, J Spencer, TJ Wilens, TE Prince, JB Faraone, SV AF Biederman, Joseph Spencer, Thomas J. Wilens, Timothy E. Prince, Jefferson B. Faraone, Stephen V. TI Treatment of ADHD with stimulant medications: Response to Nissen perspective in The New England Journal of Medicine SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC STATUS; FOLLOW-UP; CHILDREN; ADOLESCENTS; METHYLPHENIDATE; ADULTS; BRAIN; COMORBIDITY C1 Harvard Univ, Pediat Psychopharmacol Unit, Yawkey Ctr Patient Care, Massachusetts Gen Hosp,Sch Med,Clin Res Program P, Boston, MA 02114 USA. N Shore Med Ctr, Dept Child Psychiat, Salem, MA USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Biederman, J (reprint author), Harvard Univ, Pediat Psychopharmacol Unit, Yawkey Ctr Patient Care, Massachusetts Gen Hosp,Sch Med,Clin Res Program P, YAW 6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 NR 35 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2006 VL 45 IS 10 BP 1147 EP 1150 DI 10.1097/01.chi.0000227883.88521.e6 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 087MP UT WOS:000240746800001 PM 16840880 ER PT J AU Drell, MJ Josephson, A Pleak, R Riggs, P Rosenfeld, A AF Drell, Martin J. Josephson, Allan Pleak, Richard Riggs, Paula Rosenfeld, Alvin TI Clinical problem solving: The Case of John, Part II: Excerpts from sessions 2-7 SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Louisiana State Univ, Sch Med, Div Infant Child & Adolescent Psychiat, Hlth Sci Ctr, New Orleans, LA 70018 USA. Univ Louisville, Div Child Adolescent & Family Psychiat, Hlth Sci Ctr, Louisville, KY 40292 USA. Zucker Hillside Hosp, Div Child & Adolescent Psychiat, Long Isl Jewish Med Ctr, Glen Oaks, NY USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Drell, MJ (reprint author), Louisiana State Univ, Sch Med, Div Infant Child & Adolescent Psychiat, Hlth Sci Ctr, 210 State St, New Orleans, LA 70018 USA. EM mdrell@lsuhsc.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2006 VL 45 IS 10 BP 1243 EP 1251 DI 10.1097/01.chi.0000230164.46493.8c PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 087MP UT WOS:000240746800012 PM 17003670 ER PT J AU Millett, PJ Wilcox, RB O'Holleran, JD Warner, JJP AF Millett, Peter J. Wilcox, Reg B., III O'Holleran, James D. Warner, Jon J. P. TI Rehabilitation of the rotator cuff: An evaluation-based approach SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID SHOULDER IMPINGEMENT SYNDROME; SURGICAL REPAIR; SUPRASPINATUS MUSCLE; SUBACROMIAL SPACE; ANIMAL-MODEL; TEARS; TENDON; EXERCISES; ACTIVATION; STRENGTH AB Rotator cuff disease of the shoulder, a common condition, is often incapacitating. Whether nonsurgical or surgical, successful management of rotator cuff disease is dependent on appropriate rehabilitation. Numerous rehabilitation protocols for the management of rotator cuff disease are based primarily on anecdotal clinical observation. The available literature on shoulder rehabilitation, in conjunction with clinical observation that takes into consideration the underlying tissue quality and structural integrity of the rotator cuff, can be compiled into a set of rehabilitation guidelines. The four phases of rehabilitation begin with maintaining and protecting the repair in the immediate postoperative period, followed by progression from early passive range of motion through return to preoperative levels of function. C1 Steadman Hawkins Res Fdn, Vail, CO 81657 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Outpatient Serv, Dept Rehabil Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Millett, PJ (reprint author), Steadman Hawkins Res Fdn, Suite 1000,181 W Meadow Dr, Vail, CO 81657 USA. NR 43 TC 55 Z9 57 U1 0 U2 13 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD OCT PY 2006 VL 14 IS 11 BP 599 EP 609 PG 11 WC Orthopedics SC Orthopedics GA 092YA UT WOS:000241132400004 PM 17030593 ER PT J AU Hynes, DM T Stroupe, K Luo, P Giobbie-Hurder, A Reda, D Kraft, M Itani, K Fitzgibbons, R Jonasson, O Neumayer, L AF Hynes, Denise M. T Stroupe, Kevin Luo, Ping Giobbie-Hurder, Anita Reda, Domenic Kraft, Margaret Itani, Kamal Fitzgibbons, Robert Jonasson, Olga Neumayer, Leigh CA Vetterans Affairs Cooperative TI Cost effectiveness of laparoscopic versus open mesh hernia operation: Results of a Department of Veterans Affairs randomized clinical trial SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT Annual Research Meeting of the Academy-of-Health CY JUN 25-27, 2006 CL Seattle, WA SP Acad Health ID INGUINAL-HERNIA; GROIN HERNIA; AVERAGE COST; REPAIR; UTILITY; HEALTH; VA; UNCERTAINTY; GUIDELINES; ADOPTION AB BACKGROUND: Evidence comparing laparoscopic versus open hernia repair has varied with time and with changes in techniques used. Cost effectiveness is an important consideration when evidence for predominance of one surgical technique is lacking. Current cost estimates of hernia repair are not available. STUDY DESIGN: This study is a cost effectiveness analysis within a randomized controlled trial comparing open (OPEN) versus laparoscopic (LAP) hernia repair using mesh at 14 Department of Veterans Affairs medical centers, with 2-year followup for each patient. Between January 1999 and November 2001, 2,164 men with inguinal hernia were randomized and 1,983 had an operation; 1,395 patients (708 OPEN and 687 LAP) with outpatient hernia operations were included in the cost effectiveness analysis. Outcomes included surgical and postoperative costs, quality adjusted life years (QALY), and incremental cost per QALY gained or the incremental cost effectiveness ratio (ICER). RESULTS: Over 2 years, LAP cost an average of $638 more than OPEN. QALYs at 2 years were similar, resulting in $45,899 per QALY gained (95% Cl: -$669,045, $722,457). The probability that LAP is cost effective at the $50,000 per QALY level (slightly more costly but more effective), was 51%. For unilateral primary and unilateral recurrent hernia repair, the probabilities that LAP is cost effective at the $50,000 per QALY level were 64% and 81%, respectively. For bilateral hernia repair, OPEN was less costly and more effective. CONCLUSIONS: Overall, laparoscopic hernia repair is not cost effective compared with open repair. For patients with unilateral (primary or recurrent) hernia, laparoscopic repair is a cost effective treatment option. C1 VA Hosp, Feinberg Sch Med, Edward Hines Jr Dept Gen Internal Med, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. VA Hosp, Feinberg Sch Med, Edward Hines Jr Dept Gen Internal Med, Midwest Ctr Hlth Serv & Policy Res, Hines, IL USA. VA Hosp, Feinberg Sch Med, Edward Hines Jr Dept Gen Internal Med, VA Informat Resource Ctr, Hines, IL USA. Loyola Univ, Stritch Sch Med, Dept Med, Maywood, IL 60153 USA. Loyola Univ, Niehoff Sch Nursing, Maywood, IL 60153 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Illinois, Sch Publ Hlth, Dept Biostat, Chicago, IL USA. Boston Univ, Dept Surg, Boston, MA 02215 USA. Boston VA Healthcare Syst, Dept Surg, Boston, MA USA. Creighton Univ, Dept Surg, Omaha, NE 68178 USA. Univ Illinois, Coll Med, Dept Surg, Chicago, IL USA. VA Salt Lake City Healthcare Syst, Dept Surg, Salt Lake City, UT USA. Univ Utah, Dept Surg, Salt Lake City, UT USA. RP Hynes, DM (reprint author), Vet Affairs Edward Hines Jr Hosp, VA Informat Resource Ctr, Bldg 1,Room C303,POB 5000,151-V, Hines, IL 60141 USA. NR 44 TC 30 Z9 30 U1 1 U2 3 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 OCT PY 2006 VL 203 IS 4 BP 447 EP 457 DI 10.1016/j.jamcollsurg.2006.05.019 PG 11 WC Surgery SC Surgery GA 094YR UT WOS:000241275800005 PM 17000387 ER PT J AU Tsai, AG Asch, DA Wadden, TA AF Tsai, Adam Gilden Asch, David A. Wadden, Thomas A. TI Insurance coverage for obesity treatment SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc Gen Internal Med ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE; BARIATRIC SURGERY; HEALTH-CARE; MANAGEMENT; METFORMIN; SERVICES; THERAPY; SMOKING; ADULTS AB Recent work demonstrates the benefits of weight loss from intensive lifestyle modification. One barrier to counseling may be lack of reimbursement. We sought to quantify the obesity coverage policies of insurers in Pennsylvania. A three-page questionnaire was sent to eligible Pennsylvania health plans. Respondents included company medical directors and administrators from other departments, including public relations, provider relations, disease management, and utilization review. The questionnaire inquired about major treatment modalities for obesity, including details of coverage. Sixteen of 19 eligible plans (84%) responded. All plans provided some coverage for bariatric surgery. Nine out of 16 companies (56%) stated that they covered individual dietary counseling, but only five paid for intensive counseling. Less than 50% of plans reimbursed other forms of lifestyle modification or weight loss medication. Surgery was covered significantly more often than all other treatment modalities (P<0.02 for all comparisons). No differences in reimbursement were found by plan type or by number of enrollees. Insurance reimbursement for obesity in Pennsylvania does not consistently reflect recent evidence for the benefits of lifestyle modification. Given the increasing evidence for the clinical and cost-effectiveness of nonsurgical weight loss therapy, coverage policies may begin to change. C1 Univ Penn, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Tsai, AG (reprint author), Univ Penn, Ctr Weight & Eating Disorders, 3535 Market St,Suite 3022, Philadelphia, PA 19104 USA. EM gildena@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X FU NIDDK NIH HHS [K24-DK-065018] NR 25 TC 32 Z9 32 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 2006 VL 106 IS 10 BP 1651 EP 1655 DI 10.1016/j.jada.2006.07.012 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 090BI UT WOS:000240925200022 PM 17000198 ER PT J AU Steinman, MA Landefeld, CS Rosenthal, GE Berthenthal, D Sen, S Kaboli, PJ AF Steinman, Michael A. Landefeld, C. Seth Rosenthal, Gary E. Berthenthal, Daniel Sen, Saunak Kaboli, Peter J. TI Polypharmacy and prescribing quality in older people SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 26-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med DE aged; drug utilization; quality of health care; polypharmacy; drug therapy ID MEDICATION APPROPRIATENESS INDEX; ADVERSE DRUG-REACTIONS; POTENTIALLY INAPPROPRIATE; ELDERLY PATIENTS; BEERS CRITERIA; CARE PATIENTS; OF-CARE; TOO; RELIABILITY; GUIDELINES AB OBJECTIVES: To evaluate the relationship between inappropriate prescribing, medication underuse, and the total number of medications used by patients. DESIGN: Cross-sectional study. SETTING: Veterans Affairs Medical Center. PARTICIPANTS: One hundred ninety-six outpatients aged 65 and older who were taking five or more medications. MEASUREMENTS: Inappropriate prescribing was assessed using a combination of the Beers drugs-to-avoid criteria (2003 update) and subscales of the Medication Appropriateness Index that assess whether a drug is ineffective, not indicated, or unnecessary duplication of therapy. Underuse was assessed using the Assessment of Underutilization of Medications instrument. All vitamins and minerals, topical and herbal medications, and medications taken as needed were excluded from the analyses. RESULTS: Mean age was 74.6, and patients used a mean standard deviation of 8.1 +/- 2.5 medications (range 5-17). Use of one or more inappropriate medications was documented in 128 patients (65%), including 73 (37%) taking a medication in violation of the Beers drugs-to-avoid criteria and 112 (57%) taking a medication that was ineffective, not indicated, or duplicative. Medication underuse was observed in 125 patients (64%). Together, inappropriate use and underuse were simultaneously present in 82 patients (42%), whereas 25 (13%) had neither inappropriate use nor underuse. When assessed by the total number of medications taken, the frequency of inappropriate medication use rose sharply from a mean of 0.4 inappropriate medications in patients taking five to six drugs, to 1.1 inappropriate medications in patients taking seven to nine drugs, to 1.9 inappropriate medications in patients taking 10 or more drugs (P <.001). In contrast, the frequency of underuse averaged 1.0 underused medications per patient and did not vary with the total number of medications taken (P = .26). Overall, patients using fewer than eight medications were more likely to be missing a potentially beneficial drug than to be taking a medication considered inappropriate. CONCLUSION: Inappropriate medication use and underuse were common, in older people taking five or more medications, with both simultaneously present in more than 40% of patients. Inappropriate medication use is most frequent in patients taking many medications, but underuse is also common and merits attention regardless of the total number of medications taken. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Hlth Serv Res & Dev Serv Res Enhancement Award Pr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Iowa City Vet Affairs Med Ctr, Ctr Res Implementat Innovat Strategies Practice, Iowa City, IA USA. Univ Iowa, Carver Coll Med, Div Gen Internal Med, Dept Med, Iowa City, IA USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Box 181-G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU NIA NIH HHS [AG 10418, AG 00912] NR 36 TC 202 Z9 213 U1 4 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2006 VL 54 IS 10 BP 1516 EP 1523 DI 10.1111/j.1532-5415.2006.00889.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 096NY UT WOS:000241385300005 PM 17038068 ER PT J AU Zhu, CW Scarmeas, N Torgan, R Albert, M Brandt, J Blacker, D Sano, M Stern, Y AF Zhu, Carolyn W. Scarmeas, Nikolaos Torgan, Rebecca Albert, Marilyn Brandt, Jason Blacker, Deborah Sano, Mary Stern, Yaakov TI Clinical characteristics and longitudinal changes of informal cost of Alzheimer's disease in the community SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE informal care; costs; Alzheimer's disease; longitudinal study ID MOTOR SIGNS; DEMENTIA; CARE; PREDICTORS; SYMPTOMS; AD; ASSOCIATION; MULTICENTER; FEATURES; TIME AB Most estimates of the cost of informal caregiving in patients with Alzheimer's disease (AD) remain cross-sectional. Longitudinal estimates of informal caregiving hours and costs are less frequent and are from assessments covering only short periods of time. The objectives of this study were to estimate long-term trajectories of the use and cost of informal caregiving for patients with AD and the effects of patient characteristics on the use and cost of informal caregiving. The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States (n = 170). Generalized linear mixed models were used to estimate the effects of patient characteristics on use and cost of informal caregiving. Patients' clinical characteristics included cognitive status (Mini-Mental State Examination), functional capacity (Blessed Dementia Rating Scale (BDRS)), comorbidities, psychotic symptoms, behavioral problems, depressive symptoms, and extrapyramidal signs. Results show that rates of informal care use and caregiving hours (and costs) increased substantially over time but were related differently to patients' characteristics. Use of informal care was significantly associated with worse cognition, worse function, and higher comorbidities. Conditional on receiving informal care, informal caregiving hours (and costs) were mainly associated with worse function. Each additional point on the BDRS increased informal caregiving costs 5.4%. Average annual informal cost was estimated at $25,381 per patient, increasing from $20,589 at baseline to $43,030 in Year 4. C1 James Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA. James Peters VA Med Ctr, Program Res Serious Phys & Mental Illness, Targeted Res Enhancement Program, Bronx, NY 10468 USA. Mt Sinai Sch Med, Brookdale Dept Geriatr, New York, NY USA. Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, Cognit Neurosci Div, New York, NY 10027 USA. Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10027 USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Zhu, CW (reprint author), James Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM carolyn.zhu@mssm.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645, M01 RR000645]; NIA NIH HHS [R01 AG007370, R01 AG007370-07, R01-AG07370, U01 AG010483, U01AG010483] NR 31 TC 44 Z9 45 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2006 VL 54 IS 10 BP 1596 EP 1602 DI 10.1111/j.1532-5415.2006.00871.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 096NY UT WOS:000241385300017 PM 17038080 ER PT J AU Simmons, SF Schnelle, JF AF Simmons, Sandra F. Schnelle, John F. TI A continuous quality improvement pilot study: Impact on nutritional care quality SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE nutrition; quality; nursing home; assessment ID NURSING-HOME RESIDENTS; FEEDING ASSISTANCE; WEIGHT-LOSS; ACCURACY; STAFF AB Objective: All long-term care facilities are supposed to engage in quality improvement activities in an effort to improve care quality. The purpose of this pilot study was to teach long-term care staff how to conduct continuous quality improvement (CQI) related to nutritional care. Methods: Research staff conducted CQI training in one 48-bed pilot site with designated staff members. Supervisory staff were taught a standardized direct observational protocol, which was implemented weekly by both facility and research staff, to monitor defined nutritional care processes under the control of direct care staff. In addition, direct care staff received feedback on a weekly basis about care process implementation. Results: Following initial training and 12 weeks of CQI implementation, there were improvements in all 5 nutritional care processes related to the adequacy and quality of daily feeding assistance care provision according to both facility and research staff data. Weekly CQI implementation required approximately 1 hour of supervisory staff time and less than 15 minutes of direct care staff time to receive feedback. Implications: Both initial training and weekly CQI implementation were effective and required less than 2 hours of total staff time per week. Long-term care staff in this pilot site were able to improve nutritional care quality using a standardized direct observational protocol to guide CQI activities. C1 Univ Calif Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, Sch Med,Div Geriatr, Reseda, CA 91335 USA. Univ Calif Los Angeles, Sch Med, Dept Geriatr, Borun Ctr Gerontol Res, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, Sch Med,Div Geriatr, 7150 Tampa Ave, Reseda, CA 91335 USA. EM ssimmons@ucla.edu FU NIA NIH HHS [AG01026-01A1, AG10415] NR 22 TC 21 Z9 23 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD OCT PY 2006 VL 7 IS 8 BP 480 EP 485 DI 10.1016/j.jamda.2006.03.002 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 094YM UT WOS:000241275300002 PM 17027624 ER PT J AU Levy, CR Eilertsen, T Kramer, AM Hutt, E AF Levy, Cari R. Eilertsen, Terry Kramer, Andrew M. Hutt, Evelyn TI Which clinical indicators and resident characteristics are associated with health care practitioner nursing home visits or hospital transfer for urinary tract infections? SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE nursing home; hospitalization; practitioner practice patterns ID DO-NOT-RESUSCITATE; OF-LIFE CARE; PHYSICIAN; ORDERS; PREFERENCES; DEATH; BENEFIT; FEVER; SITE AB Objectives: (1) To determine factors associated with practitioner visitation and/or hospital transfer for skilled nursing facility (SNF) patients who develop a urinary tract infection (UTI) and (2) to determine if SNF patients with a Do Not Resuscitate (DNR) directive are less likely to be personally assessed and/or transferred to the hospital in the event of a UTI when compared to patients without a DNR directive. Design: Retrospective cohort study using nursing home medical record review. Participants: Participants were 564 residents from 35 nursing homes in 3 states who became acutely ill with UTI during the first 90 days of their nursing home admission. They were identified from 2832 random nursing home Medicare admissions and divided into 2 groups, those with DNR directives (n = 334) and those without (n = 230). Measurements: Logistic regression was used to determine factors associated with practitioner in-person assessment and/or hospitalization, and to determine differences in the likelihood of practitioner in-person assessment and/or hospitalization among those with DNR directives versus those without DNR directives. Results: Only one third (29%) of patients with unstable vital signs were seen by a practitioner or transferred to a hospital. Factors associated with practitioner assessment or hospital transfer were elevated temperature (OR 1.7, Cl 1.04-2.64), pulse more than 100 beats per minute (OR 1.7, Cl 1.01-2.99), and delirium (OR 2.1, Cl 1.267-3.44). White residents were less likely to be assessed by a practitioner or transferred to a hospital (OR 0.45, Cl 0.22-0.95). DNR directives were not significantly associated with fewer in-person assessments (P =.067). Conclusion: Only one third of SNF patients who developed a UTI with unstable vital signs were personally assessed by a practitioner and/or hospitalized. Patients with delirium were twice as likely to be assessed or transferred to a hospital, suggesting that practitioners use delirium as an indicator of illness severity. However, practitioner visit or transfer was also associated with ethnic background. In the absence of good evidence regarding which nursing home residents are likely to benefit from hospitalization or an urgent practitioner visit, these care decisions will continue to be associated with factors that are unknown. C1 Univ Colorado, Hlth Sci Ctr, Div Hlth Care Policy & Res, Aurora, CO 80011 USA. Univ Colorado, Hlth Sci Ctr, Div Geriatr, Aurora, CO 80011 USA. Denver VA Med Ctr, Program Res Long Term Care, Denver, CO USA. RP Levy, CR (reprint author), Univ Colorado, Hlth Sci Ctr, Div Hlth Care Policy & Res, 13611 E Colfax Ave, Aurora, CO 80011 USA. EM cari.levy@uchsc.edu NR 31 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD OCT PY 2006 VL 7 IS 8 BP 493 EP 498 DI 10.1016/j.jamda.2006.03.001 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 094YM UT WOS:000241275300004 PM 17027626 ER PT J AU Neilan, TG Ton-Nu, TT Jassal, DS Popovic, ZB Douglas, PS Halpern, EF Marshall, JE Thomas, JD Picard, MH Yoerger, DM Wood, MJ AF Neilan, Tomas G. Ton-Nu, Thanh-Thao Jassal, Davinder S. Popovic, Zoran B. Douglas, Pamela S. Halpern, Elkan F. Marshall, Jane E. Thomas, James D. Picard, Michael H. Yoerger, Danita M. Wood, Malissa J. TI Myocardial adaptation to short-term high-intensity exercise in highly trained athletes SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID PROLONGED EXERCISE; LEFT-VENTRICLE; NONINVASIVE QUANTIFICATION; TORSIONAL DEFORMATION; HEART; DIASTOLE; STRAIN; DOGS AB We aimed to clarify the myocardial adaptation to short-term high-intensity exercise among trained athletes. We screened 17 participants in the 2004 World Indoor Rowing Championships before and after a 2000-m sprint. Echocardiography included standard measurements and tissue Doppler-derived strain (epsilon), strain rate, and 2-dimensionally derived speckle-tracking imaging for left ventricular (IV) torsion. IV volumes and ejection fraction were unchanged after exercise. There was a reduction in early and an increase in late diastolic filling velocities and a decrease in the flow propagation velocity. Annular systolic velocities, slope of the systolic acceleration, septal and lateral epsilon, and speckle tracking derived torsion were increased. The increased IV torsion was a result of increased basal and apical. rotation. Right ventricular apical epsilon decreased. In conclusion, maximal intensity short-duration exercise was associated with attenuation of IV diastolic function, augmentation of IV systolic function, and a reduction in apical right ventricular contractility. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab,Div Cardiol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Div Cardiovasc Med, Durham, NC USA. Cleveland Clin Fdn, Dept Cardiol, Cardiovasc Imaging Ctr, Cleveland, OH 44195 USA. RP Wood, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab,Div Cardiol, 55 Fruit St,VBK 508, Boston, MA 02115 USA. EM mjwood@partners.orq OI Picard, Michael/0000-0002-9264-3243 NR 25 TC 42 Z9 43 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 2006 VL 19 IS 10 BP 1280 EP 1285 DI 10.1016/j.echo.2006.05.001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 097WW UT WOS:000241481200013 PM 17000368 ER PT J AU Obara, T Mangos, S Liu, Y Zhao, JH Wiessner, S Kramer-Zucker, AG Olale, F Schier, AF Drummond, IA AF Obara, Tomoko Mangos, Steven Liu, Yan Zhao, Jinhua Wiessner, Stephanie Kramer-Zucker, Albrecht G. Olale, Felix Schier, Alexander F. Drummond, Iain A. TI Polycystin-2 immunolocalization and function in zebrafish SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID KIDNEY-DISEASE PROTEIN; LEFT-RIGHT AXIS; KUPFFERS VESICLE; CATION CHANNEL; PKD2 INTERACTS; PRIMARY CILIUM; MOTILE CILIA; IN-VIVO; CELLS; LOCALIZATION AB Polycystin-2 functions as a cation-permeable transient receptor potential ion channel in kidney epithelial cells and when mutated results in human autosomal dominant polycystic kidney disease. For further exploration of the in vivo functions of Polycystin-2, this study examined its expression and function during zebrafish embryogenesis. pkd2 mRNA is ubiquitously expressed, and its presence in the larval kidney could be confirmed by reverse transcription-PCR on isolated pronephroi. Immunostaining with anti-zebrafish Polycystin-2 antibody revealed protein expression in motile kidney epithelial cell cilia and intracellular cell membranes. Intracellular localization was segment specific; in the proximal nephron segment, Polycystin-2 was localized to basolateral cell membranes, whereas in the caudal pronephric segment, Polycystin-2 was concentrated in subapical cytoplasmic vesicles. Polycystin-2 also was expressed in muscle cells and in a variety of sensory cells that are associated with mechanotransduction, including cells of the ear, the lateral line organ, and the olfactory placodes. Disruption of Polycystin-2 mRNA expression resulted in pronephric kidney cysts, body axis curvature, organ laterality defects, and hydrocephalus-defects that could be rescued by expression of a human PKD2 mRNA. In-frame deletions in the first extracellular loop and C-terminal phosphofurin acidic cluster sorting protein-1 (PACS-1) binding sites in the cytoplasmic tail caused Polycystin-2 mislocalization to the apical cell surface. Unlike zebrafish intraflagellar transport protein (IFT) mutants, cyst formation was not associated with cilia defects and instead correlated with reduced kidney fluid output, expansion of caudal duct apical cell membranes, and occlusion of the caudal pronephric nephron segment. C1 Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. NYU, Sch Med, Skirball Inst Biomol Med, New York, NY USA. Harvard Univ, Cambridge, MA 02138 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Nephrol, 149-8000 149 13th St, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU NIDDK NIH HHS [P01 DK054711, R01 DK053093, DK 54711, DK 53093, R21 DK069604, R01 DK078209]; NIGMS NIH HHS [GM 56211, R01 GM056211] NR 51 TC 62 Z9 62 U1 0 U2 10 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2006 VL 17 IS 10 BP 2706 EP 2718 DI 10.1681/ASN.2006040412 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 090BV UT WOS:000240926500010 PM 16943304 ER PT J AU Weisbord, SD Chen, HY Stone, RA Kip, KE Fine, MJ Saul, MI Palevsky, PM AF Weisbord, Steven D. Chen, Huanyu Stone, Roslyn A. Kip, Kevin E. Fine, Michael J. Saul, Melissa I. Palevsky, Paul M. TI Associations of increases in serum creatinine with mortality and length of hospital stay after coronary angiography SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CA SP Amer Soc Nephrol ID RANDOMIZED CONTROLLED-TRIAL; CONTRAST-INDUCED NEPHROPATHY; ACUTE-RENAL-FAILURE; N-ACETYLCYSTEINE; CARDIAC ANGIOGRAPHY; COMORBIDITY INDEX; RISK-FACTORS; PREVENTION; MEDIA; NEPHROTOXICITY AB The absence of a universally accepted definition of radiocontrast nephropathy (RCN) has hampered efforts to characterize effectively the incidence and the clinical significance of this condition. The objective of this study was to identify a clinically relevant definition of RCN by assessment of the relationships between increases in serum creatinine (Scr) of varying magnitude after coronary angiography and clinical outcomes. An electronic medical database was used to identify all patients who underwent coronary angiography at the University of Pittsburgh Medical Center during a 12-yr period and abstract Scr levels before and after angiography, as well as demographic characteristics and comorbid conditions. Changes in Scr after angiography were categorized into mutually exclusive categories on the basis of absolute and relative changes from baseline levels, with a separate category denoting "unknown" change. Discrete proportional odds models were used to examine the association between increases in Scr and 30-d in-hospital mortality and length of stay. A total of 27,608 patients who underwent coronary angiography were evaluated. Small absolute (0.25 to 0.5 mg/dl) and relative (25 to 50%) increases in Scr were associated with risk-adjusted odds ratios for in-hospital mortality of 1.83 and 1.39, respectively. Larger increases in Scr generally were associated with greater risks for these clinical outcomes. Small increases in Scr after the administration of intravascular radiocontrast are associated with adverse patient outcomes. This observation will help guide the postprocedure care of patients who undergo coronary angiography and has important implications for future studies that investigate RCN. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Renal & Electrolyte, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Biomed Informat, Dept Med, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Mailstop 111F-U,7E Room 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu NR 27 TC 106 Z9 113 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2006 VL 17 IS 10 BP 2871 EP 2877 DI 10.1681/ASN.2006030301 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 090BV UT WOS:000240926500026 PM 16928802 ER PT J AU Peralta, CA Shlipak, MG Fan, DJ Ordonez, J Lash, JP Chertow, GM Go, AS AF Peralta, Carmen A. Shlipak, Michael G. Fan, Dongjie Ordonez, Juan Lash, James P. Chertow, Glenn M. Go, Alan S. TI Risks for end-stage renal disease, cardiovascular events, and death in Hispanic versus non-Hispanic white adults with chronic kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEART-STUDY EVIDENCE; MEXICAN-AMERICANS; UNITED-STATES; RACIAL-DIFFERENCES; NATIONAL-HEALTH; ALL-CAUSE; MORTALITY; POPULATION; PREVALENCE; PARADOX AB Rates of ESRD are rising faster in Hispanic than non-Hispanic white individuals, but reasons for this are unclear. Whether rates of cardiovascular events and mortality differ among Hispanic and non-Hispanic white patients with chronic kidney disease (CKD) also is not well understood. Therefore, this study examined the associations between Hispanic ethnicity and risks for ESRD, cardiovascular events, and death in patients with CKD. A total of 39,550 patients with stages 3 to 4 CKD from Kaiser Permanente of Northern California were included. Hispanic ethnicity was obtained from self-report supplemented by surname matching. GFR was estimated from the abbreviated Modification of Diet in Renal Disease equation, and clinical outcomes, patient characteristics, and longitudinal medication use were ascertained from health plan databases and state mortality files. After adjustment for sociodemographic characteristics, Hispanic ethnicity was associated with an increased risk for ESRD (hazard ratio [HR] 1.93; 95% confidence interval [CI] 1.72 to 2.17) when compared with non-Hispanic white patients, which was attenuated after controlling for diabetes and insulin use (HR 1.50; 95% CI 1.33 to 1.69). After further adjustment for potential confounders, Hispanic ethnicity remained independently associated with an increased risk for ESRD (HR 1.33; 95% CI 1.17 to 1.52) as well as a lower risk for cardiovascular events (HR 0.82; 95% CI 0.76 to 0.88) and death (HR 0.72; 95% CI 0.66 to 0.79). Among a large cohort of patients with CKD, Hispanic ethnicity was associated with lower rates of death and cardiovascular events and a higher rate of progression to ESRD. The higher prevalence of diabetes among Hispanic patients only partially explained the increased risk for ESRD. Further studies are required to elucidate the cause(s) of ethnic disparities in CKD-associated outcomes. C1 Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Kaiser Permanente, Oakland Med Ctr, Div Nephrol, Oakland, CA USA. Univ Illinois, Dept Med, Div Nephrol, Chicago, IL USA. RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St,3rd Floor, Oakland, CA 94612 USA. EM alan.s.go@kp.org FU NIDDK NIH HHS [R01 DK 58411, U01 DK 60902] NR 31 TC 84 Z9 88 U1 0 U2 2 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2006 VL 17 IS 10 BP 2892 EP 2899 DI 10.1681/ASN.2005101122 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 090BV UT WOS:000240926500029 PM 16959827 ER PT J AU Chen, YW Sim, MM Smith, EE AF Chen, Yu-Wei Sim, Ming-Ming Smith, Eric E. TI Thrombolytic therapy in acute cerebral infarction complicating diagnostic cardiac catheterization SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Article DE cerebral infarction; heart catheterization; thrombolytic therapy ID RISK-FACTORS; STROKE; ANGIOGRAPHY; EMBOLISM; ARTERY; CT AB Diagnostic and interventional percutaneous coronary catheterization is associated with stroke. Many of such strokes are asymptomatic, but some are devastating. Once the diagnosis of acute cerebral infarction is confirmed, thrombolytic therapy should be administrated within the time window of 3 hours. We report a 61-year-old woman who suffered from an acute cerebral infarction during diagnostic cardiac catheterization for unstable angina, which manifested as sudden onset of global aphasia, right hemiplegia and gaze preponderance to the left side. Computed tomography of the head performed immediately after recognition of the symptoms showed a hyperdense middle cerebral artery (MCA) sign. Following prompt recognition and diagnosis, intravenous thrombolytic therapy was administered 2 hours after symptom onset. The patient had a favorable outcome. Initially, National Institutes of Health Stroke Scale score was 21, and 24 hours later it improved to 9. The hyperdense MCA lesion had resolved on the 24-hour follow-up scan. This case illustrates the clinical benefit of thrombolytic therapy in the setting of acute stroke associated with cardiac catheterization. C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Li Shin Hosp, Dept Neurol, Tao Yuan, Taiwan. Li Shin Hosp, Dept Cardiol, Tao Yuan, Taiwan. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, VBK 725,55 Fruit St, Boston, MA 02114 USA. EM eesmith@partners.org OI Smith, Eric/0000-0003-3956-1668 NR 13 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIFIC COMMUNICATIONS INTERNATIONAL LTD. PI TAIPEI PA NO 1, CHANG-TE ST, TAIPEI, 100, TAIWAN SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD OCT PY 2006 VL 105 IS 10 BP 848 EP 851 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 095FY UT WOS:000241294800010 PM 17000459 ER PT J AU Dvorkin, L Whelan, JS Timarac, S AF Dvorkin, Lana Whelan, Julia S. Timarac, Samira TI Harvesting the best: evidence-based analysis of herbal handbooks for clinicians SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article C1 Massachusetts Coll Pharm & Hlth Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Dvorkin, L (reprint author), Massachusetts Coll Pharm & Hlth Sci, 179 Longwood Ave, Boston, MA 02115 USA. EM Lana.dzurkin@mcphs.edu; jcwhelan@partners.org; ETimarac@aol.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD OCT PY 2006 VL 94 IS 4 BP 442 EP 442 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 100QH UT WOS:000241683100013 PM 17082838 ER PT J AU Wallis, LC AF Wallis, Lisa C. TI Information-seeking behavior of faculty in one school of public health SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID PROFESSIONALS; TECHNOLOGIES; RESOURCES; NEEDS C1 Massachusetts Coll Pharm & Hlth Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Wallis, LC (reprint author), Massachusetts Coll Pharm & Hlth Sci, 179 Longwood Ave, Boston, MA 02115 USA. EM lwallis@uic.edu RI Wallis, Lisa/B-2904-2008 OI Wallis, Lisa/0000-0001-8356-647X NR 16 TC 6 Z9 8 U1 1 U2 5 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD OCT PY 2006 VL 94 IS 4 BP 442 EP 446 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA 100QH UT WOS:000241683100014 PM 17082837 ER PT J AU Barbour, JR Stroud, RE Lowry, AS Clark, LL Leone, AM Jones, JA Spinale, FG Ikonomidis, JS AF Barbour, John R. Stroud, Robert E. Lowry, Abigail S. Clark, Leslie L. Leone, Allyson M. Jones, Jeffery A. Spinale, Francis G. Ikonomidis, John S. TI Temporal disparity in the induction of matrix metalloproteinases and tissue inhibitors of metalloproteinases after thoracic aortic aneurysm formation SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID NEUTROPHIL COLLAGENASE; UP-REGULATION; MURINE MODEL; T-CELLS; INFLAMMATION; EXPRESSION; LOCALIZATION; GELATINASE; GAMMA; MICE AB Background: An important component of matrix remodeling during thoracic aortic aneurysm progression is the balance between matrix metalloproteinases and their endogenous inhibitors (tissue inhibitors of metalloproteinases). However, whether and to what degree matrix metalloproteinase/tissue inhibitor of metalloproteinases profiles change over time with an evolving thoracic aortic aneurysm remains unclear. Methods: Descending thoracic aortic aneurysms were induced in mice (FVB strain, 15 minutes of 0.5 mol/L CaCl2 exposure) and followed for 24 hours, 72 hours, 1 week, 2 weeks, 4 weeks, or 8 weeks (each group, n = 13). Thoracic aortic aneurysm size was determined by means of video micrometry, and immunoblotting was used to measure aortic matrix metalloproteinase 2, 8, 9, and 12 and tissue inhibitor of metalloproteinases 1 and 4 levels (expressed as a percentage of control values, n = 13). Results: Increased aortic diameter was detected by 72 hours and reached a maximal size at 4 weeks (135% +/- 4% increase from baseline, P < .05), which is consistent with thoracic aortic aneurysm progression. Active matrix metalloproteinase 8 (collagenase) levels increased at 72 hours (178% +/- 49%, P < .05 from control), and active matrix metalloproteinase 12 (elastase) levels increased by 24 hours (138% +/- 11%, P < .05), whereas active matrix metalloproteinase 2 levels increased at 72 hours and 1 week after thoracic aortic aneurysm induction (72 hours: 158% +/- 12%, 1 week: 162% +/- 19%; P < .05). At 1 week after thoracic aortic aneurysm induction, active matrix metalloproteinase 9 and 12 levels decrease (matrix metalloproteinase 9: 55% +/- 5%; matrix metalloproteinase 12: 63% +/- 5%; P < .05); however, matrix metalloproteinase 9 and 12 levels were increased from these values at 4 and 8 weeks (P < .05). Tissue inhibitor of metalloproteinases 1 levels were decreased at 1 week (52% +/- 15%, P <. 05) and later returned to control values, whereas tissue inhibitor of metalloproteinases 4 levels increased at the late thoracic aortic aneurysm time points (4 weeks: 278% +/- 46%; 8 weeks: 213% +/- 40%; P < .05). Conclusions: These findings show 2 phases of matrix metalloproteinase abundance during murine thoracic aortic aneurysm formation. The late tissue inhibitor of metalloproteinases 4 increase might explain prevention of further aortic dilation past 4 weeks. Unique matrix metalloproteinase/tissue inhibitor of metalloproteinases temporal relationships occurred during the natural history of thoracic aortic aneurysm progression that might hold both diagnostic and therapeutic relevance. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Ikonomidis, JS (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Suite 409 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM ikonomij@musc.edu FU NHLBI NIH HHS [R01 HL059165-07, R01 HL075488-01] NR 30 TC 12 Z9 12 U1 0 U2 4 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 OCT PY 2006 VL 132 IS 4 BP 788 EP 795 DI 10.1016/j.jtcvs.2006.05.052 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 090ME UT WOS:000240954600008 PM 17000289 ER PT J AU Jassal, DS Fatima, U Thakrar, A Neilan, TG Rodriguez, N Rosenberg, A Holmvang, G AF Jassal, Davinder S. Fatima, Umaima Thakrar, Amar Neilan, Tomas G. Rodriguez, Norma Rosenberg, Andrew Holmvang, Godtfred TI Mediastinal paraganglioma: Utility of preoperative cardiac magnetic resonance imaging SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 St Boniface Gen Hosp, Inst Cardiovasc Sci, Div Cardiol, Dept Cardiac Sci, Winnipeg, MB R2H 2A6, Canada. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Royal Univ Hosp, Dept Internal Med, Saskatoon, SK S7N 0W8, Canada. RP Jassal, DS (reprint author), St Boniface Gen Hosp, Inst Cardiovasc Sci, Div Cardiol, Dept Cardiac Sci, Winnipeg, MB R2H 2A6, Canada. EM djassal@shaw.ca NR 5 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 2006 VL 132 IS 4 BP 976 EP 977 DI 10.1016/j.jtcvs.2006.06.011 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 090ME UT WOS:000240954600038 PM 17000319 ER PT J AU Okubo, C Minami, Y Tanaka, R Uchihara, T Anami, Y Furuya, S Morishita, Y Iijima, T Noguchi, M AF Okubo, Chigusa Minami, Yuko Tanaka, Ryota Uchihara, Teruhito Anami, Yoichi Furuya, Shuichiroh Morishita, Yukio Iijima, Tatsuo Noguchi, Masayuki TI Analysis of differentially expressed genes in neuroendocrine carcinomas of the lung SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE lung; neuroendocrine carcinoma; neuronatin; suppression subtractive hybridization; TALPAT ID HEREDITARY OPTIC NEUROPATHY; SUPPRESSION SUBTRACTIVE HYBRIDIZATION; HUMAN NEURONATIN GENE; CHROMOSOMAL-ABERRATIONS; SMALL-CELL; TUMORS; MUTATIONS; CLONING; IDENTIFICATION; POLYMORPHISM AB Introduction: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) show considerable differences in their histology but share neuroendocrine (NE) characteristics and also genetic and/or expression patterns. Methods: We used the subtractive expression method to identify differences in gene expression that would allow discrimination between these two types of NE lung carcinoma. Results: Eight cDNA fragments were transcribed at a higher level in LCNEC compared with SCLC, and these corresponded to five mitochondrial genes, two ribosomal genes, and one fetal regulation factor, neuronatin (NNAT). Immunohistochemically, NNAT protein was detected in 43% (6/14) of LCNECs but in only 8% (1/13) of SCLCs (p < 0.05). Positive staining for NNAT was observed in areas that did not show the NE morphology, such as palisading and rosettes. Conclusions: The present results suggest that NNAT has the potential to be used as a differential maker between LCNEC and SCLC. C1 Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan. Univ Tsukuba, Inst Clin Med, Dept Clin Pathol, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan. Univ Hosp, Dept Pathol, Tsukuba, Ibaraki, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Gunma Prefectural Canc Ctr, Dept Thorac Surg, Gunma, Japan. Univ Ryukyus, Grad Sch, Dept Internal Med, Div Infect Dis, Okinawa, Japan. Univ Ryukyus, Fac Med, Okinawa, Japan. RP Noguchi, M (reprint author), Univ Tsukuba, Inst Basic Med Sci, Dept Pathol, Grad Sch Comprehens Human Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM nmasayuk@md.tsukuba.ac.jp NR 56 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2006 VL 1 IS 8 BP 780 EP 786 DI 10.1097/01243894-200610000-00005 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 100EB UT WOS:000241649300005 PM 17409960 ER PT J AU Yang, H Reheman, A Chen, P Zhu, G Hynes, RO Freedman, J Wagner, DD Ni, H AF Yang, H. Reheman, A. Chen, P. Zhu, G. Hynes, R. O. Freedman, J. Wagner, D. D. Ni, H. TI Fibrinogen and von Willebrand factor-independent platelet aggregation in vitro and in vivo SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE fibrinogen; integrin; intravital microscopy; platelet aggregation; thrombin; thrombosis ID THROMBUS FORMATION; GLYCOPROTEIN-IIIA; BETA-3-INTEGRIN-DEFICIENT MICE; VONWILLEBRAND-FACTOR; GPIIB-IIIA; FIBRONECTIN; RECEPTOR; INTEGRIN; BINDING; MECHANISMS AB Background: Fibrinogen (Fg) has been considered essential for platelet aggregation. However, we recently demonstrated formation of occlusive thrombi in Fg-deficient mice and in mice doubly deficient for Fg and von Willebrand factor (Fg/VWF-/-). Methods and results: Here we studied Fg/VWF-independent platelet aggregation in vitro and found no aggregation in citrated platelet-rich plasma of Fg/VWF-/- mice. Surprisingly, in Fg/VWF-/- plasma without anticoagulant, adenosine diphosphate induced robust aggregation of Fg/VWF-/- platelets but not of = 1.5 mg/dL) (29%). Lesions were classified as TransAtlantic Inter-Society Consensus (TASC) A (11%), B (43%), C (41%), and D (5%). PTA was confined to the femoropopliteal segment in 77 patients (33%), and 161 (67%) underwent concurrent interventions in other anatomic locations. Femoropopliteal interventions included angioplasty only in 183 (78%), and the remaining 53 (22%) received at least one stent. Technical success was achieved in 97% of patients, with no deaths and a major morbidity rate of 3%. The 36-month actuarial primary patency was 54.3%, and assisted patency was 92.6% (37 peripheral reinterventions), resulting in a limb preservation rate of 95.4% in all patients regardless of clinical presentation. Interval conversion to bypass surgery occurred in 19 patients (8%). Comparison between critical limb ischemia and claudication revealed a primary patency of 40.8% vs 64.8%, assisted patency of 93.8% vs 92.6%, and limb salvage of 89.7% vs 100%, respectively. Negative predictors of primary patency determined by multivariate analysis included history of congestive heart failure (P = .02) and TASC C/D (P = .02). However, further evaluation of TASC C/D vs A/B revealed an assisted patency of 89.7% vs 94.3% (P = .37) and limb salvage of 94.3% vs 96.4% (P = .58). Conclusions: Femoropopliteal PTA can be performed with a low perioperative morbidity and mortality. Intermediate primary patency is directly related to TASC classification. Although secondary intervention is often necessary to maintain patency in TASC C/D lesions, these data suggest that it would be appropriate to use PTA as initial therapy for chronic femoropopliteal occlusive disease regardless of clinical classification at presentation or TASC category of lesion severity. C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Cent Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP LaMuraglia, GM (reprint author), WACC, 464 Parkman St, Boston, MA 02114 USA. OI Chung, Thomas/0000-0001-6148-1184 NR 29 TC 92 Z9 105 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 OCT PY 2006 VL 44 IS 4 BP 762 EP 769 DI 10.1016/j.jvs.2006.06.025 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 090OG UT WOS:000240960000016 PM 17012001 ER PT J AU Ulsenheimer, A Lucas, M Seth, NP Gerlach, JT Gruener, NH Loughry, A Pape, GR Wucherpfennig, KW Diepolder, HM Klenerman, P AF Ulsenheimer, A. Lucas, M. Seth, N. P. Gerlach, J. Tilman Gruener, N. H. Loughry, A. Pape, G. R. Wucherpfennig, K. W. Diepolder, H. M. Klenerman, P. TI Transient immunological control during acute hepatitis C virus infection: ex vivo analysis of helper T-cell responses SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE acute hepatitis C; CD4+T-cell; Class II tetrameric complexes; hepatitis C virus ID CLASS-II TETRAMERS; NONSTRUCTURAL PROTEIN-3; VIRAL CLEARANCE; PERSISTENCE; PHENOTYPE AB Hepatitis C virus (HCV) readily sets up persistence after acute infection. Cellular immune responses are thought to play a major role in control of the virus. Failure of CD4+ T-cell responses in acute disease is associated with viral persistence but the dynamics of this are poorly understood. We aimed to assess such responses using a novel set of Class II tetrameric complexes (tetramers) to study helper T-cells ex vivo in acute disease. We analysed the HCV-specific CD4+ T-cell response in a patient with acute hepatitis c infection. We were able to track the virus-specific CD4+ T-cells directly ex vivo with HLA DR4 tetramers. Proliferative responses were absent initially, recovered as viral load dropped and were lost again during relapse. Longitudinal tetramer analyses showed expanded populations of antiviral CD4+ T-cells throughout acute infection despite lack of proliferation. A pattern of transient CD4+ T-cell proliferative responses as HCV is partially controlled is observed. Failure to control virus is associated with emergence of 'dysfunctional' CD4+ T-cell populations. Failure to control HCV in acute disease may relate to the capacity to sustain efficient immune responses as virus attempts to 'bounce back' after partial control. C1 Univ Munich, Klinikum Grosshadern, Dept Med 2, D-81377 Munich, Germany. Univ Munich, Inst Immunol, D-8000 Munich, Germany. Nuffield Dept Clin Med, Oxford, England. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Ulsenheimer, A (reprint author), Univ Munich, Klinikum Grosshadern, Dept Med 2, Marchioninistr 15, D-81377 Munich, Germany. EM axel@ulsenheimer.de FU NIAID NIH HHS [AI45757, P01 AI045757]; Wellcome Trust NR 27 TC 29 Z9 30 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD OCT PY 2006 VL 13 IS 10 BP 708 EP 714 DI 10.1111/j.1365-2893.2006.00747.x PG 7 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 084JC UT WOS:000240528200009 PM 16970603 ER PT J AU Sagar, M Wu, XL Lee, S Overbaugh, J AF Sagar, Manish Wu, Xueling Lee, Sandra Overbaugh, Julie TI Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity SO JOURNAL OF VIROLOGY LA English DT Article ID N-LINKED GLYCOSYLATION; IN-VIVO; HETEROSEXUAL TRANSMISSION; REPLICATION-COMPETENT; DISEASE PROGRESSION; V2 REGIONS; AMINO-ACID; GP120; GLYCOPROTEIN; VARIANTS AB Over the course of infection, human immunodeficiency virus type 1 (HIV-1) continuously adapts to evade the evolving host neutralizing antibody responses. Changes in the envelope variable loop sequences, particularly the extent of glycosylation, have been implicated in antibody escape. To document modifications that potentially influence antibody susceptibility, we compared envelope variable loops I and 2 (V1-V2) from multiple sequences isolated at the primary phase of infection to those isolated around 2 to 3 years into the chronic phase of infection in nine women with HIV-1 subtype A. HIV-1 sequences isolated during chronic infection had significantly longer V1-V2 loops, with a significantly higher number of potential N-linked glycosylation sites, than the sequences isolated early in infection. To assess the effects of these V1-V2 changes on antibody neutralization and infectivity, we created chimeric envelope sequences, which incorporated a subject's V1-V2 sequences into a common subtype A envelope backbone and then used them to generate pseudotyped viruses. Compared to the parent virus, the introduction of a subject's early-infection V1-V2 envelope variable loops rendered the chimeric envelope more sensitive to that subject's plasma samples but only to plasma samples collected > 6 months after the sequences were isolated. Neutralization was not detected with the same plasma when the early-infection V1-V2 sequences were replaced with chronic-infection V1-V2 sequences, suggesting that changes in V1-V2 contribute to antibody escape. Pseudotyped viruses with V1-V2 segments from different times in infection, however, showed no significant difference in neutralization sensitivity to heterologous pooled plasma, suggesting that viruses with V1-V2 loops from early in infection were not inherently more neutralization sensitive. Pseudotyped viruses bearing chimeric envelopes with early-infection V1-V2 sequences showed a trend in infecting cells with low CD4 concentrations more efficiently, while engineered viruses with V1-V2 sequences isolated during chronic infection were moderately better at infecting cells with low CCR5 concentrations. These studies suggest that changes within the V1-V2 envelope domains over the course of an infection influence sensitivity to autologous neutralizing antibodies and may also impact host receptor/coreceptor interactions. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Brigham & Womens Hosp, Dept Med, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Overbaugh, J (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave N,C3-168, Seattle, WA 98109 USA. EM joverbau@fhcrc.org OI Sagar, Manish/0000-0001-9803-6594 FU NIAID NIH HHS [K08 AI052759, AI38515, P30 AI060354, U19 AI038515] NR 49 TC 184 Z9 192 U1 2 U2 7 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 OCT PY 2006 VL 80 IS 19 BP 9586 EP 9598 DI 10.1128/JVI.00141-06 PG 13 WC Virology SC Virology GA 086BD UT WOS:000240647200022 PM 16973562 ER PT J AU Anderson, JL Campbell, EM Wu, XL Vandegraaff, N Engelman, A Hope, TJ AF Anderson, Jenny L. Campbell, Edward M. Wu, Xiaolu Vandegraaff, Nick Engelman, Alan Hope, Thomas J. TI Proteasome inhibition reveals that a functional preintegration complex intermediate can be generated during restriction by diverse TRIM5 proteins SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; FV-1 GENE-PRODUCT; OLD-WORLD MONKEY; CYCLOPHILIN-A; RETROVIRUS RESTRICTION; TRIM5-ALPHA RESTRICTION; NUCLEAR IMPORT; TYPE-1 CORE; INFECTION AB The primate TRIM5 proteins constitute a class of restriction factors that prevent host cell infection by retroviruses from different species. The TRIM5 proteins act early after virion entry and prevent viral reverse transcription products from accumulating. We recently found that proteasome inhibitors altered the rhesus monkey TRIM5 alpha restriction of human immunodeficiency virus type 1 (HIV-1), allowing reverse transcription products to accumulate even though viral infection remained blocked. To assess whether sensitivity to proteasome inhibitors was a common feature of primate TRIM5 proteins, we conducted a similar analysis of restriction mediated by owl monkey TRIM-cyclophilin A (CypA) or human TRIM5 alpha. Similar to rhesus monkey TRIM5 alpha restriction, proteasome inhibition prevented owl monkey TRIM-CypA restriction of HIV-1 reverse transcription, even though HIV-1 infection and the output of 2-LTR circles remained impaired. Likewise, proteasome inhibition alleviated human TRIM5 alpha restriction of N-tropic murine leukemia virus reverse transcription. Finally, HIV-1 reverse transcription products escaping rhesus TRIM5 alpha restriction by proteasome inhibition were fully competent for integration in vitro, demonstrating that TRIM5 alpha likely prevents the viral cDNA from accessing chromosomal target DNA. Collectively, these data indicate that the diverse TRIM5 proteins inhibit retroviral infection in multiple ways and that inhibition of reverse transcription products is not necessary for TRIM5-mediated restriction of retroviral infection. C1 Northwestern Univ, Dept Cell & Mol Biol, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60612 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hope, TJ (reprint author), Northwestern Univ, Dept Cell & Mol Biol, Feinberg Sch Med, Ward 8-140,303 E Chicago Ave, Chicago, IL 60611 USA. EM thope@northwestern.edu OI Anderson, Jenny/0000-0003-4636-6633 FU NIAID NIH HHS [R01 AI047770, R01 AI052014, R01 AI4770, R01 AI52014] NR 41 TC 117 Z9 123 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2006 VL 80 IS 19 BP 9754 EP 9760 DI 10.1128/JVI.01052-06 PG 7 WC Virology SC Virology GA 086BD UT WOS:000240647200039 PM 16973579 ER PT J AU Zaunders, JJ Ip, S Munier, ML Kaufmann, DE Suzuki, K Brereton, C Sasson, SC Seddiki, N Koelsch, K Landay, A Grey, P Finlayson, R Kaldor, J Rosenberg, ES Walker, BD Fazekas de St Groth, B Cooper, DA Kelleher, AD AF Zaunders, John J. Ip, Susanna Munier, Mee Ling Kaufmann, Daniel E. Suzuki, Kazuo Brereton, Choechoe Sasson, Sarah C. Seddiki, Nabila Koelsch, Kersten Landay, Alan Grey, Pat Finlayson, Robert Kaldor, John Rosenberg, Eric S. Walker, Bruce D. Fazekas de St Groth, Barbara Cooper, David A. Kelleher, Anthony D. CA PHAEDRA Study Team TI Infection of CD127(+) (Interleukin-7 receptor(+)) CD4(+) cells and overexpression of CTLA-4 are linked to loss of antigen-specific CD4 T cells during primary human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY HIV-1 INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNOLOGICAL SELF-TOLERANCE; PLASMACYTOID DENDRITIC CELLS; BLOOD MONONUCLEAR-CELLS; HIGH-LEVEL REPLICATION; ACUTE SIV INFECTION; TH1 EFFECTOR-CELLS; IMMUNE-RESPONSES; LYMPHOID-TISSUE AB We recently found that human immunodeficiency virus (HIV)-specific CD4(+) T cells express coreceptor CCR5 and activation antigen CD38 during early primary HIV-1 infection (PHI) but then rapidly disappear from the circulation. This cell loss may be due to susceptibility to infection with HIV-1 but could also be due to inappropriate apoptosis, an expansion of T regulatory cells, trafficking out of the circulation, or dysfunction. We purified CD38(+++)CD4(+) T cells from peripheral blood mononuclear cells, measured their level of HIV-1 DNA by PCR, and found that about 10% of this population was infected. However, a small subset of HIV-specific CD4(+) T cells also expressed CD127, a marker of long-term memory cells. Purified CD127(+)CD4(+) lymphocytes contained fivefold more copies of HIV-1 DNA per cell than did CD127-negative CD4(+) cells, suggesting preferential infection of long-term memory cells. We observed no apoptosis of antigen-specific CD4(+) T cells in vitro and only a small increase in CD45RO(+)CD25(+)CD127dimCD4(+) T regulatory cells during PHI. However, 40% of CCR5(+)CD38(+++)CD4(+) T cells expressed gut-homing integrins, suggesting trafficking through gut-associated lymphoid tissue (GALT). Furthermore, 80% of HIV-specific CD4(+) T cells expressed high levels of the negative regulator CTLA-4 in response to antigen stimulation in vitro, which was probably contributing to their inability to produce interleukin-2 and proliferate. Taken together, the loss of HIV-specific CD4(+) T cells is associated with a combination of an infection of CCR5(+) CD127(+) memory CD4(+) T cells, possibly in GALT, and a high expression of the inhibitory receptor CTLA-4. C1 St Vincents Hosp, Ctr Immunol, Darlinghurst, NSW 2010, Australia. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Univ Sydney, Centenary Inst Canc Med & Cell Biol, Sydney, NSW 2006, Australia. Rush Univ, Chicago, IL 60612 USA. Taylor Sq Private Clin, Sydney, NSW, Australia. RP Zaunders, JJ (reprint author), St Vincents Hosp, Ctr Immunol, Victoria St, Darlinghurst, NSW 2010, Australia. EM j.zaunders@cfi.unsw.edu.au RI Koelsch, Kersten/B-6745-2008; Zaunders, John/J-6553-2012; Kaldor, John /D-4545-2011 OI Koelsch, Kersten/0000-0002-6411-4248; Zaunders, John/0000-0002-5912-5989; NR 99 TC 60 Z9 65 U1 0 U2 6 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 OCT PY 2006 VL 80 IS 20 BP 10162 EP 10172 DI 10.1128/JVI.00249-06 PG 11 WC Virology SC Virology GA 091RU UT WOS:000241046800024 PM 17005693 ER PT J AU Chew, RB Chew, LD Bradley, K AF Chew, Ryan B. Chew, Lisa D. Bradley, Katharine TI The association between number of Pap smears performed and self-reported confidence in an internal medicine residency SO JOURNAL OF WOMENS HEALTH LA English DT Article ID WOMENS HEALTH; AMBULATORY GYNECOLOGY; PROCEDURAL SKILLS; PROGRAM; CARE; EDUCATION; IMPACT AB Background: The American Board of Internal Medicine (ABIM) recommends internal medicine residents perform at least 3-5 Pap smears during training. We evaluated whether doing more than the required minimum Pap smears was associated with greater confidence and less desire for more Pap smear training. Methods: We surveyed all 142 internal medicine residents at one university training program. Participants were asked how many Pap smears they had performed during residency and to rank their confidence and desire for more training in performing Pap smears. We compared confidence and desire for more training across three groups of residents reporting varying experience (<= 5, 6-10, > 10 Pap smears performed). Results: Of 101 responding residents (71% eligible), 42 (42%), 19 (19%), and 36 (36%) reported performing <= 5, 6-10, and > 10 Pap smears, respectively. The number of Pap smears performed was significantly related to confidence and desire for more training in Pap smears (p < 0.05). Of residents who reported <= 5 Pap smears, 64% and 57%, respectively, indicated they were not confident and desired more training. Of those reporting 6-10 Pap smears, 42% were not confident, and 42% desired more training, whereas comparable proportions for those reporting > 10 Pap smears were 14% and 17%, respectively. After adjusting for gender, primary care track, year of training, continuity clinic site, women's health rotation experience, and future plans in primary care, those reporting doing > 10 Pap smears were significantly more likely to report confidence (OR 9.08, 95% CI 2.15-36.26) and less likely to want more training (OR 0.23; 0.06-0.93) than those reporting <= 5 Pap smears. Conclusions: Residents who performed over twice the number of Pap smears recommended by ABIM were much more likely to indicate confidence in their Pap smear skills compared with those completing <= 5. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev S 152, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA. Univ Washington, Div Gen Internal Med, Dept Med, Seattle, WA USA. RP Chew, RB (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev S 152, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM rbchew@hotmail.com FU NIAAA NIH HHS [K23AA00313] NR 14 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 2006 VL 15 IS 8 BP 928 EP 933 DI 10.1089/jwh.2006.15.928 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 104VX UT WOS:000241989800006 PM 17087616 ER PT J AU Ohse, T Inagi, R Tanaka, T Ota, T Miyata, T Kojima, I Ingelfinger, JR Ogawa, S Fujita, T Nangaku, M AF Ohse, T. Inagi, R. Tanaka, T. Ota, T. Miyata, T. Kojima, I. Ingelfinger, J. R. Ogawa, S. Fujita, T. Nangaku, M. TI Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal tubular cells SO KIDNEY INTERNATIONAL LA English DT Article DE end-stage renal disease; proteinuria; caspase; tubulointerstitial injury; calpain ID FACTOR-KAPPA-B; MONOCYTE CHEMOATTRACTANT PROTEIN-1; EPITHELIAL-CELLS; AMINONUCLEOSIDE NEPHROSIS; OVERLOAD PROTEINURIA; ALTERNATIVE PATHWAY; DISTAL NEPHRON; BRUSH-BORDER; ACTIVATION; CALCIUM AB Chronic proteinuria appears to be a key factor in tubulointerstitial damage. Recent studies have emphasized a pathogenic role of endoplasmic reticulum (ER) stress which is induced by the accumulation of misfolded proteins in ER, extracellular stress, etc. In the present study, we investigated ER stress and ER stress-induced apoptosis in proximal tubular cells (PTCs). Immortalized rat PTCs (IRPTCs) were cultured with bovine serum albumin (BSA). The viability of IRPTCs decreased proportionately with BSA overload in a time- dependent manner. Quantitative real-time polymerase chain reaction analysis revealed that 40mg/ml BSA increases mRNA of ER stress markers by 7.7- and 4.6-fold (glucose-regulated protein 78 (GRP78) and oxygen-regulated protein 150 (ORP150), respectively) as compared to control. The increased expression of ORP150 and GRP78 in IRPTCs with albumin overload was detected by Western blot and immunofluorescence study. These in vitro observations were supported by in vivo studies, which demonstrated that ER stress proteins were upregulated at PTCs in experimental proteinuric rats. Furthermore, increased ER stress- induced apoptosis and activation of caspase-12 were observed in IRPTCs with albumin overload and kidneys of experimental proteinuric rats. We confirmed that apoptotic cell death was attenuated by co- incubation with caspase-3 inhibitor or calpain inhibitors. These results indicate that the ER stress-induced apoptosis pathway contributed to the insult of tubular cells by proteinuria. In conclusion, renal tubular cells exposed to high protein load suffer from ER stress. ER stress may subsequently lead to tubular damage by activation of caspase-12. C1 Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 1138655, Japan. Tokai Univ, Inst Med Sci, Isehara, Kanagawa 25911, Japan. Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. Kanazawa Univ, Sch Med, Dept Neuroanat, Kanazawa, Ishikawa 920, Japan. RP Nangaku, M (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM mnangaku-tky@umin.ac.jp RI Miyata, Toshio/A-4872-2010; Nangaku, Masaomi/A-5300-2010 NR 59 TC 108 Z9 124 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2006 VL 70 IS 8 BP 1447 EP 1455 DI 10.1038/sj.ki.5001704 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 092MX UT WOS:000241102300012 PM 16955111 ER PT J AU Bhan, I Shah, A Holmes, J Isakova, T Gutierrez, O Burnett, SA Juppner, H Wolf, M AF Bhan, I. Shah, A. Holmes, J. Isakova, T. Gutierrez, O. Burnett, S-A Jueppner, H. Wolf, M. TI Post-transplant hypophosphatemia: Tertiary 'hyper-phosphatoninism'? SO KIDNEY INTERNATIONAL LA English DT Article DE transplantation; hypophosphatemia; FGF-23; PTH; calcitriol ID FIBROBLAST GROWTH FACTOR-23; RENAL-TRANSPLANT RECIPIENTS; CHRONIC KIDNEY-DISEASE; VITAMIN-D METABOLISM; PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM; IN-VIVO; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ONCOGENIC OSTEOMALACIA; PROTEOLYTIC CLEAVAGE AB Hypophosphatemia is a common complication of kidney transplantation. Tertiary hyperparathyroidism has long been thought to be the etiology, but hypophosphatemia can occur despite low parathyroid hormone (PTH) levels and can persist after high PTH levels normalize. Furthermore, even in the setting of normal allograft function, hypophosphatemia, and hyperparathyroidism, calcitriol levels remain inappropriately low following transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor-23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed a prospective, longitudinal study of 27 living donor transplant recipients to test the hypotheses that excessive FGF-23 accounts for hypophosphatemia and decreased calcitriol levels following kidney transplantation. Hypophosphatemia < 2.5mg/dl developed in 85% of subjects, including one who had previously undergone parathyroidectomy; 37% developed phosphate <= 1.5mg/dl. The mean pre-transplant FGF-23 level was 1,218 +/- 542 RU/ml. Within the first week following transplantation, mean levels decreased to 557 +/- 579 RU/ ml, which were still above normal. FGF-23 was independently associated with serum phosphate (P < 0.01), urinary excretion of phosphate (P < 0.01), and calcitriol levels (P < 0.01); PTH was not independently associated with any of these parameters. We calculated area under the curve for FGF-23 and PTH between the pre- and first post-transplant levels as a summary measure of early exposure to these phosphaturic hormones. An area under the FGF-23 curve greater than the median was associated with a relative risk of developing hypophosphatemia <= 1.5mg/dl of 5.3 (P=0.02) compared with lower levels. Increased area under the PTH curve was not associated with greater risk of hypophosphatemia. Excessive FGF-23 exposure in the early post-transplant period appears to be more strongly associated with post-transplant hypophosphatemia than PTH. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit,Dept Pediat, Boston, MA 02115 USA. RP Wolf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Bartlett 917,55 Fruit St, Boston, MA 02114 USA. EM mswolf@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X FU NCRR NIH HHS [K23RR017376, M01RR01066] NR 51 TC 106 Z9 108 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2006 VL 70 IS 8 BP 1486 EP 1494 DI 10.1038/sj.ki.5001788 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 092MX UT WOS:000241102300018 PM 16941023 ER PT J AU Williams, ME Lacson, E Teng, M Ofsthun, N Lazarus, JM AF Williams, M. E. Lacson, E., Jr. Teng, M. Ofsthun, N. Lazarus, J. M. TI Hemodialyzed type I and type II diabetic patients in the US: Characteristics, glycemic control, and survival SO KIDNEY INTERNATIONAL LA English DT Article DE diabetes; hemodialysis; hyperglycemia; survival; hemoglobin A1c; ESRD ID CHRONIC-RENAL-FAILURE; ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; GLYCOSYLATED HEMOGLOBIN; RISK-FACTORS; GLYCATED HEMOGLOBIN; MORTALITY; GLUCOSE; COMPLICATIONS; MELLITUS AB Diabetes mellitus (DM) constitutes a major end-stage renal disease (ESRD) health problem. Glycemic control is fundamental to the management of diabetes and its complications, and relies on monitoring of hyperglycemia. We therefore performed a primary data analysis of glycemic control and survival on a large national ESRD database. Ninety-five percent of patients with DM had type II diabetes (N = 23 504), and five percent had type I diabetes ( N 1371). For the combined population, the mean hemoglobin A1c (HgbA1c) was 6.77%, and the mean random blood glucose was 168mg/dl. Mean HgbA1c values were > 7.0% in 35% and > 8.5% in 14%. Mean HgbA1c values were below 5% in 11.3% of patients. Type I study patients tended to have higher HgbA1c values. Most patients (75.8%) had three or more random blood glucose determinations within 90 days preceding the HgbA1c measurement. The HgbA1c showed only a weak correlation with mean random glucose values (R-2 0.3716; s.e. = 1.36). The survival rates in the subsequent 12-month period ranged from 80 to 85% across different HgbA1c strata. Kaplan-Meier survival curves grouped by HgbA1c levels showed no correlation between HgbA1c and survival at 12 months. More studies are needed to refine recommendations for the role of HgbA1c and glycemic control in this patient population. C1 Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. Fresenius Med Care, Lexington, MA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 55 TC 109 Z9 113 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2006 VL 70 IS 8 BP 1503 EP 1509 DI 10.1038/sj.ki.5001789 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 092MX UT WOS:000241102300020 PM 16941022 ER PT J AU Kimura, K Song, CH Rastogi, A Dranoff, G Galli, SJ Lantz, CS AF Kimura, Koichi Song, Chang Ho Rastogi, Akhil Dranoff, Glenn Galli, Stephen J. Lantz, Chris S. TI Interleukin-3 and c-Kit/stem cell factor are required for normal eosinophil responses in mice infected with Strongyloides venezuelensis SO LABORATORY INVESTIGATION LA English DT Article DE basophils; host defense; mast cells; Nippostrongylus brasiliensis; parasite immunity ID COLONY-STIMULATING FACTOR; RECEPTOR GENE FAMILY; MAST-CELLS; GM-CSF; NIPPOSTRONGYLUS-BRASILIENSIS; FUNCTIONAL-PROPERTIES; IMMUNE-RESPONSE; DEFICIENT MICE; BETA-SUBUNIT; IN-VIVO AB To evaluate the potential roles of Interleukin-3 (IL-3) and c-Kit, the tyrosine kinase receptor for stem cell factor (SCF), in eosinophil responses in vivo, we examined eosinophil numbers in uninfected or nematode- infected wild-type mice, IL-3 -/- mice, and IL-3 -/- mice that also have a marked reduction in SCF/c-Kit signaling (ie, Kit(W)/Kit(W-v), IL-3 -/- mice). We found no significant differences in the numbers of eosinophils in the blood, bone marrow or various tissues of IL-3 -/- vs IL-3-/- mice, either at baseline or after the induction of bone marrow, blood or tissue eosinophilia in response to infection with Strongyloides venezuelensis (S.v.) or Nippostrongylus brasiliensis (N.b.). However, in mice with markedly impaired SCF/c-Kit signaling, IL-3 contributed significantly to the increased numbers of eosinophils that were observed in multiple tissues during S. v. infection, but not during infection with N.b. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Kurume Univ, Sch Med, Dept Pediat & Child Hlth, Kurume, Fukuoka 830, Japan. James Madison Univ, Dept Biol, Harrisonburg, VA 22807 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Galli, SJ (reprint author), Stanford Univ, Sch Med, Dept Pathol, L235,300 Pasteur Dr, Stanford, CA 94305 USA. EM sgalli@stanford.edu FU NCI NIH HHS [CA72074]; NHLBI NIH HHS [P50 HL067674]; NIAID NIH HHS [AI49932, R01 AI023990, AI23990] NR 44 TC 7 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 2006 VL 86 IS 10 BP 987 EP 996 DI 10.1038/labinvest.3700458 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 088AQ UT WOS:000240784300002 PM 16894356 ER PT J AU Robicsek, A Jacoby, GA Hooper, DC AF Robicsek, Ari Jacoby, George A. Hooper, David C. TI The worldwide emergence of plasmid-mediated quinolone resistance SO LANCET INFECTIOUS DISEASES LA English DT Review ID SPECTRUM BETA-LACTAMASE; SHIGELLA-DYSENTERIAE TYPE-1; GRAM-NEGATIVE BACTERIA; INTENSIVE-CARE UNITS; ESCHERICHIA-COLI; DNA GYRASE; KLEBSIELLA-PNEUMONIAE; SALMONELLA-ENTERICA; FLUOROQUINOLONE RESISTANCE; STREPTOCOCCUS-PNEUMONIAE AB Fluoroquinolone resistance is emerging in Gram-negative pathogens worldwide. The traditional understanding that quinolone resistance is acquired only through mutation and transmitted only vertically does not entirely account for the relative ease with which resistance develops in exquisitely susceptible organisms, or for the very strong association between resistance to quinolones and to other agents. The recent discovery of plasmid-mediated horizontally transferable genes encoding quinolone resistance might shed light on these phenomena. The Qnr proteins, capable of protecting DNA gyrase from quinolones, have homologues in water-dwelling bacteria, and seem to have been in Circulation for some time, having achieved global distribution in a variety of plasmid environments and bacterial genera. AAC(6')-Ib-cr, a variant aminoglycoside acetyltransferase capable of modifying ciprofloxacin and reducing its activity, seems to have emerged more recently, but might be even more prevalent than the Qnr proteins. Both mechanisms provide low-level quinolone resistance that facilitates the emergence of higher-level resistance in the presence of quinolones at therapeutic levels. Much remains to be understood about these genes, but their insidious promotion of substantial resistance, their horizontal spread, and their co-selection with other resistance elements indicate that a more cautious approach to quinolone use and a reconsideration of clinical breakpoints are needed. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Lahey Clin Fdn, Burlington, MA USA. Evanston Northwestern Healthcare, Evanston, IL USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [AI43312, AI57576, R01 AI057576] NR 77 TC 447 Z9 486 U1 11 U2 72 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD OCT PY 2006 VL 6 IS 10 BP 629 EP 640 DI 10.1016/S1473-3099(06)70599-0 PG 12 WC Infectious Diseases SC Infectious Diseases GA 089XD UT WOS:000240914300016 PM 17008172 ER PT J AU Ghanem, MA Monroy, A Alizadeh, FS Nicolau, Y Eavey, RD AF Ghanem, Marcielle A. Monroy, Angelo Alizadeh, Farmarz S. Nicolau, Yamileth Eavey, Roland D. TI Butterfly cartilage graft inlay tympanoplasty for large perforations SO LARYNGOSCOPE LA English DT Article DE tympanic membrane perforation; tympanoplasty; butterfly graft; cartilage graft; inlay graft AB Objective: Butterfly graft inlay tympanoplasty is a well-established technique for the repair of small perforations. However, the efficacy of the technique for medium and large tympanic membrane perforations remains unknown. Study Design: Retrospective case series. Methods: Postauricular tympanoplasty and tympanomastoidectomy using a large butterfly cartilage inlay graft (>4 mm diameter to total drum replacement) were analyzed in 90 pediatric patients (99 ears). Results: Patient ages ranged from 2 to 20 years; mean follow-up duration was 27.6 months. Successful closure occurred in 92% of the ears. No graft lateralized nor displaced into the middle ear. No retraction pocket occurred during the follow-up period. In 62 cases, intact canal wall or canal wall window tympanomastoidectomy was performed; Fifty-one (82.2%) of the patients having mastoidectomy procedures had chronic otitis media with cholesteatoma. The mean preoperative to postoperative four-tone air-bone gap improved from 23 to 21 dB; the number of patients with 0 to 10 dB hearing results increased from 16 ears preoperatively to 32 ears postoperatively. Postoperative suboptimal results included eight patients with postoperative perforations in the residual tympanic membrane adjacent to an intact cartilage graft; two of these patients were the only individuals who exhibited otorrhea. Conclusions: Cartilage butterfly graft inlay tympanoplasty is effective in the vast majority of patients with moderate to large perforations. The closure rate exceeded 90% with no graft displacement, postoperative adverse events were respectably low, and hearing results improved or remained stable despite the need for concurrent mastoidectomy in the majority of patients. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM roland_eavey@meei.harvard.edu NR 15 TC 30 Z9 33 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2006 VL 116 IS 10 BP 1813 EP 1816 DI 10.1097/01.mlg.0000231742.11048.ed PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 090ER UT WOS:000240933900018 PM 17003724 ER PT J AU Savasan, S Buck, S Raimondi, SC Becton, DL Weinstein, H Chang, M Ravindranath, Y AF Savasan, Suereyya Buck, Steven Raimondi, Susana C. Becton, David L. Weinstein, Howard Chang, Myron Ravindranath, Yaddanapudi TI CD36 (thrombospondin receptor) expression in childhood acute megakaryoblastic leukemia: In vitro drug sensitivity and outcome SO LEUKEMIA & LYMPHOMA LA English DT Article DE megakaryoblastic leukemia; CD36; cytarabine; daunorubicin; drug sensitivity; immunophenotype; Down syndrome ID ACUTE MYELOID-LEUKEMIA; TRANSIENT MYELOPROLIFERATIVE DISORDER; ACUTE MYELOBLASTIC-LEUKEMIA; DOWN-SYNDROME CHILDREN; CYTOSINE-ARABINOSIDE; LYMPHOBLASTIC-LEUKEMIA; GATA1 MUTATION; BLAST CELLS; DIFFERENTIATION; EXPERIENCE AB The outcome for children with acute megakaryoblastic leukemia (AMKL) remains poor, except for cases associated with Down syndrome (DS). This study compared immunophenotypic and drug sensitivity patterns of childhood AMKL cases with or without DS. All DS-AMKL cases showed high expression of CD36 and were very sensitive to cytarabine and daunorubicin in vitro. In children without DS, high expression of CD36 on AMKL blasts identified a sub-group with immunophenotypic and drug sensitivity patterns similar to that of DS AMKL. Among non-DS AMKL patients, CD36-high cases had a superior outcome compared with CD36-negative cases. CD36 expression in acute myeloid leukemia cases other than AMKL was not associated with increased in vitro drug sensitivity. CD36 expression in AMKL may be an indicator of megakaryoblast maturation and chemotherapy sensitivity. C1 Wayne State Univ, Childrens Hosp Michigan, Div Hematol Oncol, Barbara Ann Karmanos Canc Inst,Carman Ann Adams D, Detroit, MI 48201 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Childrens Oncol Grp, Gainesville, FL USA. RP Savasan, S (reprint author), Wayne State Univ, Childrens Hosp Michigan, Div Hematol Oncol, Barbara Ann Karmanos Canc Inst,Carman Ann Adams D, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM ssavasan@med.wayne.edu FU NCI NIH HHS [CA-21765, U10 CA 30969] NR 34 TC 10 Z9 12 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 2006 VL 47 IS 10 BP 2076 EP 2083 DI 10.1080/10428190600773180 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 099GR UT WOS:000241581800016 PM 17071479 ER PT J AU Freeman, RB Mithoefer, A Ruthazer, R Nguyen, K Schore, A Harper, A Edwards, E AF Freeman, Richard B. Mithoefer, Abigail Ruthazer, Robin Nguyen, Khanh Schore, Anthony Harper, Ann Edwards, Erick TI Optimizing staging for hepatocellular carcinoma before liver transplantation: A retrospective analysis of the UNOS/OPTN database SO LIVER TRANSPLANTATION LA English DT Article ID CIRRHOTIC LIVERS; HELICAL CT; MRI; SURVIVAL; NODULES; DISEASE AB Assignment of liver allocation priority for hepatocellular carcinoma is predicated on accurate imaging staging. We analyzed radiographically defined stage (radiologic stage (RS]) at listing and most recent extension and pathologic stage (PS) data from 789 liver transplant recipients for whom no pretransplant ablative treatment was given. There were no predetermined imaging or pathological protocols in this retrospective analysis of wait list data. Seventy-two (9.1%), 690 (87.5%), and 27 (3.4%) were listed as stage 1, 2 and >2, respectively. Computed tomography (CT) scan alone (46.4%), magnetic resonance image scan alone (37.1%), ultrasound alone (1.3%), and multiple imaging studies (15.2%) were used with no difference in time to transplant for listing or most recent scan among the recipient groups. Overall accuracy (RS = PS) was 44.1% and was not different if original listing RS or most recent RS was used for comparison with PS. No one type of imaging technique had superior accuracy (P = 0.13); however, CT scan used alone or in combination compared to not being used at all, had higher odds of being accurate (odds ratio [OR] 1.38 [1.03-1.84], P = 0.031). In addition, imaging done less than 90 days before transplant had higher odds of being accurate (OR 1.49 [1.06-2.08], P = 0.019) as did RS = 2 or 3 (OR 5.56 [2.70-11.11], P < 0.0001). We observed considerable variation in RS accuracy among the United Network for Organ Sharing and Organ Procurement and Transplantation Network regions that is unexplained. In conclusion, current imaging requirements for IRS prior to liver transplantation are unacceptably inaccurate. Future policy should require more accurate modalities or combinations of techniques. C1 Tufts New England Med Ctr, Dept Surg, Div Transplantat, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Med, Div Hepatol, Boston, MA 02114 USA. Tufts New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. United Network Organ Sharing, Res Dept, Richmond, VA USA. RP Freeman, RB (reprint author), Tufts New England Med Ctr, Div Transplant Surg, Box 40,750 Washington St, Boston, MA 02111 USA. EM rfreeman@tufts-nemc.org NR 19 TC 76 Z9 79 U1 0 U2 0 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 OCT PY 2006 VL 12 IS 10 BP 1504 EP 1511 DI 10.1002/lt.20847 PG 8 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 097LX UT WOS:000241450400013 PM 16952174 ER PT J AU Bueno, R Dong, L Richards, WG Yeap, B Mani, M Alsup, C Sugarbaker, DJ Gordon, GJ AF Bueno, R. Dong, L. Richards, W. G. Yeap, B. Mani, M. Alsup, C. Sugarbaker, D. J. Gordon, G. J. TI Prognostic gene ratio test for mesothelioma validated in a prospective clinical trial SO LUNG CANCER LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2006 VL 54 SU 1 MA 63 BP S16 EP S16 DI 10.1016/S0169-5002(07)70139-3 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 103PY UT WOS:000241900400064 ER PT J AU Janne, PA Wang, XF Krug, LM Hodgson, L Vokes, EE Kindler, HL AF Janne, P. A. Wang, X. F. Krug, L. M. Hodgson, L. Vokes, E. E. Kindler, H. L. TI Phase II trial of sorafenib (BAY 43-9006) in malignant mesothelioma: CALGB 30307 SO LUNG CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2006 VL 54 SU 1 MA 211 BP S51 EP S52 DI 10.1016/S0169-5002(07)70287-8 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 103PY UT WOS:000241900400211 ER PT J AU Janne, P AF Janne, P. A. TI Proteomic methods to identify novel therapeutic targets in malignant mesothelioma SO LUNG CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2006 VL 54 SU 1 MA 61 BP S15 EP S15 DI 10.1016/S0169-5002(07)70137-X PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 103PY UT WOS:000241900400062 ER PT J AU Liu, YT D'Arceuil, H He, JL Duggan, M Gonzalez, G Pryor, J de Crespigny, A AF Liu, Yutong D'Arceuil, Helen He, Julian Duggan, Mike Gonzalez, Gilbert Pryor, Johnny de Crespigny, Alex TI A nonlinear mesh-warping technique for correcting brain deformation after stroke SO MAGNETIC RESONANCE IMAGING LA English DT Article DE warping; MRI; histology; stroke ID MEDICAL IMAGE REGISTRATION; THIN-PLATE SPLINES; ELASTIC REGISTRATION; TEMPORAL EVOLUTION; MR-IMAGES; DIFFUSION; VALIDATION; ACCURACY; TRANSFORMATION; PERFUSION AB This article presents a warping technique for correcting brain tissue distortion on magnetic resonance imaging (MRI) scans due to stroke lesion growth and for mapping MRI scans to histological sections. Meshes are imposed upon the images for feature specification, and these features are exactly matched in the different images to be mapped, while the other voxels are matched by interpolation. This technique was tested on serial MR images and histological sections that were acquired in a nonhuman primate model of stroke. This technique was able to deliver satisfactory warping results. It is simple and robust and can be utilized in many applications for comparison of multimodality medical images and histological sections. (C) 2006 Elsevier Inc. All rights reserved. C1 AA Martinos Ctr, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Comparat Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurosurg, Endovasc Neuroradiol Sect, Boston, MA 02114 USA. RP de Crespigny, A (reprint author), AA Martinos Ctr, Dept Radiol, Charlestown, MA 02129 USA. EM alexdec@nmr.mgh.harvard.edu FU NINDS NIH HHS [1R01-NS41285] NR 35 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD OCT PY 2006 VL 24 IS 8 BP 1069 EP 1075 DI 10.1016/j.mri.2006.07.007 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 094QG UT WOS:000241253500011 PM 16997077 ER PT J AU Lin, FH Wald, LL Ahlfors, SP Hamalainen, MS Kwong, KK Belliveau, JW AF Lin, Fa-Hsuan Wald, Lawrence L. Ahlfors, Seppo P. Hamalainen, Matti S. Kwong, Kenneth K. Belliveau, John W. TI Dynamic magnetic resonance inverse imaging of human brain function SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; inverse; parallel MRI; magnetoencephalography; minimum-norm; MNE; dSPM; InI; electroencephalgraphy ID NEURONAL-ACTIVITY; MRI; ACQUISITION; FMRI; COIL; RECONSTRUCTION; SENSE; MAGNETOENCEPHALOGRAPHY; OXYGENATION; SIGNAL AB MRI is widely used for noninvasive hemodynamic-based functional brain imaging. In traditional spatial encoding, however, gradient switching limits the temporal resolution, which makes it difficult to unambiguously identify possible fast nonhemodynamic changes. In this paper we propose a novel reconstruction approach, called dynamic inverse imaging (InI), that is capable of providing millisecond temporal resolution when highly parallel detection is used. To achieve an order-of-magnitude speedup in generating time-resolved contrast estimates and dynamic statistical parametric maps (dSPMs), the spatial information is derived from an array of detectors rather than by time-consuming gradient-encoding methods. The InI approach was inspired by electroencephalography (EEG) and magnetoencephalography (MEG) source localization techniques. Dynamic MR InI was evaluated by means of numerical simulations. InI was also applied to measure BOLD hemodynamic time curves at 20-ms temporal resolution in a visual stimulation experiment using a 90-channel head array. InI is expected to improve the time resolution of MRI and provide increased flexibility in the trade-off between spatial and temporal resolution for studies of dynamic activation patterns in the human brain. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Lin, FH (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM fhlin@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; Lin, Fa-Hsuan/G-6988-2012; Wald, Lawrence/D-4151-2009; Ahlfors, Seppo/P-3644-2016 OI Lin, Fa-Hsuan/0000-0002-9539-1731; FU NCRR NIH HHS [P41 RR14075]; NIBIB NIH HHS [R01 EB00079004]; NICHD NIH HHS [R01 HD040712]; NINDS NIH HHS [R01 NS037462] NR 43 TC 57 Z9 57 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD OCT PY 2006 VL 56 IS 4 BP 787 EP 802 DI 10.1002/mrm.20997 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 089QZ UT WOS:000240897000011 PM 16964616 ER PT J AU Peterfy, M Mao, HZ Doolittle, MH AF Peterfy, Miklos Mao, Hui Z. Doolittle, Mark H. TI The cld mutation: narrowing the critical chromosomal region and selecting candidate genes SO MAMMALIAN GENOME LA English DT Article ID COMBINED LIPASE DEFICIENCY; MOUSE T-COMPLEX; LIPOPROTEIN-LIPASE; ENDOPLASMIC-RETICULUM; HEPATIC LIPASE; LETHAL MUTATION; T/T COMPLEX; MICE; HAPLOTYPES; EXPRESSION AB Combined lipase deficiency (cld) is a recessive, lethal mutation specific to the t(w73) supercript stop haplotype on mouse Chromosome 17. While the cld mutation results in lipase proteins that are inactive, aggregated, and retained in the endoplasmic reticulum (ER), it maps separately from the lipase structural genes. We have narrowed the gene critical region by about 50% using the t(w18) supercript stop haplotype for deletion mapping and a recombinant chromosome used originally to map cld with respect to the phenotypic marker tf. The region now extends from 22 to 25.6 Mbp on the wild-type chromosome, currently containing 149 genes and 50 expressed sequence tags (ESTs). To identify the affected gene, we have selected candidates based on their known role in associated biological processes, cellular components, and molecular functions that best fit with the predicted function of the cld gene. A secondary approach was based on differences in mRNA levels between mutant (cld/cld) and unaffected (+/cld) cells. Using both approaches, we have identified seven functional candidates with an ER localization and/or an involvement in protein maturation and folding that could explain the lipase deficiency, and six expression candidates that exhibit large differences in mRNA levels between mutant and unaffected cells. Significantly, two genes were found to be candidates with regard to both function and expression, thus emerging as the strongest candidates for cld. We discuss the implications of our mapping results and our selection of candidates with respect to other genes, deletions, and mutations occurring in the cld critical region. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Doolittle, MH (reprint author), Greater Los Angeles VA Healthcare Ctr, Dept Med, 11301 Wilshire Blvd,Bldg 113,Room 312, Los Angeles, CA 90073 USA. EM markdool@ucla.edu FU NHLBI NIH HHS [HL28481] NR 54 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD OCT PY 2006 VL 17 IS 10 BP 1013 EP 1024 DI 10.1007/s00335-006-0045-3 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 093JS UT WOS:000241165200003 PM 17019649 ER PT J AU Shrank, WH Asch, SM Adams, J Setodji, C Kerr, EA Keesey, J Malik, S McGlynn, EA AF Shrank, William H. Asch, Steven M. Adams, John Setodji, Claude Kerr, Eve A. Keesey, Joan Malik, Shaista McGlynn, Elizabeth A. TI The quality of pharmacologic care for adults in the United States SO MEDICAL CARE LA English DT Article DE quality; prescription drugs; prescribing; underuse ID ADVERSE DRUG EVENTS; MEDICARE BENEFICIARIES; HEART-FAILURE; OF-CARE; RACIAL-DIFFERENCES; AMBULATORY-CARE; HEALTH-CARE; RACE; COST; RISK AB Background: Despite rising annual expenditures for prescription drugs, little systematic information is available concerning the quality of pharmacologic care for adults in the United States. We evaluated how frequently appropriate pharmacologic care is ordered in a national sample of U.S. residents. Methods: The RAND/UCLA Modified Delphi process was used to select quality-of-care indicators for adults across 30 chronic and acute conditions and preventive care. One hundred thirty-three pharmacologic quality-of-care indicators were identified. We interviewed a random sample of adults living in 12 metropolitan areas in the United States by telephone and received consent to obtain copies of their medical records for the most recent 2-year period. We abstracted patient medical records and evaluated 4 domains of the prescribing process that encompassed the entire pharmacologic care experience: appropriate medication prescribing (underuse), avoidance of inappropriate medications (overuse), medication monitoring, and medication education and documentation. A total of 3457 participants were eligible for at least 1 quality indicator, and 10,739 eligible events were evaluated. We constructed aggregate scores and studied whether patient, insurance, and community factors impact quality. Results: Participants received 61.9% of recommended pharmacologic care overall (95% confidence interval 60.3-63.5%). Performance was lowest in education and documentation (46.2%); medication monitoring (54.7%) and under-use of appropriate medications (62.6%) performance were higher. Performance was best for avoiding inappropriate medications (83.5%). Patient race and health services utilization were associated with modest quality differences, while insurance status was not. Conclusions: Significant deficits in the quality of pharmacologic care were seen for adults in the United States, with large shortfalls associated with underuse of appropriate medications. Strategies to measure and improve phannacologic care quality ought to be considered, especially as we initiate a prescription drug benefit for seniors. C1 Brigham & Womens Hosp, Div Pharmacoepideiol & Pharmacoecon, Boston, MA 02120 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. VA Ann Arbor Healthcare Syst, Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Calif Irvine, Dept Med, Div Cardiol, Irvine Sch Med, Irvine, CA 92717 USA. RP Shrank, WH (reprint author), Brigham & Womens Hosp, Div Pharmacoepideiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM wshrank@partners.org RI Kim, Hyung Woo /G-7525-2011 NR 42 TC 51 Z9 51 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 2006 VL 44 IS 10 BP 936 EP 945 DI 10.1097/01.mlr.0000223460.60033.79 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 092RR UT WOS:000241115500008 PM 17001265 ER PT J AU Suzuki, K Yoshida, H Nappi, J Dachman, AH AF Suzuki, Kenji Yoshida, Hiroyuki Nappi, Janne Dachman, Abraham H. TI Massive-training artificial neural network (MTANN) for reduction of false positives in computer-aided detection of polyps: Suppression of rectal tubes SO MEDICAL PHYSICS LA English DT Article DE virtual colonoscopy; colon cancer; CT colonography; computer-aided detection; pattern recognition; artificial neural network ID CT COLONOGRAPHY; COLONIC POLYPS; LUNG NODULES; TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; VOLUMETRIC FEATURES; AUTOMATED DETECTION; DIAGNOSTIC SCHEME; CHEST RADIOGRAPHS; SMALL NUMBER AB One of the limitations of the current computer-aided detection (CAD) of polyps in CT colonography (CTC) is a relatively large number of false-positive (FP) detections. Rectal tubes (RTs) are one of the typical sources of FPs because a portion of a RT, especially a portion of a bulbous tip, often exhibits a cap-like shape that closely mimics the appearance of a small polyp. Radiologists can easily recognize and dismiss RT-induced FPs; thus, they may lose their confidence in CAD as an effective tool if the CAD scheme generates such "obvious" FPs due to RTs consistently. In addition, RT-induced FPs may distract radiologists from less common true positives in the rectum. Therefore, removal RT induced FPs as well as other types of FPs is desirable while maintaining a high sensitivity in the detection of polyps. We developed a three-dimensional (3D) massive-training artificial neural network (MTANN) for distinction between polyps and RTs in 3D CTC volumetric data. The 3D MTANN is a supervised volume-processing technique which is trained with input CTC volumes and the corresponding "teaching" volumes. The teaching volume for a polyp contains a 3D Gaussian distribution, and that for a RT contains zeros for enhancement of polyps and suppression of RTs, respectively. For distinction between polyps and nonpolyps including RTs, a 3D scoring method based on a 3D Gaussian weighting function is applied to the output of the trained 3D MTANN. Our database consisted of CTC examinations of 73 patients, scanned in both supine and prone positions (146 CTC data sets in total), with optical colonoscopy as a reference standard for the presence of polyps. Fifteen patients had 28 polyps; 15 of which were 5-9 mm and 13 were 10-25 mm in size. These CTC cases were subjected to our previously reported CAD scheme that included centerline-based segmentation of the colon, shape-based detection of polyps, and reduction of FPs by use of a Bayesian neural network based on geometric and texture features. Application of this CAD scheme yielded 96.4% (27/28) by-polyp sensitivity with 3.1 (224/73) Fps per patient, among which 20 FPs were caused by RTs. To eliminate the FPs due to RTs and possibly other normal structures, we trained a 3D MTANN with ten representative polyps and ten RTs, and applied the trained 3D MTANN, to the above CAD true- and false-positive detections. In the output volumes of the 3D MTANN, polyps were represented by distributions of bright voxels, whereas RTs and other normal structures partly similar to RTs appeared as darker voxels, indicating the ability of the 3D MTANN to suppress RTs as well as other normal structures effectively. Application of the 3D MTANN to the CAD detections showed that the 3D MTANN eliminated all RT-induced 20 FPs, as, well as 53 FPs due to other causes, without removal of any true positives. Overall, the 3D MTANN was able to reduce the FP rate of the CAD scheme from 3.1 to 2.1 FPs per patient (33% reduction), while the original by-polyp sensitivity of 96.4% was maintained. (c) 2006 American Association of Physicists in Medicine. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Suzuki, K (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM suzuki@uchicago.edu RI Suzuki, Kenji/A-1284-2007 OI Suzuki, Kenji/0000-0002-3993-8309 NR 46 TC 60 Z9 61 U1 0 U2 4 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 OCT PY 2006 VL 33 IS 10 BP 3814 EP 3824 DI 10.1118/1.2349839 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 097CN UT WOS:000241424100023 PM 17089846 ER PT J AU Keall, PJ Mageras, GS Balter, JM Emery, RS Forster, KM Jiang, SB Kapatoes, JM Low, DA Murphy, MJ Murray, BR Ramsey, CR Van Herk, MB Vedam, SS Wong, JW Yorke, E AF Keall, Paul J. Mageras, Gig S. Balter, James M. Emery, Richard S. Forster, Kenneth M. Jiang, Steve B. Kapatoes, Jeffrey M. Low, Daniel A. Murphy, Martin J. Murray, Brad R. Ramsey, Chester R. Van Herk, Marcel B. Vedam, S. Sastry Wong, John W. Yorke, Ellen TI The management of respiratory motion in radiation oncology report of AAPM Task Group 76 SO MEDICAL PHYSICS LA English DT Review ID CELL LUNG-CANCER; INSPIRATION BREATH-HOLD; TIME TUMOR-TRACKING; VOLUME HISTOGRAM ANALYSIS; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; HIGH-FREQUENCY VENTILATION; FLUENCE-CONVOLUTION METHOD; INTERNAL TARGET VOLUME; INTRA-FRACTION-MOTION; IMRT DOSE DELIVERY AB This document is the report of a task group of the AAPM and has been prepared primarily to advise medical physicists involved in the external-beam radiation therapy of patients with thoracic, abdominal, and pelvic tumors affected by respiratory motion. This report describes the magnitude of respiratory motion, discusses radiotherapy specific problems caused by respiratory motion, explains techniques that explicitly manage respiratory motion during radiotherapy and gives recommendations in the application of these techniques for patient care, including quality assurance (QA) guidelines for these devices and their use with conformal and intensity modulated radiotherapy. The technologies covered by this report are motion-encompassing methods, respiratory gated techniques, breath-hold techniques, forced shallow-breathing methods, and respiration-synchronized techniques. The main outcome of this report is a clinical process guide for managing respiratory motion. Included in this guide is the recommendation that tumor motion should be measured (when possible) for each patient for whom respiratory motion is a concern. If target motion is greater than 5 mm, a method of respiratory motion management is available, and if the patient can tolerate the procedure, respiratory motion management technology is appropriate. Respiratory motion management is also appropriate when the procedure will increase normal tissue sparing. Respiratory motion management involves further resources, education and the development of and adherence to QA procedures. (c) 2006 American Association of Physicists in Medicine. C1 Virginia Commonwealth Univ, Richmond, VA 23284 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas, SW Med Ctr, Austin, TX 78712 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, St Louis, MO 63130 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Keall, PJ (reprint author), Virginia Commonwealth Univ, Richmond, VA 23284 USA. EM PauI.Keall@stanford.edu RI van Herk, Marcel/P-6307-2015; OI van Herk, Marcel/0000-0001-6448-898X; Mageras, Gikas/0000-0001-9851-4306 NR 204 TC 795 Z9 805 U1 7 U2 60 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 OCT PY 2006 VL 33 IS 10 BP 3874 EP 3900 DI 10.1118/1.2349696 PG 27 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 097CN UT WOS:000241424100028 PM 17089851 ER PT J AU Campo-Ruiz, V Patel, D Anderson, RR Delgado-Baeza, E Gonzalez, S AF Campo-Ruiz, Vanessa Patel, Dinesh Anderson, R. Rox Delgado-Baeza, Emilio Gonzalez, Salvador TI Virtual biopsy of the joint tissues using near-infrared, reflectance confocal microscopy. A pilot study SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE knee; ligament; bone; muscle; meniscus; cartilage; orthopedics; medical imaging ID SCANNING LASER MICROSCOPY; IN-VIVO; HUMAN SKIN; HISTOLOGY; CONTRAST AB Standard noninvasive imaging techniques applied to joints provide gross morphological features, insufficient for assessing histological detail. On the other hand, biopsying is invasive, time consuming, and may involve unwanted processing artifacts. Near-infrared reflectance confocal microscopy is a technique that allows serial, high-resolution optical sectioning through intact tissues without employing exogenous fluorescent stains. The aim of this work was to evaluate the potential utility of near-infrared reflectance confocal microscopy for providing immediate histological information on meniscus, articular cartilage, epiphyseal plate, bone, muscle, and tendon. Images from near-infrared reflectance confocal microscopy were compared with mirror routine histology sections. Characteristic architectural features were readily visualized in the three dimensions of space. Additionally, the use of experimental contrast agents highlighted the localization of nuclei. Limitations include penetration depth and minor optical artifacts. In conclusion, near-infrared reflectance confocal microscopy is a useful technique for immediate, nondestructive, serial "virtual" sectioning through intact tissues, being thus a potential adjunct to current imaging techniques in orthopedics. C1 Mem Sloan Kettering Canc Ctr, Dept Dermatol, New York, NY 10022 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Autonoma Madrid, Sch Med, Dept Morphol Histol, Orthopaed Res Unit, Madrid, Spain. RP Gonzalez, S (reprint author), Mem Sloan Kettering Canc Ctr, Dept Dermatol, 160 E 53rd St,Floor 2, New York, NY 10022 USA. EM gonzals6@mskee.org NR 20 TC 1 Z9 1 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD OCT PY 2006 VL 69 IS 10 BP 794 EP 798 DI 10.1002/jemt.20348 PG 5 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 094TH UT WOS:000241261400004 PM 16758475 ER PT J AU Wong, WC Brandt, L Keenan, ME AF Wong, Waichi Brandt, Lynda Keenan, M. Edward TI Massachusetts General Hospital participation in operation unified assistance for tsunami relief in Banda Aceh, Indonesia SO MILITARY MEDICINE LA English DT Article AB When Project HOPE invited Massachusetts General Hospital (MGH) to participate in a tsunami relief mission aboard the USNS Mercy hospital ship in January 2005, MGH responded swiftly and enthusiastically. Overcoming differences in medical styles and standards, as well as a variety of cultural and institutional differences, MGH volunteers collaborated successfully with Navy personnel and volunteers from other hospitals to deliver excellent care to a large number of tsunami victims. Lessons were learned regarding the need for better initial team orientation, more-open communication, and more-transparent decision-making; still, a rapid response of tertiary medicine, joining public and private resources, proved to be a powerful effective model. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wong, WC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 1 U2 2 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 OCT PY 2006 VL 171 IS 10 SU 1 BP 37 EP 39 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 096ZK UT WOS:000241415400015 PM 17447621 ER PT J AU Moon, NS Di Stefano, L Dyson, N AF Moon, Nam-Sung Di Stefano, Luisa Dyson, Nicholas TI A gradient of epidermal growth factor receptor signaling determines the sensitivity of rbf1 mutant cells to E2F-dependent apoptosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DROSOPHILA EGF RECEPTOR; E2F FAMILY; TRANSCRIPTION FACTORS; SUPPRESSES APOPTOSIS; RETINAL DEVELOPMENT; TUMOR-SUPPRESSOR; EYE DEVELOPMENT; NERVOUS-SYSTEM; MICE DEFICIENT; S-PHASE AB The inactivation of retinoblastoma (Rb) family members sensitizes cells to apoptosis. This cell death affects the development of mutant animals and also provides a critical constraint to the malignant potential of Rb mutant tumor cells. The extent of apoptosis caused by the inactivation of Rb is highly cell type and tissue specific, but the underlying reasons for this variation are poorly understood. Here, we characterize a specific time and place during Drosophila melanogaster development where rbf1 mutant cells are exquisitely sensitive to apoptosis. During the third larval instar, many rbf1] mutant cells undergo E2F-dependent cell death in the morphogenetic furrow. Surprisingly, this pattern of apoptosis is not caused by inappropriate cell cycle progression but instead involves the action of Argos, a secreted protein that negatively regulates Drosophila epidermal growth factor receptor (EGFR [DER]) activity. Apoptosis of rbf1] mutant cells is suppressed by the activation of DER, ras, or raf or by the inactivation of argos, sprouty, or gap], and inhibition of DER strongly enhances apoptosis in rbf1 mutant discs. We show that RBF1 and a DER/ras/raf signaling pathway cooperate in vivo to suppress E2F-dependent apoptosis and that the loss of RBF1 alters a normal program of cell death that is controlled by Argos and DER. These results demonstrate that a gradient of DER/ras/raf signaling that occurs naturally during development provides the contextual signals that determine when and where the inactivation of rbf1 results in dE2F1-dependent apoptosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Res Ctr, Charlestown, MA 02129 USA. RP Dyson, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Res Ctr, Bldg 149, Charlestown, MA 02129 USA. EM Dyson@helix.mgh.harvard.edu FU NCI NIH HHS [CA64402, P01 CA095281, P01CA095281, R01 CA064402]; NIGMS NIH HHS [GM53203, R01 GM053203] NR 76 TC 47 Z9 47 U1 1 U2 5 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 OCT PY 2006 VL 26 IS 20 BP 7601 EP 7615 DI 10.1128/MCB.00836-06 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 094PU UT WOS:000241252300022 PM 16954388 ER PT J AU Pacheco, TR Moita, LF Gomes, AQ Hacohen, N Carmo-Fonseca, M AF Pacheco, Teresa Raquel Moita, Luis Ferreira Gomes, Anita Quintal Hacohen, Nir Carmo-Fonseca, Maria TI RNA interference knockdown of hU2AF(35) impairs cell cycle progression and modulates alternative splicing of Cdc25 transcripts SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID FACTOR U2AF(35); IN-VIVO; CAENORHABDITIS-ELEGANS; MAMMALIAN-CELLS; GENE-EXPRESSION; SMALL-SUBUNIT; SEX-LETHAL; SITE AG; PHOSPHATASES; MITOSIS AB U2AF is a heterodimeric splicing factor composed of a large (U2AF(65)) and a small (U2AF(35)) subunit. In humans, alternative splicing generates two U2AF(35) variants, U2AF(35)a and U2AF(35)b. Here, we used RNA interference to specifically ablate the expression of each isoform in HeLa cells. Our results show that knockdown of the major U2AF(35)a isoform reduced cell viability and impaired mitotic progression, leading to accumulation of cells in prometaphase. Microarray analysis revealed that knockdown of U2AF(35)a affected the expression level of similar to 500 mRNAs, from which > 90% were underrepresented relative to the control. Among mRNAs underrepresented in U2AF(35)a-depleted cells we identified an essential cell cycle gene, Cdc27, for which there was an increase in the ratio between unspliced and spliced RNA and a significant reduction in protein level. Furthermore, we show that depletion of either U2AF(35)a or U2AF(35)b altered the ratios of alternatively spliced isoforms of Cdc25B and Cdc25C transcripts. Taken together our results demonstrate that U2AF(35)a is essential for HeLa cell division and suggest a novel role for both U2AF(35) protein isoforms as regulators of alternative splicing of a specific subset of genes. C1 Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Univ Madeira, Dept Ciencias Saude, P-9000390 Funchal, Portugal. RP Carmo-Fonseca, M (reprint author), Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal. EM carmo.fonseca@fm.ul.pt RI Moita, Luis/L-1296-2013; Gomes, Anita/C-3580-2014; OI Moita, Luis/0000-0003-0707-315X; Gomes, Anita/0000-0002-3348-0448; Carmo-Fonseca, Maria/0000-0002-3402-7143; Pacheco, Teresa/0000-0002-5506-0233 NR 45 TC 45 Z9 45 U1 0 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD OCT PY 2006 VL 17 IS 10 BP 4187 EP 4199 DI 10.1091/mbc.E06-01-0036 PG 13 WC Cell Biology SC Cell Biology GA 092HJ UT WOS:000241087300004 PM 16855028 ER PT J AU Kono, M Dunn, IS Durda, PJ Butera, D Rose, LB Haggerty, TJ Benson, EM Kurnick, JT AF Kono, Michihiro Dunn, Ian S. Durda, Paul J. Butera, David Rose, Lenora B. Haggerty, Timothy J. Benson, Elizabeth M. Kurnick, James T. TI Role of the mitogen-activated protein kinase signaling pathway in the regulation of human melanocytic antigen expression SO MOLECULAR CANCER RESEARCH LA English DT Article ID MELANOMA-CELL-LINES; TUMOR-INFILTRATING LYMPHOCYTES; B-RAF; MALIGNANT-MELANOMA; BRAF MUTATIONS; IN-VIVO; TRANSCRIPTION FACTOR; DOWN-MODULATION; GENE-EXPRESSION; MITF AB Heterogeneous expression of melanocytic antigens occurs frequently in melanomas and represents a potent barrier to immunotherapy. We previously showed that coordinated losses of several melanocytic antigens are generally attributable to down-regulation of antigen gene expression rather than irreversible mutation. Treatment of melanoma cells with mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors blocks ERK activation and increases steady-state levels of mRNAs and corresponding protein expression for the melanocytic antigens Melan-A/MART-1, gp100, and tyrosinase. Although the degree of MEK inhibitor enhancement of antigen expression varied among different cell lines irrespective of their antigen expression status, all showed detectable responses. Notably, the antigen-enhancing effects of the MEK inhibitors could not be attributed to the master melanocytic regulator MITF-M. Because MAPK pathway activation via constitutively active mutant forms of BRAF is common in melanomas, correlation between BRAF function and antigen expression was investigated. No simple correlation of endogenous BRAF mutational status and antigen levels was observed, but transient overexpression of V600E BRAF increased ERK activation and reduced Melan-A/MART-1 levels in antigen-positive cell lines. These data indicate that whereas multiple factors may regulate antigen expression in melanomas, enhancement of MAPK signaling can act as a negative influence. Blocking such signaling with MEK inhibitors accordingly augments antigen levels, thereby enhancing Melan-A/MART-1-specific cytotoxic T-cell responses to antigen-negative cells following MEK inhibition treatment. Consequently, MAPK inhibition may assist targeting of melanomas for immunotherapy. C1 CytoCure LLC, Beverly, MA 01915 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Nagoya Univ, Grad Sch Med, Dept Dermatol, Showa Ku, Nagoya, Aichi, Japan. Westmead Hosp, Dept Immunopathol, Sydney, NSW, Australia. RP Kurnick, JT (reprint author), CytoCure LLC, 100 Cummings Ctr,Suite 430, Beverly, MA 01915 USA. EM kurnick@massmed.org RI Kono, Michihiro/I-1238-2012 OI Kono, Michihiro/0000-0003-2639-1583 FU NCI NIH HHS [R43-CA94700, R43-CA96271, R43-CA86153] NR 63 TC 74 Z9 74 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2006 VL 4 IS 10 BP 779 EP 792 DI 10.1158/1541-7786.MCR-06-0077 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 096WY UT WOS:000241408700008 PM 17050671 ER PT J AU MacConaill, LE Hughes, CM Rozenblatt-Rosen, O Nannepaga, S Meyerson, M AF MacConaill, Laura E. Hughes, Christina M. Rozenblatt-Rosen, Orit Nannepaga, Suraj Meyerson, Matthew TI Phosphorylation of the menin tumor suppressor protein on serine 543 and serine 583 SO MOLECULAR CANCER RESEARCH LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; HISTONE METHYLTRANSFERASE COMPLEX; HOX GENE-EXPRESSION; GENOMIC ORGANIZATION; TYPE-1; MUTATIONS; PRODUCT; MICE; IDENTIFICATION; METHYLATION AB Multiple endocrine neoplasia type 1 (MEN-1) is a heritable syndrome typified by tumors in multiple endocrine organs, including the pituitary, parathyroids, and pancreatic islets. MEN-1 is attributable to mutations in the MEN1 tumor-suppressor gene that encodes the menin protein. Recent studies have implicated menin in transcriptional regulation and in covalent histone modification; however, little is known about modifications of the menin protein. Here, we report that menin is subject to phosphorylation on serine residues, including Ser(543) and Ser(583). Phosphorylation-defective mutants of either or both of these residues retain the associated histone methyltransferase activity of menin, as well as binding to the trithorax complex members Ash2L, Rbbp5, and MLL2 and to RNA polymerase II. Chromatin immunoprecipitation experiments reveal that binding of menin to the Hoxc8 locus is not affected by phosphorylation on Ser(543) or Ser(583). C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 42 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD OCT PY 2006 VL 4 IS 10 BP 793 EP 801 DI 10.1158/1541-7786.MCR-06-0123 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 096WY UT WOS:000241408700009 PM 17050672 ER PT J AU Liu, T Qian, WJ Gritsenko, MA Xiao, WZ Moldawer, LL Kaushal, A Monroe, ME Varnum, SM Moore, RJ Purvine, SO Maier, RV Davis, RW Tompkins, RG Camp, DG Smith, RD AF Liu, Tao Qian, Wei-Jun Gritsenko, Marina A. Xiao, Wenzhong Moldawer, Lyle L. Kaushal, Amit Monroe, Matthew E. Varnum, Susan M. Moore, Ronald J. Purvine, Samuel O. Maier, Ronald V. Davis, Ronald W. Tompkins, Ronald G. Camp, David G., II Smith, Richard D. CA Inflammation Host Response Injury TI High dynamic range characterization of the trauma patient plasma proteome SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID HUMAN SERUM PROTEOME; MASS-SPECTROMETRY IDENTIFICATION; CYSTEINYL-PEPTIDE ENRICHMENT; HUMAN BLOOD-PLASMA; LIQUID-CHROMATOGRAPHY; REVERSED-PHASE; IN-VIVO; IMMUNOAFFINITY SUBTRACTION; QUANTITATIVE-ANALYSIS; HYDRAZIDE CHEMISTRY AB Although human plasma represents an attractive sample for disease biomarker discovery, the extreme complexity and large dynamic range in protein concentrations present significant challenges for characterization, candidate biomarker discovery, and validation. Herein we describe a strategy that combines immunoaffinity subtraction and subsequent chemical fractionation based on cysteinyl peptide and N-glycopeptide captures with two-dimensional LC-MS/MS to increase the dynamic range of analysis for plasma. Application of this "divide-and-conquer" strategy to trauma patient plasma significantly improved the overall dynamic range of detection and resulted in confident identification of 22,267 unique peptides from four different peptide populations (cysteinyl peptides, non-cysteinyl peptides, N-glycopeptides, and non-glycopeptides) that covered 3654 different proteins with 1494 proteins identified by multiple peptides. Numerous low abundance proteins were identified, exemplified by 78 "classic" cytokines and cytokine receptors and by 136 human cell differentiation molecules. Additionally a total of 2910 different N-glycopeptides that correspond to 662 N-glycoproteins and 1553 N-glycosylation sites were identified. A panel of the proteins identified in this study is known to be involved in inflammation and immune responses. This study established an extensive reference protein database for trauma patients that provides a foundation for future high throughput quantitative plasma proteomic studies designed to elucidate the mechanisms that underlie systemic inflammatory responses. C1 Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99354 USA. Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99354 USA. Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. Univ Washington, Seattle, WA 98104 USA. Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Surg, Sch Med, Shriners Burn Ctr, Boston, MA 02114 USA. RP Smith, RD (reprint author), Pacific NW Natl Lab, Environm Mol Sci Lab, Box 999,MSIN K9-98, Richland, WA 99352 USA. EM rds@pnl.gov RI Qian, Weijun/C-6167-2011; Smith, Richard/J-3664-2012; Liu, Tao/A-9020-2013; OI Smith, Richard/0000-0002-2381-2349; Liu, Tao/0000-0001-9529-6550; xiao, wenzhong/0000-0003-4944-6380; Baker, Henry/0000-0002-8273-5320 FU NCRR NIH HHS [P41 RR018522, RR18522]; NIGMS NIH HHS [U54 GM-62119-02, U54 GM062119] NR 61 TC 97 Z9 103 U1 0 U2 16 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 OCT PY 2006 VL 5 IS 10 BP 1899 EP 1913 DI 10.1074/mcp.M600068/MCP200 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098KL UT WOS:000241519300017 PM 16684767 ER PT J AU Gerszten, RE AF Gerszten, R. E. TI Novel markers of myocardial ischemia SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 OCT PY 2006 VL 5 IS 10 SU S MA 1246 BP S337 EP S337 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401353 ER PT J AU Kho, MT Sarracino, DA Guo, SZ Wang, X Lee, SR Krastins, B Lo, EH AF Kho, M. T. Sarracino, D. A. Guo, S. Z. Wang, X. Lee, S. -R. Krastins, B. Lo, E. H. TI Temporal profile of human brain endothelial cells in oxidative stress; a bench-side model for endothelial response to ischemic injury SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. NR 0 TC 0 Z9 0 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 OCT PY 2006 VL 5 IS 10 SU S MA 1146 BP S316 EP S316 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401297 ER PT J AU Ning, MM Sarracino, DA Buonanno, F Krastins, B Chou, S McMullin, D Lo, EH AF Ning, M. -M. Sarracino, D. A. Buonanno, F. Krastins, B. Chou, S. McMullin, D. Lo, E. H. TI Plasma protease substrate profiling of tPA treatment in acute ischemic stroke patients: A step toward pharmacoproteomics at the bedside SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. NYU, New York, NY USA. NR 0 TC 0 Z9 0 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 OCT PY 2006 VL 5 IS 10 SU S MA 678 BP S176 EP S176 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506400402 ER PT J AU Richmond, T Shi, X Prakash, A Bonilla, L AF Richmond, T. Shi, X. Prakash, A. Bonilla, L. TI Increasing throughput of peptide quantification using isotope dilution mass spectrometry for monitoring cardiac markers in human plasma SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Thermo BRIMS Ctr, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 OCT PY 2006 VL 5 IS 10 SU S MA 1003 BP S266 EP S266 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401190 ER PT J AU Sutton, JN Athanas, M Richmond, T Shi, X Zumwalt, A Gerszten, RE Bonilla, LE AF Sutton, J. N. Athanas, M. Richmond, T. Shi, X. Zumwalt, A. Gerszten, R. E. Bonilla, L. E. TI Analytical performance characterization of an FT-MS-based label-free platform for biomarker discovery in plasma; Standards, precision, accuracy, and directed feature investigation SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Meeting Abstract C1 Thermo BRIMS Ctr, Cambridge, MA USA. BioTeam, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 OCT PY 2006 VL 5 IS 10 SU S MA 945 BP S246 EP S246 PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 098FM UT WOS:000241506401145 ER PT J AU Tran, TT Segev, DL Gupta, V Kawakubo, H Yeo, G Donahoe, PK Maheswaran, S AF Tran, Trinh T. Segev, Dorry L. Gupta, Vandana Kawakubo, Hirofumi Yeo, Giminna Donahoe, Patricia K. Maheswaran, Shyamala TI Mullerian inhibiting substance regulates androgen-induced gene expression and growth in prostate cancer cells through a nuclear factor-kappa B-dependent Smad-independent mechanism SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID IN-VIVO; II RECEPTOR; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; INDUCED REGENERATION; SIGNAL-TRANSDUCTION; DUCT REGRESSION; MOUSE PROSTATE; HORMONE; APOPTOSIS AB Mullerian inhibiting substance (MIS), a member of the TGF beta superfamily, causes regression of the Mullerian duct in male embryos. The presence of MIS type II and type I receptors in tissues and cell lines derived from the prostate suggests that prostate is a likely target for MIS. In this report, we demonstrate that MIS inhibits androgen-stimulated growth of LNCaP cells and decreases their survival in androgen-deprived medium by preventing cell cycle progression and inducing apoptosis. Expression of dominant-negative Smad1 reversed the ability of MIS to decrease LNCaP cell survival in androgen-deprived medium but not androgen-stimulated growth, whereas abrogation of nuclear factor-kappa B (NF kappa B) activation ablated the suppressive effects of MIS on both androgen-stimulated growth and androgen-independent survival. The effect of MIS on androgen-induced growth was not due to changes in androgen receptor expression. However, MIS suppressed androgen-stimulated transcription of prostate-specific antigen; ablation of NF kappa B activation reversed MIS-mediated suppression of prostate-specific antigen. These observations suggest that MIS regulates androgen-induced gene expression and growth in prostate cancer cells through a NF kappa B-dependent but Smad1-independent mechanism. Thus, MIS, in addition to potentially regulating prostate growth indirectly by suppressing testicular testosterone synthesis, may also be a direct regulator of androgen-induced gene expression and growth in the prostate at the cellular level. C1 Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Jackson 904,55 Fruit St, Boston, MA 02114 USA. EM maheswaran@helix.mgh.harvard.edu FU NCI NIH HHS [CA89138, CA17373]; NICHD NIH HHS [HD32112] NR 50 TC 9 Z9 9 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 2006 VL 20 IS 10 BP 2382 EP 2391 DI 10.1210/me.2005-0480 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088AY UT WOS:000240785100010 PM 16740653 ER PT J AU Carlson, MJ Cummings, DE AF Carlson, Molly J. Cummings, David E. TI Prospects for an anti-ghrelin vaccine to treat obesity SO MOLECULAR INTERVENTIONS LA English DT Editorial Material ID HORMONE SECRETAGOGUE RECEPTOR; BROWN ADIPOSE-TISSUE; FOOD-INTAKE; WEIGHT-GAIN; MICE; APPETITE; STOMACH; SECRETION; DELETION; PEPTIDE AB In the battle to treat the pandemic of obesity, one therapeutic strategy is to block endogenous signals that stimulate appetite and control body weight. One such molecule is ghrelin, a gut peptide that is the only known orexigenic hormone and is a likely contributor to mealtime hunger. The relative importance of ghrelin in long-term body-weight regulation (and thus its promise as an anti-obesity target) is uncertain, however, because genetic and pharmacologic blockade of ghrelin signaling have yielded variable results to date. Using a novel approach of vaccinating rats against their own ghrelin, Zorilla et al. report that animals with high ghrelin-specific antibody titers displayed restricted body weight, without evidence of non-specific inflammation following the vaccine. These results favor a meaningful role for ghrelin in energy homeostasis, hinting at a possible new anti-obesity approach. More broadly, the work of Zorilla et al. supports the feasibility of vaccinations directed against specific autologous targets-immunopharmacotherapy that could potentially be developed to target a wide array of medical conditions. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM mollyc@u.washington.edu; davidec@u.washington.edu NR 28 TC 5 Z9 5 U1 2 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD OCT PY 2006 VL 6 IS 5 BP 249 EP + DI 10.1124/mi.6.5.5 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 099YO UT WOS:000241634000003 PM 17035664 ER PT J AU Huang, TT D'Andrea, AD AF Huang, Tony T. D'Andrea, Alan D. TI HAUSP hunting the FOX(O) SO NATURE CELL BIOLOGY LA English DT Editorial Material ID FOXO TRANSCRIPTION FACTORS; P53-MDM2 PATHWAY; P53; MDM2; RECOGNITION; LONGEVITY; STRESS AB The forkhead box O (FOXO) family of transcription factors regulate cell stress, cell cycle and cell death pathways. Their activities can be modulated by multiple posttranslational modifications, including phosphorylation and acetylation. A recent study adds a new twist to FOXO regulation, showing that coupled ubiquitination and deubiquitination of FOXO may be important for cellular responses to oxidative stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Huang, TT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu NR 15 TC 2 Z9 2 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2006 VL 8 IS 10 BP 1043 EP 1045 DI 10.1038/ncb1006-1043 PG 4 WC Cell Biology SC Cell Biology GA 096RU UT WOS:000241395300003 PM 17013413 ER PT J AU Nachtigall, LB AF Nachtigall, Lisa B. TI Acromegaly diagnosed in a young woman presenting with headache and arthritis SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Article DE acromegaly; arthritis; insulin-like growth factor 1; pituitary adenoma; trans-sphenoidal surgery ID PITUITARY-ADENOMAS; GROWTH-HORMONE; MANAGEMENT AB Background A 38-year-old woman presented with severe headaches to her primary-care physician. The patient had been diagnosed with rheumatoid arthritis and had begun having headache 4 years previously. An MRI scan revealed an 11-12 mm pituitary tumor. Her physical examination was unremarkable for the classic acral or facial changes characteristic of acromegaly, and she was referred for neuroendocrine consultation for a presumed nonfunctioning adenoma. Investigations MRI of the pituitary, and laboratory investigations that included measurement of serum insulin-like growth factor 1 (IGF1) and prolactin levels. Diagnosis In view of the elevated level of IGF1 and presence of a pituitary adenoma, the patient was diagnosed with acromegaly caused by a pituitary adenoma that secretes growth hormone. Management The patient underwent trans-sphenoidal surgery, which resulted in resolution of joint pain and headache, eradication of the tumor mass, normal IGF1 levels, and appropriate suppression of growth hormone (confirmed by oral glucose tolerance test postoperatively). C1 Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nachtigall, LB (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Zero Emerson Pl Suite 112, Boston, MA 02114 USA. EM lnachtigall@partners.org NR 17 TC 1 Z9 1 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 OCT PY 2006 VL 2 IS 10 BP 582 EP 587 DI 10.1038/ncpendmet0301 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 091UW UT WOS:000241054800013 PM 17024157 ER PT J AU Siegel, JM Boehmer, LN AF Siegel, Jerome M. Boehmer, Lisa N. TI Narcolepsy and the hypocretin system - where motion meets emotion SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Review DE immunology; major histocompatibility complex class II; narcolepsy; rapid eye movement sleep; sleep ID OREXIN-A; INTRAVENOUS IMMUNOGLOBULINS; SLEEP-DEPRIVATION; NEURONS; CATAPLEXY; ONSET; BRAIN; EXPRESSION; PEPTIDES; BEHAVIOR AB Narcolepsy is a neurological disorder that is characterized by excessive daytime sleepiness and cataplexy - a loss of muscle tone generally triggered by certain strong emotions with sudden onset. The underlying cause of most cases of human narcolepsy is a loss of neurons that produce hypocretin (Hcrt, also know as orexin). These cells normally serve to drive and synchronize the activity of monoaminergic and cholinergic cells. Sleepiness results fro the reduced activity of monoaminergic, cholinergic and other cells that are normally activated by Hcrt neurons, as well as from the loss of Hcrt itself. Cataplexy is caused by an episodic loss of activity in noradrenergic cells that support muscle tone, and a linked activation of a medial medullary cell population that suppresses muscle tone. Current treatments for narcolepsy include stimulants to combat sleepiness and antidepressants to reduce cataplexy. Sodium oxybate produces both reductions in cataplexy and improved waking alertness. Future treatments are likely to include Hcrt or Hcrt agonists to reverse the underlying neurochemical deficit. C1 Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Siegel, JM (reprint author), VA GLAHS Sepulveda, Ctr Sleep Res, Neurobiol Res 151A3,16111 Plummer St, North Hills, CA 91343 USA. EM jsiegel@ucla.edu FU NIMH NIH HHS [MH64109]; NINDS NIH HHS [NS14610] NR 58 TC 49 Z9 51 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD OCT PY 2006 VL 2 IS 10 BP 548 EP 556 DI 10.1038/ncpneuro0300 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 085QQ UT WOS:000240619000010 PM 16990828 ER PT J AU de Bakker, PIW McVean, G Sabeti, PC Miretti, MM Green, T Marchini, J Ke, XY Monsuur, AJ Whittaker, P Delgado, M Morrison, J Richardson, A Walsh, EC Gao, XJ Galver, L Hart, J Hafler, DA Pericak-Vance, M Todd, JA Daly, MJ Trowsdale, J Wijmenga, C Vyse, TJ Beck, S Murray, SS Carrington, M Gregory, S Deloukas, P Rioux, JD AF de Bakker, Paul I. W. McVean, Gil Sabeti, Pardis C. Miretti, Marcos M. Green, Todd Marchini, Jonathan Ke, Xiayi Monsuur, Alienke J. Whittaker, Pamela Delgado, Marcos Morrison, Jonathan Richardson, Angela Walsh, Emily C. Gao, Xiaojiang Galver, Luana Hart, John Hafler, David A. Pericak-Vance, Margaret Todd, John A. Daly, Mark J. Trowsdale, John Wijmenga, Cisca Vyse, Tim J. Beck, Stephan Murray, Sarah Shaw Carrington, Mary Gregory, Simon Deloukas, Panos Rioux, John D. TI A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC SO NATURE GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NONCODING SEQUENCE POLYMORPHISMS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN GENOME; LINKAGE-DISEQUILIBRIUM; CELIAC-DISEASE; REGION; RISK AB The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases(1). Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC(2,3). We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and > 7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes. C1 Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA. Univ Oxford, Dept Stat, Oxford OX1 2JD, England. Wellcome Trust Sanger Inst, Hinxton, England. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. Univ Utrecht, Med Ctr, Dept Med Genet, Complex Genet Sect, NL-3508 TC Utrecht, Netherlands. SAIC Frederick Inc, Lab Genom Divers, Frederick, MD USA. NCI, Frederick, MD 21701 USA. Illumina Inc, San Diego, CA USA. Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27706 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Cambridge, Inst Med Res, Wellcome Trust Diabet & Inflammat Lab, Juventil Diabet Res Fdn, Cambridge CB2 1TN, England. Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England. Imperial Coll Sch Med, London, England. Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. RP Rioux, JD (reprint author), Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM rioux@broad.mit.edu RI Ke, Xiayi/C-7674-2009; Todd, John/A-3542-2010; Deloukas, Panos/B-2922-2013; de Bakker, Paul/B-8730-2009; Wijmenga, Cisca/D-2173-2009; Rioux, John/A-9599-2015; OI Deloukas, Panos/0000-0001-9251-070X; de Bakker, Paul/0000-0001-7735-7858; Rioux, John/0000-0001-7560-8326; Wijmenga, Cisca/0000-0002-5635-1614 FU Intramural NIH HHS; Medical Research Council [G9800943]; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [U19 AI050864]; Wellcome Trust [, 077011] NR 29 TC 409 Z9 417 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2006 VL 38 IS 10 BP 1166 EP 1172 DI 10.1038/ng1885 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 094PJ UT WOS:000241251100016 PM 16998491 ER PT J AU Derti, A Roth, FP Church, GM Wu, CT AF Derti, Adnan Roth, Frederick P. Church, George M. Wu, C-ting TI Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; STRUCTURAL VARIATION; GENE DESERTS; VERTEBRATE; SEQUENCES; ENHANCER; TRANSVECTION; POLYMORPHISM; DROSOPHILA; REGIONS AB An earlier search in the human, mouse and rat genomes for sequences that are 100% conserved in orthologous segments and >= 200 bp in length identified 481 distinct sequences(1). These human-mouse-rat sequences, which represent ultraconserved elements (UCEs), are believed to be important for functions involving DNA binding, RNA processing and the regulation of transcription and development. In vivo and additional computational studies of UCEs and other highly conserved sequences are consistent with these functional associations, with some observations indicating enhancer-like activity for these elements(1-9). Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants. Notably, of the UCEs that are found in segmental duplications or copy number variants, the majority overlap exons, indicating, along with other findings presented, that UCEs overlapping exons represent a distinct subset. C1 Harvard Univ, Sch Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Lipper Ctr Computat Genet, Boston, MA 02115 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Wu, CT (reprint author), Harvard Univ, Sch Med, Div Genet, Boston, MA 02115 USA. EM twu@genetics.med.harvard.edu RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU NHGRI NIH HHS [HG0017115, HG003224]; NIGMS NIH HHS [GM61936] NR 28 TC 57 Z9 59 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2006 VL 38 IS 10 BP 1216 EP 1220 DI 10.1038/ng1888 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 094PJ UT WOS:000241251100024 PM 16998490 ER PT J AU Bonasio, R Scimone, ML Schaerli, P Grabie, N Lichtman, AH von Andrian, UH AF Bonasio, Roberto Scimone, M. Lucila Schaerli, Patrick Grabie, Nir Lichtman, Andrew H. von Andrian, Ulrich H. TI Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus SO NATURE IMMUNOLOGY LA English DT Article ID COMMON PRECURSOR POPULATION; REGULATORY T-CELLS; EPITHELIAL-CELLS; BONE-MARROW; ADHESION MOLECULE-1; IMMUNE-RESPONSES; LYMPH-NODES; MICE; TOLERANCE; ANTIGEN AB Dendritic cell ( DC) presentation of self antigen to thymocytes is essential to the establishment of central tolerance. We show here that circulating DCs were recruited to the thymic medulla through a three-step adhesion cascade involving P-selectin, interactions of the integrin VLA-4 with its ligand VCAM-1, and pertussis toxin-sensitive chemoattractant signaling. Ovalbumin-specific OT-II thymocytes were selectively deleted after intravenous injection of antigen-loaded exogenous DCs. We documented migration of endogenous DCs to the thymus in parabiotic mice and after painting mouse skin with fluorescein isothiocyanate. Antibody to VLA-4 blocked the accumulation of peripheral tissue-derived DCs in the thymus and also inhibited the deletion of OT-II thymocytes in mice expressing membrane-bound ovalbumin in cardiac myocytes. These findings identify a migratory route by which peripheral DCs may contribute to central tolerance. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, CBR Inst Biomed Res,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Immunol Res,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Vasc Res Div, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, CBR Inst Biomed Res,Dept Pathol, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Bonasio, Roberto/P-1356-2014 OI Bonasio, Roberto/0000-0002-0767-0889 FU NHLBI NIH HHS [HL072056, HL56949]; NIAID NIH HHS [AI061663, AI059610]; NIAMS NIH HHS [AR42689] NR 50 TC 210 Z9 211 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2006 VL 7 IS 10 BP 1092 EP 1100 DI 10.1038/ni1385 PG 9 WC Immunology SC Immunology GA 097HE UT WOS:000241437100016 PM 16951687 ER PT J AU Krause, DS Lazarides, K von Andrian, UH Van Etten, RA AF Krause, Daniela S. Lazarides, Katherine von Andrian, Ulrich H. Van Etten, Richard A. TI Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells SO NATURE MEDICINE LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW; HEMATOPOIETIC PROGENITORS; ADHESION MOLECULES; SELECTIN LIGAND; MICE; BCR/ABL; TRANSPLANTATION; PROLIFERATION; INHIBITION AB In individuals with chronic myeloid leukemia (CML) treated by autologous hematopoietic stem cell (HSC) transplantation, malignant progenitors in the graft contribute to leukemic relapse(1), but the mechanisms of homing and engraftment of leukemic CML stem cells are unknown. Here we show that CD44 expression is increased on mouse stem-progenitor cells expressing BCR-ABL and that CD44 contributes functional E-selectin ligands. In a mouse retroviral transplantation model of CML, BCR-ABL1-transduced progenitors from CD44-mutant donors are defective in homing to recipient marrow, resulting in decreased engraftment and impaired induction of CML-like myeloproliferative disease. By contrast, CD44-deficient stem cells transduced with empty retrovirus engraft as efficiently as do wild-type HSCs. CD44 is dispensable for induction of acute B-lymphoblastic leukemia by BCR-ABL, indicating that CD44 is specifically required on leukemic cells that initiate CML. The requirement for donor CD44 is bypassed by direct intrafemoral injection of BCR-ABL1-transduced CD44-deficient stem cells or by coexpression of human CD44. Antibody to CD44 attenuates induction of CML-like leukemia in recipients. These results show that BCR-ABL-expressing leukemic stem cells depend to a greater extent on CD44 for homing and engraftment than do normal HSCs, and argue that CD44 blockade may be beneficial in autologous transplantation in CML. C1 Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Tufts Univ New England Med Ctr, Mol Oncol Res Inst, 750 Washington St, Boston, MA 02111 USA. EM rvanetten@tufts-nemc.org RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL56949, P01 HL056949] NR 30 TC 240 Z9 250 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2006 VL 12 IS 10 BP 1175 EP 1180 DI 10.1038/nm1489 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 092MW UT WOS:000241102200034 PM 16998483 ER PT J AU Dagia, NM Gadhoum, SZ Knoblauch, CA Spencer, JA Zamiri, P Lin, CP Sackstein, R AF Dagia, Nilesh M. Gadhoum, Samah Z. Knoblauch, Christine A. Spencer, Joel A. Zamiri, Parisa Lin, Charles P. Sackstein, Robert TI G-CSF induces E-selectin ligand expression on human myeloid cells SO NATURE MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; GRANULOCYTE-COLONY; IN-VIVO; RHEUMATOID-ARTHRITIS; ENDOTHELIAL-CELLS; HUMAN NEUTROPHILS; BONE-MARROW; ADHESION; PSGL-1; BLOOD AB Clinical use of G-CSF can result in vascular and inflammatory complications(1-7). To investigate the molecular basis of these effects, we analyzed the adherence of G-CSF-mobilized human peripheral blood leukocytes (ML) to inflamed (TNF-alpha - stimulated) vascular endothelium. Studies using parallel plate assays under physiologic flow conditions and intravital microscopy in a mouse inflammation model each showed that ML take part in heightened adhesive interactions with endothelium compared to unmobilized (native) blood leukocytes, mediated by markedly increased E-selectin receptor-ligand interactions. Biochemical studies showed that ML express the potent E-selectin ligand HCELL (ref. 8) and another, previously unrecognized similar to 65-kDa E-selectin ligand, and possess enhanced levels of transcripts encoding glycosyltransferases (ST3GaIIIV, FucT-IV and FucT-VII) conferring glycan modifications associated with E-selectin ligand activity. Enzymatic treatments and physiologic binding assays showed that HCELL and the similar to 65-kDa E-selectin ligand contribute prominently to the observed G-CSF-induced myeloid cell adhesion to inflamed endothelium. Treatment of normal human bone marrow cells with a pharmacokinetically relevant concentration of G-CSF in vitro(9,10) resulted in increased expression of these two molecules, coincident with increased transcripts encoding pertinent glycosyltransferases and heightened E-selectin binding. These findings provide direct evidence for a role of G-CSF in the induction of E-selectin ligands on myeloid cells, thus providing mechanistic insight into the pathobiology of G-CSF complications. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu RI Spencer, Joel/A-4590-2013 FU NHLBI NIH HHS [R01 HL060528, R01 HL073714]; NIBIB NIH HHS [R01 EB000664] NR 30 TC 35 Z9 36 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2006 VL 12 IS 10 BP 1185 EP 1190 DI 10.1038/nm1470 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 092MW UT WOS:000241102200036 PM 16980970 ER PT J AU Echeverri, CJ Beachy, PA Baum, B Boutros, M Buchholz, F Chanda, SK Downward, J Ellenberg, J Fraser, AG Hacohen, N Hahn, WC Jackson, AL Kiger, A Linsley, PS Lum, L Ma, Y Mathey-Prevot, B Root, DE Sabatini, DM Taipale, J Perrimon, N Bernards, R AF Echeverri, Christophe J. Beachy, Philip A. Baum, Buzz Boutros, Michael Buchholz, Frank Chanda, Sumit K. Downward, Julian Ellenberg, Jan Fraser, Andrew G. Hacohen, Nir Hahn, William C. Jackson, Aimee L. Kiger, Amy Linsley, Peter S. Lum, Lawrence Ma, Yong Mathey-Prevot, Bernard Root, David E. Sabatini, David M. Taipale, Jussi Perrimon, Norbert Bernards, Rene TI Minimizing the risk of reporting false positives in large-scale RNAi screens SO NATURE METHODS LA English DT Article AB Large-scale RNA interference (RNAi)-based analyses, very much as other 'omic' approaches, have inherent rates of false positives and negatives. The variability in the standards of care applied to validate results from these studies, if left unchecked, could eventually begin to undermine the credibility of RNAi as a powerful functional approach. This Commentary is an invitation to an open discussion started among various users of RNAi to set forth accepted standards that would insure the quality and accuracy of information in the large datasets coming out of genome-scale screens. C1 Cenix BioSci GMBH, D-10307 Dresden, Germany. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Ludwig Inst Canc Res, Morhpogenesis Grp, UCL Branch, London W1W 7BS, England. German Canc Res Ctr, Signalling & Funct Genom, D-69120 Heidelberg, Germany. Max Planck Inst Mol Cell Biol & Genet, D-10307 Dresden, Germany. Novartis Res Fdn, Febim Inst, Div Cellular Genom, San Diego, CA 92121 USA. Canc Res UK, London Res Inst, London WC2A 3PX, England. European Mol Biol Lab, Gene Express Unit, D-69117 Heidelberg, Germany. Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Rosetta Inpharm, Seattle, WA 98109 USA. Univ Calif San Diego, Dept Cell & Dev Biol, La Jolla, CA 92093 USA. Univ Texas, Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Drosophilia RNAi Screening Ctr, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Univ Helsinki, Biomedicum, Mol & Canc Biol Program, FIN-00014 Helsinki, Finland. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands. Netherlands Canc Inst, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands. RP Echeverri, CJ (reprint author), Cenix BioSci GMBH, Tatzberg 47, D-10307 Dresden, Germany. EM echeverri@cenix-bioscience.com; r.bernards@nki.nl RI Boutros, Michael/C-3566-2008; Ellenberg, Jan/I-4688-2014; Buchholz, Frank/B-4700-2017; OI Boutros, Michael/0000-0002-9458-817X; Ellenberg, Jan/0000-0001-5909-701X; Buchholz, Frank/0000-0002-4577-3344; Bernards, Rene/0000-0001-8677-3423; Fraser, Andrew/0000-0001-9939-6014; Baum, Buzz/0000-0002-9201-6186; Downward, Julian/0000-0002-2331-4729 NR 7 TC 264 Z9 273 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD OCT PY 2006 VL 3 IS 10 BP 777 EP 779 DI 10.1038/nmeth1006-777 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 090HU UT WOS:000240942600008 PM 16990807 ER PT J AU Farrow, K Haag, J Borst, A AF Farrow, Karl Haag, Juergen Borst, Alexander TI Nonlinear, binocular interactions underlying flow field selectivity of a motion-sensitive neuron SO NATURE NEUROSCIENCE LA English DT Article ID INTRINSIC ELECTROPHYSIOLOGICAL CHARACTERISTICS; PLATE TANGENTIAL CELLS; VISUAL RESPONSE PROPERTIES; NATURALISTIC OPTIC FLOW; LOBULA PLATE; HORIZONTAL CELLS; NETWORK INTERACTIONS; MEMBRANE-PROPERTIES; INPUT ORGANIZATION; OPTOMOTOR SYSTEM AB Neurons in many species have large receptive fields that are selective for specific optic flow fields. Here, we studied the neural mechanisms underlying flow field selectivity in lobula plate tangential cells (LPTCs) of the blowfly. Among these cells, the H2 cell responds preferentially to visual stimuli approximating rotational optic flow. Through double recordings from H2 and many other LPTCs, we characterized a bidirectional commissural pathway that allows visual information to be shared between the hemispheres. This pathway is mediated by axo-axonal electrical coupling of H2 and the horizontal system equatorial (HSE) cell located in the opposite hemisphere. Using single-cell ablations, we found that this pathway is sufficient to allow H2 to amplify and attenuate dendritic input during binocular visual stimuli. This is accomplished through a modulation of H2's membrane potential by input from the contralateral HSE cell, which scales the firing rate of H2 during visual stimulation but is not sufficient to induce action potentials. C1 Max Planck Inst Neurobiol, Dept Syst & Computat Neurobiol, D-82152 Martinsried, Germany. RP Farrow, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Blossom St,Thier 429, Boston, MA 02114 USA. EM kfarrow@partners.org RI Farrow, Karl/C-6215-2008; OI Farrow, Karl/0000-0003-1409-096X NR 50 TC 29 Z9 29 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2006 VL 9 IS 10 BP 1312 EP 1320 DI 10.1038/nn1769 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 098BB UT WOS:000241493900025 PM 16964250 ER PT J AU Schapira, AHV Bezard, E Brotchie, J Calon, F Collingridge, GL Ferger, B Hengerer, B Hirsch, E Jenner, P Le Novere, N Obeso, JA Schwarzschild, MA Spampinato, U Davidai, G AF Schapira, Anthony H. V. Bezard, Erwan Brotchie, Jonathan Calon, Frederic Collingridge, Graham L. Ferger, Borris Hengerer, Bastian Hirsch, Etienne Jenner, Peter Le Novere, Nicolas Obeso, Jose A. Schwarzschild, Michael A. Spampinato, Umberto Davidai, Giora TI Novel pharmacological targets for the treatment of Parkinson's disease SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID INDUCED MOTOR COMPLICATIONS; LEVODOPA-INDUCED DYSKINESIAS; A(2A) RECEPTOR ANTAGONIST; DOPA-INDUCED DYSKINESIAS; RANDOMIZED CONTROLLED-TRIAL; SEROTONIN 5-HT1A AGONIST; SUBUNIT MESSENGER-RNA; MPTP-TREATED MONKEYS; ADENOSINE A(2A); NEUROTROPHIC FACTOR AB Dopamine deficiency, caused by the degeneration of nigrostriatal dopaminergic neurons, is the cause of the major clinical motor symptoms of Parkinson's disease. These symptoms can be treated successfully with a range of drugs that include levodopa, inhibitors of the enzymatic breakdown of levodopa and dopamine agonists delivered by oral, subcutaneous, transcutaneous, intravenous or intra-duodenal routes. However, Parkinson's disease involves degeneration of non-dopaminergic neurons and the treatment of the resulting predominantly non-motor features remains a challenge. This review describes the important recent advances that underlie the development of novel dopaminergic and non-dopaminergic drugs for Parkinson's disease, and also for the motor complications that arise from the use of existing therapies. C1 UCL, Royal Free & Univ Coll Med Sch, Univ Dept Clin Neurosci, London NW3 2PF, England. UCL, Inst Neurol, London WC1N 3BG, England. Univ Bordeaux 2, CNRS, UMR 5543, F-33076 Bordeaux, France. Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. Univ Laval, Res Ctr, Ctr Hosp, Mol Endocrinol & Oncol Res Ctr, Quebec City, PQ G1V 4G2, Canada. Univ Laval, Fac Pharm, Quebec City, PQ G1K 7P4, Canada. Univ Bristol, MRC, Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. Boehringer Ingelheim Pharma GmbH & Co KG, D-88397 Biberach, Germany. INSERM, UMR 679, Paris, France. Univ Paris 06, Hop La Pitie Salpetriere, Paris, France. Kings Coll London, Sch Hlth & Biomed Sci, Neurodegenerat Dis Res Ctr, London SE1 1UL, England. EMBL, EBI, Cambridge CB10 1SD, England. Univ Navarra Clin, Dept Neurol, Pamplona 31008, Spain. Univ Navarra Clin, Ctr Neurosci, Pamplona 31008, Spain. Univ Navarra, Sch Med, Pamplona 31008, Spain. CIMA, Pamplona 31008, Spain. Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. Univ Bordeaux 2, CNRS, UMR 5541, Ctr Natl Rech Sci,Unite Mixte Rech 14, F-33076 Bordeaux, France. Boehringer Ingelheim Pharmaceut Inc, Clin & Sci Affairs, Dept Cardiovasc Med & Neurol, Ridgefield, CT 06877 USA. RP Schapira, AHV (reprint author), UCL, Royal Free & Univ Coll Med Sch, Univ Dept Clin Neurosci, Rowland Hill St, London NW3 2PF, England. EM a.schapira@medsch.ucl.ac.uk RI Schapira, Anthony/A-1245-2010; Le Novere, Nicolas/F-9973-2010; Collingridge, Graham/C-4605-2015; OI Schapira, Anthony/0000-0002-3018-3966; Le Novere, Nicolas/0000-0002-6309-7327; Collingridge, Graham/0000-0002-9572-5359; Bezard, Erwan/0000-0002-0410-4638 NR 119 TC 166 Z9 170 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD OCT PY 2006 VL 5 IS 10 BP 845 EP 854 DI 10.1038/nrd2087 PG 10 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 094DB UT WOS:000241218500024 PM 17016425 ER PT J AU Laxman, B Tomlins, SA Mehra, R Morris, DS Wang, L Helgeson, BE Shah, RB Rubin, MA Wei, JT Chinnaiyan, AM AF Laxman, Bharathi Tomlins, Scott A. Mehra, Rohit Morris, David S. Wang, Lei Helgeson, Beth E. Shah, Rajal B. Rubin, Mark A. Wei, John T. Chinnaiyan, Arul M. TI Noninvasive detection of TMPRSS2 : ERG fusion transcripts in the urine of men with prostate cancer SO NEOPLASIA LA English DT Article DE gene fusions; prostate cancer; noninvasive detection; urine; quantitative PCR ID GENE; EXPRESSION; TRANSLOCATIONS AB We recently reported the identification of recurrent gene fusions in the majority of prostate cancers involving the 5' untranslated region of the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, and ETV4. Here we report the noninvasive detection of these gene fusions in the urine of patients with clinically localized prostate cancer. By quantitative polymerase chain reaction, we assessed the expression of ERG and TMPRSS2: ERG transcripts in urine samples obtained after prostatic massage from 19 patients (11 prebiopsy and 8 pre-radical prostatectomy) with prostate cancer. We observed a strong concordance between ERG overexpression and TMPRSS2: ERG expression, with 8 of 19 (42%) patients having detectable TMPRSS2: ERG transcripts in their urine. Importantly, by fluorescence in situ hybridization, we confirmed the presence or the absence of TMPRSS2: ERG gene fusions in matched prostate cancer tissue samples from three of three patients with fusion transcripts in their urine and from two of two patients without fusion transcripts in their urine. These results demonstrate that TMPRSS2: ERG gene fusions can be detected in the urine of patients with prostate cancer and support larger studies on prospective cohorts for noninvasive detection of prostate cancer. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Michigan Urol Ctr, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Dept Pathol, 1400 E Med Ctr Dr 5316 CCGC, Ann Arbor, MI 48109 USA. EM arul@umich.edu RI Wei, John/E-8967-2012; OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [P50 CA069568, P50CA69568, U01 CA111275, U01 CA111275-01] NR 12 TC 142 Z9 154 U1 0 U2 1 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD OCT PY 2006 VL 8 IS 10 BP 885 EP 888 DI 10.1593/neo.06625 PG 4 WC Oncology SC Oncology GA 096GK UT WOS:000241365400011 PM 17059688 ER PT J AU Srinivasan, L Eden, UT Willsky, AS Brown, EN AF Srinivasan, Lakshminarayan Eden, Uri T. Willsky, Alan S. Brown, Emery N. TI A state-space analysis for reconstruction of goal-directed movements using neural signals SO NEURAL COMPUTATION LA English DT Article ID DIRECT CORTICAL CONTROL; PRIMATE MOTOR CORTEX; TORQUE-CHANGE MODEL; ARM MOVEMENTS; REACHING MOVEMENTS; DYNAMIC-ANALYSIS; PARIETAL CORTEX; REPRESENTATION; INFORMATION; POPULATION AB The execution of reaching movements involves the coordinated activity of multiple brain regions that relate variously to the desired target and a path of arm states to achieve that target. These arm states may represent positions, velocities, torques, or other quantities. Estimation has been previously applied to neural activity in reconstructing the target separately from the path. However, the target and path are not independent. Because arm movements are limited by finite muscle contractility, knowledge of the target constrains the path of states that leads to the target. In this letter, we derive and illustrate a state equation to capture this basic dependency between target and path. The solution is described for discrete-time linear systems and gaussian increments with known target arrival time. The resulting analysis enables the use of estimation to study how brain regions that relate variously to target and path together specify a trajectory. The corresponding reconstruction procedure may also be useful in brain-driven prosthetic devices to generate control signals for goal-directed movements. C1 Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. MIT, Dept Elect Engn & Comp Sci, Informat & Decis Syst Lab, Cambridge, MA 02139 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Srinivasan, L (reprint author), Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. EM ls2@neurostat.mgh.harvard.edu; tzvi@neurostat.mgh.harvard.edu; willsky@mit.edu; brown@neurostat.mgh.harvard.edu FU NIDA NIH HHS [R01 DA015644] NR 50 TC 52 Z9 52 U1 0 U2 3 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD OCT PY 2006 VL 18 IS 10 BP 2465 EP 2494 DI 10.1162/neco.2006.18.10.2465 PG 30 WC Computer Science, Artificial Intelligence SC Computer Science GA 086JB UT WOS:000240668500008 PM 16907633 ER PT J AU Henson, J AF Henson, J. TI Advances and pitfalls in imaging brain metastases SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 294 EP 294 DI 10.1215/15228517-2006-019 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877300004 ER PT J AU Barker, FG Carter, BS Curry, WT AF Barker, Fred G. Carter, Bob S. Curry, William T. TI Racial disparities in patient outcomes after craniotomy for tumor in the united states: Provider volume, severity at presentation and trends over time SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 405 EP 405 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301056 ER PT J AU Koul, D Shen, R Edge, J Liu, TJ Powis, G Lynn Kirkpatrick, D Alfred Yung, WK AF Koul, Dimpy Shen, Ruijun Edge, Jennifer Liu, T. J. Powis, Garth Lynn Kirkpatrick, D. Alfred Yung, W. K. TI Phosphatidylinositol 3-kinase (PI3K) pathway - A therapeutic target for human glioblastoma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Ohio State Univ, Ctr Med, Dept Neurol Surg, Columbus, OH 43210 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Mol Neurooncol Lab,Sch Med, Neurosurg Serv, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 414 EP 414 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301090 ER PT J AU Sathornsumetee, S Hjelmeland, AB Keir, ST McLendon, RE Batt, D Ramsey, T Yusuff, N Ahmed Rasheed, BK Kieran, MW Laforme, A Bigner, DD Friedman, HS Rich, JN AF Sathornsumetee, Sith Hjelmeland, Anita B. Keir, Stephen T. McLendon, Roger E. Batt, David Ramsey, Timothy Yusuff, Naeem Ahmed Rasheed, B. K. Kieran, Mark W. Laforme, Andrea Bigner, Darell D. Friedman, Henry S. Rich, Jeremy N. TI AAL881, a novel small molecule inhibitor of RAF and VEGFR activities, blocks growth of malignant glioma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 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. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. Novartis Inst Biomed Res, Cambridge, MA USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 417 EP 417 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301099 ER PT J AU Sauvageot, C Barnes, J Weatherbee, J Ramakrishna, N Kesari, S Stiles, C Kieran, M Wen, P AF Sauvageot, C. Barnes, J. Weatherbee, J. Ramakrishna, N. Kesari, S. Stiles, C. Kieran, M. Wen, P. TI Effects of the HSP90 inhibitor 17-AAG in glioblastoma multiforme SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 417 EP 417 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301100 ER PT J AU Aldape, K Zhang, L Phillips, H Wei, C Nutt, C Louis, D Cairncross, JG Feuerstein, BG Wang, R Jenkins, RB Colman, H AF Aldape, K. Zhang, L. Phillips, H. Wei, C. Nutt, C. Louis, D. Cairncross, J. G. Feuerstein, B. G. Wang, R. Jenkins, R. B. Colman, H. TI Meta-analysis of gene expression profiling data from glioblastoma tumor samples identifies a robust multigene classifier predictive of survival SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Genentech Inc, San Francisco, CA 94080 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 419 EP 420 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301110 ER PT J AU Barnes, JW Cervi, D Ligon, KL Tseng, LH Longtine, JA Chaponis, DM Wen, PY Kesari, S Drappatz, J Black, PM Kieran, MW AF Barnes, J. W. Cervi, D. Ligon, K. L. Tseng, L. H. Longtine, J. A. Chaponis, D. M. Wen, P. Y. Kesari, S. Drappatz, J. Black, P. M. Kieran, M. W. TI High throughput proteomic identification and quantitation of MGMT in human brain tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA USA. Dana Farber Canc Inst, Div Adult Neuro Oncol, Boston, MA USA. Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neuropathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 420 EP 420 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301112 ER PT J AU Cahill, DP Levine, KK Romany, CA Rooks, MG Roy, JE Batchelor, TT Louis, DN AF Cahill, Daniel P. Levine, Kymberly K. Romany, Candice A. Rooks, Michelle G. Roy, Jennifer E. Batchelor, Tracy T. Louis, David N. TI Loss of the mismatch repair protein MSH6 in human recurrent glioblastomas SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 420 EP 420 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301113 ER PT J AU Khwaja, FW Reed, M Duke-Cohan, JS Brat, DJ Schmotzer, BJ Olson, JJ Gillespie, GY Guha, A Groves, MD Pohl, J Van Meir, EG AF Khwaja, F. W. Reed, M. Duke-Cohan, J. S. Brat, D. J. Schmotzer, B. J. Olson, J. J. Gillespie, G. Y. Guha, A. Groves, M. D. Pohl, J. Van Meir, E. G. TI Identificatoin of glioma-motility factor, attractin, and other new protein biomarkers in the cerebrospinal fluid (CSF) of astrocytoma patients SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Emory Univ, Sch Med, Sch Publ Hlth, Lab Mol Neurooncol,Dept Neurosurg, Atlanta, GA USA. Emory Univ, Sch Med, Sch Publ Hlth, Dept Hematol Oncol, Atlanta, GA USA. Emory Univ, Sch Med, Sch Publ Hlth, Winship Canc Inst, Atlanta, GA USA. Emory Univ, Sch Med, Sch Publ Hlth, Microchem & Proteom Facil, Atlanta, GA USA. Emory Univ, Sch Med, Sch Publ Hlth, Dept Pathol & Lab Med, Atlanta, GA USA. Emory Univ, Sch Med, Sch Publ Hlth, Gen Clin Res Ctr, Atlanta, GA USA. Harvard Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. Univ Alabama, Birmingham, AL USA. Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatts Brain Tumor Ctr, Dept Pathol,Div Neurosurg, Toronto, ON M5G 1X8, Canada. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 422 EP 422 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301120 ER PT J AU Fulci, G Breymann, L Gianni, D Rhee, SS Brat, DJ Stemmer-Rachamimov, A Yu, JH Louis, DN Weissleder, R Caligiuri, MA Chiocca, EA AF Fulci, Giulia Breymann, Laura Gianni, Davide Rhee, Sarah S. Brat, Daniel J. Stemmer-Rachamimov, Anat Yu, Jianhua Louis, David N. Weissleder, Ralph Caligiuri, Michael A. Chiocca, E. Antonio TI Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurosurg Serv, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Massachusetts Gen Hosp, Pathol Serv, Charlestown, MA USA. Ohio State Univ, Med Ctr, Solove Res Inst, Columbus, OH 43210 USA. Ohio State Univ, Med Ctr, James Canc Hosp,Dept Neurol Surg, Dardinger Ctr Neurooncol & Neurosci, Columbus, OH 43210 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 427 EP 427 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301139 ER PT J AU Fitzsimmons, A Batchelor, T O'Neill, A Henson, J AF Fitzsimmons, A. Batchelor, T. O'Neill, A. Henson, J. TI Secondary acute myelogenous leukemia in three patients treated with temozolomide for glial neoplasm SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 441 EP 442 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301196 ER PT J AU Grimm, SA Pulido, JS Jahnke, K Schiff, D Hall, AJ Shenkier, TN Siegal, T Doolittle, ND Batchelor, T Herrlinger, U Neuwelt, EA Laperriere, N Blay, JY Ferreri, AJM Omuro, A Abrey, LE AF Grimm, S. A. Pulido, J. S. Jahnke, K. Schiff, D. Hall, A. J. Shenkier, T. N. Siegal, T. Doolittle, N. D. Batchelor, T. Herrlinger, U. Neuwelt, E. A. Laperriere, N. Blay, J. Y. Ferreri, A. J. M. Omuro, A. Abrey, L. E. TI Primary intraocular lymphoma (PIOL): An international primary CNS lymphoma collaborative group report SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Rochester, MN USA. Univ Virginia, Charlottesville, VA USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Hadassah Hebrew Univ Hosp, Tel Aviv, Israel. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Tubingen, Tubingen, Germany. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Hosp Pitie Salpetriere, Int Extranodal Lymphoma Study Grp, Paris, France. RI Ferreri, Andres Jose Maria/A-6662-2013; Blay, Jean-Yves/N-3966-2016; OI Ferreri, Andres Jose Maria/0000-0001-9606-6124; Blay, Jean-Yves/0000-0001-7190-120X; Omuro, Antonio/0000-0003-4299-3664 NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 443 EP 444 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301203 ER PT J AU Grimm, SA Pulido, JS Omuro, A Blay, JY Ferreri, AJM Doolittle, N Batchelor, T Siegal, R Jahnke, K Shenkier, TN Hall, AJ Graus, F Herrlinger, U Schiff, D Raizer, J Rubenstein, J Laperiere, N Abrey, LE AF Grimm, S. A. Pulido, J. S. Omuro, A. Blay, J. Y. Ferreri, A. J. M. Doolittle, N. Batchelor, T. Siegal, R. Jahnke, K. Shenkier, T. N. Hall, A. J. Graus, F. Herrlinger, U. Schiff, D. Raizer, J. Rubenstein, J. Laperiere, N. Abrey, L. E. TI Primary central nervous system lymphoma (PCNSL) with ocular involvement: An international PCNSL collaborative group report SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Hosp Pitie Salpetriere, Paris, France. Oregon Hlth Sci Univ, Int Extranodal Lymphoma Study Grp, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hadassah Hebrew Univ Hosp, Tel Aviv, Israel. Mayo Clin, Rochester, MN USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Royal Melbourne Hosp, Melbourne, Vic, Australia. Univ Tubingen, Tubingen, Germany. Univ Virginia, Charlottesville, VA USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RI Ferreri, Andres Jose Maria/A-6662-2013; Blay, Jean-Yves/N-3966-2016; OI Ferreri, Andres Jose Maria/0000-0001-9606-6124; Blay, Jean-Yves/0000-0001-7190-120X; Omuro, Antonio/0000-0003-4299-3664 NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 443 EP 443 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301202 ER PT J AU Kesari, S Schiff, D Doherty, L Gigas, DC Batchelor, TT Muzikansky, A O'Neill, A Drappatz, J Chen-Plotkin, A Ramakrishna, N Weiss, S Levy, B Bradshaw, J Black, PM Folkman, J Kieran, M Wen, PY AF Kesari, S. Schiff, D. Doherty, L. Gigas, D. C. Batchelor, T. T. Muzikansky, A. O'Neill, A. Drappatz, J. Chen-Plotkin, A. Ramakrishna, N. Weiss, S. Levy, B. Bradshaw, J. Black, P. M. Folkman, J. Kieran, M. Wen, P. Y. TI Phase II study of antiangiogenic (metronomic) chemotherapy for recurrent malignant gliomas SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Univ Virginia, Charlottesville, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 444 EP 445 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301206 ER PT J AU Markert, JM Medlock, MD Rabkin, SD Gillespie, Y Karrasch, M Braz, E Mescheder, A Martuza, RL AF Markert, James M. Medlock, Michael D. Rabkin, Samuel D. Gillespie, Yancey Karrasch, Matthias Braz, Eunice Mescheder, Axel Martuza, Robert L. TI Local treatment of malignant glioma with G207, a genetically engineered HSV-1: Final results of a dose escalating phase 1 study SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Univ Alabama, Dept Neurosurg, Birmingham, AL USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. MedeGene AG, Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 446 EP 446 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301212 ER PT J AU Mohile, NA Lassman, AB Louis, DN Kewalramani, T Forsyth, P Stewart, D Paleologos, N Raizer, JJ DeAngelis, LM Cairncross, JG Abrey, LE AF Mohile, Nimish A. Lassman, Andrew B. Louis, David N. Kewalramani, Tarun Forsyth, Peter Stewart, Douglas Paleologos, Nina Raizer, Jeffrey J. DeAngelis, Lisa M. Cairncross, J. Gregory Abrey, Lauren E. TI High-dose chemotherapy with autologous stem cell rescue (ASCR) for newly diagnosed anaplastic oligodendrogliomal tumors: Preliminary report of an oligodendroglioma study group trial SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calgary, Calgary, AB, Canada. Northwestern Univ, Evanston, IL USA. Northwestern Univ, Chicago, IL 60611 USA. London Reg Canc Ctr, London, ON N6A 4L6, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 447 EP 447 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301216 ER PT J AU Robins, HI O'Neill, A Sapiente, R Olsen, M Gilbert, M Berkey, B Mehta, M AF Robins, H. Ian O'Neill, Anne Sapiente, Ronald Olsen, Mark Gilbert, Mark Berkey, Brian Mehta, Minesh TI A phase II study to evaluate the effect of dalteparin and radiation therapy (XRT) on survival compared to the RTOG RPA database and on thromboembolic events in patients with newly diagnosed glioblastoma multiforme (GBM): A trial of the Eastern Cooperative Oncoloby Group (ECOG) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Carle Clin Assoc, Effingham, IL USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RTOG, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 450 EP 451 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301228 ER PT J AU Wen, PY Yung, WKA Lamborn, K Cloughesy, T DeAngelis, LM Fine, HA Chang, SM Robins, HI Fink, K Abrey, LE Lassman, AB Mehta, M Kesari, S Kim, L Stiles, C Egorin, M Kaplan, R Murgo, A Prados, MD AF Wen, P. Y. Yung, W. K. A. Lamborn, K. Cloughesy, T. DeAngelis, L. M. Fine, H. A. Chang, S. M. Robins, H. I. Fink, K. Abrey, L. E. Lassman, A. B. Mehta, M. Kesari, S. Kim, L. Stiles, C. Egorin, M. Kaplan, R. Murgo, A. Prados, M. D. TI Phase II study of imatinib mesylate (ST1571) for patients with recurrent meningiomas (NABTC 01-08) SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 N Amer Brain Tumor Consortium, Boston, MA USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RI Kesari, Santosh/E-8461-2013; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 6 Z9 6 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 454 EP 454 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301243 ER PT J AU Pelloski, CE Zhang, L Lin, E Baht, K McDonald, JM Yung, WKA Colman, H Woo, SY Heimberger, AB Suki, D Prados, M Chang, S Barker, F Buckner, JC Ballman, KV Furth, AF James, CD Aldape, KD AF Pelloski, Christopher E. Zhang, Li Lin, E. Baht, Krishna McDonald, J. Matthew Yung, W. K. Alfred Colman, Howard Woo, Shiao Y. Heimberger, Amy B. Suki, Dima Prados, Michael Chang, Susan Barker, Fredrick, III Buckner, Jan C. Ballman, Karla V. Furth, Alfred F. James, C. David Aldape, Kenneth D. TI EGFRvIII status defines distinct subtypes of glioblastoma: An analysis of 649 cases SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. Univ Calif San Francisco, Sch Med, Dept Neurosurg, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Mayo Clin, Div Med Oncol, Rochester, MN USA. Mayo Clin, Div Biostat, Rochester, MN USA. Mayo Clin, Div Canc Ctr Stat, Rochester, MN USA. Mayo Clin, Div Expt Pathol, Rochester, MN USA. RI James, Charles/E-2721-2012 OI James, Charles/0000-0002-1027-203X NR 0 TC 4 Z9 4 U1 0 U2 2 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 462 EP 462 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301272 ER PT J AU Yang, ZJ Read, TA Ellis, T Machold, R Fishell, G Rowitch, DH Wainwright, BJ Wechsler-Reya, RJ AF Yang, Zeng-Jie Read, Tracy-Ann Ellis, Tammy Machold, Robert Fishell, Gord Rowitch, David H. Wainwright, Brandon J. Wechsler-Reya, Robert J. TI Lineage-restricted progenitors can serve as cells of origin for medulloblastoma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia. NYU, Sch Med, Skirball Inst, Dev Genet Program, New York, NY USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 471 EP 471 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301307 ER PT J AU Hunt, MA Muldoon, LL Palmieri, D Steeg, PS Neuwelt, EA AF Hunt, M. A. Muldoon, L. L. Palmieri, D. Steeg, P. S. Neuwelt, E. A. TI HER-2 status influences survival in a rat model of brain metastasis from breast cancer SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Natl Canc Inst, Ctr Canc Res, Womens Canc Sect, Mol Pharmacol Lab, Bethesda, MD USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 472 EP 472 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301311 ER PT J AU Knight, KR Kraemer, DF Winter, C Neuwelt, EA AF Knight, K. R. Kraemer, D. F. Winter, C. Neuwelt, E. A. TI Early changes in auditory function as a result of platinum chemotherapy: Use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions in pediatric ototoxicity monitoring SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. Oregon State Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 480 EP 480 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301343 ER PT J AU Blumenthal, DT Berkey, B Nelson, D Curran, W Leibel, S Souhami, L Michalski, J Corn, B Chakravarti, A Rogers, L Mehta, M AF Blumenthal, D. T. Berkey, B. Nelson, D. Curran, W. Leibel, S. Souhami, L. Michalski, J. Corn, B. Chakravarti, A. Rogers, L. Mehta, M. TI 'Short' delay in initiation of radiotherapy may not affect the outcome of patients with GBM: A secondary analysis from the RTOG database SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. RTOG, Philadelphia, PA USA. Mayo Clin, Rochester, MN USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. McGill Univ, Montreal, PQ, Canada. Washington Univ, St Louis, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. GammaWest Radiat Therapy, Salt Lake City, UT USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 483 EP 483 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301353 ER PT J AU Ramakrishna, NR O'Halloran, M Sullivan, S Kesari, S Wen, PY Bachoo, R Stiles, CD AF Ramakrishna, N. R. O'Halloran, M. Sullivan, S. Kesari, S. Wen, P. Y. Bachoo, R. Stiles, C. D. TI The alkylphospholipid perifosine inhibits Akt and sensitizes murine and human glioma cells to radiation in vitro and in vivo SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Neurooncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 488 EP 488 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301373 ER PT J AU Mrugala, MM Cai, W Kassarjian, A Harris, GJ Maccollin, MM Plotkin, SR AF Mrugala, Maciej M. Cai, Wenli Kassarjian, Ara Harris, Gordon J. Maccollin, Mia M. Plotkin, Scott R. TI Whole-body MRI as a useful tool in assessment of the tumor burden in patients with neurofibromatoses SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 496 EP 496 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301402 ER PT J AU Neuwelt, EA Varallyay, C Manninger, S Solymosi, D Hunt, MA Jerosch-Herold, M Nesbit, G Hoffman, JM AF Neuwelt, E. A. Varallyay, C. Manninger, S. Solymosi, D. Hunt, M. A. Jerosch-Herold, M. Nesbit, G. Hoffman, J. M. TI Comparison of ferumoxytol, an iron oxide nanoparticle, vs. gadolinium in MR perfusion of malignant brain tumors SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Univ Utah, Sch Med, Salt Lake City, UT USA. RI Jerosch-Herold, Michael/F-2496-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 496 EP 497 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301403 ER PT J AU Neuwelt, EA Wu, YJ Varallyay, C Jones, R Muldoon, LL AF Neuwelt, E. A. Wu, Y. J. Varallyay, C. Jones, R. Muldoon, L. L. TI In vivo leukocyte iron labeling with intravenous ferumoxides and protamine sulfate for cellular magnetic resonance imaging SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 497 EP 497 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301404 ER PT J AU Shah, K Hingtgen, S Kasmieh, R Weissleder, R AF Shah, Khalid Hingtgen, Shawn Kasmieh, Randa Weissleder, Ralph TI Therapeutically engineered neural stem cells for glioma therapy: In vivo gene transfer and real-time imaging of NSC fate and tumor regression SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Massachusetts Gen Hosp, Ctr Mol Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Ctr Mol Imaging, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 498 EP 498 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301408 ER PT J AU Soussain, C Muldoon, LL Varallyay, C Jahnke, K Neuwelt, EA AF Soussain, C. Muldoon, L. L. Varallyay, C. Jahnke, K. Neuwelt, E. A. TI Characterization and magnetic resonance imaging of a rat model of human B-cell central nervous system lymphoma SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 7th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 14-17, 2006 CL Vienna, AUSTRIA SP European Assoc Neuro Oncol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2006 VL 8 IS 4 BP 498 EP 498 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 089JS UT WOS:000240877301409 ER PT J AU Filley, CM Ramsberger, G Menn, L Wu, J Reid, BY Reid, AL AF Filley, Christopher M. Ramsberger, Gail Menn, Lise Wu, Jiang Reid, Bessie Y. Reid, Allan L. TI Primary progressive aphasia in a bilingual woman SO NEUROCASE LA English DT Article ID BRAIN AB Multilingual aphasias are common because most people in the world know more than one language, but little is known of these syndromes except in patients who have had a stroke. We present a 76-year-old right-handed woman, fluent in English and Chinese, who developed anomia at age 70 and then progressed to aphasia. Functional neuroimaging disclosed mild left temporoparietal hypometabolism. Neurolinguistic testing was performed in both English and Chinese, representing a unique contribution to the literature. Results revealed conduction-like aphasia that was comparable in the two languages, although English was slightly better preserved. Primary progressive aphasia has disrupted 2 languages in a similar manner, suggesting their close neuroanatomic relationship in this case. C1 Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Dept Speech Language & Hearing Sci, Boulder, CO 80309 USA. Univ Colorado, Dept Linguist, Boulder, CO 80309 USA. RP Filley, CM (reprint author), Univ Colorado, Hlth Sci Ctr, Behav Neurol Sect, B-183,4200 E 9th Ave, Denver, CO 80262 USA. EM christopher.filley@uchsc.edu OI Menn, Lise/0000-0003-2583-1292; RAMSBERGER, GAIL/0000-0003-3161-4710 NR 15 TC 10 Z9 11 U1 1 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PD OCT PY 2006 VL 12 IS 5 BP 296 EP 299 DI 10.1080/13554790601126047 PG 4 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 120KB UT WOS:000243082500005 PM 17190751 ER PT J AU Sigalovsky, IS Fischl, B Melcher, JR AF Sigalovsky, Irina S. Fischl, Bruce Melcher, Jennifer R. TI Mapping an intrinsic MR property or gray matter in auditory cortex of living humans: A possible marker for primary cortex and hemispheric differences SO NEUROIMAGE LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the Organization-for-Human-Brain-Mapping CY JUN 12-16, 2005 CL Toronto, CANADA SP Org Human Brain Mapping DE MRI; T1; cortical thickness; primary auditory cortex; Brodmann areas; brain asymmetry; temporal processing; dyslexia ID MAGNETIC-RESONANCE IMAGES; HUMAN CEREBRAL-CORTEX; HIGH-RESOLUTION MRI; MULTIPLE-SCLEROSIS; SPEECH-PERCEPTION; TEMPORAL PERCEPTION; REGIONAL VARIATION; VOLUME MEASUREMENT; CORTICAL CHANGE; VISUAL-CORTEX AB Recently, magnetic resonance properties of cerebral gray matter have been spatially mapped - in vivo - over the cortical surface. In one of the first neuroscientific applications of this approach, this study explores what can be learned about auditory cortex in living humans by mapping longitudinal relaxation rate (RI), a property related to myelin content. Gray matter R1 (and thickness) showed repeatable trends, including the following: (1) Regions of high R1 were always found overlapping posteromedial Heschl's gyros. They also sometimes occurred in planum temporale and never in other parts of the superior temporal lobe. We hypothesize that the high RI overlapping Heschl's gyrus (which likely indicates dense gray matter myelination) reflects auditory koniocortex (i.e., primary cortex), a heavily myelinated area that shows comparable overlap with the gyrus. High R1 overlapping Heschl's gyrus was identified in every instance suggesting that RI may ultimately provide a marker for koniocortex in individuals. Such a marker would be significant for auditory neuroimaging, which has no standard means (anatomic or physiologic) for localizing cortical areas in individual subjects. (2) Inter-hemispheric comparisons revealed greater R1 on the left on Heschl's gyrus, planum temporale, superior temporal gyros and superior temporal sulcus. This asymmetry suggests greater gray matter myelination in left auditory cortex, which may be a substrate for the left hemisphere's specialized processing of speech, language, and rapid acoustic changes. These results indicate that in vivo R1 mapping can provide new insights into the structure of human cortical gray matter and its relation to function. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. MIT, CSAIL, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Sigalovsky, IS (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM plumbum@alum.mit.edu FU NCRR NIH HHS [P41 RR014075, P41RR14075, R01 RR016594, R01 RR16594-01A1, U24 RR021382]; NIBIB NIH HHS [R01 EB001550]; NIDCD NIH HHS [P01 DC000119, P01 DC00119, P30 DC005209, R21 DC006071] NR 79 TC 78 Z9 79 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 1 PY 2006 VL 32 IS 4 BP 1524 EP 1537 DI 10.1016/j.neuroimage.2006.05.023 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 090RR UT WOS:000240969200004 PM 16806989 ER PT J AU Kirschner, J Osmers, U Rao, A Ehl, S Feske, S AF Kirschner, J. Osmers, U. Rao, A. Ehl, S. Feske, S. TI A new combined phenotype of congenital myopathy, hypohydrotic ectodermal dysplasia and immunodeficiency in two brothers SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 11th International Congress of the World-Muscle-Society CY OCT 04-07, 2006 CL Bruges, BELGIUM SP World Muscle Soc C1 Univ Freiburg, Dept Neuropediat & Muscle Disorders, Freiburg, Germany. CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Univ Freiburg, Dept Pediat & Adolescent Med, Freiburg, Germany. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RI Kirschner, Janbernd/H-7418-2016 OI Kirschner, Janbernd/0000-0003-1618-7386 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2006 VL 16 IS 9-10 BP 690 EP 690 DI 10.1016/j.nmd.2006.05.154 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 096HY UT WOS:000241369400151 ER PT J AU Kovalenko, OV Wiese, C Schild, D AF Kovalenko, Oleg V. Wiese, Claudia Schild, David TI RAD51AP2, a novel vertebrate- and meiotic-specific protein, shares a conserved RAD51-interacting C-terminal domain with RAD51AP1/PIR51 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRANDED-DNA; HOMOLOGOUS RECOMBINATION; BINDING-PROTEIN; SYNAPTONEMAL COMPLEXES; NUCLEAR FOCI; BREAK REPAIR; ENZYME UBC9; YEAST RAD51; INTERACTS; BRCA2 AB Many interacting proteins regulate and/or assist the activities of RAD51, a recombinase which plays a critical role in both DNA repair and meiotic recombination. Yeast two-hybrid screening of a human testis cDNA library revealed a new protein, RAD51AP2 (RAD51 Associated Protein 2), that interacts strongly with RAD51. A full-length cDNA clone predicts a novel vertebrate-specific protein of 1159 residues, and the RAD51AP2 transcript was observed only in meiotic tissue (i.e. adult testis and fetal ovary), suggesting a meiotic-specific function for RAD51AP2. In HEK293 cells the interaction of RAD51 with an ectopically-expressed recombinant large fragment of RAD51AP2 requires the C-terminal 57 residues of RAD51AP2. This RAD51-binding region shows 81% homology to the C-terminus of RAD51AP1/PIR51, an otherwise totally unrelated RAD51-binding partner that is ubiquitously expressed. Analyses using truncations and point mutations in both RAD51AP1 and RAD51AP2 demonstrate that these proteins use the same structural motif for RAD51 binding. RAD54 shares some homology with this RAD51-binding motif, but this homologous region plays only an accessory role to the adjacent main RAD51-interacting region, which has been narrowed here to 40 amino acids. A novel protein, RAD51AP2, has been discovered that interacts with RAD51 through a C-terminal motif also present in RAD51AP1. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. RP Schild, D (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM dschild@lbl.gov FU NCI NIH HHS [CA92584, P01 CA092584, P01 CA92584] NR 49 TC 9 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT PY 2006 VL 34 IS 18 BP 5081 EP 5092 DI 10.1093/nar/gkl665 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 104JQ UT WOS:000241955100016 PM 16990250 ER PT J AU Jones, DA AF Jones, Dorothy A. TI Newman's health as expanding consciousness SO NURSING SCIENCE QUARTERLY LA English DT Article DE health as expanding consciousness; Newman ID WOMEN C1 Massachusetts Gen Hosp, Boston Coll, William F Connell Sch Nursing, Boston, MA 02114 USA. RP Jones, DA (reprint author), Massachusetts Gen Hosp, Boston Coll, William F Connell Sch Nursing, Boston, MA 02114 USA. NR 17 TC 1 Z9 1 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0894-3184 J9 NURS SCI QUART JI Nurs. Sci. Q. PD OCT PY 2006 VL 19 IS 4 BP 330 EP 332 DI 10.1177/0894318406293136 PG 3 WC Nursing SC Nursing GA 087VY UT WOS:000240772100014 PM 16982719 ER PT J AU Garcia, JM Iyer, D Poston, WSC Marcelli, M Reeves, R Foreyt, J Balasubramanyam, A AF Garcia, Jose M. Iyer, Dinakar Poston, Walker S. C. Marcelli, Marco Reeves, Rebecca Foreyt, John Balasubramanyam, Ashok TI Rise of plasma ghrelin with weight loss is not sustained during weight maintenance SO OBESITY LA English DT Article DE overweight; orlistat; Mexican American; leptin; insulin ID GASTRIC BYPASS-SURGERY; INSULIN-RESISTANCE; FOOD-INTAKE; CIRCULATING GHRELIN; MEXICAN-AMERICANS; HUMAN OBESITY; US ADULTS; HUMANS; PREVALENCE; LEPTIN AB Objective: Ghrelin is postulated to be an orexigenic signal that promotes weight regain after weight loss (WL). However, it is not known whether this putative effect of ghrelin is sustained after weight stabilization. The objective of this study was to investigate the relationship of plasma ghrelin concentrations to active WL and weight maintenance in obese subjects. Research Methods and Procedures: This study was a randomized clinical trial, with a 12-month follow-up period. Obese Mexican-American women matched for age and BMI were randomized to a 12-month WL program (n = 25) or no intervention (controls, n = 23). Interventions included diet, exercise, and orlistat. Body weight and fasting ghrelin, leptin, insulin, and glucose concentrations were measured at baseline and 6 and 12 months. Results: The WL group lost 8.5% of body weight after 6 months and maintained the new weight for the next 6 months. Ghrelin concentrations increased significantly at 6 months but returned to baseline at 12 months. Baseline ghrelin concentrations were directly related to the degree of WL achieved after 12 months. Controls experienced no change in BMI or ghrelin levels. There were no associations between plasma ghrelin and leptin or insulin concentrations. Discussion: Consistent with previous results, ghrelin rises in response to WL, perhaps as a counter-regulatory mechanism. However, the present results indicate that ghrelin concentrations return to baseline with sustained weight maintenance, suggesting that its effects are unlikely to regulate long-term energy balance. Baseline ghrelin concentrations are related to the degree of WL that can be achieved by active weight reduction. C1 Baylor Coll Med, Div Endocrinol Diabet & Metab, Translat Metab Unit, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Univ Missouri, Kansas City, MO 64110 USA. Baylor Coll Med, Sect Behav Med, Houston, TX USA. Ben Taub Gen Hosp, Endocrine Serv, Houston, TX 77030 USA. RP Balasubramanyam, A (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Translat Metab Unit, Room 700B,1 Baylor Plaza, Houston, TX 77030 USA. EM ashokb@bctn.tmc.edu FU NHLBI NIH HHS [R01 HL73696] NR 39 TC 34 Z9 36 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2006 VL 14 IS 10 BP 1716 EP 1723 DI 10.1038/oby.2006.197 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 212OE UT WOS:000249605900006 PM 17062800 ER PT J AU Borello-France, D Burgio, KL Richter, HE Zyczynski, H FitzGerald, MP Kitehead, W Fine, P Nygaard, I Handa, VL Visco, AG Weber, AM Brown, MB AF Borello-France, Diane Burgio, Kathryn L. Richter, Holly E. Zyczynski, Halina FitzGerald, Mary Pat Kitehead, William Fine, Paul Nygaard, Ingrid Handa, Victoria L. Visco, Anthony G. Weber, Anne M. Brown, Morton B. CA Pelvic Floor Disorders Network TI Fecal and urinary incontinence in primiparous women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ANAL-SPHINCTER RUPTURE; VAGINAL DELIVERY; POSTPARTUM URINARY; CESAREAN DELIVERY; PREVALENCE; RISK; SYMPTOMS; DISRUPTION; INCREASE; DAMAGE AB OBJECTIVE: To prospectively investigate the relationship between anal sphincter tears and postpartum fecal and urinary incontinence. METHODS: The Childbirth and Pelvic Symptoms study was a prospective cohort study performed by the Pelvic Floor Disorders Network to estimate the prevalence of postpartum fecal and urinary incontinence in primiparous women: 407 with clinically recognized anal sphincter tears during vaginal delivery, 390 without recognized sphincter tears (vaginal controls), and 124 delivered by cesarean before labor. Women were recruited postpartum while hospitalized and interviewed by telephone 6 weeks and 6 months postpartum. We assessed fecal and urinary incontinence symptoms using the Fecal Incontinence Severity Index and the Medical, Epidemiological, and Social Aspects of Aging Questionnaire, respectively. Odds ratios were adjusted for age, race, and clinical site. RESULTS: Compared with the vaginal control group, women in the sphincter tear cohort reported more fecal incontinence (6 weeks, 26.6% versus 11.2%; adjusted odds ratio [AOR] 2.8, 95% confidence interval [CI] 1.84.3; 6 months, 17.0% versus 8.2%; AOR 1.9, 95% CI 1.2-3.2), more fecal urgency and flatal incontinence, and greater fecal incontinence severity at both times. Urinary incontinence prevalence did not differ between the sphincter tear and vaginal control groups. Six months postpartum, 22.9% of women delivered by cesarean reported urinary incontinence, whereas 7.6% reported fecal incontinence. CONCLUSION: Women with clinically recognized anal sphincter tears are more than twice as likely to report postpartum fecal incontinence than women without sphincter tears. Cesarean delivery before labor is not entirely protective against pelvic floor disorders. C1 Duquesne Univ, Dept Phys Therapy, Pittsburgh, PA 15282 USA. Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Iowa, Iowa City, IA 52242 USA. Johns Hopkins Univ, Baltimore, MD USA. Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Borello-France, D (reprint author), Duquesne Univ, Dept Phys Therapy, 111 Hlth Sci Bldg, Pittsburgh, PA 15282 USA. EM borellofrance@duq.edu FU NICHD NIH HHS [U01 HD41249, U10 HD041261, U10 HD041263, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269] NR 43 TC 132 Z9 135 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2006 VL 108 IS 4 BP 863 EP 872 DI 10.1097/01.AOG.0000232504.32589.3b PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 171XS UT WOS:000246769300007 PM 17012447 ER PT J AU Papadaki, TG Kafkala, C Zacharopoulos, IP Seyedahmadi, JB Dryja, T AF Papadaki, Thekla G. Kafkala, Chrysanthi Zacharopoulos, Ioannis P. Seyedahmadi, Jian B. Dryja, Thaddeus TI Conjunctival non-caseating granulomas in a human immunodeficiency virus (HIV) positive patient attributed to sarcoidosis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE conjunctival non-caseating granuloma; HIV; sarcoidosis ID ACTIVE ANTIRETROVIRAL THERAPY AB Purpose: To report a rare case of isolated ocular sarcoidosis in an HIV positive patient. Design: Case report. Methods: A 47-year-old HIV+ Caucasian male was referred for chronic bilateral follicular conjunctivitis. Results: A conjunctival biopsy that was performed on the right eye showed sarcoidosis. General medical evaluation including a spiral thin cut chest CT scan revealed no systemic involvement. The ocular signs and symptoms resolved completely with topical corticosteroid treatment. Conclusions: HIV infection and sarcoidosis rarely coexist, presumably because their immunopathogenesis mechanisms diverge. In the absence of systemic involvement, a definite diagnosis can only be made by biopsy of the ocular tissues. C1 Massachusetts Eye Res & Surg Inst, Ocular Immunol & Uveitis Fdn, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Univ Crete, Dept Ophthalmol, Iraklion, Greece. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Eye Pathol Serv, Boston, MA USA. RP Papadaki, TG (reprint author), 40 Anopoleos St, Iraklion 71201, Crete, Greece. EM theklapap@med.uoc.gr NR 4 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD OCT PY 2006 VL 14 IS 5 BP 309 EP 311 DI 10.1080/09273940600899676 PG 3 WC Ophthalmology SC Ophthalmology GA 097GP UT WOS:000241435500008 PM 17056466 ER PT J AU Avruch, J Hara, K Lin, Y Liu, M Long, X Ortiz-Vega, S Yonezawa, K AF Avruch, J. Hara, K. Lin, Y. Liu, M. Long, X. Ortiz-Vega, S. Yonezawa, K. TI Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase SO ONCOGENE LA English DT Review DE TOR; Rheb; TSC; S6K; raptor; leucine ID P70 S6 KINASE; TUMOR-SUPPRESSOR COMPLEX; RIBOSOMAL-PROTEIN S6; RAPAMYCIN-INDUCED INHIBITION; TSC2 GAP ACTIVITY; REPRESSOR PHAS-I; B-RAF KINASE; MAMMALIAN TARGET; CELL-GROWTH; TUBEROUS-SCLEROSIS AB Target of Rapamycin ( TOR), a giant protein kinase expressed by all eucaryotic cells, controls cell size in response to nutrient signals. In metazoans, cell and organismal growth is controlled by nutrients and the insulin/insulin-like growth factor (IGF) system, and the understanding of how these inputs coordinately regulate TOR signaling has advanced greatly in the past 5 years. In single-cell eucaryotes and Caenorhabditis elegans, TOR is a dominant regulator of overall mRNA translation, whereas in higher metazoans, TOR controls the expression of a smaller fraction of mRNAs that is especially important to cell growth. TOR signals through two physically distinct multiprotein complexes, and the control of cell growth is mediated primarily by TOR complex 1 (TORC1), which contains the polypeptides raptor and LST8. Raptor is the substrate binding element of TORC1, and the ability of raptor to properly present substrates, such as the translational regulators 4E-BP and p70 S6 kinase, to the TOR catalytic domain is essential for their TOR-catalysed phosphorylation, and is inhibited by the Rapamycin/FKBP-12 complex. The dominant proximal regulator of TORC1 signaling and kinase activity is the ras-like small GTPase Rheb. Rheb binds directly to the mTOR catalytic domain, and Rheb-GTP enables TORC1 to attain an active configuration. Insulin/IGF enhances Rheb GTP charging through the ability of activated Akt to inhibit the Rheb-GTPase-activating function of the tuberous sclerosis heterodimer (TSC1/TSC2). Conversely, energy depletion reduces Rheb-GTP charging through the ability of the adenosine monophosphate-activated protein kinase to phosphorylate TSC2 and stimulate its Rheb-GTPase activating function, as well as by HIF alpha-mediated transcriptional responses that act upstream of the TSC1/2 complex. Amino-acid depletion inhibits TORC1 acting predominantly downstream of the TSC complex, by interfering with the ability of Rheb to bind to mTOR. The components of the insulin/IGF pathway to TORC1 are now well established, whereas the elements mediating the more ancient and functionally dominant input of amino acids remain largely unknown. C1 Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Boston, MA 02114 USA. Kobe Univ, Grad Sch Med, Div Internal & Geriatr Med, Cyuo Ku, Kobe, Hyogo 657, Japan. Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo, Japan. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Simches Res Bldg 6408,185 Cambridge St, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu FU NCI NIH HHS [CA73818]; NIDDK NIH HHS [DK17776] NR 128 TC 197 Z9 207 U1 3 U2 21 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 PY 2006 VL 25 IS 48 BP 6361 EP 6372 DI 10.1038/sj.onc.1209882 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 096MH UT WOS:000241380700003 PM 17041622 ER PT J AU Abrahm, JL AF Abrahm, Janet L. TI Cancer Pain Management in the 21st century - The Grossman/Dunbar/Nesbit article reviewed SO ONCOLOGY-NEW YORK LA English DT Review C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Pain & Palliat Care Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Abrahm, JL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 4 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 OCT PY 2006 VL 20 IS 11 BP 1340 EP + PG 2 WC Oncology SC Oncology GA V44BJ UT WOS:000202977900002 ER PT J AU Brugge, WR AF Brugge, William R. TI Endoscopic ultrasound fine-needle aspiration in the staging of non-small-cell lung cancer - The Ogita/Robbins/Blum et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 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 OCT PY 2006 VL 20 IS 11 BP 1426 EP + PG 3 WC Oncology SC Oncology GA V44BJ UT WOS:000202977900018 ER PT J AU Sledge, JB AF Sledge, John B., III TI Management of femoral neck stress fractures SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE LA English DT Article DE stress fracture; femoral neck; treatment; review; imaging; diagnosis; complications AB Stress fractures are caused by repetitive submaximal loading of bone that causes microtrauma, where the bone either temporally or biomechanically does not have the ability to recover before repeated loading. Stress fractures are being diagnosed more frequently as the result of increased surveillance on the part of the physician and increased prevalence on the part of the patient. The diagnosis is made by a combination of history, physical examination, and imaging. Magnetic resonance imaging is the imaging modality of choice, after plain films, because of its greater specificity and sensitivity. Stress fractures are classified based on their cause, their location, their severity, their risk of progression, and the appearance of the fracture line. Treatment of femoral neck stress fractures is based on the duration of symptoms, the fracture classification, and the patient's expectations. Treatment starts with activity modification and progresses to cannulated screws, sliding hip screw, blade plate, and/or intertrochanteric osteotomy. Predictors of successful surgical outcomes are accurate fracture classification, early anatomic reduction, addressing of any varus deformity in the reduction or the native neck, and placing the fracture line as horizontal as reasonable when performing an osteotomy. Mild fractures in the recreational athlete will lead to a period of decreased activity, rapid healing, and return to full activity, whereas more severe fractures will require more intervention and a longer recovery period. Displaced fractures have a high rate of avascular necrosis, pseudoarthrosis, refracture, and progressive arthrosis. Elite athletes require aggressive management and, even then, are unlikely to return to their previous professional level. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sledge, JB (reprint author), Sports Med N Orthopaed Surg Inc, 1 Orthoped Dr, Peabody, MA 01960 USA. EM josledge@sportsmednorth.com NR 27 TC 3 Z9 3 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1060-1872 J9 OPER TECHN SPORT MED JI Oper. Tech. Sports Med. PD OCT PY 2006 VL 14 IS 4 BP 265 EP 269 DI 10.1053/j.otsm.2006.10.002 PG 5 WC Sport Sciences; Surgery SC Sport Sciences; Surgery GA 115ZY UT WOS:000242773500007 ER PT J AU Pletcher, SD Sindwani, R Metson, R AF Pletcher, Steven D. Sindwani, Raj Metson, Ralph TI Endoscopic orbital and optic nerve decompression SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID GRAVES OPHTHALMOPATHY; NEUROPATHY; RADIOTHERAPY; DIPLOPIA; STRUT AB The endoscopic transnasal approach is well suited for decompression of both the orbit and optic canal. High-resolution nasal endoscopes provide excellent visualization for bone removal along the orbital apex and skull base. Endoscopic orbital decompression has proved to be safe and effective for the treatment of patients with Graves' orbitopathy; however, the indications and outcomes for endoscopic decompression of the optic nerve remain controversial. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO USA. Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. RP Metson, R (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM ralph_metson@meei.harvard.edu NR 27 TC 21 Z9 25 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2006 VL 39 IS 5 BP 943 EP + DI 10.1016/j.otc.2006.06.003 PG 17 WC Otorhinolaryngology SC Otorhinolaryngology GA 094LL UT WOS:000241240800008 PM 16982256 ER PT J AU Cunningham, MJ AF Cunningham, Michael J. TI Endoscopic management of pediatric nasolacrimal anomalies SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID LACRIMAL SAC MUCOCELES; MECHANICAL ENDONASAL DACRYOCYSTORHINOSTOMY; RESPIRATORY-DISTRESS; NASAL OBSTRUCTION; DUCT OBSTRUCTION; SURGERY; CHILDREN; EXTENSION; SEQUELA; NEONATE AB Developmental anomalies of the nasolacrimal drainage system typically manifest early in childhood with epiphora and occasionally infection. Although the majority of cases of congenital nasolacrimal obstruction resolve spontaneously with conservative medical management, certain anomalies require operative intervention. Included in this latter group are dacryocystoceles or nasolacrimal duct cysts. The application of endoscopic sinus surgical techniques to children with persistent symptomatic nasolacrimal obstruction provides an alternative to external dacryocystorhinostomy that appears to be equally efficacious and concurrently allows for the potential correction of any predisposing intranasal pathology. Endonasal endoscopic dacryocystorhinostomy is best performed as a joint otolaryngologic-ophthalmologic procedure. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM michael_cunningham@meei.harvard.edu NR 49 TC 10 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2006 VL 39 IS 5 BP 1059 EP + DI 10.1016/j.otc.2006.07.004 PG 18 WC Otorhinolaryngology SC Otorhinolaryngology GA 094LL UT WOS:000241240800015 PM 16982263 ER PT J AU Mowry, SE LoTempio, MM Sadeghi, A Wang, KH Wang, MB AF Mowry, Sarah E. LoTempio, Maria M. Sadeghi, Ahmad Wang, Kevin H. Wang, Marilene B. TI Quality of life outcomes in laryngeal and oropharyngeal cancer patients after chemoradiation SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID NECK-CANCER; ORGAN PRESERVATION; ADVANCED HEAD; CONCOMITANT CHEMORADIOTHERAPY; RADIATION-THERAPY; UW-QOL; CHEMOTHERAPY; PERFORMANCE; CARCINOMA; DIAGNOSIS AB OBJECTIVE: The purpose of this study was to compare quality of life issues in patients with advanced laryngeal versus oropharyngeal cancer after treatment with chemoradiation. DESIGN: A cohort study of 31 patients with laryngeal or oropharyngeal squamous cell carcinoma treated with chemoradiation completed the University of Washington quality of life instrument version 4 (UW-QOL v4). Statistical analysis was performed with Wilcoxon rank sum and chi-square tests. SETTING: Academic tertiary care center. RESULTS: Both groups reported similar impairment in the domains of swallowing, chewing, and taste. Oropharyngeal cancer patients reported significantly worse quality of life in the domain of saliva (P < 0.007). CONCLUSION: Swallowing, chewing, and taste were adversely affected by chemoradiation for both groups. Oropharyngeal patients experienced significantly worse problems with saliva than laryngeal patients. These patients reported high levels of satisfaction with health-related quality of life issues. SIGNIFICANCE: Specific head and neck subsites have different morbidities when treated with primary chemoradiation for advanced tumors. (C) 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Radiat Oncol, Los Angeles, CA USA. NYU, Sch Med, Dept Otolaryngol, New York, NY USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, 10833 Le Conte Ave,CHS 62-132, Los Angeles, CA 90095 USA. EM mbwang@ucla.edu NR 20 TC 16 Z9 18 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2006 VL 135 IS 4 BP 565 EP 570 DI 10.1016/j.otohns.2006.06.1266 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 094AD UT WOS:000241210500015 PM 17011418 ER PT J AU Stryker, JE Wray, RJ Emmons, KM Winer, E Demetri, G AF Stryker, Jo Ellen Wray, Ricardo J. Emmons, Karen M. Winer, Eric Demetri, George TI Understanding the decisions of cancer clinical trial participants to enter research studies: Factors associated with informed consent, patient satisfaction, and decisional regret SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE informed consent; clinical trials; decision-making; cancer ID ANTICANCER DRUG TRIALS; QUALITY-OF-LIFE; PROSTATE-CANCER; PHASE-I; PERSPECTIVES; EXPERIENCES; ONCOLOGY; SCALE AB Objective: To understand the psychosocial outcomes related to decision-making processes of individuals eligible for participation in clinical trials. Methods: Individuals eligible to participate in selected clinical trials were contacted to complete two surveys; one shortly after participants were identified, and the second 6 weeks after the first survey was completed (N = 50). Measures included subjective informed consent; satisfaction with decision-making; decisional regret; and timing of consent (early versus late signers). ANOVA and correlation coefficients were used to test the relationships between variables. Results: Early signers reported themselves to be less informed about the details of their particular clinical trials than later signers (M = 81.9 versus 91.2; F = 5.5; p =.02). There was a non-significant trend for early signers to be less satisfied with their decisions than late signers. Satisfaction with decision-making and subjective informed consent were both strongly associated with later decisional regret (r = -.32 and -.30, respectively). However, there was no relationship between timing of consent and decisional regret. Conclusion: Participants who enroll in clinical trials quickly may not believe they fully understand the implications of trial participation. In general, participants who do not believe they fully understand the implications of trial participation, or who are less satisfied with their decision to enroll in the trial may ultimately feel regret about their decision to participate. Practice implications: More effort is needed to ensure that clinical trial participants fully understand the risks and benefits of participation and are satisfied with their decision to enroll in a trial prior to signing consent forms. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Emory Univ, Dept Behav Sci & Hlth Educ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. St Louis Univ, Sch Publ Hlth, Hlth Commun Res Lab, St Louis, MO 63103 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Stryker, JE (reprint author), Emory Univ, Dept Behav Sci & Hlth Educ, Rollins Sch Publ Hlth, 1518 Clifton Rd NE,Rm 572, Atlanta, GA 30322 USA. EM jestryk@sph.emory.edu NR 24 TC 53 Z9 54 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2006 VL 63 IS 1-2 BP 104 EP 109 DI 10.1016/j.pec.2005.09.006 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 093LP UT WOS:000241170100014 PM 16242898 ER PT J AU Ingelfinger, JR AF Ingelfinger, Julie R. TI The molecular basis of pediatric hypertension SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID APPARENT MINERALOCORTICOID EXCESS; SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE SCAN; GLUCOCORTICOID-SUPPRESSIBLE ALDOSTERONISM; EPITHELIAL SODIUM-CHANNEL; SYSTOLIC BLOOD-PRESSURE; PSEUDOHYPOALDOSTERONISM TYPE-II; EPIDEMIOLOGY NETWORK HYPERGEN; QUANTITATIVE TRAIT LOCUS; PLASMA-RENIN ACTIVITY AB Blood pressure, the product of cardiac output and peripheral vascular resistance, follows a circadian rhythm and is altered by a host of circulating and local substances and by many physiologic events. The number of genes, signaling pathways, and systems involved in blood pressure regulation is enormous, and dissecting OF those factors that are most important in hypertension has proven challenging. This article discusses molecular mechanisms of hypertension in several conditions in which mutations in a single gene give rise to hypertension and then considers the contribution of these and other genes to essential hypertension. C1 MassGen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ingelfinger, JR (reprint author), MassGen Hosp Children, 55 Fruit St,Yawkey 6C, Boston, MA 02114 USA. EM jingelfinger@partners.org NR 110 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 2006 VL 53 IS 5 BP 1011 EP + DI 10.1016/j.pcl.2006.08.005 PG 20 WC Pediatrics SC Pediatrics GA 102HS UT WOS:000241802200012 PM 17027621 ER PT J AU Charron-Prochownik, D Sereika, SM Falsetti, D Wang, SL Becker, D Jacober, S Mansfield, J White, NH AF Charron-Prochownik, Denise Sereika, Susan M. Falsetti, Donna Wang, Shiaw-Ling Becker, Dorothy Jacober, Scott Mansfield, Joan White, Neil H. TI Knowledge, attitudes and behaviors related to sexuality and family planning in adolescent women with and without diabetes SO PEDIATRIC DIABETES LA English DT Article DE adolescent; birth control; diabetes; reproductive health; sexual activity ID PRE-CONCEPTION CARE; PRECONCEPTION CARE; CONTRACEPTION; PREGNANCY; IMPACT; IDDM AB Background: Sexually active adolescents with diabetes are at high risk for unplanned pregnancies and reproductive complications. Objective: Knowledge, attitudes, intentions, and behaviors regarding diabetes and reproductive issues, sexuality, and contraception were examined in teens with diabetes in relation to a non-diabetic group. Methods: A multisite, case-control, theory-based structured telephone interview was conducted on adolescent women: 80 with diabetes mellitus (DM) and 37 matched controls without diabetes (non-DM). Results: Teens with diabetes appeared to lack an understanding of critical information that could prevent unplanned pregnancies and pregnancy-related complications. Although they scored significantly higher than the non-DM group on diabetes-related information, the DM group had their lowest mean average of 59% for the diabetes and pregnancy score. They did not appear to have greater protective attitudes regarding reproductive health issues than the non-DM group. The DM group felt that they were only moderately susceptible to becoming pregnant and that severe complications would not happen to them. The DM group perceived greater severity to sex-related outcomes (p = 0.001). The DM group did not report safer and more effective family planning behaviors (mean age coitus = 15.7 yr), which for them could be more detrimental. Similar trends were noted between groups regarding contraceptive methods; only a single method (e.g., pill only) rather than a dual method (e.g., pill and condom) was most frequently used. Conclusion: Having diabetes did not appear to significantly decrease the risk-taking behavior of the teens. Early and some unsafe sexual practices may increase their risk for an unplanned pregnancy that could result in pregnancy-related complications. Enhancing awareness, knowledge, and attitudes through preconception counseling and reproductive health education may reduce these risks by empowering young women to plan healthy future pregnancies. C1 Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Washington Univ, Sch Med, St Louis Childrens Hosp, St Louis, MO USA. RP Charron-Prochownik, D (reprint author), Univ Pittsburgh, Sch Nursing, 440 Victoria Bldg, Pittsburgh, PA 15261 USA. EM dcpro@pitt.edu FU NIDDK NIH HHS [P30 DK056341, P30 DK056341-05S2, P30 DK056341-06]; NINR NIH HHS [5P30NR03924] NR 35 TC 17 Z9 17 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD OCT PY 2006 VL 7 IS 5 BP 267 EP 273 DI 10.1111/j.1399-5448.2006.00197.x PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 095ZD UT WOS:000241345900006 PM 17054448 ER PT J AU Jonker, S Louey, S Thornburg, K Giraud, G AF Jonker, S. Louey, S. Thornburg, K. Giraud, G. TI In vivo administration of U0126 to the sheep fetus blocks acute and chronic cardiac ERK phosphorylation SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 47th Annual Meeting of the Midwest Society-for-Pediatric-Research CY OCT 18-20, 2006 CL Indianapolis, IN C1 Oregon Hlth Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 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 OCT PY 2006 VL 60 IS 4 MA 21 BP 494 EP 494 DI 10.1203/00006450-200610000-00043 PG 1 WC Pediatrics SC Pediatrics GA 086XX UT WOS:000240707500043 ER PT J AU Jonker, S Louey, S Thornburg, K Giraud, G AF Jonker, S. Louey, S. Thornburg, K. Giraud, G. TI Cardiac ERK activation during sustained arterial and venous hypertension in the sheep fetus SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 47th Annual Meeting of the Midwest Society-for-Pediatric-Research CY OCT 18-20, 2006 CL Indianapolis, IN C1 Oregon Hlth Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 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 OCT PY 2006 VL 60 IS 4 MA 30 BP 495 EP 495 DI 10.1203/00006450-200610000-00052 PG 1 WC Pediatrics SC Pediatrics GA 086XX UT WOS:000240707500052 ER PT J AU Feldman, MJ Barnett, GO Link, DA Coleman, MA Lowe, JA O'Rourke, EJ AF Feldman, Mitchell J. Barnett, G. Octo Link, David A. Coleman, Margaret A. Lowe, Janice A. O'Rourke, Edward J. TI Evaluation of the clinical assessment project: A computer-based multimedia tool to assess problem-solving ability in medical students SO PEDIATRICS LA English DT Article DE pediatrics; multimedia; educational measurement; medical students; computers ID SIMULATION AB OBJECTIVE. The purpose of this work was to describe Clinical Assessment, a computer-based multimedia patient simulation used to assess the problem-solving abilities of medical students and to evaluate its capacity to guide the assignment of course grade. METHODS. This was a multisite reviewer-blinded comparison of course grades, National Board of Medical Examiners pediatric examination score, and Clinical Assessment scores at 3 pediatric clerkship sites of the Harvard Medical School. Participants included 470 students completing their pediatric clerkships. Each student's performance on <= 4 Clinical Assessment patient case simulations was compared with National Board of Medical Examiners pediatric examination scores and course grades assigned by clerkship directors based on overall ward performance. RESULTS. Data from both the National Board of Medical Examiners pediatric "shelf" examination and the course grade were available for 411 students who completed >= 1 Clinical Assessment case. There was a strong correlation between Clinical Assessment score and course grade when comparing students receiving honors versus satisfactory category course grades. Students who ordered more expensive or greater numbers of laboratory tests did not achieve greater diagnostic accuracy on Clinical Assessment. Clinical Assessment had a high positive predictive value for course grade: 95% of students scoring >= 90% on Clinical Assessment achieved an honors category course grade. CONCLUSIONS. Because nearly all of the students who scored very well on Clinical Assessment received honors category course grades, future high scorers on this examination merit consideration for assigning a high course grade. A computer-based multimedia patient simulation assessment tool provides objective information that can complement a student's National Board of Medical Examiners score and course grade and may assist in evaluating clinical problem-solving ability. C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Cambridge Hosp, Dept Pediat, Cambridge, MA 02139 USA. Mt Auburn Hosp, Cambridge, MA 02238 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP Feldman, MJ (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, 50 Staniford St,7th Floor, Boston, MA 02114 USA. EM mfeldman@partners.org NR 13 TC 4 Z9 5 U1 2 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2006 VL 118 IS 4 BP 1380 EP 1387 DI 10.1542/peds.2006-0326 PG 8 WC Pediatrics SC Pediatrics GA 090NZ UT WOS:000240959300007 PM 17015526 ER PT J AU Tuchinda, C Kerr, HA Taylor, CR Jacobe, H Bergamo, BM Elmets, C Rivard, J Lim, HW AF Tuchinda, Chanisada Kerr, Holly A. Taylor, Charles R. Jacobe, Heidi Bergamo, Bettany M. Elmets, Craig Rivard, Jennifer Lim, Henry W. TI UVA1 phototherapy for cutaneous diseases: an experience of 92 cases in the United States SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE phototherapy; UVA1 ID MEDIUM-DOSE UVA1; VERSUS-HOST-DISEASE; ATOPIC-DERMATITIS; LOCALIZED SCLERODERMA; SYSTEMIC-SCLEROSIS; UVA(1) PHOTOTHERAPY; ULTRAVIOLET-A1 PHOTOTHERAPY; SCLEREDEMA ADULTORUM; LICHEN-SCLEROSUS; PUVA THERAPY AB The efficacy and safety of UVA1 (340-400 nm) phototherapy were established by studies from European countries. Evaluate experience with UVA1 phototherapy for patients with cutaneous diseases in the United States. A retrospective analysis of 92 cases of UVA1-treated cutaneous conditions from four medical centers in the United States was performed. Two-third of the patients showed a fair to good response (26-100% improvement) and one-third of the patients showed a poor response (0-25% improvement). Diseases with a moderate to good response (51-100% improvement) included scleredema adultorum, hand or foot dermatitis, atopic dermatitis, morphea (medium or medium- to high-dose UVA1), systemic sclerosis, and urticaria pigmentosa. Besides tanning, other adverse effects were found in 15% of patients, which include pruritus, erythema, tenderness, and burning sensation. Patients with skin types I-III responded better that those with a darker skin type. UVA1 phototherapy is a useful and well-tolerated treatment option for a variety of skin conditions. C1 Henry Ford Hosp, Dept Dermatol, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Dermatol, Dallas, TX USA. Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. RP Lim, HW (reprint author), Henry Ford Med Ctr, Dept Dermatol, 3031 W Grand Blvd,Suite 800, Detroit, MI 48202 USA. EM hlim1@hfhs.org NR 52 TC 30 Z9 37 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD OCT PY 2006 VL 22 IS 5 BP 247 EP 253 DI 10.1111/j.1600-0781.2006.00245.x PG 7 WC Dermatology SC Dermatology GA 081BV UT WOS:000240293100003 PM 16948826 ER PT J AU Altfeld, M Kalife, ET Qi, Y Streeck, H Lichterfeld, M Johnston, MN Burgett, N Swartz, ME Yang, A Alter, G Yu, XG Meier, A Rockstroh, JK Allen, TM Jessen, H Rosenberg, ES Carrington, M Walker, BD AF Altfeld, Marcus Kalife, Elizabeth T. Qi, Ying Streeck, Hendrik Lichterfeld, Mathias Johnston, Mary N. Burgett, Nicole Swartz, Martha E. Yang, Amy Alter, Galit Yu, Xu G. Meier, Angela Rockstroh, Juergen K. Allen, Todd M. Jessen, Heiko Rosenberg, Eric S. Carrington, Mary Walker, Bruce D. TI HLA alleles associated with delayed progression to AIDS contribute strongly to the initial CD8(+) T cell response against HIV-1 SO PLOS MEDICINE LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; LYMPHOCYTE RESPONSES; TYPE-1 INFECTION; IMMUNE-RESPONSES; DISEASE PROGRESSION; RHESUS MACAQUES; ESCAPE; VIREMIA; IMMUNODOMINATION; EXPRESSION AB Background Very little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression. Methods and Findings In a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8(+) T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized. Certain HLA alleles consistently contributed more than others to the total virus-specific CD8(+) T cell response during primary infection, and also reduced the absolute magnitude of responses restricted by other alleles if coexpressed in the same individual, consistent with immunodomination. Furthermore, individual HLA class I alleles that have been associated with slower HIV-1 disease progression contributed strongly to the total HIV-1-specific CD8(+) T cell response during primary infection. Conclusions These data demonstrate consistent immunodominance patterns of HIV-1-specific CD8(+) T cell responses during primary infection and provide a mechanistic explanation for the protective effect of specific HLA class I alleles on HIV-1 disease progression. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. SAIC Frederick, Basic Res Program, Lab Gen Divers, NCI, Frederick, MD USA. Gemeinschaftspraxis Jessen, Berlin, Germany. Univ Bonn, Dept Internal Med, D-5300 Bonn, Germany. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02114 USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011 FU NCI NIH HHS [N01CO12400]; NIAID NIH HHS [R01 AI050429, U01 AI052403] NR 53 TC 198 Z9 201 U1 2 U2 8 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 OCT PY 2006 VL 3 IS 10 BP 1851 EP 1864 AR e403 DI 10.1371/journal.pmed.0030403 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 103YU UT WOS:000241923900033 PM 17076553 ER PT J AU Granziera, C DaSilva, AFM Snyder, J Tuch, DS Hadjikhani, N AF Granziera, Cristina DaSilva, Alexandre F. M. Snyder, Josh Tuch, David S. Hadjikhani, Nouchine TI Anatomical alterations of the visual motion processing network in migraine with and without aura SO PLOS MEDICINE LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; DIFFUSION-TENSOR; SPREADING DEPRESSION; WHITE-MATTER; MULTIPLE-SCLEROSIS; CEREBRAL-CORTEX; AREA MT; WALLERIAN DEGENERATION; FUNCTIONAL-ANALYSIS; PATTERN ADAPTATION AB Background Patients suffering from migraine with aura (MWA) and migraine without aura (MWoA) show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine. Methods and Findings To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI) to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA) and 15 age-matched healthy controls ( HCs). We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing. Conclusions A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a "silent" cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Hadjikhani, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; OI Hadjikhani, Nouchine/0000-0003-4075-3106; Granziera, Cristina/0000-0002-4917-8761 FU NIBIB NIH HHS [U54 EB005149]; NINDS NIH HHS [5P01 NS 35611-09, P01 NS035611] NR 80 TC 107 Z9 111 U1 3 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD OCT PY 2006 VL 3 IS 10 BP 1915 EP 1921 AR e402 DI 10.1371/journal.pmed.0030402 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 103YU UT WOS:000241923900039 PM 17048979 ER PT J AU Bryson, D Camargo, CA Domeier, RM Gaeta, TJ Hendeles, L Hise, S Nowak, RM Russotti, R Sapien, R Wallace, D Wright, JL Boss, L Greiling, A Redd, S AF Bryson, David Camargo, Carlos A., Jr. Domeier, Robert M. Gaeta, Theodore J. Hendeles, Leslie Hise, Stephen Nowak, Richard M. Russotti, Rick Sapien, Robert Wallace, Dana Wright, Joseph L. Boss, Leslie Greiling, Andrea Redd, Stephen CA Workgroup EMS Management Participants Ctr Dis Control TI A model protocol for emergency medical services management of asthma exacerbations SO PREHOSPITAL EMERGENCY CARE LA English DT Article DE asthma; status asthmaticus; emergency medical services; ambulance; clinical protocols ID INTRAVENOUS MAGNESIUM-SULFATE; PREHOSPITAL MANAGEMENT; CHILDHOOD ASTHMA; EPINEPHRINE ABSORPTION; PEDIATRIC ASTHMA; RANDOMIZED-TRIAL; CHILDREN; LEVALBUTEROL; ALBUTEROL; PATIENT AB Emergency medical services ( EMS) is an important part of the continuum of asthma management. The magnitude of the EMS responsibility is very large, with millions of patients with asthma treated each year by EMS personnel. In response to inconsistencies between the 1997 National Asthma Education and Prevention Program asthma guidelines and a variety of existing EMS protocols on the management of asthma exacerbations, the Centers for Disease Control and Prevention convened a workgroup in 2004 to discuss the various opportunities and challenges ahead. At the meeting, and over the ensuing year, the workgroup created a model protocol that was derived from the National Asthma Education and Prevention Program guidelines. The model protocol is available in both text and algorithm format and offers guidance for EMS systems to develop and implement treatment protocols in their local areas. The workgroup recommendations emphasize flexibility, simplicity, and low-risk practices. By integrating these recommendations into existing protocols, we believe that EMS systems could improve prehospital care for patients with asthma. Demonstration projects are needed to carefully examine the implementation process and the actual impact of the model protocol on various outcomes. The workgroup also encourages more research on EMS management of asthma exacerbations. In the meantime, improved collaboration between EMS and national asthma organizations is an immediate priority and will continue to advance future discussions on how to improve asthma management in the prehospital setting. The workgroup hopes that state and local EMS systems will see the value of the model protocol and encourage its use. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 77 TC 3 Z9 3 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PD OCT-DEC PY 2006 VL 10 IS 4 BP 418 EP 429 DI 10.1080/10903120600884814 PG 12 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 110RR UT WOS:000242396900002 ER PT J AU Quintero-Rivera, F Robson, CD Reiss, RE Levine, D Benson, C Mulliken, JB Kimonis, VE AF Quintero-Rivera, Fabiola Robson, Caroline D. Reiss, Rosemary E. Levine, Deborah Benson, Carol Mulliken, John B. Kimonis, Virginia E. TI Apert syndrome: what prenatal radiographic findings should prompt its consideration? SO PRENATAL DIAGNOSIS LA English DT Article DE agenesis corpus callosum; FGFR2; Apert syndrome; prenatal diagnosis ID CORPUS-CALLOSUM; DIAGNOSIS; MUTATIONS AB Apert syndrome was diagnosed in a newborn with typical facial and digital features whose only detected prenatal abnormality had been agenesis of the corpus callosum. This prompted a review of the central nervous system findings in all cases of Apert syndrome treated at the Craniofacial Center Boston Children's Hospital between 1978 and 2004. Two of 30 patients with Apert syndrome had prenatal identification of mild dilatation of the lateral cerebral ventricles and complete agenesis of the corpus callosum (ACC) documented with both ultrasound and MRI. Both had the common S252W mutation of FGFR2. Though cranial and orbital malformations typical of Apert were eventually seen in these fetuses in the third-trimester, even in retrospect, these were not detectable at mid second-trimester, ultrasound screening for congenital malformations. Hand malformations also went undetected in the second-trimester despite extensive imaging by experienced radiologists. We conclude that prenatal ultrasonographic identification of mild ventriculomegaly or ACC should stimulate a careful search for features of Apert syndrome and prompt follow-up imaging to look for bony abnormalities that have later onset. Prenatal molecular testing for Apert mutations should be considered in cases of mild ventriculomegaly and ACC. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 Harvard Univ, Childrens Hosp, Div Genet & Metab, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Genet Training Program, Ctr Human Genet Res, Boston, MA USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Childrens Hosp, Div Plast Surg, Boston, MA 02115 USA. Childrens Hosp, Div Genet & Metab, Boston, MA 02115 USA. RP Kimonis, VE (reprint author), Harvard Univ, Childrens Hosp, Div Genet & Metab, Sch Med, 300 Longwood Ave,Fegan 10, Boston, MA 02115 USA. EM virginia.kimonis@childrens.harvard.edu OI Levine, Deborah/0000-0001-7761-6493; Robson, Caroline/0000-0001-5592-249X FU NIGMS NIH HHS [GM61354] NR 25 TC 11 Z9 12 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD OCT PY 2006 VL 26 IS 10 BP 966 EP 972 DI 10.1002/pd.1539 PG 7 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 101BP UT WOS:000241714200015 PM 16906598 ER PT J AU Marangell, LB Suppes, T Ketter, TA Dennehy, EB Zboyan, H Kertz, B Nierenberg, A Calabrese, J Wisniewski, SR Sachs, G AF Marangell, Lauren B. Suppes, Trisha Ketter, Terence A. Dennehy, Ellen B. Zboyan, Holly Kertz, Barbara Nierenberg, Andrew Calabrese, Joseph Wisniewski, Stephen R. Sachs, Gary TI Omega-3 fatty acids in bipolar disorder: Clinical and research considerations SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; PROTEIN-KINASE-C; DISCONTINUING LITHIUM MAINTENANCE; SIGNAL-TRANSDUCTION PATHWAYS; PLACEBO-CONTROLLED TRIAL; MOOD-STABILIZING AGENTS; FISH CONSUMPTION; DOUBLE-BLIND; IN-VITRO; EICOSAPENTAENOIC ACID AB Several lines of evidence suggest that omega-3 fatty acids may be important in the pathophysiology, treatment or prevention of bipolar disorder (BD). Electronic and manual searches were conducted in order to review the literature relevant to the etiology and treatment of BDs with omega-3 fatty acids. We also present data from a randomized, double-blind, placebo-controlled pilot study conducted at three sites (N = 10) comparing an omega-3 fatty acid (docosahexaenoic acid, DHA) versus placebo, added to psychosocial treatment for women with BD who chose to discontinue standard pharmacologic treatment while attempting to conceive. While some epidemiologic and preclinical data support the role of omega-3 fatty acids in BD, clinical trials to date have yielded conflicting results. In our pilot study of 10 Caucasian women taking DHA while attempting to conceive (BPI = 9, BPII = 1), age 27-42 years, DHA was well tolerated and suggests that a larger study would be feasible. The elucidation of the potential role of omega-3 fatty acids as a treatment for BD requires further study. The current data are not sufficient to support a recommendation of monotherapy treatment as a substitute for standard pharmacologic treatments. However, judicious monotherapy in selected clinical situations, or adjunctive use, may be warranted pending further data from adequately powered controlled clinical trials. Our pilot trial of DHA in women who plan to stop conventional psychotropics in order to conceive suggests that such trials are feasible. (c) 2006 Elsevier Ltd. All rights reserved. C1 Baylor Coll Med, Menninger Dept Psychiat, Mood Disorders Ctr, Houston, TX 77030 USA. VISN 16 Mental Illness Res & Clin Ctr, Dept Vet Affairs, Houston, TX USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75216 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Dept Psychiat, Partners Bipolar Res Program, Boston, MA 02114 USA. RP Marangell, LB (reprint author), Baylor Coll Med, Menninger Dept Psychiat, Mood Disorders Ctr, Houston, TX 77030 USA. EM laurenm@bcm.tmc.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH60006] NR 60 TC 21 Z9 22 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD OCT-NOV PY 2006 VL 75 IS 4-5 BP 315 EP 321 DI 10.1016/j.plefa.2006.07.008 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 097CG UT WOS:000241423400010 PM 16928441 ER PT J AU Bauer-Wu, S AF Bauer-Wu, S. TI Cancer survivorship: Theoretical perspectives from nursing SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 140 BP S60 EP S61 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900141 ER PT J AU Bernard-DuBenske, LL Cleary, JF Buss, MK Gustafson, DH McTavish, FM AF Bernard-DuBenske, L. L. Cleary, J. F. Buss, M. K. Gustafson, D. H. McTavish, F. M. TI Comparing informal caregiver and patient ratings of pain in advanced lung cancer patients: Are differences clinically significant? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Ctr Excellence Canc Commun Res, Madison, WI USA. Univ Wisconsin Comprehens Canc Ctr, Dept Oncol & Palliat care, Madison, WI USA. Lowe Ctr Thorac Oncol, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 409 BP S174 EP S174 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900410 ER PT J AU Patenaude, AF AF Patenaude, A. F. TI Prophylactic mastectomy: Ambivalent outcomes SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Canc Risk & Prevent Clin, Boston, MA 02115 USA. Harvard Med Sch, Dept Psychiat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 265 BP S112 EP S112 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900266 ER PT J AU Power, TE Dorval, M Maunsell, E Dugas, M Patenaude, AF AF Power, T. E. Dorval, M. Maunsell, E. Dugas, M. Patenaude, A. F. TI Evolution of psychological distress among French Canadian women who undergo BRCA1/2 genetic testing SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Tom Baker Canc Clin, Psychosocial Resources, Calgary, AB, Canada. Univ Quebec, Ctr Res Hosp Affilie, Unit Res Sante Populat, Quebec City, PQ, Canada. Concordia Univ, Dept Psychol, Montreal, PQ H3G 1M8, Canada. Childrens Hosp, Dana Farber Canc Inst, Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 873 BP S372 EP S372 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413901319 ER PT J AU Prigerson, H Ray, A AF Prigerson, H. Ray, A. TI Peaceful awareness of terminal illness SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Med Oncol, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 198 BP S82 EP S83 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900199 ER PT J AU Ray, A Prigerson, H AF Ray, A. Prigerson, H. TI Risks and benefits of terminal illness acknowledgement SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Med Oncol, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 199 BP S83 EP S83 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413900200 ER PT J AU Vannatta, K Fairclough, D Gerhardt, CA Kupst, MJ Meyer, ET Patenaude, A AF Vannatta, K. Fairclough, D. Gerhardt, C. A. Kupst, M. J. Meyer, E. T. Patenaude, A. TI Peer relationships of pediatric brain tumor survivors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Ohio State Univ, Ctr Behav Hlth, Columbus Childrens Res Inst, Columbus, OH 43210 USA. Colorado Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO USA. Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Dept Psychiat, Div Pediat Oncol, Boston, MA 02115 USA. RI Vannatta, Kathryn/E-4237-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2006 VL 15 IS 2 SU S MA 1038 BP S441 EP S442 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 110XF UT WOS:000242413901484 ER PT J AU Haynes, PL McQuaid, JR Ancoli-Israel, S Martin, JL AF Haynes, Patricia L. McQuaid, John R. Ancoli-Israel, Sonia Martin, Jennifer L. TI Disrupting life events and the sleep-wake cycle in depression SO PSYCHOLOGICAL MEDICINE LA English DT Article ID MAJOR DEPRESSION; MOTOR-ACTIVITY; RECURRENT DEPRESSION; CIRCADIAN-RHYTHMS; STRESS ASSESSMENT; WRIST ACTIVITY; ANTIDEPRESSANT; ACTIGRAPHY; DISORDERS; CORTISOL AB Background. Social rhythm disruption life events are significant predictors of mood relapse in bipolar patients. However, no research has examined the relationship between these events and their hypothesized mechanism of action: disrupted sleep-wake patterns. The goal of this study was to test whether participants with major depressive disorder have a greater disruption of daily sleep and motor activity following disrupting life events when compared to normal controls. Method. Over the course of 2 weeks, 39 normal controls and 39 individuals with major depressive disorder completed life events interviews and wore actigraphs to obtain estimates of sleep/wake activity. Results. Statistically significant interactions indicated that the presence of at least one disrupting life event in the previous 4 months correlated with elevations in the amount of time spent awake after sleep onset [beta=0(.)45, Delta F(1,73)=4-80,p < 0(.)05], and decreases in the percentage of time spent asleep [beta=-0(.)53, Delta F(1,73)=6(.)57,p < 0(.)05], in depressed individuals but not in normal controls. Conclusions. The results indicated that depressed individuals may be more susceptible to the effects of life events on sleep than normal controls. This is the first study to date to correlate life events with objective measures of sleep. However, prospective longitudinal research is necessary to clarify the temporal relationship among these variables. C1 Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Vet Affairs San Diego Healthcare Syst, La Jolla, CA 92093 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda, CA USA. RP Haynes, PL (reprint author), Univ Arizona, Dept Psychiat, 1501 N Campbell Ave,POB 245002, Tucson, AZ 85724 USA. EM thaynes@email.arizona.edu FU NCI NIH HHS [CA85264]; NIA NIH HHS [AG08415]; NIMH NIH HHS [1F31MH064255] NR 55 TC 22 Z9 22 U1 3 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2006 VL 36 IS 10 BP 1363 EP 1373 DI 10.1017/S0033291706008208 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 100LY UT WOS:000241671800003 PM 16834822 ER PT J AU Hoffman, WF Moore, M Templin, R McFarland, B Hitzemann, RJ Mitchell, SH AF Hoffman, William F. Moore, Meredith Templin, Raymond McFarland, Bentson Hitzemann, Robert J. Mitchell, Suzanne H. TI Neuropsychological function and delay discounting in methamphetamine-dependent individuals SO PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Dopamine 2002 Conference CY JUL 10-14, 2002 CL Portland, OR DE methamphetamine; impulsivity; delay discounting; memory ID ADJUSTING-AMOUNT PROCEDURE; ILLICIT AMPHETAMINE USERS; NEUROIMAGING EVIDENCE; DECISION-MAKING; IMPULSE CONTROL; SELF-CONTROL; REWARDS; DRUG; IMPAIRMENT; ADDICTION AB Rationale Methamphetamine (MA) dependence accounts for substantial neuropsychiatric morbidity. Furthermore, there is evidence in the literature of psychiatric and cognitive impairment in chronic users. Objectives This report compares the general psychiatric and cognitive functioning, including impulsive decision-making,of individuals dependent on MA and normal controls. Materials and methods Forty-one currently abstinent individuals in treatment for MA dependence and 41 controls participated. Controls were selected to minimize group differences in age and gender. MA users met DSM-IV criteria for MA dependence, had average daily use of 0.5 g/day (0.5-6 g/day), had been abstinent at least 2 weeks (2-24 weeks), and did not currently meet criteria for other Axis I psychiatric disorders. Psychiatric symptoms were rated on standardized scales. Cognitive function was assessed with a battery of standardized neuropsychological tests. Impulsivity was assessed using a delay discounting task, which measured preference for small, immediate, and large delayed rewards. Results The MA group reported more psychiatric symptoms than controls, and was impaired relative to controls on the Babcock Story Recall-Delayed and the Rey Auditory Verbal Learning Test. MA-dependent subjects discounted delayed rewards more than controls, and this measure of impulsivity was correlated with memory impairment in the MA group but not in the controls. Conclusions MA-dependent individuals are more impulsive than controls, and this may be causally related to memory deficits but was unrelated to any other measure of psychiatric or cognitive impairment or any drug use history variable. C1 Vet Affairs Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. Vet Affairs Med Ctr, Methamphetamine Abuse Res Ctr P35C, Portland, OR 97239 USA. Vet Affairs Med Ctr, Mental Hlth & Clin Neurosci Div P35C, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Res Serv, Portland, OR USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Nursing, Portland, OR 97201 USA. Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. RP Hoffman, WF (reprint author), Vet Affairs Med Ctr, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM hoffmanw@ohsu.edu OI Mitchell, Suzanne/0000-0002-0225-7200; McFarland, Bentson/0000-0001-9149-5616 FU NIAAA NIH HHS [AA13454, AA11034, AA00281]; NIDA NIH HHS [DA015543]; NIMH NIH HHS [MH51372] NR 54 TC 135 Z9 143 U1 8 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2006 VL 188 IS 2 BP 162 EP 170 DI 10.1007/s00213-006-0494-0 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 082IN UT WOS:000240380000004 PM 16915378 ER PT J AU Willers, H Husson, J Lee, LW Hubbe, P Gazemeier, F Powell, SN Dahm-Daphi, J AF Willers, H. Husson, J. Lee, L. W. Hubbe, P. Gazemeier, F. Powell, S. N. Dahm-Daphi, J. TI Distinct mechanisms of nonhomologous end joining in the repair of site-directed chromosomal breaks with noncomplementary and complementary ends SO RADIATION RESEARCH LA English DT Article ID DOUBLE-STRAND-BREAK; DEPENDENT PROTEIN-KINASE; CELL-FREE-EXTRACTS; MAMMALIAN-CELLS; HOMOLOGOUS RECOMBINATION; DNA ENDS; IONIZING-RADIATION; REGULATES DNA; IN-VITRO; KU AB DNA double-strand breaks (DSBs) are considered the most important type of DNA damage inflicted by ionizing radiation. The molecular mechanisms of DSB repair by nonhomologous end joining (NHEJ) have not been well studied in live mammalian cells, due in part to the lack of suitable chromosomal repair assays. We previously introduced a novel plasmidbased assay to monitor NHEJ of site-directed chromosomal I-Scel breaks. In the current study, we expanded the analysis of chromosomal NHEJ products in murine fibroblasts to focus on the error-prone rejoining of DSBs with noncomplementary ends, which may serve as a model for radiation damage repair. We found that noncomplementary ends were efficiently repaired using microhomologies of 1-2 nucleotides (nt) present in the single-stranded overhangs, thereby keeping repair-associated end degradation to a minimum (2-3 nt). Microhomology-mediated end joining was disrupted by Wortmannin, a known inhibitor of DNA-PKcs. However, Wortmannin did not significantly impair the proficiency of end joining. In contrast to noncomplementary ends, the rejoining of cohesive ends showed only a minor dependence on microhomologies but produced fivefold larger deletions than the repair of noncomplementary ends. Together, these data suggest the presence of several distinct NHEJ mechanisms in live cells, which are characterized by the degree of sequence deletion and microhomology use. Our NHEJ assay should prove a useful system to further elucidate the genetic determinants and molecular mechanisms of site-directed DSBs in living cells. (c) 2006 by Radiation Research Society. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Charlestown, MA 02129 USA. Univ Med Sch Hamburg Eppendorf, Dept Radiotherapy & Radiat Oncol, Lab Radiobiol & Expt Radiat Oncol, D-20146 Hamburg, Germany. RP Willers, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Charlestown, MA 02129 USA. EM hwillers@partners.org; dahm@uke.uni-hamburg.de NR 35 TC 17 Z9 17 U1 0 U2 0 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 2006 VL 166 IS 4 BP 567 EP 574 DI 10.1667/RR0524.1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 089LV UT WOS:000240883000001 PM 17007549 ER PT J AU Shetty, SK AF Shetty, Sanjay K. TI The MCA dot sign SO RADIOLOGY LA English DT Editorial Material ID MIDDLE CEREBRAL-ARTERY; ACUTE STROKE; CT C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Shetty, SK (reprint author), Beth Israel Med Ctr, Dept Radiol, Boston, MA 02114 USA. EM sshetty@bidmc.harvard.edu NR 11 TC 5 Z9 5 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 OCT PY 2006 VL 241 IS 1 BP 315 EP 318 DI 10.1148/radiol.2411040573 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 087TK UT WOS:000240765100038 PM 16990684 ER PT J AU Dahm-Daphi, J Schulte-Uentrop, L Hubbe, P Willers, H El-Awady, RA AF Dahm-Daphi, J. Schulte-Uentrop, L. Hubbe, P. Willers, H. El-Awady, R. A. TI Loss of XRCC4 but not Ku80 function reduces the frequency and fidelity of non-homologous end-joining of site-directed DNA double-strand breaks in mammalian cells SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Conference of the Spanish-Portuguese-and -Latin-American-Association CY OCT 09, 2006 CL Leipzig, GERMANY SP Spainsh Portuguese & Latin- Amer Assoc C1 Univ Hamburg, Hamburg, Germany. Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2006 VL 81 SU 1 MA 124 BP S48 EP S48 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115FB UT WOS:000242719100140 ER PT J AU Holloway, C O'Farrell, D Devlin, P Cormack, R AF Holloway, C. O'Farrell, D. Devlin, P. Cormack, R. TI I125 mesh implant dose penetration asymmetry in non-planar scenarios SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Conference of the Spanish-Portuguese-and -Latin-American-Association CY OCT 09, 2006 CL Leipzig, GERMANY SP Spainsh Portuguese & Latin- Amer Assoc C1 Brigham & Womens Hosp, Dana Farber Canc Ctr, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2006 VL 81 SU 1 MA 631 BP S259 EP S260 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115FB UT WOS:000242719100637 ER PT J AU Jiang, S AF Jiang, S. TI Lung tumour motion - Prospectives of application of gating techniques SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Conference of the Spanish-Portuguese-and -Latin-American-Association CY OCT 09, 2006 CL Leipzig, GERMANY SP Spainsh Portuguese & Latin- Amer Assoc C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2006 VL 81 SU 1 MA 39 BP S13 EP S13 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115FB UT WOS:000242719100055 ER PT J AU Suit, H AF Suit, H. TI Proton vs or and carbon ion radiation therapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Conference of the Spanish-Portuguese-and -Latin-American-Association CY OCT 09, 2006 CL Leipzig, GERMANY SP Spainsh Portuguese & Latin- Amer Assoc C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2006 VL 81 SU 1 MA 292 BP S118 EP S118 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115FB UT WOS:000242719100302 ER PT J AU Willers, H Dahm-Daphi, J Li, L Luo, CM Powell, S Kachnic, L AF Willers, H. Dahm-Daphi, J. Li, L. Luo, C-M. Powell, S. Kachnic, L. TI Disruption of the Fanconi Anemia D2 gene causes cellular hypersensitivity to DNA topoisomerase II inhibitors SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Conference of the Spanish-Portuguese-and -Latin-American-Association CY OCT 09, 2006 CL Leipzig, GERMANY SP Spainsh Portuguese & Latin- Amer Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hamburg, Hamburg, Germany. Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2006 VL 81 SU 1 MA 122 BP S47 EP S48 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115FB UT WOS:000242719100138 ER PT J AU Zietman, A AF Zietman, A. TI Prostate brachytherapy: Lessons for tumour biology and fractionation SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Conference of the Spanish-Portuguese-and -Latin-American-Association CY OCT 09, 2006 CL Leipzig, GERMANY SP Spainsh Portuguese & Latin- Amer Assoc C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD OCT PY 2006 VL 81 SU 1 MA 165 BP S63 EP S63 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 115FB UT WOS:000242719100179 ER PT J AU Meeker, JD Barr, DB Hauser, R AF Meeker, John D. Barr, Dana B. Hauser, Russ TI Thyroid hormones in relation to urinary metabolites of non-persistent insecticides in men of reproductive age SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE biomarker; carbaryl; chlorpyrifos; endocrine; hormone; pesticide; thyroid ID POLYCHLORINATED-BIPHENYLS; EXPOSURE; DISEASE; CHLORPYRIFOS; RECEPTOR AB Human exposure to contemporary-use insecticides is widespread, but effects of exposure on human endocrine function have gone largely untested to date. Samples of urine and blood were collected concurrently from 322 adult men between the years 2000 and 2003. Urine samples were analyzed for 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, and 1-napththol (IN), a metabolite of carbaryl and naphthalene. Serum samples were analyzed for free T-4, total T-3, and thyroid stimulating hormone (TSH). There was an association between TCPY and TSH, where an interquartile range (IQR) increase in TCPY was associated with a 9% (95% confidence interval 0-18%) increase in TSH. There was also a suggestive inverse association between TCPY and free T4. There were no associations between IN and thyroid hormones. Environmental exposure to chlorpyrifos, chlorpyrifos-methyl, or its metabolite TCPY may be associated with altered thyroid function in human males. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, M6226 SPH 2,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu RI Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013; OI Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [ES09718, ES00002, T32 ES07069] NR 25 TC 34 Z9 36 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD OCT PY 2006 VL 22 IS 3 BP 437 EP 442 DI 10.1016/j.reprotox.2006.02.005 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 090PB UT WOS:000240962100007 PM 16584866 ER PT J AU Girgis, K Hamed, H Khater, Y Kacmarek, RM AF Girgis, Karim Hamed, Hala Khater, Yehia Kacmarek, Robert M. TI A decremental PEEP trial identifies the PEEP level that maintains oxygenation after lung recruitment SO RESPIRATORY CARE LA English DT Article DE lung recruitment; acute respiratory distress syndrome; ARDS; acute lung injury; positive end-expiratory pressure; PEEP; mechanical ventilation ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; VOLUME CURVE; SUSTAINED INFLATION; MATHEMATICAL-MODEL; VENTILATION; MANEUVERS; INJURY; STRATEGY; FAILURE AB OBJECTIVE: To assess the ability of a decremental trial of positive end-expiratory pressure (PEEP) to identify an optimal PEEP level that maintains oxygenation after a lung-recruitment maneuver. DESIGN: Prospective clinical trial. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Twenty sedated patients with acute lung injury and/or acute respiratory distress syndrome, ventilated for 1.2 +/- 0.4 d. INTERVENTION: Each patient received up to 3 lung-recruitment maneuvers with continuous positive airway pressure of 40 cm H2O sustained for 40 s to increase the ratio of P-aO2 to F-IO2 by > 20%. Following the lung-recruitment maneuver, PEEP was set at 20 cm H2O and then the F-IO2, was decreased until the oxygen saturation (measured via pulse oximetry [S-pO2]) was 90-94%. PEEP was then decreased in 2-cm H2O steps until the S-pO2 dropped below 90%. The step preceding the drop to below 90% was considered the optimal PEEP. The lung was then re-recruited and PEEP and F-IO2, were set at the identified levels. The patients were followed for 4 h after the PEEP trial and the setting of PEEP and F 102. RESULTS: After the lung-recruitment maneuver, all the patients' P-aO2/F-IO2, increased > 50%. The mean +/- SD P-aO2/F-IO2, on the optimal decremental trial PEEP was 211 +/- 79 mm Hg, versus 135 +/- 37 mm Hg at baseline (p < 0.001), and was sustained at that level for the 4-h study period (227 +/- 81 mm Hg at 4 h). F-IO2 at baseline was 0.54 +/- 0.12 versus 0.38 +/- 0.12 (p < 0.001) at 4 h. PEEP was 11.9 +/- 3.0 cm H2O at baseline and 9.1 +/- 4.7 cm H2O (P = 0.011) at 4 h. CONCLUSION: A decremental PEEP trial identifies a PEEP setting that sustains for 4 h the oxygenation benefit of a 40-cm H2O, 40-s lung-recruitment maneuver. C1 Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. New Kasr El Aini Teaching Hosp, Surg Intens Care Unit, Cairo, Egypt. Cairo Univ, Cairo, Egypt. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 32 TC 54 Z9 62 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD OCT PY 2006 VL 51 IS 10 BP 1132 EP 1139 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 092ZB UT WOS:000241135400005 PM 17005058 ER PT J AU Niederman, MS Anzueto, A Sethi, S Choudhri, S Kureishi, A Haverstock, D Perroncel, R AF Niederman, M. S. Anzueto, A. Sethi, S. Choudhri, S. Kureishi, A. Haverstock, D. Perroncel, R. TI Eradication of H-influenzae in AECB: A pooled analysis of moxifloxacin phase III trials compared with macrolide agents SO RESPIRATORY MEDICINE LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the American-College-of-Chest-Physicians CY OCT 23-27, 2004 CL Seattle, WA SP Amer Coll Chest Phys DE acute exacerbations of chronic bronchitis; azithromycin; clarithromycin; Haemophilus influenzae; macrolides; moxifloxacin ID OBSTRUCTIVE PULMONARY-DISEASE; ACUTE BACTERIAL EXACERBATIONS; COURSE 5-DAY MOXIFLOXACIN; CHRONIC-BRONCHITIS; STREPTOCOCCUS-PNEUMONIAE; MORAXELLA-CATARRHALIS; EFFICACY; THERAPY; CLARITHROMYCIN; SUSCEPTIBILITY AB Haemophilus influenzae is the most common bacterial pathogen associated with acute exacerbations of chronic bronchitis (AECB). This study determined the rate of bacterial eradication of H. influenzae during AECB treated with either macrolides or moxifloxacin. Adult AECB patients with H. influenzae were included in a pooled analysis of four double-blind; multicentre, randomised trials. Patients received either moxifloxacin (400 mg qd for 5-10 days) or macrolides (azithromycin 500 mg/250 mg qd for 5 days or ctarithromycin 500 mg bid for 5-10 days). Bacterial eradication and clinical success were recorded at the test-of-cure visit (7-37 days post-therapy). Of 2555 patients in the intent-to-treat population, 910 were microbiologically valid and 292 (32%) had H. influenzae cultured at baseline. Bacterial eradication of H. influenzae was significantly higher with moxifloxacin vs. macrolide-treated patients (93.0% [133/143] vs. 73.2% [109/149], respectively, P = 0.001). Moxifloxacin also demonstrated higher eradication rates compared with azithromycin (96.8% vs. 84.6%, P = 0.019) and ctarithromycin (90.1% vs. 64.2%, P = 0.001) analysed separately. Clinical success was 89.5% (128/143) for moxifloxacin vs. 85.2% (127/149) for the macrolide group (P = 0.278); similar results were found when moxifloxacin was compared individually with each macrolide. For patients with AECB due to H. influenzae, moxifloxacin provided superior bacterial eradication rates than macrolide therapy. (c) 2006 Elsevier Ltd. All rights reserved. C1 Winthrop Univ Hosp, Dept Med, Mineola, NY 11501 USA. SUNY Stony Brook, Mineola, NY 11501 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. SUNY Buffalo, Dept Vet Affairs, Western New York Healthcare Syst, Div Pulm & Crit Care Med, Buffalo, NY 14260 USA. Bayer Pharmaceut Corp, West Haven, CT USA. RP Niederman, MS (reprint author), Winthrop Univ Hosp, Dept Med, 222 Stn Plaza N,Suite 509, Mineola, NY 11501 USA. EM mniederman@winthrop.org NR 36 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD OCT PY 2006 VL 100 IS 10 BP 1781 EP 1790 DI 10.1016/j.rmed.2006.01.025 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 091PE UT WOS:000241040000013 PM 16531032 ER PT J AU Dickerson, BC AF Dickerson, B. C. TI Functional MRI in the early detection of dementias SO REVUE NEUROLOGIQUE LA French DT Article DE Alzheimer's disease; mild cognitive impairment; functional magnetic resonance imaging ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; MEMORY IMPAIRMENT; FMRI ACTIVATION; DEFAULT-MODE; NEURAL BASIS; AD; PATTERNS; RISK AB Functional MRI is a non-invasive imaging technology that can illuminate regional brain activity during the performance of a task, such as a memory paradigm, or at rest fMRI data can be acquired during a session in which MRI data is also acquired to measure grey and white matter regional brain structure, and these measures can be analyzed together to investigate the relationships between altered regional brain function, structure, and cognitive task performance in neurologic illness. Data will be reviewed on the application of fMRI to the early detection of physiologic abnormalities associated with neurodegenerative diseases that cause dementia, and to differential diagnosis of dementias. Recent fMRI work will also be reviewed on the identification of abnormalities in regional brain function prior to dementia, the use of these measures to predict cognitive decline, and their application in investigations of alterations in regional brain networks that subserve cognitive function. Finally, the use of fMRI as a biomarker in clinical trials of putative neurotherapeutics for dementias will be discussed. C1 Massachusetts Gen Hosp East, Gerontol Res Unit, Alzheimers Dis Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp East, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Memory Disorders Unit, Div Cognit & Behav Neurol, Boston, MA 02115 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp East, Gerontol Res Unit, Alzheimers Dis Res Ctr, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu FU NIA NIH HHS [K23-AG22509] NR 38 TC 5 Z9 5 U1 1 U2 4 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0035-3787 J9 REV NEUROL-FRANCE JI Rev. Neurol. PD OCT PY 2006 VL 162 IS 10 BP 941 EP 944 DI 10.1016/S0035-3787(06)75103-7 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 095TY UT WOS:000241332400007 PM 17028561 ER PT J AU Rossman, MD Newman, LS Baughman, RP Teirstein, A Weinberger, SE Miller, W Sands, BE AF Rossman, Milton D. Newman, Lee S. Baughman, Robert P. Teirstein, Alvin Weinberger, Steven E. Miller, Wallace, Jr. Sands, Bruce E. TI A double-blinded, randomized, placebo-controlled trial of infliximab in subects with active pulmonary sarcoidosis SO SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES LA English DT Article DE infliximab; sarcoidosis; pulmonary; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; ALVEOLAR MACROPHAGES; GRANULOMA-FORMATION; CROHNS-DISEASE; COMPLICATED SARCOIDOSIS; TNF-ALPHA; THERAPY; CYTOKINES; RELEASE AB Study Objectives: To evaluate the safety and tolerability of infliximab in the treatment of active pulmonary sarcoidosis, and to provide an initial assessment of the efficacy of infliximab in the treatment of active pulmonary sarcoidosis. Design: Double-blind, randomized, placebo-controlled phase II study. Setting: Multicenter. Patients: Active Radiographic Stage II, III, and IV active pulmonary sarcoidosis despite corticosteroids or previous intolerance to corticosteroids. Intervention: Infliximab 5mg/kg (group I) or placebo (group II) at weeks 0 and 2 and open-label infliximab 5mg/kg for all subjects at weeks 6 and 14. Measurements: Pulmonary function, chest radiographs, dyspnea stage, SF-36. Results: Mean vital capacity (VC) at wk 0 was 2.47 +/- 0.2 (group 1) and 2.37 +/- 0.31 (group II). At 6 weeks the mean +/- SD relative change in VC compared to baseline was 15.22 +/- 9.91% for group I (n=13) and 8.39 +/- 3.33% for group II (n=6) (p=0.65). Four patients had serious adverse events, including decreased WBC and elevated CPK (I patient), pneumonia (I patient), cellulitis, acute renal failure, pulmonary embolus and death (I patient), and visual field defect (I patient). Conclusions: Infliximab may improve VC in patients with active PS resistant to steroids. Larger scale, longer term studies will be needed to assess both safety and efficacy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Natl Univ Colorado Denver, Hlth Sci Ctr, Denver, CO USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Sands, BE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 165 Cambridge St,9th Flr, Boston, MA 02114 USA. EM bsands@partners.org NR 48 TC 91 Z9 93 U1 0 U2 2 PU FONDAZIONE PNEUMOLOGIA U I P ONLUS PI MILANO PA VIA FRUA 15, MILANO, ITALY SN 1124-0490 J9 SARCOIDOSIS VASC DIF JI Sarcoidosis Vasc. Diffus. Lung Dis. PD OCT PY 2006 VL 23 IS 3 BP 201 EP 208 PG 8 WC Respiratory System SC Respiratory System GA 221EM UT WOS:000250210200004 PM 18038919 ER PT J AU Kee, KS Horan, WP Wynn, JK Mintz, J Green, MF AF Kee, Kimmy S. Horan, William P. Wynn, Jonathan K. Mintz, Jim Green, Michael F. TI An analysis of categorical perception of facial emotion in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; categorical perception; facial emotion; affect perception ID GENERALIZED POOR PERFORMANCE; AFFECT RECOGNITION; AFFECTIVE PROSODY; SOCIAL COGNITION; EXPRESSIONS; DEFICIT; PSYCHOPATHOLOGY; BEHAVIOR AB Background Emotion perception deficits have been extensively documented in schizophrenia and are associated with poor social functioning. Yet fundamental questions about the nature and scope of these impairments remain unanswered from commonly used experimental tasks. An alternative categorical perception paradigm that focuses on distinguishing boundaries between emotions was used to evaluate whether schizophrenia patients demonstrate atypical patterns of categorical perception and a negativity bias in the identification of ambiguous facial expressions. Method: 47 schizophrenia outpatients and 31 nonpsychiatric controls completed a forced-choice emotion identification task. Stimuli consisted of a series of digitized facial images that were morphed in 10% signal intensity increments along continua between pairs of emotions (happy-sad; fearful-happy; angry-fearful; angry-sad) and presented in a random order. For each emotion continuum, measures of the response slope and the location of the boundary shift point between emotions were calculated for each group. Results: The schizophrenia group demonstrated significantly shallower response curves than controls across all emotion continua. Despite these generally less precise demarcations between emotions, patients did not significantly differ from controls in the location of the shift point between emotions on any of the continua. Conclusions: Schizophrenia patients demonstrated impaired categorical perception of facial expressions with generally less sharp categorizations of ambiguous stimuli to one emotion category or another. However, patients did not demonstrate a negativity bias in their processing of ambiguous facial expressions. The emotional continuum paradigm can help to clarify the nature and boundaries of affect perception deficits in schizophrenia. (c) 2006 Elsevier B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Kee, KS (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,MIRECC 210A,Bldg 210, Los Angeles, CA 90073 USA. EM kee@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [MH 65707, MH-43292] NR 41 TC 31 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2006 VL 87 IS 1-3 BP 228 EP 237 DI 10.1016/j.schres.2006.06.001 PG 10 WC Psychiatry SC Psychiatry GA 095LV UT WOS:000241310100026 PM 16859896 ER PT J AU Seidman, LJ Makris, N Fischl, B Thermenos, HW Faraone, SV Tsuang, MT AF Seidman, L. J. Makris, N. Fischl, B. Thermenos, H. W. Faraone, S. V. Tsuang, M. T. TI Altered cortical thickness in adolescents and young adults at genetic risk for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 5th International Conference on Early Psychosis CY OCT 04-06, 2006 CL Birmingham, ENGLAND C1 Beth Israel Deaconess Med Ctr, Harvard Med Sch, Dept Psychiat, Boston, MA USA. Brockton W Roxbury VA Med Ctr, Harvard Med Sch, Dept Psychiat, Brockton, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Harvard Med Sch, Boston, MA 02114 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Harvard Med Sch, MIT, Charlestown, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Analysis, Harvard Med Sch, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat, SUNY Genet Res Program, Syracuse, NY USA. Univ Calif San Diego, Inst Behav Genom, Dept Psychiat, La Jolla, CA 92093 USA. EM Iseidman@bidmc.harvard.edu 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 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2006 VL 86 SU S MA TC18B BP S58 EP S59 DI 10.1016/S0920-9964(06)70175-X PG 2 WC Psychiatry SC Psychiatry GA 095RM UT WOS:000241325600174 ER PT J AU Martin, CR Walker, WA AF Martin, Camilia R. Walker, W. Allan TI Intestinal immune defences and the inflammatory response in necrotising enterocolitis SO SEMINARS IN FETAL & NEONATAL MEDICINE LA English DT Article DE enterocolitis, necrotising; infant, premature; inflammation, cytokines; chemokines; matrix metalloproteinases; growth factors; toll-like receptors; nuclear factor kappa B ID PLATELET-ACTIVATING-FACTOR; EPIDERMAL-GROWTH-FACTOR; BIRTH-WEIGHT INFANTS; NECROSIS-FACTOR-ALPHA; NEONATAL-RAT MODEL; BLOOD MONONUCLEAR-CELLS; ISCHEMIC BOWEL NECROSIS; FACTOR-ACETYLHYDROLASE; GENE-EXPRESSION; UP-REGULATION AB Necrotising enterocolitis is a devastating neonatal gastrointestinal emergency predominantly affecting low birth weight, premature infants and is accompanied by significant mortality and morbid sequelae. The pathophysiology remains obscure and the management of infants with necrotising enterocolitis has not changed since the recognition of this disease. Necrotising enterocolitis is most likely the clinical culmination of multiple different risk factors interacting with each other to produce bowel injury through a final, common inflammatory pathway. Here, we review intestinal immunity and the specific inflammatory mediators involved in this disease process. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. RP Martin, CR (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Rose 318, Boston, MA 02215 USA. EM cmartin1@bidmc.harvard.edu NR 78 TC 49 Z9 51 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1744-165X J9 SEMIN FETAL NEONAT M JI Semin. Fetal Neonatal Med. PD OCT PY 2006 VL 11 IS 5 BP 369 EP 377 DI 10.1016/j.siny.2006.03.002 PG 9 WC Pediatrics SC Pediatrics GA 090QJ UT WOS:000240965600012 PM 16690363 ER PT J AU McDermott, DF Atkins, MB AF McDermott, David F. Atkins, Michael B. TI Interteukin-2 therapy of metastatic renal cell carcinoma- Predictors of response SO SEMINARS IN ONCOLOGY LA English DT Review ID DOSE RECOMBINANT INTERLEUKIN-2; CARBONIC-ANHYDRASE-IX; SUBCUTANEOUS INTERLEUKIN-2; ADVANCED CANCER; RANDOMIZED-TRIAL; INTERFERON; SURVIVAL; IMMUNOTHERAPY; STRATIFICATION; COMBINATION C1 Beth Israel Deaconess Med Ctr, Clin Res Subcomm, DF HCC Renal Canc Program, Boston, MA 02215 USA. Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Renal Canc Program, Boston, MA 02115 USA. RP McDermott, DF (reprint author), Beth Israel Deaconess Med Ctr, Clin Res Subcomm, DF HCC Renal Canc Program, Kirstien Room 153,330 Brookline Ave, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu FU NCI NIH HHS [P50 CA101942-01] NR 32 TC 28 Z9 29 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2006 VL 33 IS 5 BP 583 EP 587 DI 10.1053/j.seminoncol.2006.06.004 PG 5 WC Oncology SC Oncology GA 098RP UT WOS:000241540800008 PM 17045087 ER PT J AU Kim, WY Kaelin, WG AF Kim, William Y. Kaelin, William G., Jr. TI Molecular pathways in renal cell carcinoma- Rationate for targeted treatment SO SEMINARS IN ONCOLOGY LA English DT Review ID LINDAU TUMOR-SUPPRESSOR; HYPOXIA-INDUCIBLE FACTOR; TRANSFORMING-GROWTH-FACTOR; RECEPTOR ANTIBODY C225; MET PROTOONCOGENE; GENE-PRODUCT; FACTOR-ALPHA; CYCLIN D1; PHASE-II; PROLYL HYDROXYLATION/ C1 Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ N Carolina, Dept Hematol Oncol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. RP Kim, WY (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM William_kaelin@dfci.harvard.edu NR 94 TC 43 Z9 45 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2006 VL 33 IS 5 BP 588 EP 595 DI 10.1053/j.seminoncol.2006.06.001 PG 8 WC Oncology SC Oncology GA 098RP UT WOS:000241540800009 PM 17045088 ER PT J AU Willett, CG Kozin, SV Duda, DG di Tomaso, E Kozak, KR Boucher, Y Jain, RK AF Willett, Christopher G. Kozin, Sergey V. Duda, Dan G. di Tomaso, Ernmanuelle Kozak, Kevin R. Boucher, Yves Jain, Rakesh K. TI Combined vascular endothelial growth factor-targeted therapy and radiotherapy for rectal cancer: Theory and clinical practice SO SEMINARS IN ONCOLOGY LA English DT Review ID IONIZING-RADIATION; TUMOR RESPONSE; VEGFR2 BLOCKADE; CARCINOMA; ANGIOGENESIS; CHEMOTHERAPY; BEVACIZUMAB; AGENTS; TRIAL C1 Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Willett, CG (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. FU NCI NIH HHS [R01 CA115767, R01 CA115767-03, P01 CA080124-08, P01 CA080124, R01-CA115767, R21 CA099237, R21 CA099237-02, R21-CA 99237, P01-CA80124] NR 23 TC 49 Z9 51 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2006 VL 33 IS 5 SU 10 BP S35 EP S40 DI 10.1053/j.seminoncol.2006.08.007 PG 6 WC Oncology SC Oncology GA 110WC UT WOS:000242411000006 PM 17145523 ER PT J AU Jiang, SB AF Jiang, Steve B. TI Radiotherapy of mobile tumors SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article DE 4D CT; inter-fraction motion; intra-fraction motion; respiratory gating; mobile tumor ID REAL-TIME TUMOR; INSPIRATION BREATH-HOLD; MODULATED RADIATION-THERAPY; DYNAMIC MULTILEAF COLLIMATOR; INTERNAL FIDUCIAL MARKERS; X-RAY SYSTEMS; DEEP-INSPIRATION; TRACKING RADIOTHERAPY; GATED RADIOTHERAPY; RESPIRATORY MOTION C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jiang, SB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM jiang.steve@mgh.harvard.edu NR 78 TC 87 Z9 91 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2006 VL 16 IS 4 BP 239 EP 248 DI 10.1016/j.semradonc.2006.04.007 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 092KG UT WOS:000241094800007 PM 17010907 ER PT J AU Morgenthaler, TI Owens, J Alessi, C Boehlecke, B Brown, TM Coleman, J Friedman, L Kapur, VK Lee-Chiong, T Pancer, J Swick, TJ AF Morgenthaler, Timothy I. Owens, Judith Alessi, Cathy Boehlecke, Brian Brown, Terry M. Coleman, Jack, Jr. Friedman, Leah Kapur, Vishesh K. Lee-Chiong, Teofilo Pancer, Jeffrey Swick, Todd J. TI Practice parameters for behavioral treatment of bedtime problems and night wakings in infants and young children - An American Academy of Sleep Medicine report SO SLEEP LA English DT Article DE practice guidelines; practice parameters; bedtime problems; night wakings in young children; treatment; behavioral; non-pharmacological; unmodified extinction; graduated extinction; extinction with parental presence; parent education; positive routines; scheduled awakenings; standardized bedtime routines; positive reinforcement AB Bedtime problems and frequent night wakings are highly prevalent in infants, toddlers, and preschoolers. Evidence suggests that sleep disruption and/or insufficient sleep have potential deleterious effects on children's cognitive development, regulation of affect, attention, health outcomes, and overall quality of life, as well as secondary effects on parental and family functioning. Furthermore, longitudinal studies have demonstrated that sleep problems first presenting in infancy may become chronic, persisting into the preschool and school-aged years. A solid body of literature now exists supporting the use of empirically-based behavioral management strategies to treat bedtime problems and night wakings in infants, toddlers, and preschoolers. The following practice parameters present recommendations for the use of behavioral (i.e., non-pharmacological) treatments of bedtime problems and night walkings in young children (aged 0-4. years 11 months). A companion review paper(1) on which the recommendations are based was prepared by a taskforce appointed by the Standards of Practice Committee (SPC) of the American Academy of Sleep Medicine (AASM), and summarizes the peer-reviewed scientific literature on this topic. The authors of the review paper evaluated the evidence presented by the reviewed studies according to modified Sackett criteria.(2) Using this information and a grading system described by Eddy(3) (i.e., standard, guideline or option), the Standards of Practice Committee and Board of Directors of the American Academy of Sleep Medicine determined levels of treatment recommendation presented in the practice parameters below. These practice parameters provide 3 types of recommendations. First, recommendations are provided indicating that behavioral interventions are effective in the treatment of bedtime problems and night wakings in young children, producing reliable and significant clinical improvement in sleep parameters. Second, recommendations are made regarding specific behavioral therapies, including: (1) unmodified extinction, extinction with parental presence, and preventive parent education are all rated as individually effective therapies in the treatment of bedtime problems and night wakings (Standards), and (2) graduated extinction, bedtime fading/positive routines and scheduled awakenings are rated as individually effective therapies in the treatment of bedtime problems and night wakings but with less certainty (Guidelines). There was insufficient evidence to recommend standardized bedtime routines and positive reinforcement as single therapies. In addition, although behavioral therapies for bedtime problems and night wakings are often combined, there was insufficient evidence available to recommend one individual therapy over another or to recommend an individual therapy over a combination of therapies. Finally, recommendations are provided regarding the beneficial effects of behavioral treatments on secondary outcomes, including daytime functioning (child) and parental well-being. C1 Mayo Clin, Mayo Sleep Disorders Ctr, Rochester, MN 55905 USA. Rhode Isl Hosp, Providence, RI USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sepulveda, CA USA. Univ N Carolina, Chapel Hill, NC USA. St Joseph Mem Hosp, Murphysboro, IL USA. Stanford Univ, Stanford, CA 94305 USA. Univ Washington, Seattle, WA 98195 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Houston Sleep Ctr, Houston, TX USA. RP Morgenthaler, TI (reprint author), Mayo Clin, Mayo Sleep Disorders Ctr, 200 1st St SW, Rochester, MN 55905 USA. EM morgenthaler.timothy@mayo.edu RI Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Morgenthaler, Timothy/0000-0002-2614-3793 NR 4 TC 78 Z9 79 U1 1 U2 17 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD OCT 1 PY 2006 VL 29 IS 10 BP 1277 EP 1281 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 100FL UT WOS:000241653400003 PM 17068980 ER PT J AU Patwardhan, AA Larson, MG Levy, D Benjamin, EJ Leip, EP Keyes, MJ Wang, TJ Gottlieb, DJ Vasan, RS AF Patwardhan, Anjali A. Larson, Martin G. Levy, Daniel Benjamin, Emelia J. Leip, Eric P. Keyes, Michelle J. Wang, Thomas J. Gottlieb, Daniel J. Vasan, Ramachandran S. TI Obstructive sleep apnea and plasma natriuretic peptide levels in a community-based sample SO SLEEP LA English DT Article DE sleep apnea syndromes; natriuretic peptides; cohort studies ID POSITIVE AIRWAY PRESSURE; HEART-FAILURE; BLOOD-PRESSURE; HEALTH; EXPRESSION; SECRETION; THERAPY; HORMONE; HYPOXIA; RELEASE AB Study Objectives: We hypothesized that alterations in cardiac hemodynamics associated with obstructive sleep apnea-hypopnea (OSAH) would be reflected in higher natriuretic peptide levels. We examined the association of OSAH with natriuretic peptides in a community-based sample. Design: Cross-sectional, retrospective, observational study. Setting: Framingham Heart Study Offspring Cohort and Sleep Heart Health Study. Participants: Community-based sample of 623 individuals. Measurements: Full-montage home polysomnography was used to determine apnea-hypopnea index (AHI) and percentage of time with an oxyhemoglobin saturation < 90% (PctLt90). Sensitive immunoradiometric assays were used to measure plasma B-type (BNP) and N-terminal pro-atrial natriuretic peptide (NT-ANP). Multivariable regression was used to examine the relations between natriuretic peptides and indicators of OSAH, adjusting for age, sex, body mass index, and clinical covariates. Results: No statistically significant relations between OSAH indices and BNP were observed in the multivariable model. Compared with an AHI < 5, relative levels of 1.20, 0.88, and 0.91 were observed for AHI categories 5-15, 15-30, > 30 events per hour, respectively. For NT-ANP, no significant relations were seen with AHI in the multivariable model (relative levels of 0.98, 0.91, and 0.90). An inverse association was observed between NT-ANP and PctLt90 in age- and sex-adjusted models (relative levels of 0,93, 0.87, and 0.80), although this association became statistically nonsignificant after adjusting for body mass index. Conclusion: Lack of association of natriuretic peptides with OSAH indices suggests that undiagnosed OSAH may not be associated with major alterations in left ventricular function, as reflected in morning natriuretic peptide levels. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Gottlieb, DJ (reprint author), Boston Univ, Sch Med, Room R-304,715 Albany St, Boston, MA 02118 USA. EM dgottlieb@lung.bumc.bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 NR 36 TC 24 Z9 24 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD OCT 1 PY 2006 VL 29 IS 10 BP 1301 EP 1306 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 100FL UT WOS:000241653400006 PM 17068983 ER PT J AU Sun, EY Weissleder, R Josephson, L AF Sun, Eric Yi Weissleder, Ralph Josephson, Lee TI Continuous analyte sensing with magnetic nanoswitches SO SMALL LA English DT Article DE analytes; nanomedicine; nanoswitches; NMR; sensors ID MOLECULAR-INTERACTIONS; NANOPARTICLES; NANOSENSORS; BIOSENSORS; DNA C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5410, Charlestown, MA 02129 USA. EM ljosephson@partners.org FU NCI NIH HHS [U54 CA119349, P50 CA86355]; NHLBI NIH HHS [U01 HL 080731]; NIBIB NIH HHS [R01 EB004626]; PHS HHS [R01 00662] NR 13 TC 47 Z9 47 U1 2 U2 12 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-6810 J9 SMALL JI Small PD OCT PY 2006 VL 2 IS 10 BP 1144 EP 1147 DI 10.1002/smll.200600204 PG 4 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 082EX UT WOS:000240370600006 PM 17193579 ER PT J AU Mason, MF Cloutier, J Macrae, CN AF Mason, Malia F. Cloutier, Jasmin Macrae, C. Neil TI On construing others: Category and stereotype activation from facial cues SO SOCIAL COGNITION LA English DT Review ID UNDERSTANDING FACE RECOGNITION; VISUAL OBJECT RECOGNITION; HUMAN EXTRASTRIATE CORTEX; SOCIAL COGNITION; PERSON PERCEPTION; ATTENTION; CATEGORIZATION; INFORMATION; FEATURES; GENDER AB Although the face is unquestionably the most valuable source of information available to social perceivers, quite how humans exploit physiognomic cues to make sense of unfamiliar social targets has yet to be fully elucidated. The present investigation explores the possibility that bottom-up visual processing of faces (e.g., the detection of diagnostic social category features) increases the accessibility of social group knowledge structures in memory. Two experiments were undertaken in which the inevitability and strength of category and stereotype activation were assessed by having participants make judgments on centrally presented words that were flanked by a varying number of congruent or incongruent distracter faces. Results showed that despite perceivers' intentions to ignore them, the mere presence of faces increased the accessibility of sex categories (Experiment 1) and gender stereotypes (Experiment 2). However, whereas category-based responding was modulated by the number of faces present, no such effect was observed for the accessibility of stereotypical knowledge. We consider the implications of these findings for contemporary treatments of person perception. C1 Massachusetts Gen Hosp, Martinos Imaging Ctr, Boston, MA 02114 USA. Dartmouth Coll, Hanover, NH 03755 USA. Univ Aberdeen, Aberdeen, Scotland. RP Mason, MF (reprint author), Harvard Univ, Martinos Imaging Ctr, MGH, Sch Med, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM malia@nmr.mgh.harvard.edu RI Macrae, Neil/C-4761-2008 NR 121 TC 27 Z9 29 U1 7 U2 14 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0278-016X J9 SOC COGNITION JI Soc. Cogn. PD OCT PY 2006 VL 24 IS 5 BP 540 EP 562 DI 10.1521/soco.2006.24.5.540 PG 23 WC Psychology, Social SC Psychology GA 099HD UT WOS:000241583200003 ER PT J AU Bambauer, KZ Zhang, B Maciejewski, PK Sahay, N Pirl, WF Block, SD Prigerson, HG AF Bambauer, Kara Zivin Zhang, Baohui Maciejewski, Paul K. Sahay, Neayka Pirl, William F. Block, Susan D. Prigerson, Holly G. TI Mutuality and specificity of mental disorders in advanced cancer patients and caregivers SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE major depressive disorder; generalized anxiety disorder; panic disorder; post-traumatic stress disorder; caregivers; oncology; end-of-life ID HEALTH-SERVICE USE; QUALITY-OF-LIFE; PSYCHIATRIC-DISORDERS; IMPACT; CARE; PARTNERS; SYMPTOMS; OUTCOMES; SUPPORT AB We sought to determine mutuality and specificity in rates of mental disorders between advanced cancer patients and their caregivers. Data from 168 non-genetically related patient-caregiver dyads participating in the multi-site Coping with Cancer (CWC) study were included in this analysis. Multivariate logistic regression analyses were conducted to examine associations between diagnoses of a psychiatric disorder in patients with diagnoses of psychiatric disorders in caregivers, and vice versa, controlling for confounders. When patients met criteria for any psychiatric diagnosis, then caregivers were 7.9 times (P < 0.0001) more likely to meet criteria for any psychiatric diagnosis, and vice versa. Caregiver Panic Disorder (PD) diagnosis was associated with patient Generalized Anxiety Disorder (GAD). Patient GAD was also associated with caregiver PD. Finally, patient PD was associated with caregiver GAD and caregiver Post-Traumatic Stress Disorder (PTSD). To our knowledge, this is the first study that demonstrates the mutuality of psychiatric disorders in both advanced cancer patients and their informal caregivers. Specifically, the presence of anxiety disorders in one partner (either caregiver or patient) was associated with a greater likelihood of anxiety disorders in the other. Results suggest that psychiatric distress should be assessed in both patients and their caregivers, and that mental illness in one should raise concern about the possibility of a psychiatric disorder in the other. Results also suggest that targeted interventions to address shared fears and concerns of patients and caregivers might reduce anxiety in the end phases of the patient's illness. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Univ, Pilgrim Hlth Care, Boston, MA 02215 USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Ctr Canc, Psychiat Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA. RP Bambauer, KZ (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM kzbambauer@post.harvard.edu FU NCI NIH HHS [CA 106370, R01 CA106370-01, R01 CA106370]; NIMH NIH HHS [MH 63892, R01 MH063892, MH 56529] NR 19 TC 30 Z9 32 U1 3 U2 10 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD OCT PY 2006 VL 41 IS 10 BP 819 EP 824 DI 10.1007/s00127-006-0103-x PG 6 WC Psychiatry SC Psychiatry GA 089WW UT WOS:000240913600010 PM 16865636 ER PT J AU Emerick, KS Deschler, DG AF Emerick, Kevin S. Deschler, Daniel G. TI Common ENT disorders SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE otolaryngology; otology; nasal; oral cavity; oropharynx; larynx ID ALLERGIC RHINITIS; PERITONSILLAR ABSCESS; APHTHOUS ULCERS; FOREIGN-BODIES; OTITIS-MEDIA; MANAGEMENT; ADULTS; EAR; EPISTAXIS; OTORRHEA AB Objective: To provide a succinct and updated discussion on common ear, nose, and throat (ENT) disorders encountered by primary care physicians. Methods: Review of recent and pertinent literature. Results: Recent data was identified via a PubMed search as well as commonly utilized texts in otolaryngology. Discussion: While it is impossible to discuss all of the ENT disorders encountered by primary care physicians, it is helpful to have a succinct resource to highlight the common disorders and their presenting signs, symptoms and initial treatments. Conclusion: Recognizing specific signs and symptoms can help primary care physicians diagnose common ENT disorders. This review discusses these presentations and provides the initial management steps, as well as when to refer patients for further evaluation. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Emerick, KS (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Kevin_Emerick@meei.harvard.edu NR 43 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD OCT PY 2006 VL 99 IS 10 BP 1090 EP 1099 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 134GZ UT WOS:000244072800012 PM 17100030 ER PT J AU Martinez-Rumayor, A Januzzi, JL AF Martinez-Rumayor, Abelardo Januzzi, James L., Jr. TI Non-ST segment elevation acute coronary syndromes: A comprehensive review SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE acute coronary syndromes; non-ST segment elevation myocardial infarction; unstable angina; risk stratification; management ID WAVE MYOCARDIAL-INFARCTION; PLATELET GLYCOPROTEIN IIB/IIIA; MOLECULAR-WEIGHT HEPARIN; ONE-YEAR SURVIVAL; UNSTABLE ANGINA; ARTERY-DISEASE; UNFRACTIONATED HEPARIN; ANTIPLATELET THERAPY; TROPONIN-I; CONSERVATIVE STRATEGIES AB As the non-ST segment elevation acute coronary syndromes (NSTEACS) include unstable angina pectoris (UAP) and the non-ST segment elevation myocardial infarction (NSTEMI), acute diagnosis and risk stratification can often prove challenging. This review will cover guidelines and strategies for risk assessment, contemporary approaches to acute patient management as well as recommendations for timing of specialist referral. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 55 TC 4 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD OCT PY 2006 VL 99 IS 10 BP 1103 EP 1110 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 134GZ UT WOS:000244072800014 PM 17100031 ER PT J AU Harley, JB Kelly, JA Kaufman, KM AF Harley, John B. Kelly, Jennifer A. Kaufman, Kenneth M. TI Unraveling the genetics of systemic lupus erythematosus SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE SLE; lupus; genetics; gene; polymorphism ID MANNOSE-BINDING LECTIN; MAJOR HISTOCOMPATIBILITY COMPLEX; SINGLE-NUCLEOTIDE POLYMORPHISM; FC-GAMMA-RIIA; LYMPHOID TYROSINE PHOSPHATASE; HLA-CLASS-II; AUTOIMMUNE THYROID-DISEASE; CONNECTIVE-TISSUE DISEASE; HEREDITARY C1Q DEFICIENCY; POPULATION-BASED COHORT AB The capacity to locate polymorphisms on a virtually complete map of the human genome coupled with the ability to accurately evaluate large numbers (by historical standards) of genetic markers has led to gene identification in complex diseases, such as systemic lupus erythematosus (SLE or lupus). While this is a phenotype with enormous clinical variation, the twin studies and the observed familial aggregation, along with the genetic effects now known, suggest a strong genetic component. Unlike type 1 diabetes, lupus genetics is not dominated by the powerful effect of a single locus. Instead, there are at least six known genetic association effects in lupus of smaller magnitude (odds ratio < 2), and at least 17 robust linkages (established and arguably confirmed independently) defining potentially responsible genes that largely remain to be discovered. The more convincing genetic associations include the human leukocyte antigen region (with multiple genes), C1q, PTPN22, PDCD1, Fc receptor-like 3, Fc gamma RIIA, Fc gamma RIIIA, interferon regulatory factor 5, and others. How they contribute to disease risk remains yet to be clarified, beyond the obvious speculation derived from what has previously been learned about these genes. Certainly, they are expected to contribute to lupus risk independently and in combination with each other, with genes not yet identified, and with the environment. A substantial number of genes (> 10) are expected to be identified to contribute to lupus or in its many subsets defined by clinical and laboratory features. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Harley, JB (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM john-harley@omrf.ouhsc.edu NR 169 TC 85 Z9 92 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD OCT PY 2006 VL 28 IS 2 BP 119 EP 130 DI 10.1007/s00281-006-0040-5 PG 12 WC Immunology; Pathology SC Immunology; Pathology GA 097OC UT WOS:000241456300005 PM 17021721 ER PT J AU Cohen, PL AF Cohen, Philip L. TI Apoptotic cell death and lupus SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE lupus; apoptosis; programmed cell death ID RECEPTOR TYROSINE KINASES; DENDRITIC CELLS; AUTOIMMUNE-DISEASE; IMPAIRED UPTAKE; TNF-ALPHA; LYMPHOPROLIFERATIVE DISEASE; AUTOANTIBODY PRODUCTION; MOUSE STRAINS; IN-VITRO; B-CELLS AB Programmed cell death and the disposal of cell corpses by phagocytic cells are highly regulated ongoing processes essential for the survival and well-being of higher organisms. Abnormalities in the susceptibility of certain cells to receptor-induced death are known to lead to certain human diseases (e.g., autoimmune lymphoproliferative syndrome) and may contribute to the pathogenesis of systemic lupus erythematosus. Impaired clearance of apoptotic cells is also likely to be an important factor in lupus pathogenesis, though the biological basis of such a defect remains elusive. Finally, the process of apoptosis has been shown to contribute to lupus disease effector mechanisms. A better understanding of the role of apoptosis in lupus very likely will lead to improved diagnosis and therapy. C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Cohen, PL (reprint author), Univ Penn, 421 Curie Blvd,Suite 757, Philadelphia, PA 19104 USA. EM philipco@mail.med.upenn.edu NR 68 TC 16 Z9 17 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD OCT PY 2006 VL 28 IS 2 BP 145 EP 152 DI 10.1007/s00281-006-0038-z PG 8 WC Immunology; Pathology SC Immunology; Pathology GA 097OC UT WOS:000241456300007 PM 16941106 ER PT J AU Zhou, XH Qin, GS Lin, HZ Li, G AF Zhou, X. H. Qin, G. S. Lin, H. Z. Li, G. TI Inferences in censored cost regression models with empirical likelihood SO STATISTICA SINICA LA English DT Article DE censored data; empirical likelihood; health care costs; prediction ID ESTIMATING MEDICAL COSTS; COLLABORATIVE CARE; MEDIAN REGRESSION; LINEAR-MODELS; POPULATION; DEPRESSION; SAMPLES; TABLES AB In many studies of health economics, we are interested in the expected total cost over a certain period for a patient with given characteristics. Problems can arise if cost estimation models do not account for distributional aspects of costs. Two such problems are (1) the skewed nature of the data, and (2) censored observations. In this paper we propose an empirical likelihood (EL) method for constructing a confidence region for the vector of regression parameters, and a confidence interval for the expected total cost of a patient with the given covariates. We show that this new method has good theoretical properties and we compare its finite-sample properties with those of the existing method. Our simulation results demonstrate that the new EL-based method performs as well as the existing method when cost data are not so skewed, and outperforms the existing method when cost data are highly skewed. Finally, we illustrate the application of our method to a data set. C1 VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. Sichuan Univ, Sch Math, Chengdu 610064, Peoples R China. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. RP Zhou, XH (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. EM azhou@u.washington.edu; gqin@gsu.edu; huazhenlin@hotmail.com; vli@ucla.edu NR 29 TC 6 Z9 7 U1 0 U2 3 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD OCT PY 2006 VL 16 IS 4 BP 1213 EP 1232 PG 20 WC Statistics & Probability SC Mathematics GA 108ZE UT WOS:000242276900008 ER PT J AU Magliocca, JF Held, IKA Odorico, JS AF Magliocca, Joseph F. Held, Inka K. A. Odorico, Jon S. TI Undifferentiated murine embryonic stem cells cannot induce portal tolerance but may possess immune privilege secondary to reduced major histocompatibility complex antigen expression SO STEM CELLS AND DEVELOPMENT LA English DT Article ID MHC CLASS-I; TRANSPLANTATION TOLERANCE; T-CELLS; MICE; RAT; DIFFERENTIATION; ANTIBODIES; CHIMERISM; DEFICIENT; RESPONSES AB Induction of donor-specific tolerance using embryonic stem (ES) cells followed by transplantation of ES cell-derived tissues from the same allogeneic strain could theoretically engender successful transplantation without immunosuppression. We sought to induce tolerance using bona fide murine ES cells in immunocompetent mice. ES cells were evaluated for the expression of markers restricted to undifferentiated cells [stage-specific embryonic antigen-1 (SSEA-1) and OCT-4] and the ability to form teratomas in immunodeficient mice. BALB/cByJ mice underwent intraportal inoculation with YC5-EYFP ES cells (129 strain; R1-derived) or saline followed by transplantation with 129X1/SvJ, CBA/J, or BALB/cByJ nonvascularized, neonatal cardiac grafts. Mice were sacrificed at graft failure and underwent histologic evaluation of transplanted grafts and lymphoid organs. ES cells and early differentiated progeny underwent real time (RT)-PCR and fluorescence-activated cell sorting (FACS) analysis to detect major histocompatibility complex (MHC) gene transcription and antigen expression. ES cells expressed markers restricted to undifferentiated cells while maintaining the ability to form teratomas in immunodeficient mice. No prolongation of allograft survival or evidence of lymphoid chimerism was observed in immunocompetent recipient mice despite hepatic teratoma formation. MHC class I, class II, and nonclassical antigens were undetectable on ES cells and early differentiated progeny despite the presence of mRNA transcripts. Class I expression was strongly up-regulated upon exposure to gamma-interferon. Intraportal inoculation with murine ES cells does not produce lymphoid chimerism or induce donor-specific unresponsiveness to neonatal cardiac grafts in unmanipulated immunocompetent hosts. However, specific differentiated cell types such as ES cell-derived dendritic cells, or alternate routes of ES cell administration, may be effective. ES cells appear to have immune privilege, allowing them to form teratomas in immunocompetent mice. C1 Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Div Transplantat, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA. WiCell Res Inst, Madison, WI 53792 USA. RP Magliocca, JF (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Div Transplantat, 600 Highland Ave,H4-780, Madison, WI 53792 USA. EM drjoemag@yahoo.com FU NIDDK NIH HHS [U19DK61244] NR 37 TC 45 Z9 48 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD OCT PY 2006 VL 15 IS 5 BP 707 EP 717 DI 10.1089/scd.2006.15.707 PG 11 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 105GQ UT WOS:000242018800011 PM 17105406 ER PT J AU Andermahr, J Jubel, A Elsner, A Prokop, A Tsikaras, P Jupiter, J Koebke, J AF Andermahr, Jonas Jubel, Axel Elsner, Andreas Prokop, Axel Tsikaras, Prokopios Jupiter, Jesse Koebke, Juergen TI Malunion of the clavicle causes significant glenoid malposition: a quantitative anatomic investigation SO SURGICAL AND RADIOLOGIC ANATOMY LA English DT Article DE clavicle fracture; malunion; glenoid; anatomy; range of motion ID MIDCLAVICULAR FRACTURES; CONSERVATIVE TREATMENT; EXTENSION OSTEOTOMY; OPERATIVE TREATMENT; FOLLOW-UP; COMPLICATIONS; BIOMECHANICS; NONUNION; FIXATION; SHOULDER AB Objective An experimental cadaver model was used to assess the effects of a malunited fracture of the middle third of the clavicle on the functional anatomy of the shoulder joint. Method Anatomic samples were prepared with simulated shortening and axial malposition of the clavicle. From these, alterations in glenoid fossa position were measured and depicted graphically. Results Healing of clavicle fractures with bony shortening leads to a ventromedialcaudal shift in glenoid fossa position. The following malpositions of the clavicle lead to the respective glenoid fossa positional changes: caudal deviation leads to a mediocaudal shift, cranial deviation leads to a dorsolateral shift of the glenoid fossa, ventral deviation causes a ventrolateral shift, dorsal deviation leads to mediocaudal shift of the fossa, cranial rotation leads to ventrolateral shift in fossa position, and caudal rotation leads to a dorsomedial shift in glenoid fossa position. Conclusion Clinical implication of these data is that bony shortening in combination with caudal displacement leads to distinct functional deficits in abduction, particularly overhead motion. Using the above data, a vector model was created to calculate position of the glenoid fossa dependent on clavicle position/malposition. The model is a valuable tool to be used for planning open reduction and fixation of clavicular fractures or malunions. C1 Univ Hosp Cologne, Dept Trauma Hand & Reconstruct Surg, D-50924 Cologne, Germany. Arestotelian Univ Thessaloniki, Lab Anat, Thessaloniki 54006, Greece. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Hand Surg Serv, Boston, MA 02114 USA. Univ Cologne, Ctr Anat, D-50924 Cologne, Germany. RP Andermahr, J (reprint author), Univ Hosp Cologne, Dept Trauma Hand & Reconstruct Surg, Joseph Stelzmann Str 9, D-50924 Cologne, Germany. EM jandermahr@t-online.de OI Jubel, Axel/0000-0003-4402-4816 NR 45 TC 29 Z9 30 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1279-8517 J9 SURG RADIOL ANAT JI Surg. Radiol. Anat. PD OCT PY 2006 VL 28 IS 5 BP 447 EP 456 DI 10.1007/s00276-006-0122-z PG 10 WC Anatomy & Morphology; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Anatomy & Morphology; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA 098VT UT WOS:000241551600003 PM 16943999 ER PT J AU Weiss, MJ Ng, CY Madsen, JC AF Weiss, Matthew J. Ng, Choo Y. Madsen, Joren C. TI Tolerance, xenotransplantation: Future therapies SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID HEMATOPOIETIC-CELL TRANSPLANTATION; THYMIC LOBE TRANSPLANTATION; DECAY-ACCELERATING FACTOR; STAGE RENAL-DISEASE; TO-BABOON MODEL; MINIATURE SWINE; HEART-TRANSPLANTATION; HYPERACUTE REJECTION; ALLOGRAFT TOLERANCE; XENOGRAFT SURVIVAL AB Solid organ transplantation is limited by an insufficient number of organs to meet the needs of a growing population of patients with end-organ failure. A second problem is that, after successful transplantation, many organs fail owing in large part to chronic immunologic injury or so-called "chronic rejection." In other circumstances, the organ "outlives" the recipient, often because the recipient succumbs to medical conditions related to chronic immunosuppression. This review focuses on two future therapies that could solve these problems, specifically, tolerance induction to permit long-term patient and graft survival and xenotransplantation to provide an unlimited supply of donor organs. The primary focuses are the most promising ongoing transplantation research that could be encountered by clinical surgeons in the near future. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, 55 Fruit St,Bullfinch 119, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01HL054211, R01HL071932, R01HL67110]; NIAID NIH HHS [U19AI066705, P01AI50157] NR 85 TC 7 Z9 11 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD OCT PY 2006 VL 86 IS 5 BP 1277 EP + DI 10.1016/j.suc.2006.06.016 PG 21 WC Surgery SC Surgery GA 093EB UT WOS:000241149500013 PM 16962414 ER PT J AU Court, LE Jahnke, L Chin, D Song, J Cormack, R Zygmanski, P Tishler, RB Chin, L AF Court, Laurence E. Jahnke, Lennart Chin, David Song, Jun Cormack, Robert Zygmanski, Piotr Tishler, Roy B. Chin, Lee TI Dynamic IMRT treatments of sinus region tumors: Comparison of Monte Carlo calculations with treatment planning system calculations and ion chamber measurements SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE IMRT; heterogeneity correction; dose calculations; and sinus ID CLINICAL IMPLEMENTATION; DOSE CALCULATION; RADIOTHERAPY; VERIFICATION; ALGORITHMS; DELIVERY; BEAM; CODE AB Results are presented comparing Monte Carlo (MC) calculations for dynamic IMRT treatments of tumors in the sinus region with Eclipse treatment planning system dose calculations, and ion chamber measurements. The EGS4nrc MC code, BEAMnrc, was commissioned to simulate a Varian 21Ex Linac for both open and IMRT fields. The accuracy of the simulation for IMRT plans was evaluated using a head phantom by comparing MC, Eclipse, TLD results, and ion chamber in solid water phantom measurements. The MC code was then used to simulate dose distributions for five patients who were treated using dynamic IMRT for tumors in the sinus region. The results were compared with absolute and relative dose distributions calculated using Eclipse (pencil beam, modified-Batho inhomogeneity correction). Absolute dose differences were also compared with ion chamber results. Comparison of the doses calculated on the head phantom using MC, compared with Eclipse, ion chamber, and TLD measurements showed differences of -3.9%, -1.4%, and -2.0%, respectively (MC is colder). Relative dose distributions for the patient plans calculated using MC agreed well with those calculated using Eclipse with respect to targets and critical organs, indicating the modified-Batho correction is adequate. Average agreement for mean absolute target doses between MC and Eclipse was -3.0 +/- 2.3% (1 s.d.). Agreement between ion chamber and Eclipse for these patients was -2.2 +/- 1.9%, compared with 0.2 +/- 2.0% for all head and neck IMRT patients. When Eclipse doses were corrected based on ion chamber results, agreement between MC and Eclipse was -0.7 2.0%, indicating a small systematic uncertainty in the doses calculated using the treatment planning system for this subset of patients. C1 Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Court, LE (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM lcourt@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 20 TC 3 Z9 3 U1 0 U2 2 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD OCT PY 2006 VL 5 IS 5 BP 489 EP 495 PG 7 WC Oncology SC Oncology GA 096HO UT WOS:000241368400006 PM 16981791 ER PT J AU Palmas, W Teresi, J Morin, P Wolff, LT Field, L Eimicke, JP Capps, L Prigollini, A Orbe, I Weinstock, RS Shea, S AF Palmas, Walter Teresi, Jeanne Morin, Philip Wolff, L. Thomas Field, Lesley Eimicke, Joseph P. Capps, Linnea Prigollini, Alejandro Orbe, Irma Weinstock, Ruth S. Shea, Steven TI Recruitment and enrollment of rural and urban medically underserved elderly into a randomized trial of telemedicine case management for diabetes care SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article ID COLUMBIA-UNIVERSITY INFORMATICS; CLINICAL-TRIALS; IDEATEL PROJECT; PARTICIPATION; NONRESPONDERS; PHYSICIANS; EDUCATION; CANCER; COMMUNITY AB Our goal was to identify reasons for enrollment or refusal to participate in a randomized trial of telemedicine case management of diabetes. We performed a prospective survey of participants and non-participants during recruitment for the Informatics for Diabetes Education and Telemedicine (IDEATel) study, a randomized trial of telemedicine case management of diabetes mellitus in medically underserved elderly. There were two recruitment areas: urban New York City, and rural upstate New York. A Participant Questionnaire (PQ) was administered at the baseline IDEATel visit, and a Non-Participant Questionnaire (NPQ) was administered during the recruitment telephone call. Both questionnaires listed possible responses; subjects could choose more than one response or give their own. Of 1,660 IDEATel participants, 99.7% completed the PQ. Most frequent reason for participation was the belief that the technology could help them (52% and 42% of urban and rural respondents, respectively). Of the 2,231 subjects refusing participation, 28% answered the NPQ (90% of respondents were from rural area). Most frequent reasons not to participate in the rural area were being too busy (23%), and discomfort with the technology (22%), and in the urban area the belief that the technology could not help them (71%), discomfort with it ( 52%), and not liking to participate in studies (52%). In multivariate analysis ( rural respondents only), knowing how to use a computer was an independent predictor of participation ( p < 0.001). In conclusion, perceptions and beliefs regarding technology, including the expectation to benefit from it, played an important role in the decision to participate. C1 Columbia Univ, Dept Med, New York, NY 10032 USA. Hebrew Home Aged, Bronx, NY USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY USA. SUNY Upstate Med Univ, Dept Family Med, Syracuse, NY USA. Harlem Hosp Med Ctr, Dept Med, New York, NY USA. St Lukes Roosevelt Hosp, Dept Med, New York, NY USA. VA Med Ctr, Dept Vet Affairs, Syracuse, NY USA. Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. Columbia Univ, Dept Biomed Informat, New York, NY USA. RP Palmas, W (reprint author), Columbia Univ, Dept Med, 622 W 168th St PH 9-E,Suite 105, New York, NY 10032 USA. EM wp56@columbia.edu NR 23 TC 15 Z9 15 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD OCT PY 2006 VL 12 IS 5 BP 601 EP 607 DI 10.1089/tmj.2006.12.601 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 101VJ UT WOS:000241768700029 PM 17042714 ER PT J AU Barr, RG Bourbeau, J Camargo, CA Ram, FSF AF Barr, R. G. Bourbeau, J. Camargo, C. A. Ram, F. S. F. TI Tiotropium for stable chronic obstructive pulmonary disease: a meta-analysis SO THORAX LA English DT Article ID AIR-FLOW LIMITATION; INHALED ANTICHOLINERGIC BRONCHODILATOR; ACTING ANTIMUSCARINIC BRONCHODILATOR; ONCE-DAILY TIOTROPIUM; COPD PATIENTS; SPIROMETRIC EFFICACY; EXERCISE TOLERANCE; HEALTH OUTCOMES; LUNG HEALTH; SALMETEROL AB Background: A systematic review was undertaken to evaluate the efficacy of tiotropium, a long acting anticholinergic drug, on clinical events, symptom scales, pulmonary function, and adverse events in stable chronic obstructive pulmonary disease ( COPD). Methods: A systematic search was made of the Cochrane trials database, MEDLINE, EMBASE, CINAHL, and a hand search of 20 respiratory journals. Missing data were obtained from authors and the manufacturer. Randomised controlled trials of >= 12 weeks' duration comparing tiotropium with placebo, ipratropium bromide, or long acting beta(2) agonists (LABA) were reviewed. Studies were pooled to yield odds ratios ( OR) or weighted mean differences with 95% confidence intervals (CI). Results: Nine trials ( 8002 patients) met the inclusion criteria. Tiotropium reduced the odds of a COPD exacerbation ( OR 0.73; 95% CI 0.66 to 0.81) and related hospitalisation ( OR 0.68; 95% CI 0.54 to 0.84) but not pulmonary ( OR 0.50; 95% CI 0.19 to 1.29) or all-cause ( OR 0.96; 95% CI 0.63 to 1.47) mortality compared with placebo and ipratropium. Reductions in exacerbations and hospitalisations compared with LABA were not statistically significant. Similar patterns were evident for quality of life and symptom scales. Tiotropium yielded greater increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline to 6-12 months than did placebo, ipratropium, and LABA. Decline in FEV1 over 1 year was 30 ml ( 95% CI 7 to 53) slower with tiotropium than with placebo and ipratropium ( data were not available for LABA). Reports of dry mouth and urinary tract infections were increased with tiotropium. Conclusions: Tiotropium reduced COPD exacerbations and related hospitalisations, improved quality of life and symptoms, and may have slowed the decline in FEV1. Long term trials are warranted to evaluate the effects of tiotropium on decline in FEV1 and to clarify its role compared with LABA. C1 Columbia Univ, Med Ctr, Div Gen Med, New York, NY 10032 USA. McGill Univ, Ctr Hlth, Montreal, PQ, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Massey Univ, Sch Hlth Sci, Auckland, New Zealand. RP Barr, RG (reprint author), Columbia Univ, Med Ctr, Div Gen Med, PH-9,E Room 105,630 W 168th St, New York, NY 10032 USA. EM rgb9@columbia.edu FU NHLBI NIH HHS [R01 HL075476-05, HL063841, R01 HL075476, HL077612, HL075476, R01 HL077612, R01 HL077612-04] NR 53 TC 138 Z9 150 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD OCT PY 2006 VL 61 IS 10 BP 854 EP 862 DI 10.1136/thx.2006.063271 PG 9 WC Respiratory System SC Respiratory System GA 088YO UT WOS:000240847200008 PM 16844726 ER PT J AU Van Poll, D Sokmensuer, C Ahmad, N Tilles, AW Berthiaume, F Toner, M Yarmush, ML AF Van Poll, Daan Sokmensuer, Cenk Ahmad, Noor Tilles, Arno W. Berthiaume, Francois Toner, Mehmet Yarmush, Martin L. TI Elevated hepatocyte-specific functions in fetal rat hepatocytes co-cultured with adult rat hepatocytes SO TISSUE ENGINEERING LA English DT Article ID LACTIC ACID SCAFFOLDS; IN-VITRO MATURATION; ACUTE LIVER-FAILURE; ONCOSTATIN-M; BIOARTIFICIAL LIVER; BONE-MARROW; STEM-CELLS; SANDWICH CONFIGURATION; EXTRACELLULAR-MATRIX; MATURE HEPATOCYTES AB Fetal hepatocytes (FHEPs) are a potential source of highly proliferative transplantable cells but express low levels of liver-specific functions. We hypothesized that the microenvironment of adult hepatocytes (AHEPs) may upregulate these functions. Primary FHEPs were seeded on top of collagen-sandwiched AHEPs directly or separated by a porous transwell membrane insert. In direct co-cultures, albumin (ALB) secretion, urea synthesis, and cytochrome P450 (CytP450) activity were all approximately 2 times as high as the sum of the corresponding monocultures. Using a transwell porous insert led to similar results, suggesting a major role for soluble factors. When AHEPs and FHEPs were separated after co-culture, they both initially showed significantly higher ALB secretion than control monocultures, whereas urea synthesis was significantly lower for the FHEPs only. Functions of previously co-cultured FHEPs normalized over the course of a week, but AHEP function remained high even after separation. In conclusion, co-culturing AHEPs with FHEPs increases expression of liver-specific functions in both cell types. The effect on FHEPs, but not AHEPs, was reversible. Unraveling the underlying mechanisms and optimizing this phenomenon will be useful in making fetal liver cells a potential cell source for hepatic tissue-engineering applications. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02115 USA. Shriners Burns Hosp, Boston, MA 02115 USA. Univ Utrecht, Med Ctr, Dept Surg, Utrecht, Netherlands. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02115 USA. EM ireis@sbi.org FU NIDDK NIH HHS [R01 DK 43371, K08 DK 066040] NR 35 TC 17 Z9 18 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD OCT PY 2006 VL 12 IS 10 BP 2965 EP 2973 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 105PU UT WOS:000242045600025 PM 17518664 ER PT J AU Whelan, P AF Whelan, P. TI Link between rheumatoid arthritis and cancer SO ZEITSCHRIFT FUR RHEUMATOLOGIE LA German DT Article DE rheumatoid arthritis (RA); Hodgkin's lymphoma; non-Hodgkin's lymphoma (NHL); EBV; methotrexate; TNF-alpha; carcinogenesis ID EPSTEIN-BARR-VIRUS; LYMPHOPROLIFERATIVE DISORDERS; AUTOIMMUNE-DISEASES; LYMPHOMA; RISK; METHOTREXATE; THERAPY; ANTIBODY; COHORT AB Because it is a systemic disorder, rheumatoid arthritis (RA) is known to predispose affected individuals to other organ manifestations as well as arthritic problems. The serious complications include pericarditis, pulmonary and cutaneous nodules, episcleritis, and rheumatoid vasculitis. Of late, a significantely increased incidence of lymphoma has also accumulated, The overall risk is about double than in the general population, but that in patients with the most severe arthritis is dramatically higher. Men with RA appear to have an extremely elevated risk of Hodgkin's disease, which has also been observed at a higher incidence among the children of affected patients. These lymphomas are not typically infected with EBV, though RA patients have a defective capacity to control systemic EBV infection. Increasing attention is being paid to the effect of RA treatments on development of lymphoma, and some patients with EBV-positive tumors who have been taking methotrexate have shown a positive response after just discontinuing this drug. More controversial is the question of whether anti-TNF alpha agents involve an increased risk of lymphoma; in light of the conflicting evidence this matter is still unresolved. C1 Massachusetts Gen Hosp, Div Pediat Rheumatol, MGH Canc Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Whelan, P (reprint author), Massachusetts Gen Hosp, Div Pediat Rheumatol, MGH Canc Ctr, Boston, MA 02114 USA. EM jwhelan@partners.org NR 34 TC 3 Z9 3 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-1855 J9 Z RHEUMATOL JI Z. Rheumatol. PD OCT PY 2006 VL 65 IS 6 BP 497 EP + DI 10.1007/s00393-006-0105-9 PG 6 WC Rheumatology SC Rheumatology GA 148MZ UT WOS:000245080600005 PM 17004050 ER PT J AU Wherry, EJ Day, CL Draenert, R Miller, JD Kiepiela, P Woodberry, T Brander, C Addo, M Klenerman, P Ahmed, R Walker, BD AF Wherry, E. John Day, Cheryl L. Draenert, Rika Miller, Joseph D. Kiepiela, Photini Woodberry, Tonia Brander, Christian Addo, Marylyn Klenerman, Paul Ahmed, Rafi Walker, Bruce D. TI HIV-specific CD8 T cells express low levels of IL-7R alpha: Implications for HIV-specific T cell memory SO VIROLOGY LA English DT Article DE HIV; CD8 T cell; immunological memory; T cell memory; chronic infection; IL-7r alpha ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; HEPATITIS-C VIRUS; VIRAL-INFECTION; EFFECTOR FUNCTION; FUNCTIONAL IMPAIRMENT; TETRAMER BINDING; IL-7 RECEPTOR; CTL RESPONSES; ANTIGEN; DIFFERENTIATION AB Chronic infections in mice can result in defects in memory CD8 T cell properties including low expression of the IL-7R alpha (CD127). To determine whether defects in memory CD8 T cell formation exist during human chronic infections and to what extent these defects may be allele- or epitope-specific, we compared influenza (Flu), vaccinia (VV) and EBV-specific CD8 T cells to HIV-specific CD8 T cells, using a panel of 13 HIV tetramers. Compared to Flu, VV or EBV, HIV tetramer+ CD8 T cells expressed significantly lower levels of CD127, and this reduction was pervasive across all epitopes and alleles tested and over a wide range of viral loads and CD4 counts. These results indicate impaired HIV-specific memory CD8 T cell differentiation, regardless of level of control of viremia, epitopes targeted or restricting HLA alleles. (c) 2006 Elsevier Inc. All rights reserved. C1 Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 2JD, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ KwaZulu, Doris Duke Med Res Inst, HIV Pathogenesis Program, Durban, South Africa. RP Wherry, EJ (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. EM jwherry@wistar.org; BWALKER@PARTNERS.ORG RI Day, Cheryl/J-9844-2012; OI Brander, Christian/0000-0002-0548-5778 NR 42 TC 36 Z9 38 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 2006 VL 353 IS 2 BP 366 EP 373 DI 10.1016/j.virol.2006.06.017 PG 8 WC Virology SC Virology GA 090DN UT WOS:000240930900012 PM 16860834 ER PT J AU Reeve, JR Rosenquist, GL Keire, DA Chew, P Nicholas, HB Davis, MT Lee, TD Shively, JE Backus, RC AF Reeve, Joseph R., Jr. Rosenquist, Grace L. Keire, David A. Chew, Peter Nicholas, Hugh B. Davis, Michael T., Jr. Lee, Terry D. Shively, John E. Backus, Robert C. TI Crucial role of position 40 for interactions of CCK-58 revealed by sequence of cat CCK-58 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE pancreas; cholecystokinin; conformations; structure-activity relationships; sequence analysis; mass spectral analysis; molecular forms ID RAT PANCREATIC ACINI; DIFFERENT CONFORMATIONS; MICROSEQUENCE ANALYSIS; CHOLECYSTOKININ; RECEPTOR; INTESTINE; SECRETIN; PERFORMANCE; PEPTIDES; TERMINUS AB Evidence suggests that amino terminal extensions of CCK-8 affect the carboxyl terminal bioactive region of CCK. Cat CCK-58 was purified by low pressure reverse phase and ion-exchange chromatography steps and several reverse phase HPLC steps. The purified peptide and its tryptic fragments were characterized by mass spectral analysis and microsequence analysis. The structure of cat CCK-58 is: AVQKVDGEPRAHLGALLARYIQQARKAPSGRMSVIKNLQSLDPSHRISDRDY(SO3) MGWMDF-amide. Cat and dog CCK-58 are identical except for position 40 which is serine in cat and asparagine in dog. Radioimmunoassay detected cat CCK-58 about 1/10th as well as dog CCK-58, indicating a marked effect on C-terminal immunoreactivity. Cat CCK-58 with a serine at position 40, the same residue found in pig, mouse, cow and rabbit CCK-58, can be used as a unique bioprobe for defining how amino terminal amino acids influence the structure and bioactivity of the carboxyl terminal region of CCK. (c) 2006 Elsevier Inc. All rights reserved. C1 Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Digest Dis Div, Los Angeles, CA 90024 USA. Univ Calif Davis, Sect Neurobiol Physiol & Behav, Davis, CA 95616 USA. Univ Pittsburgh, Pittsburgh Supercomp Ctr, Pittsburgh, PA 15203 USA. Beckman Res Inst City Hope, Div Immunol, Duarte, CA 91010 USA. RP Keire, DA (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. EM dkeire@ucla.edu FU NCI NIH HHS [CA3572]; NCRR NIH HHS [RR06009, R01-RR06217]; NIDDK NIH HHS [DK-41301]; PHS HHS [R01-33580] NR 34 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 29 PY 2006 VL 348 IS 3 BP 819 EP 825 DI 10.1016/j.bbrc.2006.07.081 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 079HM UT WOS:000240166500007 PM 16904071 ER PT J AU Lee, MF Beauchamp, RL Beyer, KS Gusella, JF Ramesh, V AF Lee, Ming-Fen Beauchamp, Roberta L. Beyer, Kim S. Gusella, James F. Ramesh, Vijaya TI Magicin associates with the Src-family kinases and is phosphorylated upon CD3 stimulation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE NF2; merlin; Src kinases; EG-1; MED28; mediator; CD3; T cell receptor; Jurkat cells ID BETA-CATENIN; GENE EG-1; TRANSCRIPTIONAL REGULATION; SIGNAL-TRANSDUCTION; MEDIATOR COMPLEX; PROTEIN; RECEPTOR; ACTIN; CELLS; FYN AB We recently identified a novel actin cytoskeleton-associated protein magicin, for merlin and Grb2 interacting cytoskeletal protein. To unravel the cellular functions of magicin, we used a yeast two-hybrid system and identified Fyn tyrosine kinase as a specific binding partner for magicin. Fyn phosphorylates magicin in vitro. In addition to Fyn, Src and Lck also interact with magicin. Upon stimulation with anti-CD3 antibody, magicin is phosphorylated in the T lymphocyte leukemia Jurkat cell line. Magicin phosphorylation is not observed in an Lck-deficient line, J.CaM1.6, indicating that Lck is the major Src family kinase for phosphorylating magicin in Jurkat cells. Employing site-directed mutagenesis along with in vitro kinase assays, we found that Y64 of magicin is phosphorylated by Lck creating a SH2-Grb2 binding motif. Magicin has also been identified as a Mediator subunit (MED28) in the nucleus involved in transcriptional regulation, therefore we propose that magicin may serve as a multi-faceted adaptor/scaffold to relay cellular signaling to the cytoskeleton and from the cytoskeleton to the nucleus. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, 185 Cambridge St, Boston, MA 02114 USA. EM ramesh@helix.mgh.harvard.edu FU NINDS NIH HHS [NS24279] NR 23 TC 7 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 29 PY 2006 VL 348 IS 3 BP 826 EP 831 DI 10.1016/j.bbrc.2006.07.126 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 079HM UT WOS:000240166500008 PM 16899217 ER PT J AU Thomas, SL Deadwyler, GD Tang, J Stubbs, EB Muir, D Hiatt, KK Clapp, DW De Vries, GH AF Thomas, Stacey L. Deadwyler, Gail D. Tang, Jun Stubbs, Evan B., Jr. Muir, David Hiatt, Kelly K. Clapp, D. Wade De Vries, George H. TI Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE neurofibromatosis; NF1; NF1-GRD; neurofibroma; MPNST; Schwann cell; Ras; morphology; proliferation; angiogenesis ID NERVE SHEATH TUMORS; GROWTH-FACTOR EXPRESSION; WILD-TYPE P53; NEUROFIBROMATOSIS TYPE-1; GENE-PRODUCT; TUMORIGENIC PROPERTIES; ADENYLYL-CYCLASE; ABERRANT GROWTH; DROSOPHILA NF1; IN-VITRO AB Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type I (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwarm cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwarm cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NFI-GRD can at least partially reverse the transformation of human NEI tumor-derived Schwarm cells. Published by Elsevier Inc. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Neurosci Program, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60680 USA. Univ Florida, Div Neurol, Dept Pediat, Gainesville, FL 32611 USA. Univ Florida, McKnight Brain Inst, Gainesville, FL 32611 USA. Univ Florida, UF Shands Canc Ctr, Gainesville, FL 32611 USA. Indiana Univ, Sch Med, Dept Microbiol Immunol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. RP De Vries, GH (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM George.Devries@med.va.gov NR 63 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 29 PY 2006 VL 348 IS 3 BP 971 EP 980 DI 10.1016/j.bbrc.2006.07.159 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 079HM UT WOS:000240166500027 PM 16908010 ER PT J AU Weissgerber, P Held, B Bloch, W Kaestner, L Chien, KR Fleischmann, BK Lipp, P Flockerzi, V Freichel, M AF Weissgerber, Petra Held, Brigitte Bloch, Wilhelm Kaestner, Lars Chien, Kenneth R. Fleischmann, Bernd K. Lipp, Peter Flockerzi, Veit Freichel, Marc TI Reduced cardiac L-type Ca2+ current in Ca-v beta(-/-)(2) embryos impairs cardiac development and contraction with secondary defects in vascular maturation SO CIRCULATION RESEARCH LA English DT Article DE L-type Ca2+ channel; cardiac development; Ca-v ss(2) subunit; heart failure; embryonic death ID ACTIVATED CALCIUM CHANNELS; GREEN FLUORESCENT PROTEIN; BETA-SUBUNIT; REGIONAL EXPRESSION; MICE; MOUSE; GENE; CARDIOMYOCYTES; INACTIVATION; DISRUPTION AB Cardiac myocyte contraction depends on transmembrane L-type Ca2+ currents and the ensuing release of Ca2+ from the sarcoplasmic reticulum. Here we show that these L-type Ca2+ currents are essential for cardiac pump function in the mouse at developmental stages where the functional significance of the heart becomes imperative to blood flow and to the continuing growth and survival of the embryo. Disruption of the Ca-v beta(2) gene, which encodes for the predominant ancillary beta subunit of cardiac Ca2+ channels, resulted in diminished L-type Ca2+ currents in cardiomyocytes of embryonic day 9.5 (E9.5). This led to a functionally compromised heart, causing defective remodeling of intra- and extraembryonic blood vessels and embryonic death following E10.5. The defects in vascular remodeling were also observed when the Ca-v beta(2) gene was selectively targeted in cardiomyocytes, demonstrating that they are secondary to cardiac failure rather than a result of the lack of Ca-v beta(2) proteins in the vasculature. Partial rescue of the Ca2+ channel currents by a Ca2+ channel agonist significantly postponed embryonic death in Ca-v beta(-/-)(2) mice. Taken together, these data strongly support the essential role of L-type Ca2+ channel activity in cardiomyocytes for normal heart development and function and that this is a prerequisite for proper maturation of the vasculature. C1 Univ Saarland, D-66421 Homburg, Germany. Deutsch Sporthsch, Inst Kreislaufforschung & Sport Med Mol & Zellulr, Cologne, Germany. Univ Saarland, Inst Mol Zellbiol, Homburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. Univ Bonn, Inst Physiol 1, D-53119 Bonn, Germany. RP Flockerzi, V (reprint author), Univ Saarland, D-66421 Homburg, Germany. EM ptvflo@uniklinikum-saarland.de; ptmfre@uniklinikum-saarland.de RI Kaestner, Lars/P-6988-2016 NR 30 TC 52 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP 29 PY 2006 VL 99 IS 7 BP 749 EP 757 DI 10.1161/01.RES.0000243978.15182.c1 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 088YK UT WOS:000240846800012 PM 16946137 ER PT J AU He, X Fan, HY Narlikar, GJ Kingston, RE AF He, Xi Fan, Hua-Ying Narlikar, Geeta J. Kingston, Robert E. TI Human ACF1 alters the remodeling strategy of SNF2h SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE-FOLD PROTEINS; HUMAN SWI/SNF; TRANSCRIPTIONAL ACTIVATION; NUCLEOSOME MOBILIZATION; CHROMATIN-STRUCTURE; IN-VITRO; COMPLEX; ISWI; DNA; SUBUNITS AB The human ACF chromatin- remodeling complex (hACF) contains the ATPase motor protein SNF2h and the non-catalytic hACF1 subunit. Here, we have compared the ability of SNF2h and a reconstituted hACF complex containing both SNF2h and hACF1 to remodel a series of nucleosomes containing different lengths of DNA overhang. Both SNF2h and hACF functioned in a manner consistent with sliding a canonical nucleosome. However, the non-catalytic subunit, hACF1, altered the remodeling properties of SNF2h by changing the nature of the requirement for a DNA overhang in the nucleosomal substrate and altering the DNA accessibility profile of the remodeled products. Surprisingly, addition of hACF1 to SNF2h increased the amount of DNA overhang needed to observe measurable amounts of DNA accessibility, but decreased the amount of overhang needed for a measurable binding interaction. We propose that these hACF1 functions might contribute to making the hACF complex more efficient at nucleosome spacing compared with SNF2h. In contrast, the SWI/SNF complex and its ATPase subunit BRG1 generated DNA accessibility profiles that were similar to each other, but different significantly from those of hACF and SNF2h. Thus, we observed divergent remodeling behaviors in these two remodeling families and found that the manner in which hACF1 alters the remodeling behavior of the ATPase is not shared by SWI/SNF subunits. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Simches Res Bldg,CPZN7811B,185 Cambridge St, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu FU NCI NIH HHS [CA-093660, K01 CA093660]; NIGMS NIH HHS [GM48405] NR 53 TC 37 Z9 37 U1 1 U2 4 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 SEP 29 PY 2006 VL 281 IS 39 BP 28636 EP 28647 DI 10.1074/jbc.M603008200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500017 PM 16877760 ER PT J AU Carroll, MC Outten, CE Proescher, JB Rosenfeld, L Watson, WH Whitson, LJ Hart, PJ Jensen, LT Culotta, VC AF Carroll, Mark C. Outten, Caryn E. Proescher, Jody B. Rosenfeld, Leah Watson, Walter H. Whitson, Lisa J. Hart, P. John Jensen, Laran T. Culotta, Valeria Cizewski TI The effects of glutaredoxin and copper activation pathways on the disulfide and stability of Cu, Zn superoxide dismutase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; YEAST SACCHAROMYCES-CEREVISIAE; PROTEIN S-GLUTATHIONYLATION; CHAPERONE CCS; CU,ZN-SUPEROXIDE DISMUTASE; ESCHERICHIA-COLI; OXIDATIVE STRESS; TRANSGENIC MICE; SOD1; MUTANT AB Mutations in Cu, Zn superoxide dismutase (SOD1) can cause amyotrophic lateral sclerosis (ALS) through mechanisms proposed to involve SOD1 misfolding, but the intracellular factors that modulate folding and stability of SOD1 are largely unknown. By using yeast and mammalian expression systems, we demonstrate here that SOD1 stability is governed by post-translational modification factors that target the SOD1 disulfide. Oxidation of the human SOD1 disulfide in vivo was found to involve both the copper chaperone for SOD1 (CCS) and the CCS-independent pathway for copper activation. When both copper pathways were blocked, wild type SOD1 stably accumulated in yeast cells with a reduced disulfide, whereas ALS SOD1 mutants A4V, G93A, and G37R were degraded. We describe here an unprecedented role for the thiol oxidoreductase glutaredoxin in reducing the SOD1 disulfide and destabilizing ALS mutants. Specifically, the major cytosolic glutaredoxin of yeast was seen to reduce the intramolecular disulfide of ALS SOD1 mutant A4V SOD1 in vivo and in vitro. By comparison, glutaredoxin was less reactive toward the disulfide of wild type SOD1. The apo-form of A4V SOD1 was highly reactive with glutaredoxin but not SOD1 containing both copper and zinc. Glutaredoxin therefore preferentially targets the immature form of ALS mutant SOD1 lacking metal co-factors. Overall, these studies implicate a critical balance between cellular reductants such as glutaredoxin and copper activation pathways in controlling the disulfide and stability of SOD1 in vivo. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Geriatr Res Educ & Clin Ctr, Dept Vet Affairs,S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Culotta, VC (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St,Rm E7626, Baltimore, MD 21205 USA. EM vculotta@jhsph.edu OI Jensen, Laran/0000-0003-3199-1743; Outten, Caryn/0000-0003-0335-6531 FU NIEHS NIH HHS [ES 07141, ES012260, K22 ES012260]; NIGMS NIH HHS [F32 GM066594, GM50016, R01 GM050016, R37 GM050016]; NINDS NIH HHS [NS39112, R01 NS039112, R01 NS039112-05]; PHS HHS [F32 66594] NR 56 TC 31 Z9 31 U1 0 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 SEP 29 PY 2006 VL 281 IS 39 BP 28648 EP 28656 DI 10.1074/jbc.M600138200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500018 PM 16880213 ER PT J AU Ubeda, M Rukstalis, JM Habener, JF AF Ubeda, Mariano Rukstalis, J. Michael Habener, Joel F. TI Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN GENE-TRANSCRIPTION; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; DIABETES-MELLITUS; GLUCOSE-CONCENTRATION; FACTOR EXPRESSION; BINDING; CDK5; DYSFUNCTION; REDUCTION AB Type 2 diabetes (T2D) and Alzheimer disease are degenerative diseases that may share common pathophysiologic mechanisms. Neuronal dysfunction in Alzheimer patients has been linked to overactivity of the cyclin-dependent kinase 5 (CDK5) and its activator p35. Both of these proteins are expressed in the insulin-producing beta cells of the pancreas. Further, glucose enhances p35 gene expression, promoting the formation of active p35/CDK5 complexes that regulate the expression of the insulin gene. In T2D, chronic elevations of glucose, glucotoxicity, impair beta cell function. We therefore postulated that CDK5 and p35 may be responsible for this beta cell impairment and that inhibition of CDK5 might have a beneficial effect. To test this hypothesis, the pancreatic cell line INS-1 was selected as a known in vitro model of glucotoxicity, and roscovitine (10 mu M) was used as a CDK5 inhibitor. Chronic exposure of INS-1 cells to high glucose (20-30 mM) reduced both insulin mRNA levels and the activity of an insulin promoter reporter gene. Inhibition of CDK5 prevented this decrease of insulin gene expression. We used DNA binding (gel shift) assays and Western immunoblots to demonstrate that cellular levels of the transcription factor PDX-1, normally decreased by glucotoxicity, were preserved with CDK5 inhibition, as was the binding of PDX-1 to the insulin promoter. Analyses of nuclear and cytoplasmic PDX-1 protein levels revealed that CDK5 inhibition restores nuclear PDX-1, without affecting its cytoplasmic concentration, suggesting that CDK5 regulates the nuclear/cytoplasm partitioning of PDX-1. Using a Myc-tagged PDX-1 construct, we showed that the translocation of PDX-1 from the nucleus to the cytoplasm during glucotoxic conditions was prevented when CDK5 was inhibited. These studies indicate that CDK5 plays a role in the loss of beta cell function under glucotoxic conditions and that CDK5 inhibitors could have therapeutic value for T2D. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. RP Ubeda, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Endocrinol Lab, THEIR 320,55 Fruit St, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK057521-06, DK55365] NR 25 TC 73 Z9 83 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 SEP 29 PY 2006 VL 281 IS 39 BP 28858 EP 28864 DI 10.1074/jbc.M604690200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 086NO UT WOS:000240680500040 PM 16887799 ER PT J AU Sohur, US Emsley, JG Mitchell, BD Macklis, JD AF Sohur, U. Shivraj Emsley, Jason G. Mitchell, Bartley D. Macklis, Jeffrey D. TI Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE dentate gyrus; subventricular zone; rostral migratory stream; olfactory bulb ID CENTRAL-NERVOUS-SYSTEM; FIBROBLAST GROWTH FACTOR-2; NEWLY GENERATED NEURONS; TARGETED APOPTOTIC DEGENERATION; MAMMALIAN SUBSTANTIA-NIGRA; SUBVENTRICULAR ZONE CELLS; ROSTRAL MIGRATORY STREAM; MOUSE DENTATE GYRUS; RADIAL GLIAL-CELLS; RAT SPINAL-CORD AB Recent work in neuroscience has shown that the adult central nervous system (CNS) contains neural progenitors, precursors and stem cells that are capable of generating new neurons, astrocytes and oligodendrocytes. While challenging the previous dogma that no new neurons are born in the adult mammalian CNS, these findings bring with them the future possibilities for development of novel neural repair strategies. The purpose of this review is to present the current knowledge about constitutively occurring adult mammalian neurogenesis, highlight the critical differences between 'neurogenic' and 'non-neurogenic' regions in the adult brain, and describe the cardinal features of two well-described neurogenic regions-the subventricular zone/olfactory bulb system and the dentate gyrus of the hippocampus. We also provide an overview of presently used models for studying neural precursors in vitro, mention some precursor transplantation models and emphasize that, in this rapidly growing field of neuroscience, one must be cautious with respect to a variety of methodological considerations for studying neural precursor cells both in vitro and in vivo. The possibility of repairing neural circuitry by manipulating neurogenesis is an intriguing one, and, therefore, we also review recent efforts to understand the conditions under which neurogenesis can be induced in non-neurogenic regions of the adult CNS. This work aims towards molecular and cellular manipulation of endogenous neural precursors in situ, without transplantation. We conclude this review with a discussion of what might be the function of newly generated neurons in the adult brain, and provide a summary of present thinking about the consequences of disturbed adult neurogenesis and the reaction of neurogenic regions to disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Program, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu FU NICHD NIH HHS [HD 18655, P30 HD018655]; NINDS NIH HHS [R01 NS041590, NS 41590, NS 45523, NS 49553, R01 NS045523, R01 NS049553, R37 NS041590] NR 211 TC 94 Z9 103 U1 2 U2 15 PU ROYAL SOCIETY PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD SEP 29 PY 2006 VL 361 IS 1473 BP 1477 EP 1497 DI 10.1098/rstb.2006.1887 PG 21 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 090RJ UT WOS:000240968400003 PM 16939970 ER PT J AU Hunter, M Backman, V Popescu, G Kalashnikov, M Boone, CW Wax, A Gopal, V Badizadegan, K Stoner, GD Feld, MS AF Hunter, Martin Backman, Vadim Popescu, Gabriel Kalashnikov, Maxim Boone, Charles W. Wax, Adam Gopal, Venkatesh Badizadegan, Kamran Stoner, Gary D. Feld, Michael S. TI Tissue self-affinity and polarized light scattering in the Born approximation: A new model for precancer detection SO PHYSICAL REVIEW LETTERS LA English DT Article ID SPECTROSCOPY; SCALE; CELLS AB Light scattered from biological tissues can exhibit an inverse power law spectral component. We develop a model based on the Born approximation and von Karman (self-affine) spatial correlation of submicron tissue refractive index to account for this. The model is applied to light scattering spectra obtained from excised esophagi of normal and carcinogen-treated rats. Power law exponents used to fit dysplastic tissue site spectra are significantly smaller than those from normal sites, indicating that changes in tissue self-affinity can serve as a potential biomarker for precancer. C1 MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. Northwestern Univ, Evanston, IL 60208 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Hunter, M (reprint author), MIT, George R Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mhunter@mit.edu RI Wax, Adam/A-4760-2008; Backman, Vadim/B-6689-2009; OI Wax, Adam/0000-0002-1827-5112 FU NCI NIH HHS [CN15011-72]; NCRR NIH HHS [RR-02594] NR 20 TC 75 Z9 76 U1 0 U2 5 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD SEP 29 PY 2006 VL 97 IS 13 AR 138102 DI 10.1103/PhysRevLett.97.138102 PG 4 WC Physics, Multidisciplinary SC Physics GA 089HZ UT WOS:000240872700068 PM 17026078 ER PT J AU Lamb, J Crawford, ED Peck, D Modell, JW Blat, IC Wrobel, MJ Lerner, J Brunet, JP Subramanian, A Ross, KN Reich, M Hieronymus, H Wei, G Armstrong, SA Haggarty, SJ Clemons, PA Wei, R Carr, SA Lander, ES Golub, TR AF Lamb, Justin Crawford, Emily D. Peck, David Modell, Joshua W. Blat, Irene C. Wrobel, Matthew J. Lerner, Jim Brunet, Jean-Philippe Subramanian, Aravind Ross, Kenneth N. Reich, Michael Hieronymus, Haley Wei, Guo Armstrong, Scott A. Haggarty, Stephen J. Clemons, Paul A. Wei, Ru Carr, Steven A. Lander, Eric S. Golub, Todd R. TI The connectivity map: Using gene-expression signatures to connect small molecules, genes, and disease SO SCIENCE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BREAST-CANCER-CELLS; CELLULAR-DRUG RESISTANCE; ALZHEIMERS-DISEASE; IN-VITRO; CHAPERONE HEAT-SHOCK-PROTEIN-90; MICROARRAY ANALYSIS; INHIBITORS; TOXICITY; ESTROGEN AB To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created the first installment of a reference collection of gene-expression profiles from cultured human cells treated with bioactive small molecules, together with pattern-matching software to mine these data. We demonstrate that this "Connectivity Map'' resource can be used to find connections among small molecules sharing a mechanism of action, chemicals and physiological processes, and diseases and drugs. These results indicate the feasibility of the approach and suggest the value of a large-scale community Connectivity Map project. C1 MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02144 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Golub, TR (reprint author), MIT, Broad Inst, Cambridge, MA 02142 USA. EM justin@broad.mit.edu; golub@broad.harvard.edu OI Haggarty, Stephen J./0000-0002-7872-168X NR 41 TC 1568 Z9 1606 U1 25 U2 155 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 SEP 29 PY 2006 VL 313 IS 5795 BP 1929 EP 1935 DI 10.1126/science.1132939 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 088SU UT WOS:000240832200043 PM 17008526 ER PT J AU Janzen, V Forkert, R Fleming, HE Saito, Y Waring, MT Dombkowski, DM Cheng, T DePinho, RA Sharpless, NE Scadden, DT AF Janzen, Viktor Forkert, Randolf Fleming, Heather E. Saito, Yoriko Waring, Michael T. Dombkowski, David M. Cheng, Tao DePinho, Ronald A. Sharpless, Norman E. Scadden, David T. TI Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16(INK4a) SO NATURE LA English DT Article ID HEMATOPOIETIC STEM; IN-VIVO; PROGENITOR CELLS; SELF-RENEWAL; MICE; SENESCENCE; EXPRESSION; ENGRAFTMENT; INCREASES; P19(ARF) AB Stem-cell ageing is thought to contribute to altered tissue maintenance and repair. Older humans experience increased bone marrow failure and poorer haematologic tolerance of cytotoxic injury. Haematopoietic stem cells (HSCs) in older mice have decreased per-cell repopulating activity, self-renewal and homing abilities, myeloid skewing of differentiation, and increased apoptosis with stress. Here we report that the cyclin-dependent kinase inhibitor p16(INK4a), the level of which was previously noted to increase in other cell types with age, accumulates and modulates specific age-associated HSC functions. Notably, in the absence of p16(INK4a), HSC repopulating defects and apoptosis were mitigated, improving the stress tolerance of cells and the survival of animals in successive transplants, a stem- cell-autonomous tissue regeneration model. Inhibition of p16(INK4a) may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu NR 33 TC 636 Z9 688 U1 5 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 28 PY 2006 VL 443 IS 7110 BP 421 EP 426 DI 10.1038/nature05159 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 088FY UT WOS:000240798800038 PM 16957735 ER PT J AU Krishnamurthy, J Ramsey, MR Ligon, KL Torrice, C Koh, A Bonner-Weir, S Sharpless, NE AF Krishnamurthy, Janakiraman Ramsey, Matthew R. Ligon, Keith L. Torrice, Chad Koh, Angela Bonner-Weir, Susan Sharpless, Norman E. TI p16(INK4a) induces an age-dependent decline in islet regenerative potential SO NATURE LA English DT Article ID PANCREATIC BETA-CELLS; PREMATURE SENESCENCE; TRANSGENIC MICE; DIABETIC MICE; EXPRESSION; CDK4; STREPTOZOTOCIN; GROWTH; ADULT; DIFFERENTIATION AB The p16(INK4a) tumour suppressor accumulates in many tissues as a function of advancing age(1-3). p16(INK4a) is an effector of senescence(4,5) and a potent inhibitor of the proliferative kinase Cdk4 (ref. 6), which is essential for pancreatic beta-cell proliferation in adult mammals(7,8). Here we show that p16(INK4a) constrains islet proliferation and regeneration in an age-dependent manner. Expression of the p16(INK4a) transcript is enriched in purified islets compared with the exocrine pancreas, and islet-specific expression of p16(INK4a), but not other cyclin-dependent kinase inhibitors, increases markedly with ageing. To determine the physiological significance of p16(INK4a) accumulation on islet function, we assessed the impact of p16(INK4a) deficiency and overexpression with increasing age and in the regenerative response after exposure to a specific beta-cell toxin. Transgenic mice that overexpress p16(INK4a) to a degree seen with ageing demonstrated decreased islet proliferation. Similarly, islet proliferation was unaffected by p16(INK4a) deficiency in young mice, but was relatively increased in p16(INK4a)-deficient old mice. Survival after toxin-mediated ablation of beta-cells, which requires islet proliferation, declined with advancing age; however, mice lacking p16(INK4a) demonstrated enhanced islet proliferation and survival after beta-cell ablation. These genetic data support the view that an age-induced increase of p16(INK4a) expression limits the regenerative capacity of beta-cells with ageing. C1 Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Sharpless, NE (reprint author), Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA. EM NES@med.unc.edu OI Ligon, Keith/0000-0002-7733-600X; Bonner-Weir, Susan/0000-0003-4682-0656 NR 32 TC 505 Z9 535 U1 2 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 28 PY 2006 VL 443 IS 7110 BP 453 EP 457 DI 10.1038/nature05092 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 088FY UT WOS:000240798800045 PM 16957737 ER PT J AU Morton, DL Thompson, JF Cochran, AJ Mozzillo, N Elashoff, R Essner, R Nieweg, OE Roses, DF Hoekstra, HJ Karakousis, CP Reintgen, DS Coventry, BJ Glass, EC Wang, HJ AF Morton, Donald L. Thompson, John F. Cochran, Alistair J. Mozzillo, Nicola Elashoff, Robert Essner, Richard Nieweg, Omgo E. Roses, Daniel F. Hoekstra, Harald J. Karakousis, Constantine P. Reintgen, Douglas S. Coventry, Brendon J. Glass, Edwin C. Wang, He-Jing CA MSLT Grp TI Sentinel-node biopsy or nodal observation in melanoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EARLY-STAGE MELANOMA; AMERICAN JOINT COMMITTEE; IN-TRANSIT METASTASIS; LYMPH-NODE; PROGNOSTIC-FACTORS; CUTANEOUS MELANOMA; MULTICENTER TRIAL; RANDOMIZED-TRIAL; REGIONAL NODES; LYMPHADENECTOMY AB Background: We evaluated the contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma. Methods: Patients with a primary cutaneous melanoma were randomly assigned to wide excision and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred, or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy. Results: Among 1269 patients with an intermediate-thickness primary melanoma, the mean (+/-SE) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6% in the biopsy group and 73.1+/-2.1% in the observation group (hazard ratio for death, 0.74; 95% confidence interval [CI], 0.59 to 0.93; P=0.009). Five-year melanoma-specific survival rates were similar in the two groups (87.1+/-1.3% and 86.6+/-1.6%, respectively). In the biopsy group, the presence of metastases in the sentinel node was the most important prognostic factor; the 5-year survival rate was 72.3+/-4.6% among patients with tumor-positive sentinel nodes and 90.2+/-1.3% among those with tumor-negative sentinel nodes (hazard ratio for death, 2.48; 95% CI, 1.54 to 3.98; P < 0.001). The incidence of sentinel-node micrometastases was 16.0% (122 of 764 patients), and the rate of nodal relapse in the observation group was 15.6% (78 of 500 patients). The corresponding mean number of tumor-involved nodes was 1.4 in the biopsy group and 3.3 in the observation group (P < 0.001), indicating disease progression during observation. Among patients with nodal metastases, the 5-year survival rate was higher among those who underwent immediate lymphadenectomy than among those in whom lymphadenectomy was delayed (72.3+/-4.6% vs. 52.4+/-5.9%; hazard ratio for death, 0.51; 95% CI, 0.32 to 0.81; P=0.004). Conclusions: The staging of intermediate-thickness (1.2 to 3.5 mm) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy. (ClinicalTrials.gov number, NCT00275496.) C1 St Johns Hlth Ctr, John Wayne Canc Inst, Dept Surg Oncol, Santa Monica, CA 90404 USA. St Johns Hlth Ctr, John Wayne Canc Inst, Dept Biostat, Santa Monica, CA 90404 USA. Royal Prince Alfred Hosp, Sydney Melanoma Unit, Camperdown, NSW 2050, Australia. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. Natl Canc Inst, Dept Surg Oncol, Naples, Italy. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. Netherlands Canc Inst, Dept Surg, Amsterdam, Netherlands. NYU, Sch Med, Dept Surg, New York, NY USA. Univ Med Ctr Groningen, Dept Surg Oncol, Groningen, Netherlands. Univ Groningen, Groningen, Netherlands. Millard Fillmore Hosp, Dept Surg, Buffalo, NY USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA. Royal Adelaide Hosp, Dept Surg, Adelaide, SA 5000, Australia. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Nucl Med, Los Angeles, CA USA. RP Morton, DL (reprint author), St Johns Hlth Ctr, John Wayne Canc Inst, Dept Surg Oncol, 2200 Santa Monica Blvd, Santa Monica, CA 90404 USA. EM mortond@jwci.org FU NCI NIH HHS [CA 29605] NR 26 TC 979 Z9 1003 U1 5 U2 25 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 SEP 28 PY 2006 VL 355 IS 13 BP 1307 EP 1317 DI 10.1056/NEJMoa060992 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 088EF UT WOS:000240793600004 PM 17005948 ER PT J AU Scadden, DT Muse, VV Hasserjian, RP Basgoz, N Harris, NL Walker, BD AF Scadden, David T. Muse, Victorine V. Hasserjian, Robert P. Basgoz, Nesli Harris, Nancy Lee Walker, Bruce D. TI A man with dyspnea, fever, and lymphadenopathy - HHV-8-associated multicentric Castleman's disease and Kaposi's sarcoma associated with HIV infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS-INFECTION; RECONSTITUTION INFLAMMATORY SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; ANTI-CD20 MONOCLONAL-ANTIBODY; BONE-MARROW; HUMAN-HERPESVIRUS-8 INFECTION; PROLONGED REMISSION; HERPES-VIRUS; IN-VIVO; AIDS C1 Massachusetts Gen Hosp, Dept Hematol Oncol, 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 Scadden, DT (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. NR 50 TC 5 Z9 5 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 SEP 28 PY 2006 VL 355 IS 13 BP 1358 EP 1368 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 088EF UT WOS:000240793600012 PM 17005954 ER PT J AU Pardini, AW Nguyen, HT Figlewicz, DP Baskin, DG Williams, DL Kim, F Schwartz, MW AF Pardini, Aaron W. Nguyen, Hong T. Figlewicz, Dianne P. Baskin, Denis G. Williams, Diana L. Kim, Francis Schwartz, Michael W. TI Distribution of insulin receptor substrate-2 in brain areas involved in energy homeostasis SO BRAIN RESEARCH LA English DT Article DE insulin receptor substrate-2; brain; energy regulation; co-localization ID CONDITIONED PLACE PREFERENCE; ARCUATE NUCLEUS; HYPOTHALAMIC NEURONS; SYNAPTIC PLASTICITY; NEUROTROPHIC FACTOR; SIGNALING PATHWAYS; INDUCED ANOREXIA; NERVOUS-SYSTEM; FOOD-INTAKE; BETA-CELLS AB Body weight regulation depends on neuronal signaling by adiposity-related hormones such as insulin and leptin. Activation of receptors for these hormones induces cell signaling via the insulin receptor substrate/phosphatidylinositol 3-kinase (IRS-PI3K) pathway, and growing evidence from knockout models implicates IRS-2 as a key component of this signal transduction mechanism. As a first step towards the identification of brain areas that utilize IRS-PI3K signaling in the control of energy homeostasis, we used immunohistochemical techniques to investigate the neuronal distribution of IRS-2 protein in rat brain. In the hypothalamus, strong IRS-2 staining was detected chiefly in the arcuate (ARC), ventromedial (VMN) nucleus and parvocellular paraventricular nucleus (PVN). Within the ARC, IRS-2 was co-localized with alpha melanocyte stimulating hormone (alpha-MSH) as well as neuropeptide Y (NPY). In the hindbrain, IRS-2 staining was detected in the area postrema (AP), medial nucleus of the solitary tract (mNTS), dorsal motor nucleus of the vagus nerve (DMV) and the hypoglossal nucleus (HN). Co-localization studies in the mNTS demonstrated the presence of IRS-2 in catecholamine neurons. IRS-2 protein was also found in the ventral tegmental area (VTA), an important area for reward perception, and was detected in dopamine neurons in this brain area. In summary, neurons containing IRS-2 immunoreactivity were identified in forebrain, midbrain and hindbrain areas and in cell types that are crucial for the control of food intake and autonomic function. An improved understanding of mechanisms underlying normal and abnormal energy homeostasis may be gained by analysis of the role played by signaling through IRS-2 in these brain areas. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Med, Harborview Med Ctr, Seattle, WA 98104 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Div Metab, Seattle, WA USA. RP Schwartz, MW (reprint author), Univ Washington, Dept Med, Harborview Med Ctr, 325 9th Ave,Box 35967, Seattle, WA 98104 USA. EM mschwart@u.washington.edu RI Schwartz, Michael/H-9950-2012; Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU NIDDK NIH HHS [DK52989, DK07247, DK12829, DK40963, DK68384]; NINDS NIH HHS [NS32273] NR 38 TC 51 Z9 51 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 27 PY 2006 VL 1112 BP 169 EP 178 DI 10.1016/j.brainres.2006.06.109 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 092XC UT WOS:000241129900018 PM 16925984 ER PT J AU Balmana, J Stockwell, DH Steyerberg, EW Stoffel, EM Deffenbaugh, AM Reid, JE Ward, B Scholl, T Hendrickson, B Tazelaar, J Burbidge, LA Syngal, S AF Balmana, Judith Stockwell, David H. Steyerberg, Ewout W. Stoffel, Elena M. Deffenbaugh, Amie M. Reid, Julia E. Ward, Brian Scholl, Thomas Hendrickson, Brant Tazelaar, John Burbidge, Lynn Anne Syngal, Sapna TI Prediction of MLH1 and MSH2 mutations in Lynch syndrome SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; DNA MISMATCH-REPAIR; REVISED BETHESDA GUIDELINES; FAMILY-HISTORY; MICROSATELLITE INSTABILITY; CARRIER PROBABILITIES; AMSTERDAM CRITERIA; GENE-MUTATIONS; BREAST-CANCER; IMMUNOHISTOCHEMISTRY AB Context Lynch syndrome is caused primarily by mutations in the mismatch repair genes MLH1 and MSH2. Objectives To analyze MLH1/MSH2 mutation prevalence in a large cohort of patients undergoing genetic testing and to develop a clinical model to predict the likelihood of finding a mutation in at-risk patients. Design, Setting, and Participants Personal and family history were obtained for 1914 unrelated probands who submitted blood samples starting in the year 2000 for full gene sequencing of MLH1/MSH2. Genetic analysis was performed using a combination of sequence analysis and Southern blotting. A multivariable model was developed using logistic regression in an initial cohort of 898 individuals and subsequently prospectively validated in 1016 patients. The complex model that we have named PREMM1,2 (Prediction of Mutations in MLH1 and MSH2) was developed into a Web-based tool that incorporates personal and family history of cancer and adenomas. Main Outcome Measure Deleterious mutations in MLH1/MSH2 genes. Results Overall, 14.5% of the probands (130/898) carried a pathogenic mutation (MLH1, 6.5%; MSH2, 8.0%) in the development cohort and 15.3% (155/1016) in the validation cohort, with 42 (27%) of the latter being large rearrangements. Strong predictors of mutations included proband characteristics (presence of colorectal cancer, especially >= 2 separate diagnoses, or endometrial cancer) and family history (especially the number of first-degree relatives with colorectal or endometrial cancer). Age at diagnosis was particularly important for colorectal cancer. The multivariable model discriminated well at external validation, with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval, 0.76-0.84). Conclusions Personal and family history characteristics can accurately predict the outcome of genetic testing in a large population at risk of Lynch syndrome. The PREMM1,2 model provides clinicians with an objective, easy-to-use tool to estimate the likelihood of finding mutations in the MLH1/MSH2 genes and may guide the strategy for molecular evaluation. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Erasmus Med Ctr, Dept Publ Hlth, Ctr Med Decis Making, Rotterdam, Netherlands. Myriad Genet Labs Inc, Salt Lake City, UT USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St, Boston, MA 02115 USA. EM ssyngal@partners.org OI Steyerberg, Ewout/0000-0002-7787-0122 FU NCI NIH HHS [K24 CA 113433] NR 32 TC 105 Z9 107 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 27 PY 2006 VL 296 IS 12 BP 1469 EP 1478 DI 10.1001/jama.296.12.1469 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 087VD UT WOS:000240770000023 PM 17003395 ER PT J AU von Arnim, CAF Spoelgen, R Peltan, ID Deng, M Courchesne, S Koker, M Matsui, T Kowa, H Lichtenthaler, SF Irizarry, MC Hyman, BT AF von Arnim, Christine A. F. Spoelgen, Robert Peltan, Ithan D. Deng, Meihua Courchesne, Stephanie Koker, Mirjam Matsui, Toshifumi Kowa, Hisatomo Lichtenthaler, Stefan F. Irizarry, Michael C. Hyman, Bradley T. TI GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; amyloid precursor protein; Golgi-localized gamma-ear-containing ARF binding protein 1; GGA1; BACE; trafficking; amyloid beta ID RESONANCE ENERGY-TRANSFER; BETA-SECRETASE CLEAVAGE; TRANS-GOLGI NETWORK; ALZHEIMERS-DISEASE; A-BETA; CELL-SURFACE; AXONAL-TRANSPORT; GAMMA-SECRETASE; ENDOCYTIC PATHWAY; ASPARTYL PROTEASE AB The beta-amyloid (A beta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the A beta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced A beta.GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimer Dis Res Lab, Charlestown, MA 02129 USA. Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. Univ Munich, Adolf Butenandt Inst, D-80336 Munich, Germany. RP Hyman, BT (reprint author), Massachusetts Gen Inst Neurodegenerat Dis, 114 16th St,Room Number 2009, Charlestown, MA 02129 USA. EM bhyman@partners.org RI Lichtenthaler, Stefan/B-6587-2016; OI Lichtenthaler, Stefan/0000-0003-2211-2575; Peltan, Ithan/0000-0003-1730-234X FU NIA NIH HHS [AG 12406] NR 59 TC 46 Z9 46 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 27 PY 2006 VL 26 IS 39 BP 9913 EP 9922 DI 10.1523/JNEUROSCI.2290-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 088QH UT WOS:000240825700011 PM 17005855 ER PT J AU Heitmann, LM Taylor, AB Hart, PJ Urbach, AR AF Heitmann, Lisa M. Taylor, Alexander B. Hart, P. John Urbach, Adam R. TI Sequence-specific recognition and cooperative dimerization of N-terminal aromatic peptides in aqueous solution by a synthetic host SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ARTIFICIAL RECEPTORS; SUPRAMOLECULAR CHEMISTRY; CUCURBITURIL HOMOLOGS; SELECTIVE RECOGNITION; SIGNAL-TRANSDUCTION; SMALL MOLECULES; BINDING; COMPLEXATION; DERIVATIVES; INCLUSION AB This article describes the selective recognition and noncovalent dimerization of N-terminal aromatic peptides in aqueous solution by the synthetic host compound, cucurbit[8]uril (Q8). Q8 is known to bind two aromatic guests simultaneously and, in the presence of methyl viologen, to recognize N- terminal tryptophan over internal and C-terminal sequence isomers. Here, the binding of Q8 to aromatic peptides in the absence of methyl viologen was studied by isothermal titration calorimetry (ITC), H-1 NMR spectroscopy, and X-ray crystallography. The peptides studied were of sequence X-Gly-Gly, Gly-X-Gly, and Gly-Gly-X (X = Trp, Phe, Tyr, and His). Q8 selectively binds and dimerizes Trp-Gly-Gly (1) and Phe-Gly-Gly (4) with high affinity (ternary K = 10(9)-10(11) M-2); binding constants for the other 10 peptides were too small to be measured by ITC. Both peptides bound in a stepwise manner, and peptide 4 bound with positive cooperativity. Crystal structures of Q8, 1 and Q8, 42 reveal the basis for selective recognition as simultaneous inclusion of the hydrophobic aromatic side chain into the cavity of Q8 and chelation of the proximal N-terminal ammonium group by carbonyl groups of Q8. The peptide sequence selectivity and positively cooperative dimerization reported here are, to the best of our knowledge, unprecedented for synthetic hosts in aqueous solution. Specific peptide recognition and dimerization by synthetic hosts such as Q8 should be important in the study of dimer-mediated biochemical processes and for the separation of peptides and proteins. C1 Trinity Univ, Dept Chem, San Antonio, TX 78212 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Geriatr Res Educ & Clin Ctr, Dept Vet Affairs,S Texas Hlth Care Syst, San Antonio, TX 78229 USA. RP Urbach, AR (reprint author), Trinity Univ, Dept Chem, 1 Trinity Pl, San Antonio, TX 78212 USA. EM aurbach@trinity.edu NR 57 TC 149 Z9 151 U1 5 U2 75 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 27 PY 2006 VL 128 IS 38 BP 12574 EP 12581 DI 10.1021/ja064323s PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 085OF UT WOS:000240612700059 PM 16984208 ER PT J AU Boskovic, S Kawai, T Smith, RN Wee, SL Nadazdin, O Koyama, I Saidman, S Cardarelli, F Elias, N Sykes, M Strom, T Colvin, RB Sachs, DH Cosimi, AB AF Boskovic, Svjetlan Kawai, Tatsuo Smith, Rex-Neal Wee, Siew-Lin Nadazdin, Ognjenka Koyama, Ichiro Saidman, Susan Cardarelli, Francesca Elias, Nahel Sykes, Megan Strom, Terry Colvin, Robert B. Sachs, David H. Cosimi, A. Benedict TI Monitoring antidonor alloantibodies as a predictive assay for renal allograft tolerance/long-term observations in nonhuman primates SO TRANSPLANTATION LA English DT Article DE tolerance; alloantibody; primates; chronic rejection ID MIXED CHIMERISM; TRANSPLANTATION TOLERANCE; MONOCLONAL-ANTIBODY; BONE-MARROW; LYMPHOHEMATOPOIETIC CHIMERISM; CYNOMOLGUS MONKEYS; CHRONIC REJECTION; MULTIPLE-MYELOMA; INDUCTION; SURVIVAL AB Background. In an effort to define reliable assays that might predict postimmunosuppressant-withdrawal development of chronic rejection (CR), despite conditioning for tolerance induction, we evaluated various immunological responses in nonhuman primate renal allograft recipients. Methods. Fourteen Cynomolgus monkeys received low dose total body irradiation, thymic irradiation, antithymocyte globulin, and peritransplant CD 154 blockade, followed by a one-month course of cyclosporine. Recipients underwent major histocompatibility complex mismatched kidney transplantation with donor bone marrow infusion (Group A, n = 8), without donor cell infusion (Group B, n = 2), or with donor splenocyte infusion (Group C, n = 4). Results. All Group A recipients developed mixed chimerism and four of them survived long-term without rejection. The remaining four rejected their kidney allografts either chronically or acutely. All recipients in Groups B and C failed to develop chimerism and rejected their allografts. Among various in vitro assays, detection of anti-donor alloantibody (ADA) by flow cytometry (FCM) was the most relevant to long-term outcome. All five recipients that developed both anti-T cell and B cell IgG ADA in Groups A, B and C, developed histological evidence of CR within 200 days of the appearance of ADA. One of two recipients that developed only anti-B cell IgG ADA eventually developed CR over two years following discontinuation of immunosuppression and 1.5 years after ADA development. Another recipient with very low anti-B cell ADA has never developed CR. Conclusion. ADA monitoring with FCM assay appears to be useful in predicting the failure of tolerance prior to the development of functional or histologic abnormalities of the renal allograft. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Unit,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Charlestown, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Immunol, Boston, MA 02215 USA. RP Boskovic, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Unit,Dept Surg, 55 Fruit St White 546, Boston, MA 02114 USA. EM sboskovic@partners.org FU NHLBI NIH HHS [P01-HL18646]; NIAID NIH HHS [5R01 AI50987-03, R01 AI037692, R01 AI037692-09, R01 AI037692-10, R01 AI37692, R21 AI037692, R21 AI037692-06] NR 23 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 27 PY 2006 VL 82 IS 6 BP 819 EP 825 DI 10.1097/01.tp.0000234786.26511.a4 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 089OD UT WOS:000240889100016 PM 17006330 ER PT J AU Greenberg, SM AF Greenberg, Steven M. TI Is "compassionate use" compassionate? rFVIIa for intracerebral hemorrhage SO NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org NR 11 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 26 PY 2006 VL 67 IS 6 BP 934 EP 935 DI 10.1212/01.wnl.0000239801.90927.80 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 087NU UT WOS:000240749900003 PM 17000956 ER PT J AU Adair, JC Rudnicki, SA Boudreau, E Weiner, WJ Coyle, PK Corboy, JR AF Adair, J. C. Rudnicki, S. A. Boudreau, E. Weiner, W. J. Coyle, P. K. Corboy, J. R. TI Survey of training programs' means for promoting neurology and attracting trainees SO NEUROLOGY LA English DT Article ID MEDICAL-STUDENTS; LIFE-STYLE; RESIDENCY; COMMITTEE; WORKFORCE; CHOICE AB Objective: To determine neurology training opportunities available to medical students and to define factors that influence program choice. Methods: All neurology residency program directors and a random sample of residents were surveyed. Resident questions related to application, interview, and training experience. Directors' questions focused on ways their department generated interest in clinical neurosciences. Results: Medical schools introduce students to clinical neurology primarily through required clerkships. Contact time averages less than 4 weeks and emphasizes inpatient encounters. Preceptorships with neurology faculty do not exist at almost 40% of schools and only 14% have neuroscience tracks. Nearly all residency applicants matched their first or second choice. The majority declined at least one interview and 39% failed to rank at least one site they visited. When choosing where to apply, the programs' reputation and geographic considerations were paramount. When making a rank list, interactions with faculty and residents at interview were most important. Residents generally reported satisfaction with their programs and attribute morale to supportive relationships with faculty and residents. Conclusions: Neurology programs may be able to enhance students' impression of neurology through changes in their clinical experience and development of venues for more meaningful relationships with faculty. Attention to the residents' personal needs may increase the likelihood of matching the best available candidates and ensuring their satisfaction. C1 Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA. New Mexico Vet Healthcare Syst, Albuquerque, NM USA. Univ Arkansas Med Sci, Dept Neurol, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Neurol, College Pk, MD 20742 USA. SUNY Stony Brook, Dept Neurol, Stony Brook, NY 11794 USA. Univ Colorado, Dept Neurol, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Adair, JC (reprint author), Univ New Mexico Hosp, Dept Neurol, ACC 2nd Floor,2211 Lomas Blvd NE, Albuquerque, NM 87131 USA. EM John.Adair@med.va.gov NR 14 TC 9 Z9 9 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 26 PY 2006 VL 67 IS 6 BP 936 EP 939 DI 10.1212/01.wnl.0000237324.47522.24 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 087NU UT WOS:000240749900004 PM 17000957 ER PT J AU Zhu, CW Scarmeas, N Torgan, R Albert, M Brandt, J Blacker, D Sano, M Stern, Y AF Zhu, C. W. Scarmeas, N. Torgan, R. Albert, M. Brandt, J. Blacker, D. Sano, M. Stern, Y. TI Longitudinal study of effects of patient characteristics on direct costs in Alzheimer disease SO NEUROLOGY LA English DT Article ID ECONOMIC-IMPACT; MOTOR SIGNS; LAST YEAR; CARE; DEMENTIA; MEDICARE; PREDICTORS; SEVERITY; SYMPTOMS; BURDEN AB Objectives: To estimate long-term trajectories of direct cost of caring for patients with Alzheimer disease ( AD) and examine the effects of patients' characteristics on cost longitudinally. Methods: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed up annually for up to 7 years in three university-based AD centers in the United States. Random effects models estimated the effects of patients' clinical and sociodemographic characteristics on direct cost of care. Direct cost included cost associated with medical and nonmedical care. Clinical characteristics included cognitive status ( measured by Mini-Mental State Examination), functional capacity (measured by Blessed Dementia Rating Scale [BDRS]), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, and comorbidities. The model also controlled for patients' sex, age, and living arrangements. Results: Total direct cost increased from approximately $9,239 per patient per year at baseline, when all patients were at the early stages of the disease, to $19,925 by year 4. After controlling for other variables, a one-point increase in the BDRS score increased total direct cost by 7.7%. One more comorbid condition increased total direct cost by 14.3%. Total direct cost was 20.8% lower for patients living at home compared with those living in an institutional setting. Conclusions: Total direct cost of caring for patients with Alzheimer disease increased substantially over time. Much of the cost increases were explained by patients' clinical and demographic variables. Comorbidities and functional capacity were associated with higher direct cost over time. C1 Bronx Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Targeted Res Enhancement Program, Bronx, NY 10468 USA. Bronx Vet Adm Med Ctr, Program Res Serious Phys & Mental Illness, Targeted Res Enhancement Program, Bronx, NY 10468 USA. Mt Sinai Sch Med, Brookdale Dept Geriatr, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Columbia Univ, Med Ctr, Cognit Neurosci Div, Taub Inst Res Alzheimers Dis & Aging Brain,Gertru, New York, NY USA. Columbia Univ, Med Ctr, Dept Neurol, New York, NY USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Zhu, CW (reprint author), Bronx Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Targeted Res Enhancement Program, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM carolyn.zhu@mssm.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370, U01AG010483] NR 56 TC 69 Z9 70 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 26 PY 2006 VL 67 IS 6 BP 998 EP 1005 DI 10.1212/01.wnl.0000230160.13272.1b PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 087NU UT WOS:000240749900015 PM 16914696 ER PT J AU Beeri, MS Schmeidler, J Sano, M Wang, J Lally, R Grossman, H Silverman, JM AF Beeri, M. S. Schmeidler, J. Sano, M. Wang, J. Lally, R. Grossman, H. Silverman, J. M. TI Age, gender, and education norms on the CERAD neuropsychological battery in the oldest old SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; PERFORMANCE; AMERICAN; DEMENTIA; ELDERS; TESTS; CONSORTIUM; ESTABLISH; REGISTRY; SAMPLE AB Objective: To evaluate the performance of nondemented subjects 85 years and older on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery, and to assess its relationship with sociodemographic variables. Methods: We studied 196 subjects enrolled in an Alzheimer's Disease Research Center study who had a complete CERAD neuropsychological assessment. We used multiple regression analysis to predict performance on the neuropsychological tests from age, education, and sex. Eight representative hypothetical individuals were created (for example, an 87-year-old man, with high education). For each test, estimates of performance at the 10th, 25th, 50th, and 75th percentiles were reported for the eight representative hypothetical individuals. Results: Mean age was 89.2 years (SD = 3.2), mean years of education was 14.9 (SD = 3.2), and 66% of the sample were women. For 11 of the 14 neuropsychological tests, there was a significant multiple regression model using education, age, and sex as predictors. Neither the models nor the predictors used individually were significant for Delayed Recall, Savings, or correct Recognition. Among the significant results, seven had education as the strongest predictor. Lower age and higher education were associated with better performance. Women performed better than men in three of four tests with significant results for sex. Conclusions: In a sample of oldest old whose primary language is English, neuropsychological testing is influenced mainly by education and age. Cutoff scores based on younger populations and applied to the oldest old might lead to increased false-positive misclassifications. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Biomath Sci, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, New York, NY USA. RP Beeri, MS (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave Levy Pl,Box 1230, New York, NY 10029 USA. EM michal.beeri@mssm.edu FU NIA NIH HHS [P01-AG02219, 1 K01 AG023515-01A2, K01 AG023515, K01 AG023515-01A2, P01 AG002219, P50 AG005138, P50-AG05138] NR 18 TC 41 Z9 43 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 26 PY 2006 VL 67 IS 6 BP 1006 EP 1010 DI 10.1212/01.wnl.0000237548.15734.cd PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 087NU UT WOS:000240749900017 PM 17000969 ER PT J AU Wu, ZD Huang, XM Feng, YJ Handschin, C Feng, Y Gullicksen, PS Bare, O Labow, M Spiegelman, B Stevenson, SC AF Wu, Zhidan Huang, Xueming Feng, Yajun Handschin, Christoph Feng, Yan Gullicksen, P. Scott Bare, Olivia Labow, Mark Spiegelman, Bruce Stevenson, Susan C. TI Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1 alpha transcription and mitochondrial biogenesis in muscle cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SKELETAL-MUSCLE; GENE-EXPRESSION; COACTIVATOR TORC2; EPITROCHLEARIS MUSCLE; RAT EPITROCHLEARIS; MAMMALIAN-CELLS; ERR-ALPHA; EXERCISE; RECEPTOR; PGC-1 AB PGC-1 alpha (peroxisome proliferator-activated receptor gamma coactivator 1 alpha) is a master regulator of mitochondrial biogenesis and plays an important role in several other aspects of energy metabolism. To identify upstream regulators of PGC-1 alpha gene transcription, 10,000 human full-length cDNAs were screened for induction of the PGC-1 alpha promoter. A number of activators of PGC-1 alpha transcription were found; the most potent activator was the transducer of regulated CREB (cAMP response element-binding protein) binding protein (TORC) 1, a coactivator of CREB. The other two members of the TORC family, TORC2 and TORC3, also strongly activated PGC-1 alpha transcription. TORCs dramatically induced PGC-1 alpha gene transcription through CREB. Forced expression of TORCs in primary muscle cells induced the endogenous mRNA of PGC-1 alpha and its downstream target genes in the mitochondrial respiratory chain and TCA cycle. Importantly, these changes in gene expression resulted in increased mitochondrial oxidative capacity measured by cellular respiration and fatty acid oxidation. Finally, we demonstrated that the action of TORCs in promoting mitochondrial gene expression and function requires PGC-1 alpha. Previous studies had indicated that TORCs function as a calcium- and cAMP-sensitive coincidence detector and mediate individual and synergistic effects of these two pathways. Our results, together with previous findings, strongly suggest that TORCs play a key role in linking these external signals to the transcriptional program of adaptive mitochondrial biogenesis by activating PGC-1 alpha gene transcription. C1 Novartis Inst Biomed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA. Novartis Inst Biomed Res, Genome & Proteome Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. RP Wu, ZD (reprint author), Novartis Inst Biomed Res, Diabet & Metab Dis Area, 100 Technol Sq, Cambridge, MA 02139 USA. EM zhidan.wu@novartis.com; bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 NR 39 TC 151 Z9 160 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 26 PY 2006 VL 103 IS 39 BP 14379 EP 14384 DI 10.1073/pnas.0606714103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 090RG UT WOS:000240968100024 PM 16980408 ER PT J AU Ahveninen, J Jaaskelainen, IP Raij, T Bonmassar, G Devore, S Hamalainen, M Levanen, S Lin, FH Sams, M Shinn-Cunningham, BG Witzel, T Belliveau, JW AF Ahveninen, Jyrki Jaaskelainen, Iiro P. Raij, Tommi Bonmassar, Giorgio Devore, Sasha Hamalainen, Matti Levanen, Sari Lin, Fa-Hsuan Sams, Mikko Shinn-Cunningham, Barbara G. Witzel, Thomas Belliveau, John W. TI Task-modulated "what" and "where" pathways in human auditory cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional MRI; magnetoencephalography; selective attention; spatiotemporal brain imaging ID GAMMA-BAND ACTIVITY; WORKING-MEMORY; HUMAN BRAIN; SELECTIVE ATTENTION; HEMISPHERIC LESIONS; SOUND RECOGNITION; PLANUM TEMPORALE; VOICE IDENTITY; FMRI STUDY/; LOCALIZATION AB Human neuroimaging studies suggest that localization and identification of relevant auditory objects are accomplished via parallel parietal-to-lateral-prefrontal "where" and anterior-temporal-toinferior-frontal "what" pathways, respectively. Using combined hemodynamic (functional MRI) and electromagnetic (magnetoencephalography) measurements, we investigated whether such dual pathways exist already in the human nonprimary auditory cortex, as suggested by animal models, and whether selective attention facilitates sound localization and identification by modulating these pathways in a feature-specific fashion. We found a double dissociation in response adaptation to sound pairs with phonetic vs. spatial sound changes, demonstrating that the human nonprimary auditory cortex indeed processes speech-sound identity and location in parallel anterior "what" (in anterolateral Heschl's gyrus, anterior superior temporal gyrus, and posterior planum polare) and posterior "where" (in planum temporale and posterior superior temporal gyrus) pathways as early as approximate to 70-150 ms from stimulus onset. Our data further show that the "where" pathway is activated approximate to 30 ms earlier than the "what" pathway' possibly enabling the brain to use top-down spatial information in auditory object perception. Notably, selectively attending to phonetic content modulated response adaptation in the "what" pathway, whereas attending to sound location produced analogous effects in the "where" pathway. This finding suggests that selective-attention effects are feature-specific in the human nonprimary auditory cortex and that they arise from enhanced tuning of receptive fields of task-relevant neuronal populations. C1 Harvard Univ, MIT, Sch Med, Massachusetts Gen Hosp,Dept Radiol,Athinoula A Ma, Charlestown, MA 02129 USA. Univ Helsinki, Cent Hosp, Biomag Lab, FIN-00029 Helsinki, Finland. Helsinki Univ Technol, Lab Computat Engn, FIN-02150 Espoo, Finland. Boston Univ, Hearing Res Ctr, Boston, MA 02215 USA. RP Ahveninen, J (reprint author), Harvard Univ, MIT, Sch Med, Massachusetts Gen Hosp,Dept Radiol,Athinoula A Ma, CNY 149 13th St, Charlestown, MA 02129 USA. EM jyrki@nmr.mgh.harvard.edu RI Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012; Hamalainen, Matti/C-8507-2013; Lin, Fa-Hsuan/G-6988-2012; Witzel, Thomas/P-1402-2014 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Lin, Fa-Hsuan/0000-0002-9539-1731; FU NCRR NIH HHS [P41 RR 14075, P41 RR014075]; NICHD NIH HHS [R01 HD 040712, R01 HD040712]; NINDS NIH HHS [R01 NS037462, R01 NS 037462] NR 61 TC 181 Z9 183 U1 2 U2 22 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 SEP 26 PY 2006 VL 103 IS 39 BP 14608 EP 14613 DI 10.1073/pnas.0510480103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 090RG UT WOS:000240968100063 PM 16983092 ER PT J AU Ozcan, A Bilenca, A Bouma, BE Tearney, GJ AF Ozcan, Aydogan Bilenca, Alberto Bouma, Brett E. Tearney, Guillermo J. TI Mirror tunnel microscope SO APPLIED PHYSICS LETTERS LA English DT Article ID PHASE-RETRIEVAL; INTERFEROMETRY; PROFILES AB A microscope paradigm, which the authors term the "mirror tunnel microscope" (MTM), is described. The MTM uses a low numerical aperture (NA) lens together with parallel mirrors positioned between the lens plane and the object plane to provide a relatively simple means for digital wide-field microscopy. In MTM, the mirror tunnel acts as a spatial periodic-bandpass filter, which creates low-resolution, bandpassed versions of the object function in the image plane. However, each low-resolution image formed by the MTM carries a unique band of spatial frequencies. Coherent addition of the phase and amplitude of the spatial frequency information contained in each of these low-resolution images enhances the effective NA of the lens without decreasing field of view. To demonstrate the proof of principle, they have utilized a two-mirror MTM to reconstruct an image of a pinhole. Along the axis perpendicular to the mirrors, the image was reconstructed with higher resolution, commensurate with an effective fivefold NA increase. Initial results indicate that MTM is a promising method for wide-field digital microscopy. (c) 2006 American Institute of Physics. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Ozcan, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM aozcan@mgh.harvard.edu NR 10 TC 4 Z9 4 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD SEP 25 PY 2006 VL 89 IS 13 AR 131124 DI 10.1063/1.2356321 PG 3 WC Physics, Applied SC Physics GA 089JE UT WOS:000240875800024 ER PT J AU Ho, PM Rumsfeld, JS Masoudi, FA McClure, DL Plomondon, ME Steiner, JF Magid, DJ AF Ho, P. Michael Rumsfeld, John S. Masoudi, Frederick A. McClure, David L. Plomondon, Mary E. Steiner, John F. Magid, David J. TI Effect of medication nonadherence on hospitalization and mortality among patients with diabetes mellitus SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol ID MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; CLINICAL-OUTCOMES; GLYCEMIC CONTROL; BLOOD-PRESSURE; DRUG-THERAPY; RISK-FACTORS; ADHERENCE; CARE; QUALITY AB Background: Medication nonadherence may reduce the effectiveness of therapies. To our knowledge, the association between medication nonadherence and mortality remains unexplored outside the context of clinical trials. Methods: A retrospective cohort study of 11 532 patients with diabetes mellitus in a managed care organization. Medication adherence was calculated as the proportion of days covered for filled prescriptions of oral hypoglycemics, antihypertensives, and statin medications. The primary outcomes of interest were all-cause hospitalization and all-cause mortality. Multivariable regression analyses were performed to assess the independent association between medication adherence and outcomes. Results: Nonadherent patients (proportion of days covered, < 80%; prevalence, 21.3%) were younger and had fewer comorbidities compared with adherent patients. During follow-up, nonadherent patients had higher glycosylated hemoglobin, systolic and diastolic blood pressure, and low-density lipoprotein cholesterol levels. In unadjusted analyses, nonadherent patients had higher all-cause hospitalization (23.2% vs 19.2%, P <.001) and higher all-cause mortality (5.9% vs 4.0%, P <.001). In multivariable analyses, medication nonadherence remained significantly associated with increased risks for all-cause hospitalization (odds ratio, 1.58; 95% confidence interval, 1.38- 1.81; P <.001) and for all-cause mortality (odds ratio, 1.81; 95% confidence interval, 1.46-2.23; P <.001). The findings were consistent across patient subgroups and using different cutoffs for the proportion of days covered. Conclusions: Medication nonadherence is prevalent among patients with diabetes mellitus and is associated with adverse outcomes. Interventions are needed to increase medication adherence so that patients can realize the full benefit of prescribed therapies. C1 Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. Univ Colorado, Colorado Hlth Outcomes Program, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Colorado, Dept Emergency Med, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Kaiser Permanente Colorado, Climat Res Unit, Denver, CO USA. Denver Hlth Med Ctr, Dept Med, Denver, CO USA. RP Ho, PM (reprint author), Denver Vet Affairs Med Ctr, Dept Med, 1055 Clermont St 111B, Denver, CO 80220 USA. EM michael.ho@uchsc.edu FU NIA NIH HHS [K08-AG01011] NR 38 TC 448 Z9 456 U1 2 U2 16 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 SEP 25 PY 2006 VL 166 IS 17 BP 1836 EP 1841 DI 10.1001/archinte.166.17.1836 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 087GI UT WOS:000240730500007 PM 17000939 ER PT J AU Ho, PM Spertus, JA Masoudi, FA Reid, KJ Peterson, ED Magid, DJ Krumholz, HM Rumsfeld, JS AF Ho, P. Michael Spertus, John A. Masoudi, Frederick A. Reid, Kimberly J. Peterson, Eric D. Magid, David J. Krumholz, Harlan M. Rumsfeld, John S. TI Impact of medication therapy discontinuation on mortality after myocardial infarction SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES COMMITTEE; ACUTE CORONARY SYNDROMES; LONG-TERM ADHERENCE; AMERICAN-COLLEGE; SECONDARY PREVENTION; RISK-FACTORS; MANAGEMENT; OUTCOMES; REGISTRY AB Background: Nonadherence to medications is common, but the determinants and consequences are poorly defined. The objectives of this study were to identify patient and myocardial infarction (MI) treatment factors associated with medication therapy discontinuation and to assess the impact of medication discontinuation 1 month after MI on 12-month mortality. Methods: This was a multicenter prospective cohort of patients with MI enrolled in the Prospective Registry Evaluating Myocardial Infarction: Event and Recovery study. The outcomes were use of aspirin, beta-blockers, and statins at 1 month after MI hospitalization among patients discharged with all 3 medications as well as 12-month mortality. Results: Of 1521 patients discharged with all 3 medications, 184 discontinued use of all 3 medications, 56 discontinued use of 2 medications, 272 discontinued use of 1 medication, and 1009 continued taking all 3 medications at 1 month. In multivariable analyses, patients not graduating from high school (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.20- 2.60) were more likely to discontinue use of all medications. The effect of increasing age on medication therapy discontinuation was greater for females (OR, 1.77; 95% CI, 1.34- 2.34) than males (OR, 1.23; 95% CI, 1.02- 1.47). Patients who discontinued use of all medications at 1 month had lower 1-year survival (88.5% vs 97.7%; log-rank P <.001) compared with patients who continued to take 1 or more medication(s). In multivariable survival analysis, medication therapy discontinuation was independently associated with higher mortality (hazards ratio, 3.81; 95% CI, 1.88-7.72). Results were consistent when evaluating discontinuation of use of aspirin, beta-blockers, and statins separately. Conclusions: Medication therapy discontinuation after MI is common and occurs early after discharge. Patients who discontinue taking evidence-based medications are at increased mortality risk. These findings suggest the need to improve the transition of care from the hospital to outpatient setting to ensure that patients continue to take medications that have mortality benefit. C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Mid Amer Heart Inst, Denver, CO USA. Denver Hlth Med Ctr, Denver, CO USA. Duke Clin Res Inst, Durham, NC USA. Kaiser Permanente Colorado, Clin Res Unit, Aurora, CO USA. Yale Univ, Sch Med, New Haven, CT USA. RP Ho, PM (reprint author), Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, 1055 Clermont St 111B, Denver, CO 80220 USA. EM michael.ho@uchsc.edu NR 28 TC 299 Z9 309 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 25 PY 2006 VL 166 IS 17 BP 1842 EP 1847 DI 10.1001/archinte.166.17.1842 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 087GI UT WOS:000240730500008 PM 17000940 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Meigs, JB Levy, D Fox, CS AF Parikh, Nisha I. Hwang, Shih-Jen Larson, Martin G. Meigs, James B. Levy, Daniel Fox, Caroline S. TI Cardiovascular disease risk factors in chronic kidney disease - Overall burden and rates of treatment and control SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHRONIC RENAL-INSUFFICIENCY; GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; BLOOD-PRESSURE; SERUM CREATININE; SYSTOLIC HYPERTENSION; MYOCARDIAL-INFARCTION; DIALYSIS PATIENTS; ELDERLY PROGRAM; UNITED-STATES AB Background: Mild to moderate chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease. The burden of cardiovascular disease risk factors in this setting is not well described. Methods: We compared the age- and sex-adjusted prevalence of cardiovascular disease risk factors and their treatment and control among persons with and without CKD in 3258 Framingham offspring cohort members who attended the seventh examination cycle (1998-2001). Glomerular filtration rate (GFR) was estimated using the simplified Modification of Diet in Renal Disease Study equation. We defined CKD as a GFR of less than 59 mL/min per 1.73 m(2) in women and less than 64 mL/min per 1.73 m(2) in men. Results: Those with CKD were older, more likely to be obese (33.5% vs 29.3%; P=.02), and more likely to have low levels of high-density lipoprotein cholesterol (45.2% vs 29.4%; P <.001) and high triglyceride levels (39.9% vs 29.8%; P <.001). Those with CKD had a higher prevalence of hypertension (71.2% vs 42.7%; P <.001) and hypertension treatment (86.0% vs 72.5%; P <.001), but were less likely to achieve optimal blood pressure control ( 27.0% vs 45.5%; P <. 001). Participants with CKD had a higher prevalence of elevated low-density lipoprotein cholesterol levels (60.5% vs 44.7%; P=.06) and lipid-lowering therapy (57.1% vs 42.6%; P=.09), although this was not statistically significant. A greater proportion of individuals with CKD than those without had diabetes (23.5% vs 11.9%; P=.02) and were receiving diabetes treatment (63.6% vs 46.9%; P=.05), but were less likely to achieve a hemoglobin A(1c) level of less than 7% (43.8% vs 59.4%; P=.03). Conclusions: Chronic kidney disease is associated with a significant burden of cardiovascular disease risk factors in the community. The diagnosis of CKD should alert the practitioner to look for potentially modifiable cardiovascular risk factors. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Endocrinol Diabet & Hypertens, Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-25195] NR 57 TC 116 Z9 120 U1 2 U2 5 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 SEP 25 PY 2006 VL 166 IS 17 BP 1884 EP 1891 DI 10.1001/archinte.166.17.1884 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 087GI UT WOS:000240730500014 PM 17000946 ER PT J AU Baehring, JM Hochberg, FH Betensky, RA Longtine, J Sklar, J AF Baehring, Joachim M. Hochberg, Fred H. Betensky, Rebecca A. Longtine, Janina Sklar, Jeffrey TI Immunoglobulin gene rearrangement analysis in cerebrospinal fluid of patients with lymphoproliferative processes SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE IgH gene rearrangement; CNS lymphoma; cerebrospinal fluid; NHL; cytology; flow cytometry ID NERVOUS-SYSTEM LYMPHOMA; POLYMERASE-CHAIN-REACTION; PRIMARY CNS LYMPHOMA; CENTER B-CELLS; MOLECULAR ANALYSIS; LEPTOMENINGEAL METASTASIS; PCR ANALYSIS; CDR-III; DIAGNOSIS; NEOPLASMS AB Objective: To determine the sensitivity and specificity of clonal immunoglobulin heavy chain gene rearrangement (IGHR) analysis in the distinction of benign and malignant lymphoproliferative diseases. Methods: A retrospective analysis was conducted of patients in whom a malignant lymphoproliferative process was suspected. Cells of CSF samples were collected by centrifugation, resuspended in 100 mu l of the supernatant and boiled. A 10 mu l aliquot of this lysate served as template for semi-nested polymerase chain reaction using variable and joining region consensus primers. PCR products were analyzed by polyacrylamide gel electrophoresis. Cytopathological diagnosis and flow cytometry results were recorded. Sensitivity and specificity of IGHR analysis, cytopathology and flow cytometry were calculated. Results: Eleven patients (12 specimens) had involvement of leptomeninges at the time of lumbar puncture. Another 25 cases (27 specimens) had normal CSF findings or were diagnosed with benign lymphoproliferative conditions. Sensitivity of CSF cytopathology, flow cytometry and IGHR analysis were 0.27 [95% confidence interval 0.06, 0.61], 0.1 [0.003, 0.45] and 0.58 [0.28, 0.85]. Specificity was 1 [0.86, 1], 0.95 [0.77, 1.0] and 0.85 [0.66, 0.96]. Interpretation: IGHR analysis appears to be a useful addition to morphological and flow cytometry analysis of cerebrospinal fluid in the evaluation of CNS lymphoproliferative processes. (c) 2006 Elsevier B.V. All rights reserved. C1 Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Baehring, JM (reprint author), Yale Univ, Sch Med, Dept Neurol, 333 Cedar St,TMP410, New Haven, CT 06510 USA. EM joachim.baehring@yale.edu NR 33 TC 18 Z9 18 U1 0 U2 1 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 SEP 25 PY 2006 VL 247 IS 2 BP 208 EP 216 DI 10.1016/j.jns.2006.05.044 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 088LH UT WOS:000240812700015 PM 16764890 ER PT J AU Kwong, JMK Lalezary, M Nguyen, JK Yang, C Khattar, A Piri, N Mareninov, S Gordon, LK Caprioli, J AF Kwong, Jacky M. K. Lalezary, Maziar Nguyen, Jessica K. Yang, Christine Khattar, Anuj Piri, Natik Mareninov, Sergey Gordon, Lynn K. Caprioli, Joseph TI Co-expression of heat shock transcription factors 1 and 2 in rat retinal ganglion cells SO NEUROSCIENCE LETTERS LA English DT Article DE heat shock protein; stress rat; heat shock factor; retina; ganglion cell ID HEAT-SHOCK RESPONSE; MOLECULAR CHAPERONES; HIPPOCAMPAL-NEURONS; STRESS-RESPONSE; GLAUCOMA MODEL; GLIAL-CELLS; HYPERTHERMIA; ACTIVATION; INDUCTION; PROTECTS AB Heat shock protein (HSP) plays an important role in the maintenance of neuronal survival during harmful conditions. Previously, we reported that metabolic stress induces HSP72 in retinal ganglion cells (RGCs) and protects against excitotoxicity, hypoxia and experimental glaucoma. To understand heat shock protein transcriptional mechanisms, we examined the cellular expression of heat shock factors 1 (HSF1) and 2 (HSF2) in the unstressed adult rat retina. Western blotting, immunohistochemistry and RT-PCR showed that mRNA and protein of HSF1 and HSF2 were present in the rat retina and predominantly expressed in RGC layer cells. Western blotting of dissociated RGC suspensions harvested with Thy-1 immuno-labeled magnetic beads confirmed that RGCs expressed HSF1, HSF2 and HSP72. Our findings suggest that both heat shock transcription factors I and 2 are linked to the heat shock response in retinal ganglion cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Ophthalmol, Jules Stein Eye Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurosci, Los Angeles, CA 90095 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Ophthalmol Sect, Los Angeles, CA USA. RP Kwong, JMK (reprint author), Univ Calif Los Angeles, Dept Ophthalmol, Jules Stein Eye Inst, David Geffen Sch Med, B-146,100 Stein Plaza, Los Angeles, CA 90095 USA. EM kwong@jsei.ucla.edu OI Caprioli, Joseph/0000-0002-2383-7263 NR 25 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 25 PY 2006 VL 405 IS 3 BP 191 EP 195 DI 10.1016/j.neulet.2006.06.070 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 083PL UT WOS:000240470600008 PM 16889897 ER PT J AU Tholouli, E Hoyland, JA Di Vizio, D O'Connell, F MacDermott, SA Twomey, D Levenson, R Yin, JAL Golub, TR Loda, M Byers, R AF Tholouli, Eleni Hoyland, Judith A. Di Vizio, Dolores O'Connell, Fionnuala MacDermott, Sarah A. Twomey, David Levenson, Richard Yin, John A. Liu Golub, Todd R. Loda, Massimo Byers, Richard TI Imaging of multiple mRNA targets using quantum dot based in situ hybridization and spectral deconvolution in clinical biopsies SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE quantum dots; in situ hybridization; multiplex in situ hybridization; messenger RNA detection; spectral deconvolution; bone marrow biopsies ID GENE-EXPRESSION; SEMICONDUCTOR NANOCRYSTALS; INSITU HYBRIDIZATION; FLUORESCENCE; MICROSCOPY; PREDICTION; CANCER; PROBES; AUTOFLUORESCENCE; RECEPTOR AB Gene expression mapping using microarray analysis has identified useful gene signatures for predicting outcome. However, little of this has been translated into clinically effective diagnostic tools as microarrays require high quality fresh-frozen tissue samples. We describe a methodology of multiplexed in situ hybridization (ISH) using a novel combination of quantum dot (QD)-labeled oligonucleotide probes and spectral imaging analysis in routinely processed, formalin-fixed paraffin embedded human biopsies. The conditions for QD-ISH were optimized using a poly d(T) oligonucleotide in decalcified bone marrow samples. Single and multiplex QD-ISH was performed in samples with acute leukemia and follicular lymphoma using oligonucleotide probes for myeloperoxidase, bcl-2, survivin, and XIAP. Spectral imaging was used for post hybridization tissue analysis, enabling separation of spatially colocalized signals. The method allows quantitative characterization of multiple gene expression using non-bleaching fluorochromes. This is expected to facilitate multiplex in situ transcript detection in routinely processed human clinical tissue. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Manchester, Div Lab & Regenerat Med, Manchester M13 9PL, Lancs, England. Univ Manchester, Dept Haematol, Manchester Royal Infirm, Manchester M13 9WL, Lancs, England. Dana Farber Canc Inst, Dept Clin Oncol, Boston, MA 02115 USA. MIT, Broad Inst, Canc Program, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. Cambridge Res & Instrumentat Inc, Woburn, MA 01801 USA. RP Byers, R (reprint author), Univ Manchester, Div Lab & Regenerat Med, Stopford Bldg,Oxford Rd, Manchester M13 9PL, Lancs, England. EM r.byers@manchester.ac.uk RI Hoyland, Judith/P-5168-2014; OI Hoyland, Judith/0000-0003-4876-5208; Byers, Richard/0000-0003-0796-0365 NR 31 TC 50 Z9 52 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 22 PY 2006 VL 348 IS 2 BP 628 EP 636 DI 10.1016/j.bbrc.2006.07.122 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 080UW UT WOS:000240275000041 PM 16893519 ER PT J AU Kuroda, T Martuza, RL Todo, T Rabkin, SD AF Kuroda, Toshihiko Martuza, Robert L. Todo, Tomoki Rabkin, Samuel D. TI Flip-Flop HSV-BAC: bacterial artificial chromosome based system for rapid generation of recombinant herpes simplex virus vectors using two independent site-specific recombinases SO BMC BIOTECHNOLOGY LA English DT Article ID LENGTH INFECTIOUS CLONE; IMMEDIATE-EARLY GENE; RIBONUCLEOTIDE REDUCTASE; IN-VIVO; HUMAN CYTOMEGALOVIRUS; ENHANCER-PROMOTER; ESCHERICHIA-COLI; REPLICATION-COMPETENT; ADENOVIRAL VECTORS; MALIGNANT GLIOMAS AB Background: Oncolytic herpes simplex virus (HSV) vectors that specifically replicate in and kill tumor cells sparing normal cells are a promising cancer therapy. Traditionally, recombinant HSV vectors have been generated through homologous recombination between the HSV genome and a recombination plasmid, which usually requires laborious screening or selection and can take several months. Recent advances in bacterial artificial chromosome (BAC) technology have enabled cloning of the whole HSV genome as a BAC plasmid and subsequent manipulation in E. coli. Thus, we sought a method to generate recombinant oncolytic HSV vectors more easily and quickly using BAC technology. Results: We have developed an HSV-BAC system, termed the Flip-Flop HSV-BAC system, for the rapid generation of oncolytic HSV vectors. This system has the following features: (i) two site-specific recombinases, Cre and FLPe, are used sequentially to integrate desired sequences and to excise the BAC sequences, respectively; and (ii) the size of the HSV-BAC-insert genome exceeds the packaging limit of HSV so only correctly recombined virus grows efficiently. We applied this to the construction of an HSV-BAC plasmid that can be used for the generation of transcriptionally-targeted HSV vectors. BAC sequences were recombined into the UL39 gene of HSV ICP4-deletion mutant d120 to generate M24-BAC virus, from which HSV-BAC plasmid pM24-BAC was isolated. An ICP4 expression cassette driven by an exogenous promoter was re-introduced to pM24-BAC by Cre-mediated recombination and nearly pure preparations of recombinant virus were obtained typically in two weeks. Insertion of the ICP4 coding sequence alone did not restore viral replication and was only minimally better than an ICP4-null construct, whereas insertion of a CMVIE promoter-ICP4 transgene (bM24-CMV) efficiently drove viral replication. The levels of bM24-CMV replication in tumor cells varied considerably compared to hrR3 (UL39 mutant). Conclusion: Our Flip-Flop HSV-BAC system enables rapid generation of HSV vectors carrying transgene inserts. By introducing a tumor-specific-promoter-driven ICP4 cassette into pM24-BAC using this system, one should be able to generate transcriptionally-targeted oncolytic HSV vectors. We believe this system will greatly facilitate the screening of a plethora of clinically useful tumor-specific promoters in the context of oncolytic HSV vectors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Mol Neurosurg Lab, Boston, MA 02114 USA. RP Kuroda, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg,Mol Neurosurg Lab, 185 Cambridge St,CPZN-3800, Boston, MA 02114 USA. EM tokuroda-gi@umin.ac.jp; rmartuza@partners.org; toudou-nsu@umin.ac.jp; rabkin@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012; OI rabkin, samuel/0000-0003-2344-2795; Kuroda, Toshihiko/0000-0001-6660-8930 FU NCI NIH HHS [CA102139, R01 CA102139]; NINDS NIH HHS [R01 NS032677] NR 50 TC 24 Z9 25 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD SEP 22 PY 2006 VL 6 AR 40 DI 10.1186/1472-6750-6-40 PG 19 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 095CS UT WOS:000241286400002 PM 16995942 ER PT J AU Chang, HC Tan, KM Hsu, YM AF Chang, Hsiu-Ching Tan, Kemin Hsu, Yen-Ming TI CD8 alpha beta has two distinct binding modes of interaction with peptide-major histocompatibility complex class I SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MHC CLASS-I; CD8 CORECEPTOR FUNCTION; DIFFERENTIAL EXPRESSION; STRUCTURAL BASIS; CD8-BETA CHAINS; LIGAND-BINDING; ALPHA-3 DOMAIN; LYMPHOCYTES-T; CELL; TCR AB Interaction of CD8 (CD8 alpha alpha or CD8 alpha beta) with the peptide-major histocompatibility complex (MHC) class I (pMHCI) is critical for the development and function of cytolytic T cells. Although the crystal structure of CD8 alpha alpha(.)pMHCI complex revealed that two symmetric CD8 alpha subunits interact with pMHCI asymmetrically, with one subunit engaged in more extensive interaction than the other, the details of the interaction between the CD8 alpha beta heterodimer and pMHCI remained unknown. The Ig-like domains of mouse CD8 alpha beta and CD8 alpha alpha are similar in the size, shape, and surface electrostatic potential of their pMHCI-binding regions, suggesting that their interactions with pMHCI could be very similar. Indeed, we found that the CD8 alpha variants CD8 alpha(R8A) and CD8 alpha(E27A), which were functionally inactive as homodimers, could form an active co-receptor with wildtype (WT) CD8 beta as a CD8 alpha(R8A)beta or CD8 alpha(E27A)beta heterodimer. We also identified CD8 beta variants that could form active receptors with WT CD8 beta but not with CD8 alpha(R8A). This observation is consistent with the notion that the CD8 beta subunit may replace either CD8 beta subunit in CD8 alpha alpha(.) pMHCI complex. In addition, we showed that both anti-CD8 alpha and anti-CD8 beta antibodies were unable to completely block the co-receptor activity of WT CD8 alpha beta. We propose that CD8 alpha beta binds to pMHCI in at least two distinguishable orientations. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Biogen Inc, Mol Discovery Dept, Cambridge, MA 02142 USA. RP Chang, HC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 77 Ave Louis Pasteur,HIM-442, Boston, MA 02115 USA. EM hsiu-ching_chang@dfci.harvard.edu FU NIAID NIH HHS [AI45789] NR 36 TC 10 Z9 10 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 SEP 22 PY 2006 VL 281 IS 38 BP 28090 EP 28096 DI 10.1074/jbc.M604931200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 084LM UT WOS:000240534400046 PM 16840780 ER PT J AU Silve, C Juppner, H AF Silve, Caroline Jueppner, Harald TI Ollier disease SO ORPHANET JOURNAL OF RARE DISEASES LA English DT Review ID GRANULOSA-CELL TUMOR; CENTRAL CHONDROSARCOMA; CARTILAGINOUS TUMORS; ENCHONDROMATOSIS; PROGRESSION; EXPRESSION; GENETICS; RECEPTOR; PTHRP; BONE AB Enchondromas are common intraosseous, usually benign cartilaginous tumors, that develop in close proximity to growth plate cartilage. When multiple enchondromas are present, the condition is called enchondromatosis also known as Ollier disease (WHO terminology). The estimated prevalence of Ollier disease is 1/100,000. Clinical manifestations often appear in the first decade of life. Ollier disease is characterized by an asymmetric distribution of cartilage lesions and these can be extremely variable (in terms of size, number, location, evolution of enchondromas, age of onset and of diagnosis, requirement for surgery). Clinical problems caused by enchondromas include skeletal deformities, limb-length discrepancy, and the potential risk for malignant change to chondrosarcoma. The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas is known as Maffucci syndrome. Until now both Ollier disease and Maffucci syndrome have only occurred in isolated patients and not familial. It remains uncertain whether the disorder is caused by a single gene defect or by combinations of (germ-line and/or somatic) mutations. The diagnosis is based on clinical and conventional radiological evaluations. Histological analysis has a limited role and is mainly used if malignancy is suspected. There is no medical treatment for enchondromatosis. Surgery is indicated in case of complications (pathological fractures, growth defect, malignant transformation). The prognosis for Ollier disease is difficult to assess. As is generally the case, forms with an early onset appear more severe. Enchondromas in Ollier disease present a risk of malignant transformation of enchondromas into chondrosarcomas. C1 [Silve, Caroline] Univ Paris 07, INSERM, U773, F-75018 Paris, France. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, MassGen Hosp Children, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Neprol Unit, MassGen Hosp Children, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Silve, C (reprint author), Univ Paris 07, INSERM, U773, 16 Rue Henri Huchard, F-75018 Paris, France. EM Caroline.Silve@bichat.inserm.fr; hjueppner@partners.org NR 25 TC 49 Z9 51 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-1172 J9 ORPHANET J RARE DIS JI Orphanet J. Rare Dis. PD SEP 22 PY 2006 VL 1 AR 37 DI 10.1186/1750-1172-1-37 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 240KA UT WOS:000251585300001 PM 16995932 ER PT J AU Salehi-Ashtiani, K Luptak, A Litovchick, A Szostak, JW AF Salehi-Ashtiani, Kourosh Luptak, Andrej Litovchick, Alexander Szostak, Jack W. TI A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene SO SCIENCE LA English DT Article ID HEPATITIS-DELTA-VIRUS; IN-VITRO SELECTION; SELF-CLEAVAGE; MESSENGER-RNA; NEURONAL ISOFORM; TRANSCRIPTION; CATALYSIS; SITE; HAMMERHEAD; EXPRESSION AB Ribozymes are thought to have played a pivotal role in the early evolution of life, but relatively few have been identified in modern organisms. We performed an in vitro selection aimed at isolating self-cleaving RNAs from the human genome. The selection yielded several ribozymes, one of which is a conserved mammalian sequence that resides in an intron of the CPEB3 gene, which belongs to a family of genes regulating messenger RNA polyadenylation. The CPEB3 ribozyme is structurally and biochemically related to the human hepatitis delta virus (HDV) ribozymes. The occurrence of this ribozyme exclusively in mammals suggests that it may have evolved as recently as 200 million years ago. We postulate that HDV arose from the human transcriptome. C1 Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, CCIB, Simches Res Ctr 7215, Boston, MA 02114 USA. Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243 FU NHLBI NIH HHS [HL66678]; NIGMS NIH HHS [GM53936] NR 34 TC 141 Z9 150 U1 2 U2 21 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 SEP 22 PY 2006 VL 313 IS 5794 BP 1788 EP 1792 DI 10.1126/science.1129308 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086ED UT WOS:000240655700049 PM 16990549 ER PT J AU Guo, SZ Wang, S Kim, WJ Lee, SR Frosch, MP Bacskai, BJ Greenberg, SM Lo, EH AF Guo, Shuzhen Wang, Sophia Kim, Woo Jean Lee, Sun-Ryung Frosch, Matthew P. Bacskai, Brian J. Greenberg, Steven M. Lo, Eng H. TI Effects of ApoE isoforms on beta-amyloid-induced matrix metalloproteinase-9 in rat astrocytes SO BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; proteolysis; ApoE ID APOLIPOPROTEIN-E EPSILON-2; ALZHEIMERS-DISEASE; MOUSE MODEL; MATRIX METALLOPROTEINASES; BRAIN; DEPOSITION; ALLELE; CELLS; MMP-9; ASSOCIATION AB Matrix metalloproteinase-9 (MMP-9) may play a role in the inflammatory glial response during Alzheimer's disease (AD). Astrocytes can degrade beta-amyloid (A beta) and extracellular proteolysis via MMP-9 may be involved. Because Apolipoprotein E (APOE) genotype is an important factor for AD, we ask whether various apoE isoforms can influence A beta-induced MMP-9 responses in primary rat astrocytes. Our data show that apoE4 significantly dampens A beta-induced MMP-9 levels, possibly by downregulating the Rho-Rho kinase (ROCK) pathway. Reduction of astrocytic MMP-9 by apoE4 may affect A beta clearance and promote A beta deposition in AD. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Charlestown, MA USA. Mt Sinai Sch Med, New York, NY USA. Cheju Natl Univ, Cheju, South Korea. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. EM Lo@helix.mgh.harvard.edu FU NIA NIH HHS [R01-AG21084, R01-AG20570]; NINDS NIH HHS [R01-NS48422, P50-NS10828, R01-NS40529] NR 31 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 21 PY 2006 VL 1111 BP 222 EP 226 DI 10.1016/j.brainres.2006.06.041 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 089TY UT WOS:000240905200027 PM 16919608 ER PT J AU Morton, GJ Cummings, DE Baskin, DG Barsh, GS Schwartz, MW AF Morton, G. J. Cummings, D. E. Baskin, D. G. Barsh, G. S. Schwartz, M. W. TI Central nervous system control of food intake and body weight SO NATURE LA English DT Review ID HYPOTHALAMIC ARCUATE NUCLEUS; PLASMA GHRELIN LEVELS; CAUDAL BRAIN-STEM; LEPTIN RECEPTOR; INSULIN-RECEPTOR; ENERGY-BALANCE; RECOMBINANT LEPTIN; PLACE PREFERENCE; INDUCED ANOREXIA; NEUROPEPTIDE-Y AB The capacity to adjust food intake in response to changing energy requirements is essential for survival. Recent progress has provided an insight into the molecular, cellular and behavioural mechanisms that link changes of body fat stores to adaptive adjustments of feeding behaviour. The physiological importance of this homeostatic control system is highlighted by the severe obesity that results from dysfunction of any of several of its key components. This new information provides a biological context within which to consider the global obesity epidemic and identifies numerous potential avenues for therapeutic intervention and future research. C1 Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. Univ Washington, Dept Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98104 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. RP Schwartz, MW (reprint author), Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. EM mschwart@u.washington.edu RI Schwartz, Michael/H-9950-2012 NR 75 TC 1126 Z9 1175 U1 28 U2 230 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 21 PY 2006 VL 443 IS 7109 BP 289 EP 295 DI 10.1038/nature05026 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085RL UT WOS:000240622000036 PM 16988703 ER PT J AU D'Orazio, JA Nobuhisa, T Cui, RT Arya, M Spry, M Wakamatsu, K Igras, V Kunisada, T Granter, SR Nishimura, EK Ito, S Fisher, DE AF D'Orazio, John A. Nobuhisa, Tetsuji Cui, Rutao Arya, Michelle Spry, Malinda Wakamatsu, Kazumasa Igras, Vivien Kunisada, Takahiro Granter, Scott R. Nishimura, Emi K. Ito, Shosuke Fisher, David E. TI Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning SO NATURE LA English DT Article ID STEM-CELL FACTOR; HUMAN MELANOCYTES; DNA-DAMAGE; TRANSCRIPTION FACTOR; ULTRAVIOLET-LIGHT; CYCLIC-AMP; EXPRESSION; GENE; KERATINOCYTES; MELANOGENESIS AB Ultraviolet-light (UV)-induced tanning is defective in numerous 'fair-skinned' individuals, many of whom contain functional disruption of the melanocortin 1 receptor (MC1R)(1-3). Although this suggested a critical role for the MC1R ligand melanocyte stimulating hormone (MSH) in this response, a genetically controlled system has been lacking in which to determine the precise role of MSH - MC1R. Here we show that ultraviolet light potently induces expression of MSH in keratinocytes, but fails to stimulate pigmentation in the absence of functional MC1R in red/blonde-haired Mc1r(e/e) mice. However, pigmentation could be rescued by topical application of the cyclic AMP agonist forskolin, without the need for ultraviolet light, demonstrating that the pigmentation machinery is available despite the absence of functional MC1R. This chemically induced pigmentation was protective against ultraviolet-light-induced cutaneous DNA damage and tumorigenesis when tested in the cancer-prone, xerodermapigmentosum-complementation-group- C-deficient genetic background. These data emphasize the essential role of intercellular MSH signalling in the tanning response, and suggest a clinical strategy for topical small-molecule manipulation of pigmentation. C1 Dana Farber Canc Inst, Melanoma Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Kentucky, Coll Med, Dept Pediat, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA. Univ Kentucky, Coll Med, Grad Ctr Toxicol, Lexington, KY 40536 USA. Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Aichi 4701192, Japan. Gifu Univ, Grad Sch Med, Dept Tissue & Organ Dev, Gifu 501, Japan. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Kanazawa Univ, Dept Stem Cell Med, Canc Res Inst, Kanazawa, Ishikawa 9200934, Japan. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Melanoma Program, 44 Binney St, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu OI Ito, Shosuke/0000-0001-9182-5144; Wakamatsu, Kazumasa/0000-0003-1748-9001 NR 30 TC 146 Z9 149 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 21 PY 2006 VL 443 IS 7109 BP 340 EP 344 DI 10.1038/nature05098 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085RL UT WOS:000240622000047 PM 16988713 ER PT J AU Day, CL Kaufmann, DE Kiepiela, P Brown, JA Moodley, ES Reddy, S Mackey, EW Miller, JD Leslie, AJ DePierres, C Mncube, Z Duraiswamy, J Zhu, BG Eichbaum, Q Altfeld, M Wherry, EJ Coovadia, HM Goulder, PJR Klenerman, P Ahmed, R Freeman, GJ Walker, BD AF Day, Cheryl L. Kaufmann, Daniel E. Kiepiela, Photini Brown, Julia A. Moodley, Eshia S. Reddy, Sharon Mackey, Elizabeth W. Miller, Joseph D. Leslie, Alasdair J. DePierres, Chantal Mncube, Zenele Duraiswamy, Jaikumar Zhu, Baogong Eichbaum, Quentin Altfeld, Marcus Wherry, E. John Coovadia, Hoosen M. Goulder, Philip J. R. Klenerman, Paul Ahmed, Rafi Freeman, Gordon J. Walker, Bruce D. TI PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression SO NATURE LA English DT Article ID CHRONIC VIRAL-INFECTION; LYMPHOCYTES; PROLIFERATION; REPLICATION; SUPERFAMILY; PHENOTYPE; RESPONSES; PERFORIN; MARKER AB Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells(1-4), is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice(5). Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load(5). To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection. C1 Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. Massachusetts Gen Hosp, Partner AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Walker, BD (reprint author), Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. EM bwalker@partners.org RI Day, Cheryl/J-9844-2012 NR 26 TC 1274 Z9 1345 U1 28 U2 123 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 21 PY 2006 VL 443 IS 7109 BP 350 EP 354 DI 10.1038/nature05115 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085RL UT WOS:000240622000049 PM 16921384 ER PT J AU Cigler, T Gilman, MD Qureshi, A Costenbader, KH Tambouret, RH Harris, NL Fidias, P AF Cigler, Tessa Gilman, Matthew D. Qureshi, Anwer Costenbader, Karen H. Tambouret, Rosemary H. Harris, Nancy Lee Fidias, Panos TI Case 29-2006: A 43-year-old woman with painful nodules on the fingertips, shortness of breath, and fatigue - Non-small-cell lung cancer with associated nonbacterial thrombotic (marantic) endocarditis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; VENOUS THROMBOEMBOLISM; CLASSIFICATION; CHEMOTHERAPY; DISEASE C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Cigler, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Rheumatol Immunol & Allergy, Boston, MA 02115 USA. NR 29 TC 2 Z9 2 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 SEP 21 PY 2006 VL 355 IS 12 BP 1263 EP 1272 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 085IT UT WOS:000240598500012 ER PT J AU Suda, Y Arano, A Fukui, Y Koshida, S Wakao, M Nishimura, T Kusumoto, S Sobel, M AF Suda, Yasuo Arano, Akio Fukui, Yasuhiro Koshida, Shuhei Wakao, Masahiro Nishimura, Tomoaki Kusumoto, Shoichi Sobel, Michael TI Immobilization and clustering of structurally defined oligosaccharides for sugar chips: An improved method for surface plasmon resonance analysis of protein-carbohydrate interactions SO BIOCONJUGATE CHEMISTRY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; VON-WILLEBRAND-FACTOR; HEPARIN-BINDING; A1 DOMAIN; MICROARRAYS; DISACCHARIDE; COMPLEXES; RECEPTOR; ARRAYS; ACID AB Oligosaccharides are increasingly being recognized as important partners in receptor-ligand binding and cellular signaling. Surface plasmon resonance (SPR) is a very powerful tool for the real-time study of the specific interactions between biological molecules. We report here an advanced method for the immobilization of oligosaccharides in clustered structures for SPR and their application to the analysis of heparin-protein interactions. Reductive amination reactions and linker molecules were designed and optimized. Using mono-, tri-, or tetravalent linker compounds, we incorporated synthetic structurally defined disaccharide units of heparin and immobilized them as ligands for SPR. Their binding to an important hemostatic protein, von Willebrand factor (vWf), and its known heparin-binding domain was quantitatively analyzed. These multivalent ligand conjugates exhibited reproducible binding behavior, with consistency of the surface conditions of the SPR chip. This novel technique for oligosaccharide immobilization in SPR studies is accurate, specific, and easily applicable to both synthetic and naturally derived oligosaccharides. C1 Kagoshima Univ, Dept Nanostruct & Adv Mat, Grad Sch Sci & Engn, Kagoshima 8900065, Japan. Kagoshima Univ, Venture Business Lab, Kagoshima 8900065, Japan. Japan Sci & Technol Agcy, Chiyoda Ku, Tokyo 1028666, Japan. Osaka Univ, Dept Chem, Grad Sch Sci, Osaka 5600043, Japan. Univ Washington, Dept Surg, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Suda, Y (reprint author), Kagoshima Univ, Dept Nanostruct & Adv Mat, Grad Sch Sci & Engn, Kagoshima 8900065, Japan. EM ysuda@eng.kagoshima-u.ac.jp FU NHLBI NIH HHS [HL079812, R01HL39903] NR 30 TC 75 Z9 75 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP 20 PY 2006 VL 17 IS 5 BP 1125 EP 1135 DI 10.1021/bc0600620 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 085LX UT WOS:000240606700003 PM 16984119 ER PT J AU Sever, S Skoch, J Newmyer, S Ramachandran, R Ko, D McKee, M Bouley, R Ausiello, D Hyman, BT Bacskai, BJ AF Sever, Sanja Skoch, Jesse Newmyer, Sherri Ramachandran, Rajesh Ko, David McKee, Mary Bouley, Richard Ausiello, Dennis Hyman, Bradley T. Bacskai, Brian J. TI Physical and functional connection between auxilin and dynamin during endocytosis SO EMBO JOURNAL LA English DT Article DE assembly; auxilin; dynamin; endocytosis; GTP binding ID CLATHRIN-MEDIATED ENDOCYTOSIS; COATED VESICLE FORMATION; G-ASSOCIATED KINASE; IN-VIVO; PIT INVAGINATION; UNCOATING ATPASE; SELF-ASSOCIATION; J-DOMAIN; GTPASE; PROTEINS AB During clathrin-mediated endocytosis, the GTPase dynamin promotes formation of clathrin-coated vesicles, but its mode of action is unresolved. We provide evidence that a switch in three functional states of dynamin (dimers, tetramers, rings/spirals) coordinates its GTPase cycle. Dimers exhibit negative cooperativity whereas tetramers exhibit positive cooperativity with respect to GTP. Our study identifies tetramers as the kinetically most stable GTP-bound conformation of dynamin, which is required to promote further assembly into higher order structures such as rings or spirals. In addition, using fluorescence lifetime imaging microscopy, we show that interactions between dynamin and auxilin in cells are GTP-, endocytosis-and tetramer-dependent. Furthermore, we show that the cochaperone activity of auxilin is required for constriction of clathrin-coated pits, the same early step in endocytosis known to be regulated by the lifetime of dynamin: GTP. Together, our findings support the model that the GTP-bound conformation of dynamin tetramers stimulates formation of constricted coated pits at the plasma membrane by regulating the chaperone activity of hsc70/auxilin. C1 Harvard Univ, Sch Med, Dept Med, Renal Unit,Nephrol Div, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Univ Calif San Francisco, GW Hooper Fdn, San Francisco, CA 94143 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA USA. RP Sever, S (reprint author), Harvard Univ, Sch Med, Dept Med, Renal Unit,Nephrol Div, Charlestown, MA 02129 USA. EM ssever@receptor.mgh.harvard.edu RI Ramachandran, Rajesh/A-1337-2011 OI Ramachandran, Rajesh/0000-0002-4645-2841 FU NIDDK NIH HHS [DK57521, 5P30DK43351-14, DK38452, DK43341, P01 DK038452, P30 DK043351, P30 DK057521, R01 (DK064787), R01 DK064787]; NIGMS NIH HHS [GM42455, R01 GM042455] NR 42 TC 23 Z9 27 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 20 PY 2006 VL 25 IS 18 BP 4163 EP 4174 DI 10.1038/sj.emboj.7601298 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 092DT UT WOS:000241077900001 PM 16946707 ER PT J AU Mel'nikova, NP Timoshin, SS Jivotova, EY Pelliniemi, LJ Jokinen, E Abdelwahid, E AF Mel'nikova, Natalia P. Timoshin, Sergey S. Jivotova, Elena Y. Pelliniemi, Lauri J. Jokinen, Eero Abdelwahid, Eltyeb TI Angiotensin-II activates apoptosis, proliferation and protein synthesis in the left heart ventricle of newborn albino rats SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE ANG-II; in vivo; apoptosis; cell proliferation; cardiomyocytes; AgNORs ID STIMULATION; FIBROBLASTS; RECEPTOR; DISEASE; AT(1) AB Angiotensin II (ANG-II) is a critical regulator of various signaling pathways involved in growth and remodeling of the vascular, cardiac, and renal cells and tissues. Although it contributes to several physiologic and pathologic events in the cardiovascular system, its role in growth and differentiation of the newborn heart is still unclear. We analyzed the effect of ANG-II treatment on apoptosis, DNA synthesis, and nucleolar organizer regions (AgNORs) activity in newborn rat myocardium. Injections of ANG-II for 5-days caused significant increase of the H-3-thymidine labeling index (M +/- m) in the myocardium of 7-day-old rats (from 6.95 +/- 0.32% to 8.53 +/- 0.22%, p < 0.05). There was also significant increase in the cross sectional surface area of cardiomyocytes (from 686 +/- 57 to 872 +/- 54 mu m(2), p < 0.05), number of nucleoli (from 2.5 +/- 0.05 to 2.8 +/- 0.1, p < 0.05), and nucleolar surface area (from 2.6 +/- 0.09 to 3.2 +/- 0.22 mu m(2), p < 0.05). These changes were accompanied by significant increase in the apoptotic indices analyzed by TDT-mediated dUTP-biotin nick end-labeling (TUNEL) (from 0.044 +/- 0.01% to 0.093 +/- 0.01%, p < 0.05). Interestingly, we found no differences in cell proliferation between the test and control animals after 21-45 days of age, which were injected with ANG-II in the first postnatal week. However, the area of cardiomyocytes and the number of nucleoli in 21-day-old rats continued to increase significantly. Our results indicate that ANG-11 modulates cardiac growth during the neonatal period via stimulation of apoptosis, cell cycle events and cellular growth of cardiomyocytes and that these effects can persist up to 15 days after injection of ANG-11 has been completed. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Far Eastern State Med Univ, Cent Res Lab, Khabarovsk, Russia. Univ Turku, Electron Microscopy Lab, SF-20500 Turku, Finland. Univ Helsinki, Dept Pediat, FIN-00014 Helsinki, Finland. Univ Turku, Dept Pediat, SF-20500 Turku, Finland. Univ Turku, Medicity Res Labs, SF-20500 Turku, Finland. RP Abdelwahid, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bldg 149,13th St, Charlestown, MA 02129 USA. EM eltyeb.abdelwahid@cbrc2.mgh.harvard.edu NR 17 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP 20 PY 2006 VL 112 IS 2 BP 219 EP 222 DI 10.1016/j.ijcard.2005.09.003 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 094YP UT WOS:000241275600013 PM 16297473 ER PT J AU Keating, NL O'Malley, AJ Smith, MR AF Keating, Nancy L. O'Malley, A. James Smith, Matthew R. TI Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HORMONE AGONIST TREATMENT; ACUTE MYOCARDIAL-INFARCTION; BONE-MINERAL DENSITY; SEER-MEDICARE DATA; QUALITY-OF-CARE; PHASE-III TRIAL; BODY-COMPOSITION; ADMINISTRATIVE DATA; ARTERIAL STIFFNESS; ADVANCED-CARCINOMA AB Purpose Androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist is associated with increased fat mass and insulin resistance in men with prostate cancer, but the risk of obesity-related disease during treatment has not been well studied. We assessed whether androgen deprivation therapy is associated with an increased incidence of diabetes and cardiovascular disease. Patients and Methods Observational study of a population-based cohort of 73,196 fee-for-service Medicare enrollees age 66 years or older who were diagnosed with locoregional prostate cancer during 1992 to 1999 and observed through 2001. We used Cox proportional hazards models to assess whether treatment with GnRH agonists or orchiectomy was associated with diabetes, coronary heart disease, myocardial infarction, and sudden cardiac death. Results More than one third of men received a GnRH agonist during follow-up. GnRH agonist use was associated with increased risk of incident diabetes (adjusted hazard ratio [HRI, 1.44; P <.001), coronary heart disease (adjusted HR, 1.16; P <.001), myocardial infarction (adjusted HR, 1.11: P =.03), and sudden cardiac death (adjusted HR, 1.16; P =.004). Men treated with orchiectomy were more likely to develop diabetes (adjusted HR, 1.34; P <.001) but not coronary heart disease, myocardial infarction, or sudden cardiac death (all P >.20). Conclusion GnRH agonist treatment for men with locoregional prostate cancer may be associated with an increased risk of incident diabetes and cardiovascular disease. The benefits of GnRH agonist treatment should be weighed against these potential risks. Additional research is needed to identify populations of men at highest risk of treatment-related complications and to develop strategies to prevent treatment-related diabetes and cardiovascular disease. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hep.med.harvard.edu FU NCI NIH HHS [P50CA90381] NR 45 TC 715 Z9 727 U1 5 U2 26 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 SEP 20 PY 2006 VL 24 IS 27 BP 4448 EP 4456 DI 10.1200/JCO.2006.06.2497 PG 9 WC Oncology SC Oncology GA 086YD UT WOS:000240708200014 PM 16983113 ER PT J AU Clark, JA Talcott, JA AF Clark, Jack A. Talcott, James A. TI Confidence and uncertainty long after initial treatment for early prostate cancer: Survivors' views of cancer control and the treatment decisions they made SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; PATIENTS PERCEPTIONS; MEN; OUTCOMES; CARCINOMA; SYMPTOMS; THERAPY AB Purpose The many years most men diagnosed with early prostate cancer live after diagnosis allow evolving assessments of their cancer control and their treatment choices, but little is known of these outcomes or the factors that influence them. Patients and Methods We surveyed an established, prospective cohort that had initiated treatment for early prostate cancer 4 to 8 years previously. We assessed perceived cancer control, quality of treatment decisions, and other domains of quality of life, along with treatment-related urinary, bowel, and sexual dysfunction. Results Most men reported high confidence in cancer control and their treatment decisions, but many reported misgivings about one or both. The diagnostic, treatment, and quality-of-life factors associated with these two outcomes were distinct. Perceived cancer control was lower among those with adverse medical factors: higher pretreatment Gleason scores, subsequent rises in prostate-specific antigen (PSA), and secondary androgen ablation therapy. Confidence in treatment decisions was unrelated to these factors and was higher in men who opted for radical prostatectomy or brachytherapy, reported close attention to current PSA, had high masculine self-esteem and little distress from sexual dysfunction, and were married. Conclusion Although perceptions of cancer control and the quality of their treatment decisions are linked, men can distinguish between these two outcomes. They incorporate objective indicators of high risk and adverse outcomes when assessing their cancer control; confidence in treatment decisions represents a more complex psychosocial adjustment to the persistent uncertainty that originates with their diagnosis. C1 Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02118 USA. Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Massachusetts Gen Hosp, Ctr Outcomes Res, MGH Canc Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Clark, JA (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Serv, 715 Albany St,T3-W, Boston, MA 02118 USA. EM jaclark@bu.edu OI Clark, Jack/0000-0002-7424-1670 NR 26 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2006 VL 24 IS 27 BP 4457 EP 4463 DI 10.1200/JCO.2006.06.2893 PG 7 WC Oncology SC Oncology GA 086YD UT WOS:000240708200015 PM 16983114 ER PT J AU Jackman, DM Holmes, AJ Lindeman, N Wen, PY Kesari, S Borras, AM Bailey, C de Jong, F Janne, PA Johnson, BE AF Jackman, David M. Holmes, Alison J. Lindeman, Neal Wen, Patrick Y. Kesari, Santosh Borras, Ana M. Bailey, Christopher de Jong, Francisca Jaenne, Pasi A. Johnson, Bruce E. TI Response and resistance in a non-small-cell lung cancer patient with an epidermal growth factor receptor mutation and leptomeningeal metastases treated with high-dose gefitinib SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TYROSINE KINASE INHIBITOR; ZD1839; IRESSA; TRIAL 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 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Transplant Res Lab, Boston, MA 02115 USA. AstraZeneca, Dept Drug Metab & Pharmacokinet, Macclesfield, Cheshire, England. Analyt Medinet BV, Breda, Netherlands. RP Jackman, DM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 FU NCI NIH HHS [1K12CA87723-01, 1R01CA114465-01, P20CA90578-02] NR 10 TC 142 Z9 153 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 20 PY 2006 VL 24 IS 27 BP 4517 EP 4520 DI 10.1200/JCO.2006.06.6126 PG 4 WC Oncology SC Oncology GA 086YD UT WOS:000240708200025 PM 16983123 ER PT J AU Darrow, KN Simons, EJ Dodds, L Liberman, MC AF Darrow, Keith N. Simons, Emmanuel J. Dodds, Leslie Liberman, M. Charles TI Dopaminergic innervation of the mouse inner ear: Evidence for a separate cytochemical group of cochlear efferent fibers SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE tyrosine hydroxylase; colocalization; hearing; feedback control; olivocochlear ID GUINEA-PIG COCHLEA; TYROSINE-HYDROXYLASE IMMUNOREACTIVITY; MEDIAL OLIVOCOCHLEAR NEURONS; ELECTRICAL-STIMULATION; ADRENERGIC INNERVATION; QUANTITATIVE-ANALYSIS; MAMMALIAN COCHLEA; SUPERIOR OLIVE; CAT COCHLEA; HAIR-CELLS AB Immunostaining mouse cochleas for tyrosine hydroxylase (TH) and dopaminep beta-hydroxylase suggests that there is a rich adrenergic innervation throughout the auditory nerve trunk and a small dopaminergic innervation of the sensory cell areas. Surgical cuts in the brainstem confirm these dopaminergic fibers as part of the olivocochlear efferent bundle. Within the sensory epithelium, TH-positive terminals are seen only in the inner hair cell area, where they intermingle with other olivocochlear terminals expressing cholinergic markers (vesicular acetylcholine transporter; VAT). Double immunostaining suggests little colocalization of TH and VAT; quantification of terminal volumes suggests that TH-positive fibers constitute only 10-20% of the efferent innervation of the inner hair cell area. Immunostaining of mouse brainstem revealed a small population of TH-positive cells in and around the lateral superior olive. Consistent with cochlear projections, double staining for the cholinergic marker acetylcholinesterase suggested that TH-positive somata are not cholinergic and vice versa. All observations are consistent with the view that a small dopaminergic subgroup of lateral olivocochlear neurons 1) projects to the inner hair cell area, 2) is distinct from the larger cholinergic group projecting there, and 3) may correspond to lateral olivocochlear "shell" neurons described by others (Warr et al. [1997] Hear. Res 108:89-111). C1 Harvard Univ, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. MIT, Cambridge, MA 02138 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM charles_liberman@meei.harvard.edu FU NIDCD NIH HHS [P30 DC05209, R01 DC 00188, R01 DC000188, P30 DC005209] NR 47 TC 40 Z9 44 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 20 PY 2006 VL 498 IS 3 BP 403 EP 414 DI 10.1002/cne.21050 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 074FB UT WOS:000239797000007 PM 16871528 ER PT J AU Lamont, EB Herndon, JE Weeks, JC Henderson, IC Earle, CC Schilsky, RL Christakis, NA AF Lamont, Elizabeth B. Herndon, James E., II Weeks, Jane C. Henderson, I. Craig Earle, Craig C. Schilsky, Richard L. Christakis, Nicholas A. CA Canc Leukemia Grp B TI Measuring disease-free survival and cancer relapse using medicare claims from CALGB breast cancer trial participants (companion to 9344) SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CHEMOTHERAPY CLAIMS; CLINICAL-TRIALS; OLDER; AGE; VALIDITY AB To determine the accuracy with which Medicare claims data measure disease-free survival in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We merged gold-standard clinical trial data of 45 elderly patients with node-positive breast cancer who were treated on the Cancer and Leukemia Group B (CALGB) adjuvant breast trial 9344 with Centers for Medicare and Medicaid Services (CMS) data files and compared the results of a CMS-based algorithm with the CALGB disease-free survival information to determine sensitivity and specificity. For 5-year disease-free survival, the sensitivity of the CMS-based algorithm was 100% (95% confidence interval [CI] = 81% to 100%), the specificity was 97% (95% CI = 83% to 100%), and the area under the receiver operator curve was 97% (95% CI = 90% to 100%). For 2-year disease-free survival, the test characteristics were less favorable: sensitivity was 83% (95% CI = 36% to 100%), specificity was 95% (95% CI = 83% to 100%), and area under the receiver operator curve was 84% (95% CI = 66% to 100%). C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Duke Univ, Med Ctr, Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Chicago, Canc & Leukemia Grp B Cent Off, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Lamont, EB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 A Longwood Ave, Boston, MA 02115 USA. EM lamont@hcp.med.harvard.edu RI Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 FU NCI NIH HHS [CA47545, CA02599, CA03927, CA04326, CA04457, CA07968, CA08025, CA11028, CA11789, CA12046, CA12449, CA16450, CA21060, CA25224, CA26806, CA31946, CA31983, CA32291, CA33601, CA35091, CA35279, CA35421, CA37135, CA41287, CA45374, CA45389, CA45418, CA45564, CA45808, CA47555, CA47559, CA47577, CA47642, CA52784, CA54697, CA60138, CA60247, CA74811, CA77298, CA77406, CA77440, CA93892, K07 CA093892, U10 CA003927, U10 CA025224, U10 CA031946, U10 CA032291, U10 CA033601, U10 CA035091, U10 CA035279, U10 CA035421, U10 CA041287, U10 CA045389, U10 CA045418, U10 CA045564, U10 CA045808, U10 CA047559, U10 CA047577, U10 CA047642, U10 CA052784, U10 CA071323, U10 CA074811, U10 CA077440] NR 13 TC 37 Z9 37 U1 0 U2 2 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 SEP 20 PY 2006 VL 98 IS 18 BP 1335 EP 1338 DI 10.1093/jnci/djj363 PG 4 WC Oncology SC Oncology GA 101EG UT WOS:000241721100014 PM 16985253 ER PT J AU Walensky, RP Paltiel, AD AF Walensky, Rochelle P. Paltiel, A. David TI Rapid HIV testing at home: Does it solve a problem or create one? SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID INFECTION; COLLECTION AB The U.S. Food and Drug Administration (FDA) is considering approval of an over-the-counter, rapid HIV test for home use. To date, testimony presented before the FDA has been overwhelmingly supportive. Advocates have argued enthusiastically that there is value in empowering individuals to manage their HIV risks and have suggested that the availability of a rapid home HIV test will dramatically increase rates of disease detection in communities that have proven difficult to reach and to link to appropriate care. The authors offer a more cautious perspective. According to what is already known about the market demand for over-the-counter HIV testing kits, their costs, and the performance of rapid HIV tests in that market, the authors do not anticipate that the rapid home test will have a profound impact either on the HIV public health crisis or on the populations in greatest need. Home HIV testing will attract a predominantly affluent clientele, composed disproportionately of HIV-uninfected new couples and "worried well" persons, as well as very recently infected persons with undetectable disease. The authors illustrate how testing in these populations may have the perverse effect of increasing both false-positive and false-negative results. A poorly functioning home HIV test may thereby undermine confidence in the reliability of HIV testing more generally and weaken critical efforts to expand HIV detection and linkage to lifesaving care for the estimated 300 000 U.S. citizens with unidentified HIV infection. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA 02115 USA. Yale Univ, Sch Med, New Haven, CT USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org FU NIAID NIH HHS [K23 AI01794, K23 AI001794, P30 AI060354, R01 AI042006, R01 AI42006]; NIDA NIH HHS [R01 DA015612]; NIMH NIH HHS [R01 MH065869, R01 MH65869] NR 25 TC 38 Z9 38 U1 2 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 19 PY 2006 VL 145 IS 6 BP 459 EP 462 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 087OU UT WOS:000240752500008 PM 16983134 ER PT J AU Potetinova, Z Barbier, JR Suen, T Dean, T Gardella, TJ Willick, GE AF Potetinova, Zhanna Barbier, Jean-Rene Suen, Tanya Dean, Thomas Gardella, Thomas J. Willick, Gordon E. TI C-terminal analogues of parathyroid hormone: Effect of C-terminus function on helical structure, stability, and bioactivity SO BIOCHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; SERINE CARBOXYPEPTIDASE-Y; RECEPTOR-BINDING REGION; BIOLOGICAL-ACTIVITY; ADENYLYL-CYCLASE; STIMULATING ACTIVITIES; CONSTRAINED ANALOGS; BONE-GROWTH; PEPTIDE; PROTEIN AB We have studied the effects of C-terminal group modifications (amide, methylamide, dimethylamide, aldehyde, and alcohol) on the conformation, adenylyl cyclase stimulation (AC), or binding of parathyroid hormone (hPTH) analogues, hPTH(1-28)NH2 and hPTH(1-31)NH2. hPTH(1-31)NH2 has a C-terminal alpha-helix bounded by residues 17-29 [Chen, Z., et al. (2000) Biochemistry 39, 12766]. In both cases, relative to the natural analogue with a carboxyl C-terminus, the amide and methylamide had increased helix content whereas the dimethylamide forms had CD spectra more similar to the carboxyl one. Conformational effects were more pronounced with hPTH(1-28) than with hPTH(1-31), with increases in helix content of similar to 30% in contrast to 10%. Stabilization of the C-terminal helix of residues 1-28 seemed to correlate with an ability of the C-terminal function to H-bond appropriately. None of the analogues affected the AC stimulating activity significantly, but there was an up to 15-fold decrease in the level of apparent binding of the carboxyl hPTH(1-28) analogue compared to that of the methylamide and a 4-fold decrease in the level of binding of the aldehyde or dimethylamide. There was no significant change in binding activities for the 1-31 analogues. These observations are consistent with previous studies that imply the importance of a region of the hormone's C-terminal alpha-helix for tight binding to the receptor. They also show that modulation of helix stability does have an effect on the binding of the hormone, but only when the C-terminus is at the putative end of the helix. The similarity of AC stimulation even when binding changed 10-fold can be explained by assuming greater efficacy of the weaker binding PTH-receptor complexes in stimulating AC. C1 Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Willick, GE (reprint author), Natl Res Council Canada, Inst Biol Sci, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada. EM gordon.willick@nrc.ca NR 50 TC 8 Z9 8 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 SEP 19 PY 2006 VL 45 IS 37 BP 11113 EP 11121 DI 10.1021/bi060500q PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 083DT UT WOS:000240436800008 PM 16964972 ER PT J AU Han, JW Lim, CJ Watanabe, N Soriani, A Ratnikov, B Calderwood, DA Puzon-McLaughlin, W Lafuente, EM Boussiotis, VA Shattil, SJ Ginsberg, MH AF Han, Jaewon Lim, Chinten James Watanabe, Naohide Soriani, Alessandra Ratnikov, Boris Calderwood, David A. Puzon-McLaughlin, Wilma Lafuente, Esther M. Boussiotis, Vassiliki A. Shattil, Sanford J. Ginsberg, Mark H. TI Reconstructing and deconstructing agonist-induced activation of integrin alpha IIb beta 3 SO CURRENT BIOLOGY LA English DT Article ID MEDIATES RAP1-INDUCED ADHESION; PROTEIN-KINASE-C; AFFINITY MODULATION; CYTOPLASMIC DOMAIN; HUMAN-PLATELETS; LIGAND-BINDING; PLAQUE PROTEIN; TALIN BINDING; RAP1; ALPHA(IIB)BETA(3) AB Background: Integrin receptors, composed of transmembrane alpha and beta subunits, are essential for the development and functioning of multicellular animals. Agonist stimulation leads cells to regulate integrin affinity ("activation"), thus controlling cell adhesion and migration, controlling extracellular-matrix assembly, and contributing to angiogenesis, tumor cell metastasis, inflammation, the immune response, and hemostasis. A final step in integrin activation is the binding of talin, a cytoskeletal protein, to integrin beta cytoplasmic domains. Many different signaling molecules that regulate integrin affinity have been described, but a pathway that connects agonist stimulation to talin binding and activation has not been mapped. Results: We used forward, reverse, and synthetic genetics to engineer and order an integrin activation pathway in cells expressing a prototype activatable integrin, platelet alpha IIb beta 3. Phorbol myristate acetate (PMA) activated alpha IIb beta 3 only after the increased expression of both recombinant protein kinase C alpha (PKC alpha) and talin to levels approximating those in platelets. Inhibition of Rap1 GTPase reduced alpha IIb beta 3 activation, whereas activated Rap1A(G12V) bypassed the requirement for PKC, establishing that Rap1 is downstream of PKC. Talin binding to integrins mediates Rap1-induced activation because Rap1A(G12V) failed to activate alpha IIb beta 3 in cells expressing integrin binding-defective talin (W359A). Rap1 activated integrins by forming an integrin-associated complex containing talin in combination with the Rap effector, RIAM. Furthermore, siRNA-mediated knockdown of RIAM blocked integrin activation. Conclusions: We have, for the first time, ordered a pathway from agonist stimulation to integrin activation and established the Rap1-induced formation of an "integrin activation complex," containing RIAM and talin, that binds to and activates the integrin. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Ginsberg, MH (reprint author), Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. EM mhginsberg@ucsd.edu RI Lafuente, Esther M/K-5684-2014; Lim, Chinten James/G-3777-2013; OI Lafuente, Esther M/0000-0001-8466-1022; Lim, Chinten James/0000-0001-6381-7585; SORIANI, Alessandra/0000-0001-5461-9026 FU NIGMS NIH HHS [U54GM064346] NR 39 TC 274 Z9 282 U1 4 U2 21 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 19 PY 2006 VL 16 IS 18 BP 1796 EP 1806 DI 10.1016/j.cub.2006.08.035 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087CK UT WOS:000240719800023 PM 16979556 ER PT J AU van Kimmenade, RR Januzzi, JL Ellinor, PT Sharma, UC Bakker, JA Low, AF Martinez, A Crijns, HJ MacRae, CA Menheere, PP Pinto, YM AF van Kimmenade, Roland R. Januzzi, James L., Jr. Ellinor, Patrick T. Sharma, Umesh C. Bakker, Jaap A. Low, Adrian F. Martinez, Abelardo Crijns, Harry J. MacRae, Calum A. Menheere, Paul P. Pinto, Yigal M. TI Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIAC TROPONIN-T; NECROSIS-FACTOR-ALPHA; ORPHAN RECEPTOR APJ; MYOCARDIAL-INFARCTION; CIRCULATING LEVELS; ENDOGENOUS LIGAND; LIFETIME RISK; PROGNOSIS; DISEASE; IDENTIFICATION AB OBJECTIVES This study sought to explore the role of new biomarkers in heart failure (HF). BACKGROUND We investigated the utility of novel serum markers alone or together with natriuretic peptide testing for diagnosis and short-term prognosis estimation in subjects with acute HF. METHODS Plasma levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), apelin, and galectin-3 were measured in 599 patients presenting with dyspnea at the emergency department, of which 209 (35%) had acute HF. RESULTS The NT-proBNP was superior to either apelin or galectin-3 for diagnosis of acute HF, although galectin-3 levels were significantly higher in subjects with HF compared with those without. Receiver operating characteristic analysis for mortality prediction showed that, for 60-day prognosis, galectin-3 had the greatest area under the curve (AUC) at 0.74 (p = 0.0001), whereas NT-proBNP and apelin had an AUC of 0.67 (p = 0.009) and 0.54 (p = 0.33). In a multivariate logistic regression analysis, an elevated level of galectin-3 was the best independent predictor of 60-day mortality (odds ratio 10.3, p < 0.01) or the combination of death/recurrent HF within 60 days (odds ratio 14.3, p < 0.001). The Kaplan-Meier analyses showed that the combination of an elevated galectin-3 with NT-proBNP was a better predictor of mortality than either of the 2 markers alone. CONCLUSIONS Our data show potential utility of galectin-3 as a useful marker for evaluation of patients with suspected or proven acute HF, whereas apelin measurement was not usefill for these indications. Moreover, the combination of galectin-3 with NT-proBNP was the best predictor for prognosis in subjects with acute HF. C1 Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Hosp Maastricht, Dept Clin Chem, Maastricht, Netherlands. RP Pinto, YM (reprint author), Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. EM y.pinto@cardio.azm.nl RI Kimmenade, R.R.J./L-4432-2015; OI Bakker, Jaap A./0000-0002-2918-7361 FU NHLBI NIH HHS [R01 HL075431] NR 43 TC 234 Z9 239 U1 1 U2 10 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 SEP 19 PY 2006 VL 48 IS 6 BP 1217 EP 1224 DI 10.1016/j.jacc.2006.03.061 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086VQ UT WOS:000240701500018 PM 16979009 ER PT J AU Goldberger, JJ Subacius, H Schaechter, A Howard, A Berger, R Shalaby, A Levine, J Kadish, AH AF Goldberger, Jeffrey J. Subacius, Haris Schaechter, Andi Howard, Adam Berger, Ronald Shalaby, Alaa Levine, Joseph Kadish, Alan H. CA DEFINITE Investigators TI Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; CORONARY-ARTERY-DISEASE; LIPID-LOWERING DRUGS; HEART-FAILURE; ATRIAL-FIBRILLATION; INFLAMMATION; CHOLESTEROL; DEATH; MORTALITY; MARKERS AB OBJECTIVES We sought to evaluate whether statins were associated with a survival benefit and significant attenuation in life-threatening arrhythmias in patients with nonischemic dilated cardiomyopathy. BACKGROUND Statins are associated with a reduction in appropriate implantable cardioverter-defibriflator (ICD) therapy in patients with coronary artery disease and improved clinical status in nonischemic dilated cardiomyopathy. METHODS The effect of statin use on time to death or resuscitated cardiac arrest and time to arrhythmic sudden death was evaluated in 458 patients enrolled in the DEFINITE (DEFIbrillators in Non-Ischemic cardiomyopathy Treatment Evaluation) study. The effect of statin use on time to first appropriate shock was analyzed only in the 229 patients who were randomized to ICD therapy. RESULTS The unadjusted hazard ratio (HR) for death among patients on versus those not on statin therapy was 0.22 (95% confidence interval [CII 0.09 to 0.55; p = 0.001). When controlled for statin effects, ICD therapy was associated with improved survival (HR 0.61; 95% CI 0.38 to 0.99; p = 0.04). There was one arrhythmic sudden death in the 110 patients receiving statin therapy (0.9%) versus 18 of 348 patients not receiving statins (5.2%; p = 0.04). The unadjusted HR for arrhythmic sudden death among patients on versus those not on statin therapy was 0.16 (95% CI 0.022 to 1.21; p = 0.08). The HR for appropriate shocks among patients on versus those not on statin therapy was 0.78 (95% CI 0.34 to 1.82) after adjustment for baseline differences in the two groups. CONCLUSIONS Statin use in the DEFINITE study was associated with a 78% reduction in mortality. This reduction was caused, in part, by a reduction in arrhythmic sudden death. These findings should be confirmed in a prospective, randomized clinical trial. C1 Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. NW Mem Hosp, Bluhm Cardiovasc Inst, Clin Trials Unit, Chicago, IL 60611 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. St Francis Hosp, Ctr Heart, Roslyn, NY USA. RP Goldberger, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, 251 E Huron,Feinberg Pavil 8-542, Chicago, IL 60611 USA. EM j-goldberger@northwestern.edu OI Subacius, Haris/0000-0003-4061-1220 NR 21 TC 71 Z9 77 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 SEP 19 PY 2006 VL 48 IS 6 BP 1228 EP 1233 DI 10.1016/j.jacc.2006.05.053 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086VQ UT WOS:000240701500020 PM 16979011 ER PT J AU Shimaoka, M Kim, M Cohen, EH Yang, W Astrof, N Peer, D Salas, A Ferrand, A Springer, TA AF Shimaoka, Motomu Kim, Minsoo Cohen, Edward H. Yang, Wei Astrof, Nathan Peer, Dan Salas, Azucena Ferrand, Audrey Springer, Timothy A. TI AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE conformational changes; activation; cell adhesion; phage display ID FUNCTION-ASSOCIATED ANTIGEN-1; CELL-CELL INTERACTIONS; I-LIKE DOMAIN; VASCULAR ENDOTHELIUM; PLAQUE PSORIASIS; STRUCTURAL BASIS; DISULFIDE BOND; ADHESION; ACTIVATION; FLOW AB Affinity of integrin lymphocyte function-associated antigen 1 (LFA-1) is enhanced by conformational changes from the low-affinity closed form to the high-affinity (HA) open form of the ligand-binding inserted (1) domain as shown by work with purified I domains. However, affinity up-regulation of LFA-1 on the cell surface by physiological agonists such as chemokines has yet to be demonstrated by monovalent reagents. We characterize a mAb, AL-57 (activated LFA-1 clone 57), that has been developed by phage display that selectively targets the HA open conformation of the LFA-1 I domain. AL-57 discriminates among low-affinity, intermediate-affinity, and HA states of LFA-1. Furthermore, AL-57 functions as a ligand mimetic that binds only upon activation and requires Mg2+ for binding. Compared with the natural ligand intercellular adhesion molecule-1, AL-57 shows a tighter binding to the open I domain and a 250-fold slower off rate. Monovalent Fab AL-57 demonstrates affinity increases on a subset (approximate to 10%) of lymphocyte cell surface LFA-1 molecules upon stimulation with CXCL-12 (CXC chemokine ligand 12). Affinity up-regulation correlates with global conformational changes of LFA-1 to the extended form. Affinity increase stimulated by CXCL-12 is transient and peaks 2 to 5 min after stimulation. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brown Univ, Sch Med, Providence, RI 02903 USA. Rhode Isl Hosp, Div Surg Res, Providence, RI 02903 USA. Dyax, Cambridge, MA 02139 USA. RP Shimaoka, M (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM shimaoka@cbrinstitute.org; springeroffice@cbrinstitute.org RI Peer, Dan/A-1785-2011; OI Peer, Dan/0000-0001-8238-0673; Salas, Azucena/0000-0003-4572-2907 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798]; NIAID NIH HHS [R01 AI063421, AI063421] NR 52 TC 40 Z9 41 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 19 PY 2006 VL 103 IS 38 BP 13991 EP 13996 DI 10.1073/pnas.0605716103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 087MN UT WOS:000240746600018 PM 16963559 ER EF