FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sims, KB Pastores, GM Weinreb, NJ Barranger, J Rosenbloom, BE Packman, S Kaplan, P Mankin, H Xavier, R Angell, J Fitzpatrick, MA Rosenthal, D AF Sims, K. B. Pastores, G. M. Weinreb, N. J. Barranger, J. Rosenbloom, B. E. Packman, S. Kaplan, P. Mankin, H. Xavier, R. Angell, J. Fitzpatrick, M. A. Rosenthal, D. TI Improvement of bone disease by imiglucerase (Cerezyme) therapy in patients with skeletal manifestations of type 1 Gaucher disease: results of a 48-month longitudinal cohort study SO CLINICAL GENETICS LA English DT Article ID ENZYME REPLACEMENT THERAPY; QUALITY-OF-LIFE; MINERAL DENSITY; GLUCOCEREBROSIDASE; OSTEOPOROSIS; EFFICACY; REGISTRY; ADULTS; BMD AB Progressive skeletal disease accounts for some of the most debilitating complications of type 1 Gaucher disease. In this 48-month, prospective, non-randomized, open-label study of the effect of enzyme replacement therapy on bone response, 33 imiglucerase-naive patients (median age 43 years with one or more skeletal manifestations such as osteopenia, history of bone crisis, or other documented bone pathology) received imiglucerase 60 U/kg/2 weeks. Substantial improvements were observed in bone pain (BP), bone crises (BC), and bone mineral density (BMD). Improvements in BP were observed at 3 months (p < 0.001 vs baseline) and continued progressively throughout the study, with 39% of patients reporting pain at 48 months vs 73% at baseline. Eleven of the 13 patients with a pre-treatment history of BC had no recurrences. Biochemical markers for bone formation increased; markers for bone resorption decreased. Steady improvement of spine and femoral neck BMD, measured using dual-energy X-ray absorptiometry was noted. Mean Z score for spine increased from -0.72 +/- 1.302 at baseline to near-normal levels (-0.09 +/- 1.503) by month 48 (p = 0.042) and for femoral neck from -0.59 +/- 1.352 to -0.17 +/- 1.206 (p = 0.035) at month 36. This increase was sustained at 48 months. With imiglucerase treatment, patients should anticipate resolution of BC, rapid improvement in BP, increases in BMD, and decreased skeletal complications. C1 [Sims, K. B.; Mankin, H.; Xavier, R.; Rosenthal, D.] Massachusetts Gen Hosp, Neurogenet Lab, Dept Neurol, Boston, MA 02114 USA. [Pastores, G. M.] NYU, Dept Neurol, New York, NY 10016 USA. [Weinreb, N. J.] Univ Res Fdn Lysosomal Storage Dis Inc, Coral Springs, FL USA. [Barranger, J.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Rosenbloom, B. E.] Tower Hematol Oncol Med Grp, Beverly Hills, CA USA. [Packman, S.] Univ Calif San Francisco, Dept Pediat Genet, San Francisco, CA 94143 USA. [Kaplan, P.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Angell, J.; Fitzpatrick, M. A.] Genzyme Corp, Cambridge, MA USA. RP Sims, KB (reprint author), Massachusetts Gen Hosp, Neurogenet Lab, Dept Neurol, Simches Res Bldg 5-238,185 Cambridge St, Boston, MA 02114 USA. EM ksims@partners.org FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-13] NR 25 TC 64 Z9 65 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAY PY 2008 VL 73 IS 5 BP 430 EP 440 DI 10.1111/j.1399-0004.2008.00978.x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 285PN UT WOS:000254788800006 PM 18312448 ER PT J AU Yeh, H Markmann, JF AF Yeh, Heidi Markmann, James F. TI Tolerance: It's in your blood SO CLINICAL IMMUNOLOGY LA English DT Editorial Material ID TRANSPLANTATION TOLERANCE; RENAL-TRANSPLANTATION; ALLOGRAFT TOLERANCE; CHIMERISM C1 [Markmann, James F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplantat,Clin Director, Boston, MA 02115 USA. RP Markmann, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplantat,Clin Director, Boston, MA 02115 USA. EM jmarkmann@partners.org NR 6 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2008 VL 127 IS 2 BP 121 EP 122 DI 10.1016/j.clim.2008.02.004 PG 2 WC Immunology SC Immunology GA 291XQ UT WOS:000255231100002 PM 18405862 ER PT J AU Ma, ZJ Choudhury, A Kang, SA Monestier, M Cohen, PL Eisenberg, RA AF Ma, Zhongjie Choudhury, Arpita Kang, Sun-Ah Monestier, Marc Cohen, Philip L. Eisenberg, Robert A. TI Accelerated atherosclerosis in ApoE deficient lupus mouse models SO CLINICAL IMMUNOLOGY LA English DT Article DE autoimmunity; atherosclerosis; apolipoprotein E; graft versus host disease; lpr; systemic lupus erythematosus ID LOW-DENSITY-LIPOPROTEIN; GRAFT-VERSUS-HOST; DNA B-CELLS; AUTOIMMUNE-DISEASE; APOPTOTIC CELLS; ANTIPHOSPHOLIPID ANTIBODIES; IMPAIRED CLEARANCE; IMMUNE-RESPONSES; FAS LIGAND; T-CELLS AB The accelerated development of atherosclerosis with increased risk of cardiovascular disease in systemic lupus erythematosus (SLE) patients is not well understood. An appropriate mouse model would greatly help to understand the mechanisms of this association. We have therefore combined the ApoE(-/-) model of atherosclerosis with three different murine models of SLE. We found that induction of cGVH in B6.ApoE(-/-) mice, breeding a Fas null gene onto the B6.ApoE(-/-) mice, and breeding the ApoE(-/-) defect onto MRL/lpr mice all caused a modest increase of atherosclerosis at 24 weeks of age compared to B6.ApoE(-/-) controls. B cells in B6.ApoE(-/-) mice had certain phenotypic differences compared to congenic C57BL/6 mice, as indicated by high expression of MHC II, Fas, CD86, and by increased number of cells bearing marginal zone phenotype. Furthermore, B6ApoE(-/-) mice had significant titers of anti-oxLDL and anti-cardiolipin autoantibodies compared to their B6 counterparts. Our studies also indicate that, following induction of cGVH, marginal zone B cells in B6.ApoE(-/-) are depleted, and there is considerable increase in anti-oxLDL and anti-cardiolipin abs along with secretion of lupus-specific autoantibodies, such as anti-dsDNA and anti-chromatin abs. Histological sections showed that cGVH and/or Fas deficiency could exacerbate atherosclerosis. The production of anti-oxLDL and anti-cardiolipin in ApoE(-/-) mice was also increased. These observations define a connection between induction of lupus-like symptoms and development of severe atherosclerosis in ApoE deficient lupus mouse models. (C) 2008 Elsevier Inc. All rights reserved. C1 [Ma, Zhongjie; Choudhury, Arpita; Cohen, Philip L.; Eisenberg, Robert A.] Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Kang, Sun-Ah; Monestier, Marc] Temple Univ, Sch Med, Dept Immunol & Microbiol, Philadelphia, PA 19104 USA. [Cohen, Philip L.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Eisenberg, RA (reprint author), Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. EM raemd@mail.med.upenn.edu OI Kang, SunAh/0000-0002-6327-184X FU NIAID NIH HHS [U19-AI-46358, R01 AI063626, R01 AI063626-22A1, R01 AI063626-23, R01 AI063626-24, R01 AI063626-25, R01-AI063626, U19 AI046358]; NIAMS NIH HHS [R01 AR034156, R01 AR034156-18, R01 AR034156-19, R01 AR034156-20, R01 AR034156-21, R01 AR034156-22A1, R01-AR-34156]; NIDDK NIH HHS [R01 DK053088, R01-DK53088] NR 45 TC 28 Z9 29 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2008 VL 127 IS 2 BP 168 EP 175 DI 10.1016/j.clim.2008.01.002 PG 8 WC Immunology SC Immunology GA 291XQ UT WOS:000255231100009 PM 18325838 ER PT J AU Galanti, G Rostagno, C Stefani, L Toncelli, L Gianassi, M Rapisarda, F Rossi, A Stefano, PL Wood, M AF Galanti, Giorgio Rostagno, Carlo Stefani, Laura Toncelli, Loira Gianassi, Marco Rapisarda, Fabio Rossi, Alessandra Stefano, Pier Luigi Wood, Malissa TI Right ventricular myxoma detected incidentally in a young athlete SO CLINICAL JOURNAL OF SPORT MEDICINE LA English DT Article C1 [Galanti, Giorgio; Stefani, Laura; Toncelli, Loira; Gianassi, Marco; Rapisarda, Fabio; Rossi, Alessandra; Stefano, Pier Luigi] AOU Careggi, Post Grad Sch Sport Med, I-50134 Florence, Italy. [Rostagno, Carlo] Univ Florence, Florence, Italy. [Wood, Malissa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Noninvas Cardiac Lab, Boston, MA USA. RP Rostagno, C (reprint author), AOU Careggi, Post Grad Sch Sport Med, I-50134 Florence, Italy. EM crostagno@katamail.com OI GALANTI, Giorgio/0000-0002-2054-8650; TONCELLI, Loira/0000-0002-7043-6710 NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1050-642X J9 CLIN J SPORT MED JI Clin. J. Sport Med. PD MAY PY 2008 VL 18 IS 3 BP 295 EP 297 PG 3 WC Orthopedics; Physiology; Sport Sciences SC Orthopedics; Physiology; Sport Sciences GA 298SG UT WOS:000255706800015 PM 18469576 ER PT J AU Rosolowsky, ET Ficociello, LH Maselli, NJ Niewczas, MA Binns, AL Roshan, B Warram, JH Krolewski, AS AF Rosolowsky, Elizabeth T. Ficociello, Linda H. Maselli, Nicholas J. Niewczas, Monika A. Binns, Amanda L. Roshan, Bijan Warram, James H. Krolewski, Andrzej S. TI High-normal serum uric acid is associated with impaired glomerular filtration rate in nonproteinuric patients with type 1 diabetes SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID URINARY ALBUMIN EXCRETION; RENAL-DISEASE; CYSTATIN-C; BLOOD-PRESSURE; MICROALBUMINURIA; HYPERURICEMIA; PROGRESSION; MELLITUS; HYPERTENSION; KIDNEY AB Background and objectives: Early renal function decline begins before the onset of proteinuria in patients with type 1 diabetes. The association of elevated serum uric acid with advanced impaired renal function prompts an examination of its role in early renal function decline in patients before proteinuria develops. Design, setting, participants, & measurements: Patients with type 1 diabetes and normoalbuminuria or microalbuminuria were recruited to the Second Joslin Kidney Study. A medical history and measurements of BP, hemoglobin A1c, albumin excretion rate, and serum concentrations of uric acid and cystatin C were obtained. Estimated glomerular filtration rate was measured by a cystatin C-based formula. Results: We studied 364 patients with normoalbuminuria and 311 patients with microalbuminuria. Mean glomerular filtration rate in these groups was 119 and 99 ml/min, respectively. Mildly or moderately impaired renal function (<90 ml/min) was present in 10% of those with normoalbuminuria and 36% of those with microalbuminuria. In univariate and multivariate analyses, lower glomerular filtration rate was strongly and independently associated with higher serum uric acid and higher urinary albumin excretion rate, older age, and antihypertensive treatment. Conclusions: Serum uric acid concentration in the high-normal range is associated with impaired renal function in patients with type 1 diabetes. Follow-up studies are needed to confirm that this level of serum uric acid is a risk factor for early renal function decline in type 1 diabetes and to determine whether its reduction would prevent the decline. C1 [Rosolowsky, Elizabeth T.; Ficociello, Linda H.; Maselli, Nicholas J.; Niewczas, Monika A.; Binns, Amanda L.; Roshan, Bijan; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Rosolowsky, Elizabeth T.] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA. [Niewczas, Monika A.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM Andrzej.Krolewski@joslin.harvard.edu FU AHRQ HHS [T32 HS00063, T32 HS000063]; NIDDK NIH HHS [DK41526, R01 DK041526] NR 43 TC 76 Z9 80 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAY PY 2008 VL 3 IS 3 BP 706 EP 713 DI 10.2215/CJN.04271007 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 294CS UT WOS:000255382300010 PM 18272826 ER PT J AU George, S Kasimis, BS Cogswell, J Schwarzenberger, P Shapiro, GI Fidias, P Bukowski, RM AF George, Saby Kasimis, Basil S. Cogswell, Janet Schwarzenberger, Paul Shapiro, Geoffrey I. Fidias, Panos Bukowski, Ronald M. TI Phase I study of flavopiridol in combination with paclitaxel and carboplatin in patients with non-small-cell lung cancer SO CLINICAL LUNG CANCER LA English DT Article DE asthenia; cardiac toxicity; CDK inhibitors; cyclin D1 ID DEPENDENT KINASE INHIBITOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; BREAST-CARCINOMA CELLS; ONCOLOGY-GROUP TRIAL; PLUS CARBOPLATIN; CYCLE ARREST; III TRIAL; P-TEFB; CISPLATIN; APOPTOSIS AB PURPOSE: The aim of this study was to evaluate the safety and tolerability of escalating doses of flavopiridol/paclitaxel/carboplatin in patients with advanced-stage non-small-cell lung cancer (NSCLC) as well as the pharmacokinetics and activity of flavopiridol when used in combination with paclitaxel/carboplatin. PATIENTS AND METHODS: Eligible patients aged 18-75 years with previously untreated stage IIIB/IV NSCLC received paclitaxel 175 mg/m(2) over 3 hours followed by carboplatin area under the curve (AUC) 5 over I hour and flavopiridol 30-85 mg/m(2) over 24 hours every 3 weeks for 3 cycles. RESULTS: Eighteen patients were enrolled at 4 sites in the United States and received flavopiridol 30 mg/m(2) (n = 3), 50 mg/m(2) (n = 6), 70 mg/m(2) (n = 3), or 85 mg/m(2) (n = 6). No dose-limiting toxicities (DLTs) occurred at the 50-mg/m(2) or 70-mg/m(2) dose levels. Two patients treated at the 85-mg/m(2) dose level experienced cardiovascular events that did not meet the criteria for DLT but were fatal in 1 case, prompting no further flavopiridol dose escalations and establishment of 70 mg/m(2) as the maximum tolerated dose. The most frequently reported adverse events across all dose levels combined were nausea (89%), asthenia (67%), and diarrhea (56%). Flavopirldol concentrations increased rapidly, reached a plateau, and showed a multiphasic decline after the 24-hour infusion. Of 12 patients evaluable for efficacy, 8 achieved a partial response, and 4 had stable disease. CONCLUSION: Flavopirldol in doses <= 70 mg/m(2) in a 24-hour infusion can safely be combined with a 3-hour infusion of paclitaxel 175 mg/m(2) and a 1-hour infusion of carboplatin AUC 5. C1 [George, Saby; Bukowski, Ronald M.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Schwarzenberger, Paul] So Canc Ctr, Mobile, AL USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA USA. [Fidias, Panos] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP George, S (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave,Desk R35, Cleveland, OH 44195 USA. EM georges2@ccf.org OI George, Saby/0000-0002-0444-5870 NR 32 TC 29 Z9 31 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD MAY PY 2008 VL 9 IS 3 BP 160 EP 165 DI 10.3816/CLC.2008.n.024 PG 6 WC Oncology SC Oncology GA 306BB UT WOS:000256220700005 PM 18621626 ER PT J AU Schneider, H Cristian, A AF Schneider, Hyon Cristian, Adrian TI Role of rehabilitation medicine in the management of pain in older adults SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID MUSCULOSKELETAL PAIN; EXERCISE; KNEE; BALANCE; PREVALENCE; THERAPIES; RESIDENTS; ARTHRITIS; ORTHOSES; EFFICACY AB Pain management may play an important role in contributing to optimal quality of life in the elderly population. Pain lowers overall quality of life in part by decreasing function and by amplifying the psychologicic stress of aging. A comprehensive, multidisciplinary approach to pain management, with preservation and restoration of function in older adults, is the cornerstone of an effective pain management program. C1 [Cristian, Adrian] James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Bronx, NY 10468 USA. [Schneider, Hyon] Mt Sinai Med Ctr, Dept Rehabil Med, New York, NY 10029 USA. [Cristian, Adrian] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Cristian, A (reprint author), James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Room 3D-16,526-117,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM adrian.cristian@va.gov NR 56 TC 3 Z9 4 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 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2008 VL 24 IS 2 BP 313 EP + DI 10.1016/j.cger.2007.12.003 PG 23 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 295KE UT WOS:000255472600009 PM 18387458 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI Major depressive disorder: Epidemiology, course of illness, and treatment SO CNS SPECTRUMS LA English DT Article ID STAR-ASTERISK-D; NATIONAL COMORBIDITY SURVEY; FAILED MEDICATION TREATMENTS; PREVALENCE; FAILURE; AUGMENTATION; POLYMORPHISM; MIRTAZAPINE; RECURRENCE; AMYGDALA C1 [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Harvard Med Sch, Boston, MA USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. NR 27 TC 1 Z9 1 U1 0 U2 2 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAY PY 2008 VL 13 IS 5 SU 8 BP 4 EP 7 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 306JB UT WOS:000256243000001 PM 18496482 ER PT J AU Wilens, TE AF Wilens, Timothy E. TI Pharmacotherapy of ADHD in adults SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EXTENDED-RELEASE; CONTROLLED-TRIAL C1 [Wilens, Timothy E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Wilens, Timothy E.] Massachusetts Gen Hosp, Subst Abuse Serv, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. NR 10 TC 13 Z9 13 U1 0 U2 2 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAY PY 2008 VL 13 IS 5 SU 8 BP 11 EP 13 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 306JB UT WOS:000256243000003 PM 18567133 ER PT J AU Spencer, TJ AF Spencer, Thomas J. TI Treatment of adult ADHD and comorbid depression SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; OPEN TRIAL; ADOLESCENTS; BUPROPION; CHILDREN; METHYLPHENIDATE; BEHAVIOR C1 [Spencer, Thomas J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Spencer, Thomas J.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 19 TC 2 Z9 2 U1 2 U2 4 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAY PY 2008 VL 13 IS 5 SU 8 BP 14 EP 16 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 306JB UT WOS:000256243000004 PM 18567134 ER PT J AU DeGaetano, N Yehuda, R AF DeGaetano, Noah Yehuda, Rachel TI Diagnosing PTSD: Does it help us heal? SO CNS SPECTRUMS LA English DT Article C1 [DeGaetano, Noah; Yehuda, Rachel] Mt Sinai Sch Med, Traumat Stress Studies Div, New York, NY 10029 USA. [Yehuda, Rachel] James J Peters Vet Affairs, PTSD Program, Bronx, NY USA. RP DeGaetano, N (reprint author), Mt Sinai Sch Med, Traumat Stress Studies Div, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAY PY 2008 VL 13 IS 5 BP 385 EP 392 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 305MS UT WOS:000256183100009 PM 18496476 ER PT J AU Sevick, MA Zickmund, S Korytkowski, M Piraino, B Sereika, S Mihalko, S Snetselaar, L Stumbo, P Hausmann, L Ren, DX Marsh, R Sakraida, T Gibson, J Safaien, M Starrett, TJ Burke, LE AF Sevick, Mary Ann Zickmund, Susan Korytkowski, Mary Piraino, Beth Sereika, Susan Mihalko, Shannon Snetselaar, Linda Stumbo, Phyllis Hausmann, Leslie Ren, Dianxu Marsh, Rita Sakraida, Teresa Gibson, Jolynn Safaien, Mehry Starrett, Terry J. Burke, Lora E. TI Design, feasibility, and acceptability of an intervention using personal digital assistant-based self-monitoring in managing type 2 diabetes SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE diabetes mellitus; type 2; self care; computers; handheld; personal digital assistant; randomized clinical trial; behavioral research; adherence ID QUALITY-OF-LIFE; OLDER ADULTS; HAND-HELD; QUESTIONNAIRE; OUTCOMES; DIARIES AB Background: The information processing demands associated with behavioral self-management of diabetes are extensive. Pairing personal digital assistant (PDA)-based self-monitoring with a behavioral self-management intervention may improve adherence and patient outcomes. Methods: ENHANCE is a randomized controlled trial to test an intervention designed to improve regimen adherence in adults with type 2 diabetes. The intervention, based on Social Cognitive Theory (SCT), is paired with PDA-based self-monitoring. In this paper we describe the: (a) manner in which PDA-based self-monitoring is integrated within the SCT-based intervention, (b) feasibility and acceptability of PDA-based dietary self-monitoring, and (c) issues encountered in teaching participants to self-monitor using a PDA. Results: During the first 30 months of this 5-year study, 232 participants were screened and 151 were randomized. To date, 6 cohorts have completed the study. The retention rate is 85% (n = 129). Of those randomized to the intervention (n = 74) and completing the study (n = 61), 88% reported understanding the usefulness of PDA-monitoring, 85% reported ease in entering foods into the device, 70% reported ease in interpreting feedback graphs, and 82% indicated that they would continue to use the PDA for self-monitoring after the study concluded. Assuming 3 meals per day, participants entered an average of 58% of their meals in their PDA, and 43% were entered assuming 4 meals per day. If we eliminate from the analysis those individuals who entered less than 10% of their expected meals (n = 12), the average rate of self-monitoring was 69% assuming 3 meals per day, and 52% assuming 4 meals per day. Conclusions: PDA-based dietary monitoring is perceived by participants to be useful and acceptable. The approach used to instruct participants in use of the PDA and lessons learned are discussed. PDA technology shows promise as a tool for assisting those with type 2 diabetes in their efforts to manage their disease. (C) 2007 Elsevier Inc. All rights reserved. C1 [Sevick, Mary Ann; Zickmund, Susan; Hausmann, Leslie] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15213 USA. [Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Sevick, Mary Ann; Zickmund, Susan; Korytkowski, Mary; Piraino, Beth; Marsh, Rita; Starrett, Terry J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Sevick, Mary Ann; Burke, Lora E.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Sereika, Susan; Ren, Dianxu] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15213 USA. [Mihalko, Shannon] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA. [Snetselaar, Linda; Stumbo, Phyllis] Univ Iowa, Iowa City, IA 52242 USA. [Sakraida, Teresa] Univ Colorado Denver, Denver, CO 80202 USA. [Sakraida, Teresa] Hlth Sci Ctr, Denver, CO USA. [Gibson, Jolynn; Safaien, Mehry] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. RP Sevick, MA (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Suite 600,230 McKee Pl, Pittsburgh, PA 15213 USA. EM sevick@pitt.edu OI Piraino, Beth/0000-0001-5061-0841 FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [M01 RR000056, M01 RR000056-440968, M01 RR000056-45, M01-RR000056, UL1 RR024153, UL1 RR024153-010004, UL1-RR024153]; NINR NIH HHS [R01 NR008792, R01 NR008792-01, R01 NR008792-02, R01 NR008792-03, R01 NR008792-04, R01 NR008792-05]; PHS HHS [R01008792] NR 38 TC 23 Z9 23 U1 4 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAY PY 2008 VL 29 IS 3 BP 396 EP 409 DI 10.1016/j.cct.2007.09.004 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 311DL UT WOS:000256580500009 PM 17997364 ER PT J AU Alston, TA AF Alston, Theodore A. TI Teasing and skinning muscles in sepsis research SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; GENE-TRANSFER; LEVOSIMENDAN; MODEL; DYSFUNCTION; IMPROVEMENT; MILRINONE; SAPONIN C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RP Alston, TA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. EM talston@partners.org NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2008 VL 36 IS 5 BP 1674 EP 1675 DI 10.1097/CCM.0b013e318170458c PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 297NJ UT WOS:000255623100060 PM 18448938 ER PT J AU Goldfine, AB Silver, R Aldhahi, W Cai, DS Tatro, E Lee, J Shoelson, SE AF Goldfine, Allison B. Silver, Robert Aldhahi, Waleed Cai, Dongsheng Tatro, Elizabeth Lee, Jongsoon Shoelson, Steven E. TI Use of Salsalate to Target Inflammation in the Treatment of Insulin Resistance and Type 2 Diabetes SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE salicylate; salsalate; inflammation; type 2 diabetes; insulin resistance; glucose; adiponectin ID NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; SODIUM-SALICYLATE; ANTIINFLAMMATORY EFFICACY; RHEUMATOID-ARTHRITIS; ASPIRIN CONTRIBUTE; MONONUCLEAR-CELLS; ENDOTHELIAL-CELLS; ACETYL GROUP; IKK-BETA AB Objectives: Chronic subacute inflammation is implicated in the pathogenesis of insulin resistance and type 2 diabetes. Salicylates were shown years ago to lower glucose and more recently to inhibit NF-kappa B activity. Salsalate, a prodrug form of salicylate, has seen extensive clinical use and has a favorable safety profile. We studied the efficacy of salsalate in reducing glycemia and insulin resistance and potential mechanisms of action to validate NF-kappa B as a potential pharmacologic target in diabetes. Methods and Results: In open label studies, both high (4.5 g/d) and standard (3.0 g/d) doses of salsalate reduced fasting and postchallenge glucose levels after 2 weeks of treatment. Salsalate increased glucose utilization during euglycemic hyperinsulinemic clamps, by approximately 50% and 15% at the high and standard doses, respectively, and insulin clearance was decreased. Dose-limiting tinnitus occurred only at the higher dose. In a third, double-masked, placebo-controlled trial, 1 month of salsalate at maximum tolerable dose (no tinnitus) improved fasting and postchallenge glucose levels. Circulating free fatty acids were reduced and adiponectin increased in all treated subjects. Conclusions: These data demonstrate that salsalate improves in vivo glucose and lipid homeostasis, and support targeting of inflammation and NF-kappa B as a therapeutic approach in type 2 diabetes. C1 [Goldfine, Allison B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Goldfine, AB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM Allison.Goldfine@Joslin.Harvard.Edu FU NIH [R01 DK51729, R01 DK45943, K23 DK02795, P30 DK36836, M01 RR02635, M01 RR01032]; William Randolph Hearst Foundation [7-04-MN-47]; Helen and Morton Adler Chair FX We thank the staff of the Brigham and Women's Hospital General Clinical Research Center for their assistance, M. Freeman and J. Manning for analyses of fatty acid composition, Drs. Ernie Schaefer and Bela Asztalos for special assays, and G. I. Shulman and G. Cline for isotope analyses. These studies were supported by NIH grants R01 DK51729 and R01 DK45943 (SES), K23 DK02795 (ABG), P30 DK36836 and M01 RR02635 (Joslin Diabetes Center), and M01 RR01032 (Brigham and Women's Hospital), fellowships from the William Randolph Hearst Foundation (RJS) and American Diabetes Association 7-04-MN-47 (SES), and the Helen and Morton Adler Chair (SES). NR 50 TC 149 Z9 154 U1 1 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD MAY PY 2008 VL 1 IS 1 BP 36 EP 43 DI 10.1111/j.1752-8062.2008.00026.x PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 532RR UT WOS:000272767700011 PM 19337387 ER PT J AU Zhuang, Y Sun, YT Zhai, S Huang, DD Zhao, SG Wang, SY Kang, WZ Li, XH Walker, BD Altfeld, M Yu, XG AF Zhuang, Yan Sun, Yongtao Zhai, Song Huang, Dedong Zhao, Shuguang Wang, Shaoyang Kang, Wenzhen Li, Xinhong Walker, Bruce D. Altfeld, Marcus Yu, Xu G. TI Relative dominance of Env-gp41-specific cytotoxic T lymphocytes responses in HIV-1 advanced infection SO CURRENT HIV RESEARCH LA English DT Article DE advanced HIV-1 infection; cytotoxic T-lymphocyte; cellular immune responses; HIV-1 Env-gp41 ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELLULAR IMMUNE-RESPONSES; VIRAL LOAD; ADVANCED DISEASE; ESCAPE VARIANTS; VACCINE DESIGN; CELLS; VIREMIA; SUPPRESSION; CD4(+) AB Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) responses provide an important defense in controlling HIV-1 replication, but they fail to control the progression of AIDS in advanced HIV-1 infection. To uncover the situation of these responses in patients with advanced HIV-1 infection, we assessed HIV-1-specific CTL responses in 20 individuals with advanced HIV-1 infection using 407 overlapping peptides spanning all expressed HIV-1 proteins using a gamma interferon-enzyme-linked immunospot (ELISpot) assay. In comparison to 20 individuals with moderately advanced HIV-1 infection, HIV-1-specific CTL responses were significantly decreased (P=0.044) and less peptides could be recognized (P=0.05) in advanced HIV-1 infection. Weakening of Env-gp120 and Gag-specific CTL responses contributed importantly to the decrease of CTL magnitude (P=0.042 and 0.078, respectively), while Env-gp41-specific CTL responses were relatively stronger during the end-stage of HIV-1 infection (P < 0.001). Nef and Env-gp41 represented the most frequently targeted HIV-1 proteins in advanced HIV-1 infection. The entropy scores of peptides targeted in two groups were not significantly different. Only the breadth and magnitude of Env-gp41-specific CTL responses were positively correlated with viral loads in advanced HIV-1 infection (P=0.005 and 0.001, respectively). These findings suggest that progressive HIV-1 infection is associated with a weakening of Env-gp120- and Gag-specific CTL responses, and a simultaneous expansion of Env-gp41-specific CTL which is likely driven by high level viral replication. C1 [Zhuang, Yan; Sun, Yongtao; Zhai, Song; Huang, Dedong; Zhao, Shuguang; Wang, Shaoyang; Kang, Wenzhen; Li, Xinhong] Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, Xian 710038, Peoples R China. [Walker, Bruce D.; Altfeld, Marcus; Yu, Xu G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02129 USA. RP Sun, YT (reprint author), Fourth Mil Med Univ, Tangdu Hosp, Dept Infect Dis, Xian 710038, Peoples R China. EM yongtaos@hotmail.com; xyu@partners.org FU NIAID NIH HHS [N01-AI-30024] NR 28 TC 6 Z9 6 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD MAY PY 2008 VL 6 IS 3 BP 239 EP 245 DI 10.2174/157016208784324921 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 311RA UT WOS:000256616100007 PM 18473787 ER PT J AU Das, A Abraham, S Deswal, A AF Das, Aparajita Abraham, Selwin Deswal, Anita TI Advances in the treatment of heart failure with a preserved ejection fraction SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE diastolic heart failure; heart failure; treatment ID VENTRICULAR SYSTOLIC FUNCTION; CONVERTING-ENZYME-INHIBITORS; PRIOR MYOCARDIAL-INFARCTION; DIASTOLIC DYSFUNCTION; ELDERLY-PATIENTS; DIGITALIS GLYCOSIDES; MORTALITY; ANGIOTENSIN; MECHANISMS; TRIAL AB Purpose of review Heart failure with preserved ejection fraction (HF-PEF) occurs in approximately 50% of patients with heart failure (HF) and is associated with high morbidity and mortality. A recent study demonstrated that, although survival improved significantly over time among HF patients with reduced ejection fraction (EF), there was no such trend toward improvement among patients with HF-PEF Therefore, there exists an urgent need to develop effective treatment strategies specifically for patients with HF-PEF Recently completed and ongoing research in the treatment of HF-PEF is reviewed in this article. Recent findings The two large randomized clinical trials completed in HF-PEF patients did not achieve statistical significance in benefit of renin-angiotensin system blockade on their primary combined endpoints of morbidity and mortality. Both trials, however, suggested the benefit of the angiotensin receptor and angiotensin-converting enzyme blockade on HF hospitalization. In addition, no clear benefit of beta-blockers has been demonstrated specifically in patients with HF-PEF. Summary Current therapeutic recommendations for HF-PEF are aimed mostly at symptomatic management and treatment of concomitant comorbidities. Results of ongoing clinical trials further evaluating inhibition of the angiotensin and the aldosterone receptors as well as examining other novel therapeutic targets in HF-PEF are keenly awaited. C1 [Deswal, Anita] Michael E DeBakey Vet Affairs Med Ctr, Winters Ctr Heart Failure Res, Cardiol Sect, Houston, TX 77030 USA. [Das, Aparajita; Abraham, Selwin] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Deswal, A (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Winters Ctr Heart Failure Res, Cardiol Sect, 111B,2002 Holcombe Blvd, Houston, TX 77030 USA. EM adeswal@bcm.tmc.edu NR 40 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAY PY 2008 VL 23 IS 3 BP 233 EP 240 DI 10.1097/HCO.0b013e3282f73317 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 290GD UT WOS:000255110400010 PM 18382212 ER PT J AU Koh, HJ Brandauer, J Goodyear, LJ AF Koh, Ho-Jin Brandauer, Josef Goodyear, Laurie J. TI LKB1 and AMPK and the regulation of skeletal muscle metabolism SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE fatty acid oxidation; glucose transport; mitochondrial biogenesis ID ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; ACETYL-COA CARBOXYLASE; GLUCOSE-TRANSPORT; INSULIN-RESISTANCE; MITOCHONDRIAL BIOGENESIS; BIOCHEMICAL ADAPTATIONS; GLUT4 TRANSLOCATION; LIPID-METABOLISM; ENZYME-ACTIVITY AB Purpose of review To address the role of LKB1 and AMP-activated protein kinase (AMPK) in glucose transport, fatty acid oxidation, and metabolic adaptations in skeletal muscle. Recent findings Contraction-mediated skeletal muscle glucose transport is decreased in muscle-specific LKB1 knockout mice, but not in whole body AMPK alpha 2 knockout mice or AMPK alpha 2 inactive transgenic mice. Chronic activation of AMPK by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) and beta-guanadinopropionic acid enhances mitochondrial function in skeletal muscle, but AICAR or exercise-induced increases in mitochondrial markers are preserved in skeletal muscles from whole body AMPKa2 or muscle-specific LKB1 knockout mice. Pharmacological activation of AMPK increases glucose transport and fatty acid oxidation in skeletal muscle. Therefore, chronic activation of AMPK may be beneficial in the treatment of obesity and type 2 diabetes. Summary LKB1 and AMPK play important roles in regulating metabolism in resting and contracting skeletal muscle. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect,Res Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM Laurie.Goodyear@joslin.harvard.edu FU NIAMS NIH HHS [R01 AR045670, AR45670, R01 AR045670-10]; NIDDK NIH HHS [T32 DK007260-29, T32-DK07260-29, R01 DK068626-04, DK68626, R01 DK068626, T32 DK007260] NR 78 TC 34 Z9 36 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 EI 1473-6519 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD MAY PY 2008 VL 11 IS 3 BP 227 EP 232 DI 10.1097/MCO.0b013e3282fb7b76 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 306AK UT WOS:000256218800006 PM 18403917 ER PT J AU de Aguilar-Nascimento, JE Kudsk, KA AF de Aguilar-Nascimento, Jose E. Kudsk, Kenneth A. TI Early nutritional therapy: the role of enteral and parenteral routes SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE critical care; enteral nutrition; parenteral nutrition; perioperative care ID CRITICALLY-ILL PATIENTS; MECHANICALLY VENTILATED PATIENTS; RANDOMIZED CLINICAL-TRIAL; INTENSIVE-CARE UNITS; OF-THE-LITERATURE; ACUTE-PANCREATITIS; SEPTIC MORBIDITY; ESPEN GUIDELINES; ABDOMINAL-TRAUMA; GLUCOSE CONTROL AB Purpose of review Early nutrition is defined as the initiation of nutritional therapy within 48 h of either hospital admission or surgery. However, optimal timing for initiation of nutritional therapy through either enteral or parenteral routes remains poorly defined with the existing data. We reviewed the recent literature investigating the role of early enteral and parenteral nutrition in critical illness and perioperative care. Recent findings Recent studies in both trauma/surgical and nonsurgical patients support the superiority of early enteral over early parenteral nutrition. However, late commencement of enteral feeding should be avoided if the gastrointestinal tract is functional. Both prolonged hypocaloric enteral feeding and hypercaloric parenteral nutrition should be avoided, although the precise caloric target remains controversial. Summary Early enteral nutrition remains the first option for the critically ill patient. However, there seems to be increased favor for combined enteral-parenteral therapy in cases of sustained hypocaloric enteral nutrition. The key issue is when the dual regimen should be initiated. Although more study is required to determine the optimal timing to initiate a combined enteral-parenteral approach, enteral nutrition should be initiated early and parenteral nutrition added if caloric-protein targets cannot be achieved after a few days. C1 [de Aguilar-Nascimento, Jose E.] Univ Fed Mato Grosso, Dept Surg, Cuiaba, Brazil. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. [Kudsk, Kenneth A.] Univ Wisconsin, Coll Med, Dept Surg, Madison, WI USA. RP de Aguilar-Nascimento, JE (reprint author), Rua Estevao Mendonca 81 Apto 801, BR-78043300 Cuiaba, Brazil. EM aguilar@terra.com.br NR 56 TC 7 Z9 9 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD MAY PY 2008 VL 11 IS 3 BP 255 EP 260 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 306AK UT WOS:000256218800010 PM 18403921 ER PT J AU Pratt, DS AF Pratt, Daniel S. TI Liver disorders SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material ID HEPATITIS-C VIRUS; TYPE-1 AUTOIMMUNE HEPATITIS; HEPATOCELLULAR-CARCINOMA; NONALCOHOLIC STEATOHEPATITIS; ETHYL GLUCURONIDE; ANTIVIRAL THERAPY; MILAN CRITERIA; TRANSPLANTATION; DISEASE; ALCOHOL C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Pratt, DS (reprint author), Massachusetts Gen Hosp, GI Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM dspratt@partners.org NR 52 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD MAY PY 2008 VL 24 IS 3 BP 265 EP 268 DI 10.1097/MOG.0b013e3282fbd371 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298SM UT WOS:000255707400001 PM 18408453 ER PT J AU Mukhopadhyay, A Peaterson, RT AF Mukhopadhyay, Arpita Peaterson, Randall T. TI Deciphering arterial identity through gene expression, genetics, and chemical biology SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE chemical biology; gridlock; hedgehog; notch; vascular endothelial growth factor ID ENDOTHELIAL-GROWTH-FACTOR; EMBRYONIC VASCULAR DEVELOPMENT; BMX TYROSINE KINASE; SONIC-HEDGEHOG; TRANSCRIPTION FACTORS; CARDIOVASCULAR DEVELOPMENT; ZEBRAFISH EMBRYOGENESIS; VENOUS DIFFERENTIATION; MICROARRAY ANALYSIS; AORTIC COARCTATION AB Purpose of review The present review presents a current view of vascular development, with a focus on the factors contributing to the establishment of arterial-venous identity and the potential of chemical biology for providing new insights into this field. Recent findings Genetics and gene expression studies have begun to define the complex network of molecular pathways that govern the formation of the embryonic vasculature, but these approaches have limited ability to spatially and temporally manipulate gene expression and function. Recently, the power of chemical biology, combined with model systems like zebrafish, has enabled discovery of additional contributors to vascular development and has provided a means of manipulating gene function with enhanced spatial and temporal control. Summary The molecular pathways directing arterial-venous specification during embryogenesis are relevant for understanding the causes of human arteriovenous malformations, tumor angiogenesis, and diabetic retinopathy. Through the complementary strengths of genetics and chemical biology, it is hoped that novel therapeutic approaches for these conditions will emerge. C1 [Mukhopadhyay, Arpita; Peaterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Peaterson, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM peterson@cvrc.mgh.harvard.edu NR 68 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD MAY PY 2008 VL 15 IS 3 BP 221 EP 227 DI 10.1097/MOH.0b013e3282f97daa PG 7 WC Hematology SC Hematology GA 296IU UT WOS:000255537500012 PM 18391789 ER PT J AU Lo, J Grinspoon, S AF Lo, Janet Grinspoon, Steven TI Cardiovascular disease in HIV-infected patients: does HIV infection in and of itself increase cardiovascular risk? SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE cardiovascular disease; cardiovascular risk factors; HIV AB Purpose of review Cardiovascular disease is increasingly recognized to be a significant cause of morbidity and mortality among patients with chronic HIV infection in the current era of effective antiretroviral therapy. HIV-infected patients treated with antiretroviral therapy have increased traditional cardiovascular risk factors, but whether HIV infection in and of itself confers a significant increase in cardiovascular risk is largely unknown. This review summarizes recent data investigating cardiovascular risk in HIV patients and the evidence for an effect of HIV per se. The potential physiological mechanisms by which HIV might contribute to coronary artery disease are reviewed. Recent findings Several interesting studies in the last year have evaluated cardiovascular endpoints and surrogate measures such as carotid intima-media thickness and endothelial function in HIV-infected patients compared with uninfected control groups. Several studies to date using surrogate measurements such as carotid intima-media thickness and endothelial dysfunction suggest a possible independent HIV effect on cardiovascular risk, but some studies have yielded conflicting results. Numerous potential mechanisms by which HIV might contribute to coronary artery disease exist. These mechanisms include effects of HIV proteins to attract monocytes to the intimal wall, and impair cholesterol efflux, and effects of activated monocytes to induce an inflammatory response. Summary More definitive prospective studies are needed to fully answer whether HIV infection per se promotes cardiovascular disease, but ample evidence suggests that HIV and related inflammatory responses could contribute to increased cardiovascular disease. C1 [Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON-207, Boston, MA 02114 USA. NR 69 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2008 VL 3 IS 3 BP 207 EP 213 DI 10.1097/COH.0b013e3282fb7ba6 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NZ UT WOS:000208418400002 PM 19372968 ER PT J AU Kaufmann, DE Walker, BD AF Kaufmann, Daniel E. Walker, Bruce D. TI Programmed death-1 as a factor in immune exhaustion and activation in HIV infection SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE CD4 T cell; CD8 T cell; HIV; immune activation; PD-1; T cell exhaustion AB Purpose of review The aim of this article is to understand the dual role of programmed death-1 (PD-1) as a physiological negative regulator of T cell activation and a mediator of T cell exhaustion in HIV infection. Recent findings Studies in the murine lymphocytic choriomeningitis virus model showed that the inhibitory receptor PD-1 was upregulated on the surface of exhausted virus-specific CD8 T cells and mediated a reversible impairment of immune responses. Studies in HIV infection demonstrated that PD-1 was upregulated on HIV-specific CD8 and CD4 T lymphocytes and that its expression correlated with markers of disease progression, mediated a proliferative defect of these cells and increased apoptosis of virus-specific CD8 T cells. Blockade of the PD-1 pathway enhanced HIV-specific T cell responses in vitro. Summary These observations demonstrate an unexpected level of reversibility in HIV-specific T cell impairment. Significant efforts are required to further understanding of the PD-1 pathway. It is essential to delineate when PD-1 expression is the signal of physiologic regulatory mechanisms of activated cells, a mere marker of exhausted cells or a major mediator of functional exhaustion. The respective importance of these components, which could vary according to the stage of infection, will determine the clinical potential for immunotherapeutic intervention and the risk of adverse effects. C1 [Kaufmann, Daniel E.; Walker, Bruce D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Kaufmann, Daniel E.; Walker, Bruce D.] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kaufmann, DE (reprint author), Massachusetts Gen Hosp E, Partners AIDS Res Ctr, Room 6618B,149 13th St, Charlestown, MA 02129 USA. EM dkaufmann@partners.org NR 42 TC 30 Z9 32 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2008 VL 3 IS 3 BP 362 EP 367 DI 10.1097/COH.0b013e3282f9ae8b PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NZ UT WOS:000208418400025 PM 19372991 ER PT J AU Campbell, KH O'Hare, AM AF Campbell, Kellie Hunter O'Hare, Ann M. TI Kidney disease in the elderly: update on recent literature SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE aging; chronic kidney disease; CKD; elderly ID CONVERTING ENZYME-INHIBITION; DEPENDENT DIABETES-MELLITUS; CHRONIC RENAL-INSUFFICIENCY; GLOMERULAR-FILTRATION RATE; BLOOD-PRESSURE CONTROL; BODY-COMPOSITION; MORTALITY RISK; UNITED-STATES; CARDIOVASCULAR OUTCOMES; TYPE-2 DIABETES/ AB Purpose of review We review recent literature on the epidemiology and outcomes of chronic kidney disease in the elderly and discuss implications for management. Recent findings Chronic kidney disease is common in the elderly and associated with substantial morbidity and mortality. The prognostic significance of a given level of estimated glomerular filtration rate, however, varies substantially by age. Estimates of the prevalence of chronic kidney disease at the population level and estimates glomerular filtration rate at the individual level are exquisitely sensitive to the methods used to arrive at these estimates. At present there is no clear consensus on the optimal approach to estimating glomerular filtration rate in elderly individuals in the clinical setting. Available evidence to guide management of chronic kidney disease is based largely on trials in younger individuals. It is unclear to what extent the results of these trials can be extrapolated to older individuals with chronic kidney disease. Summary We advise caution in applying current guidelines to the care of the large number of individuals aged 70 years and older with chronic kidney disease. Ideally, the care of these patients should be individualized and carefully integrated with the management of other comorbid conditions and with patient preferences. C1 [O'Hare, Ann M.] Univ Washington, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. [Campbell, Kellie Hunter] Univ Chicago, Sect Geriatr, Chicago, IL 60637 USA. RP O'Hare, AM (reprint author), Univ Washington, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. EM Ann.OHare@va.gov NR 59 TC 28 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2008 VL 17 IS 3 BP 298 EP 303 PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 297GS UT WOS:000255605700009 PM 18408482 ER PT J AU Laubach, HJ Makin, IRS Barthe, PG Slayton, MH Manstein, D AF Laubach, Hans J. Makin, Inder R. S. Barthe, Peter G. Slayton, Michael H. Manstein, Dieter TI Intense focused ultrasound: Evaluation of a new treatment modality for precise microcoagulation within the skin SO DERMATOLOGIC SURGERY LA English DT Article ID PROSTATE-CANCER; BREAST-CANCER; LIVER-TUMORS; LOCAL HYPERTHERMIA; NONABLATIVE LASER; HIFU TREATMENT; THERAPY; EXPERIENCE; ABLATION; SURGERY AB BACKGROUND AND OBJECTIVE Focused ultrasound can produce thermal and/or mechanical effects deep within tissue. We investigated the capability of intense focused ultrasound to induce precise and predictable subepidermal thermal damage in human skin. MATERIALS AND METHODS Postmortem human skin samples were exposed to a range of focused ultrasound pulses, using a prototype device (Ulthera Inc.) emitting up to 45 W at 7.5 MHz with a nominal focal distance of 4.2 mm from the transducer membrane. Exposure pulse duration ranged from 50 to 200 ms. Thermal damage was confirmed by light microscopy using a nitroblue tetrazolium chloride assay, as well as by loss of collagen birefringence in frozen sections. Results were compared with a computational model of intense ultrasound propagation and heating in tissue. RESULTS Depth and extent of thermal damage were determined by treatment exposure parameters (source power, exposure time, and focal depth). It was possible to create individual and highly confined lesions or thermal damage up to a depth of 4 mm within the dermis. Thermal lesions typically had an inverted cone shape. A precise pattern of individual lesions was achieved in the deep dermis by applying the probe sequentially at different exposure locations. DISCUSSION AND CONCLUSION Intense focused ultrasound can be used as a noninvasive method for spatially confined heating and coagulation within the skin or its underlying structures. These findings have a significant potential for the development of novel, noninvasive treatment devices in dermatology. C1 [Laubach, Hans J.; Manstein, Dieter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Makin, Inder R. S.; Barthe, Peter G.; Slayton, Michael H.] Ulthera Inc, Mesa, AZ USA. RP Laubach, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, BAR 305,50 Blossom St, Boston, MA 02114 USA. EM hlaubach@partners.org NR 48 TC 57 Z9 57 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 2008 VL 34 IS 5 BP 727 EP 734 DI 10.1111/j.1524-4725.2008.34196.x PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 290QG UT WOS:000255136700020 PM 18429926 ER PT J AU Rajagopal, J Carroll, TJ Guseh, JS Bores, SA Blank, LJ Anderson, WJ Yu, J Zhou, Q McMahon, AP Melton, DA AF Rajagopal, Jayaraj Carroll, Thomas J. Guseh, J. Sawalla Bores, Sam A. Blank, Leah J. Anderson, William J. Yu, Jing Zhou, Qiao McMahon, Andrew P. Melton, Douglas A. TI Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme SO DEVELOPMENT LA English DT Article DE lung organogenesis; Wnt signaling; organ growth ID REGULATES BRANCHING-MORPHOGENESIS; HELIX INHIBITOR ID2; CELL SELF-RENEWAL; MOUSE LUNG; BETA-CATENIN; STEM-CELLS; N-MYC; DIFFERENTIATION; PROLIFERATION; HEDGEHOG AB The effects of Wnt7b on lung development were examined using a conditional Wnt7b-null mouse. Wnt7b-null lungs are markedly hypoplastic, yet display largely normal patterning and cell differentiation. In contrast to findings in prior hypomorphic Wnt7b models, we find decreased replication of both developing epithelium and mesenchyme, without abnormalities of vascular smooth muscle development. We further demonstrate that Wnt7b signals to neighboring cells to activate both autocrine and paracrine canonical Wnt signaling cascades. In contrast to results from hypomorphic models, we show that Wnt7b modulates several important signaling pathways in the lung. Together, these cascades result in the coordinated proliferation of adjacent epithelial and mesenchymal cells to stimulate organ growth with few alterations in differentiation and patterning. C1 [Rajagopal, Jayaraj; Guseh, J. Sawalla; Bores, Sam A.; Blank, Leah J.; Anderson, William J.; Zhou, Qiao; McMahon, Andrew P.; Melton, Douglas A.] Harvard Univ, Harvard Stem Cell Inst, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. [Rajagopal, Jayaraj; Guseh, J. Sawalla; Bores, Sam A.; Blank, Leah J.; Anderson, William J.; Zhou, Qiao; Melton, Douglas A.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Rajagopal, Jayaraj; Guseh, J. Sawalla] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Carroll, Thomas J.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dept Internal Med, Dallas, TX 75390 USA. [Yu, Jing] Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA. RP Melton, DA (reprint author), Harvard Univ, Harvard Stem Cell Inst, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. EM dmelton@harvard.edu FU Howard Hughes Medical Institute; NHLBI NIH HHS [K08 HL076393, K08 HL076393-01A1, K08 HL076393-02, K08 HL076393-03, K08 HL076393-04]; PHS HHS [NHLBI HL076393, NIDDK 054364] NR 49 TC 78 Z9 81 U1 0 U2 0 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 MAY 1 PY 2008 VL 135 IS 9 BP 1625 EP 1634 DI 10.1242/dev.015495 PG 10 WC Developmental Biology SC Developmental Biology GA 287LF UT WOS:000254917900007 PM 18367557 ER PT J AU Orford, K Kharchenko, P Lai, W Dao, MC Worhunsky, DJ Ferro, A Janzen, V Park, PJ Scadden, DT AF Orford, Keith Kharchenko, Peter Lai, Weil Dao, Maria Carlota Worhunsky, David J. Ferro, Adam Janzen, Viktor Park, Peter J. Scadden, David T. TI Differential H3K4 methylation identifies developmentally poised hematopoietic genes SO DEVELOPMENTAL CELL LA English DT Article ID HISTONE H3; TRANSCRIPTION FACTORS; RECOGNITION; COMMITMENT; BINDING; CELLS; CODE; KEY; K4 AB Throughout development, cell fate decisions are converted into epigenetic information that determines cellular identity. Covalent histone modifications are heritable epigenetic marks and are hypothesized to play a central role in this process. In this report, we assess the concordance of histone H3 lysine 4 dimethylation (H3K4me2) and trimethylation (H3K4me3) on a genome-wide scale in erythro, development by analyzing pluripotent, multipotent, and unipotent cell types. Although H3K4me2 and H3K4me3 are concordant at most genes, multi-potential hematopoietic cells have a subset of genes that are differentially methylated (H3K4me2+/me3-). These genes are transcriptionally silent, highly enriched in lineage-specific hematopoietic genes, and uniquely susceptible to differentiation-induced H3K4 demethylation. Self-renewing embryonic stem cells, which restrict H3K4 methylation to genes that contain CpG islands (CGIs), lack H3K4me2+/me3- genes' These data reveal distinct epigenetic regulation of CGI and non-CGI genes during development and indicate an interactive relationship between DNA sequence and differential H3K4 methylation in lineage-specific differentiation. C1 [Kharchenko, Peter; Lai, Weil; Park, Peter J.] Brigham & Womens Hosp, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. [Orford, Keith; Dao, Maria Carlota; Worhunsky, David J.; Ferro, Adam; Janzen, Viktor; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. [Orford, Keith; Dao, Maria Carlota; Worhunsky, David J.; Ferro, Adam; Janzen, Viktor; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Kharchenko, Peter; Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. RP Park, PJ (reprint author), Brigham & Womens Hosp, Harvard Partners Ctr Genet & Genom, 75 Francis St, Boston, MA 02115 USA. EM peter_park@harvard.edu; scadden.david@mgh.harvard.edu NR 21 TC 82 Z9 84 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY PY 2008 VL 14 IS 5 BP 798 EP 809 DI 10.1016/j.devcel.2008.04.002 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 301LX UT WOS:000255898800019 PM 18477461 ER PT J AU Xiong, JW AF Xiong, Jing-Wei TI Molecular and developmental biology of the hemangioblast SO DEVELOPMENTAL DYNAMICS LA English DT Review DE hemangioblast; angioblasts; hematopoietic cells; mouse embryonic stem cells; human embryonic stem cells; developmental biology; zebrafish; chick; mouse ID EMBRYONIC STEM-CELLS; ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; TRANSCRIPTION FACTOR ZBP-89; DIFFERENTIATING ES CELLS; YOLK SYNCYTIAL LAYER; HOMEOBOX GENE HEX; MOUSE EMBRYO; IN-VITRO; HEMATOPOIETIC-CELLS AB The hemangioblast hypothesis was proposed a century ago. The existence of hemangioblasts is now demonstrated in mouse and human embryonic stem cell (ESC)-derived embryoid bodies (Ells), in the mouse and zebrafish gastrula, and in adults. The hemangioblast is believed to derive from mesodermal cells, and is enriched in the Bry(+)Fkl1(+) and Flk1(+)Sc1(+) cell populations in Ells and in the posterior primitive streak of the mouse gastrula and in the ventral mesoderm of the zebrafish gastrula. However, recent studies suggest that the hemangioblast does not give rise to all endothelial and hematopoietic lineages in mouse and zebrafish embryos. Although several signaling pathways are known to involve the generation of hemangioblasts, it remains largely unknown how the hemangioblast is formed and what are the master genes controlling hemangioblast development. This review will summarize our current knowledge, challenges, and future directions on molecular and developmental aspects of the hemangioblast. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nephrol Div,Dept Med, Boston, MA 01219 USA. RP Xiong, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nephrol Div,Dept Med, 149 13th St,Room 8216, Boston, MA 01219 USA. EM xiong@cvrc.mgh.harvard.edu RI Xiong, Jing-Wei/A-7113-2011 FU NIA NIH HHS [K01 AG019676-02, AG19676, K01 AG019676, K01 AG019676-01A1, K01 AG019676-03, K01 AG019676-04, K01 AG019676-05] NR 195 TC 39 Z9 43 U1 1 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2008 VL 237 IS 5 BP 1218 EP 1231 DI 10.1002/dvdy.21542 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 300RM UT WOS:000255842900002 PM 18429046 ER PT J AU Wilcox, T Bortfeld, H Woods, R Wruck, E Boas, DA AF Wilcox, Teresa Bortfeld, Heather Woods, Rebecca Wruck, Eric Boas, David A. TI Hemodynamic response to featural changes in the occipital and inferior temporal cortex in infants: a preliminary methodological exploration SO DEVELOPMENTAL SCIENCE LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; MONKEY INFEROTEMPORAL CORTEX; VISUAL OBJECT RECOGNITION; BLOOD OXYGENATION CHANGES; BRAIN ACTIVATION; NEWBORN-INFANTS; OPTICAL TOPOGRAPHY; OCCLUDED OBJECTS; YOUNG INFANTS; PERCEPTION AB Over the past 30 years researchers have learned a great deal about the development of object processing in infancy. In contrast, little is understood about the neural mechanisms that underlie this capacity, in large part because there are few techniques available to measure brain functioning in human infants. The present research examined the extent to which near-infrared spectroscopy (NIRS), an optical imaging technique, could be used to assess the relation between object processing and brain functioning. Infants aged 6.5 months were presented with an occlusion event involving objects that differed on many feature dimensions (multi-featural change), differed on shape only (shape change) or color only (color change), or did not differ (control). NIRS data were collected in the occipital and inferior temporal cortex. In the occipital cortex, a significant increase in oxyhemoglobin (HbO(2)) was observed in response to all four events and these responses did not differ significantly from each other. In the inferior temporal cortex, a significant increase in HbO(2) was observed in the multi-featural and the shape change condition but not in the control condition. An increase was also observed in the color change condition but this increase did not differ significantly from baseline nor did it differ significantly from the response obtained in the control condition. These data were discussed in terms of (a) what they suggest about the neural basis of feature processing in infants and (b) the viability of using NIRS to study brain-behavior relations in infants. C1 [Wilcox, Teresa; Bortfeld, Heather; Woods, Rebecca; Wruck, Eric] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Boas, David A.] Massachusetts Gen Hosp, Harvard Med Sch, Anthinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Wilcox, T (reprint author), Texas A&M Univ, Dept Psychol, 4235 TAMU, College Stn, TX 77843 USA. EM tgw@psyc.tamu.edu OI Bortfeld, Heather/0000-0002-3545-5449 FU NCRR NIH HHS [P41 RR014075, P41 RR014075-106006, P41-RR14075]; NICHD NIH HHS [HD 046533, HD 48943, R03 HD046533, R21 HD048943] NR 63 TC 37 Z9 39 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1363-755X J9 DEVELOPMENTAL SCI JI Dev. Sci. PD MAY PY 2008 VL 11 IS 3 BP 361 EP 370 DI 10.1111/j.1467-7687.2008.00681.x PG 10 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 297UY UT WOS:000255644100005 PM 18466370 ER PT J AU Kahn, SE Zinman, B Lachin, JM Haffner, SM Herman, WH Holman, RR Kravitz, BG Yu, DH Heise, MA Aftring, RP Viberti, G AF Kahn, Steven E. Zinman, Bernard Lachin, John M. Haffner, Steven M. Herman, William H. Holman, Rury R. Kravitz, Barbara G. Yu, Dahong Heise, Mark A. Aftring, R. Paul Viberti, Giancarlo CA Progression Trial (ADOPT) Study Gr TI Rosiglitazone-associated fractures in type 2 diabetes - An analysis from a diabetes outcome progression trial (ADOPT) SO DIABETES CARE LA English DT Article ID BONE-MINERAL DENSITY; OSTEOBLAST DIFFERENTIATION; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; HIP-FRACTURES; OLDER WHITE; PPAR-GAMMA; RISK; HEALTH; MELLITUS AB OBJECTIVE - The purpose of this study was to examine possible factors associated with the increased risk of fractures observed with rosiglitazone in A Diabetes Outcome Progression Trial (ADOPT). RESEARCH DESIGN AND METHODS - Data from the 1,840 women and 2,511 men randomly assigned in ADOPT to rosiglitazone, metformin, or glyburide for a median of 4.0 years were examined with respect to time to first fracture, rates of occurrence, and sites of fractures. RESULTS - In men, fracture rates did not differ between treatment groups. In women, at least one fracture was reported with rosiglitazone in 60 patients (9.3% of patients, 2.74 per 100 patient-years), metformin in 30 patients (5.1%, 1.54 per 100 patient-years), and glyburide in 21 patients (3.5%, 129 per 100 patient-years). The cumulative incidence (95% CI) of fractures in women at 5 years was 15.1% (11.2-19.1) with rosiglitazone, 7.3% (4.4-10.1) with metformin, and 7.7% (3.7-11.7) with glyburide, representing hazard ratios (95% CI) of 1.81 (1.17-2-80) and 2.13 (1.30-3.51) for rosiglitazone compared with metformin and glyburide, respectively. The increase in fractures with rosiglitazone occurred in pre- and postmenopausal women, and fractures were seen predominantly in the lower and upper limbs. No particular risk factor underlying the increased fractures in female patients who received rosiglitazone therapy was identified. CONCLUSIONS - Further investigation into the risk factors and underlying pathophysiology for the increased fracture rate in women taking rosiglitazone is required to relate them to preclinical data and better understand the clinical implications of and possible interventions for these findings. C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Zinman, Bernard] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Zinman, Bernard] Univ Toronto, Toronto, ON, Canada. [Lachin, John M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Haffner, Steven M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Herman, William H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Herman, William H.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Holman, Rury R.] Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford, England. [Kravitz, Barbara G.; Yu, Dahong; Heise, Mark A.; Aftring, R. Paul] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Viberti, Giancarlo] Kings Coll London, Kings Coll London Sch Med, London WC2R 2LS, England. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu RI Zinman, Bernard/E-7266-2013; OI Kahn, Steven/0000-0001-7307-9002 NR 22 TC 257 Z9 270 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2008 VL 31 IS 5 BP 845 EP 851 DI 10.2337/dc07-2270 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303CE UT WOS:000256016300002 PM 18223031 ER PT J AU Tuerk, PW Mueller, M Egede, LE AF Tuerk, Peter W. Mueller, Martina Egede, Leonard E. TI Estimating physician effects on glycemic control in the treatment of diabetes - Methods, effects sizes, and implications for treatment policy SO DIABETES CARE LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; BLOOD-PRESSURE CONTROL; PAY-FOR-PERFORMANCE; GLUCOSE CONTROL; CARE; COMPLICATIONS; QUALITY; PATIENT; METAANALYSIS; ADULTS AB OBJECTIVE - Researchers have only just begun to investigate physician-related effects on medical outcomes. Such research is necessary for developing empirically informed practice guidelines and policy. The primary goal of this study was to investigate whether glucose management in type 2 diabetes varies by randomly assigned physicians over the course of a year in treatment. A second goal of the study was to investigate whether physician-related effects vary across differential patient characteristics. A tertiary goal was to investigate potential patient-level effects on glucose management. RESEARCH DESIGN AND METHODS - Hierarchical linear models were used to investigate AlC among 1,381 patients, nested within 42 randomly assigned primary care physicians at a Veterans Affairs medical center in the southeastern U.S. The primary Outcome measure was change in AlC over the course of I year in treatment. On average, each study physician had 33 patients with diabetes. RESULTS - Overall, physician-related factors were associated with statistically significant but modest variability in AlC change (2%), whereas patient-level factors accounted for the majority of variation in AlC change (98%). Physician effects varied by patient characteristics, mattering more for black patients, patients aged 65 years, and patients whose glucose management improved over the treatment year. CONCLUSIONS - The results of this study indicate that differential physician effects have minimal impact on glycemic control. Results suggest that it is logical to support policies encouraging the development of patient-level behavioral interventions because that is the level that accounts for the majority of variance in glycemic control. C1 [Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Tuerk, Peter W.] Ralph H Johnson Vet Affairs Med Ctr, Psychol Serv, Charleston, SC USA. [Mueller, Martina] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Mueller, Martina; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Vet Affairs Targeted Res Enhancement Program, Charleston, SC USA. RP Tuerk, PW (reprint author), MUSC 165 Cannon St,3rd Fl,POB 250852, Charleston, SC 29425 USA. EM tuerk@musc.edu NR 28 TC 33 Z9 35 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2008 VL 31 IS 5 BP 869 EP 873 DI 10.2337/dc07-1662 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303CE UT WOS:000256016300006 PM 18285552 ER PT J AU Mapppsy, LKR Egede, LE Mueller, M AF Mapppsy, Lisa K. Richardson Egede, Leonard E. Mueller, Martina TI Effect of race/ethnicity and persistent recognition of depression on mortality in elderly men with type 2 diabetes and depression SO DIABETES CARE LA English DT Article ID OF-VETERANS-AFFAIRS; PRIMARY-CARE AB OBJECTIVE - To determine whether mortality risk from depression among elderly men with type 2 diabetes differs by ethnicity and persistent recognition of depression. RESEARCH DESIGN AND METHODS - Data on a cohort of 14,500 male veterans with type 2 diabetes were analyzed. Diagnoses of depression and diabetes were based on ICD-9 codes. Persistent recognition was defined as an ICD-9 code for depression documented in at least the second or third visit after the initial diagnosis of depression. Hazards of death were compared using Cox proportional hazards regression models adjusting for relevant covariates. RESULTS - Over 10 years, 2,305 deaths were documented. Mortality risk was higher for depressed than nondepressed veterans with diabetes (hazard ratio [HR] 1.6 [95% CI 1.3-1.8]). Among those with depression, mortality risk was lower with persistent recognition (0-2 visits vs. >= 3 visits after initial diagnosis, HIZ 0.58 [0.40-0.89]) but higher for whites than blacks (1.60 [1.11-2.31]). CONCLUSIONS - increased mortality from depression differs by ethnicity and persistent recognition. C1 [Mapppsy, Lisa K. Richardson] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Mapppsy, Lisa K. Richardson] Murdoch Univ, Sch Psychol, Perth, WA, Australia. [Egede, Leonard E.; Mueller, Martina] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Mueller, Martina] Med Univ S Carolina, Dept Biostat Bioinformat Epidemiol, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2008 VL 31 IS 5 BP 880 EP 881 DI 10.2337/dc07-2215 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303CE UT WOS:000256016300008 ER PT J AU Adams, AS Trinacty, CM Zhang, F Kleinman, K Grant, MW Meigs, JB Solimerai, SB Ross-Degnan, D AF Adams, Alyce S. Trinacty, Connie Mah Zhang, Fang Kleinman, Ken Grant, Mchard W. Meigs, James B. Solimerai, Stephen B. Ross-Degnan, Dennis TI Medication adherence and racial differences in AlC control SO DIABETES CARE LA English DT Article ID TERM DIABETES MANAGEMENT; ETHNIC DISPARITIES; RACE DIFFERENCES; BLOOD-GLUCOSE; CARE; ADULTS; HMO; POPULATION; OUTCOMES; US AB OBJECTIVE - The purpose of this study was to examine medication adherence and other self-management practices as potential determinants of higher glycemic risk among black relative to white patients. RESEARCH DESIGN AND METHODS - We Used a retrospective, longitudinal repeated-measures design to model the contribution of medication adherence to black-white differences in AlC among type 2 diabetic patients at a large multispecialty group practice. We identified 1,806 adult (aged >= 18 at diagnosis) patients (467 black and 1,339 white) with newly initiated oral hypoglycemic therapy between 1 December 1994 and 31 December 2000. Race was identified using an electronic medical record and patient self-report. Baseline was defined as the 13 months preceding and included the month of therapy initiation. All patients were required to have at least 12 months of follow-up. RESULTS - At initiation of therapy, black patients had higher average AlC values compared with whites (9.8 vs. 8.9, a difference of 0.88; P < 0.0001). Blacks had lower average medication adherence during the first year of therapy (72.vs. 78%; P < 0.0001). Although more frequent medication refills were associated with lower average AlC values, adjustment for adherence did not eliminate the black-white gap. CONCLUSIONS - We found persistent racial differences in AlC that were not explained by differences in medication adherence. Our findings suggest that targeting medication adherence alone is unlikely to reduce disparities in glycemic control in this setting. Further research is needed to explore possible genetic and environmental determinants of higher AlC among blacks at diagnosis, which may represent a critical period for more intensive intervention. C1 [Adams, Alyce S.; Trinacty, Connie Mah; Zhang, Fang; Kleinman, Ken; Solimerai, Stephen B.; Ross-Degnan, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Grant, Mchard W.; Meigs, James B.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Adams, AS (reprint author), 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM aadams@hms.harvard.edu OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452-04, K23 DK067452]; NIMHD NIH HHS [L60 MD000756-01, L60 MD000756] NR 28 TC 57 Z9 58 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2008 VL 31 IS 5 BP 916 EP 921 DI 10.2337/dc07-1924 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303CE UT WOS:000256016300016 PM 18235050 ER PT J AU Reaven, PD Emanuele, N Moritz, T Klein, R Davis, M Glander, K Duckworth, W Abraira, C AF Reaven, Peter D. Emanuele, Nicholas Moritz, Thomas Klein, Ronald Davis, Mathew Glander, Kathy Duckworth, William Abraira, Carlos CA Vet Affairs Diabet Trial (VADT) TI Proliferative diabetic retinopathy in type 2 diabetes is related to coronary artery calcium in the Veterans Affairs Diabetes Trial (VADT) SO DIABETES CARE LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the American-Diabetes-Association CY JUN 22-26, 2007 CL Chicago, IL SP Amer Diabet Assoc ID CARDIOVASCULAR RISK-FACTORS; ABDOMINAL AORTIC CALCIFICATION; BEAM COMPUTED-TOMOGRAPHY; HEART-DISEASE; ATHEROSCLEROSIS MESA; GLYCEMIC CONTROL; FOLLOW-UP; MELLITUS; MORTALITY; MICROALBUMINURIA AB OBJECTIVE - increasing evidence suggests that macrovascular disease and retinopathy may be more closely linked than previously believed. We determined the relationship between retinopathy and coronary atherosclerosis as measured by computed tomography-detectable coronary artery calcium (CAC). RESEARCH DESIGN AND METHODS - The cross-sectional association between CAC and retinopathy was assessed on a Veteran Affairs Diabetes Trial subsample of 204 subjects with a mean duration of type 2 diabetes of 12.3 +/- 8.3 years. RESULTS - Retinopathy was correlated with CAC (r = 0.19, P = 0.006). Median CAC increased across retinopathy categories: 197 in those with no retinopathy, 229 in those with microaneurysms only, 364 in those with mild nonproliferative diabetic retinopathy (NPDR), 300 in those with moderate to severe NPDR, and 981 in those with proliferative diabetic retinopathy (PDR). Stepwise multivariable linear regression analysis was performed to find a parsimonious subset of relevant risk factors to include along with PDR in predicting CAC. After adjustment for either this subset of standard factors (P = 0.047) or a more extensive panel of risk factors (P = 0.035), PDR was significantly associated with CAC. Moreover, using logistic regression, individuals With PDR were approximately sixfold more likely to have CAC > 400 than those with no PDR, even after adjustment for other CVD risk factors. CONCLUSIONS - These data indicate an important relationship between retinopathy and extent of CAC and suggest the potential to identify and treat shared risk factors for these common micro- and macrovascular complications. C1 [Reaven, Peter D.; Duckworth, William] Carl T Hayden VA Med Ctr, Phoenix, AZ USA. [Moritz, Thomas] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program, Coordinating Ctr, Hines, IL 60141 USA. [Klein, Ronald; Davis, Mathew; Glander, Kathy] Univ Wisconsin, Madison, WI USA. [Abraira, Carlos] Miami VA Med Ctr, Miami, FL USA. RP Reaven, PD (reprint author), Phoenix VAMC, 650,E Indian Sch Rd 111E, Phoenix, AZ 85012 USA. EM peter.reaven@va.gov OI Klein, Ronald/0000-0002-4428-6237 FU NHLBI NIH HHS [R01 HL067690]; PHS HHS [R01067690] NR 39 TC 17 Z9 19 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2008 VL 31 IS 5 BP 952 EP 957 DI 10.2337/dc07-1926 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303CE UT WOS:000256016300024 PM 18316393 ER PT J AU Seicean, S Kirchner, HL Gottlieb, DJ Punjabi, NM Resnick, H Sanders, M Budhiraja, R Singer, M Redline, S AF Seicean, Sinziana Kirchner, H. Lester Gottlieb, Daniel J. Punjabi, Naresh M. Resnick, Helaine Sanders, Mark Budhiraja, Rohit Singer, Mendel Redline, Susan TI Sleep-disordered breathing and impaired glucose metabolism in normal-weight and overweight/obese individuals: The Sleep Heart Health Study SO DIABETES CARE LA English DT Article ID INSULIN-RESISTANCE; FASTING GLUCOSE; OBESE SUBJECTS; RISK-FACTORS; APNEA; TOLERANCE; EPIDEMIOLOGY; POLYSOMNOGRAPHY; POPULATION; DEFINITION AB OBJECTIVE - To characterize the association between sleep-disordered breathing (SDB) and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG and IGT, and occult diabetes in individuals of different body habitus. RESEARCH DESIGN AND METHODS - Cross-sectional analysis of 2,588 participants (aged 52-96 years; 46% men) without known diabetes. SDB was defined as respiratory disturbance index >= 10 events/h. IFG, IGT, occult diabetes, and body weight were classified according to recent accepted guidelines. Participants with and without SDB were compared on prevalence and odds ratios for measures of impaired glucose metabolism (IGM), adjusting for age, sex, race, BMI, and waist circumference. RESULTS - SDB was observed in 209 nonoverweight and 1,036 overweight/obese participants. SDB groups had significantly higher adjusted prevalence and adjusted odds of IFG, IFG plus IGT, and occult diabetes. The adjusted odds ratio for all subjects was 1.3 (95% Cl 1.1-1.6) for IFG, 1.2 (1.0-1.4) for IGT, 1.4 (1.1-2.7) for IFG plus IGT, and 1.7 (1.1-2.7) for occult diabetes. CONCLUSIONS - SDB was associated with occult diabetes, IFG, and IFG plus IGT, after adjusting for age, sex, race, BMI, and waist circumference. The magnitude of these associations was similar in nonoverweight and over-weight participants. The consistency of associations across all measures of IGM and body habitus groups and the significant association between SDB and IFG plus IGT, a risk factor for rapid progression to diabetes, cardiovascular disease, and mortality, suggests the importance of SDB as a risk factor for clinically important levels of metabolic dysfunction. C1 [Seicean, Sinziana; Singer, Mendel] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Kirchner, H. Lester] Geisinger Hlth Syst, Geisinger Ctr Hlth Res, Danville, PA USA. [Gottlieb, Daniel J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Resnick, Helaine] Georgetown Univ, Sch Med, Hyattsville, MD USA. [Resnick, Helaine] MedStar Res Inst, Hyattsville, MD USA. [Sanders, Mark] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Budhiraja, Rohit] So Arizona VA Healthcare Syst, Tucson, AZ USA. [Budhiraja, Rohit] Univ Arizona, Coll Med, Tucson, AZ USA. [Redline, Susan] Case Western Reserve Univ, Ctr Clin Invest, Cleveland, OH 44106 USA. RP Seicean, S (reprint author), 368 Columbia Rd, Bay Village, OH 44140 USA. EM sxs223@case.edu FU NHLBI NIH HHS [U01HL53916, U01HL 53937, U01HL 63429, U01HL 63463, U01HL53931, U01HL53934, U01HL53938, U01HL53940, U01HL53941, U01HL63429] NR 35 TC 84 Z9 87 U1 0 U2 6 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 MAY PY 2008 VL 31 IS 5 BP 1001 EP 1006 DI 10.2337/dc07-2003 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303CE UT WOS:000256016300035 PM 18268072 ER PT J AU Carr, DB Newton, KM Utzschneider, KM Tong, J Gerchman, F Kahn, SE Heckbert, SR AF Carr, Darcy B. Newton, Katherine M. Utzschneider, Kristina M. Tong, Jenny Gerchman, Fernando Kahn, Steven E. Heckbert, Susan R. TI Modestly elevated glucose levels during pregnancy are associated with a higher risk of future diabetes among women without gestational diabetes mellitus SO DIABETES CARE LA English DT Article ID LIFE-STYLE; TOLERANCE AB OBJECTIVE - To determine whether 1-h oral glucose challenge test (OGCT) or 3-h oral glucose tolerance test (OGTT) results below gestational diabetes mellitus (GDM) criteria are associated with developing diabetes. RESEARCH DESIGN AND METHODS - A retrospective cohort study was performed among women without GDM who had a pregnancy OGCT (n = 24,780) or OGTT (it = 6,222). Subsequent diabetes was ascertained by ICD-9 codes or pharmacy or laboratory data over a median follow-up of 8.8 years. RESULTS - Diabetes risk increased across OGCT quartiles: adjusted hazard ratio (HR) 1.67 (95% CI 1.07-2.61) for 5.4-6.2 mmol/l, 2.13 (1.39-3.25) for 6.3-7.3 mmol/l, and 3.60 (2.41-5.39) for >= 7.4 mmol/l compared with <= 53 mmol/l. Women with one abnormal OGTT result had a higher risk compared with those with normal Values (HR 2.08 [95% CI 1.35-3.201). CONCLUSIONS - Women with modestly elevated glucose levels below the threshold for GDM had a higher risk for diabetes. C1 [Carr, Darcy B.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Newton, Katherine M.; Heckbert, Susan R.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Newton, Katherine M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Utzschneider, Kristina M.; Gerchman, Fernando; Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Heckbert, Susan R.] Cardiovasc Hlth Res Unit, Seattle, WA USA. RP Carr, DB (reprint author), Univ Washington, Dept Obstet & Gynecol, Box 356460, Seattle, WA 98195 USA. EM darcarr@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [K23RR16066, K30RR022293] NR 15 TC 31 Z9 31 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2008 VL 31 IS 5 BP 1037 EP 1039 DI 10.2337/dc07-1957 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303CE UT WOS:000256016300041 PM 18223032 ER PT J AU Kitzmiller, JL Block, JM Brown, FM Catalano, PM Conway, DL Coustan, DR Gunderson, EP Herman, WH Hoffman, LD Inturrisi, M Jovanovic, LB Kjos, SI Knopp, RH Montoro, MN Ogata, ES Paramsothy, P Reader, DM Rosenn, BM Thomas, AM Kirkman, MS AF Kitzmiller, John L. Block, Jennifer M. Brown, Florence M. Catalano, Patrick M. Conway, Deborah L. Coustan, Donald R. Gunderson, Erica P. Herman, William H. Hoffman, Lisa D. Inturrisi, Maribeth Jovanovic, Lois B. Kjos, Siri I. Knopp, Robert H. Montoro, Martin N. Ogata, Edward S. Paramsothy, Pathmaja Reader, Diane M. Rosenn, Barak M. Thomas, Alyce M. Kirkman, M. Sue TI Managing preexisting diabetes for pregnancy - Summary of evidence and consensus recommendations for care SO DIABETES CARE LA English DT Review ID CORONARY-ARTERY-DISEASE; AMERICAN-HEART-ASSOCIATION; PERIPHERAL VASCULAR-DISEASE; NATIONAL-KIDNEY-FOUNDATION; MATERNAL GLUCOSE-LEVELS; INTIMA-MEDIA THICKNESS; INFANT BIRTH-WEIGHT; HIGH BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; EATING-DISORDERS C1 [Kitzmiller, John L.] Santa Clara Valley Med Ctr, Div Maternal Fetal Med, San Jose, CA 95128 USA. [Block, Jennifer M.] Stanford Univ, Med Ctr, Div Pediat Endocrinol, Stanford, CA 94305 USA. [Brown, Florence M.] Joslin Diabet Ctr, Dept Internal Med, Boston, MA 02215 USA. [Catalano, Patrick M.] Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA. [Conway, Deborah L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Coustan, Donald R.] Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, Brown Med Sch, Providence, RI 02908 USA. [Gunderson, Erica P.] Kaiser Permanente Fdn, Div Res, Epidemiol & Prevent Sect, Oakland, CA USA. [Herman, William H.] Univ Michigan, Sch Med, Dept Med, Ann Arbor, MI 48104 USA. [Hoffman, Lisa D.] Obstetrix Med Grp, Diabetes & Pregnancy Program, San Jose, CA USA. [Inturrisi, Maribeth] Northcoast Reg UCSF, Calif Diabetes & Pregnancy Program, San Francisco, CA USA. [Jovanovic, Lois B.] Sansum Diabet Res Inst, Santa Barbara, CA USA. [Kjos, Siri I.] Harbor UCLA Med Ctr, Dept Obstet & Gynecol, Torrance, CA USA. [Knopp, Robert H.] Univ Washington, Sch Med, NW Lipid Res Clin, Seattle, WA USA. [Montoro, Martin N.] Univ So Calif, Sch Med, Div Med Endocrinol, Los Angeles, CA USA. [Ogata, Edward S.] Northwestern Univ, Sch Med, Childrens Mem Hosp, Div Neonatol, Chicago, IL USA. [Paramsothy, Pathmaja] Univ Washington, Sch Med, Div Cardiol, Seattle, WA USA. [Reader, Diane M.] Int Diabet Ctr, Minneapolis, MN USA. [Rosenn, Barak M.] St Lukes Roosevelt Hosp, Div Maternal Fetal Med, New York, NY USA. [Thomas, Alyce M.] St Josephs Reg Med Ctr, Dept Obstet & Gynecol, Paterson, NJ USA. [Kirkman, M. Sue] Amer Diabet Assoc, Alexandria, VA USA. RP Kitzmiller, JL (reprint author), Santa Clara Valley Med Ctr, Div Maternal Fetal Med, 750 S Bascom Ave,Suite 340, San Jose, CA 95128 USA. EM kitz@batnet.com FU NIDDK NIH HHS [K01 DK059944, K01 DK059944-05] NR 179 TC 157 Z9 165 U1 2 U2 8 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 MAY PY 2008 VL 31 IS 5 BP 1060 EP 1079 DI 10.2337/dc08-9020 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 303CE UT WOS:000256016300045 PM 18445730 ER PT J AU Larkin, ME Capasso, VA Chen, CL Mahoney, EK Hazard, B Cagliero, E Nathan, DM AF Larkin, Mary E. Capasso, Virginia A. Chen, Chien-Lin Mahoney, Ellen K. Hazard, Barbara Cagliero, Enrico Nathan, David M. TI Measuring psychological insulin resistance - Barriers to insulin use SO DIABETES EDUCATOR LA English DT Article ID THERAPY; COMPLICATIONS AB Purpose The purpose of this study is to explore the attitudes that contribute to psychological insulin resistance (PIR) in insulin-naive patients with type 2 diabetes and to identify predictors of PIR. Methods A prospective study using 2 self-report surveys and incorporating demographic and health variables was conducted to determine the prevalence of PIR among a sample of 100 adult, insulin-naive patients with type 2 diabetes at an outpatient diabetes center in a university-affiliated teaching hospital. Results Thirty-three percent of patients with type 2 diabetes were unwilling to take insulin. The most commonly expressed negative attitudes were concern regarding hypoglycemia, permanent need for insulin therapy, less flexibility, and feelings of failure. Less than 40% expressed fear of self-injection or thought that injections were painful. However, compared with willing subjects, unwilling subjects were more likely to fear injections and thought injections would be painful, life would be less flexible, and taking insulin meant health would deteriorate (P <.005 for all comparisons). Poorer general health and higher depression scores also correlated with PIR. Conclusions The results of the surveys, which were generally consistent, identified several remediable misconceptions regarding insulin therapy and suggest targets for educational interventions. C1 [Larkin, Mary E.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Mahoney, Ellen K.; Hazard, Barbara] Boston Coll, Boston, MA USA. RP Larkin, ME (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St,Ste 340, Boston, MA 02114 USA. EM mlarkin1@partners.org NR 14 TC 66 Z9 69 U1 3 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2008 VL 34 IS 3 BP 511 EP 517 DI 10.1177/0145721708317869 PG 7 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 309OP UT WOS:000256470400011 PM 18535324 ER PT J AU Boylel, PJ Zrebiec, J AF Boylel, Patrick J. Zrebiec, John TI Impact of therapeutic advances on hypoglycaemia in type 2 diabetes SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Review DE hypoglycaemia; insulin; insulin analogues; type 2 diabetes; oral anti-diabetic agents ID SUBCUTANEOUS INSULIN INFUSION; IMPROVES GLYCEMIC CONTROL; ORAL ANTIDIABETIC AGENTS; TREAT-TO-TARGET; PRANDIAL GLUCOSE REGULATION; RANDOMIZED CONTROLLED-TRIAL; WITHIN-SUBJECT VARIABILITY; MULTIPLE DAILY INJECTIONS; HUMAN REGULAR INSULIN; BEDTIME NPH INSULIN AB Patients with type 2 diabetes experience hypoglycaemia less frequently than those with type I diabetes. Some protection against hypoglycaemia is afforded by the relatively intact glucose counter-regulatory pathways that characterize the pathophysiology of early type 2 diabetes. To some extent, this protection explains why hypoglycaemic episodes in intensively treated individuals with type 2 diabetes, when they occur, are rarely severe. As diabetes progresses and therapy intensifies to achieve recommended glycaemic goals, hypoglycaemia frequency and severity increase. Thus, when it comes to instituting intensive therapy, fear of hypoglycaemia may contribute to health-care providers' 'clinical inertia'. Because maintaining glycaemic control is so important to both public and individual health, many new therapies and technologies have been developed. This manuscript reviews and considers whether these advancements in therapy make glycaemic goals easier to achieve by minimizing hypoglycaemia. Putting the hypoglycaemia experienced by type 2 diabetes patients into appropriate clinical perspective, the impact of recent progress made in pharmacotherapy, drug delivery systems, and BG monitoring on hypoglycaemia incidence is largely positive. The extent to which this progress can effect improvement over traditional therapies will, however, depend upon patient (and provider) education, motivation and behaviour change. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Boylel, Patrick J.] Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. [Zrebiec, John] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Boylel, PJ (reprint author), Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. EM pboyle@salud.unm.edu NR 220 TC 6 Z9 6 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAY-JUN PY 2008 VL 24 IS 4 BP 257 EP 285 DI 10.1002/dmrr.795 PG 29 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 308RR UT WOS:000256408200001 PM 18232062 ER PT J AU Lipsky, BA AF Lipsky, Benjamin A. TI New developments in diagnosing and treating diabetic foot infections SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article; Proceedings Paper CT 5th International Symposium on Diabetic Foot CY MAY 09-12, 2007 CL Noordwijkerhout, NETHERLANDS DE diabetic foot infection; diagnosis of infection; antimicrobial therapy; microbiology ID RESISTANT STAPHYLOCOCCUS-AUREUS; VS. SUPERFICIAL SWAB; RISK-FACTORS; ULCERS; OSTEOMYELITIS; PREVALENCE; PATHOGENS; TRIAL; BONE; MICROORGANISMS AB Foot infections are common in persons with diabetes and are often the proximate cause of lower extremity amputation. There have been many publications in the past few years dealing with the appropriate ways to diagnose and treat diabetic foot infections. This review presents information gathered from a comprehensive, ongoing surveillance of the literature (published and abstracts) over the past 4 years. Prospective studies have now defined the epidemiology of diabetic foot infections, as well as methods to score and classify the wounds. Several recently published guidelines can assist clinicians in managing these infections. The etiologic agents of infection have been well-defined, and the prevalence of multi-drug-resistance pathogens is growing. Molecular methods offer great promise for quicker and more sensitive diagnosis of infection. New antimicrobial agents, both systemic and topical, as well as novel local treatments, have been shown to be effective in various studies. Improved methods of deploying older agents have added to the variety of treatment approaches now available. Several adjunctive treatments may benefit some patients but their role is as yet unclear. While there is much yet to learn about the most cost-effective ways to diagnose and treat diabetic foot infections the main effort is now to disseminate the available information and facilitate employing the evidence-based guideline recommendations. Published in 2008 by John Wiley & Sons, Ltd. C1 Univ Washington, Primary Care Clin, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Lipsky, BA (reprint author), Univ Washington, Primary Care Clin, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way S-111-PCC, Seattle, WA 98108 USA. EM balipsky@u.washington.edu RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 67 TC 22 Z9 27 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAY-JUN PY 2008 VL 24 SU 1 BP S66 EP S71 DI 10.1002/dmrr.828 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 308RS UT WOS:000256408300014 PM 18395871 ER PT J AU Klupa, T Skupien, J Gorczynska-Kosiorz, S Wanic, K Kusnierz-Cabala, B Solnica, B Sieradzki, J Malecki, MT AF Klupa, T. Skupien, J. Gorczynska-Kosiorz, S. Wanic, K. Kusnierz-Cabala, B. Solnica, B. Sieradzki, J. Malecki, M. T. TI Pancreatic exocrine insufficiency is not common in HNF-1 alpha MODY SO DIABETIC MEDICINE LA English DT Article DE exocrine insufficiency; MODY; mutation ID FECAL ELASTASE-1 CONCENTRATIONS; TRANSCRIPTION FACTORS; DIABETES-MELLITUS/; MUTATIONS; GENE; EXPRESSION; MARKER AB Aims Exocrine pancreatic insufficiency has been described in Type 1 and Type 2 diabetes. The hepatocyte nuclear factor (HNF)-1 alpha gene associated with maturity-onset diabetes of the young (MODY3) is expressed in several organs, including the exocrine pancreas. The aim of this study was to determine the prevalence of exocrine pancreas dysfunction in HNF-1 alpha MODY patients. Methods Thirty-one diabetic HNF-1 alpha MODY patients (mean age 37.2 +/- 14.6 years) and 35 healthy control subjects (39.1 +/- 13.9 years) participated. In addition, 25 Type 1 diabetic (T1DM) subjects were also examined (mean age 30.6 +/- 10.1 years). Exocrine pancreas function was assessed by measurement of stool elastase 1 (E1) activity. All diabetic patients and control subjects completed a gastrointestinal (GI) symptoms questionnaire. Results In all but two individuals, stool E1 levels were normal (> 200 mu g/g). The only case of severely impaired pancreas exocrine function (E1 = 47.5 mu g/g) was observed in the MODY3 group. The mean stool E1 elastase level in the HNF-1 alpha MODY group was significantly lower than in the control subjects (401.0 +/- 118.4 vs. 482.7 +/- 151.1 mu g/g, P = 0.001). Similarly, E1 levels in T1DM were lower than in control subjects (344.8 +/- 132.1 mu g/g, P = 0.001); one patient with a moderate enzyme decrease was identified in this group. In addition, more frequent GI complaints were reported by HNF-1 alpha MODY patients when compared with control subjects and also with T1DM patients. Conclusion Pancreatic exocrine insufficiency is not common in HNF-1 alpha MODY diabetic patients, although their stool E1 levels are lower than in healthy control subjects. C1 [Klupa, T.; Skupien, J.; Sieradzki, J.; Malecki, M. T.] Jagiellonian Univ, Dept Metab Dis, Coll Med, PL-31501 Krakow, Poland. [Gorczynska-Kosiorz, S.] L Warynski Silesian Med Acad, Dept Internal Med Diabetol & Nephrol, Zabrze, Poland. [Wanic, K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Wanic, K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kusnierz-Cabala, B.; Solnica, B.] Jagiellonian Univ, Dept Clin Biochem, Coll Med, PL-31501 Krakow, Poland. RP Malecki, MT (reprint author), Jagiellonian Univ, Dept Metab Dis, Coll Med, 15 Kopernika St, PL-31501 Krakow, Poland. EM malecki_malecki@yahoo.com NR 17 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAY PY 2008 VL 25 IS 5 BP 627 EP 630 DI 10.1111/j.1464-5491.2008.02432.x PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 292SE UT WOS:000255285600018 PM 18445177 ER PT J AU Olson, JS Lieberman, DA Sonnenberg, A AF Olson, Jeffrey S. Lieberman, David A. Sonnenberg, Amnon TI Empiric dilation in non-obstructive dysphagia SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE dysphagia; esophageal dilation; esophageal ring; gastro-esophageal reflux disease; peptic stricture; schatzki ring ID ESOPHAGEAL DILATION; REFLUX ESOPHAGITIS; PH; ENDOSCOPY AB Aims To study practice patterns in the management of non-obstructive dysphagia among U.S. gastroenterologists. Data source Endoscopic data repository from 100 U.S. gastroenterology practices during 1998-2003 (Clinical Outcomes Research Initiative, CORI). Methods All initial esophago-gastro-duodenoscopies (EGDs) performed in adult patients between 1998 and 2003 (n = 181,261) were evaluated for demographic data, endoscopic findings, and the occurrence of esophageal dilation. A case population of 7256 patients receiving empiric dilation for dysphagia for non-obstructive dysphagia was compared to a control population of 5764 patients with dilation for peptic strictures. Results The group of patients with empiric dilation was younger than the group of patients with peptic strictures and contained more women. Reflux symptoms and erosive esophagitis were less frequent in the empiric dilation group than in the strictures group. Empiric dilations were mostly performed using rubber bougies, whereas strictures were most frequently dilated over a guidewire. For all types of dilators, the diameters were significantly larger in empiric than stricture dilation. Repeat dilations within 1 year after the initial procedure occurred in 4% of the empiric and 13% of the stricture dilations. Conclusions Compared with the dilation of peptic strictures, empiric dilation of non-obstructive dysphagia is a more common clinical practice that is performed in a different patient population and utilizes different techniques. C1 [Olson, Jeffrey S.; Lieberman, David A.; Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Lieberman, David A.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu FU NIDDK NIH HHS [U01 DK 057132-06A1, R33 DK061778, U01 DK057132] NR 18 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2008 VL 53 IS 5 BP 1192 EP 1197 DI 10.1007/s10620-007-0024-x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 286LU UT WOS:000254848200004 PM 17932762 ER PT J AU Wang, JF Shackelford, JM Selliah, N Shivers, DK O'Neill, E Garcia, JV Muthumani, K Weiner, D Yu, XF Gabuzda, D Finkel, TH AF Wang, Jiangfang Shackelford, Jason M. Selliah, Nithianandan Shivers, Debra K. O'Neill, Eduardo Garcia, J. Victor Muthumani, Karuppiah Weiner, David Yu, Xiao-Fang Gabuzda, Dana Finkel, Terri H. TI The HIV-1 Vif protein mediates degradation of Vpr and reduces Vpr-induced cell cycle arrest SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; E3 UBIQUITIN LIGASE; TYPE-1 VPR; HUMAN APOBEC3G; T-CELLS; REVERSE TRANSCRIPTION; NUCLEAR-LOCALIZATION; MUTATIONAL ANALYSIS; REGULATORY PROTEIN; HUMAN-LYMPHOCYTES AB Prior work has implicated viral protein R (Vpr) in the arrest of human immunodeficiency virus type 1 (HIV-1) infected cells in the G2 phase of the cell cycle, associated with increased viral replication and host cell apoptosis. We and others have recently shown that virion infectivity factor (Vif) also plays a role in the G2 arrest of HIV-1 infected cells. Here, we demonstrate that, paradoxically, at early time points postinfection, Vif expression blocks Vpr-mediated G2 arrest, while deletion of Vif from the HIV-1 genome leads to a marked increase in G2 arrest of infected CD4 T-cells. Consistent with this increased G2 arrest, T-cells infected with Vif-deleted HIV-1 express higher levels of Vpr protein than cells infected with wild-type virus. Further, expression of exogenous Vif inhibits the expression of Vpr, associated with a decrease in G2 arrest of both infected and transfected cells. Treatment with the proteasome inhibitor MG132 increases Vpr protein expression and G2 arrest in wild-type, but not Vif-deleted, NL4-3-infected cells, and in cells cotransfected with Vif and Vpr. In addition, Vpr coimmunoprecipitates with Vif in cotransfected cells in the presence of MG132. This suggests that inhibition of Vpr by Vif is mediated at least in part by proteasomal degradation, similar to Vif-induced degradation of APOBEC3G. Together, these data show that Vif mediates the degradation of Vpr and modulates Vpr-induced G2 arrest in HIV-1-infected T-cells. C1 [Muthumani, Karuppiah; Weiner, David] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Finkel, Terri H.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Gabuzda, Dana] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Yu, Xiao-Fang] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Garcia, J. Victor] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Infect Dis, Dallas, TX 75390 USA. [O'Neill, Eduardo] Ctr Dis Control & Prevent, Mol Virol & Vaccines Branch, Div Influenza, Atlanta, GA USA. [Wang, Jiangfang; Shackelford, Jason M.; Selliah, Nithianandan; Shivers, Debra K.; Finkel, Terri H.] Childrens Hosp Philadelphia, Dept Pediat, Div Rheumatol, Philadelphia, PA 19104 USA. RP Finkel, TH (reprint author), Childrens Hosp Philadelphia, Dept Pediat, Div Rheumatol, 3516 Civic Ctr Blvd,Room 1102, Philadelphia, PA 19104 USA. EM finkelt@email.chop.edu RI Muthumani, Karuppiah/D-1092-2009 FU NIAID NIH HHS [R01-AI62555, R01-AI40003, R01-AI35513, R01-AI33331, R01 AI062644, R01 AI062555-04, R01 AI062555-02, R01 AI062555, R01 AI062555-01, R01 AI062555-03, R01 AI062644-04, R21-AI068527] NR 81 TC 15 Z9 18 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAY PY 2008 VL 27 IS 5 BP 267 EP U38 DI 10.1089/dna.2007.0707 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 299WA UT WOS:000255784600007 PM 18462066 ER PT J AU Slade, EP Stuart, EA Alkever, DSS Karakus, M Green, KM Ialongo, N AF Slade, Eric P. Stuart, Elizabeth A. Alkever, David S. S. Karakus, Mustafa Green, Kerry M. Ialongo, Nicholas TI Impacts of age of onset of substance use disorders on risk of adult incarceration among disadvantaged urban youth: A propensity score matching approach SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE incarceration; substance use disorder; adolescence; longitudinal; African American ID NATIONAL-COMORBIDITY-SURVEY; EFFECTS REGRESSION-ANALYSIS; DRUG-USE; YOUNG ADULTHOOD; PSYCHOSOCIAL ADJUSTMENT; AGGRESSIVE-BEHAVIOR; MULTIPLE IMPUTATION; SURVEY REPLICATION; TOBACCO SMOKING; ABUSE TREATMENT AB Background: Age of onset of substance use disorders in adolescence and early adulthood could be associated with higher rates of adult criminal incarceration in the U.S., but evidence of these associations is scarce. Methods: Propensity score matching was used to estimate the association between adolescent-onset substance use disorders and the rate of incarceration, as well as incarceration costs and self-reported criminal arrests and convictions, of young men predominantly from African American, lower income, urban households. Age of onset was differentiated by whether onset of the first disorder occurred by age 16. Results: Onset of a substance use disorder by age 16, but not later onset, was associated with a fourfold greater risk of adult incarceration for substance related offenses as compared to no disorder (0.35 vs. 0.09, P = 0.044). Onset by age 16 and later onset were both positively associated with incarceration costs and risk of arrest and conviction, though associations with crime outcomes were more consistent with respect to onset by age 16. Results were robust to propensity score adjustment for observable predictors of substance use in adolescence and involvement in crime as an adult. Conclusion: Among young men in this high risk minority sample, having a substance use disorder by age 16 was associated with higher risk of incarceration for substance related offenses in early adulthood and with more extensive criminal justice system involvement as compared to having no disorder or having a disorder beginning at a later age. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Slade, Eric P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Slade, Eric P.] US Dept Vet Affairs, Baltimore, MD 21201 USA. [Stuart, Elizabeth A.; Alkever, David S. S.; Green, Kerry M.; Ialongo, Nicholas] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Alkever, David S. S.] Univ Maryland, Dept Publ Policy, Baltimore, MD 21250 USA. [Karakus, Mustafa] WESTAT Corp, Rockville, MD 20850 USA. RP Slade, EP (reprint author), Univ Maryland, Sch Med, 737 W Lombard St,Room 526, Baltimore, MD 21201 USA. EM eslade@psych.umaryland.edu OI Stuart, Elizabeth/0000-0002-9042-8611 FU NIMH NIH HHS [P30 MH066247-01A29002, P30 MH066247, R34-MH081303, R03 MH069796-03, R34 MH081303, R03 MH069796, P30-MH066247, R34 MH081303-01] NR 65 TC 36 Z9 37 U1 5 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2008 VL 95 IS 1-2 BP 1 EP 13 DI 10.1016/j.drugalcdep.2007.11.019 PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 290WG UT WOS:000255152900001 PM 18242006 ER PT J AU Fenton, MS Marion, KM Hershman, JM AF Fenton, Mike S. Marion, Kenneth M. Hershman, Jerome M. TI Identification of cyclic adenosine 3 ',5 '- monophosphate response element modulator as an activator of the human Sodium/Iodide symporter upstream enhancer SO ENDOCRINOLOGY LA English DT Article ID THYROID TRANSCRIPTION FACTOR; CARCINOMA CELL-LINES; NA+/I-SYMPORTER; GENE-EXPRESSION; PROTEIN-LEVELS; PROMOTER CHARACTERIZATION; DIFFERENTIAL REGULATION; MESSENGER-RNA; FRTL-5 CELLS; CANCER CELLS AB The lack of Na+/ I- symporter (NIS) gene expression in some thyroid cancer patients has been a major hurdle that limits the efficacy of standard radioactive iodide therapy. The molecular mechanism that contributes to low NIS expression is not well understood. Activated NIS gene expression is stimulated by thyroid-stimulating hormone-mediated cAMP/ protein kinase A signaling through a NIS upstream enhancer (NUE). The cAMP pathway is also stimulated by forskolin. In the current work, we studied the mechanism of transcriptional activation of NIS in normal thyroid cells and thyroid cancer cells. We identified the cAMP response element modulator ( CREM) activator as a new component of the transcription complex that is important for NIS gene expression. The CREM complex is seen in the normal thyroid cells and BRAF ( V600E) thyroid cancer cells ( BHP 17 - 10) but is missing in rearranged in transformation/papillary thyroid carcinoma-1 rearrangement thyroid cancer cells ( BHP 2 - 7). This complex is believed to be responsible for the loss of NUE activity and reduced NIS expression in the BHP 2 - 7 cell line. In BHP 2 - 7 cells, forskolin stimulated the thyroid-specific transcription factor Pax 8, but CREM activator mRNA did not increase, and this produced a small increase in NUE activity. Ectopic expression of CREM activator enhanced activity of the NUE, indicating that CREM is an essential regulator of NIS gene expression. C1 [Fenton, Mike S.; Marion, Kenneth M.; Hershman, Jerome M.] Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol Res Lab,Endocrinol Div, Los Angeles, CA 90073 USA. [Fenton, Mike S.; Marion, Kenneth M.; Hershman, Jerome M.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Fenton, MS (reprint author), Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol Res Lab,Endocrinol Div, Bldg 114,Room 200,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM fenton@ucla.edu NR 40 TC 9 Z9 9 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 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2008 VL 149 IS 5 BP 2592 EP 2606 DI 10.1210/en.2007-1390 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 291LX UT WOS:000255200000060 PM 18202121 ER PT J AU Ryou, M Fong, DG Pai, RD Rattner, DW Thompson, CC AF Ryou, M. Fong, D. G. Pai, R. D. Rattner, D. W. Thompson, C. C. TI Transluminal closure for NOTES: an ex vivo study comparing leak pressures of various gastrotomy and colotomy closure modalities SO ENDOSCOPY LA English DT Article ID FULL-THICKNESS RESECTION; PORCINE MODEL; ABDOMINAL EXPLORATION; ENDOLUMINAL CLOSURE; ORGAN RESECTION; NOTES SURVIVAL; CHOLECYSTECTOMY; PERFORATIONS; STAPLER; DEVICE AB Background and study aims: Transluminal closure is fundamental to the safe introduction of natural orifice transluminal endoscopic surgery (NOTES) into humans. Suture, staples, and clips have been used. We aimed to evaluate the acute strength of various gastrotomy and colotomy closure techniques in an ex vivo porcine model by assessing air leak pressures. Patients and methods: The following closure modalities were assessed with at least five samples per arm: conventional open/laparoscopic suturing techniques including full-thickness interrupted sutures, double-layer sutures, and purse-string sutures, as well as endoscopic clips and endoscopic staples. Historical values for transgastric closures with hand-sewn interrupted sutures, endoscopic clips, and a prototype endoscopic suture device were used from our laboratory's prior study. Results: Using Kruskal-Wallis analysis, the overall comparisons were significant (P= 0.0038 for gastrotomy closure; P= 0.0018 for colotomy closure). Post hoc paired comparisons revealed that the difference between all closure arms versus negative control were significant. Significance could not be established among the various closure arms. However, trends suggested hand-sewn double-layer sutures, endoscopic staples, and both hand-sewn and endoscopically-placed purse-string sutures produced the strongest closures. Furthermore, endoscopic clips appeared sufficient for colotomy closure when ideally placed. Conclusions: Suture (both hand-sewn and endoscopically deployed) appears to produce the strongest closures in both stomach and colon, with the important caveats that (1) a continuous through-thickness suture track be avoided, such as in the full-thickness closure, or (2) suture holes be buried, such as in the purse-string configuration. When suture tracks are full-thickness, they can serve as leak sites. Staples and clips can produce comparable closures, but only under ideal conditions. C1 [Ryou, M.; Fong, D. G.; Pai, R. D.; Thompson, C. C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA USA. [Rattner, D. W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol & Hepatol, 75 Francis St, Boston, MA 02115 USA. EM ccthompson@partners.org NR 18 TC 51 Z9 52 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD MAY PY 2008 VL 40 IS 5 BP 432 EP 436 DI 10.1055/s-2007-995691 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 306EX UT WOS:000256232200012 PM 18404600 ER PT J AU Hermann, B Seidenberg, M Sager, M Carlsson, C Gidal, B Sheth, R Rutecki, P Asthana, S AF Hermann, Bruce Seidenberg, Michael Sager, Mark Carlsson, Cynthia Gidal, Barry Sheth, Raj Rutecki, Paul Asthana, Sanjay TI Growing old with epilepsy: The neglected issue of cognitive and brain health in aging and elder persons with chronic epilepsy SO EPILEPSIA LA English DT Review DE aging; cognition; chronic epilepsy; risk factors ID TEMPORAL-LOBE EPILEPSY; CARDIOVASCULAR RISK-FACTORS; ELEVATED PLASMA-CONCENTRATIONS; APOLIPOPROTEIN-E EPSILON-4; VOXEL-BASED MORPHOMETRY; MIDLIFE BLOOD-PRESSURE; ALZHEIMERS-DISEASE; LATE-LIFE; ANTIEPILEPTIC DRUGS; WHITE-MATTER AB The purpose of this review is to examine what is known about cognitive and brain aging in elders with chronic epilepsy. We contend that much remains to be learned about the ultimate course of cognition and brain structure in persons with chronic epilepsy and concern appears warranted. Individuals with chronic epilepsy are exposed to many risk factors demonstrated to be associated with abnormal cognitive and brain aging in the general population, with many of these risk factors present in persons with chronic epilepsy as early as midlife. We suggest that a research agenda be developed to systematically identify and treat known modifiable risk factors in order to protect and promote cognitive and brain health in aging and elder persons with chronic epilepsy. C1 [Hermann, Bruce; Sheth, Raj; Rutecki, Paul] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Mathews Neuropsychol Lab, Madison, WI 53792 USA. [Seidenberg, Michael] Rosalind Franklin Sch Med & Sci, Dept Psychol, N Chicago, IL USA. [Sager, Mark; Carlsson, Cynthia; Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Dept Geriatr Med, Madison, WI 53792 USA. [Hermann, Bruce; Sager, Mark] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53792 USA. [Carlsson, Cynthia; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. [Gidal, Barry] Univ Wisconsin, Sch Med & Publ Hlth, Sch Pharm, Madison, WI 53792 USA. [Rutecki, Paul] William S Middleton Mem Vet Adm Med Ctr, Dept Neurol, Madison, WI USA. RP Hermann, B (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Mathews Neuropsychol Lab, 600 N Highland, Madison, WI 53792 USA. EM hermann@neurology.wisc.edu FU NIA NIH HHS [K07 AG021582, K07 AG021582-03]; NINDS NIH HHS [R01 NS037738, R01 NS037738-02]; PHS HHS [R01 44351, 2R01 37738] NR 159 TC 19 Z9 19 U1 2 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2008 VL 49 IS 5 BP 731 EP 740 DI 10.1111/j.1528-1167.2007.01435.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 295NF UT WOS:000255480500001 PM 18031544 ER PT J AU Morrow, DA Sabatine, MS Brennan, ML de Lemos, JA Murphy, SA Ruff, CT Rifai, N Cannon, CP Hazen, SL AF Morrow, David A. Sabatine, Marc S. Brennan, Marie-Luise de Lemos, James A. Murphy, Sabina A. Ruff, Christian T. Rifai, Nader Cannon, Christopher P. Hazen, Stanley L. TI Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic events in TACTICS-TIMI 18 SO EUROPEAN HEART JOURNAL LA English DT Article DE unstable angina; myocardial infarction; biomarkers; prognosis ID C-REACTIVE PROTEIN; NATRIURETIC PEPTIDE; MYOCARDIAL-INFARCTION; TROPONIN-T; CARDIOVASCULAR-DISEASE; PREDICT MORTALITY; PROGNOSTIC VALUE; ARTERY-DISEASE; REVASCULARIZATION; STRATIFICATION AB Aims We investigated the prognostic performance of myeloperoxidase (MPO), and soluble CD40 ligand (sCD40L) along with B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), and cardiac troponin I (cTnI) for non-fatal recurrent ischaemic events in non-ST elevation acute coronary syndrome (ACS). Methods and results We measured plasma MPO and sCD40L in 1524 patients with ACS treated with tirofiban and randomized to early invasive vs. conservative management in the TACTICS-TIMI 18 trial who survived to 180 days. Patients with elevated baseline MPO (> 884 pM) were at higher risk of non-fatal myocardial infarction or rehospitalization for ACS at 30 days (9.3 vs. 4.6%, P < 0.001). In contrast, no difference was observed with higher sCD40L (> 989 pg/mL, 7.6 vs. 6.3%, P = 0.31). MPO remained associated with recurrent ischaemic events after adjustment for age, ST-deviation, diabetes, prior coronary artery disease, heart failure, cTnI, hsCRP, and sCD40L (OR 2.10; 95% CI 1.36-3.23, P = 0.001). This association was attenuated by 180 days (OR 1.26; 0.95-1.68). Stratification using baseline MPO, BNP, and cTnI identified a > 3-fold gradient of risk. Conclusion MPO adds to BNP and cTnI for short-term risk assessment for recurrent ischaemic events in non-ST elevation ACS. sCD40L was not associated with risk in this population treated with a platelet GPIIb/IIIa receptor antagonist. C1 [Morrow, David A.; Sabatine, Marc S.; Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Brennan, Marie-Luise; Hazen, Stanley L.] Cleveland Clin, Dept Cell Biol, Cleveland, OH 44106 USA. [de Lemos, James A.] Univ Texas SW Med Ctr Dallas, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA. [Rifai, Nader] Childrens Hosp, Med Ctr, Boston, MA 02115 USA. [Hazen, Stanley L.] Cleveland Clin Fdn, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44195 USA. [Hazen, Stanley L.] Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org FU NHLBI NIH HHS [P01 HL076491, P01 HL076491-05, U01 HL083-1341] NR 31 TC 105 Z9 113 U1 0 U2 7 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 MAY PY 2008 VL 29 IS 9 BP 1096 EP 1102 DI 10.1093/eurheartj/ehn071 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 296DK UT WOS:000255523500007 PM 18339606 ER PT J AU Muller-Krebs, S Kihm, LP Zeier, B Gross, ML Deppisch, R Wieslander, A Henle, T Penndorf, I Oh, J Reiser, J Nawroth, PP Zeier, M Schwenger, V AF Mueller-Krebs, S. Kihm, L. P. Zeier, B. Gross, M. L. Deppisch, R. Wieslander, A. Henle, T. Penndorf, I. Oh, J. Reiser, J. Nawroth, P. P. Zeier, M. Schwenger, V. TI Renal toxicity mediated by glucose degradation products in a rat model of advanced renal failure SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE advanced glycation end-products; carbonyl compounds; glucose degradation products; peritoneal dialysis fluids; peritoneal dialysis; systemic toxicity ID GLYCATION END-PRODUCTS; PERITONEAL-DIALYSIS FLUID; DIABETIC-NEPHROPATHY; GLOMERULOSCLEROSIS; APOPTOSIS; PODOCYTE; GROWTH; DAMAGE; HYPERTENSION; DYSFUNCTION AB Background In peritoneal dialysis (PD) residual renal function contributes to improved patient survival and quality of life. Glucose degradation products (GDP) generated by heat sterilization of PD fluids do not only impair the peritoneal membrane, but also appear in the systemic circulation with the potential for organ toxicity. Here we show that in a rat model of advanced renal failure, GDP affect the structure and function of the remnant kidney. Materials and methods Sprague-Dawley rats were randomly assigned to a two stage subtotal nephrectomy (SNX) or sham operation and were left untreated for 3 weeks. The SNX + GDP group continuously received chemically defined GDP intravenously for 4 weeks; the SNX and the sham-operated rats remained without GDP. The complete follow-up for all groups was 7 weeks postoperatively. We analysed renal damage using urinary albumin excretion as well as a semiquantitative score for glomerulosclerosis and tubulointerstitial damage, as well as for immunohistochemical analyses. Results The SNX + GDP rats developed significantly more albuminuria and showed a significantly higher score of glomerulosclerosis index (GSI) and tubulointerstitial damage index (TII) as compared to SNX or control rats. In the SNX + GDP group the expression of carboxymethyllysine and methylglyoxal was significantly higher in the tubulointerstitium and the glomeruli compared to the SNX rats. Caspase 3 staining and TUNEL assay were more pronounced in the tubulointerstitium and the glomeruli of the SNX + GDP group. In SNX + GDP animals, the expression of the slit diaphragm protein nephrin, was significantly lower compared to SNX or control animals. Conclusion In summary, our data suggests that GDP can significantly advance chronic kidney disease and argues that PD solutions containing high GDP might deteriorate residual renal function in PD. C1 [Mueller-Krebs, S.; Kihm, L. P.; Zeier, B.; Nawroth, P. P.; Zeier, M.; Schwenger, V.] Med Univ Heidelberg, Dept Nephrol, D-69120 Heidelberg, Germany. [Mueller-Krebs, S.; Kihm, L. P.; Zeier, B.; Nawroth, P. P.; Zeier, M.; Schwenger, V.] Med Univ Heidelberg, Dept Endocrinol & Nephrol, Heidelberg, Germany. [Gross, M. L.] Univ Heidelberg, Dept Pathol, D-6900 Heidelberg, Germany. [Deppisch, R.; Wieslander, A.] Gambro Res, Hechingen, Germany. [Deppisch, R.; Wieslander, A.] Gambro Res, Lund, Sweden. [Henle, T.; Penndorf, I.] Tech Univ Dresden, Inst Food Chem, Dresden, Germany. [Oh, J.] Univ Hosp, Pediat Hosp, Dept Paediat 1, Heidelberg, Germany. [Reiser, J.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02129 USA. [Reiser, J.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Muller-Krebs, S (reprint author), Med Univ Heidelberg, Dept Nephrol, Im Neuenheimer Feld 162, D-69120 Heidelberg, Germany. NR 34 TC 24 Z9 24 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAY PY 2008 VL 38 IS 5 BP 296 EP 305 DI 10.1111/j.1365-2362.2008.01945.x PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 283AZ UT WOS:000254610200003 PM 18346151 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Diminishing returns on sequential interventions of gastroenterology SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE gastrointestinal endoscopy; law of diminishing returns; medical decision analysis; random walk; side effects of medical interventions AB Gastroenterological treatment is often comprised of a series of multiple interventions, each one associated with a potential benefit, as well as harm. The analysis addresses the question of when to stop a series of consecutive interventions and maximize medical benefit. The benefit and harm associated with gastroenterological interventions are modeled as 'continuous' influences on patient health or as a 'discrete' sequence of random events. The analysis suggests that the benefit of a sequence of gastroenterological interventions is likely to accumulate following few interventions at the beginning of therapy and that any prolonged sequence is likely to inflict as much harm as benefit. It is impossible to reach a state of perfect health with inherently imperfect interventions. Health cannot be raised above a level that equals the ratio of expected benefit/(expected benefit+expected harm). As the achievement of perfect health constitutes an unattainable goal, a sequence of gastroenterological interventions should not be continued much further beyond its initial success. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Gastroenterol Sect, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Gastroenterol Sect, P3-Gl,3710 SW US Veterans Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 8 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD MAY PY 2008 VL 20 IS 5 BP 465 EP 468 DI 10.1097/MEG.0b013e3282f47982 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 325WR UT WOS:000257619900014 PM 18403949 ER PT J AU Pozdeyev, N Tosini, G Li, L Ali, F Rozov, S Lee, RH Iuvone, PM AF Pozdeyev, Nikita Tosini, Gianluca Li, Li Ali, Fatima Rozov, Stanislav Lee, Rehwa H. Iuvone, P. Michael TI Dopamine modulates diurnal and circadian rhythms of protein phosphorylation in photoreceptor cells of mouse retina SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE circadian clocks; dopamine D4 receptors; phosducin; retina ID TRANSDUCIN BETA-GAMMA; MAMMALIAN RETINA; MELATONIN SYNTHESIS; D4 RECEPTORS; IN-VIVO; PHOSDUCIN; CLOCK; COMPLEX; PHOSPHOPROTEIN; RELEASE AB Many aspects of photoreceptor metabolism are regulated as diurnal or circadian rhythms. The nature of the signals that drive rhythms in mouse photoreceptors is unknown. Dopamine amacrine cells in mouse retina express core circadian clock genes, leading us to test the hypothesis that dopamine regulates rhythms of protein phosphorylation in photoreceptor cells. To this end we investigated the phosphorylation of phosducin, an abundant photoreceptor-specific phosphoprotein. In mice exposed to a daily light-dark cycle, robust daily rhythms of phosducin phosphorylation and retinal dopamine metabolism were observed. Phospho-phosducin levels were low during the daytime and high at night, and correlated negatively with levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid. The effect of light on phospho-phosducin levels was mimicked by pharmacological activation of dopamine D4 receptors. The amplitude of the diurnal rhythm of phospho-phosducin was reduced by > 50% in D4 receptor-knockout mice, due to higher daytime levels of phospho-phosducin. In addition, the daytime level of phospho-phosducin was significantly elevated by L-745,870, a dopamine D4 receptor antagonist. These data indicate that dopamine and other light-dependent processes cooperatively regulate the diurnal rhythm of phosducin phosphorylation. Under conditions of constant darkness a circadian rhythm of phosducin phosphorylation was observed, which correlated negatively with the circadian rhythm of 3,4-dihydroxyphenylacetic acid levels. The circadian fluctuation of phospho-phosducin was completely abolished by constant infusion of L-745,870, indicating that the rhythm of phospho-phosducin level is driven by dopamine. Thus, dopamine release in response to light and circadian clocks drives daily rhythms of protein phosphorylation in photoreceptor cells. C1 [Pozdeyev, Nikita; Li, Li; Ali, Fatima; Rozov, Stanislav; Iuvone, P. Michael] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. [Pozdeyev, Nikita; Rozov, Stanislav] IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 194223, Russia. [Tosini, Gianluca] Morehouse Sch Med, Inst Neurosci, Atlanta, GA 30310 USA. [Lee, Rehwa H.] VA Greater LA Healthcare Syst Sepulveda, North Hills, CA USA. [Lee, Rehwa H.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. [Iuvone, P. Michael] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA. RP Iuvone, PM (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. EM miuvone@pharm.emory.edu RI Li, Li/C-8981-2011; OI tosini, gianluca/0000-0003-3645-4533 FU NCATS NIH HHS [UL1 TR000454]; NEI NIH HHS [EY004864, EY014764, P30 EY006360, R01 EY014764-04, R01 EY004864, R01 EY004864-25, R01 EY014764]; NINDS NIH HHS [R56 NS043459, NS43459, R01 NS043459-05A2, R01 NS043459] NR 53 TC 38 Z9 38 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X EI 1460-9568 J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2008 VL 27 IS 10 BP 2691 EP 2700 DI 10.1111/j.1460-9568.2008.06224.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 308MX UT WOS:000256395800021 PM 18547251 ER PT J AU Gulati, K Shah, ZK Sainani, N Uppot, R Sahani, DV AF Gulati, Kavita Shah, Zarine K. Sainani, Nisha Uppot, Raul Sahani, Dushyant V. TI Gastrointestinal tract labeling for MDCT of abdomen: Comparison of low density barium and low density barium in combination with water SO EUROPEAN RADIOLOGY LA English DT Article DE MDCT abdomen; neutral oral constrast media; gastrointestinal tract ID ORAL CONTRAST AGENT; ABDOMINAL COMPUTED-TOMOGRAPHY; HELICAL CT; CROHNS-DISEASE; BOWEL; ENTEROGRAPHY; STOMACH AB The purpose of the study was to compare the quality of stomach and small bowel marking/labeling using 1,350 ml of low-density barium alone (VoLumen) with 900 ml of low-density barium and 450 ml of water for 16-MDCT scans of the abdomen and pelvis and assess cost benefits with the two protocols. In this IRB approved study, 80 consecutive patients scheduled for routine CECT (contrast-enhanced CT) of the abdomen-pelvis were studied. Patients were randomized into two groups and were administered either 1,350 ml of VoLumen (two bottles at 20-min intervals, one half bottle at 50 min and the last half on the table) or 900 ml of VoLumen (two bottles at 20-min intervals and 450 ml water on the table). Portal venous phase scanning (detector collimation=0.625 mm, speed=18.75 mm, thickness=5 mm) was subsequently performed. Images were reconstructed in axial and coronal plane at the CT console. Two blinded readers used a pre-designed template to assess distension and wall characteristics of the stomach and small bowel on a 5-point scale. Median scores with the two protocols were compared using the Wilcoxon rank sum test. The stomach and small bowel labeling was rated fair to optimal in all patients and did not differ significantly in the two protocols. The mean scores for distension of the small bowel and stomach were comparable. Inter-observer agreement for bowel labeling was found to be excellent (k 0.81). With the use of coronal images there was increased reader confidence in tracing the small bowel with both protocols. Acceptance for two bottles of VoLumen and water was greater among patients as compared to three bottles of VoLumen. Use of two bottles of VoLumen and water combination cost less than three bottles of VoLumen. Stomach and small bowel labeling with administration of 900 ml of VoLumen followed by 450 ml of water is cost effective and compares well to 1,350 ml of VoLumen alone. C1 [Gulati, Kavita; Shah, Zarine K.; Sainani, Nisha; Uppot, Raul; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM kgulati@partners.org; zarine.shah@gmail.com; nsainani@partners.org; ruppot@partners.org; dsahani@partners.org RI Shah, Zarine/E-4064-2011 OI Shah, Zarine/0000-0002-0354-9678 NR 19 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD MAY PY 2008 VL 18 IS 5 BP 868 EP 873 DI 10.1007/s00330-007-0841-5 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 286LW UT WOS:000254848400002 PM 18183403 ER PT J AU Gingo, MR Silveira, LJ Miller, YE Friedlander, AL Cosgrove, GP Chan, ED Maier, LA Bowler, RP AF Gingo, M. R. Silveira, L. J. Miller, Y. E. Friedlander, A. L. Cosgrove, G. P. Chan, E. D. Maier, L. A. Bowler, R. P. TI Tumour necrosis factor gene polymorphisms are associated with COPD SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE gene polymorphism; genetics; smoking ID OBSTRUCTIVE PULMONARY-DISEASE; ALPHA TNF-ALPHA; SINGLE NUCLEOTIDE POLYMORPHISMS; INFLAMMATORY-BOWEL-DISEASE; PROMOTER POLYMORPHISM; CHRONIC-BRONCHITIS; MACROPHAGE METALLOELASTASE; MULTIPLE-SCLEROSIS; LYMPHOTOXIN-ALPHA; GENOTYPE CHANGES AB Tumour necrosis factor (TNF)-alpha has been shown to be an important factor in animal models of chronic obstructive pulmonary disease (COPD). However, human studies of TNF polymorphisms in COPD have been equivocal. Six TNF single nucleotide polymorphisms (-1031C/T, -863C/A, -857C/T, -237G/A, -308G/A and +487G/A) and their haplotypes were investigated in 423 Caucasian smokers (298 patients with spirometric evidence of COPD and 125 without airflow obstruction). The -308 minor allele (A) had a higher odds ratio (OR) of being associated with COPD in multivariate analysis (controlling for age, sex, pack-yrs; OR 1.9, 95% confidence interval (CI) 1.1-3.2) and was also associated with worse forced expiratory volume in one second/forced vital capacity. The -237 minor allele (A) had a lower OR of being associated with COPD (OR 0.40, 95% CI 0.19-0.86). In COPD patients, the -857 minor allele (T) had a lower OR of being associated with severe stages of COPD (Global Initiative for Obstructive Lung Disease stage III and IV versus stage I and II, OR 0.46, 95% CI 0.24-0.88). Other TNF single nucleotide polymorphisms were not associated with COPD but the -1031/-863 haplotype CC/TC had a lower OR in COPD patients versus smoking controls (OR 0.22, 95% CI 0.05-0.97). The present study adds further evidence that tumour necrosis factor genotypes play a role in susceptibility to cigarette smoke. C1 [Bowler, R. P.] Natl Jewish Med & Res Ctr, Div Pulm Med, Dept Med, Denver, CO 80206 USA. [Gingo, M. R.; Chan, E. D.] Univ Colorado, Dept Med, Denver, CO USA. [Gingo, M. R.; Chan, E. D.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Miller, Y. E.; Chan, E. D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. RP Bowler, RP (reprint author), Natl Jewish Med & Res Ctr, Div Pulm Med, Dept Med, 1400 Jackson St,Room K715a, Denver, CO 80206 USA. EM BowlerR@njc.org RI Gingo, Matthew/K-7203-2013 FU NCI NIH HHS [CA58187]; NCRR NIH HHS [M01 RR000051] NR 64 TC 35 Z9 40 U1 0 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD MAY PY 2008 VL 31 IS 5 BP 1005 EP 1012 DI 10.1183/09031936.00100307 PG 8 WC Respiratory System SC Respiratory System GA 298SI UT WOS:000255707000017 PM 18256059 ER PT J AU Fernandez, L Rodriguez, S Huang, H Chora, A Fernandes, J Murnaw, C Cruz, E Pollok, K Cristina, F Price, JE Ferkowicz, MJ Scadden, DT Clauss, M Cardoso, AA Carlesso, N AF Fernandez, Luis Rodriguez, Sonia Huang, Hui Chora, Angelo Fernandes, Jacquenilson Murnaw, Christin Cruz, Eugenia Pollok, Karen Cristina, Filipa Price, Joanne E. Ferkowicz, Michael J. Scadden, David T. Clauss, Matthias Cardoso, Angelo A. Carlesso, Nadia TI Tumor necrosis factor-alpha and endothelial cells modulate Notch signaling in the bone marrow microenvironment during inflammation SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; REPOPULATING ABILITY; FATE DETERMINATION; PROGENITOR CELLS; SELF-RENEWAL; IN-VITRO; KAPPA-B; EXPRESSION; LIGAND AB Objective. Homeostasis of the hematopoietic compartment is challenged and maintained during conditions of stress by mechanisms that are poorly defined. To understand how the bone marrow (BM) microenvironment influences hematopoiesis, we explored the role of Notch signaling and BM endothelial cells in providing microenvironmental cues to hematopoietic cells in the presence of inflammatory stimuli. Materials and Methods. The human BM endothelial cell line (BMEC) and primary human BM endothelial cells were analyzed for expression of Notch ligands and the ability to expand hematopoietic progenitors in an in vitro coculture system. In vivo experiments were carried out to identify modulation of Notch signaling in BM endothelial and hematopoietic cells in mice challenged with tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccluaride (LPS), or in Tie2-tmTNF-alpha transgenic mice characterized by constitutive TNF-alpha activation. Results. BM endothelial cells were found to express Jagged ligands and to greatly support progenitor's colony-forming ability. This effect was markedly decreased by Notch antagonists and augmented by increasing levels of Jagged2. Physiologic upregulation of Jagged2 expression on BMEC was observed upon TNF-alpha activation. Injection of TNF-alpha or LPS upregulated three- to fourfold Jagged2 expression on marine BM endothelial cells in vivo and resulted in increased Notch activation on murine hematopoietic stem/progenitor cells. Similarly, constitutive activation of endothelial cells in Tie2-tmTNF-alpha mice was characterized by increased expression of Jagged2 and by augmented Notch activation on hematopoietic stem/progenitor cells. Conclusions. Our results provide the first evidence that BM endothelial cells promote expansion of hematopoietic progenitor cells by a Notch-dependent mechanism and that TNF-alpha and LPS can modulate the levels of Notch ligand expression and Notch activation in the BM microenvironment in vivo. @ 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Carlesso, Nadia] Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Simon Canc Ctr, Indianapolis, IN 46202 USA. [Fernandez, Luis; Huang, Hui; Fernandes, Jacquenilson; Scadden, David T.; Carlesso, Nadia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA USA. [Chora, Angelo; Cristina, Filipa] Univ Lisbon, Inst Mol Med, P-1699 Lisbon, Portugal. [Cruz, Eugenia] Inst Mol & Cellular Biol, Oporto, Portugal. [Price, Joanne E.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. [Clauss, Matthias] Indiana Univ, Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN USA. [Clauss, Matthias] Indiana Univ, Sch Med, Indiana Ctr Vasc Biol & Med, Indianapolis, IN USA. [Cardoso, Angelo A.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. [Cardoso, Angelo A.] Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN USA. RP Carlesso, N (reprint author), Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Simon Canc Ctr, 1044 W Walnut,Bldg R4,Room 421, Indianapolis, IN 46202 USA. EM ncarless@iupui.edu OI Ferreira Chora, Angelo/0000-0002-7941-7196 FU NHLBI NIH HHS [R01 HL068256, R01 HL068256-03, R01 HL068256-04, R01 HL68256-01] NR 56 TC 27 Z9 28 U1 0 U2 5 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 MAY PY 2008 VL 36 IS 5 BP 545 EP 558 DI 10.1016/j.exphem.2007.12.012 PG 14 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 296XS UT WOS:000255579800003 PM 18439488 ER PT J AU Starr, PA Kang, GA Heath, S Shimamoto, S Turner, RS AF Starr, Philip A. Kang, Gail A. Heath, Susan Shimamoto, Shoichi Turner, Robert S. TI Pallidal neuronal discharge in Huntington's disease: Support for selective loss of striatal cells originating the indirect pathway SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Huntington's disease; Parkinson's disease; globus pallidus; microelectrode recording; electrophysiology; basal ganglia; indirect pathway ID DEEP BRAIN STIMULATORS; HUMAN BASAL GANGLIA; PARKINSONS-DISEASE; GLOBUS-PALLIDUS; SUBTHALAMIC NUCLEUS; SOMATOTOPIC ORGANIZATION; TECHNICAL APPROACH; PREFERENTIAL LOSS; DIFFERENTIAL LOSS; CORTEX NEURONS AB Chorea is the predominant motor manifestation in the early symptomatic phase of adult onset Huntington's disease (HD). Pathologically, this stage is marked by differential loss of striatal neurons contributing to the indirect pathway. This pattern of neuronal loss predicts decreased neuronal firing rates in GPi and increased firing rates in GPe, the opposite of the changes in firing rate known to occur in Parkinson's disease (PD). We present single-unit discharge characteristics (33 neurons) observed in an awake patient with HD (41 CAG repeats) undergoing microelectrode guided surgery for pallidal deep brain stimulation. Pallidal single-unit activity at "rest" and during voluntary movement was discriminated off line by principal component analysis and evaluated with respect to discharge rate, bursting, and oscillatory activity in the 0-200 Hz range. 24 GPi and 9 GPe units were studied, and compared with 132 GPi and 50 GPe units from 14 patients with PD. The mean (+/-SEM) spontaneous discharge rate for HD was 58+/-4 for GPi and 73+/-5 for GPe. This contrasted with discharge rates in PD of 95+/-2 for GPi and 57+/-3 for GPe. HD GPi units showed more bursting than PD GPi units but much less oscillatory activity in the 2-35 Hz frequency range at rest. These findings are consistent with selective early loss of striatal cells originating the indirect pathway. (C) 2008 Elsevier Inc. All rights reserved. C1 [Starr, Philip A.; Shimamoto, Shoichi; Turner, Robert S.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Starr, Philip A.; Kang, Gail A.; Heath, Susan; Turner, Robert S.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA 94143 USA. [Turner, Robert S.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15261 USA. [Turner, Robert S.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15261 USA. RP Starr, PA (reprint author), Univ Calif San Francisco, Dept Neurosurg, 533 Parnassus Box 0445, San Francisco, CA 94143 USA. EM starrp@neurosurg.ucsf.edu RI Turner, Robert/A-9695-2008 OI Turner, Robert/0000-0002-6074-4365 FU NINDS NIH HHS [K08 NS 02201, R01 NS044551, R01 NS044551-05, K08 NS002201] NR 38 TC 35 Z9 35 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2008 VL 211 IS 1 BP 227 EP 233 DI 10.1016/j.expneurol.2008.01.023 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 298ZM UT WOS:000255725600023 PM 18342309 ER PT J AU Wardell, DW Rintala, D Tan, G AF Wardell, Diane Wind Rintala, Diana Tan, Gabriel TI Study descriptions of Healing Touch with veterans experiencing chronic neuropathic pain from spinal cord injury SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING LA English DT Article DE Healing Touch; qualitative; case study; energy field; biofield therapy; energy medicine AB Context: Spinal cord injury often results in chronic pain syndromes that conventional pain management is unable to resolve. Healing Touch (HT) is a biofield therapy that involves using the hands to promote healing and mediate the perception of pain by affecting the energy field of the person. The practice of HT is based on the premise that the energy field has the ability to provide valuable information about the person's physical, emotional, mental, and spiritual condition and can influence the dense matter of physical form. Objective: This secondary analysis using case study reviews describes two different experiences of receiving a HT session for management of chronic neuropathic pain and its sequelae, utilizing energy field data and reports of participants and their HT practitioners. Design: Qualitative case study approach was used. Setting: Data were obtained from 42 HT sessions that took place within the homes of seven veterans with spinal cord injury. Method: Two cases involving the most common patterns of response were selected from seven cases to represent the participants' and practitioners' experiences. A descriptive qualitative approach informed the results. Results: The findings indicate that a variety of experiences can exist in individuals with chronic pain due to spinal cord injury; experiences will also vary with their healing touch practitioners. There are commonalities in the perception of the practitioners in the damage to the energy field and energy centers, with individualized and consistent resolution of the field over time. C1 [Wardell, Diane Wind] Univ Texas Houston, Hlth Sci Ctr, Sch Nursing, Houston, TX USA. [Rintala, Diana; Tan, Gabriel] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Wardell, DW (reprint author), 6901 Bertner Ave Suite 793, Houston, TX 77030 USA. EM diane.wardell@uth.tmc.edu NR 28 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-8307 J9 EXPLORE-NY JI Explore-J Sci. Heal. PD MAY-JUN PY 2008 VL 4 IS 3 BP 187 EP 195 DI 10.1016/j.explore.2008.02.003 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 306FZ UT WOS:000256235000010 PM 18466849 ER PT J AU Hadlock, T AF Hadlock, Tessa TI Facial paralysis: Research and future directions SO FACIAL PLASTIC SURGERY LA English DT Article DE facial paralysis; research; face-gram ID GRACILIS MUSCLE TRANSPLANTATION; NERVE GRADING SYSTEMS; BELLS-PALSY; HOUSE-BRACKMANN; SYNKINESIS; FACE; RECONSTRUCTION; REGENERATION; PREDNISOLONE; RELIABILITY AB Facial paralysis has fascinated physicians through the centuries. Management of the condition has evolved extensively over the past 50 years, relying largely upon neural repair techniques and static techniques prior to the 1940s, followed by heavy emphasis on regional muscle transfer by the 1970s.(1) With the advent of the operating microscope and the development of microinstrumentation, in the mid-1970s free tissue transfer became technically feasible, and new techniques quickly ensued that introduced functioning muscle as a viable and valuable option in the management of the paralyzed face.(2) These techniques have been subject to continual refinement to improve their reliability and reduce morbidity. In the modern era of evidence-based medicine, the field of facial nerve management has expanded exponentially with critical questions that will help future facial reanimation surgeons refine the approach for patients with acute and long-standing facial paralysis. This article will discuss current research areas with respect to assessment and management of the facial nerve patient, as well as future surgical outcomes. We win also present the state of both clinical research and contemporary basic science issues relevant to facial nerve disorders. C1 [Hadlock, Tessa] Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, Boston, MA 02114 USA. [Hadlock, Tessa] Harvard Univ, Sch Med, Boston, MA USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Facial Nerve Ctr, 243 Charles St, Boston, MA 02114 USA. NR 43 TC 10 Z9 12 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0736-6825 J9 FACIAL PLAST SURG JI Facial Plast. Surg. PD MAY PY 2008 VL 24 IS 2 BP 260 EP 267 DI 10.1055/s-2008-1075842 PG 8 WC Surgery SC Surgery GA 305OJ UT WOS:000256187400014 PM 18470838 ER PT J AU Scholz, J Toska, K Luborzewski, A Maass, A Schunemann, V Haavik, J Moser, A AF Scholz, Joachim Toska, Karen Luborzewski, Alexander Maass, Astrid Schuenemann, Volker Haavik, Jan Moser, Andreas TI Endogenous tetrahydroisoquinolines associated with Parkinson's disease mimic the feedback inhibition of tyrosine hydroxylase by catecholamines SO FEBS JOURNAL LA English DT Article DE enzyme stability; feedback inhibition; Parkinson's disease; tetrahydroisoquinolines; tyrosine hydroxylase ID AMINO-ACID HYDROXYLASES; N-METHYL-NORSALSOLINOL; ACTIVE-SITE IRON; DOPAMINERGIC NEUROTOXIN; PHENYLALANINE-HYDROXYLASE; CEREBROSPINAL-FLUID; CRYSTAL-STRUCTURE; IN-VITRO; PHOSPHORYLATION; RAT AB N-methyl-norsalsolinol and related tetrahydroisoquinolines accumulate in the nigrostriatal system of the human brain and are increased in the cerebrospinal fluid of patients with Parkinson's disease. We show here that 6,7-dihydroxylated tetrahydroisoquinolines such as N-methyl-norsalsolinol inhibit tyrosine hydroxylase, the key enzyme in dopamine synthesis, by imitating the mechanisms of catecholamine feedback regulation. Docked into a model of the enzyme's active site, 6,7-dihydroxylated tetrahydroisoquinolines were ligated directly to the iron in the catalytic center, occupying the same position as the catecholamine inhibitor dopamine. In this position, the ligands competed with the essential tetrahydropterin cofactor for access to the active site. Electron paramagnetic resonance spectroscopy revealed that, like dopamine, 6,7-dihydroxylated tetrahydroisoquinolines rapidly convert the catalytic iron to a ferric (inactive) state. Catecholamine binding increases the thermal stability of tyrosine hydroxylase and improves its resistance to proteolysis. We observed a similar effect after incubation with N-methyl-norsalsolinol or norsalsolinol. Following an initial rapid decline in tyrosine hydroxylation, the residual activity remained stable for 5 h at 37 degrees C. Phosphorylation by protein kinase A facilitates the release of bound catecholamines and is the most prominent mechanism of tyrosine hydroxylase reactivation. Protein kinase A also fully restored enzyme activity after incubation with N-methyl-norsalsolinol, demonstrating that tyrosine hydroxylase inhibition by 6,7-dihydroxylated tetrahydroisoquinolines mimics all essential aspects of catecholamine end-product regulation. Increased levels of N-methyl-norsalsolinol and related tetrahydroisoquinolines are therefore likely to accelerate dopamine depletion in Parkinson's disease. C1 [Scholz, Joachim] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA 02129 USA. [Scholz, Joachim; Luborzewski, Alexander; Moser, Andreas] Univ Lubeck, Dept Neurol, Neurochem Res Grp, Lubeck, Germany. [Scholz, Joachim] Harvard Med Sch, Charlestown, MA USA. [Toska, Karen; Haavik, Jan] Univ Bergen, Dept Biomed, Sect Biochem & Mol Biol, N-5020 Bergen, Norway. [Maass, Astrid] SCAI, Fraunhofer Inst Algorithms & Sci Comp, St Augustin, Germany. [Schuenemann, Volker] Tech Univ Kaiserslautern, Dept Phys, Kaiserslautern, Germany. RP Scholz, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Room 4309, Charlestown, MA 02129 USA. EM scholz.joachim@mgh.harvard.edu RI Schunemann, Volker/C-6603-2016; OI Haavik, Jan/0000-0001-7865-2808 NR 60 TC 5 Z9 6 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD MAY PY 2008 VL 275 IS 9 BP 2109 EP 2121 DI 10.1111/j.1742-4658.2008.06365.x PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290QR UT WOS:000255137800015 PM 18355318 ER PT J AU Mostoslavsky, R AF Mostoslavsky, Raul TI DNA repair, insulin signaling and sirtuins: at the crossroads between cancer and aging SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE lifespan; cancer; sirtuins; SIRT6; genomic instability; DNA repair; DNA damage; insulin signaling; metabolic homeostasis; review ID BASE EXCISION-REPAIR; DOUBLE-STRAND BREAKS; HEMATOPOIETIC STEM-CELLS; PANCREATIC BETA-CELLS; FOXO TRANSCRIPTION FACTORS; TUMOR-SUPPRESSOR GENE; LIFE-SPAN EXTENSION; ATM-DEFICIENT MICE; FACTOR-I RECEPTOR; CAENORHABDITIS-ELEGANS AB For many years organismal aging and cancer were viewed as separate entities. Recent studies however have suggested that these two seemingly disparate biological processes may in fact share common biochemical pathways. One area of emerging convergence involves the intersection of pathways known to mediate DNA repair with pathways previously implicated in insulin signaling. Recent evidence suggests that the sirtuin family of proteins act as central mediators of this molecular crosstalk. The coordination of DNA repair with overall energy balance may be essential for reducing the risk of developing cancer as well as for determining the rate at which we age. This review will summarize our current knowledge on how the maintenance of genomic integrity and insulin signaling intersect, the potential regulation of sirtuins in this crosstalk, and how this coordinated regulation may have important implication for both tumor-free and overall survival. C1 Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02114 USA. RP Mostoslavsky, R (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Canc Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM rmostoslavsky@mgh.harvard.edu NR 229 TC 8 Z9 8 U1 0 U2 7 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD MAY PY 2008 VL 13 BP 6966 EP 6990 DI 10.2741/3203 PG 25 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 301GS UT WOS:000255885000283 PM 18508709 ER PT J AU Joshi, VA Kucherlapati, R AF Joshi, Victoria A. Kucherlapati, Raju TI Genetics and genomics in the practice of medicine SO GASTROENTEROLOGY LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMORS; COLORECTAL-CANCER; PHARMACOGENETICS; IRINOTECAN; IMATINIB; TRIAL; GIST C1 [Joshi, Victoria A.; Kucherlapati, Raju] Harvard Univ, Sch Med, Partners HlthCare ctr Genet & Genom, Boston, MA 02115 USA. [Joshi, Victoria A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kucherlapati, R (reprint author), Harvard Univ, Sch Med, Partners HlthCare ctr Genet & Genom, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM rkucheriapati@partners.org NR 14 TC 5 Z9 5 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 MAY PY 2008 VL 134 IS 5 BP 1284 EP 1288 DI 10.1053/j.gastro.2008.03.046 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298HJ UT WOS:000255676700006 PM 18471501 ER PT J AU Wolpin, BM Mayer, RJ AF Wolpin, Brian M. Mayer, Robert J. TI Systemic treatment of colorectal cancer SO GASTROENTEROLOGY LA English DT Review ID III COLON-CANCER; GROWTH-FACTOR RECEPTOR; FLUOROURACIL PLUS LEUCOVORIN; SURGICAL ADJUVANT BREAST; RANDOMIZED CONTROLLED-TRIAL; HOSPITAL PROCEDURE VOLUME; WEEKLY BOLUS FLUOROURACIL; TOTAL MESORECTAL EXCISION; AMERICAN JOINT COMMITTEE; BLACK-WHITE DIFFERENCES AB Colorectal cancer is the fourth most common noncutaneous malignancy in the United States and the second most frequent cause of cancer-related death. Over the past 12 years, significant progress has been made in the systemic treatment of this malignant condition. Six new chemotherapeutic agents have been introduced, increasing median overall survival for patients with metastatic colorectal cancer from less than 9 months with no treatment to approximately 24 months. For patients with stage Ell (lymph node positive) colon cancer, an overall survival benefit for fluorouracil-based chemotherapy has been firmly established, and recent data have shown further efficacy for the inclusion of oxaliplatin in such adjuvant treatment programs. For patients with stage H colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at higher risk for disease recurrence. Ongoing randomized clinical trials are evaluating how best to combine currently available therapies, while smaller studies are evaluating new agents, with the goal of continued progress in prolonging life among patients with metastatic colorectal. cancer and increasing cure rates among those with resectable disease. C1 [Mayer, Robert J.] Dana Farber Canc Inst, Ctr Gastrointestinal Oncol, Boston, MA 02115 USA. [Wolpin, Brian M.; Mayer, Robert J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wolpin, Brian M.; Mayer, Robert J.] Dept Med Oncol, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Ctr Gastrointestinal Oncol, 44 Binney St, Boston, MA 02115 USA. EM robert_mayer@dfci.harvard.edu FU NCI NIH HHS [IP50CA127003-01, T32 CA009172, T32 CA009172-34, T32CA09001] NR 182 TC 215 Z9 227 U1 1 U2 20 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2008 VL 134 IS 5 BP 1296 EP 1310 DI 10.1053/j.gastro.2008.02.098 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298HJ UT WOS:000255676700009 PM 18471507 ER PT J AU Ioannou, GN Perkins, JD Carithers, RL AF Ioannou, George N. Perkins, James D. Carithers, Robert L., Jr. TI Liver transplantation for hepatocellular carcinoma: Impact of the MELD allocation system and predictors of survival SO GASTROENTEROLOGY LA English DT Article ID RADIOFREQUENCY ABLATION; ETHANOL INJECTION; EXPANDED CRITERIA; RECURRENCE; CIRRHOSIS; RESECTION AB Background & Aims: Since February 27, 2002, patients with early-stage hepatocellular carcinoma (HCC) have received priority for liver transplantation in the United States under the Model for End-Stage Liver Disease (MELD) allocation system. We aimed to determine the impact of this system on liver transplantation for HCC. Methods: Data were provided by the United Network for Organ Sharing on 19,404 first-time, cadaveric, adult liver transplantations performed in the United States between 2002 and 2007 and 15,906 performed between 1997 and 2002, an equal-duration period immediately preceding the MELD allocation system. Results: in 1997-2002, 4.6% of liver transplant recipients had HCC compared with 26% in 2002-2007, the majority of whom received "HCC-MELD-exceptions" allowing expedited transplantation. Posttransplantation survival of patients with HCC without an "HCC-MELD-exception" was significantly worse than the survival of patients without HCC. In 20022007, patients with an "HCC-MELD-exception" had similar survival to patients without HCC. However, for the subgroup of patients with tumors 3-5 cm in size had significantly worse survival. When compared with patients with similar MELD scores, patients in the "HCC-MELD-exception" group had worse posttransplantation survival than patients without HCC. The most important predictors of poor posttransplantation survival were MELD score >= 20 (hazard ratio, 1.61; 95% CI: 1.3-2.1) and serum a-fetoprotein level >= 455 ng/mL (hazard ratio, 2.15; 95% CI: 1.5-2.0). Conclusions: The adoption of the MELD allocation system has led to a 6-fold increase in the proportion of transplantation patients with HCC. Patients with larger (3-5 cm) tumors, serum a-fetoprotein level >= 455 ng/mL, or a MELD score >= 20 have poor posttransplantation survival. C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98108 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. [Perkins, James D.] Univ Washington, Dept Surg, Div Transplantat, Seattle, WA 98195 USA. [Ioannou, George N.; Carithers, Robert L., Jr.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, S 111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU PHS HHS [231-00-0115] NR 21 TC 134 Z9 138 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2008 VL 134 IS 5 BP 1342 EP 1351 DI 10.1053/j.gastro.2008.02.013 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298HJ UT WOS:000255676700014 PM 18471511 ER PT J AU Buchler, MW Warshaw, AL AF Buechler, Markus W. Warshaw, Andrew L. TI Resection versus drainage in treatment of chronic pancreatitis SO GASTROENTEROLOGY LA English DT Editorial Material ID PYLORUS-PRESERVING PANCREATICODUODENECTOMY; TERM-FOLLOW-UP; RANDOMIZED-TRIAL; HEAD RESECTION; NATURAL COURSE; PAIN; PANCREATICOJEJUNOSTOMY; SURGERY; THERAPY; WHIPPLE C1 [Buechler, Markus W.] Univ Heidelberg, Dept Surg, D-6900 Heidelberg, Germany. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. RP Buchler, MW (reprint author), Univ Heidelberg, Dept Surg, Im Neuenheimer Feld 110, D-6900 Heidelberg, Germany. NR 37 TC 21 Z9 23 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 MAY PY 2008 VL 134 IS 5 BP 1605 EP 1607 DI 10.1053/j.gastro.2008.03.029 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298HJ UT WOS:000255676700038 PM 18471528 ER PT J AU Yusuf, TE Matthes, K Brugge, WR AF Yusuf, Tony E. Matthes, Kai Brugge, William R. TI EUS-guided photodynamic therapy with verteporfin for ablation of normal pancreatic tissue: a pilot study in a porcine model (with video) SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 3rd International Symposium on Natural Orifice Translumenal Endoscopic Surgery CY JUL 10, 2008 CL San Francisco, CA ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; HIGH-GRADE DYSPLASIA; BARRETTS-ESOPHAGUS; MACULAR DEGENERATION; 5-AMINOLEVULINIC ACID; CANCER; FEASIBILITY AB Background: EUS-guided photodynamic therapy (PDT) with the photosensitizing agent porfimer sodium has been shown to he effective in ablation of pancreatic tissue. Objective: The objective of this study was to determine the effectiveness and safety of EUS PDT with verteporfin, a photosensitizer associated with less photosensitivity. Design: Prospective investigation of 6 swine that received an IV injection of 6 mg/m2 of verteporfin before EUS. Setting: Hospital animal laboratory. Interventions: The tail of the pancreas was located with EUS and was used to guide the placement of a light catheter. The pancreatic tail was exposed to 10, 15, or 20 minutes of laser light (689 nm). Main Outcome Measurements: Follow-up abdominal CT, liver and renal function tests, and serum pancreatic enzymes levels were performed. Histology of the pancreas was obtained 7 clays after the procedure on necropsy Results: Localized tissue necrosis within the pancreatic tail (range 6.6-30.5 mm in diameter) was seen in all animals. The diameter of the necrotic tissue was directly related to the close of light. No post-procedural complications were observed. Limitations: Normal animal model (lack of malignant tissue). Conclusions: EUS-guided PDT of porcine pancreas with verteporfin achieved localized pancreatic tissue ablation in a dose-related fashion. C1 [Yusuf, Tony E.; Matthes, Kai; Brugge, William R.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, 55 Fruit St,Blake 452C, Boston, MA 02114 USA. NR 21 TC 39 Z9 39 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2008 VL 67 IS 6 BP 957 EP 961 DI 10.1016/j.gie.2007.08.020 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 300LA UT WOS:000255824100029 PM 18178203 ER PT J AU Moeller, CC Mangos, S Drummond, IA Reiser, J AF Moeller, Clemens C. Mangos, Steve Drummond, Iain A. Reiser, Jochen TI Expression of trpC1 and trpC6 orthologs in zebrafish SO GENE EXPRESSION PATTERNS LA English DT Article DE transient receptor potential; ion channel; smooth muscle; in situ hybridization ID PECTORAL FIN; CHANNEL; MUTATION; PODOCIN; CELLS; GUT AB Transient receptor potential (TRP) genes encode subunits that form cation-selective ion channels in a variety of organisms and cell types. TRP channels serve diverse functions ranging from thermal, tactile, taste, and osmolar sensing to fluid flow sensing. TRPC1 and TRPC6 belong to the TRPC subfamily, members of which are thought to contribute to several cellular events such as regulated migration of neuronal dendrites, contractile responses of smooth muscle cells and maintenance of the structural integrity of kidney podocytes. Pathogenic roles have been suggested for TRPC1 in asthma and chronic obstructive pulmonary disease, and TRPC6 dysfunction was recently linked to proteinuric kidney disease. To explore the potential roles for TRPC channels in zebrafish organ function, we cloned zebrafish trpC1 and trpC6 cDNAs, and investigated their expression during zebrafish development. We detected trpC1 expression in the head, in cells surrounding the outflow tract of the heart, and in the ganglion cells as well as the inner nuclear layer of the eye. trpC6 expression was detected in the head, pectoral fins, aortic endothelial cells, and gastrointestinal smooth muscle cells. Our results point to roles of TRPC channels in several tissues during zebrafish development, and suggest that the zebrafish may be a suitable model system to study the pathophysiology of TRPC1 and TRPC6 in specific cell types. (c) 2008 Elsevier B.V. All rights reserved. C1 [Moeller, Clemens C.; Mangos, Steve; Drummond, Iain A.; Reiser, Jochen] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02129 USA. [Moeller, Clemens C.; Mangos, Steve; Drummond, Iain A.; Reiser, Jochen] Massachusetts Gen Hosp, Program Glomerular Dis, Boston, MA 02129 USA. [Moeller, Clemens C.; Mangos, Steve; Drummond, Iain A.; Reiser, Jochen] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Moeller, Clemens C.] Univ Heidelberg, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany. RP Reiser, J (reprint author), Massachusetts Gen Hosp, Div Nephrol, Suite 8214,CNY 149 13th St, Boston, MA 02129 USA. EM jreiser@partners.org NR 29 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD MAY PY 2008 VL 8 IS 5 BP 291 EP 296 DI 10.1016/j.gep.2008.02.002 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 304YX UT WOS:000256146100001 ER PT J AU Kontos, N Freudenreich, O Querques, J AF Kontos, Nicholas Freudenreich, Oliver Querques, John TI Ownership, responsibility and hospital care: lessons for the consultation psychiatrist SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE consultation; practice; advocacy; teams ID MEDICAL-CARE; LIAISON PSYCHIATRY; MAJOR DEPRESSION; ADVERSE EVENTS; PATIENT-CARE; MENTALLY-ILL; WORK HOURS; SCHIZOPHRENIA; CONCORDANCE; PHYSICIANS AB Objective: To identify scenarios in which consultation psychiatrists encounter difficulty reconciling their clinical role with consultees' expectations and to suggest concepts that help navigate these situations. Methods: The authors' clinical experiences are used to generate and discuss three major categories of situations that require psychiatric consultants to thoughtfully adjust the breadth and depth of their obligation to patients and consultees. Results: "Occam's razor 'dulled," "Conflation of the psychosocial with the psychiatric" and "Disposition preoccupation" are proposed as the major categories leading to conflicting patient management views between consultant and consultee. Each has, at its core, a compromise of patient ownership that blurs the boundaries of the consulting psychiatrist's responsibility. Conclusions: Understanding and channeling ownership back to the consultee, while appropriately gauging and embracing one's responsibility, form a two-pronged approach to clarifying one's role in consultations. (c) 2008 Elsevier Inc. All rights reserved. C1 [Freudenreich, Oliver; Querques, John] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Kontos, Nicholas] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA 02139 USA. RP Kontos, N (reprint author), Cambridge Hosp, Dept Psychiat, Cambridge, MA 02139 USA. EM nkontos@challiance.org NR 44 TC 4 Z9 4 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY-JUN PY 2008 VL 30 IS 3 BP 257 EP 262 DI 10.1016/j.genhosppsych.2007.11.001 PG 6 WC Psychiatry SC Psychiatry GA 294TN UT WOS:000255428900008 PM 18433658 ER PT J AU Yang, XH Shiotani, B Classon, M Zou, L AF Yang, Xiaohong H. Shiotani, Bunsyo Classon, Marie Zou, Lee TI Chk1 and claspin potentiate PCNA ubiquitination SO GENES & DEVELOPMENT LA English DT Article DE Chk1; claspin; ATR; PCNA; ubiquitination; replication ID REPLICATION FORK PROGRESSION; DNA-POLYMERASE-ETA; S-PHASE; MONOUBIQUITINATED PCNA; CHECKPOINT; ATR; DAMAGE; MRC1; COMPLEX; CHROMATIN AB Chk1 is a kinase crucial for genomic integrity and an effector of ATR (ATM and Rad3-realated) in DNA damage response. Here, we show that Chk1 regulates the DNA damage-induced ubiquitination of proliferating cell nuclear antigen ( PCNA), which facilitates the continuous replication of damaged DNA. Surprisingly, this Chk1 function requires the DNA replication protein Claspin but not ATR. Claspin, which is stabilized by Chk1, regulates the binding of the ubiquitin ligase Rad18 to chromatin. Timeless, a Claspin-associating protein, is also required for efficient PCNA ubiquitination. Thus, Chk1 and the Claspin-Timeless module of replication forks not only participate in ATR signaling, but also protect stressed forks independently of ATR. C1 [Yang, Xiaohong H.; Shiotani, Bunsyo; Classon, Marie; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Zou, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu FU NIGMS NIH HHS [GM076388, R01 GM076388] NR 35 TC 65 Z9 66 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 2008 VL 22 IS 9 BP 1147 EP 1152 DI 10.1101/gad.1632808 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 295WJ UT WOS:000255504500005 PM 18451105 ER PT J AU Yoshida, T Hazan, I Zhang, J Ng, SY Naito, T Snippert, HJ Heller, EJ Qi, XQ Lawton, LN Williams, CJ Georgopoulos, K AF Yoshida, Toshimi Hazan, Idit Zhang, Jiangwen Ng, Samuel Y. Naito, Taku Snippert, Hugo J. Heller, Elizabeth J. Qi, Xiaoqing Lawton, Lee N. Williams, Christine J. Georgopoulos, Katia TI The role of the chromatin remodeler Mi-2 beta in hematopoietic stem cell self-renewal and multilineage differentiation SO GENES & DEVELOPMENT LA English DT Article DE Mi-2 beta; chromatin; HSC; multipotency; self-renewal; lineage priming ID GENE-EXPRESSION; LINEAGE COMMITMENT; HISTONE DEACETYLASE; PRECEDES COMMITMENT; ERYTHROID-CELLS; COMPLEX; NICHE; IKAROS; MICE; IDENTIFICATION AB The ability of somatic stem cells to self-renew and differentiate into downstream lineages is dependent on specialized chromatin environments that keep stem cell-specific genes active and key differentiation factors repressed but poised for activation. The epigenetic factors that provide this type of regulation remain ill-defined. Here we provide the first evidence that the SNF2-like ATPase Mi-2 beta of the Nucleosome Remodeling Deacetylase (NuRD) complex is required for maintenance of and multilineage differentiation in the early hematopoietic hierarchy. Shortly after conditional inactivation of Mi-2 beta, there is an increase in cycling and a decrease in quiescence in an HSC (hematopoietic stem cell)-enriched bone marrow population. These cycling mutant cells readily differentiate into the erythroid lineage but not into the myeloid and lymphoid lineages. Together, these effects result in an initial expansion of mutant HSC and erythroid progenitors that are later depleted as more differentiated proerythroblasts accumulate at hematopoietic sites exhibiting features of erythroid leukemia. Examination of gene expression in the mutant HSC reveals changes in the expression of genes associated with self-renewal and lineage priming and a pivotal role of Mi-2 beta in their regulation. Thus, Mi-2 beta provides the hematopoietic system with immune cell capabilities as well as with an extensive regenerative capacity. C1 [Yoshida, Toshimi; Hazan, Idit; Ng, Samuel Y.; Naito, Taku; Snippert, Hugo J.; Heller, Elizabeth J.; Qi, Xiaoqing; Lawton, Lee N.; Williams, Christine J.; Georgopoulos, Katia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Zhang, Jiangwen] Harvard Univ, Sch Med, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. RP Yoshida, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM toshimi.yoshida@cbrc2.mgh.harvard.edu; katia.georgopoulos@cbrc2.mgh.harvard.edu RI Zhang, Jiangwen/A-7654-2013 FU NIAID NIH HHS [R01AI42254-12, R01 AI042254] NR 76 TC 89 Z9 89 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 2008 VL 22 IS 9 BP 1174 EP 1189 DI 10.1101/gad.1642808 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 295WJ UT WOS:000255504500008 PM 18451107 ER PT J AU Pe'er, I Yelensk, R Altshuler, D Daly, MJ AF Pe'er, Itsik Yelensk, Roman Altshuler, David Daly, Mark J. TI Estimation of the multiple testing burden for genomewide association studies of nearly all common variants SO GENETIC EPIDEMIOLOGY LA English DT Article DE human genetics; association studies; testing burden ID WIDE ASSOCIATION; REPLICATION; EFFICIENT; PROJECT; SCANS AB Genomewide association studies are an exciting strategy in genetics, recently becoming feasible and harvesting many novel genes linked to multiple phenotypes. Determining the significance of results in the face of testing a genomewide set of multiple hypotheses, most of which are producing noisy, null-distributed association signals, presents a challenge to the wide community of association researchers. Rather than each study engaging in independent evaluation of significance standards, we have undertaken the task of developing such standards for genomewide significance, based on data collected by the International Haplotype Map Consortium. We report an estimated testing burden of a million independent tests genomewide in Europeans, and twice that number in Africans. We further identify the sensitivity of the testing burden to the required significance level, with implications to staged design of association studies. C1 [Altshuler, David; Daly, Mark J.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. [Yelensk, Roman; Altshuler, David; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yelensk, Roman] Harvard MJT, Div Hlth Sci & Technol, Cambridge, MA USA. [Altshuler, David] Broad Inst MIT & Harvard, Cambridge, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Daly, Mark J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Diabet Unit, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [5 U54 CA121852]; NIDDK NIH HHS [F32 DK070527] NR 24 TC 309 Z9 309 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD MAY PY 2008 VL 32 IS 4 BP 381 EP 385 DI 10.1002/gepi.20303 PG 5 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 295JP UT WOS:000255471100009 PM 18348202 ER PT J AU Bodensteiner, D Scott, CR Sims, KB Shepherd, GM Cintron, RD Germain, DP AF Bodensteiner, David Scott, C. Ronald Sims, Katherine B. Shepherd, Gillian M. Cintron, Rebecca D. Germain, Dominique P. TI Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme SO GENETICS IN MEDICINE LA English DT Article DE Fabry disease; agalsidase beta; enzyme replacement therapy; lysosomal storage disease; X-linked disorder ID REPLACEMENT THERAPY; DESENSITIZATION; EFFICACY; SAFETY; ALPHA AB Purpose: To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme (R)), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta. Methods: The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled. Results: During rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug. Conclusions: Agalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme. C1 [Bodensteiner, David] Univ Kansas, Med Ctr, Div Hematol Oncol, Kansas City, KS 66103 USA. [Scott, C. Ronald] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Scott, C. Ronald] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sims, Katherine B.] Harvard Univ, Sch Med, Boston, MA USA. [Shepherd, Gillian M.] Cornell Univ, Dept Med, Weill Med Coll, New York, NY 10021 USA. [Cintron, Rebecca D.] Genzyme Corp, Pharmacovigilance Dept, Cambridge, MA USA. [Germain, Dominique P.] Hop Raymond Poincare, AP HP, Ctr Reference Malad Fabry & Malad Hereditaires Ti, Garches, France. [Germain, Dominique P.] Univ Versailles St Quentin Yvelines, Garches, France. RP Bodensteiner, D (reprint author), Univ Kansas, Div Hematol Oncol, Med Ctr, 2330 Shawnce Mission Pkwy, Westwood, KS 66205 USA. EM dbodenst@kumc.edu; dominique.gemian@rpc.aphp.fr NR 11 TC 32 Z9 33 U1 0 U2 2 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 MAY PY 2008 VL 10 IS 5 BP 353 EP 358 DI 10.1097/GIM.0b013e318170f868 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 303VU UT WOS:000256069800010 PM 18496035 ER PT J AU Jiao, Y Jin, XD Yan, J Zhang, C Jiao, F Li, XM Roe, BA Mount, DB Gu, WK AF Jiao, Yan Jin, Xiudong Yan, Jian Zhang, Chi Jiao, Feng Li, Xinmin Roe, Bruce A. Mount, David B. Gu, Weikuan TI A deletion mutation in Slc12a6 is associated with neuromuscular disease in gaxp mice SO GENOMICS LA English DT Article DE genome; giant axonopathy; high-throughput screening; microarray; mouse; mutation ID KINASE-ASSOCIATED NEURODEGENERATION; HALLERVORDEN-SPATZ-SYNDROME; CL COTRANSPORTER KCC3; CORPUS-CALLOSUM; BRAIN; HETEROGENEITY; NEUROPATHY; GIGAXONIN; SURVIVAL; FAMILY AB Giant axonopathy (gaxp), an autosomal recessive mouse mutation, exhibits ataxia of the hind legs with a slight side-to-side wobble while walking. Within the genomic region of the gaxp locus, a total of 94 transcripts were identified; the annotation of these genes using OMIM and PubMed yielded three potential candidate genes. By cDNA microarray analysis, 54 genes located on or near the gaxp locus were found to exhibit differential expression between gaxp and littermate controls. Based on microarray data and the known function of genes identified, Slc12a6 was selected as the primary candidate gene and analyzed using the Reveal technology of SpectruMedix. A 17-base deletion was detected from within exon 4 of Slc12a6. Reverse transcriptase polymerase chain reaction validated the difference in Slc12a6 expression in different types of mice at the mRNA level, revealing a marked reduction in gaxp mice. Western blot analysis indicated that the protein product of Slcl2a6, the K+-Cl- cotransporter Kcc3, was not detectable in gaxp mice. The causative role of the exon 4 mutation within Sle12a6 in the gaxp phenotype was further confirmed by screening multiple inbred strains and by excluding the mutation of nearby genes within the gaxp locus. (c) 2008 Elsevier Inc. All rights reserved. C1 [Jiao, Yan; Yan, Jian; Zhang, Chi; Jiao, Feng; Gu, Weikuan] Univ Tennessee, Ctr Hlth Sci, Campbell Clin, Dept Orthopaed Surg, Memphis, TN 38163 USA. [Jiao, Yan; Yan, Jian; Zhang, Chi; Jiao, Feng; Gu, Weikuan] Univ Tennessee, Ctr Hlth Sci, Dept Pathol, Memphis, TN 38163 USA. [Jin, Xiudong] Mudanjian Med Coll, Mudanjian 157001, Peoples R China. [Li, Xinmin] Univ Chicago, Chicago, IL 60637 USA. [Roe, Bruce A.] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA. [Mount, David B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Gu, WK (reprint author), Univ Tennessee, Ctr Hlth Sci, Campbell Clin, Dept Orthopaed Surg, Memphis, TN 38163 USA. EM wgu@utmem.edu FU NIAMS NIH HHS [R01 AR51190, R01 AR051190-03, R01 AR051190-01, R01 AR051190, R01 AR051190-02, R01 AR051190-04]; NIDDK NIH HHS [R01 DK57708, R01 DK057708] NR 31 TC 7 Z9 7 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 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 2008 VL 91 IS 5 BP 407 EP 414 DI 10.1016/j.ygeno.2007.12.010 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 296KE UT WOS:000255541100002 PM 18343091 ER PT J AU Mccue, ME Valberg, SJ Miller, MB Wade, C DiMauro, S Akman, HO Mickelson, JR AF McCue, Molly E. Valberg, Stephanie J. Miller, Michael B. Wade, Claire DiMauro, Salvatore Akman, Hasan O. Mickelson, James R. TI Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis SO GENOMICS LA English DT Article DE genome-wide association; horse; glycogen storage disease; glycogen synthase; gain-of-function mutation; polysaccharide storage myopathy ID POLYSACCHARIDE STORAGE MYOPATHY; GLUCOSE-BINDING-SITE; HORSE-RELATED BREEDS; GLY-GLY SEQUENCE; ESCHERICHIA-COLI; ACTIVE-SITE; QUARTER HORSES; EXERTIONAL RHABDOMYOLYSIS; SACCHAROMYCES-CEREVISIAE; COS CELLS AB Polysaccharide storage myopathy (PSSM) is a novel glycogenosis in horses characterized by abnormal glycogen accumulation in skeletal muscle and muscle damage with exertion. It is unlike glycogen storage diseases resulting from known defects in glycogenolysis, glycolysis, and glycogen synthesis that have been described in humans and domestic animals. A genome-wide association identified GYS1, encoding skeletal muscle glycogen synthase (GS), as a candidate gene for PSSM. DNA sequence analysis revealed a mutation resulting in an arginine-to-histidine substitution in a highly conserved region of GS. Functional analysis demonstrated an elevated GS activity in PSSM horses, and haplotype analysis and allele age estimation demonstrated that this mutation is identical by descent among horse breeds. This is the first report of a gain-of-function mutation in GYS1 resulting in a glycogenosis. (c) 2008 Elsevier Inc. All rights reserved. C1 [McCue, Molly E.; Valberg, Stephanie J.] Univ Minnesota, Coll Vet Med, Dept Vet Populat Med, St Paul, MN 55108 USA. [Miller, Michael B.] Univ Minnesota, Sch Publ Hlth, Dept Epidemiol, Minneapolis, MN 55454 USA. [Wade, Claire] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [DiMauro, Salvatore; Akman, Hasan O.] Columbia Univ, Med Ctr, H Houston Merritt Clin Res Ctr, Dept Neurol, New York, NY 10027 USA. [Mickelson, James R.] Univ Minnesota, Sch Publ Hlth, Coll Vet Med, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. RP Mccue, ME (reprint author), Univ Minnesota, Coll Vet Med, Dept Vet Populat Med, St Paul, MN 55108 USA. EM mccu0173@umn.edu OI Wade, Claire/0000-0003-3413-4771 FU NCRR NIH HHS [T32 RR018719, T32 RR018719-02, T32RR018719-02]; NIH HHS [T32 OD010993] NR 54 TC 72 Z9 72 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 2008 VL 91 IS 5 BP 458 EP 466 DI 10.1016/j.ygeno.2008.01.011 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 296KE UT WOS:000255541100008 PM 18358695 ER PT J AU Folkins, AK Jarboe, EA Saleemuddin, A Lee, Y Callahan, MJ Drapkin, R Garber, JE Muto, MG Tworoger, S Crum, CP AF Folkins, Ann K. Jarboe, Elke A. Saleemuddin, Aasia Lee, Yonghee Callahan, Michael J. Drapkin, Ronny Garber, Judy E. Muto, Michael G. Tworoger, Shelley Crum, Christopher P. TI A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian neoplasms; BRCA; serous carcinoma; carcinogenesis; fallopian tube neoplasms; precancer; precursor; p53 ID PROPHYLACTIC OOPHORECTOMY SPECIMENS; SURFACE EPITHELIAL-CELLS; DNA; EXPRESSION; CARCINOMA; CARRIERS; DAMAGE; H2AX; HISTOPATHOLOGY AB Background. Early serous carcinomas predominate in the fimbria of women with BRCA mutations (BRCA+). An entity in non-neoplastic mucosa sharing several properties of early serous carcinomas - the "p53 signature" - has been described in the distal fallopian tube and proposed as a precursor to serous carcinomas. This study compared the prevalence of p53 signatures in ovarian cortical inclusion cysts (CICs) and fallopian tubes from BRCA+ women and explored their relationship. Design. All tissues from 75 completely excised ovaries and tubes obtained during prophylactic surgery were studied by conventional microscopy, immunostaining for p53, and in selected cases, gamma-H2AX (DNA damage). P53 signatures were defined as 12 or more consecutive p53-positive secretory cell nuclei. Their prevalence in fallopian tubes and CICs was recorded, compared to an existing database of consecutive women without a suspicion of BRCA+ or ovarian cancer, and correlated with the number of CICs. Results. Tubal p53 signatures were detected in 29 of 75 cases (38%); 20 of 30 (66%) signatures examined were gamma-H2AX-positive. One ovary contained a small gamma-H2AX negative p53 signature on the ovarian surface; no p53 signatures were identified in CICs. The prevalence of BRCA+ p53 tubal signatures was similar to that of women with unknown BRCA status (38 v 33%). Presence of p53 signatures did not correlate with number of CICs. Conclusions. p53 signatures were common in the fallopian tubes of BRCA+ women, were not identified in CICs, and did not correlate with the latter. The tubal p53 signature merits serious consideration as an important early event in serous carcinogenesis in BRCA+ women. (c) 2008 Elsevier Inc. All rights reserved. C1 [Folkins, Ann K.; Jarboe, Elke A.; Saleemuddin, Aasia; Crum, Christopher P.] Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Callahan, Michael J.; Muto, Michael G.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Drapkin, Ronny; Garber, Judy E.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Tworoger, Shelley] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Tworoger, Shelley] Harvard Univ, Sch Med, Boston, MA USA. [Tworoger, Shelley] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lee, Yonghee] Univ Ulsan, Coll Med, Dept Pathol, Seoul, South Korea. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; Tworoger, Shelley/0000-0002-6986-7046 FU NCI NIH HHS [1 R21 CA124688, P50 CA10500, P50 CA105009, P50 CA105009-05, R21 CA124688, R21 CA124688-01A1] NR 27 TC 129 Z9 135 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2008 VL 109 IS 2 BP 168 EP 173 DI 10.1016/j.ygyno.2008.01.012 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 305VJ UT WOS:000256205600004 PM 18342932 ER PT J AU Litkouhi, B Litkouhi, B Fleming, E Welch, WR Berkowitz, RS Birrer, MJ Mok, SC AF Litkouhi, Behrang Litkouhi, Babak Fleming, Evelyn Welch, William R. Berkowitz, Ross S. Birrer, Michael J. Mok, Samuel C. TI Overexpression of CEACAM6 in borderline and invasive mucinous ovarian neoplasms SO GYNECOLOGIC ONCOLOGY LA English DT Article DE mucinous ovarian neoplasms; CEACAM6; gene expression ID PANCREATIC ADENOCARCINOMA CELLS; GENE-EXPRESSION; CANCER; ADHESION; TUMORS; TUMORIGENESIS; DETERMINANT; PROFILE AB Objective. Identifying markers specific for mucinous ovarian neoplasms (MON) is important for cancer diagnosis and surveillance, and will help improve our general understanding of the pathobiology of these tumors. CEACAM6 overexpression appears to be an early molecular event with prognostic significance in gastrointestinal carcinomas. Microarray analysis previously demonstrated high CEACAM6 overexpression in MON's and this study sought to validate this finding. Methods. Western blot compared CEACAM6 expression in normal human ovarian surface epithelium (HOSE) and ovarian cancer cell lines. Quantitative RT-PCR (qRT-PCR) was performed on 75 laser-microdissected HOSE and ovarian cancer tissue samples. Inummohistochemistry (IHC) was performed and slides were analyzed in a semi-quantitative manner. Results. CEACAM6 was expressed in 2 of 3 mucinous cancer cell lines. Expression was absent in all 2 HOSE, 7 serous cancer, and 2 clear cell cancer cell lines. 100-fold CEACAM6 overexpression (qRT-PCR) was demonstrated in 13/16 (81%) borderline, low-grade, and high-grade invasive MON's, compared to 5150 (10%) serous and 1/5 (20%) benign mucinous samples. CEACAM6 expression was not different between borderline and invasive MON's (p = 0.55) or across tumor stage (p = 0.76). CEACAM6 staining was present in 24/28 (86%) borderline, low-grade, and high-grade invasive MON's; 13/28 (46%) exhibited moderate-strong staining. Neither CEACAM6 expression (p=0.36) nor staining intensity (p=0.51) was different between borderline and invasive MON's. None of the serous or benign mucinous tumors exhibited CEACAM6 staining. Conclusions. CEACAM6 is overexpressed in borderline and invasive MON's. (c) 2008 Elsevier Inc. All rights reserved. C1 [Litkouhi, Babak; Fleming, Evelyn; Berkowitz, Ross S.; Mok, Samuel C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA 02115 USA. [Litkouhi, Behrang] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. [Litkouhi, Babak; Fleming, Evelyn; Welch, William R.; Berkowitz, Ross S.; Mok, Samuel C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Welch, William R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Birrer, Michael J.] NCI, Cell & Canc Biol Branch, NIH, Rockville, MD USA. RP Mok, SC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, BLI-447,221 Longwood Ave, Boston, MA 02115 USA. EM scmok@rics.bwh.harvard.edu FU Intramural NIH HHS; NCI NIH HHS [R33CA103595, P50CA165009] NR 26 TC 8 Z9 14 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 MAY PY 2008 VL 109 IS 2 BP 234 EP 239 DI 10.1016/j.ygyno.2008.01.031 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 305VJ UT WOS:000256205600015 PM 18331757 ER PT J AU Moskowitz, MA AF Moskowitz, Michael A. TI Defining a pathway to discovery from bench to bedside: The trigeminovascular system and sensitization SO HEADACHE LA English DT Article AB Over the past 50 years, investigations into the pathophysiology of migraine have yielded discoveries that both illuminate the various components of the "migraine process" and lend promise to the identification of new therapies unheralded in their specificity and effectiveness. C1 [Moskowitz, Michael A.] Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02114 USA. [Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, Boston, MA USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02114 USA. NR 0 TC 27 Z9 27 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-8748 J9 HEADACHE JI Headache PD MAY PY 2008 VL 48 IS 5 BP 688 EP 690 DI 10.1111/j.1526-4610.2008.01110.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 298SZ UT WOS:000255708700006 PM 18471111 ER PT J AU Chandwani, BP Kulich, RK Kanavakis, G Noshir, M Steven, SJ AF Chandwani, B. P. Kulich, R. K. Kanavakis, G. Noshir, M. Steven, S. J. TI Review of salivary biomarkers: An objective research and clinical tool in assessment of headache disorders SO HEADACHE LA English DT Meeting Abstract CT 50th Annual Scientific Meeting of the American-Headache-Society CY JUN 26-29, 2008 CL Boston, MA SP Amer Headache Soc C1 [Chandwani, B. P.; Kulich, R. K.; Kanavakis, G.; Noshir, M.; Steven, S. J.] Tufts Univ, Sch Dent Med, Craniofacial Pain & Headache Ctr, Boston, MA 02111 USA. [Kulich, R. K.] Massachusetts Gen Hosp, Anesthesia Pain Clin, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-8748 J9 HEADACHE JI Headache PD MAY PY 2008 VL 48 SU 1 BP S53 EP S53 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 305RG UT WOS:000256194900123 ER PT J AU Levy, D Zhang, XC AF Levy, D. Zhang, X. -C. TI Modulation of meningeal nociceptors mechanosensitivity by peripheral proteinase-activated receptor-2: The role of mast cells SO HEADACHE LA English DT Meeting Abstract CT 50th Annual Scientific Meeting of the American-Headache-Society CY JUN 26-29, 2008 CL Boston, MA SP Amer Headache Soc C1 [Levy, D.; Zhang, X. -C.] Harvard Univ, Sch Med, Boston, MA USA. [Levy, D.; Zhang, X. -C.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-8748 J9 HEADACHE JI Headache PD MAY PY 2008 VL 48 SU 1 BP S6 EP S6 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 305RG UT WOS:000256194900013 ER PT J AU Maloney, G Kulich, RJ Brijesh, CP Mehta, N AF Maloney, G. Kulich, R. J. Brijesh, C. P. Mehta, N. TI History of headache research and management in Boston SO HEADACHE LA English DT Meeting Abstract CT 50th Annual Scientific Meeting of the American-Headache-Society CY JUN 26-29, 2008 CL Boston, MA SP Amer Headache Soc C1 [Maloney, G.; Kulich, R. J.; Brijesh, C. P.; Mehta, N.] Tufts Univ, Sch Dent Med, Craniofacial Pain Headache & Sleep Ctr, Boston, MA 02111 USA. [Kulich, R. J.] Massachusetts Gen Hosp, Anesthesia Pain Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-8748 J9 HEADACHE JI Headache PD MAY PY 2008 VL 48 SU 1 BP S17 EP S17 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 305RG UT WOS:000256194900038 ER PT J AU Campbell, EG AF Campbell, Eric G. TI Science for sale: The perils, rewards, and delusions of campus capitalism SO HEALTH AFFAIRS LA English DT Book Review C1 [Campbell, Eric G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02115 USA. RP Campbell, EG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02115 USA. EM ecampbell@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2008 VL 27 IS 3 BP 888 EP 889 DI 10.1377/hlthaff.27.3.888 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 296XT UT WOS:000255579900038 ER PT J AU O'Cleirigh, C Safren, S AF O'Cleirigh, Conall Safren, Steven TI Optimizing the effects of stress management interventions in HIV SO HEALTH PSYCHOLOGY LA English DT Editorial Material DE stress management interventions; HIV; immunity; psychopathology; psychoneuroimmunology ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED GAY MEN; IMMUNE-SYSTEM RECONSTITUTION; SUBSTANCE USE DISORDERS; VIRAL LOAD; PSYCHOLOGICAL DISTRESS; DISEASE PROGRESSION; POSITIVE MEN; ANTIBODY-TITERS; CORTISOL OUTPUT AB Scott-Sheldon, Kalichman, Carey, and Fiedler (2008) present a thoughtful, important, and timely meta-analysis of randomized controlled trials of stress management interventions in HIV. They differentiate controlled effect sizes across classes of acute outcomes including psychological distress, psychosocial processes, biological processes (immune status, viral, and hormonal) and fatigue. The authors join Scott-Sheldon et al., in considering future directions for this type of clinical psychosocial intervention research in HIV. Recommendations for addressing the high prevalence of psychosocial problems including diagnosable mental health disorders comorbid with HIV are presented. Suggestions for addressing medication adherence and accommodating interventions with concomitant substance use treatment are also considered. These recommendations are presented with an emphasis on expanding both the efficacy and effectiveness of psychosocial interventions in HIV. These recommendations are presented as realistic strategies for improving the modest treatment effect sizes for psychosocial outcomes and identifying meaningful effects on distal physiological outcomes associated with traditional stress management interventions in HIV. C1 [Safren, Steven] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Fenway Community Hlth, Fenway Inst, Boston, MA USA. RP Safren, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ssafren@partners.org FU NIDA NIH HHS [R01 DA018603]; NIMH NIH HHS [1R34MH081760, R34 MH081760, R34 MH081760-02] NR 42 TC 7 Z9 7 U1 2 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2008 VL 27 IS 3 BP 297 EP 301 DI 10.1037/a0012607 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA 323LE UT WOS:000257446800001 PM 18624592 ER PT J AU Denollet, J Martens, EJ Nyklicek, I Conraads, VM de Gelder, B AF Denollet, Johan Martens, Elisabeth J. Nyklicek, Ivan Conraads, Viviane M. de Gelder, Beatrice TI Clinical events in coronary patients who report low distress: Adverse effect of repressive coping SO HEALTH PSYCHOLOGY LA English DT Article DE CAD; depression; Type-D personality; repressive coping; prognosis ID HEART-DISEASE; MYOCARDIAL-INFARCTION; CARDIAC EVENTS; BLOOD-PRESSURE; TRAIT ANXIETY; D PERSONALITY; DEPRESSION; DEFENSIVENESS; STRESS; HEALTH AB Objective: Coronary artery disease (CAD) patients who report low distress are considered to be at low psychological risk for clinical events. However, patients with a repressive coping style may fail to detect and report signals of emotional distress. The authors hypothesized that repressive CAD patients are at risk for clinical events, despite low self-rated distress. Design: This was a prospective 5- to 10-year follow-up study, with a mean follow-up of 6.6 years. At baseline, 731 CAD patients filled out Trait-Anxiety (distress), Marlowe-Crowne (defensiveness), and Type D scales; 159 patients were classified as "repressive," 360 as "nonrepressive," and 212 as "Type D." Main Outcome Measures: The primary endpoint was a composite of total mortality or myocardial infaretion (MI); the secondary endpoint was cardiac mortality/MI. Results: No patients were lost to follow-up; 91 patients had a clinical event (including 35 cardiac death and 32 MI). Repressive patients reported low levels of anxiety, anger and depression at baseline, but were at increased risk for death/MI (21/159 = 13%) compared with nonrepressive patients (22/360 = 6%), p =.009. Poor systolic function, poor exercise tolerance, 3-vessel disease, index MI and Type-D personality-but not depression, anxiety or anger-also independently predicted clinical events. After controlling for these variables, repressive patients still had a twofold increased risk of death/MI, OR = 2.17, 95% CI = 1.10-4.08, p =.025). These findings were replicated for cardiac mortality/MI. Conclusion: CAD patients who use a repressive coping style are at increased risk for clinical events, despite their claims of low emotional distress. This phenomenon may cause an underestimation of the effect of stress on the heart. C1 [Denollet, Johan] Tilburg Univ, Dept Med Psychol, CoRPS, Ctr Res Psychol Somat Dis, NL-5000 LE Tilburg, Netherlands. [Denollet, Johan; Conraads, Viviane M.] Univ Antwerp Hosp, Dept Cardiol, Antwerp, Belgium. [de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, Tilburg, Netherlands. [de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Denollet, J (reprint author), Tilburg Univ, Dept Med Psychol, CoRPS, Ctr Res Psychol Somat Dis, POB 90153, NL-5000 LE Tilburg, Netherlands. EM denollet@uvt.nl OI Conraads, Viviane/0000-0002-5819-1503 NR 39 TC 35 Z9 36 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2008 VL 27 IS 3 BP 302 EP 308 DI 10.1037/0278-6133.27.3.302 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA 323LE UT WOS:000257446800002 PM 18624593 ER PT J AU Frosch, DL Kimmel, S Volpp, K AF Frosch, Dominick L. Kimmel, Stephen Volpp, Kevin TI What role do lay beliefs about hypertension etiology play in perceptions of medication effectiveness? SO HEALTH PSYCHOLOGY LA English DT Article DE hypertension; medication adherence; lay beliefs ID HIGH BLOOD-PRESSURE; JOINT NATIONAL COMMITTEE; AFRICAN-AMERICAN; KIDNEY-DISEASE; TRUST; PHYSICIAN; ADHERENCE; PATIENT; CARE; PREVENTION AB Background: Some people take the disease label "hypertension" literally; leading to the belief that increasing relaxation instead of medication is the best treatment for this condition. We experimentally tested the effect of such underlying beliefs on ratings of interventions for hypertension and compared alternative communication strategies to increase medication effectiveness ratings. Methods: Outpatients (N = 152) with a known diagnosis of hypertension read a vignette describing an asymptomatic condition and recommended treatment. Experimental factors were the disease label (Hypertension vs. Korotkoff s Syndrome) and type of argument designed to persuade the reader that medication is most effective (Causal vs. Correlational). Measures: Background measures included demographics, beliefs that stress causes health problems and trust in physicians. Outcomes were effectiveness ratings for interventions to treat the condition. Results: Participants who read a vignette describing "Hypertension" rated "relaxing more" as significantly more effective than participants exposed to the same condition but with the unfamiliar "Korotkoff's Syndrome" label, [F(1, 14 1) = 5.22, p =.024]. However, medication, reducing salty foods and losing weight were rated as more effective than relaxing more. Intervention ratings did not differ by type of argument presented. There was a significant interaction of disease label and trust in physicians [F(1, 125) = 7.01, p =.009]. Individuals with low trust rated medication as significantly less effective when exposed to an unfamiliar disease label. Conclusions: This study confirms the effect of the hypertension disease label on ratings of different interventions for the condition. However, participants rated biomedically recommended interventions as more effective than those not endorsed. C1 [Frosch, Dominick L.] Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Kimmel, Stephen; Volpp, Kevin] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Kimmel, Stephen] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Volpp, Kevin] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Volpp, Kevin] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Frosch, DL (reprint author), Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, 911 Broxton Ave, Los Angeles, CA 90024 USA. EM dfrosch@mednet.ucla.edu NR 27 TC 5 Z9 5 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2008 VL 27 IS 3 BP 320 EP 326 DI 10.1037/0278-6133.27.3.320 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA 323LE UT WOS:000257446800005 PM 18624596 ER PT J AU Hurley, AC Rothschild, JM Moore, ML Snydeman, C Dykes, PC Fotakis, S AF Hurley, Ann C. Rothschild, Jeffrey M. Moore, Mary Lou Snydeman, Colleen Dykes, Patricia C. Fotakis, Sofronia TI A model of recovering medical errors in the coronary care unit SO HEART & LUNG LA English DT Article ID ADVERSE DRUG EVENTS; INTENSIVE-CARE; NURSES; COLLABORATION; QUALITY AB OBJECTIVE: The purpose of this study was to explore the thoughts, interpersonal processes, and actions used by nurses who had recently intervened to protect coronary care unit (CCU) patients from potential medical errors. METHODS: The study used semistructured interviews conducted with 18 very experienced CCU nurses in two academic medical centers. Content analysis was used to code and analyze text segments. Core codes were used for developing an empirically derived model. RESULTS: There were more than 1000 data bits of accounts of involvement in the near-miss events, thought processes and actions surrounding the events, communication strategies used, feelings, outcomes, reflection about the event and consequences, and environment/context in which the events occurred. A three-stage temporally ordered model illustrates the process of recovering medical errors. in stage one, the presence of the evolving clinical scenario and nursing knowledge and expertise plus the CCU context are the antecedents that lead to processes and actions of identification, interruption, and correction of the error in stage two. Outcomes of whether or not the near miss was recovered lead to an adverse event (or not), and reflections on the process and outcome lead to the nurse's feelings about the event in stage three. CONCLUSIONS: The model can guide nursing administration, practice, education, and research to recognize and value this responsibility, to teach others, and to test strategies to enhance the vital nursing role of recovering near-miss events that leads to safer and better patient care. C1 [Hurley, Ann C.; Moore, Mary Lou; Fotakis, Sofronia] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Hurley, Ann C.] Northeastern Univ, Sch Nursing, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Rothschild, Jeffrey M.] Brigham & Womens Hosp, Dept Gen Med, Boston, MA 02115 USA. [Rothschild, Jeffrey M.] Harvard Univ, Sch Med, Boston, MA USA. [Snydeman, Colleen] Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. [Dykes, Patricia C.] Partners Hlth Care Syst, Informat Syst, Boston, MA USA. RP Hurley, AC (reprint author), Brigham & Womens Hosp, Dept Nursing, 75 Francis St, Boston, MA 02115 USA. NR 31 TC 10 Z9 11 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD MAY-JUN PY 2008 VL 37 IS 3 BP 219 EP 226 DI 10.1016/j.hrtlng,2007.06.002 PG 8 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 306LD UT WOS:000256248800008 PM 18482634 ER PT J AU Groeneved, PW Farmer, SA Suh, JJ Matta, MA Yang, FF AF Groeneved, Peter W. Farmer, Steven A. Suh, Janice J. Matta, Mary Anne Yang, Feifei TI Outcomes and costs of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death among the elderly SO HEART RHYTHM LA English DT Article DE death; sudden; defibrittation; prognosis; survival; cost-benefit analysis ID PROPENSITY SCORE METHODS; HEART-FAILURE; MEDICARE BENEFICIARIES; MYOCARDIAL-INFARCTION; COMPLICATIONS; TECHNOLOGIES; AMIODARONE; THERAPY; BIAS AB BACKGROUND The clinical outcomes and costs of implantable cardioverter-defibrillators (ICDs) used for primary prevention of sudden cardiac death in nonexperimental settings are uncertain. OBJECTIVE The purpose of this study was to measure the health outcomes and costs among a nationally representative cohort of elderly, primary-prevention ICD recipients. METHODS We collected health-care cost and utilization data from all Medicare beneficiaries hospitalized for congestive heart failure (CHF) who had received primary-prevention ICDs between October 2003 and September 2005 as well as propensity-score-matched control Medicare beneficiaries hospitalized for CHF during the same period. A muttivariable Cox proportional hazards model was fitted to the cohort, which comprised 7125 ICD recipients and 7125 controls and which was followed through December 2005. Medicare claims in the first year inclusive of the index hospitalization were used to assess differences in health-care costs. RESULTS ICD receipt was associated with a significant reduction in mortality (adjusted hazard ratio = 0.62, 95% confidence interval 0.58-0.67). ICD patients had higher median hospital costs in the first 30 days after initial hospitalization (median difference = $41,542, P <.001) and at 1 year (median difference = $41,503, P <.001) as well as higher outpatient and physician costs at 6 months (median difference = $1828, P <.001). CONCLUSIONS ICD implantation was associated with reduced mortality in a nonexperimental, elderly, primary-prevention patient population hospitalized for CHF. The additional health-care costs of ICD implantation were substantial but comparable to published cost-effectiveness models that have projected ICDs to be cost-effective. C1 [Groeneved, Peter W.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Groeneved, Peter W.; Suh, Janice J.; Matta, Mary Anne; Yang, Feifei] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Groeneved, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Farmer, Steven A.] Univ Penn, Sch Med, Div Cardiol, Philadelphia, PA 19104 USA. RP Groeneved, PW (reprint author), 1229 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.groeneveld@va.gov FU PHS HHS [IRDIHS016478] NR 32 TC 30 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAY PY 2008 VL 5 IS 5 BP 646 EP 653 DI 10.1016/j.hrthm.2008.01.038 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 297OV UT WOS:000255626900003 PM 18452864 ER PT J AU Nahmias, Y Goldwasser, J Casali, M van Poll, D Wakita, T Chung, RT Yarmush, ML AF Nahmias, Yaakov Goldwasser, Jonathan Casali, Monica van Poll, Daan Wakita, Takaji Chung, Raymond T. Yarmush, Martin L. TI Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin SO HEPATOLOGY LA English DT Article ID HEPATOCYTE APO-B; VERY-LOW; CONTAINING LIPOPROTEINS; DENSITY-LIPOPROTEINS; CITRUS FLAVONOIDS; B100 SECRETION; EXPRESSION; PROTEINS; CELLS; REPLICATION AB Hepatitis C virus (HCV) infects over 3% of the world population and is the leading cause of chronic liver disease worldwide. HCV has long been known to associate with circulating lipoproteins, and its interactions with the cholesterol and lipid pathways have been recently described. In this work, we demonstrate that HCV is actively secreted by infected cells through a Golgi-dependent mechanism while bound to very low density lipoprotein (vLDL). Silencing apolipoprotein B (ApoB) messenger RNA in infected cells causes a 70% reduction in the secretion of both ApoB-100 and HCV. More importantly, we demonstrate that the grapefruit flavonoid naringenin, previously shown to inhibit vLDL secretion both in vivo and in vitro, inhibits the microsomal triglyceride transfer protein activity as well as the transcription of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase and acyl-coenzyme A:cholesterol acyltransferase 2 in infected cells. Stimulation with naringenin reduces HCV secretion in infected cells by 80%. Moreover, we find that naringenin is effective at concentrations that are an order of magnitude below the toxic threshold in primary human hepatocytes and in mice. Conclusion: These results suggest a novel therapeutic approach for the treatment of HCV infection. C1 [Nahmias, Yaakov; Goldwasser, Jonathan; Casali, Monica; van Poll, Daan; Yarmush, Martin L.] Shriners Burns Hosp, Ctr Engn Med, Boston, MA USA. [Nahmias, Yaakov; Casali, Monica; van Poll, Daan; Chung, Raymond T.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Goldwasser, Jonathan] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. [Wakita, Takaji] Natl Inst Infect Dis, Tokyo, Japan. RP Nahmias, Y (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, 114 16th St,Room 1402, Charlestown, MA 02129 USA. EM ynahmias@partners.org RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-13, R01 DK043371] NR 34 TC 121 Z9 125 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2008 VL 47 IS 5 BP 1437 EP 1445 DI 10.1002/hep.22197 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 295XK UT WOS:000255507500003 PM 18393287 ER PT J AU van Poll, D Parekkadan, B Cho, CH Berthiaume, F Nahmias, Y Tilles, AW Yarmush, ML AF van Poll, Daan Parekkadan, Biju Cho, Cheul H. Berthiaume, Francois Nahmias, Yaakov Tilles, Arno W. Yarmush, Martin L. TI Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo SO HEPATOLOGY LA English DT Article ID ACUTE LIVER-FAILURE; FULMINANT HEPATIC-FAILURE; MARROW STROMAL CELLS; BIOARTIFICIAL LIVER; CONTROLLED-TRIAL; BONE; HEPATOCYTES; MULTICENTER; EXPRESSION; LUNG AB Orthotopic liver transplantation is the only proven effective treatment for fulminant hepatic failure (FHF), but its use is limited because of organ donor shortage, associated high costs, and the requirement for lifelong immunosuppression. FHF is usually accompanied by massive hepatocellular death with compensatory liver regeneration that fails to meet the cellular losses. Therefore, therapy aimed at inhibiting cell death and stimulating endogenous repair pathways could offer major benefits in the treatment of FHF. Recent studies have demonstrated that mesenchymal stem cell (MSC) therapy can prevent parenchymal cell loss and promote tissue repair in models of myocardial infarction, acute kidney failure, and stroke through the action of trophic secreted molecules. In this study, we investigated whether MSC therapy can protect the acutely injured liver and stimulate regeneration. In a D-galactosamine-induced rat model of acute liver injury, we show that systemic infusion of MSC-conditioned medium (MSC-CM) provides a significant survival benefit and prevents the release of liver injury biomarkers. Furthermore, MSC-CM therapy resulted in a 90% reduction of apoptotic hepatocellular death and a three-fold increment in the number of proliferating hepatocytes. This was accompanied by a dramatic increase in the expression levels of 10 genes known to be up-regulated during hepatocyte replication. Direct antiapoptotic and promitotic effects of MSC-CM on hepatocytes were demonstrated using in vitro assays. Conclusion: These data provide the first dear evidence that MSC-CM therapy provides trophic support to the injured liver by inhibiting hepatocellular death and stimulating regeneration, potentially creating new avenues for the treatment of FHF. C1 [van Poll, Daan; Parekkadan, Biju; Cho, Cheul H.; Berthiaume, Francois; Nahmias, Yaakov; Tilles, Arno W.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA USA. [van Poll, Daan] Univ Utrecht, Univ Med Ctr, Dept Surg, Utrecht, Netherlands. [Parekkadan, Biju; Yarmush, Martin L.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA. RP Yarmush, ML (reprint author), 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X FU NIDDK NIH HHS [K08 DK66040, K18 DK076819, R01 DK43371] NR 31 TC 229 Z9 235 U1 1 U2 20 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2008 VL 47 IS 5 BP 1634 EP 1643 DI 10.1002/hep.22236 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 295XK UT WOS:000255507500023 PM 18395843 ER PT J AU Kuperberg, GR Lakshmanan, BM Greve, DN West, WC AF Kuperberg, Gina R. Lakshmanan, Balaji M. Greve, Douglas N. West, W. Caroline TI Task and semantic relationship influence both the polarity and localization of hemodynamic modulation during lexico-semantic processing SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; semantic priming; semantic memory; language; fusiform : left inferior frontal; temporal cortex; lexical decision; relatedness judgment ID EVENT-RELATED POTENTIALS; SPREADING ACTIVATION THEORY; DEPTH-RECORDED POTENTIALS; SURFACE-BASED ANALYSIS; LEXICAL DECISION TASK; CORTICAL SURFACE; FUNCTIONAL MRI; NEURAL BASIS; SPATIOTEMPORAL STAGES; PREFRONTAL CORTEX AB This study examined how task (implicit vs. explicit) and semantic relationship (direct vs. indirect) modulated hemodynamic activity during lexico-semantic processing. Participants viewed directly related, indirectly related, and unrelated prime-target word-pairs as they performed (a) an implicit lexical decision (LD) task in which they decided whether each target was a real word or a nonword, and (b) an explicit relatedness judgment (RJ) task in which they determined whether each word-pair was related or unrelated in meaning. Task influenced both the polarity and neuroanatomical localization of hemodynamic modulation. Semantic relationship influenced the neuroanatomical localization of hemodynamic modulation. The implicit LD task was primarily associated with inferior prefrontal and ventral inferior temporal/fusiform hemodynamic response suppression to directly related (relative to unrelated) word-pairs, and with more widespread temporal-occipital response suppression to indirectly related (relative to unrelated) word-pairs. In contrast, the explicit RJ task was primarily associated with left inferior parietal hemodynamic response enhancement to both directly and indirectly related (relative to unrelated) word-pairs, as well as with additional left inferior prefrontal hemodynamic response enhancement to indirectly related (relative to unrelated) word-pairs. These findings are discussed in relation to the specific neurocognitive processes thought to underlie implicit and explicit semantic processes. C1 [Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Kuperberg, Gina R.; Lakshmanan, Balaji M.; Greve, Douglas N.; West, W. Caroline] MGH, MIT, HMS Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [West, W. Caroline] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp East, CNY-2,Bldg 149, Boston, MA 02129 USA. EM kuperber@nmr.mgh.harvard.edu FU NIMH NIH HHS [K01 MH065356, K01 MH65356, R01 MH071635, R01 MH071635-03] NR 74 TC 31 Z9 31 U1 7 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2008 VL 29 IS 5 BP 544 EP 561 DI 10.1002/hbm.20419 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 298GH UT WOS:000255673900005 PM 17674356 ER PT J AU Chen, XW Weaver, J Bove, BA Vanderveer, LA Weil, SC Miron, A Daly, MB Godwin, AK AF Chen, Xiaowei Weaver, JoEllen Bove, Betsy A. Vanderveer, Lisa A. Weil, Susan C. Miron, Alexander Daly, Mary B. Godwin, Andrew K. TI Allelic imbalance in BRCA1 and BRCA2 gene expression is associated with an increased breast cancer risk SO HUMAN MOLECULAR GENETICS LA English DT Article ID SPORADIC BREAST; MESSENGER-RNA; PROMOTER DELETIONS; OVARIAN CARCINOMAS; MUTATIONS; SEQUENCE; WOMEN; PCR; HYPERMETHYLATION; IDENTIFICATION AB The contribution of BRCA1 and BRCA2 to familial and non-familial forms of breast cancer has been difficult to accurately estimate because of the myriad of potential genetic and epigenetic mechanisms that can ultimately influence their expression and involvement in cellular activities. As one of these potential mechanisms, we investigated whether allelic imbalance (AI) of BRCA1 or BRCA2 expression was associated with an increased risk of developing breast cancer. By developing a quantitative approach utilizing allele-specific real-time PCR, we first evaluated AI caused by nonsense-mediated mRNA decay in patients with frameshift mutations in BRCA1 and BRCA2. We next measured AI for BRCA1 and BRCA2 in lymphocytes from three groups: familial breast cancer patients, non-familial breast cancer patients and age-matched cancer-free females. The AI ratios of BRCA1, but not BRCA2, in the lymphocytes from familial breast cancer patients were found to be significantly increased as compared to cancer-free women (BRCA1: 0.424 versus 0.211, P = 0.00001; BRCA2: 0.206 versus 0.172, P = 0.38). Similarly, the AI ratios were greater for BRCA1 and BRCA2 in the lymphocytes of non-familial breast cancer cases versus controls (BRCA1: 0.353, P = 0.002; BRCA2: 0.267, P = 0.03). Furthermore, the distribution of under-expressed alleles between cancer-free controls and familial cases was significantly different for both BRCA1 and BRCA2 gene expression (P < 0.02 and P < 0.02, respectively). In conclusion, we have found that AI affecting BRCA1 and to a lesser extent BRCA2 may contribute to both familial and non-familial forms of breast cancer. C1 [Chen, Xiaowei; Weaver, JoEllen; Bove, Betsy A.; Vanderveer, Lisa A.; Godwin, Andrew K.] Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. [Weil, Susan C.] Morphotek Inc, Exton, PA 19341 USA. [Miron, Alexander] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Godwin, AK (reprint author), Fox Chase Canc Ctr, Div Med Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM andrew.godwin@fccc.edu FU NCI NIH HHS [P50 CA83638, R25 CA057708, U01 CA69631] NR 44 TC 43 Z9 43 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2008 VL 17 IS 9 BP 1336 EP 1348 DI 10.1093/hmg/ddn022 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 290VR UT WOS:000255151300014 PM 18204050 ER PT J AU Gejman, R Swearingen, B Hedley-Whyte, ET AF Gejman, Roger Swearingen, Brooke Hedley-Whyte, E. Tessa TI Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas SO HUMAN PATHOLOGY LA English DT Article DE immunohistochemistry; pituitary adenoma; proliferation indices ID CELL NUCLEAR ANTIGEN; MONOCLONAL-ANTIBODY KI-67; MIB-1 LABELING INDEX; STAINING INDEXES; IMAGE-ANALYSIS; GROWTH; INVASIVENESS; IMMUNOHISTOCHEMISTRY; CARCINOMAS; TUMORS AB Pituitary adenomas sometimes progress after surgery and can be locally invasive. Ki-67 and p53 expression are referred to as indicators of aggressive behavior in the World Health Organization Classification of Endocrine Tumors. The real value of these markers including an appropriate threshold for Ki-67 labeling index correlating with tumor progression is controversial. We identified 24 consecutive pituitary adenomas from patients who required surgery for recurrence within 5 years of their first procedure and 31 consecutive adenomas with no evidence of postsurgical progression within 5 years of first surgery. Case selection was based upon availability of complete clinical information, blocks, and slides for study. Immunohistochemistry for Ki-67 revealed that the tumors without progression had a proliferation index of 0.41% +/- 0.01% (mean +/- SEM) (n = 31) (range, 0.08%-1.2%) and the first biopsy from those tumors which progressed had a mean proliferation index of 1.45% +/- 0.09% (mean +/- SEM) (n = 24) (range, 0.1%-10.6%) (P = .01). With the use of ROC analysis, a threshold level of Ki-67 expression greater than 1.3% predicts progression with a high specificity. The group with progression had a higher 2 proportion of nonfunctioning tumors (P < .005, chi(2)). There was no significant difference between the 2 groups with regard to invasion, suprasellar extension, size, tumor type, postoperative radiotherapy, extent of resection, sex, and age. Ki-67 labeling index was an independent predictor of progression (multivariate analysis, P < .011). p53 was positive in 12.5% of cases with surgical progression and in 9.6% of cases without progression, but the difference was not significant (P = .7; chi(2), 0.11). (C) 2008 Elsevier Inc. All rights reserved. C1 [Gejman, Roger; Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Gejman, Roger; Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Swearingen, Brooke] Massachusetts Gen Hosp, Div Neurosurg, Boston, MA 02114 USA. [Swearingen, Brooke] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Hedley-Whyte, ET (reprint author), Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. EM ehedleywhyte@partners.org NR 37 TC 51 Z9 55 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2008 VL 39 IS 5 BP 758 EP 766 DI 10.1016/j.humpath.2007.10.004 PG 9 WC Pathology SC Pathology GA 299BN UT WOS:000255730900015 PM 18439942 ER PT J AU Palmas, W Pickering, TG Teresi, J Schwartz, JE Field, L Weinstock, RS Shea, S AF Palmas, Walter Pickering, Thomas G. Teresi, Jeanne Schwartz, Joseph E. Field, Lesley Weinstock, Ruth S. Shea, Steven TI Telemedicine home blood pressure measurements and progression of albuminuria in elderly people with diabetes SO HYPERTENSION LA English DT Review DE albuminuria; diabetes mellitus; home blood pressure; ambulatory blood pressure ID TARGET-ORGAN DAMAGE; FOLLOW-UP; CARDIOVASCULAR EVENTS; HYPERTENSIVE PATIENTS; PULSE PRESSURE; EXCRETION; RISK; MICROALBUMINURIA; POPULATION; MORTALITY AB We assessed whether home blood pressure monitoring improved the prediction of progression of albuminuria when added to office measurements and compared it with ambulatory blood pressure monitoring in a multiethnic cohort of older people (n = 392) with diabetes mellitus, without macroalbuminuria, participating in the telemedicine arm of the Informatics for Diabetes Education and Telemedicine Study. Albuminuria was assessed by measuring the spot urine albumin: creatinine ratio at baseline and annually for 3 years. The ambulatory sleep: wake systolic blood pressure ratio was categorized as dipping (ratio: <= 0.9), nondipping (ratio: >0.9 to 1.0), and nocturnal rise (ratio: >1.0). In a repeated-measures mixed linear model, after adjustment that included office pulse pressure, home pulse pressure was independently associated with a higher follow-up albumin: creatinine ratio (P = 0.001). That association persisted (P = 0.01) after adjusting for 24-hour pulse pressure and nocturnal rise, which were also independent predictors (P = 0.02 and P = 0.03, respectively). Cox proportional hazards models examined the progression of albuminuria (n = 74) as defined by cutoff values used by clinicians. After the adjustment for office pulse pressure, the hazards ratio (95% CI) per 10-mm Hg increment of home pulse pressure was 1.34 (range: 1.1 to 1.7; P = 0.01). Home pulse pressure was not an independent predictor in the model including ambulatory monitoring data; a nocturnal rise was the only independent predictor (P = 0.035). Cox models built separately for home pulse pressure and ambulatory monitoring exhibited similar calibration and discrimination. In conclusion, nocturnal blood pressure elevation was the strongest predictor of worsening albuminuria. Home blood pressure measurements added to office measurements and may constitute an adequate substitute for ambulatory monitoring. C1 [Palmas, Walter; Field, Lesley; Shea, Steven] Columbia Univ, Dept Med, New York, NY USA. [Pickering, Thomas G.] Columbia Univ, Behav Cardiovasc Hlth & Hypertens Program, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Epidemiol, Joseph Mailman Sch Publ Hlth, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Biomed Informat, New York, NY USA. [Teresi, Jeanne] Columbia Univ, Stroud Ctr, Fac Med, New York State Psychiat Inst, New York, NY USA. [Teresi, Jeanne] Hebrew Home Aged, Div Res, Bronx, NY USA. [Schwartz, Joseph E.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Weinstock, Ruth S.] Vet Affairs Med Ctr, Dept Vet Affairs, Syracuse, NY USA. [Weinstock, Ruth S.] SUNY Syracuse, Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. [Weinstock, Ruth S.] SUNY Syracuse, Upstate Med Univ, Div Endocrinol, Syracuse, NY USA. RP Palmas, W (reprint author), Div Gen Med, 622 W 168th St,PH 9-E, New York, NY 10032 USA. EM wp56@columbia.edu FU NHLBI NIH HHS [P01 HL047540]; PHS HHS [95-C-90998] NR 42 TC 14 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2008 VL 51 IS 5 BP 1282 EP 1288 DI 10.1161/HYPERTENSIONAHA.107.108589 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 288WK UT WOS:000255016500008 PM 18378859 ER PT J AU Dorsett, Y McBride, KM Jankovic, M Gazumyan, A Thai, TH Robbiani, DF Di Virgilio, M San-Martin, BR Heidkamp, G Schwickert, TA Eisenreich, T Rajewsky, K Nussenzweig, MC AF Dorsett, Yair McBride, Kevin M. Jankovic, Mila Gazumyan, Anna Thai, To-Ha Robbiani, Davide F. Di Virgilio, Michela San-Martin, Bernardo Reina Heidkamp, Gordon Schwickert, Tanja A. Eisenreich, Thomas Rajewsky, Klaus Nussenzweig, Michel C. TI MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation SO IMMUNITY LA English DT Article ID CLASS SWITCH RECOMBINATION; KINASE-A PHOSPHORYLATION; B-CELL LYMPHOMAS; SOMATIC HYPERMUTATION; C-MYC; TRANSGENIC MICE; POSTTRANSCRIPTIONAL REGULATION; ANTIBODY DIVERSIFICATION; BURKITT-LYMPHOMA; GENE-EXPRESSION AB MicroRNAs (miRNAs) are small noncoding RNAs that regulate vast networks of genes that share miRNA target sequences. To examine the physiologic effects of an individual miRNA-mRNA interaction in vivo, we generated mice that carry a mutation in the putative microRNA-155 (miR-155) binding site in the T-untranslated region of activation-induced cytidine deaminase (AID), designated Aicda(155) mice. AID Is required for immunoglobulin gene diversification in B lymphocytes, but it also promotes chromosomal translocations. Aicda(155) caused an increase in steady-state Aicda mRNA and protein amounts by increasing the half-life of the mRNA, resulting in a high degree of Myc-Igh translocations. A similar but more pronounced translocation phenotype was also found in miR-155-deficient mice. Our experiments indicate that miR-155 can act as a tumor suppressor by reducing potentially oncogenic translocations generated by AID. C1 [Dorsett, Yair; McBride, Kevin M.; Jankovic, Mila; Gazumyan, Anna; Robbiani, Davide F.; Di Virgilio, Michela; Heidkamp, Gordon; Schwickert, Tanja A.; Eisenreich, Thomas; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Gazumyan, Anna; Nussenzweig, Michel C.] Howard Hughes Med Inst, New York, NY 10065 USA. [Thai, To-Ha; Rajewsky, Klaus] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [San-Martin, Bernardo Reina] ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Strasbourg, France. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. EM nussen@rockefeller.edu RI mcbride, kevin/E-8230-2011; Reina-San-Martin, Bernardo/I-9484-2016 OI Reina-San-Martin, Bernardo/0000-0003-2083-6166 FU Howard Hughes Medical Institute; NIAID NIH HHS [R01 AI037526-12, AI06231, AI064345, R01 AI037526, R01 AI037526-06, R01 AI037526-07, R01 AI037526-08, R01 AI037526-09, R01 AI037526-10, R01 AI037526-11, R01 AI037526-13, R01 AI037526-14, R01 AI037526-15, R01 AI064345] NR 72 TC 277 Z9 294 U1 0 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2008 VL 28 IS 5 BP 630 EP 638 DI 10.1016/j.immuni.2008.04.002 PG 9 WC Immunology SC Immunology GA 302XS UT WOS:000256003900010 PM 18455451 ER PT J AU Pipkin, ME Monticelli, S AF Pipkin, Matthew E. Monticelli, Silvia TI Genomics and the immune system SO IMMUNOLOGY LA English DT Review DE epigenetic; genome-wide; lymphocytes; non-coding RNAs; transcription ID DNASE HYPERSENSITIVE SITES; LOCUS-CONTROL REGION; T-CELL DEVELOPMENT; RNA-POLYMERASE-II; BETA-GLOBIN LOCUS; TRANSCRIPTION FACTOR; CHROMATIN DOMAINS; ACTIVE CHROMATIN; NUCLEAR-ORGANIZATION; REGULATORY ELEMENTS AB While the hereditary information encoded in the Watson-Crick base pairing of genomes is largely static within a given individual, access to this information is controlled by dynamic mechanisms. The human genome is pervasively transcribed, but the roles played by the majority of the non-protein-coding genome sequences are still largely unknown. In this review we focus on insights to gene transcriptional regulation by placing special emphasis on genome-wide approaches, and on how non-coding RNAs, which derive from global transcription of the genome, in turn control gene expression. We review recent progress in the field with highlights on the immune system. C1 [Monticelli, Silvia] Biomed Res Inst, CH-6500 Bellinzona, Switzerland. [Pipkin, Matthew E.] Immune Dis Inst, Boston, MA USA. [Pipkin, Matthew E.] Harvard Univ, Sch Med, Boston, MA USA. RP Monticelli, S (reprint author), Biomed Res Inst, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. EM silvia.monticelli@irb.unisi.ch FU NCI NIH HHS [F32 CA126247, F32 CA126247-01] NR 78 TC 5 Z9 5 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAY PY 2008 VL 124 IS 1 BP 23 EP 32 DI 10.1111/j.1365-2567.2008.02818.x PG 10 WC Immunology SC Immunology GA 288MI UT WOS:000254990100003 PM 18298549 ER PT J AU Morra, M Geigenmuller, U Curran, J Rainville, IR Brennan, T Curtis, J Reichert, V Hovhannisyan, H Majzoub, J Miller, DT AF Morra, Massimo Geigenmuller, Ute Curran, John Rainville, Irene R. Brennan, Tim Curtis, Judd Reichert, Vienna Hovhannisyan, Hayk Majzoub, Joseph Miller, David T. TI Genetic diagnosis of primary immune deficiencies SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID PRIMARY-IMMUNODEFICIENCY-DISEASES; LINKED LYMPHOPROLIFERATIVE DISEASE; COMMON VARIABLE IMMUNODEFICIENCY; ADENOSINE-DEAMINASE DEFICIENCY; AFFECT PROTEIN FUNCTION; CLASSIFICATION-COMMITTEE; INTERNATIONAL-UNION; INHERITED MUTATION; MISSENSE MUTATIONS; SINGLE NUCLEOTIDE AB Gene testing in primary immune deficiencies (PIDs) once was limited to expert academic laboratories, but now is easily available to physicians with a broad range of clinical expertise. Such testing can establish or confirm a suspected diagnosis and also may predict future disease risk in advance of clinical signs and symptoms, inform reproductive decision making, and guide clinicians in selecting the most appropriate therapeutic options. This article, based on the authors' experience and a review of the published literature, discusses some of the advances and challenges currently encountered in the clinical molecular genetic diagnosis of PIDs. C1 [Morra, Massimo; Geigenmuller, Ute; Curran, John; Rainville, Irene R.; Brennan, Tim; Curtis, Judd; Reichert, Vienna; Hovhannisyan, Hayk; Majzoub, Joseph; Miller, David T.] Correlagen Diagnost Inc, Waltham, MA 02452 USA. [Rainville, Irene R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, David T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA. [Miller, David T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA. RP Morra, M (reprint author), Correlagen Diagnost Inc, 307 Waverley Oaks Rd,Suite 101, Waltham, MA 02452 USA. EM mmorra@correlagen.com NR 103 TC 5 Z9 5 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 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 2008 VL 28 IS 2 BP 387 EP + DI 10.1016/j.iac.2008.01.004 PG 27 WC Allergy; Immunology SC Allergy; Immunology GA 305KC UT WOS:000256176300011 PM 18424339 ER PT J AU Stenson, WF Snapper, SB Duerr, RH Cho, JH Kugathasan, S Rioux, JD Sartor, RB Autenreith, IB Darfeuille-Michaud, A Fox, J Tannock, GW Versalovic, J Young, VB Elson, CO Mayer, LF Weaver, CT Snapper, SB Lencer, WI Colgan, SP Parkos, CA Silverberg, MS Targan, SR Rubin, DT Loftus, EV Vasiliauskas, EA Sands, BE Higgins, P D'Haens, G Feagan, BG Hanauer, SB Sandborn, WJ Steinhart, H Fazio, V Galandiuk, S Kotun, WA Strong, SA Sylvester, FA Bousvaros, A Dubinsky, M Faubion, W Guthery, S Hyams, J Polk, DB Szigethy, E Griffiths, AM AF Stenson, William F. Snapper, Scott B. Duerr, Richard H. Cho, Judy H. Kugathasan, Subra Rioux, John D. Sartor, R. Balfour Autenreith, Ingo B. Darfeuille-Michaud, Arlette Fox, James Tannock, Gerald W. Versalovic, James Young, Vincent B. Elson, Charles O. Mayer, Lloyd F. Weaver, Casey T. Snapper, Scott B. Lencer, Wayne I. Colgan, Sean P. Parkos, Charles A. Silverberg, Mark S. Targan, Stephan R. Rubin, David T. Loftus, Edward V. Vasiliauskas, Eric A. Sands, Bruce E. Higgins, Peter D'Haens, Geert Feagan, Brian G. Hanauer, Stephen B. Sandborn, William J. Steinhart, Hillary Fazio, Victor Galandiuk, Susan Kotun, Walter A. Strong, Scott A. Sylvester, Francisco A. Bousvaros, Athos Dubinsky, Marla Faubion, William Guthery, Stephen Hyams, Jeffrey Polk, D. Brent Szigethy, Eva Griffiths, Anne Marie TI Challenges in IBD research: Assessing progress and rethinking the research agenda SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; GENOME-WIDE ASSOCIATION; PEDIATRIC CROHNS-DISEASE; PLACEBO-CONTROLLED TRIAL; INNATE IMMUNE-RESPONSE; EFFICACY END-POINTS; TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; ULCERATIVE-COLITIS C1 [Stenson, William F.] Washington Univ, St Louis, MO 63130 USA. [Snapper, Scott B.; Snapper, Scott B.; Sands, Bruce E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Duerr, Richard H.] Univ Pittsburgh, Pittsburgh, PA USA. [Cho, Judy H.] Yale Univ, New Haven, CT USA. [Kugathasan, Subra] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Rioux, John D.] Univ Montreal, Montreal, PQ, Canada. [Sartor, R. Balfour] Univ N Carolina, Chapel Hill, NC USA. [Autenreith, Ingo B.] Univ Tubingen, Tubingen, Germany. [Darfeuille-Michaud, Arlette] Univ Auvergne, Clermont Ferrand, France. [Fox, James] MIT, Cambridge, MA 02139 USA. [Tannock, Gerald W.] Univ Otago, Dunedin, New Zealand. [Versalovic, James] Texas Childrens Hosp, Houston, TX 77030 USA. [Young, Vincent B.] Michigan State Univ, E Lansing, MI 48824 USA. [Elson, Charles O.; Weaver, Casey T.] Univ Alabama, Birmingham, AL USA. [Mayer, Lloyd F.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Lencer, Wayne I.; Bousvaros, Athos] Boston Childrens Hosp, Boston, MA USA. [Colgan, Sean P.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Parkos, Charles A.] Emory Univ, Atlanta, GA 30322 USA. [Silverberg, Mark S.; Steinhart, Hillary] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Targan, Stephan R.; Vasiliauskas, Eric A.; Dubinsky, Marla] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Rubin, David T.; Hanauer, Stephen B.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Loftus, Edward V.; Sandborn, William J.; Faubion, William] Mayo Clin, Rochester, MN USA. [Higgins, Peter] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [D'Haens, Geert] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Feagan, Brian G.] London Clin Trials Res Grp, London, ON, Canada. [Fazio, Victor; Strong, Scott A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Galandiuk, Susan] Univ Louisville, Louisville, KY 40292 USA. [Kotun, Walter A.] Milton S Hershey Med Ctr, Hershey, PA USA. [Sylvester, Francisco A.; Hyams, Jeffrey] Connecticut Childrens Med Ctr, Hartford, CT USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Guthery, Stephen] Univ Utah, Sch Med, Salt Lake City, UT USA. [Polk, D. Brent] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Szigethy, Eva] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Griffiths, Anne Marie] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Stenson, WF (reprint author), Washington Univ, St Louis, MO 63130 USA. RI Higgins, Peter/A-3511-2009; Parkos, Charles/B-3896-2009; Colgan, Sean/B-4573-2009; Loftus, Edward/E-8304-2011; Szigethy, Eva/I-7860-2013; Feagan, Brian/M-4283-2015 OI Higgins, Peter/0000-0003-1602-4341; NR 113 TC 5 Z9 5 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2008 VL 14 IS 5 BP 687 EP 708 DI 10.1002/ibd.20371 PG 22 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296YJ UT WOS:000255581500014 PM 18260124 ER PT J AU Carvalho, KAT Simeoni, RB Guarita-Souza, LC Francisco, JC Abdelwahid, E Myiague, NI Chachques, JC Rivetti, LA Oliveira, L Malvezzi, M Olandoski, M Gremski, W AF Carvalho, K. A. T. Simeoni, R. B. Guarita-Souza, L. C. Francisco, J. C. Abdelwahid, E. Myiague, N. I. Chachques, J. C. Rivetti, L. A. Oliveira, L. Malvezzi, M. Olandoski, M. Gremski, W. TI Angiogenesis without functional outcome after mononuclear stem cell transplant in a doxorubicin-induced dilated myocardiopathy murine model SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article DE bone marrow stem cells; dilated myocardiopathy; doxorubicin; echocardiographic ID BONE-MARROW-CELLS; INDUCED CARDIOMYOPATHY; INFARCTED MYOCARDIUM; SKELETAL MYOBLASTS; HEART FUNCTION; CARDIOMYOCYTES; REGENERATION; COCULTURE; SCAR AB Objectives: Cell transplantation is considered a novel approach in the treatment of myocardiopathy, The objective of this study was to evaluate the effects of autologous mononuclear stem cell therapy in doxorubicin-induced dilated myocardiopathy by conducting both functional and histopathologic analysis. Methods: Seventy male rats were doxorubicin injected intraperitoneally for 2 weeks. At 1 month, the animals that had demonstrated left ventricular ejection fractions less than 40% were randomly divided into a mononuclear stem cell group and controls. Mononuclear stem cells were isolated. All animals underwent echocardiographic study: baseline, pre-cell therapy, and at 1 month post-cell therapy, and analyzed by the nonparametric Mann-Whitney test. Transplants were performed by subepicardial injections. Standard staining was performed. Results: Twenty-three animals were randomly treated: mononuclear stem cell and control groups, with 11 rats completing the study. Cell viability was 85%. Mononuclear stem cells (n=5; 5x10(6) cells 1300 mu L medium) and control (n=6; 300 mu L medium) were used. The resulting left ventricular ejection fraction in the cell therapy group was not significantly different compared with controls (p=0.54). New vessels were demonstrated in the subepicardial region. Conclusions: Autologous mononuclear stem cell therapy was not functionally effective in doxorubicin-induced dilated myocardiopathy in the animal model under study with the experimental conditions, despite occurrence of angiogenic activity. C1 [Carvalho, K. A. T.] Pele Pequeno Principe Inst Child & Adolescent Hlt, BR-80430180 Curitiba, Parana, Brazil. [Carvalho, K. A. T.; Simeoni, R. B.; Guarita-Souza, L. C.; Francisco, J. C.; Myiague, N. I.; Olandoski, M.; Gremski, W.] Pontifcia Univ Parana, Posgrad Ciencias Saude Univ, Curitiba, Parana, Brazil. [Carvalho, K. A. T.] Univ Fed Parana, Centro Politecn, Div Biotecnol, BR-80060000 Curitiba, Parana, Brazil. [Abdelwahid, E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC, Charlestown, MA USA. [Chachques, J. C.] George Pompidou European Hosp, Paris, France. [Oliveira, L.; Malvezzi, M.] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. [Rivetti, L. A.] Hosp Santa Casa de Misericordia Sao Paulo, Sao Paulo, Brazil. RP Carvalho, KAT (reprint author), Catholic Univ Parana, Alameda Carlos de Carvalho 655,Conj 1405, BR-80430180 Curitiba, Parana, Brazil. EM katherinecarv@gmail.com NR 28 TC 2 Z9 2 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD MAY PY 2008 VL 31 IS 5 BP 431 EP 438 PG 8 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 321MZ UT WOS:000257310700009 PM 18609517 ER PT J AU Heshka, S Ruggiero, A Bray, GA Foreyt, J Kahn, SE Lewis, CE Saad, M Schwartz, AV AF Heshka, S. Ruggiero, A. Bray, G. A. Foreyt, J. Kahn, S. E. Lewis, C. E. Saad, M. Schwartz, A. V. CA Look AHEAD Res Grp TI Altered body composition in type 2 diabetes mellitus SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE type 2 diabetes mellitus; fat mass; lean mass; men; women ID X-RAY ABSORPTIOMETRY; INSULIN SENSITIVITY; FAT DISTRIBUTION; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; ARTERIAL STIFFNESS; GLUCOSE-TOLERANCE; ABDOMINAL FAT; WEIGHT-LOSS; THIGH FAT AB Objective: To identify differences in amount and distribution of fat and lean soft tissue in a cross-sectional study of subjects with and without type 2 diabetes and to determine whether any differences are affected by race/ethnicity or sex. Design and methods: Overweight and obese (body mass index, BMI >= 25 kg m(-2)) Black, White and Hispanic men (490) and women (825) with type 2 diabetes ((mean +/- s.d.) age 58.5 +/- 6.6; BMI 35.3 +/- 5.3) who had a baseline dual energy X-ray absorptiometry whole-body scan at the time of enrollment in the Look AHEAD clinical trial, and 242 healthy controls, 91 males and 151 females (age 55.3 +/- 8.6 years, BMI 30.7 +/- 4.2 kg m(-2)) who were participating in unrelated research and were scanned on the same densitometers. Results: Adjusted for gender, age, race, clinical site and body size, total fat mass was smaller in persons with type 2 diabetes than in controls (-1.4 +/- 0.3 (s.e.); 34.5 vs 35.8 kg, P<0.001) while trunk fat was larger (1.3 +/- 0.2 (s.e.); 19.9 vs 18.6 kg, P<0.001) and leg fat was smaller (-1.5 +/- 0.2 (s.e.); 10.7 vs 12.3 kg, P<0.001). The arms of subjects with type 2 diabetes did not have significantly less fat compared to controls. Adjusted trunk lean mass was larger in type 2 diabetes by 0.6 kg (28.4 vs 27.8 kg, P<0.001) while leg lean was smaller by 0.5 kg (18.1 vs 18.6 kg, P<0.001). Conclusions: Type 2 diabetes is associated with less total fat, leg fat and leg lean mass and more truncal fat and lean mass than controls. The physiological processes producing these deviations in tissue distribution and their metabolic significance warrant further investigation. C1 [Heshka, S.] St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10025 USA. [Ruggiero, A.] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Bray, G. A.] Louisiana State Univ, Pennington Biomed Res Ctr, Dept Clin Res, Baton Rouge, LA USA. [Foreyt, J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kahn, S. E.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. [Lewis, C. E.] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL USA. [Saad, M.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY USA. [Schwartz, A. V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. RP Schwartz, AV (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Suite 5700, San Francisco, CA 94107 USA. EM aschwartz@psg.ucsf.edu OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [M01 RR000051, M01 RR000056, M01 RR000211, M01 RR001066, M01 RR002719]; NIDDK NIH HHS [U01 DK056990, P30 DK046204, P30 DK048520, U01 DK056992, U01 DK057002, U01 DK057008, U01 DK057078, U01 DK057131, U01 DK057135, U01 DK057136, U01 DK057136-09, U01 DK057149, U01 DK057151, U01 DK057154, U01 DK057171, U01 DK057177, U01 DK057178, U01 DK057182, U01 DK057219] NR 27 TC 22 Z9 25 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2008 VL 32 IS 5 BP 780 EP 787 DI 10.1038/sj.ijo.0803802 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 299LB UT WOS:000255756000008 PM 18227843 ER PT J AU Silva-Boghossian, C Castro, GF Teles, RP De Souza, IPR Colombo, APV AF Silva-Boghossian, Carina Castro, Gloria Fernanda Teles, Ricardo Palmier De Souza, Ivete P. R. Colombo, Ana Paula V. TI Salivary microbiota of HIV-positive children and its correlation with HIV status, oral diseases, and total secretory IgA SO INTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY LA English DT Article ID ANTIRETROVIRAL THERAPY; CHRONIC PERIODONTITIS; SUBGINGIVAL MICROBIOTA; INFECTED PATIENTS; HERPESVIRUSES; PREVALENCE; HAART; ASSOCIATION; BRAZILIANS; BACTERIA AB Aim. This study aimed to investigate the prevalence and levels of salivary microorganisms in HIV-positive children, and their correlation to HIV status, oral lesions, and salivary IgA levels. Design. Forty-two HIV-positive and 36 control children were clinically examined, had their saliva collected and processed for the microbiological analysis of 38 bacterial taxa by the checkerboard method, and salivary IgA quantification by ELISA. Results. The majority of the species tested were more prevalent in control children than in the HIV group. Mean concentration of total salivary IgA was similar in both groups. High levels of Veillonella parvula were found in children with cheilitis and herpes. Tannerella forsythia, Eikenella Corrodens, and Propionibacterium acnes were prevalent in children with gingivitis, while Fusobacterium periodonticum, Streptococcus gordonii, and Streptococcus oralis were significantly more frequent in children with no oral lesions. Significant negative correlations between salivary IgA levels and Eubacterium nodatum and oral streptococci were observed (P < 0.05). Conclusion. HIV-seropositive children presented significantly lower prevalence and levels of several bacterial species in saliva; HIV-positive children are able to mount a mucosal immune response; HIV-seropositive children under highly active antiretroviral therapy presented low prevalence of oral lesions. C1 [Silva-Boghossian, Carina; Colombo, Ana Paula V.] Univ Fed Rio de Janeiro, Inst Microbiol, BR-21941 Rio De Janeiro, Brazil. [Castro, Gloria Fernanda; De Souza, Ivete P. R.] Univ Fed Rio de Janeiro, Dept Paediat Dent, BR-21941 Rio De Janeiro, Brazil. [Teles, Ricardo Palmier] Forsyth Inst, Boston, MA USA. RP Silva-Boghossian, C (reprint author), Rua Barao Guaratiba 228, BR-22211150 Rio De Janeiro, RJ, Brazil. EM carinabogho@hotmail.com RI Inbeb, Inct/K-2317-2013; Silva-Boghossian, Carina M./G-9440-2012 OI Silva-Boghossian, Carina M./0000-0002-4500-4350 NR 32 TC 8 Z9 8 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0960-7439 J9 INT J PAEDIATR DENT JI Int. J. Paediatr. Dent. PD MAY PY 2008 VL 18 IS 3 BP 205 EP 216 DI 10.1111/j.1365-263X.2007.00864.x PG 12 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA 283BW UT WOS:000254612600007 PM 18384349 ER PT J AU D'Amico, AV Halabi, S Tempany, C Titflbaum, D Philips, GK Loffredo, M Mcmahon, E Sanford, B Vogelzang, NJ Small, EJ AF D'Amico, Anthony V. Halabi, Susan Tempany, Clare Titflbaum, David Philips, George K. Loffredo, Marian Mcmahon, Elizabeth Sanford, Ben Vogelzang, Nicholas J. Small, Eric J. CA Canc TI Tumor volume changes on 1.5 Tesla endorectal MRI during neoadjuvant androgen suppression therapy for higher-risk prostate cancer and recurrence in men treated using radiation therapy results of the phase IICALGB 9682 study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RADICAL PROSTATECTOMY; ANTIGEN; MORTALITY; MITOXANTRONE; RADIOTHERAPY; PREDNISONE; PREDICTION; DOCETAXEL AB Purpose: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. Patients and Methods: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). Results: After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5;p = 0.025]) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. Conclusion: Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST. (c) 2008 Elsevier Inc. C1 [D'Amico, Anthony V.; Tempany, Clare; Titflbaum, David; Loffredo, Marian; Mcmahon, Elizabeth] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.; Tempany, Clare; Titflbaum, David; Loffredo, Marian; Mcmahon, Elizabeth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Halabi, Susan; Sanford, Ben] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. [Philips, George K.] Univ Vermont, Ctr Canc, Burlington, VT USA. [Vogelzang, Nicholas J.] Las Vegas Canc Ctr, Las Vegas, NV USA. [Small, Eric J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. EM adamico@partners.org FU NCI NIH HHS [R01 CA111288, U10 CA077651, U10 CA041287, CA33601, U10 CA003927, CA31946, CA41287, U10 CA031946, U10 CA032291, U10 CA031946-18, U10 CA033601, R01 CA111288-01A1] NR 24 TC 7 Z9 7 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 MAY 1 PY 2008 VL 71 IS 1 BP 9 EP 15 DI 10.1016/j.ijrobp.2007.09.033 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 290UV UT WOS:000255149000003 PM 18037582 ER PT J AU Corn, BW Moughan, J Knisely, JPS Fox, SW Chakravarti, A Yung, WKA Curran, WJ Robins, HI Brachman, DG Henderson, RH Mehta, MP Movsas, B AF Corn, Benjamin W. Moughan, Jennifer Knisely, Jonathan P. S. Fox, Sherry W. Chakravarti, Arnab Yung, W. K. Alfred Curran, Walter J., Jr. Robins, H. Ian Brachman, David G. Henderson, Randal H. Mehta, Minesh P. Movsas, Benjamin TI Prospective evaluation of quality of life and neurocognitive effects in patients with multiple brain metastases receiving whole-brain radiotherapy with or without thalidomide on Radiation Therapy Oncology Group (RTOG) trial 0118 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE brain metastases; whole-brain radiotherapy; thalidomide; quality of life; neurocognition ID MENTAL-STATE-EXAMINATION; HIGH-GRADE GLIOMA; CELL LUNG-CANCER; COGNITIVE FUNCTION; MOTEXAFIN GADOLINIUM; OUTCOME RESEARCH; PHASE-II; SURVIVAL; CHEMOTHERAPY; TUMORS AB Purpose: Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) +/- thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. Methods and Materials: Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. Results: Baseline SQLI predicted survival. patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. Conclusions: Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population. (c) 2008 Elsevier Inc. C1 Tel Aviv Med Ctr & Sch Med, Inst Radiotherapy, Dept Radiat Oncol, Tel Aviv, Israel. [Moughan, Jennifer] Radiat Therapy Oncol Grp, Stat Unit, Philadelphia, PA USA. [Fox, Sherry W.] Cullather Brain Tumor Qual Life Ctr, Richmond, VA USA. [Knisely, Jonathan P. S.] Yale Univ, Dept Radiat Oncol, New Haven, CT USA. [Chakravarti, Arnab] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Yung, W. K. Alfred] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Curran, Walter J., Jr.] Emory Univ, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Brachman, David G.] St Josephs Hosp, Dept Radiat Oncol, Phoenix, AZ USA. [Henderson, Randal H.] Univ Florida, Dept Radiat Oncol, Gainesville, FL USA. [Robins, H. Ian; Mehta, Minesh P.] Univ Wisconsin, Dept Radiat Oncol, Madison, WI USA. [Movsas, Benjamin] Henry Ford Hosp, Dept Radiat Oncol, Detroit, MI 48202 USA. RP Corn, BW (reprint author), Tel Aviv Med Ctr & Sch Med, Inst Radiotherapy, Dept Radiat Oncol, 6 Wizeman St, Tel Aviv, Israel. EM bencorn@tasinc.health.gov.il OI Henderson, Randal/0000-0002-1740-738X; mehta, minesh/0000-0002-4812-5713 NR 36 TC 28 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2008 VL 71 IS 1 BP 71 EP 78 DI 10.1016/j.ijrobp.2007.09.015 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 290UV UT WOS:000255149000012 PM 18164829 ER PT J AU Knisely, JPS Berkey, B Chakravarti, A Yung, AWK Curran, WJ Robins, HI Movsas, B Brachman, DG Henderson, RH Mehta, MP AF Knisely, Jonathan P. S. Berkey, Brian Chakravarti, Arnab Yung, Al W. K. Curran, Walter J., Jr. Robins, H. Ian Movsas, Benjamin Brachman, David G. Henderson, Randall H. Mehta, Minesh P. TI A phase III study of conventional radiation therapy plus thalidomide versus conventional radiation therapy for multiple brain metastases (RTOG 0118) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE brain metastases; whole-brain radiotherapy; thalidomide; phase III trial; antiangiogenesis ID NONSMALL CELL LUNG; ANGIOGENESIS INHIBITORS; RANDOMIZED-TRIAL; RENAL-CELL; CANCER; BEVACIZUMAB; PROLIFERATION; RADIOTHERAPY; COMBINATION; APOPTOSIS AB Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, p rogressio n -free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol -planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects. (c) 2008 Elsevier Inc. C1 [Knisely, Jonathan P. S.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. [Knisely, Jonathan P. S.] Yale Canc Ctr, New Haven, CT 06520 USA. [Berkey, Brian] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Chakravarti, Arnab] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Chakravarti, Arnab] Harvard Univ, Sch Med, Boston, MA USA. [Yung, Al W. K.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Yung, Al W. K.] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA. [Curran, Walter J., Jr.] Emory Univ, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Robins, H. Ian] Univ Wisconsin, Dept Human Oncol, Madison, WI USA. [Robins, H. Ian; Mehta, Minesh P.] Univ Wisconsin, Dept Med, Madison, WI USA. [Movsas, Benjamin] Henry Ford Hlth Syst, Dept Radiat Oncol, Detroit, MI USA. [Brachman, David G.] AZ Oncol Serv, Dept Radiat Oncol, Phoenix, AZ USA. [Brachman, David G.] St Josephs Hosp, Phoenix, AZ USA. [Henderson, Randall H.] Univ Florida, Proton Therapy Inst, Jacksonville, FL USA. RP Knisely, JPS (reprint author), Yale Univ, Sch Med, Dept Therapeut Radiol, 333 Cedar St,133 HRT,POB 208040, New Haven, CT 06520 USA. EM jonathan.knisely@yale.edu OI Henderson, Randal/0000-0002-1740-738X; mehta, minesh/0000-0002-4812-5713 NR 46 TC 58 Z9 58 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2008 VL 71 IS 1 BP 79 EP 86 DI 10.1016/j.ijrobp.2007.09.016 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 290UV UT WOS:000255149000013 PM 18164847 ER PT J AU Mauldin, PD Simpson, KN Palesch, YY Spilker, JS Hill, MD Khatri, P Broderick, JP AF Mauldin, Patrick D. Simpson, Kit N. Palesch, Yuko Y. Spilker, Judy S. Hill, Michael D. Khatri, Pooja Broderick, Joseph P. CA IMS III Investigators TI Design of the economic evaluation for the Interventional Management of Stroke (III) trial SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE cost-effectiveness; economic evaluation; quality of life; resource utilization ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC-STROKE; COST-EFFECTIVENESS; UNITED-STATES; HOSPITAL COSTS; HEALTH; CARE; SERVICES; MODEL AB Rationale Stroke is a common and costly condition where an effective early treatment may be expected to affect patients' future quality of life, the cost of acute medical treatment, and the cost of rehabilitation and any supportive care needed for their remaining lifetime. To assist in informing discussions on early adoption of potential treatments, economic analyses should accompany investigations that seek to improve outcomes for stroke patients. Aims The primary aim is to assess whether i.v./i.a. rt-PA therapy is cost-effective at 3 months compared with i.v. rt-PA, and provides cost-savings or is cost-neutral by 12 months. Design Cost-effectiveness of the two treatment arms will be measured at months 3, 6, 9, and 12. Cost-effectiveness will be calculated using 1.standard cost-effectiveness methodology (incremental cost-effectiveness ratios), and 2an econometric model to assess multiple outcome measures while controlling for multiple subject and treatment-related factors that are known to affect both outcomes and costs. Study outcomes Total cost for the initial hospitalization of treating stroke subjects randomized to either i.v./i.a. or i.v. rt-PA treatment arms will be measured, as will differences in types of resource utilization over 12 months between the two arms of the trial. Quality-of-life data (EuroQol EQ-5D) will be collected over a 12-month period and quality-adjusted life years will be used as a morbidity-adjusted measure of effectiveness. Subgroup analyses will include dichotomized NIH Stroke Scale (< 20, >= 20), country, time between onset and randomization, and i.a. devices. C1 [Mauldin, Patrick D.] Med Univ S Carolina, Coll Pharm, Dept Pharm & Clin Sci, Charleston, SC 29425 USA. [Mauldin, Patrick D.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Simpson, Kit N.] Med Univ S Carolina, Dept Hlth Adm & Policy, Charleston, SC 29425 USA. [Palesch, Yuko Y.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Spilker, Judy S.; Khatri, Pooja; Broderick, Joseph P.] Univ Cincinnati, Acad Hlth Ctr, Dept Neurol, Cincinnati, OH USA. [Hill, Michael D.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. RP Mauldin, PD (reprint author), Med Univ S Carolina, Coll Pharm, Dept Pharm & Clin Sci, POB 250144,QF213B, Charleston, SC 29425 USA. EM mauldinp@musc.edu OI Hill, Michael/0000-0002-6269-1543 FU NINDS NIH HHS [U01 NS054630-04, T32 NS047996, U01 NS052220, U01 NS052220-04, U01 NS054630] NR 27 TC 9 Z9 9 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD MAY PY 2008 VL 3 IS 2 BP 138 EP 144 DI 10.1111/j.1747-4949.2008.00190.x PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 289NF UT WOS:000255060500011 PM 18706008 ER PT J AU Menzies, D Gardiner, G Farhat, M Greenaway, C Pai, M AF Menzies, D. Gardiner, G. Farhat, M. Greenaway, C. Pai, M. TI Thinking in three dimensions: a web-based algorithm to aid the interpretation of tuberculin skin test results SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculin skin test; latent TB infection; prediction rules; clinical decision aids; software ID TRANSPLANT RECIPIENTS; MYCOBACTERIUM-TUBERCULOSIS; MAINTENANCE HEMODIALYSIS; PULMONARY TUBERCULOSIS; UNITED-STATES; RISK-FACTORS; INFECTION; EPIDEMIOLOGY; SENSITIVITY; PREVALENCE AB BACKGROUND: The tuberculin skin test (TST) is the most widely used test for detecting tuberculosis (TB) infection. Accurate interpretation of TST requires consideration of three dimensions-the size of the skin reaction, the positive predictive value (PPV) and risk of disease. METHODS: We developed a web-based algorithm incorporating epidemiological, medical and radiographic risk factors to help in the interpretation of positive TST results in adults (http://www.meakins.mcgill.ca/meakins/ NEW TST Calculator/homeE.htm). We used summary estimates from published reviews on the prevalence of latent TB infection, the likelihood of false-positive TST and risk of active TB disease. RESULTS: The algorithm calculations show that the most important determinants of risk of active disease arc the presence of medical and radiographic risk factors, while the size of the reaction is of modest importance. In persons who have received bacille Calmette-Guerin vaccination after infancy, the algorithm calculations show that the PPV will be low. In such persons, the risk of disease is predicted to be very low, unless there are medical or radiographic risk factors that increase the risk of reactivation. CONCLUSIONS: Our web-based algorithm can generate clinically useful estimates of the annual and cumulative lifetime risk of developing TB in adults with a positive TST. C1 [Menzies, D.; Gardiner, G.; Farhat, M.; Greenaway, C.; Pai, M.] McGill Univ, Resp Epidemiol & Clin Res Unit, Montreal Chest Inst, Montreal, PQ H2X 2P4, Canada. [Gardiner, G.; Farhat, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Greenaway, C.] McGill Univ, Sir Mortimer B Davis Jewish Hosp, Div Infect Dis & Microbiol, Montreal, PQ, Canada. [Pai, M.] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. RP Menzies, D (reprint author), McGill Univ, Resp Epidemiol & Clin Res Unit, Montreal Chest Inst, 3650 St Urbain,Rm K1 24, Montreal, PQ H2X 2P4, Canada. EM dick.menzies@mcgill.ca NR 56 TC 43 Z9 43 U1 1 U2 3 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 MAY PY 2008 VL 12 IS 5 BP 498 EP 505 PG 8 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 293SM UT WOS:000255355000005 PM 18419884 ER PT J AU Davis, MD Bressler, SB Aiello, LP Bressler, NM Browning, DJ Flaxel, CJ Fong, DS Foster, WJ Glassman, AR Hartnett, MER Kollman, C Li, HK Qin, HJ Scott, IU AF Davis, Matthew D. Bressler, Susan B. Aiello, Lloyd Paul Bressler, Neil M. Browning, David J. Flaxel, Christina J. Fong, Donald S. Foster, William J. Glassman, Adam R. Hartnett, Mary Elizabeth R. Kollman, Craig Li, Helen K. Qin, Haijing Scott, Ingrid U. CA Diabet Retinopathy Clinical Res TI Comparison of time-domain OCT and fundus photographic assessments of retinal thickening in eyes with diabetic macular edema SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; RETINOPATHY; PHOTOCOAGULATION; THICKNESS AB PURPOSE. To explore the correlation between optical coherence tomography (OCT) and stereoscopic fundus photographs (FP) for the assessment of retinal thickening (RT) in diabetic macular edema (DME) within a clinical trial. METHODS. OCT, FP, and best corrected visual acuity (VA) measurements were obtained in both eyes of 263 participants in a trial comparing two photocoagulation techniques for DME. Correlation coefficients (r) were calculated comparing RT measured by OCT, RT estimated from FP, and VA. Principal variables were central subfield retinal thickness (CSRT) obtained from the OCT fast macular map and DME severity assessed by a reading center using a seven-step photographic scale combining the area of thickened retina within 1 disc diameter of the foveal center and thickening at the center. RESULTS. Medians (quartiles) for retinal thickness within the center subfield by OCT at baseline increased from 236 (214, 264) mu m in the lowest level of the photographic scale to 517 (455, 598) mu m in the highest level (r = 0.67). However, CSRT interquartile ranges were broad and overlapping between FP scale levels, and there were many outliers. Correlations between either modality and VA were weaker (r = 0.57 for CSRT, and r = 0.47 for the FP scale). OCT appeared to be more reproducible and more sensitive to change in RT between baseline and 1 year than was FP. CONCLUSIONS. There was a moderate correlation between OCT and FP assessments of RT in patients with DME and slightly less correlation of either measure with VA. OCT and FP provide complementary information but neither is a reliable surrogate for VA. C1 [Glassman, Adam R.; Kollman, Craig; Qin, Haijing] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Davis, Matthew D.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Bressler, Susan B.; Bressler, Neil M.] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. [Browning, David J.] Charlotte Eye Ear Nose & Throat Associates, Charlotte, NC USA. [Flaxel, Christina J.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. [Fong, Donald S.] Kaiser Permanente So Calif, Dept Ophthalmol, Baldwin Pk, CA USA. [Fong, Donald S.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Foster, William J.] Methodist Hosp, Weill Cornell Med Coll, Dept Ophthalmol, Houston, TX 77030 USA. [Foster, William J.] Univ Houston, Dept Phys, Houston, TX USA. [Hartnett, Mary Elizabeth R.] Univ N Carolina, Sch Med, Dept Ophthalmol, Chapel Hill, NC USA. [Li, Helen K.] Univ Texas Galveston, Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX 77550 USA. [Scott, Ingrid U.] Penn State Coll Med, Dept Ophthalmol & Publ Hlth Sci, Hershey, PA USA. RP Glassman, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrnet@jaeb.org FU NEI NIH HHS [EY 14231, K08 EY017112-01, U10 EY014229-06, U10 EY014231, U10 EY014231-07, U10 EY014269-04, K08 EY017112, U10 EY023207, U10 EY014269, U10 EY014229, K08 EY017112-02, EY 14269, EY 14229] NR 17 TC 40 Z9 40 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2008 VL 49 IS 5 BP 1745 EP 1752 DI 10.1167/iovs.07-1257 PG 8 WC Ophthalmology SC Ophthalmology GA 292UH UT WOS:000255291100001 PM 18316700 ER PT J AU Kang, JH Willett, WC Rosner, BA Hankinson, SE Pasquale, LR AF Kang, Jae Hee Willett, Walter C. Rosner, Bernard A. Hankinson, Susan E. Pasquale, Louis R. TI Caffeine consumption and the risk of primary open-angle glaucoma: A prospective cohort study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 06-10, 2007 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID FOOD FREQUENCY QUESTIONNAIRE; TOTAL-ENERGY-INTAKE; INTRAOCULAR-PRESSURE; OCULAR HYPERTENSION; EYE; REPRODUCIBILITY; VALIDITY; DISEASE; PREVALENCE; COFFEE AB PURPOSE. To investigate whether caffeine, which transiently increases intraocular pressure (IOP) is associated with the risk of primary open-angle glaucoma (POAG). METHODS. A total of 79,120 women from 1980 to 2004 and 42,052 men from 1986 to 2004, who were 40 + years of age, did not have POAG, and reported undergoing eye examinations, were observed. Information on caffeine consumption, potential confounders, and POAG diagnoses were repeatedly updated in validated follow-up questionnaires. One thousand eleven incident POAG cases were confirmed with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariate rate ratios (RRs). RESULTS. Compared with daily intake of less than 150 mg, the pooled multivariate RRs were 1.05 (95% confidence interval [CI], 0.89-1.25) for consumption of 150 to 299 mg/d, 1.19 (95% CI, 0.99-1.43) for 300 to 449 mg/d, 1.13 (95% CI, 0.89 - 1.43) for 450 to 559 mg/d, and 1.17 (95% CI, 0.90-1.53) for 600 + mg/d (P for trend = 0.11). However, for consumption of five or more cups of caffeinated coffee daily, the RR was 1.61 (95% CI, 1.00 - 2.59; P for trend = 0.02); tea or caffeinated cola intake were not associated with risk. Greater caffeine intake was more adversely associated with POAG among those reporting a family history of glaucoma, particularly in relation to POAG with elevated IOP (P for trend = 0.0009; P interaction = 0.04). CONCLUSIONS. Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high-tension POAG among those with a family history of glaucoma. This result may be due to chance, but warrants further study. C1 [Kang, Jae Hee; Willett, Walter C.; Rosner, Bernard A.; Hankinson, Susan E.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Kang, Jae Hee; Willett, Walter C.; Rosner, Bernard A.; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosner, Bernard A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. RP Kang, JH (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM nhjhk@channing.harvard.edu FU NCI NIH HHS [P01 CA087969, CA 55075, CA 87969, P01 CA055075, P01 CA055075-17, P01 CA087969-01]; NEI NIH HHS [EY 015473, EY 09611, R01 EY009611, R01 EY009611-09, R01 EY015473, R01 EY015473-08]; NHLBI NIH HHS [HL 35464, R01 HL035464, R01 HL035464-22] NR 47 TC 18 Z9 19 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2008 VL 49 IS 5 BP 1924 EP 1931 DI 10.1167/iovs.07-1425 PG 8 WC Ophthalmology SC Ophthalmology GA 292UH UT WOS:000255291100025 PM 18263806 ER PT J AU Levine, RA Durst, R AF Levine, Robert A. Durst, Ronen TI Mitral Valve Prolapse A Deeper Look SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material C1 [Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Yawkey 5-068,55 Fruit St, Boston, MA 02114 USA. EM rlevine@partners.org FU NHLBI NIH HHS [K24 HL067434, K24 HL067434-07, R01 HL038176] NR 36 TC 4 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2008 VL 1 IS 3 BP 304 EP 306 DI 10.1016/j.jcmg.2008.04.003 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V13EJ UT WOS:000207649800005 PM 19225572 ER PT J AU Bryan, CJ Songer, TJ Brooks, MM Thase, ME Gaynes, BN Klinkman, M Rush, AJ Trivedi, MH Fava, M Wisniewski, SR AF Bryan, Charlene J. Songer, Thomas J. Brooks, Maria Mori Thase, Michael E. Gaynes, Bradley N. Klinkman, Michael Rush, A. John Trivedi, Madhukar H. Fava, Maurizio Wisniewski, Stephen R. TI A comparison of baseline sociodemographic and clinical characteristics between major depressive disorder patients with and without diabetes: A STAR*D report SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE diabetes; major depressive disorder; depression treatment ID PLACEBO-CONTROLLED TRIAL; MEDICAL CONDITIONS; SOCIOECONOMIC-STATUS; COMORBID DEPRESSION; GLYCEMIC CONTROL; DOUBLE-BLIND; POPULATION; PREVALENCE; AGREEMENT; SYMPTOMS AB Background: Patients with major depressive disorder (MDD) have high rates of medical comorbidities which can impair MDD treatment. Yet little is known regarding associations between the presence of a serious comorbidity and MDD treatment. The purpose of this study was to examine the baseline sociodemographic and clinical characteristics of MDD outpatients with and without diabetes mellitus to evaluate possible associations between these characteristics and the presence of comorbid diabetes. Methods: We gathered baseline sociodemographic and clinical data for 4041 participants with non-psychotic MDD who enrolled in the STAR*D, a large-scale depression treatment protocol, and made comparisons between participants with and without diabetes. Results: Participants with diabetes were more likely to be male, older, black, Hispanic, unemployed, and have less education, a lower income, higher mental functioning, lower physical functioning, atypical features, increased appetite, psychomotor slowing and leaden paralysis, and were less likely to have concurrent alcohol abuse/dependence, mood reactivity or problems with concentration. We found no significant differences between groups regarding depression severity. Limitations: The primary limitation is the lack of a clinical diagnosis of diabetes. Conclusions: We found no difference in depression severity between participants with and without diabetes. Diabetes was associated with physical symptoms of depression. Thus treatments for these participants should be directed toward these symptoms. (C) 2007 Elsevier B.V. All rights reserved. C1 [Brooks, Maria Mori; Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Bryan, Charlene J.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Songer, Thomas J.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst, Mood Disorders Program, Pittsburgh, PA USA. [Gaynes, Bradley N.] Univ N Carolina, Chapel Hill, NC USA. [Klinkman, Michael] Univ Michigan, Ann Arbor, MI 48109 USA. [Rush, A. John; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Wisniewski, SR (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. EM wisniew@edc.pitt.edu OI Songer, Thomas/0000-0002-5253-2514; Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382; Brooks, Maria/0000-0002-2030-7873 FU NIMH NIH HHS [N01MH90003] NR 33 TC 8 Z9 9 U1 0 U2 3 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 MAY PY 2008 VL 108 IS 1-2 BP 113 EP 120 DI 10.1016/j.jad.2007.10.003 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 295AB UT WOS:000255446300012 PM 18037497 ER PT J AU Nierenberg, AA Alpert, JE Gaynes, BN Warden, D Wisniewski, SR Biggs, MM Trivedi, MH Barkin, JL Rush, AJ AF Nierenberg, Andrew A. Alpert, Jonathan E. Gaynes, Bradley N. Warden, Diane Wisniewski, Stephen R. Biggs, Melanie M. Trivedi, Madhukar H. Barkin, Jennifer L. Rush, A. John TI Family history of completed suicide and characteristics of major depressive disorder: A STAR*D (sequenced treatment alternatives to relieve depression) study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE family history; suicide; major depressive disorder ID DIAGNOSTIC SCREENING QUESTIONNAIRE; DELIBERATE SELF-HARM; REPORT QIDS-SR; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; PSYCHIATRIC-DISORDERS; MOOD DISORDERS; RATING-SCALE; BEHAVIOR; SYMPTOMATOLOGY AB Background: Clinicians routinely ask patients with non-psychotic major depressive disorder (MDD) about their family history of suicide. It is unknown, however, whether patients with a family member who committed suicide differ from those without such a history. Methods: Patients were recruited for the STAR*D multicenter trial. At baseline, patients were asked to report first-degree relatives who bad died from suicide. Differences in demographic and clinical features for patients with and without a family history of suicide were assessed. Results: Patients with a family history of suicide (n = 142/400 1; 3.5%) were more likely to have a family history of MDD, bipolar disorder, or any mood disorder, and familial substance abuse disorder, but not suicidal thoughts as compared to those without such a history. The group with familial suicide had a more pessimistic view of the future and an earlier age of onset of MDD. No other meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. Conclusions: A history of completed suicide in a family member was associated with minimal clinical differences in the cros-ssectional presentation of outpatients with MDD. Limitations of the study include lack of information about family members who had attempted suicide and the age of the probands when their family member died. STAR*D assessments were limited to those needed to ascertain diagnosis and treatment response and did not include a broader range of psychological measures. (C) 2007 Published by Elsevier B.V. C1 [Nierenberg, Andrew A.; Alpert, Jonathan E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Clin & Res Program, Boston, MA 01224 USA. [Gaynes, Bradley N.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Warden, Diane; Biggs, Melanie M.; Trivedi, Madhukar H.; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wisniewski, Stephen R.; Barkin, Jennifer L.] Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 01224 USA. EM anierenberg@partners.org RI Biggs, Dr. Melanie/C-1468-2010; OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 29 TC 6 Z9 6 U1 0 U2 4 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 MAY PY 2008 VL 108 IS 1-2 BP 129 EP 134 DI 10.1016/j.jad.2007.10.011 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 295AB UT WOS:000255446300014 PM 18006073 ER PT J AU Alden, LE Taylor, CT Mellings, TMJB Laposa, JM AF Alden, Lynn E. Taylor, Charles T. Mellings, Tanna M. J. B. Laposa, Judith M. TI Social anxiety and the interpretation of positive social events SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE social anxiety disorder; positive affect; negative interpretation ID STATE WORRY QUESTIONNAIRE; TRIPARTITE MODEL; COGNITIVE SPECIFICITY; MOOD DISORDERS; PHOBIA SCALE; VALIDATION; DEPRESSION; SENSITIVITY; DIMENSIONS; INDIVIDUALS AB We report four independent studies that examined the relationship between social interaction anxiety and the tendency to interpret positive social events in a threat-maintaining manner. Study I described the development of a scale that measures negative interpretations of positive social events, the interpretation of positive events scale (IPES). Study 2 cross-validated the structure of the IPES and established that social interaction anxiety explained significant variance in negative interpretations of positive social events beyond negative affect in general. Study 3 demonstrated that negative interpretation of positive events was significantly greater in a clinical sample of patients with generalized social anxiety disorder (GSAD) than a matched group of non-anxious community controls. In addition, within the GSAD group, the IPES was associated with negative social predictions following a positive interaction. Finally, study 4 confirmed that negative interpretations of positive social events mediated the relationship between social interaction anxiety and low positive affect. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Alden, Lynn E.; Mellings, Tanna M. J. B.] Univ British Columbia, Dept Psychol, Vancouver, BC V6T 1Z4, Canada. [Taylor, Charles T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Alden, LE (reprint author), Univ British Columbia, Dept Psychol, 2136 W Mall, Vancouver, BC V6T 1Z4, Canada. EM lalden@psych.ubc.ca NR 52 TC 52 Z9 58 U1 6 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAY PY 2008 VL 22 IS 4 BP 577 EP 590 DI 10.1016/j.janxdis.2007.05.007 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 296TM UT WOS:000255568700001 PM 17587542 ER PT J AU Calvo, JA Daniels, TG Wang, X Paul, A Lin, J Spiegelman, BM Stevenson, SC Rangwala, SM AF Calvo, Jennifer A. Daniels, Thomas G. Wang, Xiaomei Paul, Angelika Lin, Jiandie Spiegelman, Bruce M. Stevenson, Susan C. Rangwala, Shamina M. TI Muscle-specific expression of PPAR gamma coactivator-1 alpha improves exercise performance and increases peak oxygen uptake SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE exercise capacity; peak oxygen uptake; peroxisome proliferator-activated receptor gamma-coactivator-1 alpha ID ACTIVATED RECEPTOR-ALPHA; HUMAN SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; ENERGY-METABOLISM; TRANSCRIPTIONAL COACTIVATORS; INSULIN SENSITIVITY; PHYSICAL-ACTIVITY; PGC-1-ALPHA; PGC-1-BETA; GENE AB The induction of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), a key regulator of mitochondriogenesis, is well-established under multiple physical exercise regimens, including, endurance, resistance, and sprint training. We wanted to determine if increased expression of PGC-1 alpha in muscle is sufficient to improve performance during exercise in vivo. We demonstrate that muscle-specific expression of PGC-1 alpha improves the performance during voluntary as well as forced exercise challenges. Additionally, PGC-1 alpha transgenic mice exhibit an enhanced performance during a peak oxygen uptake exercise test, demonstrating an increased peak oxidative capacity, or whole body oxygen uptake. This increased ability to perform in multiple exercise paradigms is supported by enhanced mitochondrial function as suggested by increased mitochondrial gene expression, mitochondrial DNA, and mitochondrial enzyme activity. Thus this study demonstrates that upregulation of PGC-1 alpha in muscle in vivo is sufficient to greatly improve exercise performance under various exercise paradigms as well as increase peak oxygen uptake. C1 [Calvo, Jennifer A.; Daniels, Thomas G.; Wang, Xiaomei; Stevenson, Susan C.; Rangwala, Shamina M.] Novartis Inst BioMed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA. [Paul, Angelika] Novartis Inst BioMed Res, Musculoskeletal Dis Area, Cambridge, MA 02139 USA. [Lin, Jiandie; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rangwala, SM (reprint author), Novartis Inst BioMed Res, Diabet & Metab Dis Area, 100 Technol Sq, Cambridge, MA 02139 USA. EM shamina.rangwala@novartis.com NR 46 TC 189 Z9 194 U1 1 U2 21 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 2008 VL 104 IS 5 BP 1304 EP 1312 DI 10.1152/japplphysiol.01231.2007 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 295VB UT WOS:000255500900011 PM 18239076 ER PT J AU Weiss, M Safren, SA Solanto, MV Hechtman, L Rostain, AL Ramsay, JR Murray, C AF Weiss, Margaret Safren, Steven A. Solanto, Mary V. Hechtman, Lily Rostain, Anthony L. Ramsay, J. Russell Murray, Candice TI Research Forum on Psychological Treatment of Adults With ADHD SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ADHD; adult; psychosocial treatment; psychotherapy; cognitive behavioral therapy; dialectic behavioral therapy AB Background: A literature search found five empirical studies of psychological treatment for adults with ADHD, out of 1,419 articles on ADHD in adults. Practice guidelines to date all recommend multimodal intervention, given that a significant number of patients cannot tolerate, do not respond to, or fail to reach optimal outcomes with medication alone. Method: This article provides a literature review and the recommendations of a forum of experts in the psychological treatment of adults with ADHD. Results: Empirical studies of brief, structured, and short-term psychological interventions for adults with ADHD to date demonstrate moderate to large effect sizes. Methodological challenges include selection of control groups, broad-based measures of outcome, and the need for larger samples. Conclusion: Psychological treatment may play a critical role in the management of adults with ADHD who are motivated and developmentally ready to acquire new skills as symptoms remit. (J. of Att. Dis. 2008; 11(6) 642-651) C1 [Weiss, Margaret; Murray, Candice] Childrens & Womens Hlth Ctr, ADHD Clin, Vancouver, BC V6H 3N1, Canada. [Weiss, Margaret] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Solanto, Mary V.] Mt Sinai Sch Med, Dept Psychiat, ADHD Ctr, New York, NY 10029 USA. [Hechtman, Lily] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Rostain, Anthony L.; Ramsay, J. Russell] Univ Penn, Philadelphia, PA 19104 USA. RP Weiss, M (reprint author), Childrens & Womens Hlth Ctr, ADHD Clin, Box 178,4500 Oak St, Vancouver, BC V6H 3N1, Canada. EM mweiss@cw.bc.ca OI Solanto, Mary/0000-0002-3153-9610 FU Canadian ADHD Resource Alliance through Shire pharmaceuticals FX This article provides a written summary of a research focus group that took place at the annual meeting of the American Psychiatric Association in 2006. The meeting was sponsored by the Canadian ADHD Resource Alliance through an unrestricted educational grant from Shire pharmaceuticals. The article summarizes the key contributions of the participants, including Jim McGough, Annick Vincent, Martin Gignac, Craig Surman, Paul Hammerness, Tony Rostain, Russell Ramsay, Scott Kollins, Ross Clarke, Candice Murray, Lily Hechtman, Attilla Turgay, Susan Sprich, Stephen McDermott, Lily Hechtman, Candice Murray, J. Russell Ramsay, Anthony L. Rostain, Steven Safren, Mary V. Solanto, and Margaret Weiss. The event was facilitated and made possible by the continued efforts of Isabelle Poirier. Although the authors have borrowed heavily from the contributions of all the participants, the ideas expressed are the sole responsibility of the authors. Address correspondence to Margaret Weiss, Box 178, Children's and Women's Health Centre, 4500 Oak Street, Vancouver, BC V6H 3N1 Canada; e-mail: mweiss@cw.bc.ca. NR 39 TC 31 Z9 31 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD MAY PY 2008 VL 11 IS 6 BP 642 EP 651 DI 10.1177/1087054708315063 PG 10 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA V11GR UT WOS:000207520600005 PM 18417729 ER PT J AU Adler, LA Faraone, SV Spencer, TJ Michelson, D Reimherr, FW Glatt, SJ Marchant, BK Biederman, J AF Adler, Lenard A. Faraone, Stephen V. Spencer, Thomas J. Michelson, David Reimherr, Frederick W. Glatt, Stephen J. Marchant, Barrie K. Biederman, Joseph TI The Reliability and Validity of Self- and Investigator Ratings of ADHD in Adults SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE CAARS; self-rating, investigator rating; atomoxetine; reliability; validity ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; METHYLPHENIDATE; SYMPTOMS; EFFICACY; PLACEBO; SCALE AB Objective: Little information is available comparing self-versus investigator ratings of symptoms in adult ADHD. The authors compared the reliability, validity, and utility in a sample of adults with ADHD and also as an index of clinical improvement during treatment of self-and investigator ratings of ADHD symptoms via the Conners Adult ADHD Rating Scale (CAARS). Method: We analyzed data from two double-blind, parallel-design studies of 536 adult ADHD patients, randomized to 10-week treatment with atomoxetine or placebo. Outcome variables included ADHD symptom severity (CAARS self-and investigator ratings), psychiatric symptom comorbidity, and functioning. Results: All five CAARS sub-scales showed good internal consistency at each time point. Similarly, interrater reliability was acceptable for each subscale. Following treatment, CAARS total scores and subscale scores improved significantly from baseline. CAARS subscales also predicted changes in other psychiatric symptoms and functioning. Overall, baseline investigator ratings were stronger predictors of treatment outcome than baseline self-report scores. Conclusions: The CAARS demonstrated good internal consistency and inter-rater reliability, as well as sensitivity to treatment outcome. The finding of greater predictive power of investigator-rated baseline scores merits further investigation. (J. of Att. Dis. 2008; 11(6) 711-719) C1 [Adler, Lenard A.] NYU, Sch Med, New York, NY 10016 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, New York, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, New York, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychol, New York, NY USA. [Spencer, Thomas J.; Biederman, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Reimherr, Frederick W.; Marchant, Barrie K.] Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. [Glatt, Stephen J.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, San Diego, CA 92103 USA. RP Adler, LA (reprint author), NYU, Sch Med, 530 1st Ave,Suite 5A, New York, NY 10016 USA. EM Lenard.adler@med.nyu.edu OI Glatt, Stephen/0000-0002-0360-7567; Adler, Len/0000-0002-9812-8234; Faraone, Stephen/0000-0002-9217-3982 FU Eli Lilly and Company FX This work was supported by a research grant that Dr. Faraone received from Eli Lilly and Company. NR 18 TC 40 Z9 40 U1 1 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD MAY PY 2008 VL 11 IS 6 BP 711 EP 719 DI 10.1177/1087054707308503 PG 9 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA V11GR UT WOS:000207520600011 PM 18025250 ER PT J AU Adler, LA Spencer, TJ Levine, LR Ramsey, JL Tamura, R Kelsey, D Ball, SG Allen, AJ Biederman, J AF Adler, Lenard A. Spencer, Thomas J. Levine, Louise R. Ramsey, Janet L. Tamura, Roy Kelsey, Douglas Ball, Susan G. Allen, Albert J. Biederman, Joseph TI Functional Outcomes in the Treatment of Adults With ADHD SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ADHD; functional outcomes; atomoxetine; AAQoL; EWPS; long-term AB Objective: ADHD is associated with significant functional impairment in adults. The present study examined functional outcomes following 6-month double-blind treatment with either atomoxetine or placebo. Method: Patients were 410 adults (58.5% male) with DSM-IV-defined ADHD. They were randomly assigned to receive either atomoxetine 40 mg/day to 80 mg/day (n = 271) or placebo (n = 139). The primary functional outcome measure was the Endicott Work Productivity Scale (EWPS), and the secondary measure was the Adult ADHD Quality of Life (AAQoL). Patients were seen for four visits in 6 months. Results: At 6 months, both groups had nonsignificantly different improvements in EWPS total scores. Atomoxetine-treated patients showed significantly greater improvement than placebo-treated patients on the AAQoL after controlling for baseline severity of ADHD. Both treatment groups had low 6-month study completion rates. Conclusion: Following 6-month treatment with atomoxetine, adults with ADHD showed significantly greater improvement in functioning on disease-specific measures of quality of life than patients treated with placebo. (J. of Att. Dis. 2008; 11(6) 720-727) C1 [Adler, Lenard A.] NYU, Sch Med, Dept Psychiat, VA NY Harbor Healthcare Syst, New York, NY 10010 USA. [Spencer, Thomas J.; Biederman, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Spencer, Thomas J.; Biederman, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Adler, LA (reprint author), NYU, Sch Med, Dept Psychiat, VA NY Harbor Healthcare Syst, 423 E 23rd St,12 North,Room 12122C, New York, NY 10010 USA. EM Lenard.adler@med.nyu.edu OI Adler, Len/0000-0002-9812-8234 NR 23 TC 38 Z9 39 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD MAY PY 2008 VL 11 IS 6 BP 720 EP 727 DI 10.1177/1087054707308490 PG 8 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA V11GR UT WOS:000207520600012 PM 17968028 ER PT J AU Goldman, SR Tu, YP Goldberg, MB AF Goldman, Seth R. Tu, Yupeng Goldberg, Marcia B. TI Differential regulation by magnesium of the two MsbB paralogs of Shigella flexneri SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; ESCHERICHIA-COLI O157-H7; SALMONELLA-TYPHIMURIUM; LIPID-A; OUTER-MEMBRANE; PHOP-PHOQ; MOLECULAR CHARACTERIZATION; ANTIMICROBIAL PEPTIDES; POLYMYXIN RESISTANCE; HELA-CELLS AB Shigella flexneri, a gram-negative enteric pathogen, is unusual in that it contains two nonredundant paralogous genes that encode the myristoyl transferase MsbB (LpxM) that catalyzes the final step in the synthesis of the lipid A moiety of lipopolysaccharide. MsbB1 is encoded on the chromosome, and MsbB2 is encoded on the large virulence plasmid present in all pathogenic shigellae. We demonstrate that myristoyl transferase activity due to MsbB2 is detected in limited magnesium medium, but not in replete magnesium medium, whereas that due to MsbB1 is detected under both conditions. MsbB2 increases overall hexa-acylation of lipid A under limited magnesium conditions. Regulation of MsbB2 by magnesium occurs at the level of transcription and is dependent on the conserved magnesium-inducible PhoPQ two-component regulatory pathway. Direct hexanucleotide repeats within the promoter upstream of msbB2 were identified as a putative PhoP binding site, and mutations within the repeats led to diminished PhoP-dependent expression of a transcriptional fusion of lacZ to this promoter. Thus, the virulence plasmid-encoded paralog of msbB is induced under limited magnesium in a PhoPQ-dependent manner. PhoPQ regulates the response of many Enterobacteriaceae to environmental signals, which include modifications of lipid A that confer increased resistance of the organism to stressful environments and antimicrobial peptides. The findings reported here are the first example of gene duplication in which one paralog has selectively acquired the mechanism for differential regulation by PhoPQ. Our findings provide molecular insight into the mechanisms by which each of the two MsbB proteins of S. flexneri likely contributes to pathogenesis. C1 [Goldman, Seth R.; Tu, Yupeng; Goldberg, Marcia B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. RP Goldberg, MB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 65 Landsdowne St, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [AI059675, R21 AI059675] NR 67 TC 12 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2008 VL 190 IS 10 BP 3526 EP 3537 DI 10.1128/JB.00151-08 PG 12 WC Microbiology SC Microbiology GA 297ND UT WOS:000255622500012 PM 18359815 ER PT J AU Lee, S Zhu, LY Minhaj, AM Hinds, MF Vu, DH Rosen, DI Davis, SJ Hasan, T AF Lee, Seonkyung Zhu, Leyun Minhaj, Ahmed M. Hinds, Michael F. Vu, Danthu H. Rosen, David I. Davis, Steven J. Hasan, Tayyaba TI Pulsed diode laser-based monitor for singlet molecular oxygen SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE photodynamic therapy; singlet oxygen; light dosimetry ID PHOTODYNAMIC THERAPY; LUMINESCENCE; OPTIMIZATION; EFFICACY; KINETICS; CANCER AB Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O-2((1)Delta) are believed to be the species that destroys cancerous cells during PDT. Monitoring singlet oxygen produced by PDT may lead to more precise and effective PDT treatments. Our approach uses a pulsed diode laser-based monitor with optical fibers and a fast data acquisition system to monitor singlet oxygen during PDT. We present results of in vitro singlet oxygen detection in solutions and in a rat prostate cancer cell line as well as PDT mechanism modeling. (C) 2008 Society of Photo-Optical Instrumentation Engineers. C1 [Lee, Seonkyung; Zhu, Leyun; Minhaj, Ahmed M.; Hinds, Michael F.; Vu, Danthu H.; Rosen, David I.; Davis, Steven J.] Phys Sci Inc, Andover, MA 01810 USA. [Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Lee, S (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM lee@psicorp.com FU NCI NIH HHS [R43 CA096243, 1R43CA96243-01, P01 CA484203, R43 CA096243-01] NR 19 TC 24 Z9 25 U1 1 U2 11 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY-JUN PY 2008 VL 13 IS 3 AR 034010 DI 10.1117/1.2927465 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 330NX UT WOS:000257951200038 PM 18601555 ER PT J AU Pogue, BW Sheng, C Benevides, J Forcione, D Puricelli, B Nishioka, N Hasan, T AF Pogue, Brian W. Sheng, Chao Benevides, Juan Forcione, David Puricelli, Bill Nishioka, Norm Hasan, Tayyaba TI Protoporphyrin IX fluorescence photobleaching increases with the use of fractionated irradiation in the esophagus SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescence; photodetection; fiber optic sensors; photodynamic therapy; fiber optics; targets ID HAIRLESS MOUSE SKIN; PHOTODYNAMIC THERAPY; IN-VIVO; TUMORS; DOSIMETRY; TISSUE; QUANTIFICATION; LIGHT AB Fluorescence measurements have been used to track the dosimetry of photodynamic therapy (PDT) for many years, and this approach can be especially important for treatments with aminolevulinic-acid-induced protoporphyrin IX (ALA-PpIX). PpIX photobleaches rapidly, and the bleaching is known to be oxygen dependent, and at the same time, fractionation or reduced irradiance treatments have been shown to significantly increase efficacy. Thus, in vivo measurement of either the bleaching rate and/or the total bleaching yield could be used to track the deposited dose in tissue and determine the optimal treatment plans. Fluorescence in rat esophagus and human Barrett's esophagus are measured during PDT in both continuous and fractionated light delivery treatment, and the bleaching is quantified. Reducing the optical irradiance from 50 to 25 mW/cm did not significantly alter photobleaching in rat esophagus, but fractionation of the light at 1-min on and off intervals did increase photobleaching up to 10% more (p value=0.02) and up to 25% more in the human Barrett's tissue (p value<0.001). While two different tissues and two different dosimetry systems are used, the data support the overall hypothesis that light fractionation in ALA-PpIX PDT esophageal treatments should have a beneficial effect on the total treatment effect. (C) 2008 Society of Photo-Optical Instrumentation Engineers. C1 [Pogue, Brian W.; Sheng, Chao] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Pogue, Brian W.; Benevides, Juan; Forcione, David] Dartmouth Coll, Dept Surg, Hanover, NH 03755 USA. [Pogue, Brian W.; Puricelli, Bill; Nishioka, Norm; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Nishioka, Norm] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. EM pogue@dartmouth.edu FU NCI NIH HHS [P01 CA084203, P01CA84203] NR 19 TC 20 Z9 20 U1 0 U2 6 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY-JUN PY 2008 VL 13 IS 3 AR 034009 DI 10.1117/1.2937476 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 330NX UT WOS:000257951200037 PM 18601554 ER PT J AU Piper, SL Kim, HT AF Piper, Samantha L. Kim, Hubert T. TI Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTHROSCOPIC KNEE SURGERY; IN-VITRO; CARTILAGE; CELLS AB Background: It has been shown that bupivacaine, the most commonly used local anesthetic for postoperative intra-articular use, is cytotoxic to bovine articular chondrocytes in vitro. Ropivacaine is as effective as bupivacaine for intra-articular analgesia and has less systemic toxicity. We compared the in vitro viability of human articular chondrocytes after exposure to bupivacaine, ropivacaine, and saline solution control. Methods: Macroscopically normal human articular cartilage was harvested from the femoral head or tibial plateau of five patients. Full-thickness cartilage explants and cultured chondrocytes isolated from these patients were treated with 0.9% normal saline solution, 0.5% ropivacaine, or 0.5% bupivacaine for thirty minutes. Twenty-four hours after treatment, chondrocyte viability was measured with use of the LIVE/DEAD Viability/Cytotoxicity Kit for cartilage explants and with use of the CellTiter-Glo Luminescent Cell Viability Assay for cultured chondrocytes. Results: Chondrocyte viability in cartilage explants was significantly greater after treatment with ropivacaine as compared with bupivacaine (94.4%+/- 9.0% compared with 78%+/- 12.6%; p = 0.0004). There was no difference in viability after treatment with ropivacaine as compared with saline solution (94.4% 9.0% compared with 95.8% +/- 5.7%; p = 0.6). The viability of cultured chondrocytes was significantly greater after treatment with ropivacaine as compared with bupivacaine (63.9%+/- 19% as compared with 37.4%+/- 12% of the value in the saline solution group; p < 0.0001). Conclusions: In vitro, 0.5% ropivacaine is significantly less toxic than 0.5% bupivacaine in both intact human articular cartilage and chondrocyte culture. Clinical Relevance: Although bupivacaine is the most commonly used local anesthetic for intra-articular analgesia, the demonstrated toxicity to human articular chondrocytes is cause for concern. The present study demonstrated that ropivacaine is less chondrotoxic than bupivacaine and, therefore, may be safer for intra-articular analgesia. C1 [Piper, Samantha L.; Kim, Hubert T.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Piper, SL (reprint author), 360 Frederick St 3, San Francisco, CA 94117 USA. EM Samantha.piper@ucsf.edu; kimh@orthosurg.ucsf.edu NR 15 TC 140 Z9 142 U1 1 U2 7 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 2008 VL 90A IS 5 BP 986 EP 991 DI 10.2106/JBJS.G.01033 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 297KG UT WOS:000255615000006 PM 18451389 ER PT J AU Goodlin, SJ Wingate, S Pressler, SJ Teerlink, JR Storey, CP AF Goodlin, Sarah J. Wingate, Sue Pressler, Susan J. Teerlink, John R. Storey, C. Porter TI Investigating pain in heart failure patients: Rationale and design of the pain assessment, incidence & nature in heart failure (PAIN-HF) study SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure; symptoms; pain; advanced heart failure ID QUALITY-OF-LIFE; SYMPTOM ASSESSMENT SCALE; ELDERLY-PATIENTS; COGNITIVE IMPAIRMENT; HEALTH-STATUS; ILL PATIENTS; MINI-COG; QUESTIONNAIRE; VALIDATION; EXPERIENCE AB Background: Heart failure is a major cause of morbidity and mortality and is increasing in prevalence. Treatments for heart failure permit a growing number of persons to live with the illness for many years. The burden of symptoms in persons with advanced heart failure is high. Fatigue, limited exertion, dyspnea, and depression are commonly associated with heart failure, but pain is common as well. Methods and Results: Although it is known that underlying comorbidities modify the response to and experience of pain, the interaction between pain and the clinical syndrome of heart failure has not been studied to date. The Pain Assessment, Incidence & Nature in Heart Failure (PAIN-HF) study will evaluate pain in patients with advanced heart failure. Specifically, PAIN-HF will examine the anatomical location of pain, prevalence of pain, its association with aspects of patients' heart failure and comorbid conditions, and its relation to interventions and medications to treat pain. Conclusions: This study to identify the nature, incidence, and character of pain is an important step in relieving distress and discomfort in persons with heart failure. C1 [Goodlin, Sarah J.] Inst Hlth Care Delivery Res, Salt Lake City, UT 84111 USA. [Wingate, Sue] Kaiser Permanente Mid Atlantic States, Silver Spring, MD USA. [Pressler, Susan J.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Storey, C. Porter] Palliat Care, Denver, CO USA. RP Goodlin, SJ (reprint author), Inst Hlth Care Delivery Res, 36 S State St,21st Floor, Salt Lake City, UT 84111 USA. RI Teerlink, John/D-2986-2012 NR 53 TC 13 Z9 13 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD MAY PY 2008 VL 14 IS 4 BP 276 EP 282 DI 10.1016/j.cardfail.2008.01.008 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 304IS UT WOS:000256103800002 PM 18474339 ER PT J AU Cowan, SW Fiser, SM Albrecht, M Fifer, M Vlahakes, GJ Madsen, JC AF Cowan, Scott W. Fiser, Steven M. Albrecht, Meredith Fifer, Michael Vlahakes, Gus J. Madsen, Joren C. TI Management of coronary artery compression caused by recurrent aortic root abscess SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID RARE CAUSE; ENDOCARDITIS; OBSTRUCTION; ANGINA AB Extrinsic coronary artery compression is a rare cause of coronary ischemia. We report the case of a 61-year-old male who developed a recurrent aortic root abscess causing extrinsic coronary artery compression. This complication occurred one year after undergoing aortic valve replacement and pericardial patch exclusion of an aortic root abscess. Surgical correction required debridement of the abscess and replacement of the aortic root with a homograft resulting in resolution of coronary compression. C1 [Madsen, Joren C.] Harvard Univ, Sch Med, Div Cardiac Surg, Dept Surg, Boston, MA 02114 USA. [Madsen, Joren C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Sch Med, Div Cardiac Surg, Dept Surg, Boston, MA 02114 USA. EM jcmadsen@partners.org NR 12 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD MAY-JUN PY 2008 VL 23 IS 3 BP 195 EP 197 DI 10.1111/j.1540-8191.2008.00640.x PG 3 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 300PX UT WOS:000255838800002 PM 18435630 ER PT J AU Thomas, D Giugliano, RP AF Thomas, Deepak Giugliano, Robert P. TI Antiplatelet therapy in early management of non-ST-segment elevation acute coronary syndrome: The 2002 and 2007 guidelines from North America and Europe SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Review DE non-ST elevation acute coronary syndrome; guidelines; glycoprotein IIb/IIIa inhibitors; percutaneous coronary intervention; myocardial infarction ID ACUTE MYOCARDIAL-INFARCTION; HIGH-RISK PATIENTS; RANDOMIZED-TRIAL; UNSTABLE ANGINA; CLOPIDOGREL THERAPY; DOSE ASPIRIN; CURE TRIAL; TASK-FORCE; INTERVENTION; EVENTS AB The American College of Cardiology, American Heart Association, and the European Society of Cardiology published updated guidelines in 2007 for patients with non-ST elevation acute coronary syndrome. In this article, we review the recommendations for antiplatelet therapy and supporting data, highlight new changes, and describe differences between the European and North American guidelines. The new guidelines provide more details regarding the selection of an early conservative versus an early invasive approach based on the patient's profile and balance between ischemic and bleeding risks. Important new recommendations include wider endorsement for low-dose aspirin maintenance therapy, longer duration of clopidogrel following percutaneous coronary intervention, additional guidance regarding surgery in selected patients on clopidogrel, identification of patients most likely to benefit from glycoprotein IIb/IIIa inhibitors (with appropriate dose modification in patients with renal failure), and the option to use early clopidogrel with bivalirudin in patients managed invasively who are at increased risk of bleeding. The new guidelines also discourage the concomitant use of nonsteroidal anti-inflammatory drugs and delineate indications for adding warfarin to antiplatelet therapy. Because antiplatelet therapy is the cornerstone of management of patients with non-ST elevation acute coronary syndrome, health care providers should make themselves familiar with the new data and latest guideline recommendations. C1 [Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, TIMI Study Off, Boston, MA 02115 USA. [Thomas, Deepak] Brigham & Womens Hosp, Dept Nucl Cardiol, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, TIMI Study Off, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 45 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAY PY 2008 VL 51 IS 5 BP 425 EP 433 DI 10.1097/FJC.0b013e31816a35a2 PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 309IO UT WOS:000256454100001 PM 18418272 ER PT J AU Inada, A Kanamori, H Arai, H Akashi, T Araki, M Weir, GC Fukatsu, A AF Inada, Akari Kanamori, Hiroshi Arai, Hidenori Akashi, Tomoyuki Araki, Makoto Weir, Gordon C. Fukatsu, Atsushi TI A model for diabetic nephropathy: Advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin-induced diabetic mouse SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID INDUCED PANCREATIC INSULITIS; BETA-CELLS; RAT MODEL; KIDNEY; PROLIFERATION; HYPERGLYCEMIA; TRANSCRIPTION; MELLITUS; GROWTH; GENE AB We have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER 1 gamma) transgenic (Tg) mice. The ICER 1 gamma Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin-producing beta cells. Here in a longitudinal study we further analyzed diabetic nephropathy and structural and functional alterations in other organs, comparing our model with streptozotocin (STZ)-diabetic model mice. The high-dose STZ-diabetic model showed marked variation in blood glucose levels and severe toxicity of STZ in the liver and kidney. The low-dose STZ-diabetic model showed less toxicity, but the survival rate was very low. STZ-diabetic mice had much more variation of glomerular hypertrophy and sclerosis. Furthermore, non-specific toxicity of STZ or insulin injections to maintain optimal blood glucose levels might have another effect upon the diabetic renal changes. In contrast, ICER 1 gamma Tg mice exhibited a stable and progressive phenotype of diabetic kidney disease solely due to chronic hyperglycemia without other modulating factors. Thus, ICER 1 gamma Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model. C1 [Arai, Hidenori] Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Sakyo Ku, Kyoto 6068507, Japan. [Inada, Akari] Kyushu Univ, Grad Sch Med, SSP Stem Cell Unit, Fukuoka 812, Japan. [Inada, Akari; Akashi, Tomoyuki; Weir, Gordon C.] Joslin Diabet Ctr, Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Kanamori, Hiroshi; Araki, Makoto; Fukatsu, Atsushi] Kyoto Univ, Grad Sch Med, Dept Nephrol, Kyoto 6068507, Japan. RP Arai, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Geriatr Med, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan. EM harai@kuhp.kyoto-u.ac.ip NR 41 TC 22 Z9 22 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 2008 VL 215 IS 2 BP 383 EP 391 DI 10.1002/jcp.21316 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 286ZZ UT WOS:000254887100011 PM 18270980 ER PT J AU Peng, H Tan, L Osaki, M Zhan, Y Ijiri, K Tsuchimochi, K Otero, M Wang, H Choy, BK Grall, FT Gu, X Libermann, TA Oettgen, P Goldring, MB AF Peng, Haibing Tan, Lujian Osaki, Makoto Zhan, Yumei Ijiri, Kosei Tsuchimochi, Kaneyuki Otero, Miguel Wang, Hong Choy, Bob K. Grall, Franck T. Gu, Xuesong Libermann, Towia A. Oettgen, Peter Goldring, Mary B. TI ESE-1 is a potent repressor of type II collagen gene (COL2A1) transcription in human chondrocytes SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; HUMAN OSTEOARTHRITIC CARTILAGE; CCAAT/ENHANCER-BINDING PROTEIN; CD-RAP GENE; ARTICULAR CHONDROCYTES; RHEUMATOID-ARTHRITIS; FACTOR-ALPHA; IN-VITRO; DERMAL FIBROBLASTS AB The epithelium-specific ETS (ESE)-1 transcription factor is induced in chondrocytes by interleukin-1 beta (IL-1 beta). We reported previously that early activation of EGR-1 by IL-1 beta results in suppression of the proximal COL2A1 promoter activity by displacement of Sp1 from GC boxes. Here we report that ESE-1 is a potent transcriptional suppressor of COL2A1 promoter activity in chondrocytes and accounts for the sustained, NF-kappa B-dependent inhibition by IL-1 beta. Of the ETS factors tested, this response was specific to ESE-1, since ESE-3, which was also induced by IL-1 beta, suppressed COL2A1 promoter activity only weakly. In contrast, overexpression of ETS-1 increased COL2A1 promoter activity and blocked the inhibition by IL-1 beta. These responses to ESE-1 and ETS-1 were confirmed using siRNA-ESE1 and siRNA-ETS1. In transient cotransfections, the inhibitory responses to ESE-1 and IL-1 beta colocalized in the -577/-132 bp promoter region, ESE-1 bound specifically to tandem ETS sites at -403/-381 bp, and IL-1-induced binding of ESE-1 to the COL2A1 promoter was confirmed in vivo by Chip. Our results indicate that ESE-1 serves a potent repressor function by interacting with at least two sites in the COL2A1 promoter. However, the endogenous response may depend upon the balance of other ETS factors such as ETS-1, and other IL-1-induced factors, including EGR-1 at any given time. Intracellular ESE-1 staining in chondrocytes in cartilage from patients with osteoarthritis (OA), but not in normal cartilage, further suggests a fundamental role for ESE-1 in cartilage degeneration and suppression of repair. C1 [Tsuchimochi, Kaneyuki; Otero, Miguel; Goldring, Mary B.] Cornell Univ, Hosp Special Surg, Weill Coll Med, Lab Cartilage Biol,Res Div, New York, NY 10021 USA. [Peng, Haibing; Tan, Lujian; Osaki, Makoto; Zhan, Yumei; Ijiri, Kosei; Tsuchimochi, Kaneyuki; Otero, Miguel; Wang, Hong; Choy, Bob K.; Grall, Franck T.; Gu, Xuesong; Libermann, Towia A.; Oettgen, Peter; Goldring, Mary B.] Beth Israel Deaconess Med Ctr, Dept Med, New England Baptist Bone & Joint Inst, Boston, MA 02215 USA. [Choy, Bob K.; Grall, Franck T.; Gu, Xuesong; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, New England Baptist Bone & Joint Inst, Boston, MA USA. RP Goldring, MB (reprint author), Cornell Univ, Hosp Special Surg, Weill Coll Med, Lab Cartilage Biol,Res Div, Caspary Res Bldg,535 E 70th St, New York, NY 10021 USA. EM goldringm@hss.edu RI Libermann, Towia/F-9866-2010; Wang, Hong/H-6298-2012; OI Libermann, Towia/0000-0002-4006-8179 FU NIA NIH HHS [R01 AG022021, R01 AG022021-07A2, R01 AG022021-08, R01-AG022021]; NIAID NIH HHS [R01 AI049527, R01-AI49527]; NIAMS NIH HHS [R01 AR047952, R01-AR45378, R01-AR47952] NR 60 TC 28 Z9 28 U1 4 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 2008 VL 215 IS 2 BP 562 EP 573 DI 10.1002/jcp.21338 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 286ZZ UT WOS:000254887100029 PM 18044710 ER PT J AU Qiu, J Nishimura, M Wang, Y Sims, JR Qiu, S Savitz, SI Salomone, S Moskowitz, MA AF Qiu, Jianhua Nishimura, Masaki Wang, Yumei Sims, John R. Qiu, Sumei Savitz, Sean I. Salomone, Salvatore Moskowitz, Michael A. TI Early release of HMGB-1 from neurons after the onset of brain ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE HMGB-1; NeuN; brain ischemia; MCAO; neuroinflammation ID FOCAL CEREBRAL-ISCHEMIA; TUMOR-NECROSIS-FACTOR; MOBILITY GROUP BOX-1; INTERLEUKIN-1-BETA CONVERTING-ENZYME; MICROGLIAL-MACROPHAGE SYNTHESIS; CHROMATIN PROTEIN HMGB1; TOLL-LIKE RECEPTORS; END-PRODUCTS RAGE; NF-KAPPA-B; ENDOTHELIAL-CELLS AB The nuclear protein high-mobility group box 1 (HMGB-1) promotes inflammation in sepsis, but little is known about its role in brain ischemia-induced inflammation. We report that HMGB-1 and its receptors, receptor for advanced glycation end products (RAGE), Toll-like receptor 2 (TLR2), and TLR4, were expressed in normal brain and in cultured neurons, endothelia, and glial cells. During middle cerebral artery occlusion (MCAO), in mice, HMGB-1 immunostaining rapidly disappeared from all cells within the striatal ischemic core from 1 h after onset of occlusion. High-mobility group box 1 translocation from nucleus to cytoplasm was observed within the cortical periinfarct regions 2 h after ischemic reperfusion (2 h MCAO). High-mobility group box 1 predominantly translocated to the cytoplasm or disappeared in cells that colabeled with the neuronal marker NeuN. Furthermore, RAGE was robustly expressed in the periinfarct region after MCAO. Cellular release of HMGB-1 was detected by immunoblotting of cerebrospinal fluid as early as 2 h after ischemic reperfusion (2 h MCAO). High-mobility group box 1 released from neurons, in vitro, after glutamate excitotoxicity, maintained biologic activity and induced glial expression of tumor necrosis factor alpha (TNF alpha). AntiHMGB-1 antibody suppressed TNF alpha upregulation in astrocytes exposed to conditioned media from glutamate-treated neurons. Moreover, TNF alpha and the cytokine intercellular adhesion molecule-1 increased in cultured glia and endothelial cells, respectively, after adding recombinant HMGB-1. In conclusion, HMGB-1 is released early after ischemic injury from neurons and may contribute to the initial stages of the inflammatory response. C1 [Qiu, Jianhua; Nishimura, Masaki; Wang, Yumei; Sims, John R.; Qiu, Sumei; Savitz, Sean I.; Salomone, Salvatore; Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Qiu, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM jqiu@partners.org RI Moskowitz, Michael/D-9916-2011; OI Salomone, Salvatore/0000-0001-5307-6103 FU NINDS NIH HHS [P30-NS045776, K08 NS049241, R01NS048198, R21NS056212-01A1] NR 62 TC 207 Z9 218 U1 2 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2008 VL 28 IS 5 BP 927 EP 938 DI 10.1038/sj.jcbfm.9600582 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 292JC UT WOS:000255261300008 PM 18000511 ER PT J AU Yager, PH You, Z Qin, T Kim, HH Takahashi, K Ezekowitz, AB Stahl, GL Carroll, MC Whalen, MJ AF Yager, Phoebe H. You, Zerong Qin, Tao Kim, Hyung-Hwan Takahashi, Kazue Ezekowitz, Alan B. Stahl, Gregory L. Carroll, Michael C. Whalen, Michael J. TI Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cell death; complement; inflammation; lectins; mice; traumatic brain injury ID CORTICAL IMPACT INJURY; CLOSED-HEAD INJURY; NITRIC-OXIDE; COMPLEMENT INHIBITION; ISCHEMIA-REPERFUSION; SPATIAL MEMORY; WATER MAZE; RATS; NEURODEGENERATION; DISEASE AB Mannose binding lectin (MBL) initiates complement activation and exacerbates tissue damage after systemic ischemia/reperfusion. We tested the hypothesis that MBL activates complement and worsens outcome using two levels of controlled cortical impact (CCI) in mice. After moderate CCI (0.6 mm depth), MBL immunostaining was detected on injured endothelial cells of wild-type (WT) mice and C3d was detected in MBL KO (deficient in MBL A/C) and WT mice, suggesting that MBL is dispensable for terminal complement activation after CCI. Brain neutrophils, edema, blood-brain barrier permeability, gross histopathology, and motor dysfunction were similar in injured MBL KO and WT mice. In mice subjected to mild CCI (0.2 mm), MBL KO mice had almost two-fold increased acute CA3 cell degeneration at 6 h (P< 0.01 versus WT). Naive MBL KO mice had decreased brain volume but performed similar to WT mice in two distinct Morris water maze (MWM) paradigms. However, injured MBL KO mice had impaired performance in cued platform trials (P< 0.05 versus WT), suggesting a transient nonspatial learning deficit in injured MBL KO mice. The data suggest that MBL deficiency increases susceptibility to CCI through C3-independent mechanisms and that MBL-deficient patients may be at increased risk of poor outcome after traumatic brain injury. C1 [Yager, Phoebe H.; You, Zerong; Whalen, Michael J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Charlestown, MA USA. [Yager, Phoebe H.; You, Zerong; Qin, Tao; Whalen, Michael J.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. [Kim, Hyung-Hwan] Harvard Med Sch, Brigham & Womens Hosp, Vasc Med Res Unit, Boston, MA USA. [Takahashi, Kazue; Ezekowitz, Alan B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat, Dev Immunol Lab, Charlestown, MA USA. [Stahl, Gregory L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Carroll, Michael C.] Harvard Med Sch, CBR Inst Biomed Res Inc, Boston, MA USA. RP Whalen, MJ (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Charlestown, MA USA. EM mwhalen@partners.org FU NHLBI NIH HHS [HL52886, HL56086]; NIAID NIH HHS [AI42788-04]; NINDS NIH HHS [P30 NS045776, R01NS47447] NR 42 TC 24 Z9 24 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2008 VL 28 IS 5 BP 1030 EP 1039 DI 10.1038/sj.jcbfm.9600605 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 292JC UT WOS:000255261300017 PM 18183030 ER PT J AU Kimball, WR Carwood, CM Chang, Y McKenna, JM Peters, LE Ballantyne, JC AF Kimball, William R. Carwood, Caroline M. Chang, Yuchiao McKenna, Jennifer M. Peters, Lauren E. Ballantyne, Jane C. TI Effect of effort pain after upper abdominal surgery on two independent measures of respiratory function SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE effort pain; manometry; pain score; pulmonary function; spirometry; upper abdominal surgery ID CONTROLLED EPIDURAL ANALGESIA; PULMONARY-FUNCTION; LAPAROSCOPIC CHOLECYSTECTOMY; POSTOPERATIVE PAIN; GYNECOLOGICAL SURGERY; MUSCLE STRENGTH; LAPAROTOMY; RELIEF; ROPIVACAINE; VOLUME AB Study Objective: To determine how effort pain interacts with changing pulmonary function after upper abdominal incisions. Design: Prospective, case-controlled study. Setting: Academic teaching hospital. Patients: 34 ASA physical status I, II, and III patients recovering from elective, major incisional, upper abdominal surgery. Measurements: Manometry (maximal inspiratory and expiratory pressure) and spirometry (forced vital capacity, forced expiratory volume during the first second, peak expiratory flow) for three postoperative days. Pain scores (Visual Analog Pain Scale; VAS) at rest and after the manometric or spirometric efforts. Main Results: Effort pain during either manometry or spirometry was greater than pain at rest on the first postoperative day. Maximal respiratory pressure concomitantly recovered with pain during daily efforts (slopes: -0.429 and -0.278% max/min VAS; P < 0.05). Spirometric measurements showed minimal improvement. Conclusion: The direct relationship between resolution of pain with effort and direct measures of respiratory muscle effort using manometry, but not those obtained less directly by spirometry, suggests that assessing interactions between pain and effort requires a direct, quantifiable measure of effort. (c) 2008 Elsevier Inc. All rights reserved. C1 [Kimball, William R.; Carwood, Caroline M.; McKenna, Jennifer M.; Peters, Lauren E.; Ballantyne, Jane C.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Kimball, William R.; Ballantyne, Jane C.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Ballantyne, Jane C.] Massachusetts Gen Hosp, MGH Pain Ctr, Boston, MA 02114 USA. RP Kimball, WR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM wkimball@partners.org NR 40 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD MAY PY 2008 VL 20 IS 3 BP 200 EP 205 DI 10.1016/j.jclinane.2007.10.009 PG 6 WC Anesthesiology SC Anesthesiology GA 313HD UT WOS:000256730800009 PM 18502364 ER PT J AU Nieman, LK Biller, BMK Findling, JW Newell-Price, J Savage, MO Stewart, PM Montori, VM AF Nieman, Lynnette K. Biller, Beverly M. K. Findling, James W. Newell-Price, John Savage, Martin O. Stewart, Paul M. Montori, Victor M. TI The diagnosis of Cushing's syndrome: An endocrine society clinical practice guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID DEXAMETHASONE-SUPPRESSION TEST; CORTICOTROPIN-RELEASING HORMONE; URINARY FREE CORTISOL; MIDNIGHT SERUM CORTISOL; PITUITARY-ADRENAL AXIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; NIGHTTIME SALIVARY CORTISOL; CHRONIC-RENAL-FAILURE; STIMULATION TEST; SUBCLINICAL HYPERCORTISOLISM AB Objective: The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome. Participants: The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, membersresponding to awebposting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments. Conclusions: After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time. C1 [Nieman, Lynnette K.] NIH, Program Reprod & Adult Endocrinol, NICHHD, Bethesda, MD 20892 USA. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Findling, James W.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Newell-Price, John] Univ Sheffield, Sheffield S10 2JF, S Yorkshire, England. [Savage, Martin O.] Univ London, William Harvey Res Inst, London EC1M 6BQ, England. [Montori, Victor M.] Mayo Clin, Rochester, MN 55905 USA. [Stewart, Paul M.] Univ Birmingham, Birmingham B15 2TT, W Midlands, England. RP Nieman, LK (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. EM govt-prof@endo.society.org OI Montori, Victor/0000-0003-0595-2898 FU Intramural NIH HHS [Z01 HD008833-02] NR 109 TC 679 Z9 737 U1 1 U2 29 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2008 VL 93 IS 5 BP 1526 EP 1540 DI 10.1210/jc.2008-0125 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 298CD UT WOS:000255663100002 PM 18334580 ER PT J AU Shifren, JL Rifai, N Desindes, S McIlwain, M Doros, G Mazer, NA AF Shifren, Jan L. Rifai, Nader Desindes, Sophie McIlwain, Marilyn Doros, Gheorghe Mazer, Norman A. TI A comparison of the short-term effects of oral conjugated equine estrogens versus transdermal estradiol on C-reactive protein, other serum markers of inflammation, and other hepatic proteins in naturally menopausal women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE REPLACEMENT THERAPY; HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR RISK-FACTORS; ENDOTHELIAL FUNCTION; BINDING GLOBULIN; VENOUS THROMBOEMBOLISM; ADHESION MOLECULES; INSULIN-RESISTANCE; PREGNANT-WOMEN AB Objective: Our objective was to compare the effects of oral vs. transdermal estrogen therapy on C-reactive protein (CRP), IL-6, E- and P-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1, serum amyloid A, transferrin, prealbumin, IGF-I, SHBG, thyroxine-binding globulin (TBG), and cortisol-binding globulin (CBG) in naturally menopausal women. Design: This was a randomized, open-label crossover clinical trial. A 6-wk withdrawal from prior hormone therapy (baseline) was followed in randomized order by 12-wk oral conjugated equine estrogens (CEEs) (0.625 mg/d) and 12-wk transdermal estradiol (E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both regimens. Results: A total of 27 women enrolled, and 25 completed both treatment periods. Nine parameters changed significantly during oral CEE (median percent change from baseline; P value): CRP (192%; P < 0.001); E-selectin (-16.3%; P = 0.003); P-selectin (-15.3%; P = 0.012); ICAM-1 (-5%; P = 0.015); transferrin (5.3%; P = 0.024); IGF-I (-30.5%; P < 0.001); SHBG (113%; P < 0.001); TBG (38%; P < 0.001); and CBG (20%; P < 0.001). With transdermal E2, only three parameters changed significantly and to a lesser degree: ICAM-1 (-2.1%; P = 0.04); IGF-I (-12.5%; P < 0.001); and SHBG(2.6%; P = 0.042). During oral CEE the intrasubject changes in CRP correlated strongly with the changes in serum amyloid A (r = 0.805; P < 0.001), and were only weakly associated with the changes in SHBG (r = 0.248; nonsignificant), TBG (0.430; P = 0.031), and CBG (r = 0.072; nonsignificant). The log-log relationship between CRP and IL-6 observed at baseline showed a parallel shift during oral CEE, suggesting an amplified hepatic response or a greater sensitivity to IL-6 stimulation. Conclusion: Compared with oral CEE, transdermal E2 exerts minimal effects on CRP and the other inflammation and hepatic parameters. C1 [Shifren, Jan L.] Harvard Univ, Sch Med, Childrens Hosp Med Ctr, Vincent Obstet & Gynecol Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Childrens Hosp Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Childrens Hosp Med Ctr, Boston, MA 02115 USA. [Desindes, Sophie] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. [McIlwain, Marilyn] Watson Labs Inc, Morristown, NJ 07960 USA. [Doros, Gheorghe] Boston Univ, Sch Med, Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Doros, Gheorghe] Boston Univ, Sch Med, Sect Endocrinol Diabets & Nutr, Boston, MA 02118 USA. RP Mazer, NA (reprint author), Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, 670 Albany St,2nd Floor, Boston, MA 02118 USA. EM jshifren@partners.org; nmazer@bu.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 54 TC 41 Z9 41 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 MAY PY 2008 VL 93 IS 5 BP 1702 EP 1710 DI 10.1210/jc.2007-2193 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 298CD UT WOS:000255663100025 PM 18303079 ER PT J AU Liu, PY Swerdloff, RS Anawalt, BD Anderson, RA Bremner, WJ Elliesen, J Gu, YQ Kersemaekers, WM McLachlan, RI Meriggiola, MC Nieschlag, E Sitruk-Ware, R Vogelsong, K Wang, XH Wu, FCW Zitzmann, M Handelsman, DJ Wang, C AF Liu, Peter Y. Swerdloff, Ronald S. Anawalt, Bradley D. Anderson, Richard A. Bremner, William J. Elliesen, Joerg Gu, Yi-Qun Kersemaekers, Wendy M. McLachlan, Robert. I. Meriggiola, M. Cristina Nieschlag, Eberhard Sitruk-Ware, Regine Vogelsong, Kirsten Wang, Xing-Hai Wu, Frederick C. W. Zitzmann, Michael Handelsman, David J. Wang, Christina TI Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: An integrated analysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INTRAMUSCULAR TESTOSTERONE UNDECANOATE; DEPOT-MEDROXYPROGESTERONE ACETATE; NORMAL MEN; CYPROTERONE-ACETATE; NORETHISTERONE ENANTHATE; LEVONORGESTREL IMPLANTS; INJECTABLE TESTOSTERONE; ETONOGESTREL IMPLANTS; ORAL DESOGESTREL; CLINICAL-TRIAL AB Context: Male hormonal contraceptive methods require effective suppression of sperm output. Objective: The objective of the study was to define the covariables that influence the rate and extent of suppression of spermatogenesis to a level shown in previous World Health Organization-sponsored studies to be sufficient for contraceptive purposes (<= 1 million/ml). Design: This was an integrated analysis of all published male hormonal contraceptive studies of at least 3 months' treatment duration. Setting: Deidentified individual subject data were provided by investigators of 30 studies published between 1990 and 2006. Participants: A total of 1756 healthy men (by physical, blood, and semen exam) aged 18-51 yr of predominantly Caucasian (two thirds) or Asian (one third) descent were studied. This represents about 85% of all the published data. Intervention(s): Men were treated with different preparations of testosterone, with or without various progestins. Main Outcome Measure: Semen analysis was the main measure. Results: Progestin coadministration increased both the rate and extent of suppression. Caucasian men suppressed sperm output faster initially but ultimately to a less complete extent than did non-Caucasians. Younger age and lower initial blood testosterone or sperm concentration were also associated with faster suppression, but the independent effect sizes for age and baseline testicular function were relatively small. Conclusion: Male hormonal contraceptives can be practically applied to a wide range of men but require coadministration of an androgen with a second agent (i.e. progestin) for earlier and more complete suppression of sperm output. Whereas considerable progress has been made toward defining clinically effective combinations, further optimization of androgen-progestin treatment regimens is still required. C1 [Liu, Peter Y.; Handelsman, David J.] Univ Sydney, Dept Androl, ANZAC Res Inst, Concord, NSW 2139, Australia. [Liu, Peter Y.] Concord Hosp, Concord, NSW 2139, Australia. [Wang, Christina] Harbor UCLA Med Ctr, Gen Clin Res Ctr, Torrance, CA 90509 USA. [Swerdloff, Ronald S.] LABiomed, Div Endocrinol, Dept Med, Torrance, CA 90509 USA. Univ Washington, Seattle, WA 98195 USA. [Anawalt, Bradley D.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. [Anderson, Richard A.] Univ Edinburgh, Queens Med Res Inst, Div Reprod & Dev Sci, Edinburgh EH16 4TJ, Midlothian, Scotland. [Bremner, William J.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Elliesen, Joerg] Schering Pharma AG, Berlin, Germany. [Gu, Yi-Qun] Natl Res Inst Family Planning, Dept Endocrinol, Beijing 100081, Peoples R China. [Kersemaekers, Wendy M.] Schering Plough Corp, NV Organon, Translat Med Dept, NL-5340 BH Oss, Netherlands. [McLachlan, Robert. I.] Monash Univ, Monash Med Ctr, Clayton, Vic 3168, Australia. [McLachlan, Robert. I.] Monash Univ, Prince Henrys Inst, Clayton, Vic 3168, Australia. Univ Bologna, I-40138 Bologna, Italy. [Meriggiola, M. Cristina] St Orsola Marcello Malpighi Hosp, Dept Obstet, I-40138 Bologna, Italy. [Meriggiola, M. Cristina] St Orsola Marcello Malpighi Hosp, Dept Gynecol, I-40138 Bologna, Italy. [Nieschlag, Eberhard; Zitzmann, Michael] Univ Hosp, Inst Reprod Med, D-48149 Munster, Germany. Rockefeller Univ, New York, NY 10021 USA. [Sitruk-Ware, Regine] Populat Council, Ctr Biomed Res, New York, NY 10021 USA. [Vogelsong, Kirsten] WHO, Dept Reprod Hlth & Res, World Bank Special Programme Res, United Nations Fund Populat Act,United Nations De, CH-1211 Geneva 27, Switzerland. [Wang, Xing-Hai] Jiangsu Family Planning Res Inst, Jiangsu 210029, Peoples R China. [Wu, Frederick C. W.] Univ Manchester, Manchester Royal Infirm, Dept Endocrinol, Manchester M13 9WL, Lancs, England. [Wang, Christina] LABiomed, Gen Clin Res Ctr, Torrance, CA 90509 USA. RP Liu, PY (reprint author), Univ Sydney, Dept Androl, ANZAC Res Inst, Concord, NSW 2139, Australia. EM pliu@mail.usyd.edu.au; wang@labiomed.org RI Kersemaekers, Wendy/F-8034-2016 FU NICHD NIH HHS [U54 HD029990] NR 73 TC 43 Z9 44 U1 2 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2008 VL 93 IS 5 BP 1774 EP 1783 DI 10.1210/jc.2007-2768 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 298CD UT WOS:000255663100034 PM 18303073 ER PT J AU Samelson, EJ Broe, KE Demissie, S Beck, TJ Karasik, D Kathiresan, S Kiel, DP AF Samelson, Elizabeth J. Broe, Kerry E. Demissie, Serkalem Beck, Thomas J. Karasik, David Kathiresan, Sekar Kiel, Douglas P. TI Increased plasma osteoprotegerin concentrations are associated with indices of bone strength of the hip SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CIRCULATING OSTEOPROTEGERIN; SERUM OSTEOPROTEGERIN; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; FRAMINGHAM OSTEOPOROSIS; RECEPTOR ACTIVATOR; FRACTURES; TURNOVER; LIGAND; MEN AB Objective: Osteoprotegerin (OPG) is an important regulator of bone turnover through its effects on osteoclastogenesis, yet findings from previous studies of circulating OPG and commonly measured bone indices in humans have been conflicting. We conducted a cross-sectional study to evaluate the association between plasma OPG and femoral neck (FN) bone density (BMD) and geometry in a large cohort of women and men. Design: Participants included 1379 postmenopausal women and 1165 men, aged 50-89 yr (mean, 64 yr), in the Framingham Offspring Study. Dual x-ray absorptiometry was used to evaluate FN BMD and geometry (bone width, section modulus, and cross-sectional area at the narrow neck region). Plasma OPG concentrations were measured by ELISA. Sex-specific analysis of covariance was used to calculate means and assess linear trend in BMD and geometry values across OPG quartiles, adjusted for confounders. Results: OPG concentrations were greater in women than men, increased with age, and were greater in smokers and those with diabetes and heart disease. Multivariable-adjusted mean FN BMD in women increased from the lowest to the highest OPG quartile (trend, P < 0.01). However, no linear trend between FN BMD and OPG was observed in men (trend, P = 0.34). Section modulus and bone width increased with OPG in men (trend, P < 0.01), whereas no association between hip geometry indices and OPG was observed in women. Conclusion: Higher OPG concentration may indicate greater skeletal strength in women and men, possibly through reducing bone loss in women and increasing periosteal apposition in men. C1 [Samelson, Elizabeth J.; Broe, Kerry E.; Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA. [Samelson, Elizabeth J.; Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Demissie, Serkalem] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Beck, Thomas J.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21224 USA. [Kathiresan, Sekar] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Samelson, EJ (reprint author), Hebrew SeniorLife, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM samelson@hrca.harvard.edu OI Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530 FU NHLBI NIH HHS [N01 HC 25195, N01HC25195, R01 HL 076784, R01 HL076784]; NIA NIH HHS [R01 AG028321, R01 AG 028321, R01 AR/AG 41398]; NIAMS NIH HHS [K01 AR 053118, K01 AR053118, R01 AR 050066, R01 AR041398, R01 AR050066] NR 38 TC 26 Z9 28 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 MAY PY 2008 VL 93 IS 5 BP 1789 EP 1795 DI 10.1210/jc.2007-2492 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 298CD UT WOS:000255663100036 PM 18303076 ER PT J AU Boepple, PA Hayes, FJ Dwyer, AA Raivio, T Lee, H Crowley, WF Pitteloud, N AF Boepple, Paul A. Hayes, Frances J. Dwyer, Andrew A. Raivio, Taneli Lee, Hang Crowley, William F., Jr. Pitteloud, Nelly TI Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone in men across the full spectrum of seminiferous epithelium function SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; MONKEY MACACA-MULATTA; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; CLINICAL RESEARCH-CENTER; SERTOLI-CELL; GERM-CELLS; AUTOCRINE REGULATION; GNRH REPLACEMENT; DIMERIC INHIBIN; FSH-SECRETION AB Context and Objective: Our aim was to explore the relative roles of gonadal sex steroids and inhibin B in the regulation of FSH across a spectrum of seminiferous epithelium function. Subjects: The study included three groups: group I, healthy men (n = 31); group II, men with idiopathic hypogonadotropic hypogonadism receiving pulsatile GnRH (n = 12) selected to represent a spectrum of seminiferous tubular development, testicular size, and baseline inhibin B levels; and group III, men with functional anorchia (n = 3) receiving testosterone replacement. Design: Subjects were studied before and after 3 d of acute sex steroid withdrawal. Setting: The study was conducted at the Mallinckrodt General Clinical Research Center of Massachusetts General Hospital. Interventions: Acute biochemical castration was achieved using high-dose ketoconazole (groups I and II) or withdrawal of androgen therapy (group III). Main Outcome Measures: The relationship between FSH and inhibin B in both normal and castrate sex steroid milieu was measured. Results: In both normal and castrate sex steroid milieus, there was a negative relationship between inhibin B and FSH, best described by a logarithmic model. Acute biochemical castration resulted in the most dramatic increases in FSH in men with the lowest baseline inhibin B levels. Conclusions: We came to the following conclusions: 1) in the human male, inhibin B is the principal gonadal feedback regulator of FSH secretion unless seminiferous tubular function is severely compromised, and a logarithmic model best describes this relationship; and 2) sex steroid inhibition of FSH secretion is most apparent when serum inhibin B levels fall well below the normal range. C1 [Boepple, Paul A.; Hayes, Frances J.; Dwyer, Andrew A.; Raivio, Taneli; Crowley, William F., Jr.; Pitteloud, Nelly] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX5,55 Fruit St, Boston, MA 02114 USA. EM pitteloud.nelly@mgh.harvard.edu RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NCRR NIH HHS [M01 RR 01066, M01 RR001066]; NICHD NIH HHS [R01 HD 15788, R01 HD015788, U54 HD 028138, U54 HD028138, U54 HD029164] NR 38 TC 18 Z9 18 U1 0 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 MAY PY 2008 VL 93 IS 5 BP 1809 EP 1814 DI 10.1210/jc.2007-2450 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 298CD UT WOS:000255663100039 PM 18270253 ER PT J AU Tsai, CL Hodder, RV Page, JH Cydulka, RK Rowe, BH Carnargo, CA AF Tsai, Chu-Lin Hodder, Richard V. Page, John H. Cydulka, Rita K. Rowe, Brian H. Carnargo, Carlos A., Jr. TI The short-form chronic respiratory disease questionnaire was a valid, reliable, and responsive quality-of-life instrument in acute exacerbations of chronic obstructive pulmonary disease SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE chronic obstructive pulmonary disease; emergency department; exacerbation; psychometrics; quality of life ID HEALTH-STATUS; COPD EXACERBATION; DYSPNEA; ASTHMA; MULTICENTER AB Objective: To assess the psychometric properties of the short-form chronic respiratory disease questionnaire (SF-CRQ) as a quality-oflife QOL) instrument in chronic obstructive pulmonary disease (COPD) exacerbations. Study Design and Setting: In a prospective multicenter cohort study, consecutive emergency department (ED) patients with COPD exacerbation were interviewed using the SF-CRQ and other instruments. Baseline information was collected in the ED and from follow-up data 2 weeks later. The results of the SF-CRQ were compared with the results of the other instruments and clinical variables by correlation and factor analyses. Results: Of the 301 enrolled patients, 80% reported improvements across each of the domains of the SF-CRQ over the 2-week post-ED period. Overall median changes for the dyspnea, fatigue, emotional function, and mastery domains were 2, 1, 1, and 1.5, respectively (P < 0.001 for each domain). Correlation and factor analyses support their convergent/divergent validity and construct validity. The reliability for the change score of the SF-CRQ was high (Cronbach's alpha coefficient, 0.82). Overall minimal clinically important difference for improvement in the SF-CRQ was 1.01 (95% confidence interval, 0.72-1.31). Conclusion: SF-CRQ is a valid, reliable, and responsive instrument for the assessment of short-term QOL change in patients with COPD exacerbations. (c) 2008 Elsevier Inc. All rights reserved. C1 [Tsai, Chu-Lin; Carnargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. [Tsai, Chu-Lin; Page, John H.; Carnargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hodder, Richard V.] Univ Ottawa, Div Pulm & Crit Care, Ottawa, ON, Canada. [Cydulka, Rita K.] Case Western Reserve Univ, Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH 44106 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. RP Tsai, CL (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM cltsai@hsph.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 NR 28 TC 22 Z9 22 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 2008 VL 61 IS 5 BP 489 EP 497 DI 10.1016/j.jclinepi.2007.07.003 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 288HX UT WOS:000254978200012 PM 18394543 ER PT J AU Vignesh, S Brugge, WR AF Vignesh, Shivakumar Brugge, William R. TI Endoscopic diagnosis and treatment of pancreatic cysts SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE endoscopic ultrasound (EUS); EUS-guided fine needle aspiration; pancreatic cystic lesions (PCL); cystic pancreatic tumors (CPT); magnetic resonance pancreatography; intraductal papillary mucinous neoplasm; EUS-guided ethanol ablation ID FINE-NEEDLE-ASPIRATION; PAPILLARY-MUCINOUS TUMOR; TERM FOLLOW-UP; ULTRASOUND-GUIDED DRAINAGE; SINGLE-CENTER EXPERIENCE; DIFFERENTIAL-DIAGNOSIS; TRANSMURAL DRAINAGE; FLUID ANALYSIS; PATHOLOGICAL CORRELATION; NONOPERATIVE MANAGEMENT AB Pancreatic cystic neoplasms have emerged as an important new opportunity for many disciplines to participate in the diagnosis and management of early pancreatic neoplasia. With an increase in an understanding of these lesions and their potential for malignant transformation, there has been a dramatic increase in the frequency of diagnosis. We critically examined the literature on diagnostic methods for pancreatic cystic lesions over the past 5 years. The methods of endoscopic pancreatic pseudocyst drainage and clinical outcomes are also discussed. Morphologic studies of cystic lesions using crosssectional imaging or endoscopic ultrasound have a low diagnostic rate. Cyst fluid analysis with the use of tumor markers (eg, carcinoembryonic antigen) increases the accuracy of diagnosis. The management of cystic lesions is heavily dependent on the type of cyst, the neoplastic potential, and the risk of surgery. The traditional therapy is pancreatic resection and not cyst enucleation. In contrast to cystic neoplasms, pseudocysts are localized collections of inflammatory fluid that mimic cystic neoplasms. The fluid collections arise from chronic pancreatitis and ductal leaks. Because pseudocysts have no neoplastic potential, they can be drained rather than resected. Drainage can be safely accomplished with external catheters or endoscopically with internal catheters. As we learn more about the pathophysiology of the various cystic lesions, treatment will be tailored to the specific cyst lesion. Endoscopic ultrasound has an important role in the characterization of pancreatic cystic lesions and helps in selection of the optimal treatment modality. C1 [Vignesh, Shivakumar] Penn State Coll Med, Div Gastroenterol & Hepatol, Hershey, PA USA. [Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, Boston, MA 02114 USA. RP Vignesh, S (reprint author), Penn State Univ Hosp, Milton S Hershey Med Ctr, POB 850,H045,500 Univ Dr, Hershey, PA 17033 USA. EM svignesh@hmc.psu.edu NR 128 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY-JUN PY 2008 VL 42 IS 5 BP 493 EP 506 DI 10.1097/MCG.0b013e3181616159 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 294QA UT WOS:000255419400014 PM 18344889 ER PT J AU Goyal, RK Chaudhury, A AF Goyal, Raj K. Chaudhury, Arun TI Physiology of normal esophageal motility SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Workshop on Esophageal Reflux and Motility Update - GERD, NERD and Spasm CY SEP 28, 2007 CL Yale Univ, New Haven, CT HO Yale Univ DE lower esophageal sphincter; classification of esophageal motility disorders; peristalsis; neural control of peristalsis; deglutitive inhibition ID BASAL SPHINCTER PRESSURE; NITRIC-OXIDE; SMOOTH-MUSCLE; VAGAL-STIMULATION; OPOSSUM ESOPHAGUS; CONTRACTIONS; PERISTALSIS; RELAXATION; RESPONSES; NEURONS AB The esophagus consists of 2 different parts. In humans, the cervical esophagus is composed of striated muscles and the thoracic esophagus is composed of phasic smooth muscles. The striated muscle esophagus is innervated by the lower motor neurons and peristalsis in this segment is due to sequential activation of the motor neurons in the nucleus ambiguus. Both primary and secondary peristaltic contractions are centrally mediated. The smooth muscle of esophagus is phasic in nature and is innervated by intramural inhibitory (nitric oxide releasing) and excitatory (acetylcholine releasing) neurons that receive inputs from separate sets of preganglionic neurons located in the dorsal motor nucleus of vagus. The primary peristalsis in this segment involves both central and peripheral mechanisms. The primary peristalsis consists of inhibition (called deglutitive inhibition) followed by excitation. The secondary peristalsis is entirely due to peripheral mechanisms and also involves inhibition followed by excitation. The lower esophageal sphincter (LES) is characterized by tonic muscle that is different from the muscle of the esophageal body. The LES, like the esophageal body smooth muscle, is also innervated by the inhibitory and excitatory neurons. The LES maintains tonic closure because of its myogenic property. The LES tone is modulated by the inhibitory and the excitatory nerves. Inhibitory nerves mediate LES relaxation and the excitatory nerves mediate reflex contraction or rebound contraction of the LES. Clinical disorders of esophageal motility can be classified on the basis of disorders of the inhibitory and excitatory innervations and the smooth muscles. C1 [Goyal, Raj K.; Chaudhury, Arun] Ctr Swallowing & Motil Disorders, Boston, MA USA. [Goyal, Raj K.; Chaudhury, Arun] VA Boston Healthcare Syst, Boston, MA USA. [Goyal, Raj K.; Chaudhury, Arun] Harvard Univ, Sch Med, Boston, MA USA. RP Goyal, RK (reprint author), VA Med Ctr, 1400 VFW Parkway, Boston, MA 02132 USA. EM raj_goyal@hms.harvard.edu FU NIDDK NIH HHS [R01 DK062867, R01 DK062867-04, DK062867] NR 42 TC 76 Z9 79 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY-JUN PY 2008 VL 42 IS 5 BP 610 EP 619 DI 10.1097/MCG.0b013e31816b444d PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 294QA UT WOS:000255419400035 PM 18364578 ER PT J AU Pober, BR Johnson, M Urban, Z AF Pober, Barbara R. Johnson, Mark Urban, Zsolt TI Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID SUPRAVALVULAR AORTIC-STENOSIS; PULMONARY-ARTERY STENOSIS; AMBULATORY BLOOD-PRESSURE; MAIN CORONARY-ARTERY; ELASTIN GENE; MYOCARDIAL-INFARCTION; MENTAL-RETARDATION; SMOOTH-MUSCLE; SUDDEN-DEATH; CELL-PROLIFERATION AB Williams-Beuren syndrome (WBS) is a microdeletion disorder caused by heterozygous loss of approximately 1.5-Mb pairs of DNA from chromosome 7. Patients with WBS have a characteristic constellation of medical and cognitive findings, with a hallmark feature of generalized arteriopathy presenting as stenoses of elastic arteries and hypertension. Human and mouse studies establish that defects in the elastin gene, leading to elastin haploinsufficiency, underlie the arteriopathy. In this review we describe potential links between elastin expression and arteriopathy, possible explanations for disease variability, and current treatment options and their limitations, and we propose several new directions for the development of nonsurgical preventative therapies based on insights from elastin biology. C1 [Pober, Barbara R.] MassGen Hosp Children, Dept Pediat, Childrens Hosp Boston, Dept Surg, Boston, MA 02114 USA. [Pober, Barbara R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Johnson, Mark] Washington Univ, Sch Med, Dept Pediat, Div PediatCardiol,St Louis Childrens Hosp, St Louis, MO 63110 USA. [Urban, Zsolt] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Pober, BR (reprint author), MassGen Hosp Children, Dept Pediat, Childrens Hosp Boston, Dept Surg, Simches Res Bldg,Rm 222,185 Cambridge St, Boston, MA 02114 USA. EM pober.barbara@mgh.harvard.edu RI Urban, Zsolt/A-2018-2013 OI Urban, Zsolt/0000-0003-3890-1843 FU NHLBI NIH HHS [HL084922, P50 HL084922] NR 121 TC 76 Z9 80 U1 2 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2008 VL 118 IS 5 BP 1606 EP 1615 DI 10.1172/JCI35309 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 295QX UT WOS:000255490100003 PM 18452001 ER PT J AU Etminan, M Carleton, BC Samii, A AF Etminan, Mahyar Carleton, Bruce C. Samii, Ali TI Non-steroidal anti-inflammatory drug use and the risk of Parkinson disease: A retrospective cohort study SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Parkinson disease; NSAID; inflammation; neuroprotection; apoptosis ID INFLAMMATION AB Using the British Columbia Linked Health Databases, we explored the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of developing Parkinson's disease (PD). We followed a cohort of older adults in the Province of British Columbia from 1997 to 2003. A time-dependent Cox model was used to estimate adjusted rate ratios for users and non-users of NSAIDs. The results of our study did not show a protective effect of NSAIDs for PD (rate ratio 0.84, 95% CI 0.81-1.09). (C) 2007 Elsevier Ltd. All rights reserved. C1 [Etminan, Mahyar] Vancouver Gen Hosp, Ctr Clin Epidemiol & Evaluat, Vancouver, BC, Canada. [Carleton, Bruce C.] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada. [Carleton, Bruce C.] Childrens & Womens Hlth Ctr British Columbia, Pharmaceut Outcomes & Policy Innovat, Vancouver, BC, Canada. [Carleton, Bruce C.] Child & Family Res Inst, Vancouver, BC, Canada. [Samii, Ali] Univ Washington, Seattle, WA 98195 USA. [Samii, Ali] Seattle VA Parkinson Dis Res Educ & Clin Ctr, Seattle, WA USA. RP Samii, A (reprint author), VA Puget Sound Hlth Care Syst, Dept Neurol, 1660 S Columbian Way,MS-127, Seattle, WA 98108 USA. EM asamii@u.washington.edu OI /0000-0002-4485-4054 NR 7 TC 30 Z9 30 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD MAY PY 2008 VL 15 IS 5 BP 576 EP 577 DI 10.1016/j.jocn.2007.02.095 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 293MI UT WOS:000255339000016 PM 18343119 ER PT J AU Katz, A Smith, BL Golshan, M Niemierko, A Kobayashi, W Raad, RA Kelada, A Rizk, L Wong, JS Bellon, JR Gadd, M Specht, M Taghian, AG AF Katz, Angela Smith, Barbara L. Golshan, Mehra Niemierko, Andrzej Kobayashi, Wendy Raad, Rita Abi Kelada, Alexandra Rizk, Levi Wong, Julia S. Bellon, Jennifer R. Gadd, Michele Specht, Michelle Taghian, Alphonse G. TI Nomogram for the prediction of having four or more involved nodes for sentinel lymph node-positive breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 05-09, 2006 CL Philadelphia, PA SP Amer Soc Therapeut Radiol & Oncol ID RADIATION-THERAPY; CONSERVATIVE SURGERY; PATTERNS; FAILURE; CHEMOTHERAPY; RADIOTHERAPY; IRRADIATION; MASTECTOMY; CARCINOMA; FIELDS AB Purpose The standard of care for patients with a positive (+) sentinel lymph node (SLN) is axillary dissection; however, for various reasons, some SLN+ patients do not undergo dissection. The purpose of this study was to define possible predictors of having four or more involved nodes to provide information for clinicians and patients making decisions about adjuvant chemotherapy and radiation. Patients and Methods We reviewed the records of 402 patients with invasive breast cancer and one to three involved SLNs who underwent completion axillary dissection at two academic cancer centers. None of these patients received neoadjuvant chemotherapy. Factors associated with having four or more involved axillary nodes ( SLNs and non-SLNs) were evaluated by univariate and multivariate logistic regression analysis. Results Eighty-seven patients had four or more positive nodes. On multivariate analysis, having four or more SLNs was associated with tumor histology, primary tumor size, lymphovascular space invasion, extranodal extension, the number of involved SLNs, the number of uninvolved SLNs, and the size of the largest SLN metastasis. A nomogram to predict the probability of having four or more nodes based on patients' pathologic data was developed from the multivariate logistic regression model. A separate previously published data set of 206 SLN+ patients treated at a community hospital in another city was used to validate this model. Conclusion Patients with a low probability of having four or more nodes can be identified from known pathologic features. The nomogram developed will be helpful to clinicians making adjuvant treatment recommendations. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg & Radiat, Boston, MA 02115 USA. RP Katz, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 301, Boston, MA 02114 USA. EM abkatz@partners.org FU NCI NIH HHS [CA21239, CA50628, P50 CA89393] NR 14 TC 64 Z9 65 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2008 VL 26 IS 13 BP 2093 EP 2098 DI 10.1200/JCO.2007.11.9479 PG 6 WC Oncology SC Oncology GA 294ZB UT WOS:000255443700008 PM 18445838 ER PT J AU Lee, SJ Joffe, S Artz, AS Champlin, RE Davies, SM Jagasia, M Kernan, NA Loberiza, FR Soiffer, RJ Eapen, M AF Lee, Stephanie J. Joffe, Steven Artz, Andrew S. Champlin, Richard E. Davies, Stella M. Jagasia, Madan Kernan, Nancy A. Loberiza, Fausto R., Jr. Soiffer, Robert J. Eapen, Mary TI Individual physician practice variation in hematopoietic cell transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol ID BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; JUVENILE MYELOMONOCYTIC LEUKEMIA; VERSUS-HOST-DISEASE; TREATMENT RECOMMENDATIONS; MYELODYSPLASTIC SYNDROME; CURRENT CONTROVERSIES; APLASTIC-ANEMIA; BREAST-CANCER; CHRONIC GVHD AB Purpose Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT. Methods An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making. Results Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning. Conclusion These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice. C1 [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH USA. Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA. Mem Sloan Kettering Canc Ctr, Pediat Bone Marrow Transplantat Serv, New York, NY 10021 USA. Univ Nebraska, Dept Med, Omaha, NE 68182 USA. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA. EM sjlee@fhcrc.org OI Kernan, Nancy/0000-0003-1417-1823; Joffe, Steven/0000-0002-0667-7384 NR 37 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2008 VL 26 IS 13 BP 2162 EP 2170 DI 10.1200/JCO.2007.15.0169 PG 9 WC Oncology SC Oncology GA 294ZB UT WOS:000255443700018 PM 18378566 ER PT J AU McDermott, DF Sosman, JA Gonzalez, R Hodi, FS Linette, GP Richards, J Jakub, W Beeram, M Tarantolo, S Agarwala, S Frenette, G Puzanov, I Cranmer, L Lewis, K Kirkwood, J White, JM Xia, C Patel, K Hersh, E AF McDermott, David F. Sosman, Jeffrey A. Gonzalez, Rene Hodi, F. Stephen Linette, Gerald P. Richards, Jon Jakub, W. Beeram, Muralidhar Tarantolo, Stefano Agarwala, Sanjiv Frenette, Gary Puzanov, Igor Cranmer, Lee Lewis, Karl Kirkwood, John White, J. Michael Xia, Chenghua Patel, Kiran Hersh, Evan TI Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: A report from the 11715 study group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 14th European Cancer Conference (ECCO 14) CY SEP 23-27, 2007 CL Barcelona, SPAIN SP European Canc Org ID RECOMBINANT INTERLEUKIN-2 THERAPY; METASTATIC MELANOMA; MALIGNANT-MELANOMA; CANCER; TRIAL; PATHWAY; RAF AB Purpose This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma. Patients and Methods This randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-naive patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine ( n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m(2) for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progression-free survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival ( OS). Results Median PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm ( hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP ( median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed ( median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile. Conclusion Sorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population. C1 [McDermott, David F.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Biol Therapy Program, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. Washington Univ, Sch Med, St Louis, MO USA. Lutheran Gen Canc Care Ctr, Park Ridge, IL USA. Lakeland Reg Canc Ctr, Lakeland, FL USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Nebraska Methodist Hosp, Omaha, NE USA. St Lukes Hlth Syst, Bethlehem, PA USA. Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. Carolinas Hematol Oncol Assoc, Charlotte, NC USA. Univ Arizona, Inst Canc, Tucson, AZ USA. Onyx Pharmaceut Inc, Emeryville, CA USA. Bayer Healthcare Pharmaceut, West Haven, CT USA. RP McDermott, DF (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Biol Therapy Program, 330 Brook Line Ave,E KS-159, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu RI Puzanov, Igor/A-7179-2009 NR 32 TC 178 Z9 186 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2008 VL 26 IS 13 BP 2178 EP 2185 DI 10.1200/JCO.2007.14.8288 PG 8 WC Oncology SC Oncology GA 294ZB UT WOS:000255443700020 PM 18445842 ER PT J AU Nelligan, JA Loftis, JM Matthews, AM Zucker, BL Linke, AM Hauser, P AF Nelligan, Julie A. Loftis, Jennifer M. Matthews, Annette M. Zucker, Betsy L. Linke, Alex M. Hauser, Peter TI Depression comorbidity and antidepressant use in veterans with chronic hepatitis C: Results from a retrospective chart review SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERFERON-ALPHA; VIRUS-INFECTION; PSYCHIATRIC-DISORDERS; PLUS RIBAVIRIN; COPING STYLES; UNITED-STATES; PRIMARY-CARE; PREVALENCE; THERAPY; SYMPTOMS AB Background. The 2002 National Institutes of Health Consensus Conference Statement recommended that both clinical and research efforts be made to increase the availability of hepatitis C virus (HCV) treatment to patients who were previously ineligible because of comorbid psychiatric illness and substance use disorders. However, little research on patients with HCV and comorbid depression has been conducted that can serve to inform and guide treatment of HCV. In this study we characterize the prevalence and severity of comorbid depression, as well as antidepressant and other psychotropic prescribing patterns, in a sample of U.S. veterans with HCV. Method: Participants were recruited between November 2002 and July 2005 from the liver specialty clinic and from a 1-time HCV patient education class conducted through the Portland Department of Veterans Affairs Northwest Hepatitis C Resource Center. Patients who signed informed consent were asked to complete the Beck Depression Inventory, Second Edition (BDI-II), and their medical records were reviewed for information regarding active prescriptions for psychotropic medications and prior psychiatric diagnoses. Results: Of-the 881 veterans enrolled in the study, 783 (89%) completed the BDI-II. Approximately one third (34%, 264/783) of the veterans endorsed moderate to severe symptoms of depression (BDI-II score >= 20), and 37% (290/783) were prescribed an antidepressant; however, 48% (140/290) of veterans prescribed an antidepressant continued to endorse moderate to severe depressive symptoms. Furthermore, of all veterans endorsing moderate to severe symptoms of depression (N = 264), only about half (56%, 148/264) were prescribed an antidepressant. Conclusion: On the basis of BDI-II scores, a significant proportion of veterans with HCV experience moderate to severe depressive symptoms. Although antidepressants were the most commonly prescribed psychotropic medication, many who were prescribed an antidepressant continued to experience high levels of depressive symptoms, an important consideration when deciding whether to initiate antiviral therapy to treat HCV. C1 [Zucker, Betsy L.; Hauser, Peter] Oregon Hlth & Sci Univ, Div Gastroenterol, Dept Internal Med, Portland, OR 97201 USA. [Hauser, Peter] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Nelligan, Julie A.; Loftis, Jennifer M.; Matthews, Annette M.; Hauser, Peter] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Nelligan, Julie A.; Loftis, Jennifer M.; Matthews, Annette M.; Hauser, Peter] Portland Dept VA Med Ctr, Behav Hlth & Clin Neurosci, Portland, OR USA. [Nelligan, Julie A.; Loftis, Jennifer M.; Matthews, Annette M.; Hauser, Peter] Portland Dept VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR USA. RP Hauser, P (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,POB 1034 P3MHADM, Portland, OR 97207 USA. EM peter.hauser2@va.gov NR 39 TC 23 Z9 23 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2008 VL 69 IS 5 BP 810 EP 816 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 306WU UT WOS:000256279600014 PM 18426262 ER PT J AU Bellinger, DC Trachtenberg, F Zhang, A Tavares, M Daniel, D McKinlay, S AF Bellinger, D. C. Trachtenberg, F. Zhang, A. Tavares, M. Daniel, D. McKinlay, S. TI Dental amalgam and psychosocial status: The new England children's amalgam trial SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental amalgam; children; psychosocial function; randomized trial ID RANDOMIZED CLINICAL-TRIAL; MERCURY EXPOSURE; NEUROPSYCHOLOGICAL FUNCTION; MENTAL-HEALTH; FILLINGS; RESTORATIONS; POLYMORPHISM; SYMPTOMS; DISORDER; BEHAVIOR AB High-dose exposures to elemental mercury vapor cause emotional dysfunction, but it is uncertain whether the levels of exposure that result from having dental amalgam restorations do so. As part of the New England Children's Amalgam Trial, a randomized trial involving 6- to 10-year-old children, we evaluated the hypothesis that restoration of caries using dental amalgam resulted in worse psychosocial outcomes than restoration using mercury-free composite resin. The primary outcome was the parent-completed Child Behavior Checklist. The secondary outcome was children's self-reports using the Behavior Assessment System for Children. Children's psychosocial status was evaluated in relation to three indices of mercury exposure: treatment assignment, surface-years of amalgam, and urinary mercury excretion. All significant associations favored the amalgam group. No evidence was found that exposure to mercury from dental amalgams was associated with adverse psychosocial outcomes over the five-year period following initial placement of amalgams. C1 [Trachtenberg, F.; Zhang, A.; McKinlay, S.] New England Res Inst, Watertown, MA 02472 USA. [Bellinger, D. C.] Harvard Univ, Sch Publ Hlth, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Daniel, D.] Univ No Colorado, Greeley, CO 80639 USA. [Tavares, M.] Forsyth Inst, Boston, MA USA. RP McKinlay, S (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM Smckinlay@neriscience.com FU NIDCR NIH HHS [U01 DE11886, U01 DE011886-04, U01 DE011886] NR 32 TC 20 Z9 22 U1 1 U2 4 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 2008 VL 87 IS 5 BP 470 EP 474 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 292ZC UT WOS:000255303600011 PM 18434579 ER PT J AU Marill, KA AF Marill, Keith A. TI Serum D-dimer is a sensitive test for the detection of acute aortic dissection: A pooled meta-analysis SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE acute; aorta; dissection; D-dimer; sensitivity ID PULMONARY-EMBOLISM; DIAGNOSTIC-ACCURACY; EMERGENCY-DEPARTMENT; EPIDEMIOLOGY; BEDSIDE; SURGERY; BIAS AB 0 Abstract-Acute aortic dissection is a rare but devastating condition with high mortality. Unfortunately, there is no sensitive screening indicator of disease in common use. The objective of this study was to assess the sensitivity and utility of the serum D-dimer as a test for acute aortic dissection. A pooled analysis was performed of all original research studies testing the sensitivity of serum D-dimer for acute aortic dissection. A search of MEDLINE, EMBASE, and the Cochrane Register using the terms "aortic dissection" and "d-dimer" was made of all English language publications. All original reports of consecutively enrolled patients with acute aortic dissection and a measured serum D-dimer were included. Case reports were excluded. A value of 0.5 microgram per milliliter was defined as the threshold for a positive D-dimer. The primary outcome was the pooled sensitivity of the D-dimer test for acute aortic dissection. There were 21 original reports of patients with acute aortic dissection and D-dimer measurements. Eleven studies were included and a total of 349 acute aortic dissection patients were described. The sensitivity of the D-dimer test was 327/349, 94% (95% confidence interval 91-96), and the point estimate was essentially unchanged in a sensitivity analysis, 183/192, 95% (95% confidence interval 91-98). Specificity ranged from 40% to 100%. Serum D-dimer is sensitive for acute aortic dissection and potentially represents a useful test for patients who present with a low likelihood of this disease. (C) 2008 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Marill, KA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. NR 44 TC 48 Z9 52 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2008 VL 34 IS 4 BP 367 EP 376 DI 10.1016/j.jemermed.2007.06.030 PG 10 WC Emergency Medicine SC Emergency Medicine GA 296RL UT WOS:000255563400002 PM 18207693 ER PT J AU Tiamfook-Morgan, TO Brown, DFM Nadel, ES AF Tiamfook-Morgan, Tami O. Brown, David F. M. Nadel, Eric S. TI Bradycardia and confusion SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID DIGITALIS INTOXICATION; DIGOXIN TOXICITY; FRAGMENTS C1 [Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Tiamfook-Morgan, Tami O.; Brown, David F. M.; Nadel, Eric S.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. [Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 114,Fruit Str, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2008 VL 34 IS 4 BP 451 EP 455 DI 10.1016/j.jemermed.2008.03.001 PG 5 WC Emergency Medicine SC Emergency Medicine GA 296RL UT WOS:000255563400013 PM 18394851 ER PT J AU Crippa, S Dominguez, I Rodriguez, JR Razo, O Thayer, SP Ryan, DP Warshaw, AL Fernandez-del Castillo, C AF Crippa, Stefano Dominguez, Ismael Rodriguez, J. Ruben Razo, Oswaldo Thayer, Sarah P. Ryan, David P. Warshaw, Andrew L. Fernandez-del Castillo, Carlos TI Quality of life in pancreatic cancer: Analysis by stage and treatment SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2007 CL Washington, DC SP Soc Surg Alimentary Tract DE pancreatic cancer; quality of life; meaningful important difference; palliation; survival ID PROSPECTIVE RANDOMIZED-TRIAL; CELIAC PLEXUS BLOCK; PERIAMPULLARY ADENOCARCINOMA; FUNCTIONAL ASSESSMENT; SURGICAL-TREATMENT; PHASE-II; SURVIVAL; OUTCOMES; PANCREATICODUODENECTOMY; CARCINOMA AB In pancreatic cancer patients, survival and palliation of symptoms should be balanced with social and functional impairment, and for this reason, health-related quality of life measurements could play an important role in the decision-making process. The aim of this work was to evaluate the quality of life and survival in 92 patients with different stages of pancreatic adenocarcinoma who underwent surgical and/or medical interventions. Patients were evaluated with the Functional Assessment of Cancer Therapy questionnaires at diagnosis and follow-up (3 and 6 months). At diagnosis, 28 patients (30.5%) had localized disease (group 1) and underwent surgical resection, 34 (37%) had locally advanced (group 2), and 30 (32.5%) metastatic disease (Group 3). Improvement in quality of life was found in group 1, while in group 3, it decreased at follow-up (p = 0.03). No changes in quality of life in group 2 were found. Chemotherapy/chemoradiation seems not to significantly modify quality of life in groups 2 and 3. Median survival time for the entire cohort was 9.8 months (range, 1-24). One-year survival was 74%, 30%, and 16% for groups 1, 2, and 3 respectively (p = 0.001). Pancreatic cancer prognosis is still dismal. In addition to long-term survival benefits, surgery impacts favorably quality of life. C1 [Crippa, Stefano; Dominguez, Ismael; Rodriguez, J. Ruben; Razo, Oswaldo; Thayer, Sarah P.; Warshaw, Andrew L.; Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Wang Ambulatory Care Ctr 460, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ryan, David P.] Harvard Univ, Sch Med, Wang Ambulatory Care Ctr 460, Dept Oncol,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Sch Med, Wang Ambulatory Care Ctr 460, Dept Surg,Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org FU NCI NIH HHS [P01 CA117969]; NIDDK NIH HHS [K08 DK071329] NR 40 TC 35 Z9 35 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2008 VL 12 IS 5 BP 783 EP 793 DI 10.1007/s11605-007-0391-9 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 291KF UT WOS:000255195200001 PM 18317851 ER PT J AU Tatum, RP Shalhub, S Oelschlager, BK Pellegrini, CA AF Tatum, Roger P. Shalhub, Sherene Oelschlager, Brant K. Pellegrini, Carlos A. TI Complications of PTFE mesh at the diaphragmatic hiatus SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE paraesophageal hernia; surgical mesh; PTFE; visceral erosion; dysphagia ID LAPAROSCOPIC NISSEN FUNDOPLICATION; ANGELCHIK ANTIREFLUX PROSTHESIS; PARAESOPHAGEAL HERNIA REPAIR; ADHESION FORMATION; POLYTETRAFLUOROETHYLENE MESH; POLYPROPYLENE MESH; RANDOMIZED-TRIAL; RECURRENCE; MANAGEMENT; CLOSURE AB Paraesophageal hernia repair has been associated with a recurrence rate of up to 42%. Thus, in the last decade, there has been increasing interest in the use of mesh reinforcement of the hiatal repair. Polytetrafluoroethylene (PTFE) is one of the materials that have been used for this purpose, as it is thought to induce minimal tissue reaction. We report two cases in which complications specific to the use of PTFE mesh in this location developed over time. In the first patient, a gastrectomy was required to remove a large PTFE mesh which had eroded into the esophagogastric junction and gastric cardia. The second patient experienced severe dysphagia resulting from a stricture caused by the implant, requiring removal of the mesh. Although such complications have only rarely been reported, the severity and consequences of these incidents, as reported in the literature and in light of our observations, suggest that an alternative to PTFE should be considered for crural reinforcement during paraesophageal hernia repair. C1 [Tatum, Roger P.; Shalhub, Sherene; Oelschlager, Brant K.; Pellegrini, Carlos A.] Univ Washington, Dept Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Tatum, RP (reprint author), Univ Washington, Dept Surg, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-112-Gs, Seattle, WA 98108 USA. EM rtatum@u.washington.edu NR 31 TC 53 Z9 57 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY PY 2008 VL 12 IS 5 BP 953 EP 957 DI 10.1007/s11605-007-0316-7 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 291KF UT WOS:000255195200026 PM 17882502 ER PT J AU Gaynes, BN Rush, AJ Trivedi, MH Wisniewski, SR Balasubramani, GK McGrath, PJ Thase, ME Klinkman, M Nierenberg, AA Yates, WR Fava, M AF Gaynes, Bradley N. Rush, A. John Trivedi, Madhukar H. Wisniewski, Stephen R. Balasubramani, G. K. McGrath, Patrick J. Thase, Michael E. Klinkman, Michael Nierenberg, Andrew A. Yates, William R. Fava, Maurizio TI Primary versus specialty care outcomes for depressed outpatients managed with measurement-based care: Results from STAR*D SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; depression; clinical trial; outcomes ID SEQUENCED TREATMENT ALTERNATIVES; RANDOMIZED CONTROLLED-TRIAL; DIAGNOSTIC SCREENING QUESTIONNAIRE; REPORT QIDS-SR; MAJOR DEPRESSION; RELIEVE DEPRESSION; ANTIDEPRESSANT TREATMENT; QUICK INVENTORY; CHRONIC ILLNESS; RATING-SCALE AB BACKGROUND: Whether the acute outcomes of major depressive disorder (MDD) treated in primary (PC) or specialty care (SC) settings are different is unknown. OBJECTIVE: To compare the treatment and outcomes for depressed outpatients treated in primary versus specialty settings with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a broadly inclusive effectiveness trial. DESIGN: Open clinical trial with citalopram for up to 14 weeks at 18 primary and 23 specialty sites. Participants received measurement-based care with 5 recommended treatment visits, manualized pharmacotherapy, ongoing support and guidance by a clinical research coordinator, the use of structured evaluation of depressive symptoms and side effects at each visit, and a centralized treatment monitoring and feedback system. PARTICIPANTS: A total of 2,876 previously established outpatients in primary (n=1091) or specialty (n=1785) with nonpsychotic depression who had at least 1 post-baseline measure. MEASUREMENTS AND MAIN RESULTS: Remission (Hamilton Depression Rating Scale for Depression [Hamilton] or 16-item Quick Inventory of Depressive Symptomatology-Self-Rated [QIDS-SR16]); response (QIDS-SR16); time to first remission (QIDS-SR16). Remission rates by Hamilton (26.6% PC vs 28.0% SC, p=.40) and by QIDS-SR16 (32.5% PC vs 33.1% SC, p=.78) and response rates by QIDS-SR16 (45.7% PC vs 47.6% SC, p=.33) were not different. For those who reached remission or response at exit, the time to remission (6.2 weeks PC vs 6.9 weeks SC, p=.12) and to response (5.5 weeks PC vs 5.4 weeks SC, p=.97) did not differ by setting. CONCLUSIONS: Identical remission and response rates can be achieved in primary and specialty settings when identical care is provided. C1 [Gaynes, Bradley N.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Rush, A. John; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [McGrath, Patrick J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [McGrath, Patrick J.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Klinkman, Michael] Univ Michigan, Ann Arbor, MI 48109 USA. [Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yates, William R.] Univ Oklahoma, Coll Med, Tulsa, OK USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Gaynes, BN (reprint author), Univ N Carolina, Sch Med, Dept Psychiat, CB 7160, Chapel Hill, NC 27599 USA. EM bngaynes@med.unc.edu RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [N01MH90003, K23 MH001951, K23 MH01951-03] NR 68 TC 45 Z9 46 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 551 EP 560 DI 10.1007/s11606-008-0522-3 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300007 PM 18247097 ER PT J AU Chew, LD Griffin, JM Partin, MR Noorbaloochi, S Grill, JP Snyder, A Bradley, KA Nugent, SM Baines, AD VanRyn, M AF Chew, Lisa D. Griffin, Joan M. Partin, Melissa R. Noorbaloochi, Siamak Grill, Joseph P. Snyder, Annamay Bradley, Katharine A. Nugent, Sean M. Baines, Alisha D. VanRyn, Michelle TI Validation of screening questions for limited health literacy in a large VA outpatient population SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE health literacy; screening; validation; questions ID IDENTIFY PATIENTS; HOSPITAL ADMISSION; LIKELIHOOD RATIOS; DIAGNOSTIC-TEST; CARE; KNOWLEDGE; RISK; ASSOCIATION; SKILLS AB OBJECTIVES: Previous studies have shown that a single question may identify individuals with inadequate health literacy. We evaluated and compared the performance of 3 health literacy screening questions for detecting patients with inadequate or marginal health literacy in a large VA population. METHODS: We conducted in-person interviews among a random sample of patients from 4 VA medical centers that included 3 health literacy screening questions and 2 validated health literacy measures. Patients were classified as having inadequate, marginal, or adequate health literacy based on the Short Test of Functional Health Literacy in Adults (S-TOFHLA) and the Rapid Estimate of Adult Literacy in Medicine (REALM). We evaluated the ability of each of 3 questions to detect: 1) inadequate and the combination of "inadequate or marginal" health literacy based on the S-TOFHLA and 2) inadequate and the combination of "inadequate or marginal" health literacy based on the REALM. MEASUREMENTS AND MAIN RESULTS: Of 4,384 patients, 1,796 (41%) completed interviews. The prevalences of inadequate health literacy were 6.8% and 4.2%, based on the S-TOHFLA and REALM, respectively. Comparable prevalences for marginal health literacy were 7.4% and 17%, respectively. For detecting inadequate health literacy, "How confident are you filling out medical forms by yourself?" had the largest area under the Receiver Operating Characteristic Curve (AUROC) of 0.74 (95% CI: 0.69-0.79) and 0.84 (95% CI: 0.79-0.89) based on the S-TOFHLA and REALM, respectively. AUROCs were lower for detecting "inadequate or marginal" health literacy than for detecting inadequate health literacy for each of the 3 questions. CONCLUSIONS: A single question may be useful for detecting patients with inadequate health literacy in a VA population. C1 [Chew, Lisa D.] Univ Washington, Harborview Med Ctr, Dept Med, Div Gen Internal Med, Seattle, WA 98104 USA. [Griffin, Joan M.; Partin, Melissa R.; Noorbaloochi, Siamak; Grill, Joseph P.; Snyder, Annamay; Nugent, Sean M.; Baines, Alisha D.] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Griffin, Joan M.; Partin, Melissa R.; Noorbaloochi, Siamak] Univ Minnesota, Dept Med, Div Gen Internal Med, Minneapolis, MN 55455 USA. [Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA USA. [Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Primary & Special Med Care, Seattle, WA USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Bradley, Katharine A.] Univ Washington, Hlth Serv, Seattle, WA 98195 USA. [VanRyn, Michelle] Univ Minnesota, Dept Family Med & Commun Hlth, Minneapolis, MN 55455 USA. RP Chew, LD (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Gen Internal Med, 352 9Th Ave,Box 359780, Seattle, WA 98104 USA. EM lchew@u.washington.edu RI VAN RYN, MICHELLE/B-1664-2010 NR 30 TC 290 Z9 294 U1 6 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 561 EP 566 DI 10.1007/s11606-008-0520-5 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300008 PM 18335281 ER PT J AU Singhal, R Rubenstein, LV Wang, M Lee, ML Raza, A Holschneider, CH AF Singhal, Rita Rubenstein, Lisa V. Wang, Mingming Lee, Martin L. Raza, Anwar Holschneider, Christine H. TI Variations in practice guideline adherence for abnormal cervical cytology in a county healthcare system SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT AcademyHealth Annual Meeting CY JUN, 2004 CL San Diego, CA DE cytology; quality of care; practice guidelines; cervical cancer ID ATYPICAL GLANDULAR CELLS; SCREENING FOLLOW-UP; PAP-SMEARS; CLINICAL-SIGNIFICANCE; RANDOMIZED-TRIAL; UNITED-STATES; WOMEN; MANAGEMENT; CANCER; GYNECOLOGISTS AB BACKGROUND: Reduction in cervical cancer incidence and mortality is not only dependant on promoting cervical cancer screening but also on providing appropriate follow-up and treatment of abnormal cervical cytology. OBJECTIVES: The objective of this study was to determine variations in guideline adherence for women requiring abnormal cervical cytology follow-up. SUBJECTS: Subjects of the study are women 18 years or older with an abnormal Pap test in 2000 within a large county healthcare system (n=8,571). MEASUREMENTS: Guideline adherence was determined by the presence or absence of the appropriate follow-up procedure within an acceptable time interval for each degree of cytological abnormality. Patients with no follow-up studies were deemed to be lost to follow-up. RESULTS: Of study subjects, 18.5% were lost to follow-up care. Of the remaining 6,987 women, 60.3% received optimal care, 9.4% received suboptimal care, and 30.3% received poor care. Follow-up rates were higher for patients with higher degree of cytological abnormality (OR, 1.29, 95% CI, 1.17-1.42), older patients (OR, 1.03, 95% CI, 1.02-1.030) and those receiving the index Pap test at a larger healthcare facility (OR, 1.13; 95% CI, 1.01-1.27). Receiving optimal care was positively correlated with higher degree of cytological abnormality (p<.0001) and larger facility size (p=.002). Regional variations in care demonstrated the largest cluster having the lowest lost to follow-up rate and the most optimal care. CONCLUSIONS: A significant number of women with abnormal cervical cytology are receiving less than optimal care. Further studies are required to determine the specific healthcare delivery practices that need to be targeted to improve guideline adherence for follow-up of abnormal cytology. C1 [Singhal, Rita] Off Womens Hlth, Los Angeles Cty Dept Publ Hlth, El Monte, CA 91731 USA. [Singhal, Rita] Olive View UCLA Med Ctr, Dept Med, Sylmar, CA 91342 USA. [Rubenstein, Lisa V.; Wang, Mingming; Lee, Martin L.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. [Raza, Anwar] Univ So Calif, Womens & Childrens Hosp, Los Angeles, CA USA. [Holschneider, Christine H.] Olive View UCLA Med Ctr, Dept Obstet & Gynecol, Sylmar, CA 91342 USA. RP Singhal, R (reprint author), Off Womens Hlth, Los Angeles Cty Dept Publ Hlth, 3400 Aerojet Ave,3rd Floor, El Monte, CA 91731 USA. EM risinghal@ph.lacounty.gov NR 29 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 575 EP 580 DI 10.1007/s11606-008-0528-x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300010 PM 18286344 ER PT J AU Moore, EE Hawes, SE Scholes, D Boyko, EJ Hughes, JP Fihn, SD AF Moore, Elya E. Hawes, Stephen E. Scholes, Delia Boyko, Edward J. Hughes, James P. Fihn, Stephan D. TI Sexual intercourse and risk of symptomatic urinary tract infection in post-menopausal women SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Infectious-Disease-Society-for-Obstetrics-and-Gynecology CY AUG 03-05, 2006 CL Monterey, CA SP Infect Dis Soc Obstet & Gynecol DE coitus; diaries; postmenopause; urinary tract infections ID ASYMPTOMATIC BACTERIURIA; UNITED-STATES; YOUNG-WOMEN; EPIDEMIOLOGY; PREDICTORS; VALIDITY; HEALTH; COSTS AB BACKGROUND: Sexual intercourse increases the risk of symptomatic urinary tract infections (UTI) in young women, but its role among post-menopausal women is unclear. OBJECTIVE: To determine whether recent sexual intercourse, as documented by daily diaries, is associated with an increased risk of symptomatic UTI in post-menopausal women. DESIGN: A 2-year prospective cohort study conducted from 1998 to 2002. PARTICIPANTS: One thousand and seventeen randomly selected post-menopausal women enrolled at Group Health Cooperative (GHC), a Washington State HMO. MEASUREMENTS AND MAIN RESULTS: Women were asked to enter daily diary information on vaginal intercourse, medication use, and genito-urinary symptoms. The outcome of interest, symptomatic UTI, was defined as a positive urine culture >= 10(5) CFU/mL of a uropathogen and the presence of >= 2 acute urinary symptoms. Nine hundred thirteen women returned diaries and were included in this study. Seventy-eight women experienced 108 symptomatic UTIs, and 361 (40%) reported sexual intercourse in their diaries. There was an increased hazard for UTI 2 calendar days after the reporting of sexual intercourse in the diaries (adjusted hazard ratio [HR], 3.42, 95% CI 1.49-7.80), while there was no evidence for an increased hazard associated with intercourse at other times. When the UTI criterion was relaxed from >= 10(5) CFU/mL to >= 10(4) CFU/mL, adding 9 UTI events to the analysis, the HR for UTI 2 days after intercourse changed slightly to 3.26 (95% CI 1.43-7.43). CONCLUSIONS: Our data suggest that, as with younger women, recent sexual intercourse is strongly associated with incident UTI in generally healthy post-menopausal women. C1 [Moore, Elya E.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Moore, Elya E.; Hawes, Stephen E.; Scholes, Delia; Boyko, Edward J.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Moore, Elya E.; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Scholes, Delia] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. [Boyko, Edward J.; Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Hughes, James P.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Moore, Elya E.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. RP Moore, EE (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM elya.moore@mcri.edu.au FU NIAID NIH HHS [T32 AI007140, T32AI07140]; NIDDK NIH HHS [K23 DK002660, K23DK02660, R01 DK43134] NR 30 TC 13 Z9 13 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 595 EP 599 DI 10.1007/s11606-008-0535-y PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300013 PM 18266044 ER PT J AU Bianchi, MT AF Bianchi, Matt T. TI Desiderata or dogma: What the evidence reveals about physician attire SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE dress code; white coat; tradition ID WEAR WHITE COATS; DOCTORS; APPEARANCE; PROFESSIONALISM AB INTRODUCTION: Physician-patient interactions are complex and depend on multiple factors including common cultural definitions and evolving social norms. The once purely philosophical debate over what constitutes appropriate physician attire can benefit from a growing evidence base in the literature. DISCUSSION: Although this literature is commonly regarded as supporting traditional attire, the data actually represent a more balanced distribution of opinions held by patients and by physicians. Perhaps interpretations favoring a conservative approach are expected given the history and tradition of the physician-patient relationship. CONCLUSION: Nevertheless, in the age of evidence-based medicine, it is difficult to argue against scrutiny of the available literature. Evidence that challenges the importance of traditional physician attire is reviewed. C1 [Bianchi, Matt T.] Brigham & Womens Hosp, Neurol Clin, Wang Ambulatory Ctr, Boston, MA 02114 USA. [Bianchi, Matt T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, 8th Floor, Boston, MA 02114 USA. EM mtbianchi@partners.org NR 23 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 641 EP 643 DI 10.1007/s11606-008-0546-8 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300022 PM 18286342 ER PT J AU Saha, S Freeman, M Toure, J Tippens, KM Weeks, C Ibrahim, S AF Saha, Somnath Freeman, Michele Toure, Joahd Tippens, Kimberly M. Weeks, Christine Ibrahim, Said TI Racial and ethnic disparities in the VA health care system: A systematic review SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE racial and ethnic disparities; medication adherence; health care utilization ID OF-VETERANS-AFFAIRS; ACUTE MYOCARDIAL-INFARCTION; INVASIVE CARDIAC PROCEDURES; WHITE MALE VETERANS; CAROTID-ENDARTERECTOMY; RACIAL/ETHNIC VARIATIONS; AFRICAN-AMERICAN; PHYSICIAN COMMUNICATION; CARDIOVASCULAR-DISEASE; SMOKING-CESSATION AB OBJECTIVES: To better understand the causes of racial disparities in health care, we reviewed and synthesized existing evidence related to disparities in the "equal access" Veterans Affairs (VA) health care system. METHODS: We systematically reviewed and synthesized evidence from studies comparing health care utilization and quality by race within the VA. RESULTS: Racial disparities in the VA exist across a wide range of clinical areas and service types. Disparities appear most prevalent for medication adherence and surgery and other invasive procedures, processes that are likely to be affected by the quantity and quality of patient-provider communication, shared decision making, and patient participation. Studies indicate a variety of likely root causes of disparities including: racial differences in patients' medical knowledge and information sources, trust and skepticism, levels of participation in health care interactions and decisions, and social support and resources; clinician judgment/bias; the racial/cultural milieu of health care settings; and differences in the quality of care at facilities attended by different racial groups. CONCLUSIONS: Existing evidence from the VA indicates several promising targets for interventions to reduce racial disparities in the quality of health care. C1 [Saha, Somnath; Freeman, Michele] Portland VA Med Ctr, Portland, OR 97239 USA. [Saha, Somnath; Freeman, Michele] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Toure, Joahd] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Tippens, Kimberly M.] Natl Coll Nat Med, Helfgott Res Inst, Portland, OR USA. [Weeks, Christine; Ibrahim, Said] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Ibrahim, Said] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Saha, S (reprint author), Portland VA Med Ctr, 3710 SW US,Vet Hosp Rd, Portland, OR 97239 USA. EM sahas@ohsu.edu FU HSRD VA [ESP 05-225] NR 84 TC 86 Z9 86 U1 4 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 654 EP 671 DI 10.1007/s11606-008-0521-4 PG 18 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300026 PM 18301951 ER PT J AU Washington, DL Bowles, J Saha, S Horowitz, CR Moody-Ayers, S Brown, AF Stone, VE Cooper, LA AF Washington, Donna L. Bowles, Jacqueline Saha, Somnath Horowitz, Carol R. Moody-Ayers, Sandra Brown, Arleen F. Stone, Valerie E. Cooper, Lisa A. CA Writing Grp Soc Gen Internal Med TI Transforming clinical practice to eliminate racial-ethnic disparities in healthcare SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE racial disparities; race; ethnicity; health care delivery; cultural competence; ethnic groups; continental population groups ID MEDICAL-CARE; UNITED-STATES; RACIAL/ETHNIC DISPARITIES; CULTURAL COMPETENCE; CONSUMER ASSESSMENT; INSURANCE-COVERAGE; PATIENT; ACCESS; COMMUNICATION; RACE AB Racial-ethnic minorities receive lower quality and intensity of health care compared with whites across a wide range of preventive, diagnostic, and therapeutic services and disease entities. These disparities in health care contribute to continuing racial-ethnic disparities in the burden of illness and death. Several national medical organizations and the Institute of Medicine have issued position papers and recommendations for the elimination of health care disparities. However, physicians in practice are often at a loss for how to translate these principles and recommendations into specific interventions in their own clinical practices. This paper serves as a blueprint for translating principles for the elimination of racial-ethnic disparities in health care into specific actions that are relevant for individual clinical practices. We describe what is known about reducing racial-ethnic disparities in clinical practice and make recommendations for how clinician leaders can apply this evidence to transform their own practices. C1 [Washington, Donna L.; Bowles, Jacqueline; Brown, Arleen F.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, VA Greater Los Angeles Healthcare Syst,Dept Med, Los Angeles, CA 90073 USA. [Washington, Donna L.; Bowles, Jacqueline] VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. [Saha, Somnath] Portoland Vet Affairs Med Ctr, Gen Internal Med Sect, Portland, OR USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Horowitz, Carol R.] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY USA. [Horowitz, Carol R.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Moody-Ayers, Sandra] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Stone, Valerie E.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Cooper, Lisa A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. RP Washington, DL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, VA Greater Los Angeles Healthcare Syst,Dept Med, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov FU NHLBI NIH HHS [K24HL083113, K24 HL083113]; NIA NIH HHS [K23 AG026748]; NIMHD NIH HHS [P60 MD000270, P20MD00148, P20 MD000148, P60 MD00270] NR 87 TC 22 Z9 22 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 685 EP 691 DI 10.1007/s11606-007-0481-0 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300029 PM 18196352 ER PT J AU Haas, JS Earle, CC Orav, JE Brawarsky, P Neville, BA Williams, DR AF Haas, Jennifer S. Earle, Craig C. Orav, John E. Brawarsky, Phyllis Neville, Bridget A. Williams, David R. TI Racial segregation and disparities in cancer stage for seniors SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE race; ethnicity; cancer stage; segregation ID BLACK-AND-WHITE; NEW-YORK-CITY; RESIDENTIAL SEGREGATION; BREAST-CANCER; PROSTATE-CANCER; SOCIOECONOMIC-STATUS; ETHNIC-DIFFERENCES; CERVICAL-CANCER; HEALTH-CARE; SURVIVAL AB BACKGROUND: Disparities in cancer survival may be related to differences in stage. Segregation may be associated with disparities in stage, particularly for cancers for which screening promotes survival. OBJECTIVES: The objective of the study was to examine whether segregation modifies racial/ethnic disparities in stage. DESIGN: The design of the study was analysis of Surveillance, Epidemiology, and End Results Medicare data for seniors with breast, colorectal, lung, and prostate cancer (n=410,870). MEASUREMENTS AND MAIN RESULTS: The outcome was early- versus late-stage diagnosis. Area of residence was categorized into 4 groups: low segregation/high income (potentially the most advantaged), high segregation/high income, low segregation/low income, and high segregation/low income (possibly the most disadvantaged). Blacks were less likely than whites to be diagnosed with early-stage breast, colorectal, or prostate cancer, regardless of area. For colorectal cancer, the black/white disparity was largest in low-segregation/low-income areas (black/white odds ratio [OR] of early stage 0.51) and smallest in the most segregated areas (ORs 0.71 and 0.74, P<.005). Differences in disparities in stage by area category were not apparent for breast, prostate, or lung cancer. Whereas there were few Hispanic-white differences in early-stage diagnosis, the Hispanic/white disparity in early-stage diagnosis of breast cancer was largest in low-segregation/low-income areas (Hispanic/white OR of early stage 0.54) and smallest in high-segregation/low-income areas (OR 0.96, P<.05 compared to low-segregation/low-income areas). CONCLUSIONS: Disparities in stages for cancers with an established screening test were smaller in more segregated areas. C1 [Haas, Jennifer S.; Orav, John E.; Brawarsky, Phyllis] Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Haas, Jennifer S.; Orav, John E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Earle, Craig C.; Neville, Bridget A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Haas, Jennifer S.; Williams, David R.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Haas, JS (reprint author), Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. EM jhaas@partners.org FU NCI NIH HHS [R01 CA112451, R01 CA112451-03] NR 51 TC 30 Z9 30 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 699 EP 705 DI 10.1007/s11606-008-0545-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300031 PM 18338215 ER PT J AU Egede, LE Bosworth, H AF Egede, Leonard E. Bosworth, Hayden TI The future of health disparities research: 2008 and beyond SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID QUALITY-OF-CARE; RACIAL DISPARITIES; DIABETES CARE; IMPROVEMENT C1 [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlt Disparities Res, Charleston, SC 29425 USA. [Bosworth, Hayden] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Bosworth, Hayden] Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Bosworth, Hayden] Duke Univ, Dept Med, Durham, NC USA. [Bosworth, Hayden] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Bosworth, Hayden] Duke Univ, Ctr Aging & Human Dev, Durham, NC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Div Gen Internal Med, Ctr Hlt Disparities Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu NR 16 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2008 VL 23 IS 5 BP 706 EP 708 DI 10.1007/s11606-008-0580-6 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 291KG UT WOS:000255195300032 PM 18392662 ER PT J AU Miller, E Wieneke, KM Murphy, JM Desmond, S Schiff, A Canenguez, KM Kleinman, RE AF Miller, Elizabeth Wieneke, Kristin M. Murphy, J. Michael Desmond, Sheila Schiff, Andrew Canenguez, Katia M. Kleinman, Ronald E. TI Child and parental poor health among families at risk for hunger attending a community health center SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE hunger; food insecurity; screening; pediatrics; childhood obesity; community health center; mental health; physical health ID FOOD INSUFFICIENCY; MATERNAL PERCEPTIONS; UNITED-STATES; INSECURITY; INCOME; ADOLESCENTS; PERFORMANCE; OVERWEIGHT; NUTRITION; OUTCOMES AB Background. Hunger is prevalent in low-income families. Community clinics offer an opportunity to identify families who experience hunger and to address hunger-related health problems. Methods. Parents of pediatric patients seen in an urban clinic completed a single question hunger screen. A subsample of parents participated in an interview. Patient and parental medical and mental health diagnoses were collected from medical records. Results. Children from families reporting hunger were more likely than those from families not reporting hunger to be obese and to have more documented medical diagnoses. Parents reporting hunger were also more likely to have mental health problems noted and to describe poor health status. Conclusion. Hunger is associated with specific health problems among children and parents in a low-income community clinic. A simple screen to identify hungry families in clinics may assist in recognition of hunger's contribution to child and parental poor health and development of targeted interventions. C1 [Miller, Elizabeth] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA. [Miller, Elizabeth] Massachusetts Gen Hosp, Community Benefit Program, Boston, MA 02114 USA. [Murphy, J. Michael; Kleinman, Ronald E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Wieneke, Kristin M.; Murphy, J. Michael; Canenguez, Katia M.] Child Psychiat Serv Mass Gen, Boston, MA USA. [Desmond, Sheila] Mass Gen Chelsea Hlth Ctr, Boston, MA USA. RP Miller, E (reprint author), Univ Calif Davis, Sch Med, Dept Pediat, Ticon II,2516 Stockton Blvd,Room 382, Sacramento, CA 95817 USA. EM elizabeth.miller@ucdmc.ucdavis.edu RI Miller, Elizabeth/E-7939-2012 NR 33 TC 4 Z9 4 U1 1 U2 13 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2008 VL 19 IS 2 BP 550 EP 561 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 297YM UT WOS:000255653300021 PM 18469425 ER PT J AU Conway, PH Konetzka, RT Zhu, JS Volpp, KG Sochalski, J AF Conway, Patrick H. Konetzka, R. Tamara Zhu, Jingsan Volpp, Kevin G. Sochalski, Julie TI Nurse staffing ratios: Trends and policy implications for hospitalists and the safety net SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE nurse staffing; hospital staffing; hospitalist; nurse workforce; safety net ID WORKING-CONDITIONS; PATIENT SAFETY; CALIFORNIA; OUTCOMES; SUPPORT AB BACKGROUND: Mandated minimum nurse-to-patient staffing ratio legislation was passed in California in 1999 and implemented January 1, 2004. Nurse staffing legislation is being considered in at least 25 other states. OBJECTIVES: The objectives of this study were: (1) to evaluate nurse staffing trends in California from 1993 to 2004, (2) to identify types of hospitals below minimum staffing ratios and staffing changes in 2004, the first year post-implementation; and (3) to discuss possible implications of nurse staffing on hospitalists and their hospital-based initiatives. DESIGN, SETTING, PATIENTS: We analyzed data from the medical-surgical units of all short-term acute-care general hospitals in California from 1993 to 2004. The annual hospital staffing ratio is composed of the combined hours of registered nurses and licensed vocational nurses and total number of patient days on medical-surgical units. RESULTS: Nurse staffing ratios were relatively unchanged from 1993 to 1999 and then increased significantly from 1999 to 2004, with the largest increase in 2004, the year the nurse staffing ratio was implemented. Types of hospitals more likely to be below minimum ratios had a high Medicaid/uninsured patient population and were government owned, nonteaching, urban, and in more competitive markets. Most hospitals below ratios were considered part of the health care "safety net." CONCLUSIONS: Nurse staffing legislation may increase nurse staffing. However, mandated nurse staffing ratios without mechanisms to help achieve ratios may force hospitals, especially safety-net hospitals, to make tradeoffs in other services or investments with unintended negative consequences for patients. Nurse staffing likely influences the outcomes of hospitalist-led quality initiatives, but these effects need to be explored further. C1 [Conway, Patrick H.] Cincinnati Childrens Hosp, Med Ctr, Ctr Hlth Care Qual, Cincinnati, OH 45215 USA. [Conway, Patrick H.] Cincinnati Childrens Hosp, Med Ctr, Div Hlth Policy & Clin Effectiveness, Cincinnati, OH 45215 USA. [Conway, Patrick H.] Cincinnati Childrens Hosp, Med Ctr, Div Gen Pediat, Cincinnati, OH 45215 USA. [Conway, Patrick H.] Univ Penn, Clin Scholars Program, Robert Wood Johnson Fdn, Philadelphia, PA 19104 USA. [Conway, Patrick H.; Volpp, Kevin G.; Sochalski, Julie] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Konetzka, R. Tamara] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Zhu, Jingsan; Volpp, Kevin G.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. [Sochalski, Julie] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Conway, PH (reprint author), Cincinnati Childrens Hosp, Med Ctr, Ctr Hlth Care Qual, 3333 Burnet Ave,MLC 2044, Cincinnati, OH 45215 USA. EM patrick.conway@cchmc.org NR 18 TC 14 Z9 14 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD MAY-JUN PY 2008 VL 3 IS 3 BP 193 EP 199 DI 10.1002/jhm.314 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 320JQ UT WOS:000257229900004 PM 18570346 ER PT J AU Sasaki, H Suzuki, N Ralph, K Kawashima, N Takeda, J Stashenko, P AF Sasaki, Hajime Suzuki, Noriyuki Kent, Ralph, Jr. Kawashima, Nobuyuki Takeda, Junji Stashenko, Philip TI T cell response mediated by myeloid cell-derived IL-12 is responsible for Porphyromonas gingivalis-induced periodontitis in IL-10-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALVEOLAR BONE LOSS; INFLAMMATORY BOWEL-DISEASE; HUMAN DENDRITIC CELLS; IFN-GAMMA PRODUCTION; RESORPTION IN-VIVO; CROHNS-DISEASE; CHRONIC ENTEROCOLITIS; METABOLIC SYNDROME; SIGNALING MECHANISMS; IMMUNE-RESPONSES AB Periodontal disease is a chronic inflammatory disease in the oral cavity, which culminates in alveolar bone loss. Porphyromonas gingivalis is a consensus periodontal pathogen that has been implicated in adult forms of periodontitis. We previously demonstrated that IIL-10-deficient mice exhibit a hyperinflammatory phenotype and are highly susceptible to P. gingivalis-induced periodontitis, indicating an important anti-inflammatory effect of IL-10 in suppressing bone loss. In this study, we analyzed the pathway(s) by which IL-10 deficiency leads to severe A gingivalis-induced periodontitis. Because Stat3 is essential in IL-10 signaling, immune cell-specific Stat3-deficient mice were subjected to A gingivalis infection to identify the key IIL-10-responsive cells in preventing periodontitis. Myeloid cell-specific Stat3-deficient mice exhibited increased periodontal bone loss (v < 0.001), whereas T cell- and B cell-specific Stat3 mice were resistant, suggesting that macrophages (MP) and/or polymorphonuclear leukocytes are the key target cells normally suppressed by IL-10. Myeloid cell-specific Stat3-deficient mice exhibited elevated gingival CD40L gene expression in vivo compared with wild-type controls (P < 0.01), and Stat3-deficient MPs exhibited vigorous P. gringivalis-stimulated IL-12 production in vitro and induced elevated Ag-specific T cell proliferation compared with wild-type NWs (p < 0.01). Of importance, both IIL-12p40/IL-10 and T cell/IL-10 double-deficient mice were resistant to P. gingivalis-induced periodontitis, demonstrating roles for both IL-12p40 and T cells in pathogenesis in a hyperinflammatory model of disease. These data demonstrate that P. gingivalis-induced periodontitis in IIL-10-deficient mice is dependent upon IL-12p40-mediated proinflammatory T cell responses. C1 [Sasaki, Hajime; Stashenko, Philip] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Suzuki, Noriyuki; Kawashima, Nobuyuki] Tokyo Med & Dent Univ, Grad Sch, Dept Restorat Sci, Div Oral Hlth Sci, Tokyo, Japan. [Kent, Ralph, Jr.] Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. [Takeda, Junji] Osaka Univ, Grad Sch Med, Dept Social & Environm Med, Osaka, Japan. RP Sasaki, H (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM hsasaki@forsyth.org FU NIDCR NIH HHS [DE 09018, DE 15888] NR 65 TC 27 Z9 29 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 MAY 1 PY 2008 VL 180 IS 9 BP 6193 EP 6198 PG 6 WC Immunology SC Immunology GA 324GV UT WOS:000257507000053 PM 18424741 ER PT J AU Dienstag, JL AF Dienstag, Jules L. TI Hepatitis A: The vaccine dividend SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID C VIRUS-INFECTION; CHRONIC LIVER-DISEASE; UNITED-STATES; PREVENTION; PREVALENCE; OUTBREAK C1 [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02111 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Jackson 7,55 Fruit St, Boston, MA 02111 USA. EM jdienstag@partners.org NR 22 TC 1 Z9 1 U1 0 U2 0 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 MAY 1 PY 2008 VL 197 IS 9 BP 1220 EP 1222 DI 10.1086/586900 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 290KC UT WOS:000255120700002 PM 18422432 ER PT J AU Walensky, RP Wood, R Weinstein, MC Martinson, NA Losina, E Fofana, MO Goldie, SJ Divi, N Yazdanpanah, Y Wang, B Paltiel, AD Freedberg, KA AF Walensky, Rochelle P. Wood, Robin Weinstein, Milton C. Martinson, Neil A. Losina, Elena Fofana, Mariam O. Goldie, Sue J. Divi, Nomita Yazdanpanah, Yazdan Wang, Bingxia Paltiel, A. David Freedberg, Kenneth A. CA CEPAC Int Investigators TI Scaling up antiretroviral therapy in South Africa: The impact of speed on survival SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA ID RESOURCE-POOR SETTINGS; TOTAL LYMPHOCYTE COUNT; HIV-INFECTED PATIENTS; COST-EFFECTIVENESS; COTE-DIVOIRE; TUBERCULOSIS; PROPHYLAXIS; OUTCOMES; COHORT AB Background. Only 33% of eligible human immunodeficiency virus (HIV)-infected patients in South Africa receive antiretroviral therapy (ART). We sought to estimate the impact of alternative ART scale-up scenarios on patient outcomes from 2007-2012. Methods. Using a simulation model of HIV infection with South African data, we projected HIV-associated mortality with and without effective ART for an adult cohort in need of therapy (2007) and for adults who became eligible for treatment (2008-2012). We compared 5 scale-up scenarios: (1) zero growth, with a total of 100,000 new treatment slots; (2) constant growth, with 600,000; (3) moderate growth, with 2.1 million; (4) rapid growth, with 2.4 million); and (5) full capacity, with 3.2 million. Results. Our projections showed that by 2011, the rapid growth scenario fully met the South African need for ART; by 2012, the moderate scenario met 97% of the need, but the zero and constant growth scenarios met only 28% and 52% of the need, respectively. The latter scenarios resulted in 364,000 and 831,000 people alive and on ART in 2012. From 2007 to 2012, cumulative deaths in South Africa ranged from 2.5 million under the zero growth scenario to 1.2 million under the rapid growth scenario. Conclusions. Alternative ART scale-up scenarios in South Africa will lead to differences in the death rate that amount to more than 1.2 million deaths by 2012. More rapid scale-up remains critically important. C1 [Walensky, Rochelle P.; Fofana, Mariam O.; Divi, Nomita; Wang, Bingxia; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, Rochelle P.; Losina, Elena; Wang, Bingxia; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Weinstein, Milton C.; Goldie, Sue J.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Martinson, Neil A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Paltiel, A. David] Yale Univ, Sch Med, New Haven, CT USA. [Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu Res Ctr, ZA-7925 Cape Town, South Africa. [Martinson, Neil A.] Wits Hlth consortium, Perinatal HIV Res Unit, Johannesburg, South Africa. [Yazdanpanah, Yazdan] Univ Maladies, Serv Infec & Voyageur, Lille, France. [Yazdanpanah, Yazdan] Fac Med Lille, Ctr Hosp Tourcoing, F-59045 Lille, France. [Yazdanpanah, Yazdan] Inst Pasteur, Ctr Immunol & Biol Parasitaire, CNRS, URA 362,Lab Rech Econom & Sociales, F-59019 Lille, France. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org RI Wood, Robin/G-8509-2011; Anglaret, Xavier/F-7333-2013; OI Fofana, Mariam/0000-0002-2874-471X; Walensky, Rochelle P./0000-0002-8795-379X; Lipsitch, Marc/0000-0003-1504-9213 FU NIAID NIH HHS [K24 AI062476-04, K24 AI062476, K25 AI050436, K25 AI050436-05, K25 AI50436, P30 AI060354, P30 AI060354-04, R01 AI058736, R01 AI058736-04] NR 39 TC 51 Z9 51 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2008 VL 197 IS 9 BP 1324 EP U23 DI 10.1086/587184 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 290KC UT WOS:000255120700015 PM 18422445 ER PT J AU Monnard, PA Szostak, JW AF Monnard, Pierre-Alain Szostak, Jack W. TI Metal-ion catalyzed polymerization in the eutectic phase in water-ice: A possible approach to template-directed RNA polymerization SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 13th International Conference on Biological Inorganic Chemistry CY JUL 15-20, 2007 CL Vienna, AUSTRIA DE template-directed RNA polymerization; metal-ion catalyzed polymerization; eutectic phase in water-ice; micro-environment ID HAIRPIN OLIGONUCLEOTIDES; AQUEOUS-SOLUTIONS; RESIDUES; NUCLEOSIDES; ADENOSINE; ORIGIN; WORLD; STEPS AB The emergence of an RNA world requires among other processes the non-enzymatic, template-directed replication of genetic polymers such as RNA or related nucleic acids, possibly catalyzed by metal-ions. The absence of uridilate derivative polymerization on adenine containing templates has been the main issue preventing an efficient template-directed RNA polymerization. We report here the investigation of template-directed RNA polymerization in the eutectic phase in water-ice. In particular, it was found that activated uridilate monomers in the presence of metal-ion catalysts could efficiently elongate RNA hairpins whose 5'-overhangs served as the templating sequence. The same applies for every other pyrimidine and purine nucleobase. Moreover, the initial elongation rates were always higher in the presence of a template complementary to the nucleotide than in systems without proper base-pairing opportunities. These results suggest that a template-directed RNA polymerization catalyzed by metal-ions could be carried out under eutectic phase in water-ice conditions. (C) 2008 Elsevier Inc. All rights reserved. C1 [Monnard, Pierre-Alain] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Ctr, Boston, MA 02114 USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Simches Res Ctr, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Monnard, PA (reprint author), Los Alamos Natl Lab, POB 1663,EES-6,MS-D462, Los Alamos, NM 87545 USA. EM pmonnard@lanl.gov; szostak@molbio.mgh.harvard.edu NR 22 TC 24 Z9 26 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD MAY-JUN PY 2008 VL 102 IS 5-6 BP 1104 EP 1111 DI 10.1016/j.jinorgbio.2008.01.026 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 306HT UT WOS:000256239600013 PM 18329104 ER PT J AU Korosogiou, G Tang, LJ Kedziorek, D Cosby, K Gilson, WD Vonken, EJ Schaer, M Sosnovik, D Kraitchman, DL Weiss, RG Weissleder, R Stuber, M AF Korosogiou, Grigorios Tang, Lijun Kedziorek, Dorota Cosby, Kenyatta Gilson, Wesley D. Vonken, Evert-Jan Schaer, Michael Sosnovik, David Kraitchman, Dara L. Weiss, Robert G. Weissleder, Ralf Stuber, Matthias TI Positive contrast MR-lymphography using inversion recovery with ON-resonant water suppression (IRON) SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE inversion recovery with ON-resonant water suppression (IRON); off-resonance imaging; monocrystalline iron oxide nanoparticle (MION-47); magnetic resonance lymphography ID LYMPH-NODE METASTASES; MAGNETIC NANOPARTICLES; PROSTATE-CANCER; RABBIT MODEL; OXIDE; VISUALIZATION; AGENT; GRASP; USPIO; NECK AB Purpose: To investigate the utility of inversion recovery with ON-resonant water suppression (IRON) to create positive signal in normal lymph nodes after injection of superparamagnetic nanoparticles. Materials and Methods: Experiments were conducted on six rabbits, which received a single bolus injection of 80 p,mol Fe/kg monocrystalline iron oxide nanoparticle (MION-47). Magnetic resonance imaging (MRI) was performed at baseline, I day, and 3 days after MION-47 injection using conventional T-1- and T-2*-weighted sequences and IRON. Contrast-to-noise ratios (CNR) were measured in blood and in paraaortic lymph nodes. Results: On T-2*-weighted images, as expected, signal attenuation was observed in areas of paraaortic lymph nodes after MION-47 injection. However, using IRON the paraaortic lymph nodes exhibited very high contrast enhancement, which remained 3 days after injection. CNR with IRON was 2.2 +/- 0.8 at baseline, increased markedly 1 day after injection (23.5 +/- 5.4, P < 0.01 vs. baseline), and remained high after 3 days (21.8 +/- 5.7, *P < 0.01 vs. baseline). CNR was also high in blood I day after injection (42.7 +/- 7.2 vs. 1.8 +/- 0.7 at baseline, P < 0.01) but approached baseline after 3 days (1.9 +/- 1.4, P = NS vs. baseline). Conclusion: IRON in conjunction with superparamagnetic nanoparticles can be used to perform 'positive contrast' MR-lymphography, particularly 3 days after injection of the contrast agent, when signal is no longer visible within blood vessels. The proposed method may have potential as an adjunct for nodal staging in cancer screening. C1 [Korosogiou, Grigorios; Tang, Lijun; Kedziorek, Dorota; Cosby, Kenyatta; Gilson, Wesley D.; Vonken, Evert-Jan; Schaer, Michael; Kraitchman, Dara L.; Weiss, Robert G.; Stuber, Matthias] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Korosogiou, Grigorios] Univ Heidelberg, Dept Cardiol, D-6900 Heidelberg, Germany. [Schaer, Michael] Philips Med Syst, Cleveland, OH USA. [Sosnovik, David; Weissleder, Ralf] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02115 USA. [Weiss, Robert G.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. RP Stuber, M (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, JHOC 4223,601 N Caroline St, Baltimore, MD 21287 USA. EM mstuber@mri.jhu.edu RI Kedziorek, Dorota/B-8742-2008; Stuber, Matthias/B-2949-2010; OI Stuber, Matthias/0000-0001-9843-2028; Schar, Michael/0000-0002-7044-9941 FU NCI NIH HHS [P50 CA086355, R24CA92782, P50CA86355, R24 CA092782-05, P50 CA086355-01, R24 CA092782]; NHLBI NIH HHS [R01 HL084186, R01 HL073223, R01 HL073223-04]; NIBIB NIH HHS [K08 EB004922, 1 K08 EB004922-01] NR 20 TC 17 Z9 17 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2008 VL 27 IS 5 BP 1175 EP 1180 DI 10.1002/jmri.21337 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 297NF UT WOS:000255622700031 PM 18425827 ER PT J AU Ratai, EM Hancu, I Blezek, DJ Turk, KW Halpern, E Gonzalez, RG AF Ratai, Eva-Maria Hancu, Ileana Blezek, Daniel J. Turk, Katherine W. Halpern, Elkan Gonzalez, R. Gilberto TI Automatic repositioning of MRSI voxels in longitudinal studies: Impact on reproducibility of metabolite concentration measurements SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE automatic repositioning; prospective realignment; magnetic resonance spectroscopy (MRS); brain; MR spectroscopic imaging (MRSI) ID MAGNETIC-RESONANCE-SPECTROSCOPY; H-1 MRS; IMAGE REGISTRATION; MUTUAL INFORMATION; BRAIN-TUMORS; IN-VIVO; MAXIMIZATION AB Purpose: To study an automatic repositioning method to reduce variability in longitudinal MRSI exams based on a priori image registration. Longitudinal proton MR spectroscopic imaging (H-1 MRSI) exams to study the effects of disease or treatment are becoming increasingly common. However, one source of variability in such exams arises from imperfect relocalization of the MRSI grid in the follow-up exams. Materials and Methods: Six healthy subjects were each scanned three times during the course of 1 day. In each follow-up exam a manually placed MRSI grid was acquired in addition to the automatically repositioned MRSI grid. Then coefficients of variance between baseline and follow-up scans were calculated for N-acetylaspartate, creatine. and choline. In addition. the overall MRSI grid overlap and individual voxel overlaps were also calculated for both the visually and automatically repositioned voxels. Results: Streamlined workflow, reduced variability of metabolite concentration measurements, and increased voxel overlaps are noted when this automatic repositioning procedure is compared to the visual MRSI grid repositioning approach. Conclusion: Our results suggest that this approach is able to improve reproducibility in longitudinal MRS exams. C1 [Ratai, Eva-Maria; Turk, Katherine W.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Neuroradiol Div, Charlestown, MA 02129 USA. [Hancu, Ileana; Blezek, Daniel J.] GE Global Res Ctr, Niskayuna, NY USA. [Halpern, Elkan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Halpern, Elkan] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Ratai, EM (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Neuroradiol Div, Bldg 149,13th St,Rm 2301, Charlestown, MA 02129 USA. EM ratai@nmr.mgh.harvard.edu FU NCRR NIH HHS [P51 RR000164, P51 RR000164-455226]; NIAID NIH HHS [P30 AI028691, AI028691]; NINDS NIH HHS [R01 NS050041, R01 NS050041-04, R01NS050041] NR 21 TC 7 Z9 8 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2008 VL 27 IS 5 BP 1188 EP 1193 DI 10.1002/jmri.21365 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 297NF UT WOS:000255622700033 PM 18425834 ER PT J AU Yamaoka, Y AF Yamaoka, Yoshio TI Roles of the plasticity regions of Helicobacter pylori in gastroduodenal pathogenesis SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Review ID CAG PATHOGENICITY-ISLAND; GASTRIC EPITHELIAL-CELLS; COMPLETE GENOME SEQUENCE; OUTER-MEMBRANE PROTEINS; IV SECRETION APPARATUS; ULCER-PROMOTING GENE; DUODENAL-ULCER; NATURAL TRANSFORMATION; CLINICAL PRESENTATION; VIRULENCE FACTORS AB Putative virulence genes of Helicobacter pylori are generally classified into three categories: strain-specific genes, phase-variable genes and genes with variable structures/genotypes. Among these, there has recently been considerable interest in strain-specific genes found outside of the cag pathogenicity island, especially genes in the plasticity regions. Nearly half of the strain-specific genes of H. pylori are located in the plasticity regions in strains 26695 and J99. Strain HPAG1, however, seems to lack a typical plasticity region; instead it has 43 HPAG1-specific genes which are either undetectable or incompletely represented in the genomes of strains 26695 and J99. Recent studies showed that certain genes or combination of genes in this region may play important roles in the pathogenesis of H. pylori-associated gastroduodenal diseases. Most previous studies have focused on the plasticity region in strain J99 (jhp0914-jhp0961) and the jhp0947 gene and the buodenal ulcer promoting (dupA) gene are good candidate markers for gastroduodenal diseases although there are some paradoxical findings. The jhp0947 gene is reported to be associated with an increased risk of both duodenal ulcers and gastric cancers, whereas the dupA gene, which encompasses jhp0917 and jhp0918, is reported to be associated with an increased risk of duodenal ulcers and protection against gastric cancers. In addition, recent studies showed that approximately 10-30 % of clinical isolates possess a 16.3 kb type IV secretion apparatus (tfs3) in the plasticity region. Studies on the plasticity region have only just begun, and further investigation is necessary to elucidate the roles of genes in this region in gastroduodenal pathogenesis. C1 [Yamaoka, Yoshio] Baylor Coll Med, Dept Med Gastroenterol, Houston, TX 77030 USA. [Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. RP Yamaoka, Y (reprint author), Baylor Coll Med, Dept Med Gastroenterol, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU NIDDK NIH HHS [R01 DK062813-05, R01 DK062813, R01 DK62813] NR 51 TC 53 Z9 56 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD MAY PY 2008 VL 57 IS 5 BP 545 EP 553 DI 10.1099/jmm.0.2008/000570-0 PG 9 WC Microbiology SC Microbiology GA 299AF UT WOS:000255727500002 PM 18436586 ER PT J AU Lutton, BV Callard, IP AF Lutton, B. V. Callard, I. P. TI Morphological relationships and leukocyte influence on steroid production in the epigonal organ-ovary complex of the skate, Leucoraja erinacea SO JOURNAL OF MORPHOLOGY LA English DT Article DE elasmobranch; reproduction; immunology ID TUMOR-NECROSIS-FACTOR; RAT GRANULOSA-CELLS; HORMONE-INDUCED DIFFERENTIATION; FACTOR-ALPHA; AROMATASE-ACTIVITY; ESTROGEN-RECEPTOR; PROGESTERONE-RECEPTOR; REPRODUCTIVE ACTIVITY; SQUALUS-ACANTHIAS; SEX STEROIDS AB In elasmobranchs, a unique association exists between an immune tissue, the epigonal organ (EO), and the gonads. In this study, the histological and vascular relationships of the EO and ovarian follicles of the little skate, Leucoraja erinacea, were assessed. Perfusions of Evans blue dye and Batson's monomer showed a shared vascular pathway from the gonadal artery into the epigonal-ovary complex, with blood first entering the EO and then perfusing the ovarian follicles. Histological studies demonstrated direct cellular contact between epigonal leukocytes and the follicle wall (FW), as well as the presence of leukocytes between the steroidogenic theca and granulosa cells. In vitro analyses demonstrated that epigonal cells co-cultured with FW cells cause a dose-dependent inhibition of estrogen (E-2) and testosterone (T) production. In contrast, conditioned media from epigonal leukocytes, stimulated or unstimulated with lipopolysaccharide (10 mu g/ml), increase the production of E-2 and T from FW cells of the ovaries. These studies provide a basis for further investigations of leukocyte secreted factors and cell contact modulation of follicular steroid production. C1 [Lutton, B. V.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. [Callard, I. P.] Boston Univ, Dept Biol, Boston, MA 02215 USA. RP Lutton, BV (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019 13th St, Charlestown, MA 02129 USA. EM bram.lutton@mgh.tbrc.harvard.edu FU NICHD NIH HHS [T32-HD07387]; NIEHS NIH HHS [P42-ES07381] NR 61 TC 6 Z9 6 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0362-2525 J9 J MORPHOL JI J. Morphol. PD MAY PY 2008 VL 269 IS 5 BP 620 EP 629 DI 10.1002/jmor.10614 PG 10 WC Anatomy & Morphology SC Anatomy & Morphology GA 296PQ UT WOS:000255558700008 PM 18302243 ER PT J AU Jakupcak, M Luterek, J Hunt, S Conybeare, D McFall, M AF Jakupcak, Matthew Luterek, Jane Hunt, Stephen Conybeare, Daniel McFall, Miles TI Posttraumatic stress and its relationship to physical health functioning in a sample of Iraq and Afghanistan War veterans seeking postdeployment VA health care SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Afghanistan; combat; Iraq; physical health functioning; posttraumatic stress ID COMBAT VETERANS; GULF-WAR; DISORDER; SYMPTOMS; PREDICTORS; TRAUMA AB The relationship between posttraumatic stress and physical health functioning was examined in a sample of Iraq and Afghanistan War veterans seeking postdeployment VA care. Iraq and Afghanistan War veterans (N = 108) who presented for treatment to a specialty postdeployment care clinic completed self-report questionnaires that assessed symptoms of postraumatic stress disorder (PTSD), chemical exposure, combat exposure, and physical health functioning. As predicted, PTSD symptom severity was significantly associated with poorer health functioning, even after accounting for demographic factors, combat and chemical exposure, and health risk behaviors. These results highlight the unique influence of PTSD on the physical health in treatment seeking Iraq and Afghanistan War veterans. C1 [Jakupcak, Matthew] Puget Sound Hlth Care Syst, Deployment Hlth Clin, Seattle, WA 98108 USA. [Jakupcak, Matthew; Luterek, Jane; Hunt, Stephen; Conybeare, Daniel; McFall, Miles] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Luterek, Jane; Conybeare, Daniel; McFall, Miles] Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. RP Jakupcak, M (reprint author), Puget Sound Hlth Care Syst, Deployment Hlth Clin, Seattle, WA 98108 USA. EM matthew.jakupcak@va.gov NR 20 TC 59 Z9 60 U1 0 U2 2 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 MAY PY 2008 VL 196 IS 5 BP 425 EP 428 DI 10.1097/NMD.0b013e31817108ed PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 303QM UT WOS:000256055600011 PM 18477887 ER PT J AU Sher, DJ Henson, JW Avutu, B Hochberg, FH Batchelor, TT Martuza, RL Barker, FG Loeffler, JS Chakravarti, A AF Sher, David J. Henson, John W. Avutu, Bindu Hochberg, Fred H. Batchelor, Tracy T. Martuza, Robert L. Barker, Fred G., II Loeffler, Jay S. Chakravarti, Arnab TI The added value of concurrently administered temozolomide versus adjuvant temozolomide alone in newly diagnosed glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE combined modality therapy; glioblastoma multiforme; radiosensitization; radiotherapy; temozolomide ID RANDOMIZED TRIAL; CHEMOTHERAPY; RADIATION; RADIOTHERAPY; SURVIVAL; CANCER AB Purpose Temozolomide (TMZ), given concurrently with radiotherapy (RT) and as adjuvant monotherapy afterwards, has led to improved survival in glioblastoma multiforme (GBM). However, it is unclear whether its primary mechanism of action is through enhancement of radiation response, independent cytotoxicity, or both. We sought to determine the relative contribution of concomitant temozolomide in patients treated by concurrent and adjuvant TMZ versus adjuvant TMZ alone in the setting of newly diagnosed GBM. Methods and Materials We identified patients diagnosed with GBM and treated with surgery, involved-field radiotherapy, and chemotherapy at MGH between 2002 and 2004. Eligible patients received either adjuvant temozolomide alone (group 1) or temozolomide concurrently with RT followed by adjuvant TMZ (group 2). The primary endpoint of this retrospective analysis was overall survival (OS). Results Forty-three patients (group 1, n = 21; group 2, n = 22) were included in this study. The median follow-up was 33.7 months for surviving patients. There were no significant differences in baseline characteristics between these two groups. On univariate analysis, patients who received concurrent and adjuvant temozolomide experienced a 2-year OS of 51% and median survival of 25.5 months, compared with a 2-year OS of 36% and median survival of 15.6 months for group 1 patients (P < 0.05). On multivariable analysis, the hazard ratio (HR) favoring concurrent TMZ trended towards significance (HR = 0.51, P = 0.08) despite modest patient numbers. Conclusions Concurrent and adjuvant TMZ was associated with improved survival compared to adjuvant TMZ alone, highlighting the potentiation of radiation effect by temozolomide in the clinical setting. C1 [Loeffler, Jay S.; Chakravarti, Arnab] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Sher, David J.] Harvard Radiat Oncol Program, Boston, MA USA. [Henson, John W.; Hochberg, Fred H.; Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Avutu, Bindu] Wright State Univ, Boonshoft Sch Med, Dayton, OH 45435 USA. [Martuza, Robert L.; Barker, Fred G., II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM achakravarti@partners.org FU NINDS NIH HHS [R01 NS032677, R01 NS032677-16] NR 14 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2008 VL 88 IS 1 BP 43 EP 50 DI 10.1007/s11060-008-9530-8 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 288CR UT WOS:000254964300006 PM 18231723 ER PT J AU Busl, KM Alcalay, RN AF Busl, Katharina M. Alcalay, Roy N. TI A surprising cause of sinusitis SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article ID PARANASAL SINUSES C1 [Alcalay, Roy N.] Columbia Univ, Neurol Inst, New York, NY 10032 USA. [Busl, Katharina M.; Alcalay, Roy N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Busl, Katharina M.; Alcalay, Roy N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Alcalay, RN (reprint author), Columbia Univ, Neurol Inst, 710 W 168th St,3rd Floor, New York, NY 10032 USA. EM royalcalay@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2008 VL 87 IS 3 BP 295 EP 297 DI 10.1007/s11060-007-9509-x PG 3 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 285VU UT WOS:000254805100007 PM 18094937 ER PT J AU Akar, S Drappatz, J Hsu, L Blinder, RA Black, PM Kesari, S AF Akar, Serra Drappatz, Jan Hsu, Liangge Blinder, Russell A. Black, Peter McL. Kesari, Santosh TI Hypertrophic olivary degeneration after resection of a cerebellar tumor SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE cerebellar tumor; hypertrophic olivary degeneration; Guillain-Mollaret triangle ID PONTINE HEMORRHAGE; CAVERNOUS HEMANGIOMA; PALATAL TREMOR AB We report a case of hypertrophic olivary degeneration due to cerebellar surgery for a low-grade tumor. A 27-year-old female presented with right-sided paresthesias and intermittent leg paresis following a right cerebellar resection of a tumor 2 weeks prior. One month later, her symptoms remained stable while her neurological examination demonstrated slight right hemi-body hypoesthesia and subtle appendicular ataxia in her right upper extremity. An MRI scan revealed a hypertrophied left anterolateral medulla with increased T2 signal and no diffusion abnormality. The T2 hyperintensity and hypertrophy slowly resolved and she clinically improved without further intervention. Hypertrophic olivary degeneration may be mistaken for tumor progression, post-operative vasculopathy or granulation tissue and should be considered in patients undergoing cerebellar surgery. C1 [Akar, Serra; Drappatz, Jan; Kesari, Santosh] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Akar, Serra] Hacettepe Univ, Sch Med, Ankara, Turkey. [Drappatz, Jan; Kesari, Santosh] Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, Boston, MA 02115 USA. [Drappatz, Jan; Hsu, Liangge; Blinder, Russell A.; Black, Peter McL.; Kesari, Santosh] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hsu, Liangge; Blinder, Russell A.] Brigham & Womens Hosp, Div Neuroradiol, Dept Radiol, Boston, MA 02115 USA. [Black, Peter McL.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Kesari, S (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW460,44 Binney St, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 17 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2008 VL 87 IS 3 BP 341 EP 345 DI 10.1007/s11060-008-9523-7 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 285VU UT WOS:000254805100013 PM 18217209 ER PT J AU Paintlia, MK Paintlia, AS Khan, M Singh, I Singh, AK AF Paintlia, Manjeet K. Paintlia, Ajaib S. Khan, Mushfiquddin Singh, Inderjit Singh, Avtar K. TI Modulation of peroxisome proliferator-activated receptor-alpha activity by N-acetyl cysteine attenuates inhibition of oligodendrocyte development in lipopolysaccharide stimulated mixed glial cultures SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cerebral white matter injury; lipopolysaccharide; oligodendrocyte; peroxisome proliferator-activated receptor-alpha and N-acetyl cysteine; reactive oxygen species ID NECROSIS-FACTOR-ALPHA; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; OXIDATIVE STRESS; BRAIN-INJURY; KAPPA-B; PERIVENTRICULAR LEUKOMALACIA; INTRAUTERINE INFECTION; DEMYELINATING DISEASES; INFLAMMATORY DISEASE AB Glial cells secrete proinflammatory mediators in the brain in response to exogenous stimuli such as infection and injury. Previously, we documented that systemic maternal lipopolysaccharide (LPS)-exposure at embryonic gestation day 18 causes oligodendrocyte (OL)-injury/hypomyelination in the developing brain which can be attenuated by N-acetyl cysteine (NAC; precursor of glutathione). The present study delineates the underlying mechanism of NAC-mediated attenuation of inhibition of OL development in LPS-stimulated mixed glial cultures. Factors released by LPS-stimulated mixed glial cultures inhibited OL development as shown by decrease in both proliferation 3bromo-deoxyuridine(+)/chondroitin sulfate proteoglycan-NG2(+), hereafter BrdU(+)/NG(+) and differentiation (O4(+) and myelin basic protein(+)) of OL-progenitors. Correspondingly, an impairment of peroxisomal proliferation was shown by a decrease in the level of peroxisomal proteins in the developing OLs following exposure to LPS-conditioned media (LCM). Both NAC and WY14643, a peroxisome proliferator-activated receptor (PPAR)-alpha agonist attenuated these LCM-induced effects in OL-progenitors. Similar to WY14643, NAC attenuated LCM-induced inhibition of PPAR-alpha activity in developing OLs. Studies conducted with cytokines and diamide (a thiol-depleting agent) confirmed that cytokines are active agents in LCM which may be responsible for inhibition of OL development via peroxisomal dysfunction and induction of oxidative stress. These findings were further corroborated by similar treatment of developing OLs generated from PPAR-alpha((-/-)) and wild-type mice or B12 oligodendroglial cells co-transfected with PPAR-alpha small interfering RNAs/pTK-PPREx3-Luc plasmids. Collectively, these data provide evidence that the modulation of PPAR-alpha activity, thus peroxisomal function by NAC attenuates LPS-induced glial factors-mediated inhibition of OL development suggesting new therapeutic interventions to prevent the devastating effects of maternal infections. C1 [Paintlia, Manjeet K.; Paintlia, Ajaib S.; Khan, Mushfiquddin; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst 513, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pediat, Darby Childrens Res Inst 513, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NCRR NIH HHS [C06 RR015455, C06 RR018823]; NINDS NIH HHS [R01 NS040810, R01 NS034741-12, NS-37766, NS-22576, R01 NS034741, R01 NS037766-10, NS-40810, R37 NS022576, R01 NS037766, NS-34741, R37 NS022576-24, R01 NS022576, R01 NS022576-17] NR 67 TC 21 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2008 VL 105 IS 3 BP 956 EP 970 DI 10.1111/j.1471-4159.2007.05199.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 290RF UT WOS:000255139200035 PM 18205750 ER PT J AU Won, JS Im, YB Khan, M Contreras, M Singh, AK Singh, I AF Won, Je-Seong Im, Yeong-Bin Khan, Mushfiquddin Contreras, Miguel Singh, Avtar K. Singh, Inderjit TI Lovastatin inhibits amyloid precursor protein (APP) beta-cleavage through reduction of APP distribution in Lubrol WX extractable low density lipid rafts SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE beta-amyloid and endocytosis; Alzheimer's disease; geranylgeranylation; lipid rafts; lovastatin ID CELL-SURFACE RECEPTOR; ALZHEIMERS-DISEASE; A-BETA; CHOLESTEROL DEPLETION; ENDOCYTIC PATHWAY; ANCHORED PROTEINS; MEMBRANE DOMAINS; PLASMA-MEMBRANE; ALPHA-SECRETASE; GAMMA-SECRETASE AB Previous studies have described that statins (inhibitors of cholesterol and isoprenoid biosynthesis) inhibit the output of amyloid-beta (A beta) in the animal model and thus decrease risk of Alzheimer's disease. However, their action mechanism(s) in A beta precursor protein (APP) processing and A beta generation is not fully understood. In this study, we report that lovastatin treatment reduced A beta output in cultured hippocampal neurons as a result of reduced APP levels and beta-secretase activities in low density Lubrol WX (non-ionic detergent) extractable lipid rafts (LDLR). Rather than altering cholesterol levels in lipid raft fractions and thus disrupting lipid raft structure, lovastatin decreased A beta generation through down-regulating geranylgeranyl-pyrophosphate dependent endocytosis pathway. The inhibition of APP endocytosis by treatment with lovastatin and reduction of APP levels in LDLR fractions by treatment with phenylarsine oxide (a general endocytosis inhibitor) support the involvement of APP endocytosis in APP distribution in LDLR fractions and subsequent APP beta-cleavage. Moreover, lovastatin-mediated down-regulation of endocytosis regulators, such as early endosomal antigen 1, dynamin-1, and phosphatidylinositol 3-kinase activity, indicates that lovastatin modulates APP endocytosis possibly through its pleiotropic effects on endocytic regulators. Collectively, these data report that lovastatin mediates inhibition of LDLR distribution and beta-cleavage of APP in a geranylgeranyl-pyrophosphate and endocytosis-dependent manner. C1 [Won, Je-Seong; Singh, Avtar K.; Singh, Inderjit] Med Univ S Carolina, Charles P Darby Childrens Res Inst, Dept Pathol, Charleston, SC 29425 USA. [Won, Je-Seong; Im, Yeong-Bin; Khan, Mushfiquddin; Contreras, Miguel] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson Vet Adm Med Ctr, Lab Med Serv, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Charles P Darby Childrens Res Inst, Dept Pathol, 173 Ashley Ave,Rm 516, Charleston, SC 29425 USA. EM singhi@musc.edu FU NCRR NIH HHS [RR015455, C06 RR018823, C06 RR015455, RR018823]; NIA NIH HHS [AG-25307, R56 AG025307-02, R56 AG025307]; NINDS NIH HHS [R01 NS034741-12, NS-34741, R37 NS022576, R01 NS037766, R01 NS022576-17, R01 NS034741, NS-22576, NS-37766, R01 NS022576, R01 NS037766-10] NR 66 TC 28 Z9 29 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2008 VL 105 IS 4 BP 1536 EP 1549 DI 10.1111/j.1471-4159.2008.05283.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 292SO UT WOS:000255286600041 PM 18266936 ER PT J AU Rhodes, ME Rubin, RT McKlveen, JM Karwoski, TE Fulton, BA Czambel, RK AF Rhodes, M. E. Rubin, R. T. McKlveen, J. M. Karwoski, T. E. Fulton, B. A. Czambel, R. K. TI Pituitary-adrenal responses to oxotremorine and acute stress in male and female M-1 muscarinic receptor knockout mice: Comparisons to M-2 muscarinic receptor knockout mice SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE cholinergic; diergism; knockout; muscarinic; sex differences ID ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTORS; SEXUAL DIERGISM; CORTICAL RESPONSES; SEIZURE ACTIVITY; AXIS RESPONSES; RAT PITUITARY; M1 RECEPTOR; YOUNG; M2 AB Both within the brain and in the periphery, M-1 muscarinic receptors function primarily as postsynaptic receptors and M-2 muscarinic receptors function primarily as presynaptic autoreceptors. In addition to classical parasympathetic effectors, cholinergic stimulation of central muscarinic receptors influences the release of adrenocorticotrophic hormone (ACTH) and corticosterone. We previously reported that oxotremorine administration to male and female M-2 receptor knockout and wild-type mice increased ACTH to a significantly greater degree in knockout males compared to all other groups, and that M-2 knockout mice of both sexes were significantly more responsive to the mild stress of saline injection than were wild-type mice. These results accord with the primary function of M-2 receptors as presynaptic autoreceptors. In the present study, we explored the role of the M-1 receptor in pituitary-adrenal responses to oxotremorine and saline in male and female M-1 knockout and wild-type mice. Because these mice responded differently to the mild stress of saline injection than did the M-2 knockout and wild-type mice, we also determined hormone responses to restraint stress in both M-1 and M-2 knockout and wild-type mice. Male and female M-1 knockout and wild-type mice were equally unresponsive to the stress of saline injection. Oxotremorine increased both ACTH and corticosterone in M-1 wild-type mice to a significantly greater degree than in knockout mice. In both M-1 knockout and wild-type animals, ACTH responses were greater in males compared to females, and corticosterone responses were greater in females compared to males. Hormone responses to restraint stress were increased in M-2 knockout mice and decreased in M-1 knockout mice compared to their wild-type counterparts. These findings suggest that M-1 and M-2 muscarinic receptor subtypes differentially influence male and female pituitary-adrenal responses to cholinergic stimulation and stress. The decreased pituitary-adrenal sensitivity to oxotremorine and restraint stress noted in M-1 knockout mice is consistent with M-1 being primarily a postsynaptic receptor. Conversely, the increased pituitary-adrenal sensitivity to these challenges noted in M-2 knockout mice is consistent with M-2 being primarily a presynaptic autoreceptor. C1 [Rhodes, M. E.; McKlveen, J. M.] St Vincent Coll, Dept Biol, Latrobe, PA 15650 USA. [Rubin, R. T.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA USA. [Karwoski, T. E.; Fulton, B. A.; Czambel, R. K.] Drexel Univ, Coll Med, Neurosci Res Ctr, Pittsburgh, PA USA. RP Rhodes, ME (reprint author), St Vincent Coll, Dept Biol, 300 Fraser Purchase Rd, Latrobe, PA 15650 USA. EM michael.rhodes@email.stvincent.edu FU NIMH NIH HHS [MH28380] NR 48 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 2008 VL 20 IS 5 BP 617 EP 625 DI 10.1111/j.1365-2826.2008.01700.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 289FR UT WOS:000255040900009 PM 18363805 ER PT J AU Olausson, KH Learner, E Ligon, KL AF Olausson, Karl Holmberg Learner, Emily Ligon, Keith Lloyd TI CD133 RNA expression marks a rare and widely distributed cell population in the adult mouse brain SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 84th Annual Meeting of the American-Association-of-Neuropathologists CY APR 04-07, 2008 CL San Diego, CA SP Amer Assoc Neuropathologists C1 [Olausson, Karl Holmberg; Learner, Emily] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ligon, Keith Lloyd] Harvard Univ, Sch Med, Boston, MA USA. [Ligon, Keith Lloyd] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2008 VL 67 IS 5 BP 490 EP 490 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 294YN UT WOS:000255442300027 ER PT J AU Frosch, MP Prada, CM Garci-Alloza, M Betensky, RA Bacskai, BJ Greenberg, SM Kubik, CS AF Frosch, Matthew P. Prada, Claudia M. Garci-Alloza, Monica Betensky, Rebecca A. Bacskai, Brian J. Greenberg, Steven M. Kubik, C. S. TI Effect of gelsolin on cerebral amyloid angiopathy (CAA) in transgenic mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 84th Annual Meeting of the American-Association-of-Neuropathologists CY APR 04-07, 2008 CL San Diego, CA SP Amer Assoc Neuropathologists C1 [Frosch, Matthew P.; Kubik, C. S.] Mass Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA USA. [Frosch, Matthew P.; Prada, Claudia M.; Garci-Alloza, Monica; Bacskai, Brian J.; Greenberg, Steven M.] Mass Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2008 VL 67 IS 5 BP 494 EP 494 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 294YN UT WOS:000255442300046 ER PT J AU Yip, S Cahill, DP Louis, DN AF Yip, Stephen Cahill, Daniel P. Louis, David N. TI Mismatch repair defects underlying temozolomide chemoresistance in recurrent glioblastomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 84th Annual Meeting of the American-Association-of-Neuropathologists CY APR 04-07, 2008 CL San Diego, CA SP Amer Assoc Neuropathologists C1 [Yip, Stephen; Cahill, Daniel P.; Louis, David N.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2008 VL 67 IS 5 BP 495 EP 496 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 294YN UT WOS:000255442300053 ER PT J AU Snuderl, M Chi, SN DeSantis, S Stemmer-Rachamimov, A Betensky, RA DeGirolami, U Kieran, MW AF Snuderl, Matija Chi, Susan N. DeSantis, Stacia Stemmer-Rachamimov, Anat Betensky, Rebecca A. DeGirolami, Umberto Kieran, Mark W. TI Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 84th Annual Meeting of the American-Association-of-Neuropathologists CY APR 04-07, 2008 CL San Diego, CA SP Amer Assoc Neuropathologists C1 [Snuderl, Matija; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chi, Susan N.; Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [DeSantis, Stacia; Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [DeGirolami, Umberto] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2008 VL 67 IS 5 BP 502 EP 502 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 294YN UT WOS:000255442300083 ER PT J AU Lawlor, MW Roumm, E DeChene, ET Geggel, A Moghadasadeh, B Beggs, AH AF Lawlor, Michael William Roumm, Emily DeChene, Elizabeth Taylor Geggel, Amelia Moghadasadeh, Behzad Beggs, Alan H. TI Morphologic assessment of muscle biopsy abnormalities in patients with congenital fiber type disproportion and tropomyosin 3 mutation SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 84th Annual Meeting of the American-Association-of-Neuropathologists CY APR 04-07, 2008 CL San Diego, CA SP Amer Assoc Neuropathol C1 [Lawlor, Michael William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lawlor, Michael William; Roumm, Emily; Moghadasadeh, Behzad; Beggs, Alan H.] Harvard Med Sch, Boston, MA USA. [DeChene, Elizabeth Taylor; Geggel, Amelia; Moghadasadeh, Behzad; Beggs, Alan H.] Childrens Hosp, Program Gen, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2008 VL 67 IS 5 BP 520 EP 520 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 294YN UT WOS:000255442300164 ER PT J AU Smith, ZM Delgutte, B AF Smith, Zachary M. Delgutte, Bertrand TI Sensitivity of inferior colliculus neurons to interaural time differences in the envelope versus the fine structure with bilateral cochlear implants SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID AMPLITUDE-MODULATED TONES; MEDIAL SUPERIOR OLIVE; STIMULATED AUDITORY-NERVE; HIGH-FREQUENCY NEURONS; ELECTRICAL-STIMULATION; SOUND LOCALIZATION; LEVEL DIFFERENCE; UNANESTHETIZED RABBIT; BINAURAL INTERACTION; EXCITATION PATTERNS AB Bilateral cochlear implantation seeks to improve hearing by taking advantage of the binaural processing of the central auditory system. Cochlear implants typically encode sound in each spectral channel by amplitude modulating (AM) a fixed-rate pulse train, thus interaural time differences (ITD) are only delivered in the envelope. We investigated the ITD sensitivity of inferior colliculus (IC) neurons with sinusoidally AM pulse trains. ITD was introduced independently to the AM and/or carrier pulses to measure the relative efficacy of envelope and fine structure for delivering ITD information. We found that many IC cells are sensitive to ITD in both the envelope (ITDenv) and fine structure (ITDfs) for appropriate modulation frequencies and carrier rates. ITDenv sensitivity was generally similar to that seen in normal-hearing animals with AM tones. ITDenv tuning generally improved with increasing modulation frequency up to the maximum modulation frequency that elicited a sustained response in a neuron (tested <= 160 Hz). ITDfs sensitivity was present in about half the neurons for 1,000 pulse/s (pps) carriers and was nonexistent at 5,000 pps. The neurons that were sensitive to ITDfs at 1,000 pps were those that showed the best ITD sensitivity to low-rate pulse trains. Overall, the best ITD sensitivity was found for ITD contained in the fine structure of a moderate rate AM pulse train (1,000 pps). These results suggest that the interaural timing of current pulses should be accurately controlled in a bilateral cochlear implant processing strategy that provides salient ITD cues. C1 [Smith, Zachary M.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Smith, Zachary M.; Delgutte, Bertrand] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Smith, Zachary M.] Cochlear Americas, Res & Applicat, Englewood, CO 80112 USA. RP Smith, ZM (reprint author), Cochlear Americas, Res & Applicat, 400 Inverness Pkwy,Suite 400, Englewood, CO 80112 USA. EM zsmith@alum.mit.edu RI Smith, Zachary/B-2879-2009; OI Smith, Zachary/0000-0002-0819-4562; , /0000-0003-1349-9608 FU NIDCD NIH HHS [T32 DC000038, T32 DC 00038, R01 DC005775-05, P30 DC005209, P30 DC 005209, R01 DC005775, R01 DC 005775] NR 75 TC 13 Z9 14 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2008 VL 99 IS 5 BP 2390 EP 2407 DI 10.1152/jn.00751.2007 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 300GE UT WOS:000255811500030 PM 18287556 ER PT J AU Vierling-Claassen, D Siekmeier, P Stufflebeam, S Kopell, N AF Vierling-Claassen, Dorea Siekmeier, Peter Stufflebeam, Steven Kopell, Nancy TI Modeling GABA alterations in schizophrenia: A link between impaired inhibition and altered gamma and beta range auditory entrainment SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RAT SOMATOSENSORY CORTEX; PREFRONTAL CORTEX; NEOCORTICAL NEURONS; PYRAMIDAL NEURONS; CORTICAL-NEURONS; NEURAL SYNCHRONY; GENE-EXPRESSION; AXON TERMINALS; VISUAL-CORTEX; EEG COHERENCE AB The disorganized symptoms of schizophrenia, including severely disordered thought patterns, may be indicative of a problem with the construction and maintenance of cell assemblies during sensory processing and attention. The gamma and beta frequency bands (15-70 Hz) are believed relevant to such processing. This paper addresses the results of an experimental examination of the cortical response of 12 schizophrenia patients and 12 control subjects when presented with auditory click-train stimuli in the gamma/beta frequency band during measurement using magnetoencephalography (MEG), as well as earlier work by Kwon et al. These data indicate that control subjects show an increased 40-Hz response to both 20-and 40-Hz stimulation as compared with patients, whereas schizophrenic subjects show a preference for 20-Hz response to the same driving frequencies. In this work, two computational models of the auditory cortex are constructed based on postmortem studies that indicate cortical interneurons in schizophrenic subjects have decreased GAT-1 (a GABA transporter) and GAD 67 (1 of 2 enzymes responsible for GABA synthesis). The models transition from control to schizophrenic frequency response when an extended inhibitory decay time is introduced; this change captures a possible effect of these GABA alterations. Modeling gamma/beta range auditory entrainment in schizophrenia provides insight into how biophysical mechanisms can impact cognitive function. In addition, the study of dynamics that underlie auditory entrainment in schizophrenia may contribute to the understanding of how gamma and beta rhythms impact cognition in general. C1 [Vierling-Claassen, Dorea; Kopell, Nancy] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA. [Siekmeier, Peter] Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02178 USA. [Vierling-Claassen, Dorea; Stufflebeam, Steven] Massachusetts Gen Hosp, Ahinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Vierling-Claassen, Dorea; Kopell, Nancy] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Vierling-Claassen, D (reprint author), Boston Univ, Dept Math, Boston, MA 02215 USA. EM dorea@math.bu.edu FU NCRR NIH HHS [P41 RR 14075, P41 RR014075]; NICHD NIH HHS [R01 HD 040712, R01 HD040712]; NIMH NIH HHS [5K08 MH 067966, K08 MH067966, K08 MH072771, K08 MH072771-02, P50 MH 060450, P50 MH060450] NR 82 TC 78 Z9 79 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2008 VL 99 IS 5 BP 2656 EP 2671 DI 10.1152/jn.00870.2007 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 300GE UT WOS:000255811500050 PM 18287555 ER PT J AU Czanner, G Eden, UT Wirth, S Yanike, M Suzuki, WA Brown, EN AF Czanner, Gabriela Eden, Uri T. Wirth, Sylvia Yanike, Marianna Suzuki, Wendy A. Brown, Emery N. TI Analysis of between-trial and within-trial neural spiking dynamics SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RECEPTIVE-FIELD PLASTICITY; GOAL-DIRECTED MOVEMENTS; TRAIN DATA-ANALYSIS; BEHAVIORAL-EXPERIMENTS; MAXIMUM-LIKELIHOOD; SINGLE NEURONS; FIRING PATTERNS; POINT-PROCESSES; HIPPOCAMPUS; MODELS AB Recording single-neuron activity from a specific brain region across multiple trials in response to the same stimulus or execution of the same behavioral task is a common neurophysiology protocol. The raster plots of the spike trains often show strong between-trial and within-trial dynamics, yet the standard analysis of these data with the peristimulus time histogram (PSTH) and ANOVA do not consider between-trial dynamics. By itself, the PSTH does not provide a framework for statistical inference. We present a state-space generalized linear model (SS-GLM) to formulate a point process representation of between-trial and within-trial neural spiking dynamics. Our model has the PSTH as a special case. We provide a framework for model estimation, model selection, goodness-of-fit analysis, and inference. In an analysis of hippocampal neural activity recorded from a monkey performing a location-scene association task, we demonstrate how the SS-GLM may be used to answer frequently posed neurophysiological questions including, What is the nature of the between-trial and within-trial task-specific modulation of the neural spiking activity? How can we characterize learning-related neural dynamics? What are the timescales and characteristics of the neuron's biophysical properties? Our results demonstrate that the SS-GLM is a more informative tool than the PSTH and ANOVA for analysis of multiple trial neural responses and that it provides a quantitative characterization of the between-trial and within-trial neural dynamics readily visible in raster plots, as well as the less apparent fast (1-10 ms), intermediate (11-20 ms), and longer (>20 ms) timescale features of the neuron's biophysical properties. C1 [Czanner, Gabriela; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Brown, Emery N.] Harvard Univ, Sch Med, Div Hlth Sci & Technol, MIT, Cambridge, MA 02138 USA. [Brown, Emery N.] Harvard Univ, MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Wirth, Sylvia] CNRS, Inst Cognit Sci, Bron, France. [Yanike, Marianna; Suzuki, Wendy A.] NYU, Ctr Neural Sci, New York, NY USA. RP Czanner, G (reprint author), Univ Warwick, WMG,IMC-368, Coventry CV4 7AL, W Midlands, England. EM g.czanner@warwick.ac.uk FU NIDA NIH HHS [DA 015644, R01 DA015644, R01 DA015644-05]; NIH HHS [DP1 OD003646]; NIMH NIH HHS [R01 MH059733-09, MH 58733, MH 58847, R01 MH058847, R01 MH059733] NR 72 TC 54 Z9 54 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2008 VL 99 IS 5 BP 2672 EP 2693 DI 10.1152/jn.00343.2007 PG 22 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 300GE UT WOS:000255811500051 PM 18216233 ER PT J AU Szentirmai, O Baker, CH Bullain, SS Lin, N Takahashi, M Folkman, J Mulligan, RC Carter, BS AF Szentirmai, Oszkar Baker, Cheryl H. Bullain, Szofia S. Lin, Ning Takahashi, Masaya Folkman, Judah Mulligan, Richard C. Carter, Bob S. TI Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2 SO JOURNAL OF NEUROSURGERY LA English DT Article DE antiangiogenesis; endostatin; gene therapy; glioblastoma multiforme; vascular endothelial growth factor ID ANTIANGIOGENIC GENE-THERAPY; HUMAN PANCREATIC-CARCINOMA; IN-VIVO; MALIGNANT GLIOMAS; BRAIN-TUMORS; FACTOR VEGF; MICROVESSEL DENSITY; ANTITUMOR-ACTIVITY; ENGINEERED CELLS; TYROSINE KINASE AB Object. Glioblastoma multiforme (GBM) is characterized by neovascularization, raising the question of whether angiogenic blockade may be a useful therapeutic strategy for this disease. It has been suggested, however, that, to be useful, angiogenic blockade must be persistent and at levels sufficient to overcome proangiogenic signals from tumor cells. In this report, the authors tested the hypothesis that sustained high concentrations of 2 different antiangiogenic proteins, delivered using a systemic gene therapy strategy, could inhibit the growth of established intracranial U87 human GBM xenografts in nude mice. Methods. Mice harboring established U87 intracranial tumors received intravenous injections of adenoviral vectors encoding either the extracellular domain of vascular endothelial growth factor receptor-2-Fc fusion protein (Ad-VEGFR2-Fc) alone, soluble endostatin (Ad-ES) alone, a combination of Ad-VEGFR2-Fc and Ad-ES, or immunoglobulin 1-Fc (Ad-Fc) as a control. Results. Three weeks after treatment, magnetic resonance imaging-based determination of tumor volume showed that treatment with Ad-VEGFR2-Fc, Ad-ES, or Ad-VEGFR2-Fc in combination with Ad-ES, produced 69, 59, and 74% growth inhibition, respectively. Bioluminescent monitoring of tumor growth revealed growth inhibition in the same treatment groups to be 62, 74, and 72%, respectively. Staining with proliferating cell nuclear antigen and with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling showed reduced tumor cell proliferation and increased apoptosis in all antiangiogenic treatment groups. Conclusions. These results suggest that systemic delivery and sustained production of endostatin and soluble VEGFR2 can slow intracranial glial tumor growth by both reducing cell proliferation and increasing tumor apoptosis. This work adds further support to the concept of using antiangiogenesis therapy for intracranial GBM. C1 Harvard Univ, Inst Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Carter, Bob S.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. [Takahashi, Masaya] Harvard Univ, Beth Israel Med Ctr, Inst Med, Dept Radiol, Boston, MA USA. [Folkman, Judah] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Carter, BS (reprint author), Massachusetts Gen Hosp, Neurol Serv, Yawkey 9026, Boston, MA 02114 USA. EM bcarter@partners.org FU NCI NIH HHS [K08 CA082773, K08 CA082773-01A1] NR 92 TC 18 Z9 19 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2008 VL 108 IS 5 BP 979 EP 988 DI 10.3171/JNS/2008/108/5/0979 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 293RE UT WOS:000255351600012 PM 18447716 ER PT J AU Chang, K Jaffer, F AF Chang, Kiyuk Jaffer, Farouc TI Advances in fluorescence imaging of the cardiovascular system SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID TIME FLOW MEASUREMENT; IN-VIVO; MYOCARDIAL-INFARCTION; CHEMOATTRACTANT PROTEIN-1; ATHEROSCLEROTIC PLAQUES; INDOCYANINE GREEN; PROTEASE ACTIVITY; CARDIAC RUPTURE; BYPASS GRAFTS; CORONARY C1 [Chang, Kiyuk; Jaffer, Farouc] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Chang, Kiyuk; Jaffer, Farouc] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02129 USA. [Jaffer, Farouc] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Jaffer, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St,Room 4220, Boston, MA 02129 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU Howard Hughes Medical Institute NR 69 TC 13 Z9 13 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD MAY-JUN PY 2008 VL 15 IS 3 BP 417 EP 428 DI 10.1016/j.nuclcard.2008.03.001 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 308KR UT WOS:000256389300016 PM 18513648 ER PT J AU Dewsnup, NC Susarla, SM Paquin, WC Faquin, WC Kaban, LB August, M AF Dewsnup, Nathan C. Susarla, Srinivas M. Abulikemu, Mailikai Faquin, William C. Kaban, Leonard B. August, Meredith TI Immunohistochemical evaluation of giant cell tumors of the jaws using CD34 density analysis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ANTIANGIOGENIC THERAPY; INFANTILE HEMANGIOMAS; INTERFERON ALPHA-2A; GRANULOMA; LESIONS AB Purpose: To compare CD34 expression in both aggressive and nonaggressive giant cell lesions of the jaws and identify any associations between tumor vascular density and biologic behavior. Materials and Methods: This was a retrospective study of subjects treated for giant cell lesions of the jaws at Massachusetts General Hospital from 1992 to 2006. The primary predictor variable was tumor classification (aggressive or nonaggressive); tumors were considered aggressive if they were greater than 5 cm in size, recurred after treatment, or exhibited 3 of the following: presence of root resorption, tooth displacement, or cortical bone thinning or perforation. Secondary predictor variables, recorded for each patient, were demographic, anatomic, and clinical measures. The outcome variable was the average CD34 staining density of histologic specimens quantified in 2 different areas. Descriptive and bivariate statistics were computed to identify predictors associated with vascular density. Results: The study sample was composed of 32 subjects with a mean age of 24.4 +/- 19.77 years (range: 2-83); 23 subjects (71.8%) were female. Of the tumors included, 11 (34.4%) were located in the maxilla, 21 (65.6%) in the mandible. Twenty-six tumors (81.2%) were classified as aggressive; the remainder (18.8%) were nonaggressive. There were no statistically significant differences between subjects with aggressive versus nonaggressive tumors with regard to age, gender, or location. Subjects with aggressive tumors had a significantly higher CD34 staining density (P = .02). None of the secondary predictors was associated with vascular density. Conclusion: Vascular density of giant cell tumors of the jaws is significantly increased in aggressive tumors. (c) 2008 American Association of Oral and Maxillofacial Surgeons. C1 [Dewsnup, Nathan C.; Faquin, William C.; Kaban, Leonard B.; August, Meredith] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Susarla, Srinivas M.; Abulikemu, Mailikai; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP August, M (reprint author), 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM maugust@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 31 TC 14 Z9 15 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2008 VL 66 IS 5 BP 928 EP 933 DI 10.1016/j.joms.2008.01.033 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 296JY UT WOS:000255540500015 PM 18423282 ER PT J AU Papadaki, ME McCain, JP Kim, K Katz, RL Kahan, LB Troulis, MJ AF Papadaki, Maria E. McCain, Joseph P. Kim, King Katz, Ronald L. Kahan, Leonard B. Troulis, Maria J. TI Interventional sialoendoscopy: Early clinical results SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID EXTRACORPOREAL SHOCKWAVE LITHOTRIPSY; LASER LITHOTRIPSY; URETERAL CALCULI; INTRACORPOREAL LITHOTRIPSY; WAVE LITHOTRIPSY; SALIVARY-GLANDS; SIALOLITHIASIS; DIAGNOSIS; MANAGEMENT; EXPERIENCE AB Purpose: Sialoendoscopy is a novel minimally invasive technique to explore the salivary duct system and to treat obstructive salivary disease. This article describes the early clinical experience with endoscopic salivary duct exploration and sialolithectomy in 2 medical centers. Patients and Methods: This is a retrospective case series of 94 patients, with submandibular (n = 77) or parotid (n = 17) sialadenitis secondary to sialotithiasis, strictures, or mucous plugs. Patients underwent sialoendoscopy at Baptist Hospital, Miami (n = 52) or at Massachusetts General Hospital, Boston (n = 42). Dilatation of the duct through the natural orifice was accomplished with salivary dilators. Three endoscope systems with diameters from 1.1 to 2.3 mm were used. Using a basket, grasper, lithotripsy, laser, or a combination of these, stones were fragmented or removed endoscopically. Strictures were dilated and mucous plugs removed. All cases were carried out under general anesthesia. Results: Salivary duct navigation was accomplished in 91/94 patients. In 3 cases, duct dilatation was not possible due to scarring. Symptomatic relief was achieved in 81/91 patients (89.4%). Strictures and mucous plugs were visualized and managed in 18/18 patients. Sialotiths were visualized in 73 patients and stone fragmentation or retrieval was accomplished in 84-93% (62/73) of cases. Complications included 2 patients with temporary lingual nerve paresthesia and 1 patient with excess extravasation of irrigation fluid. Conclusion: The results of this study indicate that interventional sialoendoscopy is an effective, minimally invasive alternative treatment for obstructive salivary gland disease. (c) 2008 American Association of Oral and Maxillofacial Surgeons. C1 [Papadaki, Maria E.] Harvard Univ, Sch Dent Med,Residency Program, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Troulis, Maria J.] Harvard Univ, Sch Dent Med,Minimally Invas Surg Program, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [McCain, Joseph P.] Nova SE Univ, Baptist Hosp, Dept Oral & Maxillofacial Surg, Residency Program, Miami, FL USA. RP Troulis, MJ (reprint author), Harvard Univ, Sch Dent Med,Residency Program, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA. EM mtroulis@partners.org NR 43 TC 27 Z9 27 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2008 VL 66 IS 5 BP 954 EP 962 DI 10.1016/j.joms.2008.01.017 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 296JY UT WOS:000255540500019 PM 18423286 ER PT J AU Lindenhovius, ALC Brouwer, KM Doornberg, JN Ring, DC Kloen, P AF Lindenhovius, Anneluuk L. C. Brouwer, Kim M. Doornberg, Job N. Ring, David C. Kloen, Peter TI Long-term outcome of operatively treated fracture-dislocations of the olecranon SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE fracture-dislocation of the olecranon; long-term outcome; elbow ID MONTEGGIA FRACTURES; RADIAL HEAD; ELBOW; ULNA AB Objectives: To report the long-term results of operative treatment of anterior and posterior olecranon fracture-dislocations and compare them with the results recorded fewer than 2 years after surgery. Design: Retrospective case series with long-term evaluation. Setting: Level I trauma center. Patients and Participants: Ten patients with anterior olecranon fracture-dislocation and ten patients with posterior olecranon fracture-dislocation were evaluated after an average of 18 years (range, 11 to 28 years) after injury. Fifteen patients had an early follow-up available at an average 14 months (range, 6 to 24 months) after surgery. The average age at injury was 30 years (range, 14 to 53 years). Intervention: Treatment included plate and screw fixation (11 patients), tension band wiring (8 patients), and radiocapitellar transfixation (1 patient). Six patients had additional elbow surgery before the final evaluation. Main Outcome Measurements: Flexion arc, arthrosis, Mayo Elbow Performance Index (MEPI), Disability of Arm Shoulder and Hand questionnaire (DASH). Results: The mean arc of elbow flexion was 105 degrees (range, 15 to 140 degrees) at 1 year and 122 degrees (range 10 to 145 degrees; P = 0.01) at final evaluation. Radiographic arthrosis was observed in 14 patients (70%): severe in 3, moderate in 2, and mild in 9 patients. Five patients (25%) had ulnar nerve dysfunction at the final evaluation. The MEPI was excellent in 13 patients, good in 4, fair in 2, and poor in 1. The mean DASH score was 9 points (range, 0 to 53 points). Conclusion: The initial results of operative treatment of fracture-dislocations of the olecranon are durable over time. C1 [Ring, David C.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Lindenhovius, Anneluuk L. C.; Brouwer, Kim M.; Doornberg, Job N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kloen, Peter] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Traumatol, NL-1105 AZ Amsterdam, Netherlands. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 24 TC 28 Z9 31 U1 0 U2 1 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 MAY-JUN PY 2008 VL 22 IS 5 BP 325 EP 331 DI 10.1097/BOT.0b013e31817283f7 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 298QA UT WOS:000255701000007 PM 18448986 ER PT J AU Nourissat, G Mudgal, CS Ring, D AF Nourissat, Geoffrey Mudgal, Chaitanya S. Ring, David TI Bridge plating of the wrist for temporary stabilization of concomitant radiocarpal, intercarpal, and carpometacarpal injuries: A report of two cases SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE bridge; span; plating; wrist; complex; radiocarpal; fractures ID EXTERNAL FIXATION; FRACTURES AB Concomitant injuries of the radiocarpal, intercarpal, and carpometacarpal joints are rare and usually result from very high-energy trauma. The skeletal injury is often accompanied by severe soft tissue trauma. Repair of the radiocarpal and intercarpal ligaments needs to be augmented with immobilization. Traditional methods of immobilization, such as casts and external fixators have limitations. We describe our experience in 2 patients using a technique in which a wrist arthrodesis plate is temporarily placed from the radius to metacarpal to span the carpus and protect the radiocarpal and intercarpal repairs. The plate is removed after 3 months. C1 [Nourissat, Geoffrey; Mudgal, Chaitanya S.; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed, Orthopaed Hand Serv, Boston, MA 02114 USA. [Mudgal, Chaitanya S.; Ring, David] Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed, Orthopaed Hand Serv, Suite 2100,Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 7 TC 1 Z9 2 U1 0 U2 0 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 MAY-JUN PY 2008 VL 22 IS 5 BP 368 EP 371 DI 10.1097/BOT.0b013e318177816d PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 298QA UT WOS:000255701000015 PM 18448994 ER PT J AU Goy, ER Carter, J Ganzini, L AF Goy, Elizabeth Ruth Carter, Julie Ganzini, Linda TI Neurologic disease at the end of life: Caregiver descriptions of Parkinson disease and amyotrophic lateral sclerosis SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PALLIATIVE CARE; MORTALITY; PROXY AB Objective: Amyotrophic lateral sclerosis (ALS) is well recognized as a terminal illness with an established need for palliative care. Parkinson's disease is a substantially more common cause of death, yet little has been written about the palliative needs of these patients at the end of life. To highlight the palliative care needs and experiences of patients with Parkinson's disease and related disorders (PDRD), we compared them to patients with ALS. Methods: Family caregivers of decedent PDRD and ALS patients in Oregon and Washington were surveyed about their loved one's symptoms, treatment preferences, health care usage, and psychosocial experiences during the last month of life. Results: Fifty-two PDRD and 50 ALS caregivers completed the survey. Overall suffering (1 = none to 6 = severe) was rated a median of 4 for both groups. Pain was moderately severe or worse in 42% of PDRD patients and 52% of ALS patients; of these, 27% of PDRD and 19% of ALS patients received no pain medication in the last month. PDRD featured more severe effects of confusion than ALS, although less dyspnea and difficulty eating. PDRD patients had significantly shorter hospice enrollments than ALS patients (p = 0.01). Conclusions: In the views of caregivers, suffering associated with ALS is no more severe than suffering associated with PDRD, and both groups appear to have unmet palliative care needs in the last months of life. Studies to define hospice readiness and special needs in hospice might improve end-of-life care for PDRD patients. C1 [Goy, Elizabeth Ruth] Portland VA Med Ctr, Dept Res Mental Hlth, Portland, OR 97207 USA. [Carter, Julie] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Ganzini, Linda] Portland VA Med Ctr, Dept Psychiat, Portland, OR 97207 USA. RP Goy, ER (reprint author), Portland VA Med Ctr, Dept Res Mental Hlth, R&D 66,3710 SW US Vet Hop Rd,POB 1034, Portland, OR 97207 USA. EM elizabeth.goy@va.gov NR 22 TC 19 Z9 19 U1 0 U2 4 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 MAY PY 2008 VL 11 IS 4 BP 548 EP 554 DI 10.1089/jpm.2007.0258 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 306IK UT WOS:000256241300005 PM 18454605 ER PT J AU Kunisaki, SM Fauza, DO Craig, N Jennings, RW AF Kunisaki, Shaun M. Fauza, Dario O. Craig, Nancy Jennings, Russett W. TI Extracorporeal membrane oxygenation as a bridge to definitive tracheal reconstruction in neonates SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Canadian-Assocaition-of-Pediatric-Surgeons CY AUG 23-26, 2007 CL St Johns Newfoundland, CANADA SP Canadian Assoc Pediat Surg DE extracorporeal membrane oxygenation; ECMO; congenital tracheal stenosis; tracheal reconstruction ID STENOSIS; MANAGEMENT; CHILDREN; SURGERY; SUPPORT; EXPERIENCE; RESECTION; REPAIR AB Purpose: Infants born with severe tracheal anomalies may not survive beyond the first few hours of life without aggressive cardiopulmonary support and/or emergent airway surgery. The purpose of this study was to review our experience with critically ill neonates supported on extracorporeal membrane oxygenation (ECMO) before tracheal reconstruction. Methods: A retrospective review of a single institution ECMO registry was conducted. Outcomes of neonates requiring tracheal repair were examined. Results: Three children with tracheal anomalies (complete tracheal rings [n = 2]; bronchogenic cyst [n = 1]) underwent definitive airway reconstruction. All were placed on ECMO (venovenous [n = 2]; venoarterial [n 1]) within 24 hours after birth. Tracheoplasties (tracheal resection with end-to-end anastomosis [n = 1]; slide tracheoplasty [n = 1]; carinal resection and reconstruction [n = 1]) were performed at 3.7 +/- 2.2 days of life. There were no hemorrhagic or thrombotic complications for an ECMO time of 117.3 +/- 60.1 hours. The postoperative durations until extubation and hospital discharge were 12.0 +/- 3.2 and 34.3 +/- 11.6 days, respectively. All children remain alive and well without cardiopulmonary and neurologic sequelae at a mean follow-up of 4.5 years. Conclusions: Excellent clinical outcomes can be achieved in neonates born with severe tracheal anomalies using ECMO as a bridge to definitive tracheal reconstruction. Published by Elsevier Inc. C1 [Kunisaki, Shaun M.; Fauza, Dario O.; Craig, Nancy; Jennings, Russett W.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Kunisaki, SM (reprint author), Massachusetts Gen Hosp, Surg HST, GRB 425, Boston, MA 02114 USA. EM skunisaki@partners.org NR 18 TC 7 Z9 8 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAY PY 2008 VL 43 IS 5 BP 800 EP 804 DI 10.1016/j.jpedsurg.2007.12.014 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 310SU UT WOS:000256551300005 PM 18485942 ER PT J AU Kamath, BD Box, TL Simpson, M Hernandez, JA AF Kamath, B. D. Box, T. L. Simpson, M. Hernandez, J. A. TI Infants born at the threshold of viability in relation to neonatal mortality: Colorado, 1991 to 2003 SO JOURNAL OF PERINATOLOGY LA English DT Article DE neonatal mortality rate; threshold of viability; regionalization; ELBW infants; prematurity ID LOW-BIRTH-WEIGHT; PERINATAL-CARE; REGIONALIZATION; SURFACTANT AB Objective: To determine the contribution of infants born at the threshold of viability (defined as <750 g birth weight) and the role of regionalization of perinatal care on the neonatal mortality rate (NMR) in Colorado. Study Design: We performed a retrospective cohort study, evaluating all live births in Colorado from 1991 to 2003, and comparing the periods 1991 to 1996 versus 1997 to 2003. Result: The overall unadjusted NMR of the two time periods was 4.3 and 4.4 per 1000 live births, respectively (P=0.42). The contribution of infants with birth weights <750 g to the overall NMR increased from 45.0 to 54.5% (P<0.01). The odds of death for infants <750 g increased between time periods (Odd ratio 1.3, 95% Confidence interval 1.11, 1.61). However, NMR decreased between time periods for all birth weight categories, until infants <600 g. With respect to regionalization, the number of infants <750 g born in a level III care center increased slightly between the two time periods (69.6 versus 73.3%; P=0.04); however, adjusted analysis showed no difference in the practice of regionalization between time periods. Regardless of time period, infants who weighed <750 g born in a level III center had 60% lower mortality risk when compared to <750 g infants born in a non-level III center (P<0.01; 95% CI 0.30, 0.52). Conclusion: Despite advances in neonatal medicine, the overall NMR in the state of Colorado remained unchanged between the time periods of 1991 to 1996 and 1997 to 2003. Infants at the threshold of viability continue to have a large impact on the Colorado NMR, making up a larger proportion of overall neonatal deaths. While the results demonstrate that the risk of mortality is significantly reduced for <750 g infants born in a level III center, the practice of regionalization has not changed between the two time periods. Improved efforts to standardize the referral practices to ensure delivery of <750 g infants in level III centers could potentially reduce the impact of these infants on the NMR. While the overall NMR in Colorado has not changed between the two time periods, the NMR for infants >600 g has significantly decreased, suggesting that the boundary delineating the threshold of viability needs reevaluation, as it may have been pushed lower than previously defined. C1 [Kamath, B. D.] Univ Colorado, Dept Pediat, Sect Neonatol, Denver, CO 80045 USA. [Box, T. L.] Denver VA Med Ctr, Eastern Colorado Hlth Care Syst, Denver, CO USA. [Simpson, M.] Univ Colorado, Dept Epidemiol, Denver, CO 80045 USA. [Hernandez, J. A.] Childrens Hosp, Hlth Sci Ctr, Denver, CO 80218 USA. RP Kamath, BD (reprint author), Univ Colorado, Dept Pediat, Sect Neonatol, Mail Stop 8402,Educ 2 S,Box 6508,13121 E 17th Ave, Denver, CO 80045 USA. EM Beena.Kamath@uchsc.edu OI Kamath-Rayne, Beena/0000-0002-8482-4802 FU NICHD NIH HHS [T32 HD007186] NR 21 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD MAY PY 2008 VL 28 IS 5 BP 354 EP 360 DI 10.1038/sj.jp.7211918 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 294MZ UT WOS:000255411500008 PM 18273030 ER PT J AU Teles, RP Patel, M Socransky, SS Haffajee, AD AF Teles, R. P. Patel, M. Socransky, S. S. Haffajee, A. D. TI Disease progression in periodontally healthy and maintenance subjects SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE bacteria; biofilm; gingivitis; health; maintenance; periodontitis ID PROBING ATTACHMENT LOSS; LONG-TERM; TOOTH LOSS; CLINICAL CHARACTERISTICS; GINGIVAL RECESSION; THERAPY; PREVALENCE; PLAQUE; SITES; CARE AB Background: The aim of this study was to determine whether the rate of attachment loss in periodontally healthy subjects in a prevention regimen would differ from the rate of disease progression in periodontitis subjects enrolled in a maintenance program. Methods: Fifty-five periodontally healthy subjects and 57 periodontitis subjects were clinically and microbiologically monitored at baseline and at 1, 2, and 3 years. Clinical parameters measured at six sites per tooth included bleeding on probing, visible plaque, probing depth, and attachment level. Subgingival plaque samples were taken from the mesiobuccal aspect of every tooth and were analyzed for the levels of 40 bacterial species using checkerboard DNA-DNA hybridization. The significance of differences over time in the clinical parameters was determined using repeated-measures analysis of variance, whereas the significance of differences between groups was determined using the unpaired t test. The Mann-Whitney test was used for microbial analyses, and P values were adjusted for multiple comparisons. Results: Mean clinical parameters improved for both groups over time. By the end of the study, 4% of the sites in maintenance subjects lost >= 2 mm of attachment, whereas in the prophylaxis subjects only 1% of the sites lost >= 2 mm of attachment. Maintenance subjects lost attachment primarily at shallow buccal and lingual sites. The maintenance subjects harbored significantly higher levels of most test species throughout the study. The maintenance program did not reduce the levels of red complex species to those typical of healthy subjects. Conclusions: Treated periodontitis subjects under maintenance displayed more rapid attachment loss than periodontally healthy subjects in a preventive regimen. The greater propensity to disease progression may be related to an elevated exposure to periodontal pathogens. C1 [Teles, R. P.; Patel, M.; Socransky, S. S.; Haffajee, A. D.] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Teles, RP (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM rteles@forsyth.org FU NIDCR NIH HHS [DE 014242, DE 016700, DE 012861] NR 26 TC 20 Z9 21 U1 0 U2 3 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 2008 VL 79 IS 5 BP 784 EP 794 DI 10.1902/jop.2008.070485 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 302IH UT WOS:000255961500004 PM 18454656 ER PT J AU Bogren, A Teles, RP Torresyap, G Haffajee, AD Socransky, SS Wennstrom, JL AF Bogren, Anna Teles, Ricardo P. Torresyap, Gay Haffajee, Anne D. Socransky, Sigmund S. Wennstrom, Jan L. TI Locally delivered doxycycline during supportive periodontal therapy: A 3-year study SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE doxycycline; periodontitis; randomized controlled trial ID SUPRAGINGIVAL PLAQUE CONTROL; PROBING ATTACHMENT LOSS; DNA-DNA HYBRIDIZATION; MINOCYCLINE MICROSPHERES; SUBGINGIVAL MINOCYCLINE; CONTROLLED MULTICENTER; ADULT PERIODONTITIS; MAINTENANCE; DISEASE; TETRACYCLINE AB Background: Adjunctive locally delivered antibiotics during maintenance may favor the control of periodontal infections. This study evaluated the long-term clinical and microbiologic effects of yearly locally delivered controlled-release doxycycline as an adjunct to mechanical debridement. Methods: A total of 128 periodontal maintenance patients having at least four teeth with probing depth (PD) >= 5 mm were randomly assigned to local application of doxycycline gel at baseline and 1 and 2 years as an adjunct to mechanical debridement (test) or mechanical debridement only (control). Supportive periodontal therapy (mechanical debridement, polishing, and oral hygiene reinforcement) was provided every 6 months. Plaque, bleeding on probing (BOP), PD, and relative attachment level (RAL) were scored at baseline; 3 months; and 1, 2, and 3 years. Subgingival plaque samples were taken at each examination and analyzed for their content of 40 bacterial species. Data analyses were performed on an intention-to-treat basis with the subject as the statistical unit. Results: Significant reductions in BOP, PD, RAL, and the mean counts of a number of target species between baseline and 3 years were documented for both treatment groups, whereas plaque scores remained unchanged. A statistically significant difference in favor of the adjunctive doxycycline therapy was found between the two groups only at the 3-month examination for BOP, PD, and RAL and for a minority of bacterial species at 2 years. Conclusion: Although short-term effects on clinical parameters were found with the adjunctive use of locally delivered doxycycline, repeated applications annually had no clinical or microbiologic effects beyond those observed with mechanical debridement alone in maintenance patients. C1 [Bogren, Anna; Wennstrom, Jan L.] Univ Gothenburg, Sahlgrenska Acad, Dept Periodontol, Inst Odontol, SE-40530 Gothenburg, Sweden. [Teles, Ricardo P.; Torresyap, Gay; Haffajee, Anne D.; Socransky, Sigmund S.] Forsyth Inst, Boston, MA USA. RP Bogren, A (reprint author), Univ Gothenburg, Sahlgrenska Acad, Dept Periodontol, Inst Odontol, Box 450, SE-40530 Gothenburg, Sweden. EM anna.bogren@odontologi.gu.se FU NIDCR NIH HHS [DE 12861] NR 28 TC 18 Z9 20 U1 1 U2 3 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 2008 VL 79 IS 5 BP 827 EP 835 DI 10.1902/jop.2008.070515 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 302IH UT WOS:000255961500009 PM 18454661 ER PT J AU Tarica, DY Brajevic, FJ AF Tarica, Diane Yoshinobu Brajevic, Frank J. TI Duplication of an existing implant-supported bar for an auricular prosthesis SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID OSSEOINTEGRATED IMPLANTS; FACIAL PROSTHESES; RETENTION; CONSTRUCTION C1 [Tarica, Diane Yoshinobu; Brajevic, Frank J.] Vet Adm Greater Los Angeles Healthcare Syst, Dent Dept 160, Los Angeles, CA 90073 USA. RP Tarica, DY (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Dent Dept 160, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dctarica@earthlink.net NR 17 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD MAY PY 2008 VL 99 IS 5 BP 408 EP 409 DI 10.1016/S0022-3913(08)60092-X PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 303IR UT WOS:000256034700011 PM 18456053 ER PT J AU Marina, O Biernacki, MA Brusic, V Wu, CJ AF Marina, Ovidiu Biernacki, Melinda A. Brusic, Vladimir Wu, Catherine J. TI A concentration-dependent analysis method for high density protein microarrays SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE immune responses; proteomic; protein microarray; antigen identification; ProtoArray ID BIOMARKER DISCOVERY; IDENTIFICATION; NORMALIZATION; INFORMATION; EXPRESSION; PROTEOMICS; RESPONSES; PLATFORM; GENE; CHIP AB Protein microarray technology is rapidly growing and has the potential to accelerate the discovery of targets of serum antibody responses in cancer, autoimmunity and infectious disease. Analytical tools for interpreting this high-throughput array data, however, are not well-established. We developed a concentration-dependent analysis (CDA) method which normalizes protein microarray data based on the concentration of spotted probes. We show that this analysis samples a data space that is complementary to other commonly employed analyses, and demonstrate experimental validation of 92% of hits identified by the intersection of CDA with other tools. These data support the use of CDA either as a preprocessing step for a more complete proteomic microarray data analysis or as a stand-alone analysis method. C1 [Marina, Ovidiu; Brusic, Vladimir; Wu, Catherine J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Biernacki, Melinda A.] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. [Wu, Catherine J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Marina, Ovidiu] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Room 416,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org FU Howard Hughes Medical Institute; NCI NIH HHS [5R21CA115043-2] NR 36 TC 14 Z9 14 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAY PY 2008 VL 7 IS 5 BP 2059 EP 2068 DI 10.1021/pr700892h PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 296CD UT WOS:000255520200026 PM 18393456 ER PT J AU Sachs, GS AF Sachs, Gary S. TI Psychosocial interventions as adjunctive therapy for bipolar disorder SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE psychosocial interventions; bipolar disorder; relapse prevention; cognitive-behavioral therapy (CBT); family-focused therapy (FFT); interpersonal and social rhythm therapy (IPSRT); systematic care management ID RANDOMIZED CONTROLLED-TRIAL; FAMILY-FOCUSED TREATMENT; COGNITIVE THERAPY; GROUP PSYCHOEDUCATION; RELAPSE PREVENTION; CARE PROGRAM; EFFICACY; PSYCHOTHERAPY; DEPRESSION; PHARMACOTHERAPY AB Evidence suggests that adjunctive psychosocial interventions in bipolar disorder are clinically beneficial and cost effective when used in conjunction with pharmacotherapy. Appropriate adjunctive psychosocial interventions in bipolar disorder have been found to be associated with improved treatment adherence, greater stability, fewer hospitalizations, fewer days hospitalized, less need for crisis interventions, decreased relapse risk, and fewer acute episodes. Specific types of therapy that have shown efficacy include bipolar-specific cognitive-behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, and systematic care management. A positive impact on medication adherence is a major goal of these adjunctive treatments. Studies show variable efficacy depending on patient characteristics, phase of illness, and presence of comorbid conditions so that therapies should be selected and administered on an individualized basis that takes into account each specific patient's current presentation and treatment history. For example, psychosocial interventions have been found to be more effective in patients with depressive than manic symptoms and during maintenance treatment. Given findings showing benefits of psychosocial interventions in the treatment of bipolar disorder, the STAndards for BipoLar Excellence (STABLE) project has developed and tested a performance measure to evaluate the use of this critical treatment component. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, Boston, MA 02114 USA. RP Sachs, GS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, Boston, MA 02114 USA. EM gsachs@partners.org NR 30 TC 9 Z9 9 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAY PY 2008 VL 14 SU 2 BP 39 EP 44 DI 10.1097/01.pra.0000320125.99423.b7 PG 6 WC Psychiatry SC Psychiatry GA 311RT UT WOS:000256618000005 PM 18677198 ER PT J AU Bjorgvinsson, T Wetterneck, CT Powell, DM Chasson, GS Webb, SA Hart, J Heffelfinger, S Azzouz, R Entricht, TL Davidson, JE Stanley, MA AF Bjorgvinsson, Throstur Wetterneck, Chad T. Powell, Dana M. Chasson, Gregory S. Webb, Sarah A. Hart, John Heffelfinger, Susan Azzouz, Renee Entricht, Terri L. Davidson, Joyce E. Stanley, Melinda A. TI Treatment outcome for adolescent obsessive-compulsive disorder in a specialized hospital setting SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE obsessive-compulsive disorder; cognitive-behavior therapy; treatment resistance; treatment effectiveness; inpatient; exposure and response prevention; Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS); Reynolds Adolescent Depression Scale, 2nd edition (RADS-2); State-Trait Anxiety Inventory (STAI); Thought Action Fusion Scale-Revised (TAF-R); the Intolerance of Uncertainty Scale (IUS-12); Obsessional Belief Questionnaire (OBQ-44) ID THOUGHT-ACTION FUSION; INTRUSIONS INVENTORY; PSYCHOMETRIC VALIDATION; BELIEFS QUESTIONNAIRE; SCALE; SYMPTOMS; EPIDEMIOLOGY; RELIABILITY; VALIDITY; VERSION AB Although few data are available concerning adolescents with obsessive-compulsive disorder (OCD), the existing literature suggests that cognitive-behavioral therapy (CBT) is the first-line treatment of choice for adolescents with mild to moderate OCD. A combination of CBT and serotonin reuptake inhibitors (SRIs) is recommended for more severe forms of OCD, based on the Expert Consensus Guidelines for the Treatment of Obsessive-Compulsive Disorder and the Pediatric OCD Treatment Study (POTS). Despite the effectiveness of CBT, a recent meta-analysis found that 27% of adolescent outpatients fail to show clinically significant improvement following CBT and many also fail to show improvement with pharmacotherapy. One alternative for those who do not improve with outpatient treatment is an intensive inpatient program. Within the last 10 years, two specialty hospitals have created programs that provide intensive CBT milieu treatment with multidisciplinary support (e.g., nursing, psychopharmacology) to treat adolescents with OCD. This naturalistic study describes treatment outcomes in 23 patients who received treatment in one of these programs between 2005 and 2006. Results suggest significant improvements on the majority of outcome measures, with 70% of the patients judged to meet criteria for clinically significant change. Thus, inpatient treatment appears potentially efficacious, although future controlled trials with larger samples are needed. C1 [Bjorgvinsson, Throstur; Powell, Dana M.; Chasson, Gregory S.; Hart, John; Heffelfinger, Susan; Azzouz, Renee; Entricht, Terri L.; Davidson, Joyce E.] Menninger Clin, Houston, TX 77080 USA. [Bjorgvinsson, Throstur; Powell, Dana M.; Heffelfinger, Susan; Davidson, Joyce E.; Stanley, Melinda A.] Baylor Coll Med, Houston, TX 77030 USA. [Stanley, Melinda A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Bjorgvinsson, T (reprint author), Menninger Clin, 2801 Gessner Rd, Houston, TX 77080 USA. EM tbjorgvinsson@menninger.edu OI Barrera, Terri/0000-0003-0854-4216 NR 38 TC 19 Z9 19 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAY PY 2008 VL 14 IS 3 BP 137 EP 145 PG 9 WC Psychiatry SC Psychiatry GA 310IS UT WOS:000256522700002 PM 18520782 ER PT J AU Kraus, CA Seignourel, P Balasubramanyam, V Snow, AL Wilson, NL Kunik, ME Schulz, PE Stanley, MA AF Kraus, Cynthia A. Seignourel, Paul Balasubramanyam, Valli Snow, A. Lynn Wilson, Nancy L. Kunik, Mark E. Schulz, Paul E. Stanley, Melinda A. TI Cognitive-behavioral treatment for anxiety in patients with dementia: two case studies SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE dementia; anxiety; cognitive-behavioral therapy; caregivers; collaterals ID CONTROLLED CLINICAL-TRIAL; ALZHEIMERS-DISEASE; PRIMARY-CARE; MAJOR DEPRESSION; NURSING-HOME; OLDER-ADULTS; DISORDER; INTERVENTION; MANAGEMENT; THERAPY AB Anxiety is common in dementia and is associated with decreased independence and increased risk of nursing home placement. However, little is known about the treatment of anxiety in dementia. This article reports results from two patients who were treated with a modified version of cognitive-behavioral therapy for anxiety in dementia (CBT-AD). Modifications were made in the content, structure, and learning strategies of CBT to adapt skills to the cognitive limitations of these patients and include collaterals (i.e., family members, friends, or other caregivers) in the treatment process. The patients received education and awareness training and were taught the skills of diaphragmatic breathing, coping self-statements, exposure, and behavioral activation. The Clinical Dementia Rating (CDR) Scale was used to characterize dementia severity and determine eligibility for treatment (a CDR score of 0.5 to 2.0 was required for participation). Other measures included the Rating Anxiety in Dementia scale, the Neuropsychiatric Inventory Anxiety subscale, and the Mini International Neuropsychiatric Interview. Outcome data showed improvement in anxiety as measured by standardized rating scales. We conclude that CBT AD is potentially useful in treating anxiety in dementia patients and that this technique merits further study. C1 [Wilson, Nancy L.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Seignourel, Paul] Univ Texas Houston, Sch Med, Houston, TX USA. [Snow, A. Lynn] Univ Alabama, Tuscaloosa Vet Affairs Med Ctr, Tuscaloosa, AL 35487 USA. [Snow, A. Lynn] VA S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Wilson, Nancy L.] Baylor Coll Med, Houston, TX 77030 USA. [Stanley, Melinda A.] Michael E DeBakey Vet Affairs Med Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX USA. RP Stanley, MA (reprint author), Michael E DeBakey VAMC 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mstanley@bcm.tmc.edu FU NIMH NIH HHS [R34 MH078925, R34 MH078925-01A1, R34 MH078925-02]; PHS HHS [53932] NR 41 TC 21 Z9 22 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1527-4160 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD MAY PY 2008 VL 14 IS 3 BP 186 EP 192 DI 10.1097/01.pra.0000320120.68928.e5 PG 7 WC Psychiatry SC Psychiatry GA 310IS UT WOS:000256522700010 PM 18520790 ER PT J AU Sacks, MB Flood, AM Dennis, MF Hertzberg, MA Beckham, JC AF Sacks, Matthew B. Flood, Amanda M. Dennis, Michelle F. Hertzberg, Michael A. Beckham, Jean C. TI Self-mutilative behaviors in male veterans with posttraumatic stress disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE self-mutilation; self-injury; posttraumatic stress disorder; male veterans ID BORDERLINE PERSONALITY-DISORDER; SUICIDAL-BEHAVIOR; RISK-FACTORS; DRUG-DEPENDENCE; MENTAL-HEALTH; SKIN-PICKING; HARM; PTSD; POPULATION; PREVALENCE AB Self-mutilative behaviors (SMB) were examined in a sample of male veterans with posttraumatic stress disorder (PTSD). The primary objective was to determine the prevalence of SMB and any physical, cognitive, or affective antecedents and correlates for these behaviors. Participants included 509 male veterans with PTSD and levels of PTSD, depression, alcohol use, hostility, and impulsivity were evaluated to determine if these variables were related to SMB. Antecedents and sequelae of SMB were also examined to generate hypotheses regarding the functions of these behaviors. A second type of habit behavior, body-focused repetitive behaviors (BFRB), was also examined as part of the study. Findings indicated that veterans who engaged in either type of habit behavior were younger than those who did not engage in SMB or BFRB. Veterans reporting SMB also reported higher levels of PTSD, depression, hostility, and impulsivity compared to the BFRB and no-habit groups. Examination of habit antecedents and sequelae showed support for the automatic-positive reinforcement function of SMB. These findings are discussed in the context of research and treatment involving male veterans with PTSD who engage in SMB. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Hertzberg, Michael A.; Beckham, Jean C.] Durham Vet Affairs Med Ctr, Durham, NC 27705 USA. [Sacks, Matthew B.] San Francisco VA Med Ctr, San Francisco, CA USA. [Flood, Amanda M.; Dennis, Michelle F.; Hertzberg, Michael A.; Beckham, Jean C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Beckham, Jean C.] MIRECC, VA Mid Atlantic Reg, Durham, NC USA. RP Beckham, JC (reprint author), Durham Vet Affairs Med Ctr, 116B,508 Fulton St, Durham, NC 27705 USA. EM beckham@duke.edu FU NCI NIH HHS [2R01CA081595, R01 CA081595, R01 CA081595-06]; NIDA NIH HHS [R21 DA019704, R21DA019704, K24 DA016388, K24 DA016388-05, R21 DA019704-02, K24DA016388]; NIMH NIH HHS [R01 MH062482-04, R01 MH062482, R01MH62482] NR 58 TC 27 Z9 27 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAY PY 2008 VL 42 IS 6 BP 487 EP 494 DI 10.1016/j.jpsychires.2007.05.001 PG 8 WC Psychiatry SC Psychiatry GA 284QG UT WOS:000254720300008 PM 17606271 ER PT J AU Brunet, A Orr, SP Tremblay, J Robertson, K Nader, K Pitman, RK AF Brunet, Alain Orr, Scott P. Tremblay, Jacques Robertson, Kate Nader, Karim Pitman, Roger K. TI Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE stress disorders; post-traumatic; memory; conditioning; propranolol; imagery; psychophysiology ID MEMORIES; FEAR; AMYGDALA; RECONSOLIDATION; CONSOLIDATION; BLOCKADE AB The beta-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event. Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events. Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol (n = 9) or placebo (n = 10), randomized and double-blind. A week later, they engaged in script-driven mental imagery of their traumatic event while heart rate, skin conductance, and left corrugator electromyogram were measured. Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier. Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Brunet, Alain; Tremblay, Jacques; Robertson, Kate] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Brunet, Alain; Tremblay, Jacques; Robertson, Kate] Douglas Hosp, Montreal, PQ, Canada. [Orr, Scott P.] VA Med Ctr, Manchester, NH USA. [Nader, Karim] McGill Univ, Dept Psychol, Montreal, PQ, Canada. [Orr, Scott P.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Orr, Scott P.; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp E, Room 2616,Bldg 149,13th St, Charlestown, MA 02129 USA. EM roger_pitman@hms.harvard.edu FU NIMH NIH HHS [MH068603] NR 15 TC 238 Z9 244 U1 4 U2 39 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAY PY 2008 VL 42 IS 6 BP 503 EP 506 DI 10.1016/j.jpsychires.2007.05.006 PG 4 WC Psychiatry SC Psychiatry GA 284QG UT WOS:000254720300010 PM 17588604 ER PT J AU Braun, IM Liang, MH Orav, EJ Ahern, DK Barsky, AJ AF Braun, Ilana M. Liang, Matthew H. Orav, E. John Ahern, David K. Barsky, Arthur J. TI A personality characteristic, somatic absorption, and the perception of somatic symptoms in rheumatoid arthritis patients SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; personality; psychology; somatic absorption ID PAIN COPING STRATEGIES; DISEASE-ACTIVITY; PSYCHOLOGICAL-FACTORS; CLINICAL-TRIALS; HEALTH-STATUS; DEPRESSION; HYPNOTIZABILITY; HELPLESSNESS; VARIABLES; INDEX AB Objective. This study tested the hypothesis that a personality trait, somatic absorption, is correlated with symptom severity in patients with rheumatoid arthritis (RA). Methods. Patients completed self-report questionnaires assessing intensity of their RA symptoms, somatic absorption, and psychiatric distress. Disease activity and severity were measured through erythrocyte sedimentation rate, joint examination, and aggressiveness of medication regimen. We examined the cross-sectional association between somatic absorption and RA symptoms using multivariable regression analyses. Results. Somatic absorption was significantly (p < 0.05) associated with an overall measure of RA symptoms, and this association persisted after taking into account demographic data, disease severity, and extent of psychological distress. Somatic absorption was more closely associated with constitutional symptoms than with localized, articular symptoms of arthritis. Somatic symptoms were also independently associated with psychiatric distress (p < 0.001). Psychiatric distress was a more powerful predictor of extraarticular or constitutional symptoms than were measures of arthritis activity and severity. Conclusion. Our findings suggest that there may be a role for psychological intervention in the management of extraarticular symptoms of RA as these symptoms are relatively more influenced by a personality characteristic than the localized articular symptoms of the disease. C1 [Braun, Ilana M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Barsky, Arthur J.] Harvard Univ, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Liang, Matthew H.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Orav, E. John] Brigham & Womens Hosp, Div Gen Internal Med, Dept Med, Boston, MA 02115 USA. RP Braun, IM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Warren Bldg,Room 605,55 Fruit St, Boston, MA 02114 USA. EM ibraun@partners.org FU NIAMS NIH HHS [1R01 AR4701401] NR 47 TC 3 Z9 3 U1 1 U2 5 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2008 VL 35 IS 5 BP 782 EP 789 PG 8 WC Rheumatology SC Rheumatology GA 304FG UT WOS:000256094800011 PM 18322988 ER PT J AU Nolla, J Ring, D Lozano-Calderon, S Jupiter, JB AF Nolla, Jose Ring, David Lozano-Calderon, Santiago Jupiter, Jesse B. TI Interposition arthroplasty of the elbow with hinged external fixation for post-traumatic arthritis SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID UPPER EXTREMITY; DISTRACTOR; HEAD AB This retrospective case series reviewed 9 men and 4 women (mean age, 41 years) with severe post-traumatic elbow arthrosis treated with interposition arthroplasty and temporary hinged external fixation. In 2 patients, treatment was considered to have failed because of early postoperative instability, and their results were classified as poor. The remaining 11 were followed up for a mean of 4 years (range, 1-11 years). The mean arc of flexion improved from 48 degrees before surgery to 110 degrees after surgery. The mean postoperative Broberg-Morrey score was 77 points, reflecting a mean improvement of 41 points (range, 13-68 points) and corresponding with 1 excellent, 4 good, 4 fair, and 4 poor results. Four patients had severe instability associated with bone loss of the distal humerus or trochlear notch. Interposition arthroplasty can improve elbow motion and function but at the expense of elbow stability despite hinged external fixation. C1 [Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 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 26 Z9 28 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAY-JUN PY 2008 VL 17 IS 3 BP 459 EP 464 DI 10.1016/j.jse.2007.11.008 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 302TS UT WOS:000255993000015 PM 18342545 ER PT J AU Kallemeier, PM Beaubien, BP Buttermann, GR Polga, DJ Wood, KB AF Kallemeier, Patricia M. Beaubien, Brian P. Buttermann, Glenn R. Polga, David J. Wood, Kirkham B. TI In vitro analysis of anterior and posterior fixation in an experimental unstable burst fracture model SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article DE biomechanics; burst fracture; plate; anterior fixation; posterior fixation ID THORACOLUMBAR SPINE INJURIES; BIOMECHANICAL EVALUATION; INSTRUMENTATION SYSTEMS; PEDICLE SCREWS; KANEDA DEVICE; STABILIZATION; BONE; DECOMPRESSION; FLEXIBILITY AB Study Design: A biomechanical comparison of fixation constructs in an experimental fracture model. Objective: To determine the relative postoperative stability of anterior graft and plating with that of posterior or combined fixation constructs in an unstable thoracolumbar burst fracture model. Summary of Background Data: Several treatment modalities have been proposed for unstable thoracolumbar burst fractures, but the optimal technique is unclear. Previous cadaveric biomechanical studies in unstable burst fracture models have not considered the commonly used posterior (interpedicular) and anterior (plate) constructs. Methods: Nine human spine segments (TI1-1-3) were potted in epoxy and scanned using dual energy x-ray absorptiometry and computed tomography. Intact specimens had baseline flexibility testing. Unstable L1 burst fractures as verified by computed tomography were created using an impulse load and posterior surgical osteoligamentous destabilization (ie, transection of the lamina, interspinous ligaments, facet capsules, and ligamentum flavum). Specimens were instrumented posteriorly with pedicle screws and rods and tested to 6 Nm in flexion-extension, lateral bending, and torsion. Corpectomy and strut grafting were then performed, and testing was repeated in varying order with posterior fixation, anterior plating and circumferential fixation. Range of motion (ROM) and neutral zone was calculated for each test and fixation groups were compared using analysis of variance. Results: All specimens had AO B1.2 (unstable burst) fractures. Mean ROM for posterior-only constructs was significantly less than that of the intact in lateral bending, flexion, and extension (P < 0.001). Anterior-only constructs after corpectomy and strut grafting generally resulted in a smaller ROM versus intact in flexion (NS: P = 0.1) and lateral bending (P < 0.001). In contrast, all anterior-only and posterior constructs had greater ROM than intact in torsion (all at P < 0.05). Circumferential fixation resulted in statistically smaller ROM compared with all other constructs (P <= 0.04), and reached that of the intact specimen in torsion. Increased ROM was correlated with greater fracture comminution for posterior-only fixation (P < 0.05), and was weakly correlated with lower dual energy x-ray absorptiometry score (R-2 = 0.3) for anterior-only fixation. Conclusions: Circumferential instrumentation provided the most rigid fixation, followed by posterior fixation with anterior strut grafting, posterior fixation alone, and by anterior fixation with strut grafting. These results were dependent on bone quality and the comminution severity of the fracture. These results should aid surgical decision making in addition to other factors in the overall clinical situation. C1 [Beaubien, Brian P.] Midwest Orthopaed Res Fdn, Minneapolis, MN USA. [Kallemeier, Patricia M.; Polga, David J.] Univ Minnesota, Minneapolis, MN USA. [Buttermann, Glenn R.] Midwest Spine Inst, Stillwater, MN USA. [Wood, Kirkham B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Beaubien, BP (reprint author), Midwest Orthopaed Res Fdn, Mail Code 860C,914 S 8th St, Minneapolis, MN USA. EM bbeaubien@gustilocenter.com NR 37 TC 29 Z9 42 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD MAY PY 2008 VL 21 IS 3 BP 216 EP 224 DI 10.1097/BSD.0b013e31807a2f61 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 300CD UT WOS:000255801000012 PM 18458594 ER PT J AU Zhao, WD Pan, JP Zhao, ZB Wu, Y Bauman, WA Cardozo, CP AF Zhao, Weidong Pan, Jiangping Zhao, Zingbo Wu, Yong Bauman, William A. Cardozo, Christopher P. TI Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE glucocorticods; muscle atrophy; testosterone; ubiquitin ligases; protein catabolism ID SKELETAL-MUSCLE; UBIQUITIN LIGASE; GENE-EXPRESSION; MEN; ATROGIN-1; SEPSIS; GLUCOCORTICOIDS; PROTEOLYSIS; MECHANISMS; PROTEASOME AB Administration of glucocorticoids in pharmacological amounts results in muscle atrophy due, in part, to accelerated degradation of muscle proteins by the ubiquitin-proteasome pathway. The ubiquitin ligase MAFbx is upregulated during muscle loss including that caused by glucocorticoids and has been implicated in accelerated muscle protein catabolism during such loss. Testosterone has been found to reverse glucocorticoid-induced muscle loss due to prolonged glucocorticoid administration. Here, we tested the possibility that testosterone would block muscle loss, upregulation of MAFbx, and protein catabolism when begun at the time of glucocorticoid administration. Coadministration of testosterone to male rats blocked dexamethasone-induced reduction in gastrocnernius muscle mass and upregulation of MAFbx mRNA levels. Administration of testosterone together with dexamethasone also prevented glucocorticoid induced upregulation of MAFbx mRNA levels and protein catabolism in C2C12 myotube expressing the androgen receptor. Half-life of MAFbx was not altered by testosterone, dexamethasone or the combination. Testosterone blocked dexamethasone-induced increases in activity of the human MAFbx promotor. The findings indicate that administration testosterone prevents glucocorticoid-induced muscle atrophy and suggest that this results, in part at least, from reductions in muscle protein catabolism and expression of MAFbx. (c) Published by Elsevier Ltd. C1 [Zhao, Weidong; Pan, Jiangping; Zhao, Zingbo; Wu, Yong; Bauman, William A.; Cardozo, Christopher P.] James J Peters VA Med Ctr, Dept Vet Affairs, Bronx, NY 10468 USA. [Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. RP Cardozo, CP (reprint author), James J Peters VA Med Ctr, Dept Vet Affairs, Room 1E-02, Bronx, NY 10468 USA. EM Chris.Cardozo@mssm.edu NR 31 TC 40 Z9 41 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD MAY PY 2008 VL 110 IS 1-2 BP 125 EP 129 DI 10.1016/j.jsbmb.2008.03.024 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 322XQ UT WOS:000257409000014 PM 18436443 ER PT J AU Gradus, JL Street, AE Kelly, K Stafford, J AF Gradus, Jaimie L. Street, Amy E. Kelly, Kacie Stafford, Jane TI Sexual harassment experiences and harmful alcohol use in a military sample: Differences in gender and the mediating role of depression SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID WORKPLACE HARASSMENT; DRINKING; ABUSE; QUESTIONNAIRE; DISTRESS AB Objective: Researchers and clinicians alike are interested in the effects of sexual harassment on mental health, including associations with problem drinking. The aim of the current investigation was to examine depression symptoms as a mediator of the association between sexual harassment during military service and current harmful alcohol use in a sample of former military personnel, stratified by gender. Method: Using a cross-sectional design, 3,946 former reservists were surveyed regarding their experiences of sexual harassment in the military and their current depression symptoms and harmful alcohol use. Fifty-nine percent of the final sample were female. Results: As expected, women endorsed experiencing sexual harassment more than men, and men endorsed harmful drinking more than women. Sexual harassment was associated with increased depression symptoms among both men and women; however, depression symptoms mediated the association between sexual harassment and harmful alcohol use among women only Sexual harassment was not a significant predictor of harmful alcohol use among men. Conclusions: The associations between sexual harassment, depression symptoms, and harmful alcohol use differ between men and women in this sample. Consistent with the self-medication hypothesis, sexual harassment is associated with harmful drinking among women, and this association can be accounted for by symptoms of depression. The high prevalence of harmful drinking among men and the lack of an association with sexual harassment suggest that, in this sample, men's harmful drinking is influenced by factors other than sexual harassment. C1 [Gradus, Jaimie L.; Street, Amy E.; Kelly, Kacie; Stafford, Jane] Vet Affairs Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. [Gradus, Jaimie L.; Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Stafford, Jane] Univ S Carolina Aiken, Dept Psychol, Aiken, SC USA. RP Street, AE (reprint author), Vet Affairs Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr Posttraumat Stress Disorder, 150 S Huntington Ave, Boston, MA 02130 USA. EM Amy.Street@va.gov NR 18 TC 21 Z9 21 U1 0 U2 4 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2008 VL 69 IS 3 BP 348 EP 351 PG 4 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 295OK UT WOS:000255483600002 PM 18432376 ER PT J AU Maisto, SA Conigliaro, JC Gordon, AJ McGinnis, KA Justice, AC AF Maisto, Stephen A. Conigliaro, Joseph C. Gordon, Adam J. McGinnis, Kathleen A. Justice, Amy C. TI An experimental study of the agreement of self-administration and telephone administration of the timeline followback interview SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID ALCOHOL; BEHAVIOR; VETERANS AB Objective: The Timeline Followback (TLFB) interview has become state-of-the-science for the collection of retrospective selfreports of daily alcohol consumption. Such data are especially useful for addressing questions of the co-occurrence of quantity of alcohol consumption and other behaviors, such as HIV-related risky sex, on the event level. The purpose of this study was to determine if the TLFB could be used effectively by self-administration compared with the more costly telephone interview in a large, multisite observational study of HIV-positive and HIV-negative adults. Method: An experimental design was used to compare self-administered and telephone-administered TLFB modes in a subsample (N = 70) of the Veterans Aging Cohort Study, an ongoing longitudinal study of more than 6,000 HIV-positive and HIV-negative men and women presenting for treatment at eight Department of Veterans Affairs Infectious Disease or General Medicine clinics. Participants were randomly assigned to one of four experimental groups defined by mode and sequence of a TLFB administration on two occasions occurring within 1 week: telephone-telephone, telephone-self, self-telephone, and self-self. Results: Analyses showed no differences in median total number of drinks reported between modes of TLFB administration or sequence of mode of administration. The same findings held for classification of participants as "hazardous" drinkers. Additional analyses showed good-to-excel lent test-retest reliability of self-reports for both modes of TLFB administration. Conclusions: The data derived from this study provide strong experimental evidence for the utility of the self-administered, 30-day TLFB in collecting daily alcohol consumption in large observational studies of HIV-positive and HIV-negative individuals. C1 [Maisto, Stephen A.; Conigliaro, Joseph C.; Gordon, Adam J.; McGinnis, Kathleen A.; Justice, Amy C.] Syracuse Univ, Dept Psychol, Ctr Hlth & Behav, Syracuse, NY 13244 USA. [Conigliaro, Joseph C.] Univ Kentucky, Albert B Chandler Med Ctr, Lexington, KY 40536 USA. [Gordon, Adam J.; McGinnis, Kathleen A.] Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Justice, Amy C.] Yale Univ, Vet Aging Cohort Study, New Haven, CT USA. RP Maisto, SA (reprint author), Syracuse Univ, Dept Psychol, Ctr Hlth & Behav, 430 Huntington Hall, Syracuse, NY 13244 USA. EM samaisto@syr.edu FU NIAAA NIH HHS [U10 AA013566-08, U10 AA013566-07, U10 AA13566, U10 AA013566] NR 9 TC 16 Z9 16 U1 0 U2 3 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2008 VL 69 IS 3 BP 468 EP 471 PG 4 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 295OK UT WOS:000255483600017 PM 18432391 ER PT J AU Hazen, E AF Hazen, Eric TI Monochrome days: A firsthand account of one teenager's experience with depression. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Hazen, Eric] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Hazen, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM ehazen@partners.org 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 MAY PY 2008 VL 47 IS 5 BP 605 EP 606 DI 10.1097/CHI.0b013e3181676b94 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 292IZ UT WOS:000255261000018 ER PT J AU Frangos, JE Alavian, CN Kimball, AB AF Frangos, Jason E. Alavian, Christina N. Kimball, Alexa B. TI Acne and oral contraceptives: Update on women's health screening guidelines SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER; PELVIC EXAMINATION; ETHINYL ESTRADIOL; OVARIAN-CANCER; HORMONAL CONTRACEPTIVES; ISCHEMIC STROKE; RISK; NORGESTIMATE AB Oral contraceptives (OCs) have been shown to be safe and effective for the treatment of acne in most women of childbearing potential, and several have been approved by the Food and Drug Administration for this purpose. However, dermatologists have historically been reluctant to prescribe OCs for acne because of long-standing recommendations requiring a preliminary pelvic examination and Papanicolaou smear before initiation of therapy. In recent guideline shifts, expert panels and major health organizations have reached a consensus that OC provision no longer necessitates the performance of a pelvic examination and Papanicolaou smear. These new guideline revisions could change the way dermatologists treat acne in their healthy female patients of child-bearing age. C1 [Frangos, Jason E.] Yale Univ, Sch Med, New Haven, CT USA. [Alavian, Christina N.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA. [Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Clin Unit Res Trials Skin, 50 Staniford St,246 Dermatol, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 50 TC 9 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2008 VL 58 IS 5 BP 781 EP 786 DI 10.1016/j.jaad.2007.12.040 PG 6 WC Dermatology SC Dermatology GA 292VA UT WOS:000255293000007 PM 18359534 ER PT J AU Holzmann, RD Liang, M Nadiminti, H McCarthy, J Gharia, M Jones, J Neel, V Schanbacher, CF AF Holzmann, Ruth D. Liang, Michelle Nadiminti, Hari McCarthy, Joanne Gharia, Manish Jones, Jennifer Neel, Victor Schanbacher, Carl F. TI Blood exposure risk during procedural dermatology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID HEPATITIS-C; EYE SPLASH; TRANSMISSION; CONJUNCTIVA; SURGEONS; INFECTION; CONTAMINATION; DISEASES; NURSE; HIV AB Background: Dermatologists ire at risk Of body-fluid contamination during procedures. Objective: We sought to determine the frequency of blood splash during procedural dermatology. Methods: In all, 500 consecutive excisions were performed. Postoperatively, blood droplets on face shields and surgical gowns were counted. A survey regarding universal precautions during procedures was also conducted with members of the American College of Mohs Surgery (ACMS). Results: Contamination from blood splashes during dermatologic procedures (Mohs micrographic surgery, excision, repair) occurred in 66.4%. Reconstruction type, anticoagulation use, wound location, and wound size correlated with a higher blood splash rate. Our survey showed that face shields and goggles are used inconsistently. Limitations: The 4 participating dermatologists do not represent all practicing dermatologists. It may be possible to generalize the survey results directed at physicians in the ACMS. Conclusion. Physician body-fluid contamination risk with procedural dermatology is clinically significant. Dermatologists and their assistants should wear preventive barriers during procedures to minimize the risk of viral transmission. C1 [Holzmann, Ruth D.; Liang, Michelle; Nadiminti, Hari; McCarthy, Joanne; Jones, Jennifer; Schanbacher, Carl F.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Dermatol, Boston, MA 02115 USA. [Gharia, Manish] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Neel, Victor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. [Holzmann, Ruth D.] Humboldt Univ, Univ Hosp Charite, Berlin, Germany. RP Holzmann, RD (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Dermatol, 44 Binney St, Boston, MA 02115 USA. EM rdholzmann@mac.com NR 24 TC 6 Z9 6 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2008 VL 58 IS 5 BP 817 EP 825 DI 10.1016/j.jaad.2008.01.010 PG 9 WC Dermatology SC Dermatology GA 292VA UT WOS:000255293000013 PM 18423259 ER PT J AU Hawn, MT Itani, KM Gray, SH Vick, CC Henderson, W Holiston, TK AF Hawn, Mary T. Itani, Kamal M. Gray, Stephen H. Vick, Catherine C. Henderson, William Holiston, Thomas K. TI Association of timely administration of prophylactic antibiotics for major surgical procedures and surgical site infection SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 119th Annual Meeting of the Southern-Surgical-Association CY DEC 02-05, 2007 CL Hot Springs, VA SP So Surg Assoc ID OF-VETERANS-AFFAIRS; WOUND INFECTION; PREVENTION; QUALITY; CARE; SURGERY; RISK AB BACKGROUND: Prophylactic antibiotic (PA) administration 1 to 2 hours before surgical incision (SIP-1) is a publicly reported process measure proposed for performance pay. We performed an analysis of patients undergoing major surgical operations to determine if SIP-1 was associated with surgical site infection (SSI) rates in Department of Veterans Affairs (VA) hospitals. STUDY DESIGN: Patients with External Peer Review Program Surgical Care Improvement Project (SCIP)-1 data with matched National Surgical Quality Improvement Program data were included in the study. Patient and facility level analyses comparing SCIP-1 and SSI were performed. We adjusted for clustering effects within hospitals, validated SSI risk score, and procedure type (percentage of colon, vascular, orthopaeclic) using generalized estimating equations and linear modeling. RESULTS: The study population included 9,195 elective procedures (5,981 orthopaedic, 1,966 colon, and 1,248 vascular) performed in 95 VA hospitals. Timely PA occurred in 86.4% of patients. Untimely PA was associated with a rate of SSI of 5.8%, compared with 4.6% in the timely group (odds ratio = 1.29, 95% CI 0.99, 1.67) in bivariable unadjusted analysis. Patient level risk-adjusted multivariable generalized estimating equation modeling found the SSI risk scorewas predictive of SSI (p < 0.001); SIP-1 was not associated with SSI. Hospital level multivariable generalized linear modeling found procedure mix (p < 0.000 1), but not SIP-1 rate or facility volume, to be associated with facility SSI rate. The study had 80% power to detect a 1.75% difference for patient level SSI rates. CONCLUSIONS: Timely PA did not markedly contribute to overall patient or facility SSI rates. These data are important for the ongoing discourse on how to measure and pay for quality of surgical care. C1 [Hawn, Mary T.; Gray, Stephen H.; Vick, Catherine C.; Holiston, Thomas K.] Univ Alabama, Deep S Ctr Effectiveness Res, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Hawn, Mary T.; Gray, Stephen H.; Vick, Catherine C.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Gray, Stephen H.] Univ Alabama, Hlth Serv & Outcomes Res Training Program, Dept Med, Birmingham, AL 35294 USA. [Itani, Kamal M.] VA Boston Hlth Care Syst, Dept Surg, W Roxbury, MA USA. [Itani, Kamal M.] Boston Univ, Dept Surg, Boston, MA 02215 USA. [Henderson, William] Colorado Hlth Outcomes Program, Denver, CO USA. RP Hawn, MT (reprint author), KB 429,1530 3rd Ave S, Birmingham, AL 35294 USA. OI Gray, Stephen/0000-0002-5702-7226 FU AHRQ HHS [HS013852, 5 T32 HS013852]; None [HS013852] NR 14 TC 62 Z9 63 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 MAY PY 2008 VL 206 IS 5 BP 814 EP 821 DI 10.1016/j.jamcollsurg.2007.12.013 PG 8 WC Surgery SC Surgery GA 297NW UT WOS:000255624400006 PM 18471703 ER PT J AU Lee, J El-Tamer, M Schifftner, T Turrentme, FE Henderson, WG Khuri, S Hanks, JB Inabnet, WB AF Lee, James El-Tamer, Mahmoud Schifftner, Tracy Turrentme, Florence E. Henderson, William G. Khuri, Shukri Hanks, John B. Inabnet, William B., III TI Open and laparoscopic adrenalectomy: Analysis of the national surgical quality improvement program SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 119th Annual Meeting of the Southern-Surgical-Association CY DEC 02-05, 2007 CL Hot Springs, VA SP So Surg Assoc ID VETERANS-AFFAIRS; RISK ADJUSTMENT; MEDICAL-CENTERS; PATIENT SAFETY; CARE; SURGERY; MORBIDITY; MORTALITY; IMPACT AB BACKGROUND: Numerous series demonstrate the benefits of laparoscopic versus open adrenalectomy, but fail to adjust for confounding factors. This study uses the Veterans Affairs National Surgical Quality Improvement Program database to compare these two approaches, adjusting for baseline differences. STUDY DESIGN: Laparoscopic (n = 358) and open (n = 311) adrenalectomy data were collected at 123 Department of Veterans Affairs and 14 University hospitals from October 1, 2001 to Septembet-30, 2004. Preoperative characteristics, operative data, and 30-day outcomes were compared using the chi-square or Fisher's exact test for categorical variables and the t-test for continuous variables. Unadjusted odds ratio (OR) and 95% confidence interval (CI) were computed for the effect of operative approach on postoperative morbidity. Adjusted odds ratios and 95% Cl were computed for this same effect, adjusting for variables that were predictive of outcomes or imbalanced at baseline. Data are reported as means +/- SD, unless otherwise indicated. RESULTS: Patients undergoing open adrenalectomy were more likely to be older (57.8 +/- 11.9 years versus 53.5 +/- 13.2 years, p < 0.0001), harbor malignancy (44.5% versus 13.5%, p < 0.0001), have higher American Society of Anesthesiologists classifications (p = 0.0037), smoke (35.4% versus 22.6%, p = 0.0003), and have lower serum albumin levels (3.9 +/- 0.5 g/dL versus 4.0 +/- 0.5 g/dL, p = 0.0241). Open procedures had increased operative times (3.9 +/- 1.8 hours versus 2.9 +/- 1.3 hours, p < 0.0001), transfusion requirements (0.7 +/- 1.8 U versus 0.1 +/- 0.5 U, p < 0.0001), reoperations (4.8% versus 1.4%, p = 0.0094), length of stay (9.4 +/- 11.0 days versus 4.1 +/- 4.7 days, p < 0.0001) and 30-day morbidity rates (17.4% versus 3.6%, p < 0.0001) with unadjusted and adjusted odds ratio (95% CI) of 5.52 (2.94, 10.33), and 3.97 (1.92, 8.22), respectively. Open procedures resulted in more pneumonia, unplanned inulbation, Unsuccessful ventilator wean, systemic sepsis, cardiac arrest, renal insufficiency, and wound infections. CONCLUSIONS: Even after adjustment for confounding factors, 30-day morbidity was much higher for patients having open adrenalectomy. C1 [Lee, James; El-Tamer, Mahmoud; Inabnet, William B., III] Columbia Univ, Div Gastroenterol & Endocrine Surg, New York, NY USA. [Schifftner, Tracy] Vet Adm Med Ctr, NSQIP Denver Data Anal Ctr, Denver, CO USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. [Turrentme, Florence E.; Hanks, John B.] Univ Virginia Hlth Syst, Dept Surg, Div Gen Surg, Sect Endocrine Surg, Charlottesville, VA USA. [Khuri, Shukri] VA Boston Healthcare Syst, W Roxbury, MA USA. [Khuri, Shukri] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Inabnet, WB (reprint author), 161 Ft Washington Ave, New York, NY 10032 USA. RI Turrentine, Florence/F-6937-2015 OI Turrentine, Florence/0000-0002-0313-2813 NR 22 TC 66 Z9 72 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAY PY 2008 VL 206 IS 5 BP 953 EP 961 DI 10.1016/j.jamcollsurg.2008.01.018 PG 9 WC Surgery SC Surgery GA 297NW UT WOS:000255624400021 PM 18471733 ER PT J AU DePaola, DP AF DePaola, Dominick P. TI Saliva - The precious body fluid SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 [DePaola, Dominick P.] Forsyth Inst, Boston, MA USA. [DePaola, Dominick P.] Nova SE Univ, Coll Dent Med, Ft Lauderdale, FL 33314 USA. EM DDePaola@forsyth.org NR 6 TC 1 Z9 1 U1 0 U2 3 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2008 VL 139 SU S BP 5S EP 6S PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 305GV UT WOS:000256167000001 PM 18460673 ER PT J AU Haffajee, AD Yaskell, T Socransky, SS AF Haffajee, Anne D. Yaskell, Tina Socransky, Sigmund S. TI Antimicrobial effectiveness of an herbal mouthrinse compared with an essential oil and a chlorhexidine mouthrinse SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE antimicrobial mouthrinse; oral bacteria; natural oral antimicrobial agent ID GRAPEFRUIT-SEED EXTRACT; ALOE-VERA GEL; IN-VITRO; ANTIBACTERIAL AGENT; GINGIVITIS; PLAQUE; VIVO; DISEASE; 6-MONTH; TRIAL AB Background. The authors investigated mouthrinses' antimicrobial effectiveness against predominant oral-bacteria, as determined by the minimum inhibitory concentration they evaluated an (MIC). Specifically, herbal mouthrinse, an essential oil rinse and a 0.12 percent chlorhexidine gluconate rinse. Methods. The authors assessed the inhibitory effects of the three test agents against 40 oral bacteria at concentrations of 1, 2, 4, 8, 16, 32, 64, 128, 256 and 512 micrograms per millliter. They inoculated plates containing basal medium and the test agents with suspensions of the test species and incubated them anaerobically at 35 degrees C. The authors interpreted the MIC as the lowest concentration of the agent that completely inhibited the growth of the test species. Results. The herbal mouthrinse inhibited the growth of most of the 40 test species. Compared with the essential oil mouthrinse, the herbal mouthrinse exhibited significantly lower MICs for Actinomyces species, periodontal pathogens Eubacterium nodatum, Tannerella forsythia and Prevotella species, as well as the cariogenic pathogen Streptococcus mutans. The chlorhexidine gluconate rinse had the lowest MICs compared with the essential oil rinse and the herbal rinse for an test species examined. Conclusions. Although less potent than the chlorhexidine gluconate rinse, the herbal rinse was more effective than-the essential oil rinse in inhibiting the growth of oral bacteria in vitro. Clinical Implications. The data suggest that the herbal mouthrinse may provide oral health benefits by inhibiting the growth of periodontal and cariogenic: pathogens. In vivo clinical testing is essential to confirm in vitro results. C1 [Haffajee, Anne D.] Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. EM ahaffajee@forsyth.org NR 25 TC 25 Z9 26 U1 4 U2 12 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2008 VL 139 IS 5 BP 606 EP 611 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 302JS UT WOS:000255965200024 PM 18451378 ER PT J AU Handler, SM Hanlon, JT Perera, S Roumani, YF Nace, DA Fridsma, DB Saul, MI Castle, NG Studenski, SA AF Handler, Steven M. Hanlon, Joseph T. Perera, Subashan Roumani, Yazan F. Nace, David A. Fridsma, Douglas B. Saul, Melissa I. Castle, Nicholas G. Studenski, Stephanie A. TI Consensus list of signals to detect potential adverse drug reactions in nursing homes SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE adverse drug events; adverse drug reactions; nursing homes; Delphi technique ID HEALTH INFORMATION NETWORK; COMPUTERIZED SURVEILLANCE; RESPONSE RATES; EVENTS; CARE; INDICATORS; OUTPATIENTS; MORBIDITY; MONITOR; QUALITY AB OBJECTIVES: To develop a consensus list of agreed-upon laboratory, pharmacy, and Minimum Data Set signals that a computer system can use in the nursing home to detect potential adverse drug reactions (ADRs). DESIGN: Literature search for potential ADR signals, followed by an internet-based, a two-round, modified Delphi survey. SETTING: A nationally representative survey of experts in geriatrics. PARTICIPANTS: Panel of 13 physicians, 10 pharmacists, and 13 advanced practitioners. MEASUREMENTS: Mean score and 95% confidence interval (CI) for each of 80 signals rated on a 5-point Likert scale (5=strong agreement with likelihood of indicating potential ADRs). Consensus agreement indicated by a lower-limit 95% CI of 4.0 or greater. RESULTS: Panelists reached consensus agreement on 40 signals: 15 laboratory and medication combinations, 12 medication concentrations, 10 antidotes, and three Resident Assessment Protocols (RAPs). Highest consensus scores (4.6, 95% CI=4.4-4.9 or 4.4-4.8) were for naloxone when taking opioid analgesics; phytonadione when taking warfarin; dextrose, glucagon, or liquid glucose when taking hypoglycemic agents; medication-induced hypoglycemia; supratherapeutic international normalized ratio when taking warfarin; and triggering the Falls RAP when taking certain medications. CONCLUSION: A multidisciplinary expert panel was able to reach consensus agreement on a list of signals to detect potential ADRs in nursing home residents. The results of this study can be used to prioritize an initial list of signals to be included in paper- or computer-based methods for potential ADR detection. C1 [Handler, Steven M.; Fridsma, Douglas B.; Saul, Melissa I.] Vet Affairs Pittsburgh Healthcare Syst, Sch Med, Dept Biomed Informat, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Hanlon, Joseph T.; Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Handler, Steven M.; Hanlon, Joseph T.; Perera, Subashan; Roumani, Yazan F.; Nace, David A.; Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Div Geriatr Med, Dept Med, Pittsburgh, PA USA. [Perera, Subashan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Castle, Nicholas G.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA. RP Handler, SM (reprint author), Univ Pittsburgh, Div Geriatr Med, Dept Med, 3471 5th Ave,Suite 500, Pittsburgh, PA 15213 USA. EM handler@pitt.edu RI Nace, David/D-2638-2014; Perera, Subashan/D-7603-2014; OI Handler, Steven/0000-0002-3940-3224 FU NCRR NIH HHS [1 KL2 RR024154-01, KL2 RR024154]; NIA NIH HHS [5T32AG021885, P30 AG024827, P30 AG024827-05, P30AG024827, R01 AG027017, R01AG027017, T32 AG021885] NR 52 TC 20 Z9 21 U1 6 U2 6 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 MAY PY 2008 VL 56 IS 5 BP 808 EP 815 DI 10.1111/j.1532-5415.2008.01665.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 295PI UT WOS:000255486000004 PM 18363678 ER PT J AU Connor, KI McNeese-Smith, DK Vickrey, BG van Servellen, GM Chang, BL Lee, ML Vassar, SD Chodosh, J AF Connor, Karen I. McNeese-Smith, Donna K. Vickrey, Barbara G. van Servellen, Gwen M. Chang, Betty L. Lee, Martin L. Vassar, Stefanie D. Chodosh, Joshua TI Determining care management activities associated with mastery and relationship strain for dementia caregivers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE mastery; relationship strain; care management; dementia; family ID ALZHEIMERS-DISEASE; BEHAVIOR PROBLEMS; INTERVENTION; HEALTH; PREDICTORS; SYMPTOMS; QUALITY; IMPACT AB OBJECTIVES: To identify specific care management activities within a dementia care management intervention that are associated with 18-month change in caregiver mastery and relationship strain. DESIGN: Exploratory analysis, using secondary data (care management processes and caregiver outcomes) from the intervention arm of a clinic-level randomized, controlled trial of a dementia care management quality improvement program. SETTING: Nine primary care clinics in three managed care and fee-for-service southern California healthcare organizations. PARTICIPANTS: Two hundred thirty-eight pairs: individuals with dementia and their informal, nonprofessional caregivers. MEASUREMENTS: Care management activity types extracted from an electronic database were used as predictors of caregiver mastery and relationship strain, which were measured through mailed surveys. Multivariable linear regression models were used to predict caregiver mastery and relationship strain. RESULTS: For each care manager home environment assessment, caregiver mastery increased 4 points (range 0-100, mean +/- standard deviation 57.1 +/- 26.6, 95% confidence interval (CI)=2.4-5.7; P=.001) between baseline and 18 months. For every action linking caregivers to community agencies for nonspecific needs, caregiver mastery decreased 6.2 points (95% CI=-8.5 to -3.9; P <.001). No other care management activities were significantly associated with this outcome, and no specific activities were associated with a change in caregiver relationship strain. CONCLUSION: Home assessments for specific needs of caregivers and persons with dementia are associated with improvements in caregivers' sense of mastery. Future work is needed to determine whether this increase is sustained over time and decreases the need for institutionalization. C1 [Connor, Karen I.; McNeese-Smith, Donna K.; van Servellen, Gwen M.; Chang, Betty L.] Greater Los Angeles Vet Affairs Med Ctr, Sch Nursing, Los Angeles, CA USA. [Connor, Karen I.; Vickrey, Barbara G.; Vassar, Stefanie D.] Greater Los Angeles Vet Affairs Med Ctr, Dept Neurol, Los Angeles, CA USA. [Lee, Martin L.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Lee, Martin L.] Vet Affairs Greater Los Angeles, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Chodosh, Joshua] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Chodosh, Joshua] Univ Calif Los Angeles, Multi Campus Program Geriatr Med & Gerontol, Los Angeles, CA USA. [Chodosh, Joshua] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Connor, KI (reprint author), C-109 RNRC,Box 951769, Los Angeles, CA 90095 USA. EM kiconnor@ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 NR 34 TC 11 Z9 13 U1 0 U2 2 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 MAY PY 2008 VL 56 IS 5 BP 891 EP 897 DI 10.1111/j.1532-5415.2008.01643.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 295PI UT WOS:000255486000016 PM 18384590 ER PT J AU Ries, ML Carlsson, CM Rowley, HA Sager, MA Gleason, CE Asthana, S Johnson, SC AF Ries, Michele L. Carlsson, Cynthia M. Rowley, Howard A. Sager, Mark A. Gleason, Carey E. Asthana, Sanjay Johnson, Sterling C. TI Magnetic resonance imaging characterization of brain structure and function in mild cognitive impairment: A review SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; mild cognitive impairment; MRI ID VOXEL-BASED MORPHOMETRY; EARLY ALZHEIMERS-DISEASE; TEMPORAL-LOBE ATROPHY; GRAY-MATTER LOSS; ENTORHINAL CORTEX; HIPPOCAMPAL ATROPHY; PREDICTS DEMENTIA; MRI; MEMORY; AD AB Given the predicted increase in prevalence of Alzheimer's disease (AD) in the coming decades, early detection and intervention in persons with the predementia condition known as mild cognitive impairment (MCI) is of paramount importance. Recent years have seen remarkable advances in the application of neuroimaging and other biomarkers to the study of MCI. This article reviews the most recent developments in the use of magnetic resonance imaging (MRI) to characterize brain changes and to prognosticate clinical outcomes of patients with MCI. The review begins with description of methods and findings in structural MRI research, delineating findings regarding both gross atrophy and microstructural brain changes in MCI. Second, we describe the most recent findings regarding brain function in MCI, enumerating findings from functional MRI and brain perfusion studies. Third, we will make recommendations regarding the current clinical use of MRI in identification of MCI. As a conclusion, we will look to the future of neuroimaging as a tool in early AD detection. C1 [Ries, Michele L.; Carlsson, Cynthia M.; Gleason, Carey E.; Asthana, Sanjay; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. [Ries, Michele L.; Carlsson, Cynthia M.; Rowley, Howard A.; Sager, Mark A.; Gleason, Carey E.; Asthana, Sanjay; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Sect Geriatr, Madison, WI USA. RP Ries, ML (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terrace 11G, Madison, WI 53705 USA. EM mlr@medicine.wisc.edu FU NCRR NIH HHS [8K12RR023268-02]; NIA NIH HHS [L30 AG026886-01, L30 AG026886-02, R01 AG021155, R01 AG021155-02, R01 AG021155-03, R01 AG021155-04, R01 AG021155-05] NR 81 TC 71 Z9 74 U1 0 U2 12 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 MAY PY 2008 VL 56 IS 5 BP 920 EP 934 DI 10.1111/j.1532-5415.2008.01684.x PG 15 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 295PI UT WOS:000255486000021 PM 18410325 ER PT J AU Drummond, IA AF Drummond, Iain A. TI Some assembly required: Renal hypodysplasia and the problem with faulty parts SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID KIDNEY DEVELOPMENT; ZEBRAFISH; MUTATIONS; DISEASE; SIX2; GENE C1 [Drummond, Iain A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA. RP Drummond, IA (reprint author), MGH Nephrol 149-8000,149 13th St, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK071041] NR 18 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC 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 MAY PY 2008 VL 19 IS 5 BP 834 EP 836 DI 10.1681/ASN.2008030281 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 294RN UT WOS:000255423300002 PM 18385415 ER PT J AU Korgaonkar, SN Feng, XB Ross, MD Lu, TC D'Agati, V Iyengar, R Klotman, PE He, JCJ AF Korgaonkar, Sonal Navin Feng, Xiaobei Ross, Michael D. Lu, Ting-Chi D'Agati, Vivette Iyengar, Ravi Klotman, Paul E. He, John Cijiang TI HIV-1 upregulates VEGF in podocytes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Nephrology CY NOV 14-19, 2006 CL San Diego, CA SP Amer Soc Nephrol ID ENDOTHELIAL GROWTH-FACTOR; GENE-EXPRESSION; IN-VIVO; NEF; GLOMERULOSCLEROSIS; SURVIVAL; DEDIFFERENTIATION; PROLIFERATION; ANGIOGENESIS; NEPHROPATHY AB HIV-associated nephropathy (HIVAN) is characterized by collapsing FSGS. Because transgenic mice with podocyte-specific overexpression of the vascular endothelial growth factor 164 (VEGF(164)) isoform also develop collapsing FSGS, we sought to determine whether VEGF plays a role in HIVAN. Compared with controls, immunohistochemistry revealed that kidneys from HIV-1-transgenic mice (Tg26) and from patients with HIVAN had greater expression of both VEGF and its transcriptional regulator, hypoxia-inducible factor 2 alpha (HIF-2 alpha). Similarly, mRNA and protein levels of VEGF and HIF-2a were increased in HIV-infected podocytes in vitro, and this transcriptional upregulation was found to be stimulated by the HIV viral protein Nef in a Src kinase- and Stat3-dependent manner. HIV-1 also upregulated VEGFR2 and its co-receptor neuropilin-1 and suppressed the expression of semaphorin 3a in the podocyte. Exogenous VEGF stimulated proliferation and de-differentiation of podocytes, which are features of collapsing FSGS, and VEGFR2 neutralizing antibodies reversed these features in podocytes infected with HIV-1 or isolated from Tg26 mice. In conclusion, HIV-1 induces VEGF and VEGFR2 expression in podocytes, and this may be a critical step in the pathogenesis of HIVAN. C1 [Korgaonkar, Sonal Navin; Ross, Michael D.; Lu, Ting-Chi; Klotman, Paul E.; He, John Cijiang] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Iyengar, Ravi] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA. [Lu, Ting-Chi; He, John Cijiang] James J Peters VA Med Ctr, Bronx, NY USA. [D'Agati, Vivette] Columbia Univ, Dept Pathol, New York, NY USA. [Feng, Xiaobei] Ruijin Hosp, Dept Nephrol, Shanghai, Peoples R China. RP He, JCJ (reprint author), 1 Gustave Levy Pl, New York, NY 10029 USA. EM cijiang.he@mssm.edu FU NIDDK NIH HHS [DK056492, DK038761, DK065495, DK076523, DK078897, DK079781, F32 DK076523, K08 DK065495, K08 DK079781, P01 DK056492, R01 DK038761, R01 DK078897]; NIGMS NIH HHS [R01 GM054508] NR 30 TC 41 Z9 44 U1 0 U2 1 PU AMER SOC 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 MAY PY 2008 VL 19 IS 5 BP 877 EP 883 DI 10.1681/ASN2007050629 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 294RN UT WOS:000255423300011 PM 18443354 ER PT J AU Tran, S Chen, YW Chenier, I Chan, JSD Quaggin, S Hebert, MJ Ingelfinger, JR Zhang, SL AF Tran, Stella Chen, Yun-Wen Chenier, Isabelle Chan, John S. D. Quaggin, Susan Hebert, Marie-Josee Ingelfinger, Julie R. Zhang, Shao-Ling TI Maternal diabetes modulates renal morphogenesis in offspring SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NF-KAPPA-B; PROXIMAL TUBULAR CELLS; ANGIOTENSINOGEN GENE-EXPRESSION; URETERAL BUD MORPHOGENESIS; HIGH D-GLUCOSE; IN-VITRO; BRANCHING MORPHOGENESIS; CONGENITAL-ANOMALIES; ADULT HYPERTENSION; KIDNEY DEVELOPMENT AB Maternal diabetes leads to an adverse in utero environment, but whether maternal diabetes impairs nephrogenesis is unknown. Diabetes was induced with streptozotocin in pregnant Hoxb7-green fluorescence protein mice at embryonic day 13, and the offspring were examined at several time points after birth. Compared with offspring of nondiabetic controls, offspring of diabetic mice had lower body weight, body size, kidney weight, and nephron number. The observed renal dysmorphogenesis may be the result of increased apoptosis, because immunohistochemical analysis revealed significantly more apoptotic podocytes as well as increased active caspase-3 immunostaining in the renal tubules compared with control mice. Regarding potential mediators of these differences, offspring of diabetic mice had increased expression of intrarenal angiotensinogen and renin mRNA, upregulation of NF-kappa B isoforms p50 and p65, and activation of the NF-kappa B pathway. In conclusion, maternal diabetes impairs nephrogenesis, possibly via enhanced intrarenal activation of the renin-angiotensin system and NF-kappa B signaling. C1 [Tran, Stella; Chen, Yun-Wen; Chenier, Isabelle; Chan, John S. D.; Hebert, Marie-Josee; Zhang, Shao-Ling] Univ Montreal, Hotel Dieu, Ctr Hosp, Res Ctr, Montreal, PQ H2W 1T7, Canada. [Quaggin, Susan] Univ Toronto, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Zhang, SL (reprint author), Univ Montreal, Hotel Dieu, Ctr Hosp, Res Ctr, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T7, Canada. EM shao.ling.zhang@umontreal.ca NR 75 TC 41 Z9 43 U1 0 U2 1 PU AMER SOC 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 MAY PY 2008 VL 19 IS 5 BP 943 EP 952 DI 10.1681/ASN.2007080864 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 294RN UT WOS:000255423300018 PM 18305124 ER PT J AU Tumlin, J Wali, R Williams, W Murray, P Tolwani, AJ Vinnikova, AK Szerlip, HM Ye, JM Paganini, EP Dworkin, L Finkel, KW Kraus, MA Humes, HD AF Tumlin, James Wali, Ravinder Williams, Winfred Murray, Patrick Tolwani, Ashita J. Vinnikova, Anna K. Szerlip, Harold M. Ye, Jiuming Paganini, Emil P. Dworkin, Lance Finkel, Kevin W. Kraus, Michael A. Humes, H. David TI Efficacy and safety of renal tubule cell therapy for acute renal failure SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID TISSUE-ENGINEERED KIDNEY; BIOARTIFICIAL KIDNEY; UREMIC ANIMALS; SEPTIC SHOCK; REPLACEMENT; MORTALITY; DISEASE; SEPSIS AB The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase 11, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAID, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 cl, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF. C1 [Humes, H. David] Univ Michigan, Div Nephrol, Dept Internal Med, Ann Arbor, MI 48109 USA. [Tumlin, James] Presbyterian Hosp, Charlotte, NC USA. [Wali, Ravinder] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Williams, Winfred] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Murray, Patrick] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Tolwani, Ashita J.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Vinnikova, Anna K.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA. [Szerlip, Harold M.] Med Coll Georgia, Dept Med, Augusta, GA 30912 USA. [Ye, Jiuming] Western New England Renal & Transplant Associates, Springfield, MA USA. [Paganini, Emil P.] Cleveland Clin Fdn, Dept Hypertens & Nephrol, Cleveland, OH 44195 USA. [Dworkin, Lance] Rhode Isl Hosp, Providence, RI USA. [Finkel, Kevin W.] Univ Texas Houston, Dept Internal Med, Houston, TX USA. [Kraus, Michael A.] Indiana Univ, Dept Med, Indianapolis, IN USA. RP Humes, HD (reprint author), Univ Michigan, Div Nephrol, Dept Internal Med, 4520 MSRB I,SPC 5651,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM dhumes@med.umich.edu OI Humes, David/0000-0002-4309-1614 NR 20 TC 98 Z9 105 U1 0 U2 8 PU AMER SOC 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 MAY PY 2008 VL 19 IS 5 BP 1034 EP 1040 DI 10.1681/ASN.2007080895 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 294RN UT WOS:000255423300028 PM 18272842 ER PT J AU Verfaellie, M Rajaram, S Fossum, K Williams, L AF Verfaellie, Mieke Rajaram, Suparna Fossum, Karen Williams, Lisa TI Not all repetition is alike: Different benefits of repetition in amnesia and normal memory SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE neuropsychology; amnesia; memory disorders; anoxia; encephalitis; Korsakoff syndrome ID RECOGNITION MEMORY; ENCODING VARIABILITY; RECOLLECTIVE EXPERIENCE; FUNCTIONAL-ASPECTS; RECALL; FAMILIARITY; DEFICITS; REMEMBER; WORDS; PET AB While it is well known that repetition can enhance memory in amnesia, little is known about Which forms of repetition are most beneficial. This study compared the effect on recognition memory of repetition of words in the same semantic context and in varied semantic contexts. To gain insight into the mechanisms by which these forms of repetition affect performance, participants were asked to make Remember/Know judgments during recognition. These judgments were Used to make inferences about the contribution of recollection and familiarity to performance. For individuals With intact memory, the two forms of repetition were equally beneficial to overall recognition, and were associated with both enhanced Remember and Know responses. However, varied repetition was associated with a hi,,her likelihood of Remember responses than was fixed repetition. The two forms of repetition also conferred equivalent benefits on overall recognition in amnesia, but in both cases. this enhancement was manifest exclusively in enhanced Know responses. We conclude that the repetition of information, and especially repetition in varied contexts, enhances recollection in individuals with intact memory, but exclusively affects familiarity in patients with severe amnesia. C1 [Verfaellie, Mieke; Fossum, Karen; Williams, Lisa] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. [Verfaellie, Mieke; Fossum, Karen; Williams, Lisa] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rajaram, Suparna] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP Verfaellie, M (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, 150 S Huntington Ave, Boston, MA 02130 USA. EM Verf@bu.edu OI LaRocque, Karen/0000-0002-6058-2706; Verfaellie, Mieke/0000-0001-5535-4584 FU NIMH NIH HHS [R01 MH071783, MH71783, R01 MH071783-02, MH57861] NR 43 TC 14 Z9 14 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2008 VL 14 IS 3 BP 365 EP 372 DI 10.1017/S1355617708080612 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 338VK UT WOS:000258537300002 PM 18419835 ER PT J AU Hallam, BJ Brown, WS Ross, C Buckwalter, JG Bigler, ED Tschanz, JT Norton, MC Welsh-Bohmer, KA Breitner, JCS AF Hallam, Bradley J. Brown, Warren S. Ross, Chris Buckwalter, J. Galen Bigler, Erin D. Tschanz, Joann T. Norton, Maria C. Welsh-Bohmer, Kathleen A. Breitner, John C. S. CA Cache Cty Investigators TI Regional atrophy of the corpus callosum in dementia SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Alzheimer's disease; vascular dementia; corpus callosum; neurodegnerative diseases; magnetic resonance imaging; mild cognitive impairment; MRI morphology; corpus callosum regions; brain atrophy; white matter degeneration ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE CERAD; PROGRESSIVE SUPRANUCLEAR PALSY; TEMPORAL-LOBE ATROPHY; NEUROPSYCHOLOGICAL ASSESSMENT; CORTICAL HYPOMETABOLISM; FRONTOTEMPORAL DEMENTIA; CACHE COUNTY; REGISTRY; PATTERN AB The regional distribution of degeneration of the corpus callosum (CC) in dementia is not yet clear. This Study compared regional CC size in participants (n = 179) from the Cache County Memory and Aging Study. Participants represented a range of cognitive function: Alzheimer's disease (AD). vascular dementia (VaD). mild ambiguous (MA-cognitive problems. but not severe enough for diagnosis of dementia), and health), older adults. CC Outlines obtained from midsagittal magnetic resonance images were divided into 99 equally spaced widths. Factor analysis of these callosal widths identified 10 callosal regions. Multivariate analysis of variance revealed significant group differences for anterior and posterior callosal regions. Post-hoc pairwise comparisons of CC regions in patient groups as compared to the control group (controlling for age) revealed trends toward smaller anterior and posterior re-ions, but riot all were statistically significant. As compared to controls, significantly smaller anterior and posterior CC regions were found in the AD group: significantly smaller anterior CC regions in the VaD group: but no significant CC regional differences in the MA group. Findings suggest that dementia-related CC atrophy occurs primarily in the anterior and posterior portions. C1 [Hallam, Bradley J.; Brown, Warren S.; Ross, Chris; Buckwalter, J. Galen] Fuller Grad Sch Psychol, Ctr Biopsychosocial Res, Travis Res Inst, Pasadena, CA 91101 USA. [Bigler, Erin D.] Brigham Young Univ, Dept Psychol, Brain Imaging & Behav Lab, Provo, UT 84602 USA. [Bigler, Erin D.] Brigham Young Univ, Dept Neurosci, Brain Imaging & Behav Lab, Provo, UT 84602 USA. [Buckwalter, J. Galen] eHarmony, Res & Dev, Pasadena, CA USA. [Bigler, Erin D.] Univ Utah, Utah Brain Inst, Salt Lake City, UT USA. [Bigler, Erin D.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Tschanz, Joann T.; Norton, Maria C.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Tschanz, Joann T.; Norton, Maria C.] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC USA. [Breitner, John C. S.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Breitner, John C. S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA. [Hallam, Bradley J.] Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 1W5, Canada. RP Brown, WS (reprint author), Fuller Grad Sch Psychol, Ctr Biopsychosocial Res, Travis Res Inst, 180 N Oakland Ave, Pasadena, CA 91101 USA. EM wsbrown@fuller.edu RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU National Institutes of Health [AG-11380, MH-14592]; Ira Fulton Foundation FX This research was supported in part by National Institutes of Health Grants AG-11380 and MH-14592 and the Ira Fulton Foundation. Patricia Cowell is gratefully acknowled for providing LIS With a copy of KSS Stereology, and David Wright for rewriting the source code for a Java based application. Lastly, the technical assistance of Tracy J. Abildskov and the Support of the entire Cache County, Utah, Memory and Aging research team are gratefully acknowledged. NR 67 TC 22 Z9 22 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2008 VL 14 IS 3 BP 414 EP 423 DI 10.1017/S1355617708080533 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 338VK UT WOS:000258537300007 PM 18419840 ER PT J AU Leung, WW Bowie, CR Harvey, PD AF Leung, Winnie W. Bowie, Christopher R. Harvey, Philip D. TI Functional implications of neuropsychological normality and symptom remission in older outpatients diagnosed with schizophrenia: A cross-sectional study SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE cognition; normal range; outcome; adjustment; social behavior; independent living ID DOUBLE-BLIND; NEUROCOGNITIVE DEFICITS; SOCIAL COGNITION; MENTAL-ILLNESS; SKILLS; PERFORMANCE; CRITERIA; TRIAL; EMPLOYMENT; OLANZAPINE AB Cognitive impairments in schizophrenia are well documented and correlated with functional disability. Although some patients demonstrate normal neuropsychological (NP) functioning, little is known about their functional disability. We examined the cross-sectional functional implications of NP normality and symptomatic remission in older Outpatients diagnosed with schizophrenia or schizoaffective disorder, who were administered a NP battery and performance-based measures Of functional and social competence, with their real-world functioning rated by case managers. NP status was classified by the General Deficit Score (GDS) and remission status was based on the Positive and Negative Syndrome Scale (PANSS), yielding four subsamples of patients: NP normal-remitted (n = 21), NP normal-symptomatic (n = 22), NP impaired-remitted (n = 90), and NP impaired-symptomatic (n = 97). NP normal patients demonstrated better functional and social competence and better ratings of real world functioning, after controlling for premorbid abilities. However, compared to normative date, NP normal patients manifested disability in several real-world domains, including residential status. These results suggest that NP status is a better predictor of functional outcome then symptom status or the interaction of the two factors. The disability seen in NP normal cases indicates that factors other than cognitive impairments may determine aspects of everyday outcomes in schizophrenia. C1 [Leung, Winnie W.] VISN Mental Illness Res Educ & Clin Ctr MIRECC 3, Dept Vet Affairs, Bronx, NY USA. [Leung, Winnie W.; Bowie, Christopher R.; Harvey, Philip D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Bowie, Christopher R.] James J Peters Bronx VA Med Ctr, Bronx, NY USA. [Harvey, Philip D.] Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA 30322 USA. RP Leung, WW (reprint author), New York State Psychiat Inst & Hosp, Lieber Ctr Schizophrenia Res & Treatment, 1051 Riverside Dr,Unit 14, New York, NY 10032 USA. EM leungwi@pi.cpmc.columbia.edu FU NIMH [MH 63116]; Conte Neuroscience Center [NIMH MH 36692] FX This research was supported by NIMH Grant Number MH 63116 to Dr. Harvey, the Mt. Sinai Silvio Conte Neuroscience Center (NIMH MH 36692: KL Davis PI), and the VA VISN 3 MIRECC. NR 61 TC 51 Z9 52 U1 8 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2008 VL 14 IS 3 BP 479 EP 488 DI 10.1017/S1355617708080600 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 338VK UT WOS:000258537300013 PM 18419846 ER PT J AU Shen, KR Austen, WG Mathisen, DJ AF Shen, K. Robert Austen, William Gerald, Jr. Mathisen, Douglas J. TI Use of a prefabricated pectoralis major muscle flap and pedicled jejunal interposition graft for salvage esophageal reconstruction after failed gastric pull-up and colon interposition SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 [Shen, K. Robert; Mathisen, Douglas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Thorac Surg, Boston, MA USA. [Austen, William Gerald, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. RP Shen, KR (reprint author), Mayo Clin, Div Gen Thorac Surg, 200 1st St Sw,Mayo Bldg 1263 W, Rochester, MN 55905 USA. EM shen.krobert@mayo.edu NR 5 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2008 VL 135 IS 5 BP 1186 EP 1187 DI 10.1016/j.jtcvs.2007.08.079 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 295ZH UT WOS:000255512800037 PM 18455610 ER PT J AU Kline, JA Courtney, DM Kabrhel, C Moore, CL Smithline, HA Plewa, MC Richman, PB O'Neil, BJ Nordenholz, K AF Kline, J. A. Courtney, D. M. Kabrhel, C. Moore, C. L. Smithline, H. A. Plewa, M. C. Richman, P. B. O'Neil, B. J. Nordenholz, K. TI Prospective multicenter evaluation of the pulmonary embolism rule-out criteria SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE computerized tomography angiography; D-dimer; decision rule; decision-making; diagnosis; medical malpractice; pulmonary embolism; venous thromboembolism ID EMERGENCY-DEPARTMENT PATIENTS; DEEP-VEIN THROMBOSIS; COMPUTED-TOMOGRAPHY; D-DIMER; DIAGNOSTIC RESEARCH; RADIATION-EXPOSURE; CLINICAL-FEATURES; SUDDEN-DEATH; RISK; ANGIOGRAPHY AB Backgound: Over-investigation of low-risk patients with suspected pulmonary embolism (PE) represents a growing problem. The combination of gestalt estimate of low suspicion for PE, together with the PE rule-out criteria [PERC(-): age < 50 years, pulse < 100 beats min(-1), SaO(2) >= 95%, no hemoptysis, no estrogen use, no surgery/trauma requiring hospitalization within 4 weeks, no prior venous thromboembolism (VTE), and no unilateral leg swelling], may reduce speculative testing for PE. We hypothesized that low suspicion and PERC(-) would predict a post-test probability of VTE(+) or death below 2.0%. Methods: We enrolled outpatients with suspected PE in 13 emergency departments. Clinicians completed a 72-field, web-based data form at the time of test order. Low suspicion required a gestalt pretest probability estimate of < 15%. The main outcome was the composite of image-proven VTE(+) or death from any cause within 45 days. Results: We enrolled 8138 patients, 85% of whom had a chief complaint of either dyspnea or chest pain. Clinicians reported a low suspicion for PE, together with PERC(-), in 1666 patients (20%). At initial testing and within 45 days, 561 patients (6.9%, 95% confidence interval 6.5-7.6) were VTE(+), and 56 others died. Among the low suspicion and PERC(-) patients, 15 were VTE(+) and one other patient died, yielding a false-negative rate of 16/1666 (1.0%, 0.6-1.6%). As a diagnostic test, low suspicion and PERC(-) had a sensitivity of 97.4% (95.8-98.5%) and a specificity of 21.9% (21.0-22.9%). Conclusions: The combination of gestalt estimate of low suspicion for PE and PERC(-) reduces the probability of VTE to below 2% in about 20% of outpatients with suspected PE. C1 [Kline, J. A.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Courtney, D. M.] Northwestern Mem Hosp, Dept Emergency Med, Chicago, IL USA. [Kabrhel, C.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Moore, C. L.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Smithline, H. A.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Plewa, M. C.] St Vincent Mercy Med, Dept Emergency Med, Toledo, OH USA. [Richman, P. B.] Mayo Clin, Dept Emergency Med, Scottsdale, AZ USA. [O'Neil, B. J.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48072 USA. [Nordenholz, K.] Univ Colorado, Sch Hlth Sci, Dept Surg, Denver, CO 80202 USA. RP Kline, JA (reprint author), Med Carolinas Med Ctr, Dept Emergency, POB 32861, Charlotte, NC 28323 USA. EM jkline@carolinas.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU NHLBI NIH HHS [K23HL077404, R01 HL074384, R41HL074415, R42HL074415] NR 39 TC 115 Z9 115 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD MAY PY 2008 VL 6 IS 5 BP 772 EP 780 DI 10.1111/j.1538-7836.2008.02944.x PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 288MV UT WOS:000254991400010 PM 18318689 ER PT J AU Hamilton, RJ Aronson, WJ Terris, MK Kane, CJ Presti, JC Amling, CL Freedland, SJ AF Hamilton, Robert J. Aronson, William J. Terris, Martha K. Kane, Christopher J. Presti, Joseph C., Jr. Amling, Christopher L. Freedland, Stephen J. TI Limitations of prostate specific antigen doubling time following biochemical recurrence after radical prostatectomy: Results from the SEARCH database SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; neoplasm recurrence; local; prostatectomy; prostate-specific antigen ID CANCER-SPECIFIC MORTALITY; RADIATION-THERAPY; HORMONAL-THERAPY; OBESITY; RADIOTHERAPY; PROGRESSION AB Purpose: Prostate specific antigen doubling time following biochemical recurrence after radical prostatectomy is a powerful predictor of prostate cancer specific and overall death. To calculate prostate specific antigen doubling time requires multiple prostate specific antigen determinations that are unaltered by secondary therapy and separated by sufficient time. Physicians and patients may be unwilling to wait before starting secondary therapy, especially for high risk recurrences. Hence, those with calculable prostate specific antigen doubling time may represent a select lower risk group relative to all men with biochemical recurrence. Materials and Methods: We compared clinical and pathological features between patients with and without calculable prostate specific antigen doubling time. We assessed time trends in the proportion with calculable prostate specific antigen doubling time in 535 patients with biochemical recurrence after radical prostatectomy at 5 Veterans Affairs medical centers comprising the SEARCH (Shared Equal Access Regional Cancer Hospital) database between 1988 and 2003. Results: Prostate specific antigen doubling time was not calculable in 187 patients (35%) due to secondary therapy in 155 (83%). With time the proportion of patients with calculable prostate specific antigen doubling time decreased significantly (p < 0.001). Adverse pathological features, more rapid time to recurrence, higher body mass index and differing surgical centers were associated with not having a calculable prostate specific antigen doubling time. Of all men with recurrence in the most recent year of analysis the adjusted probability of having a calculable prostate specific antigen doubling time was only 43%, that is 61% in patients with favorable pathological results but only 30% in those with seminal vesicle invasion. Conclusions: Those with calculable prostate specific antigen doubling time represented a select, lower risk cohort and the proportion of patients with calculable prostate specific antigen doubling time decreased with time. This highlights the need for alternative markers in men with recurrent prostate cancer because one of our best current markers, prostate specific antigen doubling time, is only available in a limited number of patients. C1 [Hamilton, Robert J.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC 27710 USA. [Hamilton, Robert J.; Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Hamilton, Robert J.] Univ Toronto, Dept Surg, Div Urol, Toronto, ON, Canada. [Aronson, William J.] Univ Calif Los Angeles, Dept Surg, Urol Sect, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Kane, Christopher J.] Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. [Kane, Christopher J.] Vet Affairs Med Ctr, Urol Sect, San Francisco, CA 94121 USA. [Presti, Joseph C., Jr.] Vet Affairs Med Ctr Palo Alto, Urol Sect, Palo Alto, CA USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Vet Affairs Med Ctr, Augusta, GA 30912 USA. [Amling, Christopher L.] Univ Alabama, Dept Urol, Birmingham, AL USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Div Urol, Box 2626 DUMC, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Hamilton, Robert/0000-0002-6715-5934; Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50 CA092131-01A1, R01 CA100938, P50 CA92131-01A1, P50 CA092131, R01CA100938] NR 20 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2008 VL 179 IS 5 BP 1785 EP 1789 DI 10.1016/j.juro.2008.01.040 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 288SE UT WOS:000255005300038 PM 18343434 ER PT J AU Jayachandran, J Banez, LL Levy, DE Aronson, WJ Terris, MK Presti, JC Amling, CL Kane, CJ Freedland, SJ AF Jayachandran, Jayakrishnan Banez, Lionel L. Levy, Donna E. Aronson, William J. Terris, Martha K. Presti, Joseph C., Jr. Amling, Christopher L. Kane, Christopher J. Freedland, Stephen J. CA SEARCH Database Study Grp TI Risk stratification for biochemical recurrence in men with positive surgical margins or extracapsular disease after radical prostatectomy: Results from the SEARCH database SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostatectomy; prostate-specific antigen; risk ID RETROPUBIC PROSTATECTOMY; ADJUVANT THERAPY; CANCER; PROGRESSION; RADIOTHERAPY; SELECTION; IMPACT; TRIAL AB Purpose: In men with extracapsular disease or positive surgical margins after radical prostatectomy immediate adjuvant therapy decreases the risk of biochemical recurrence at the cost of increased toxicity. We further stratified these men into a low risk group in which watchful waiting after surgery may be preferred and a high risk cohort in which adjuvant therapy may be preferred. Materials and Methods: We performed a retrospective analysis of the records of 902 men treated with radical prostatectomy in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database between 1988 and 2007 with positive surgical margins and/or extracapsular disease without seminal vesicle invasion or lymph node metastasis. The significant independent predictors of biochemical recurrence were determined using a multivariate Cox proportional hazards model. Based on the recurrence risk generated from the multivariate Cox proportional hazards regression model we generated tables to estimate the risk of recurrence-free survival 1, 3 and 5 years after surgery. Results: At a median of 3 years of followup, 346 patients (39%) had biochemical recurrence. On multivariate analysis the significant predictors of biochemical recurrence were age more than 60 years, prostate specific antigen more than 10 ng/ml, Gleason score 4 + 3 and 8-10, 2 or more sites of positive surgical margins and prostate specimen weight 30 gm or less. As determined by the concordance index, the overall predictive accuracy of the model was 0.67, while it was 0.60 for the postoperative Kattan nomogram in this patient population. Conclusions: We have developed a simple instrument that, once validated, may aid in the postoperative decision making process for men at intermediate risk for recurrence after prostatectomy. C1 [Jayachandran, Jayakrishnan; Banez, Lionel L.; Levy, Donna E.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC USA. [Jayachandran, Jayakrishnan; Banez, Lionel L.; Levy, Donna E.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Div Urol Surg, Durham, NC USA. [Jayachandran, Jayakrishnan; Banez, Lionel L.; Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Urol Sect, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Presti, Joseph C., Jr.] Vet Affairs Med Ctr, Urol Sect, Palo Alto, CA 94304 USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. [Kane, Christopher J.] Vet Affairs Med Ctr, Urol Sect, San Francisco, CA 94121 USA. [Kane, Christopher J.] Univ Calif San Francisco, Dept Urol, San Francisco Sch Med, San Francisco, CA 94143 USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Terris, Martha K.] Vet Affairs Med Ctr Augusta, Urol Sect, Augusta, GA 30912 USA. [Amling, Christopher L.] Univ Alabama, Dept Urol, Birmingham, AL USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Div Urol, Box 2626 DUMC, Durham, NC 27706 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50 CA092131-07, P50 CA092131, R01CA100938, R01 CA100938, P50 CA92131-01A1] NR 20 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2008 VL 179 IS 5 BP 1791 EP 1796 DI 10.1016/j.juro.2008.01.043 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 288SE UT WOS:000255005300040 PM 18343426 ER PT J AU Makaroun, MS Dillavou, ED Wheatley, GH Cambria, RP AF Makaroun, Michel S. Dillavou, Ellen D. Wheatley, Grayson H. Cambria, Richard P. CA Gore RAG Investigators TI Five-year results of endovascular treatment with the Gore TAG device compared with open repair of thoracic aortic aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the Society-for-Vascular-Surgery CY JUN 06-10, 2007 CL Philadelphia, PA SP Soc Vasc Surg ID OPEN-SURGICAL REPAIR; EXCLUDER DEVICE; GRAFT REPAIR; STENT-GRAFT; ENDOPROSTHESIS; EXPERIENCE; TRIAL AB Objectives: Report the results of a phase II multicenter, prospective trial comparing endovascular treatment of descending thoracic aneurysm (TEVAR) with the TAG device to surgical controls after 5 years of follow-up. Methods: The Gore TAG trial compared the TAG endograft patients (n = 140) with standard open surgical controls (n = 94) with enrollment from September of 1999 to May of 2001. An additional 51 patients were enrolled in 2003 after revision of the endograft. Follow-up consisted of patient visits, computed tomography (CT) scans and x-rays at 1, 6, and 12 months and yearly. Significant sac size change was defined as >= 5 mm increase or decrease from the 1 month baseline measurement. Migration was defined as >= 10 mm cranial or caudal movement of the device inside the aorta. Significance was determined as P <= .05. Results. At 5 years, aneurysm-related mortality was lower for TAG patients at 2.8% compared with open controls at 11.7% (P = .008). No differences in all-cause mortality were noted, with 68% of TAG patients and 67% of open controls surviving to 5 years (P = .43). Major adverse events at 5 years were significantly reduced in the TAG group; 57.9% vs 78.7% (P = .001). Endoleaks in the TAG group decreased from 8.1% at 1 month to 4.3% at 5 years. Five TAG patients have undergone major aneurysm-related re-interventions at 5 years (3.6%), including one arch aneurysm repair for type 1 endoleak and migration, one open conversion and five endovascular procedures for endoleaks in three patients. There were fewer secondary procedures not directly related to aneurysm repair in the TAG vs the open repair group at 5 years, 15.0% vs 31.9%, (P = .01). For TAG patients, sacsizeat 60 months decreased in 50% and increased in 19% compared with the 1-month baseline. Comparison with the modified low-porosity device at 24 months showed sac increase in 12.9% of original vs 2.9% in modified grafts (P = .11). At 5 years, there have been no ruptures, one migration, no collapse, and 20 instances of fracture in 19 patients, all before the revision of the TAG graft. Conclusions. In anatomically suitable patients, TAG treatment of thoracic aneurysms is superior to surgical repair at 5 years. Although sac enlargement is concerning, early modified device results indicate this issue may be resolved. C1 [Makaroun, Michel S.; Dillavou, Ellen D.] Univ Pittsburgh, Med Ctr, Div Vasc Surg, Pittsburgh, PA 15213 USA. [Wheatley, Grayson H.] Arizona Heart Inst, Div Cardiovasc Surg, Phoenix, AZ USA. [Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA USA. RP Dillavou, ED (reprint author), Univ Pittsburgh, Med Ctr, Div Vasc Surg, Suite A-1011,PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM dillavoued@upumc.edu RI Wheatley, Grayson/G-2828-2016 OI Wheatley, Grayson/0000-0003-1181-5232 NR 14 TC 181 Z9 185 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2008 VL 47 IS 5 BP 912 EP 918 DI 10.1016/j.jvs.2007.12.006 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 292VR UT WOS:000255294700003 PM 18353605 ER PT J AU Huang, IC Li, WH Sui, JH Marasco, W Choe, H Farzan, M AF Huang, I-Chueh Li, Wenhui Sui, Jianhua Marasco, Wayne Choe, Hyeryun Farzan, Michael TI Influenza A virus neuraminidase limits viral superinfection SO JOURNAL OF VIROLOGY LA English DT Article ID ION-CHANNEL ACTIVITY; MEMBRANE-FUSION; RECEPTOR-BINDING; DOWN-MODULATION; HUMAN AIRWAY; ACTIVE-SITE; H3N2 VIRUS; B VIRUSES; IN-VITRO; HEMAGGLUTININ AB Enveloped viruses use multiple mechanisms to inhibit infection of a target cell by more than one virion. These mechanisms may be of particular importance for the evolution of segmented viruses, because superinfection exclusion may limit the frequency of reassortment of viral genes. Here, we show that cellular expression of influenza A virus neuraminidase (NA), but not hemagglutinin (HA) or the M2 proton pump, inhibits entry of HA-pseudotyped retroviruses. Cells infected with H1N1 or H3N2 influenza A virus were similarly refractory to HA-mediated infection and to superinfection with a second influenza A virus. Both HA-mediated entry and viral superinfection were rescued by the neuraminidase inhibitors oseltamivir carboxylate and zanamivir. These inhibitors also prevented the removal of alpha-2,3- and alpha-2,6-linked sialic acid observed in cells expressing NA or infected with influenza A viruses. Our data indicate that NA alone among viral proteins limits influenza A virus superinfection. C1 [Huang, I-Chueh; Li, Wenhui; Farzan, Michael] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. [Sui, Jianhua; Marasco, Wayne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Choe, Hyeryun] Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP Farzan, M (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, 1 Pin Hill Dr, Southborough, MA 01772 USA. EM farzan@hms.harvard.edu OI Li, Wenhui/0000-0003-1305-7404; SUI, JIANHUA/0000-0002-1272-9662 NR 56 TC 69 Z9 69 U1 0 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2008 VL 82 IS 10 BP 4834 EP 4843 DI 10.1128/JVI.00079-08 PG 10 WC Virology SC Virology GA 297MA UT WOS:000255619600015 PM 18321971 ER PT J AU de Oliveira, AP Glauser, DL Laimbacher, AS Strasser, R Schraner, EM Wild, P Ziegler, U Breakefield, XO Ackermann, M Fraefel, C AF de Oliveira, Anna Paula Glauser, Daniel L. Laimbacher, Andrea S. Strasser, Regina Schraner, Elisabeth M. Wild, Peter Ziegler, Urs Breakefield, Xandra O. Ackermann, Mathias Fraefel, Cornel TI Live visualization of herpes simplex virus type 1 compartment dynamics SO JOURNAL OF VIROLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; OPEN READING FRAME; GLYCOPROTEIN-H; TEGUMENT PROTEINS; CAPSID PROTEIN; REPLICATION COMPARTMENTS; ADENOASSOCIATED-VIRUS; IN-VITRO; INFECTIOUS VIRUS; DNA-REPLICATION AB We have constructed a recombinant herpes simplex virus type 1 (HSV-1) that simultaneously encodes selected structural proteins from all three virion compartments-capsid, tegument, and envelope-fused with autofluorescent proteins. This triple-fluorescent recombinant, rHSV-RYC, was replication competent, albeit with delayed kinetics, incorporated the fusion proteins into all three virion compartments, and was comparable to wild-type HSV-1 at the ultrastructural level. The VP26 capsid fusion protein (monomeric red fluorescent protein [mRFP]-VP26) was first observed throughout the nucleus and later accumulated in viral replication compartments. In the course of infection, mRFP-VP26 formed small foci in the periphery of the replication compartments that expanded and coalesced over time into much larger foci. The envelope glycoprotein H (gH) fusion protein (enhanced yellow fluorescent protein [EYFP]-gH) was first observed accumulating in a vesicular pattern in the cytoplasm and was then incorporated primarily into the nuclear membrane. The VP16 tegument fusion protein (VP16-enhanced cyan fluorescent protein [ECFP]) was first observed in a diffuse nuclear pattern and then accumulated in viral replication compartments. In addition, it also formed small foci in the periphery of the replication compartments which, however, did not colocalize with the small mRFP-VP26 foci. Later, VP16-ECFP was redistributed out of the nucleus into the cytoplasm, where it accumulated in vesicular foci and in perinuclear clusters reminiscent of the Golgi apparatus. Late in infection, mRFP-VP26, EYFP-gH, and VP16-ECFP were found colocalizing in dots at the plasma membrane, possibly representing mature progeny virus. In summary, this study provides new insights into the dynamics of compartmentalization and interaction among capsid, tegument, and envelope proteins. Similar strategies can also be applied to assess other dynamic events in the virus life cycle, such as entry and trafficking. C1 [de Oliveira, Anna Paula; Glauser, Daniel L.; Laimbacher, Andrea S.; Strasser, Regina; Ackermann, Mathias; Fraefel, Cornel] Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. [Schraner, Elisabeth M.; Wild, Peter] Univ Zurich, Inst Vet Anat, CH-8057 Zurich, Switzerland. [Ziegler, Urs] Univ Zurich, Inst Anat, CH-8057 Zurich, Switzerland. [Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Mol Neurogenet Unit, Boston, MA USA. RP Fraefel, C (reprint author), Univ Zurich, Inst Virol, Winterthurerstr 266a, CH-8057 Zurich, Switzerland. EM cornel.fraefel@vetvir.uzh.ch FU NCI NIH HHS [CA69246, P01 CA069246] NR 70 TC 25 Z9 25 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2008 VL 82 IS 10 BP 4974 EP 4990 DI 10.1128/JVI.02431-07 PG 17 WC Virology SC Virology GA 297MA UT WOS:000255619600029 PM 18337577 ER PT J AU Bowen, DG Shoukry, NH Grakoui, A Fuller, MJ Cawthon, AG Dong, C Hasselschwert, DL Brasky, KM Freeman, GJ Seth, NP Wucherpfernnig, KW Houghton, M Walker, CM AF Bowen, David G. Shoukry, Naglaa H. Grakoui, Arash Fuller, Michael J. Cawthon, Andrew G. Dong, Christine Hasselschwert, Dana L. Brasky, Kathleen M. Freeman, Gordon J. Seth, Nilufer P. Wucherpfernnig, Kai W. Houghton, Michael Walker, Christopher M. TI Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID PD-1 EXPRESSION; VIRAL-INFECTION; LYMPHOCYTES; DYSFUNCTION; PHENOTYPE; RESPONSES; DIFFERENTIATION; EXHAUSTION AB The inhibitory receptor programmed death-1 (PD-1) is present on CD8(+) T cells in chronic hepatitis C virus (HCV), but expression patterns in spontaneously resolving infections are incompletely characterized. Here we report that PD-1 was usually absent on memory CD8(+) T cells from chimpanzees with resolved infections, but sustained low-level expression was sometimes observed in the absence of apparent virus replication. PD-1-positive memory T cells expanded and displayed antiviral activity upon reinfection with HCV, indicating conserved function. This animal model should facilitate studies of whether PD-1 differentially influences effector and memory T-cell function in resolved versus persistent human infections. C1 [Bowen, David G.; Fuller, Michael J.; Cawthon, Andrew G.; Walker, Christopher M.] Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH 43205 USA. [Shoukry, Naglaa H.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Shoukry, Naglaa H.] Univ Montreal Hosp Ctr, Montreal, PQ, Canada. [Grakoui, Arash] Emory Univ, Atlanta, GA 30322 USA. [Hasselschwert, Dana L.] New Iberia Res Ctr, New Iberia, LA USA. [Brasky, Kathleen M.] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Seth, Nilufer P.; Wucherpfernnig, Kai W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Dong, Christine; Houghton, Michael] Novartis Corp, Emeryville, CA USA. [Walker, Christopher M.] Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA. RP Walker, CM (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, WA4011,700 Childrens Dr, Columbus, OH 43205 USA. EM Christopher.Walker@nationwidechildrens.org FU NCI NIH HHS [1CO6RR1643-01]; NCRR NIH HHS [U42 RR015087, P51 RR000165, C06 RR014491, 1C06RR014491-01, 5U42RR15087, RR-00165]; NIAID NIH HHS [R56 AI070101, R01 AI070101, F32 AI055193, AI070101, U19 AI048231, U19 AI48231]; PHS HHS [R01 A147367] NR 22 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2008 VL 82 IS 10 BP 5109 EP 5114 DI 10.1128/JVI.00060-08 PG 6 WC Virology SC Virology GA 297MA UT WOS:000255619600043 PM 18337576 ER PT J AU Norton, MC Singh, A Skoog, I Corcoran, C Tschanz, JT Zandi, PP Breitner, JCS Welsh-Bohmer, KA Steffens, DC AF Norton, Maria C. Singh, Archana Skoog, Ingmar Corcoran, Christopher Tschanz, JoAnn T. Zandi, Peter P. Breitner, John C. S. Welsh-Bohmer, Kathleen A. Steffens, David C. CA Cache Cty Investigators TI Church attendance and new episodes of major depression in a community study of older adults: The Cache County Study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE church attendance; depression; Latter Day Saints ID DIAGNOSTIC-INTERVIEW-SCHEDULE; LATE-LIFE DEPRESSION; MENTAL-HEALTH; GERIATRIC DEPRESSION; ELDERLY POPULATION; GENDER-DIFFERENCES; FOLLOW-UP; RELIGIOSITY; PREVALENCE; AGE AB We examined the relation between church attendance, membership in the Church of Jesus Christ of Latter-Day Saints (LDS), and major depressive episode, in a population-based study of aging and dementia in Cache County, Utah. Participants included 2,989 nondemented individuals aged between 65 and 100 years who were interviewed initially in 1995 to 1996 and again in 1998 to 1999. LDS church members reported twice the rate of major depression that non-LDS members did (odds ratio = 2.56, 95% confidence interval = 1.07-6.08). Individuals attending church weekly or more often had a significantly lower risk for major depression. After controlling for demographic and health variables and the strongest predictor of future episodes of depression, a prior depression history, we found that church attendance more often than weekly remained a significant protectant (odds ratio = 0.51, 95% confidence interval = 0.28-0.92). Results suggest that there may be a threshold of church attendance that is necessary for a person to garner long-term protection from depression. We discuss sociological factors relevant to LDS culture. C1 [Norton, Maria C.; Singh, Archana] Utah State Univ, Dept Family Consumer & Human Dev, Cache Cty Study Memory Hlth & Aging, Logan, UT 84322 USA. [Norton, Maria C.; Tschanz, JoAnn T.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Corcoran, Christopher] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. [Norton, Maria C.; Corcoran, Christopher; Tschanz, JoAnn T.] Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. [Skoog, Ingmar] Univ Gothenburg, Inst Clin Neurosci, Gothenburg, Sweden. [Zandi, Peter P.] Johns Hopkins Univ, Dept Mental Hyg, Baltimore, MD USA. [Breitner, John C. S.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Breitner, John C. S.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Welsh-Bohmer, Kathleen A.; Steffens, David C.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Welsh-Bohmer, Kathleen A.] Duke Univ, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC USA. RP Norton, MC (reprint author), Utah State Univ, Dept Family Consumer & Human Dev, Cache Cty Study Memory Hlth & Aging, 4440 Old Main Hill, Logan, UT 84322 USA. EM maria.norton@usu.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013 FU NIA NIH HHS [R01 AG011380, AG 11380, AG 21136, R01 AG011380-13, R01 AG021136, R01 AG021136-05] NR 67 TC 9 Z9 9 U1 5 U2 8 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD MAY PY 2008 VL 63 IS 3 BP P129 EP P137 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 316CF UT WOS:000256925800002 PM 18559677 ER PT J AU Phipps, JA Feener, EP AF Phipps, J. A. Feener, E. P. TI The kallikrein-kinin system in diabetic retinopathy: Lessons for the kidney SO KIDNEY INTERNATIONAL LA English DT Review ID BRADYKININ B2 RECEPTOR; CONVERTING-ENZYME-INHIBITION; MOLECULAR-WEIGHT KININOGEN; OXIDE SYNTHASE ACTIVATION; NF-KAPPA-B; VASCULAR-PERMEABILITY; B-1 RECEPTOR; TISSUE KALLIKREIN; UP-REGULATION; ISCHEMIA/REPERFUSION INJURY AB Diabetic retinopathy and diabetic nephropathy are common microvascular complications of diabetes. The kallikrein-kinin system (KKS) has been implicated in the development of both conditions, and, in particular, bradykinin and its receptors have been shown to exert angiogenic and proinflammatory actions. Several of the key processes that underlie the development of diabetic retinopathy, such as increased vascular permeability, edema, neovascularization, and inflammatory changes, have been associated with the KKS, and recent work has shown that components of the KKS, including plasma kallikrein, factor XIIa, and high-molecular-weight kininogen, are present in the vitreous of people with diabetic retinopathy. The role of the KKS in the development of diabetic nephropathy is controversial, with both adverse and protective effects of bradykinin and its receptors reported. The review examines the role of the KKS in pathways central to the development of diabetic retinopathy and compares this with reported actions of this system in diabetic nephropathy. The possibility of therapeutic intervention targeting bradykinin and its receptors as treatment for diabetic microvascular conditions is considered. C1 [Phipps, J. A.; Feener, E. P.] Harvard Univ, Sch Med, Div Res, Dept Med,Joslin Diabet Ctr, Boston, MA 02115 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Div Res, Dept Med,Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM edward.feener@joslin.harvard.edu FU NIDDK NIH HHS [DK 60165, P30 DK036836] NR 45 TC 24 Z9 24 U1 1 U2 2 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 MAY PY 2008 VL 73 IS 10 BP 1114 EP 1119 DI 10.1038/ki.2008.9 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 294NA UT WOS:000255411600004 PM 18272958 ER PT J AU Wingert, RA Davidson, AJ AF Wingert, R. A. Davidson, A. J. TI The zebrafish pronephros: A model to study nephron segmentation SO KIDNEY INTERNATIONAL LA English DT Review ID CYSTIC KIDNEY-DISEASE; PECTORAL FIN BUD; RETINOIC ACID; PANCREAS DEVELOPMENT; DISTAL TUBULE; TRANSPORT PROCESSES; MAMMALIAN NEPHRON; CELL FATE; XENOPUS; EXPRESSION AB Nephrons possess a segmental organization where each segment is specialized for the secretion and reabsorption of particular solutes. The developmental control of nephron segment patterning remains one of the enigmas within the field of renal biology. Achieving an understanding of the mechanisms that direct nephron segmentation has the potential to shed light on the causes of kidney birth defects and renal diseases in humans. Researchers studying embryonic kidney development in zebrafish and Xenopus have recently demonstrated that the pronephric nephrons in these vertebrates are segmented in a similar fashion as their mammalian counterparts. Further, it has been shown that retinoic acid signaling establishes proximodistal segment identities in the zebrafish pronephros by modulating the expression of renal transcription factors and components of signaling pathways that are known to direct segment fates during mammalian nephrogenesis. These findings present the zebrafish model as an excellent genetic system in which to interrogate the conserved developmental pathways that control nephron segmentation in both lower vertebrates and mammals. C1 [Wingert, R. A.; Davidson, A. J.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Davidson, A. J.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Davidson, AJ (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,CPZN 4265A, Boston, MA 02114 USA. EM ajdavidson@partners.org NR 65 TC 77 Z9 78 U1 0 U2 10 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 MAY PY 2008 VL 73 IS 10 BP 1120 EP 1127 DI 10.1038/ki.2008.37 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 294NA UT WOS:000255411600005 PM 18322540 ER PT J AU Shipitsin, M Polyak, K AF Shipitsin, Michail Polyak, Kornelia TI The cancer stem cell hypothesis: in search of definitions, markers, and relevance SO LABORATORY INVESTIGATION LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BREAST-TUMOR HETEROGENEITY; PROSPECTIVE IDENTIFICATION; RENEWAL; NICHE; LINES AB Cancer is a disease of genes. Inherited or somatic alterations in genes are what make a normal cell ignore growth-controlling signals and form a tumor that eventually leads to the destruction of the organism. Based on accumulated knowledge on the genetic composition of cancer cells, the clonal evolution model of tumorigenesis was established, which explains multiple aspects of human disease and clinical observations. However, the recently popularized cancer stem cell hypothesis questions that all or most tumor cells can participate in tumor evolution and restricts this property to a subset of them defined as 'cancer stem cells' due to their stem cell- like characteristics. Enthusiasm surrounding this area of investigation and its presumed clinical implications led to a spurt of studies in various cancer types and model systems. Rigorous study design and critical data interpretation have to be employed to test the scientific and clinical relevance of the cancer stem cell hypothesis and its relationship to the clonal evolution model. C1 [Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Shipitsin, Michail; Polyak, Kornelia] Harvard Med Sch, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. EM Kornelia_polyak@dfci.harvard.edu FU NCI NIH HHS [R01 CA116235-02, P50 CA089393, P50 CA089393-060014, P50 CA089393-070014, P50 CA089393-080014, R01 CA094074, R01 CA094074-05, R01 CA116235, R01 CA116235-01A1, R01 CA116235-03] NR 28 TC 110 Z9 119 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2008 VL 88 IS 5 BP 459 EP 463 DI 10.1038/labinvest.2008.14 PG 5 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 292IN UT WOS:000255259800002 PM 18379567 ER PT J AU Van Deerlin, VM Leverenz, JB Bekris, LM Bird, TD Yuan, WX Elman, LB Clay, D Wood, EM Chen-Plotkin, AS Martinez-Lage, M Steinbart, E McCluskey, L Grossman, M Neumann, M Wu, IL Yang, WS Kalb, R Galasko, DR Montine, TJ Trojanowski, JQ Lee, VMY Schellenberg, GD Yu, CE AF Van Deerlin, Vivianna M. Leverenz, James B. Bekris, Lynn M. Bird, Thomas D. Yuan, Wuxing Elman, Lauren B. Clay, Dona Wood, Elisabeth McCarty Chen-Plotkin, Alice S. Martinez-Lage, Maria Steinbart, Ellen McCluskey, Leo Grossman, Murray Neumann, Manueia Wu, I-Lin Yang, Wei-Shiung Kalb, Robert Galasko, Douglas R. Montine, Thomas J. Trojanowski, John Q. Lee, Virginia M-Y Schellenberg, Gerard D. Yu, Chang-En TI TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis SO LANCET NEUROLOGY LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; MOTOR-NEURON DISEASE; NUCLEAR FACTOR TDP-43; ALPHA-SYNUCLEIN; CHROMOSOME 9P; DEMENTIA; PROTEIN; EXON-9; ALS; IMPAIRMENT AB Background TDP-43 is a major component of the ubiquitinated inclusions that characterise amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitin inclusions (FTLD-U). TDP-43 is an RNA-binding and DNA-binding protein that has many functions and is encoded by the TAR DNA-binding protein gene (TARDBP) on chromosome 1. Our aim was to investigate whether TARDBP is a candidate disease gene for familial ALS that is not associated with mutations in superoxide dismutase 1 (SOD1). Methods TARDBP was sequenced in 259 patients with ALS, FTLD, or both. We used TaqMan-based SNP genotyping to screen for the identified variants in control groups matched to two kindreds of patients for age and ethnic origin. Additional clinical, genetic, and pathological assessments were made in these two families. Findings We identified two variants in TARDBP, which would encode Gly290Ala and Gly298Ser forms of TDP-43, in two kindreds with familial ALS. The variants seem to be pathogenic because they co-segregated with disease in both families, were absent in controls, and were associated with TDP-43 neuropathology in both members of one of these families for whom CNS tissue was available. Interpretation The Gly290Ala and Gly298Ser mutations are located in the glycine-rich domain of TDP-43, which regulates gene expression and mediates protein-protein interactions such as those with heterogeneous ribonucleoproteins. Owing to the varied and important cellular functions of TDP-43, these mutations might cause neurodegeneration through both gains and losses of function. The finding of pathogenic mutations in TARDBP implicates TDP-43 as an active mediator of neurodegeneration in TDP-43 proteinopathies, a class of disorder that includes ALS and FTLD-U. Funding National Institutes of Health (AG10124, AG17586, AG005136-22, PO1 AG14382), Department of Veterans Affairs, Friedrich-Baur Stiftung (0017/2007), US Public Health Service, ALS Association, and Fundacio 'la Caixa'. C1 [Van Deerlin, Vivianna M.; Yuan, Wuxing; Clay, Dona; Wood, Elisabeth McCarty; Chen-Plotkin, Alice S.; Martinez-Lage, Maria; Trojanowski, John Q.; Lee, Virginia M-Y] Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Elman, Lauren B.; McCluskey, Leo; Grossman, Murray] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Van Deerlin, Vivianna M.; Trojanowski, John Q.; Lee, Virginia M-Y] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. [Bekris, Lynn M.; Bird, Thomas D.; Steinbart, Ellen; Schellenberg, Gerard D.; Yu, Chang-En] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Yu, Chang-En] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Neumann, Manueia] Univ Munich, Ctr Neuropathol & Pr Res, Munich, Germany. [Wu, I-Lin; Yang, Wei-Shiung] Natl Taiwan Univ, Grad Inst Clin Med, Taipei, Taiwan. [Wu, I-Lin; Yang, Wei-Shiung] Natl Taiwan Univ Hosp, Dept Internal Med, Div Endocrinol & Metab, Taipei, Taiwan. [Kalb, Robert] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Galasko, Douglas R.] Univ San Diego, Dept Neurosci, La Jolla, CA USA. RP Schellenberg, GD (reprint author), Vet Adm Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zachdad@u.washington.edu RI Neumann, Manuela/F-6558-2011; OI Martinez-Lage, Maria/0000-0002-5859-7562; YANG, WEI-SHIUNG/0000-0001-5087-373X FU NIA NIH HHS [P01 AG014382, P01 AG017586, P30 AG010124, P50 AG005136, P50 AG005136-25] NR 38 TC 362 Z9 369 U1 3 U2 36 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAY PY 2008 VL 7 IS 5 BP 409 EP 416 DI 10.1016/S1474-4422(08)70071-1 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 296AB UT WOS:000255514800013 PM 18396105 ER PT J AU Stankovic, KM Goldsztein, H Reh, DD Platt, MP Metson, R AF Stankovic, Konstantina M. Goldsztein, Hernan Reh, Douglas D. Platt, Michael P. Metson, Ralph TI Gene Expression Profiling of Nasal Polyps Associated With Chronic Sinusitis and Aspirin-Sensitive Asthma SO LARYNGOSCOPE LA English DT Article DE Sinonasal polyposis; chronic rhinosinusitis; sinusitis; asthma; triad asthma; aspirin-sensitive asthma; microarray; periostin; POSTN; c-Met; met protooncogene; prolactin-induced protein; zinc alpha2-glycoprotein; protein phosphatase 1 ID CONNECTIVE TISSUES; BRONCHIAL-ASTHMA; CLASS DISCOVERY; MICROARRAY; PERIOSTIN; RHINOSINUSITIS; PATTERNS; SIGNALS; GROWTH; CANCER AB Objective: To identify genes whose expression is most characteristic of chronic rhinosinusitis and aspirinsensitive asthma through genome-wide transcriptional profiling of nasal polyp tissue. Study Design: Prospective, controlled study conducted at a tertiary care institution. Methods: Thirty genome-wide expression microarrays were used to compare nasal polyp tissue from patients with chronic rhinosinusitis alone (CRS, n = 10) or chronic rhinosinusitis and a history of aspirin-sensitive asthma (ASA, n = 10) to normal sinonasal mucosa from patients who underwent surgery for non-sinus related conditions (controls, n = 10). Genes found to be most characteristic of each polyp phenotype, as determined from bioinformatic analyses, were validated using real-time quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry in different patient sets. Results: The transcriptional signature of the control mucosa was distinctly different from that of either polyp phenotype. Genes most characteristic of the CRS phenotype included two upregulated genes-met protooncogene (MET) and protein phosphatase I regulatory subunit 9B (PPP1R9B)-and two downregulated genes-prolactin-induced protein (PIP) and zinc alpha2-glycoprotein (AZGP1). The gene most characteristic of the ASA phenotype was periostin (POSTN), which was upregulated relative to controls. Differences between the CRS and ASA phenotypes were associated with alterations in the 6p22, 22q13, and 1q23 chromosomal regions. Conclusions: Nasal polyps appear to have characteristic transcriptional signatures compared to normal sinonasal mucosa. The five genes identified in this study likely play roles in the pathogenesis of polyps associated with CRS and ASA, and are therefore attractive targets for novel medical therapies for these common debilitating diseases. C1 [Stankovic, Konstantina M.; Goldsztein, Hernan; Reh, Douglas D.; Platt, Michael P.; Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Stankovic, Konstantina M.; Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Metson, R (reprint author), 0 Emerson Pl, Boston, MA 02114 USA. EM ralph_metson@meei.harvard.edu FU Massachusetts Eye and Ear Infirmary FX Funding for this study was provided by a Foundation Research Endowment Grant from the Massachusetts Eye and Ear Infirmary. NR 42 TC 52 Z9 54 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2008 VL 118 IS 5 BP 881 EP 889 DI 10.1097/MLG.0b013e31816b4b6f PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 368ZK UT WOS:000260662100022 PM 18391768 ER PT J AU Lai, DW Loughran, TP Maciejewski, JP Sasu, S Song, SX Epling-Burnette, PK Paquette, RL AF Lai, Dominic W. Loughran, Thomas P., Jr. Maciejewski, Jaroslaw P. Sasu, Sebastian Song, Sophie X. Epling-Burnette, P. K. Paquette, Ronald L. TI Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia associated with an occult large granular lymphocyte leukemia SO LEUKEMIA RESEARCH LA English DT Article DE large granular lymphocyte leukemia; pure red cell aplasia; amegakaryocytic thrombocytopenia; cyclosporine; glucocorticoids; intravenous immunoglobulin ID T-CELL; LYMPHOPROLIFERATIVE DISEASE; SJOGRENS-SYNDROME; NATURAL-KILLER; CLINICAL COURSE; RECEPTORS; SEROREACTIVITY; ABNORMALITIES; EXPRESSION; DISORDERS AB Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia rarely occur concurrently. We report a case in which these disorders were associated with an occult large granular lymphocyte leukemia. The peripheral blood cytopenias improved after glucocorticoids and intravenous immunoglobulin were administered, and response was maintained with cyclosporine. Large granular lymphocyte leukemia should be suspected in the setting of unexplained bone marrow failure. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Paquette, Ronald L.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Lai, Dominic W.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Loughran, Thomas P., Jr.] Penn State Coll Med, Penn State Canc Inst, Hershey, PA USA. [Maciejewski, Jaroslaw P.] Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Cleveland, OH 44195 USA. [Sasu, Sebastian; Song, Sophie X.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Epling-Burnette, P. K.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. RP Paquette, RL (reprint author), Univ Calif Los Angeles, Dept Med, 42-121 Ctr Hlth Sci,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM paquette@ucla.edu FU CSRD VA [I01 CX000114] NR 25 TC 12 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2008 VL 32 IS 5 BP 823 EP 827 DI 10.1016/j.leukres.2007.08.012 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 284FK UT WOS:000254692000018 PM 17915315 ER PT J AU Stone, ME AF Stone, Martha E. TI Making room in the clinic: Nurse practitioners and the evolution of modern health care SO LIBRARY JOURNAL LA English DT Book Review C1 [Stone, Martha E.] Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU REED BUSINESS INFORMATION PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD MAY 1 PY 2008 VL 133 IS 8 BP 89 EP 89 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 293TY UT WOS:000255359400162 ER PT J AU Tsai, SY Otazo, R Posse, S Lin, YR Chung, HW Wald, LL Wiggins, GC Lin, FH AF Tsai, Shang-Yueh Otazo, Ricardo Posse, Stefan Lin, Yi-Ru Chung, Hsiao-Wen Wald, Lawrence L. Wiggins, Graham C. Lin, Fa-Hsuan TI Accelerated proton echo planar spectroscopic Imaging (PEPSI) using GRAPPA with a 32-channel phased-array coil SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE proton echo planar spectroscopic. imaging; PEPSI; MR spectroscopic imaging; parallel MRI; 32-channel phase array; GRAPPA ID TO-NOISE RATIO; MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN BRAIN; CHEMICAL-SHIFT; 3 TESLA; GLUTAMATE; RECONSTRUCTION; ARTIFACTS; SENSE; WATER AB Parallel imaging has been demonstrated to reduce the encoding time of MR spectroscopic imaging (MRSI). Here we investigate up to 5-fold acceleration of 2D proton echo planar spectroscopic imaging (PEPSI) at 3T using generalized autocalibrating partial parallel acquisition (GRAPPA) with a 32-channel coil array, 1.5 cm(3) voxel size, TR/TE of 15/2000 ms, and 2.1 Hz spectral resolution. Compared to an 8-channel array, the smaller RIF coil elements in this 32-channel array provided a 3.1-fold and 2.8-fold increase in signal-to-noise ratio (SNR) in the peripheral region and the central region, respectively, and more spatial modulated information. Comparison of sensitivity-encoding (SENSE) and GRAPPA reconstruction using an 8-channel array showed that both methods yielded similar quantitative metabolite measures [P > 0.1). Concentration values of N-acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (ml), and the sum of glutamate and glutamine (Glx) for both methods were consistent with previous studies. Using the 32-channel array coil the mean Cramer-Rao lower bounds (CRLB) were less than 8% for NAA, tCr, and Cho and less than 15% for ml and Glx at 2-fold acceleration. At 4-fold acceleration the mean CRLB for NAA, tCr, and Cho was less than 11 %. In conclusion, the use of a 32-channel coil array and GRAPPA reconstruction can significantly reduce the measurement time for mapping brain metabolites. C1 [Wald, Lawrence L.; Wiggins, Graham C.; Lin, Fa-Hsuan] Athinoula A Martinos Ctr Biomed Imaging, MGH, HMS, MIT, Charlestown, MA 02129 USA. [Tsai, Shang-Yueh; Chung, Hsiao-Wen] Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. [Otazo, Ricardo; Posse, Stefan] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Posse, Stefan] Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA. [Lin, Yi-Ru] Natl Taiwan Univ Sci & Technol, Dept Elect Engn, Taipei, Taiwan. [Lin, Fa-Hsuan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei, Taiwan. RP Lin, FH (reprint author), Athinoula A Martinos Ctr Biomed Imaging, MGH, HMS, MIT, Bldg 149,13th St,Mail Code 149-2301, Charlestown, MA 02129 USA. EM fhlin@nmr.mgh.harvard.edu RI Lin, Fa-Hsuan/G-6988-2012; Tsai, Shang-Yueh/O-2226-2013; Wald, Lawrence/D-4151-2009; OI Lin, Fa-Hsuan/0000-0002-9539-1731; Tsai, Shang-Yueh/0000-0002-6310-4750; Otazo, Ricardo/0000-0002-3782-4930; Chung, Hsiao-Wen/0000-0001-7127-1244 FU NCRR NIH HHS [P41 RR 14075]; NIBIB NIH HHS [R21 EB 007928, R01 EB 000790]; NICHD NIH HHS [R01 HD 040712]; NINDS NIH HHS [R01 NS 037462] NR 45 TC 32 Z9 33 U1 0 U2 3 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 MAY PY 2008 VL 59 IS 5 BP 989 EP 998 DI 10.1002/mrm.21545 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 291XN UT WOS:000255230700007 PM 18429025 ER PT J AU Liu, S Gonen, O Fleysher, L Fleysher, R Soher, BJ Pilkenton, S Lentz, MR Ratai, EM Gonzalez, RG AF Liu, Songtao Gonen, Oded Fleysher, Lazar Fleysher, Roman Soher, Brian J. Pilkenton, Sarah Lentz, Margaret R. Ratai, Eva-Maria Gonzalez, R. Gilberto TI Regional metabolite T-2 in the healthy rhesus macaque brain at 7T SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE animal models; MR spectroscopic imaging; rhesus macaque; transverse relaxation time; brain metabolites, 7 Tesla ID MR SPECTROSCOPY; TIME; RELAXATION; NOISE; MODEL; TESLA; WATER; 4T AB Although the rhesus macaque brain is an excellent model system for the study of neurological diseases and their responses to treatment, its small size requires much higher spatial resolution, motivating use of ultra-high-field (B-0) imagers. Their weaker radio-frequency fields, however, dictate longer pulses; hence longer TE localization sequences. Due to the shorter transverse relaxation time (T-2) at higher B(0)s, these longer TEs subject metabolites to T-2-weighting, that decrease their quantification accuracy. To address this we measured the T(2)s of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in several gray matter (GM) and white matter (WM) regions of four healthy rhesus macaques at 7T using three-dimensional (3D) proton MR spectroscopic imaging at (0.4 cm)(3) = 64 mu l spatial resolution. The results show that macaque T2s are in good agreement with those reported in humans at 7T: 169 +/- 2.3 ms for NAA (mean +/- SEM), 114 +/- 1.9 ms for Cr, and 128 +/- 2.4 ms for Cho, with no significant differences between GM and WM. The T-2 histograms from 320 voxels in each animal for NAA, Cr, and Cho were similar in position and shape, indicating that they are potentially characteristic of "healthy" in this species. C1 [Liu, Songtao; Gonen, Oded; Fleysher, Lazar; Fleysher, Roman] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. [Soher, Brian J.] Duke Univ, Med Ctr, Dept Radiol, Ctr Adv MR Dev, Durham, NC 27710 USA. [Pilkenton, Sarah; Lentz, Margaret R.; Ratai, Eva-Maria; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, AA Martinos Ctr, Biomed Imaging & Neuroradiol Div, Charlestown, MA USA. RP Gonen, O (reprint author), NYU, Sch Med, Dept Radiol, 650 1st Ave 6th Floor, New York, NY 10016 USA. EM oded.gonen@med.nyu.edu OI Gonen, Oded/0000-0002-3148-2028 FU NCRR NIH HHS [P41 RR014075, P41 RR 14075]; NIAID NIH HHS [AI 028691, P30 AI028691]; NIBIB NIH HHS [EB 01015, R01 EB001015]; NINDS NIH HHS [K25 NS051129, K25 NS051129-04, R56 NS050520, NS 050041, NS 051129, NS 050520, R01 NS050520, R01 NS050041] NR 19 TC 6 Z9 6 U1 0 U2 1 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 MAY PY 2008 VL 59 IS 5 BP 1165 EP 1169 DI 10.1002/mrm.21574 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 291XN UT WOS:000255230700026 PM 18429024 ER PT J AU Sun, PZ Murata, Y Lu, J Wang, X Lo, EH Sorensen, AG AF Sun, Phillip Zhe Murata, Yoshihiro Lu, Jie Wang, Xiaoying Lo, Eng H. Sorensen, A. Gregory TI Relaxation-compensated fast multislice amide proton transfer (APT) imaging of acute ischemic stroke SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE acute ischemia; amide proton transfer (APT); chemical exchange saturation transfer (CEST); pH; middle cerebral artery occlusion (MCAO); stroke; tissue acidosis ID SATURATION-TRANSFER CEST; CHEMICAL-EXCHANGE; QUANTITATIVE DESCRIPTION; CEREBRAL-ISCHEMIA; MRI; AGENTS; PH; ARTIFACTS; PEPTIDES; PROTEINS AB Amide proton transfer (APT) imaging is a variant form of chemical exchange saturation transfer (CEST) imaging that is based on the magnetization exchange between bulk water and labile endogenous amide protons. Given that chemical exchange is pH-dependent, APT imaging has been shown capable of imaging ischemic tissue acidosis, and as such, may serve as a surrogate metabolic imaging marker complementary to perfusion and diffusion MRI. In order for APT imaging to properly diagnose heterogeneous pathologies such as stroke and cancer, fast volumetric APT imaging has to be developed. In this study the evolution of CEST contrast after RF irradiation was solved showing that although the CEST steady state is reached by the apparent longitudinal relaxation rate, the decreases of CEST contrast after irradiation is governed by the intrinsic relaxation constant. A volumetric APT imaging sequence is proposed that acquires multislice images immediately after a single long continuous wave (CW) RF irradiation, wherein the relaxation-induced loss of CEST contrast is compensated for during postprocessing. The proposed technique was verified by numerical simulation, a tissue-like dual-pH phantom, and demonstrated on an embolic stroke animal model. In summary, our study has established a fast volumetric pH-weighted APT imaging technique, allowing further investigation to fully evaluate its diagnostic power. C1 [Sun, Phillip Zhe; Sorensen, A. Gregory] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Murata, Yoshihiro; Lu, Jie; Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Lu, Jie] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing, Peoples R China. RP Sun, PZ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Rm 2301,149 13th St, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR 14075]; NINDS NIH HHS [5R01 NS 038477-09] NR 20 TC 43 Z9 45 U1 4 U2 7 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 MAY PY 2008 VL 59 IS 5 BP 1175 EP 1182 DI 10.1002/mrm.21591 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 291XN UT WOS:000255230700028 PM 18429031 ER PT J AU Hendricks, A AF Hendricks, Ann TI Hospitals as multiproduct firms: Issues of scale and scope, supply and demand SO MEDICAL CARE LA English DT Editorial Material C1 VA Boston HCS, Boston, MA 02130 USA. RP Hendricks, A (reprint author), VA Boston HCS, 152 H,150 S Huntingon Ave, Boston, MA 02130 USA. EM Ann.Hendricks@med.va.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2008 VL 46 IS 5 BP 458 EP 459 DI 10.1097/MLR.0b013e318172e064 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 295CH UT WOS:000255452100002 PM 18438192 ER PT J AU Kang-Kim, M Betancourt, JR Ayanian, JZ Zaslavsky, AM Yucel, RM Weissman, JS AF Kang-Kim, Minah Betancourt, Joseph R. Ayanian, John Z. Zaslavsky, Alan M. Yucel, Recai M. Weissman, Joel S. TI Access to care and use of preventive services by Hispanics - State-based variations from 1991 to 2004 SO MEDICAL CARE LA English DT Article DE access to care; disparities; race/ethnicity ID HEALTH-CARE; RENAL-TRANSPLANTATION; INSURANCE-COVERAGE; CERVICAL-CANCER; RISK-FACTORS; DISPARITIES; MEXICAN; ADULTS; POPULATION; ETHNICITY AB Background: State-level disparities in access to physicians and preventive services between Hispanics and whites may have changed over time. Objective: To assess state-based changes in Hispanics' access to physicians and preventive services from 1991 to 2004. Methods: Using data from the Behavioral Risk Factor Surveillance System in the 10 states with the largest Hispanic populations, we examined 4 preventive services for eligible adults (mammography, Papanicolaou testing, colorectal cancer screening, and cholesterol testing) and 2 measures of access to physicians (obtaining routine checkup in prior 2 years and avoiding seeing physician when needed due to cost in prior year). In each state we assessed unadjusted and adjusted Hispanic-white access gaps and changes over time. Results: Hispanic-white access gaps persisted over time and varied widely by state. Disparities narrowed and became nonsignificant in 2 states (Arizona and California) for mammography and 3 states (Nevada, New Mexico, and New York) for Pap testing. Other disparities increased and became significant (mammography in Texas; colorectal cancer screening in California, Colorado, and Texas; cholesterol testing in Florida and Nevada; routine checkups in Arizona and New Mexico). Disparities in lacking doctor visits due to cost remained large and significant over time in all states. Insurance status and education were the main contributors to Hispanic-white disparities and their impact increased over time. Conclusions: Although use of preventive services and access to physicians improved for both whites and Hispanics nationally, access gaps varied widely among states. Therefore, efforts to monitor and eliminate disparities should be conducted at both the national and state levels. C1 [Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Kang-Kim, Minah] Ewha Womans Univ, Seoul, South Korea. [Betancourt, Joseph R.] Disparities Solut Ctr, Boston, MA USA. [Ayanian, John Z.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Yucel, Recai M.] Hlth State Univ Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY USA. [Ayanian, John Z.; Zaslavsky, Alan M.; Weissman, Joel S.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jweissman@partners.org NR 49 TC 36 Z9 37 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2008 VL 46 IS 5 BP 507 EP 515 DI 10.1097/MLR.0b013e31816dd966 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 295CH UT WOS:000255452100009 PM 18438199 ER PT J AU Cuite, CL Weinstein, ND Emmons, K Colditz, G AF Cuite, Cara L. Weinstein, Neil D. Emmons, Karen Colditz, Graham TI A test of numeric formats for communicating risk probabilities SO MEDICAL DECISION MAKING LA English DT Article DE risk; risk likelihood; probability; risk format; risk communication; patient-provider communication ID ASSESSING PERCEPTIONS; INFORMATION; DECISIONS; FREQUENCY; SCALE AB Background. Because people frequently encounter information about the probability of health risks, there is a need for research to help identify the best formats for presenting these probabilities. Methods. Three waves of participants were recruited from visitors to a cancer-related Internet site, Participants were presented with a hypothetical scenario that required them to perform 2 mathematical operations of the types that might be encountered in discussions of risk. Each wave encountered different operations. The operations used were compare, halve, triple, add, sequence, and tradeoff. Three numeric formats for communicating risk likelihoods were tested: percentages (e.g., 12%), frequencies (e.g., 12 in 100), and 1 in n (e.g., 1 in 8), and many levels of risk magnitude were crossed with the 3 formats. Results. The total sample of 16,133 individuals represented an overall participation rate of 36.1 %. Although the relative performance of the formats varied by operation, aggregated across operations, the percentage and frequency formats had higher overall accuracy rates than the 1-in-n format (57% and 55% v. 45%, respectively). Participants with less education, African Americans, Hispanics, and women had more difficulty with the mathematical operations. Discussion. Percentage and frequency formats facilitate performance of simple operations on risk probabilities compared with the 1-in-n format, which should usually be avoided. C1 [Cuite, Cara L.] State Univ New Jersey, Food Policy Inst, New Brunswick, NJ 08901 USA. Univ Arizona, Coll Med, Dept Family & Community Med, Phoenix, AZ USA. [Emmons, Karen] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Ctr, Boston, MA 02115 USA. [Colditz, Graham] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. RP Cuite, CL (reprint author), State Univ New Jersey, Food Policy Inst, ASB 3,3 Rutgers Pl, New Brunswick, NJ 08901 USA. EM cuite@aesop.rutgers.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 23 TC 45 Z9 45 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY-JUN PY 2008 VL 28 IS 3 BP 377 EP 384 DI 10.1177/0272989X08315246 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 306RC UT WOS:000256264500009 PM 18480036 ER PT J AU Jaradat, AK Biggs, PJ AF Jaradat, Adnan K. Biggs, Peter J. TI Measurement of the neutron leakage from a dedicated intraoperative radiation therapy electron linear accelerator and a conventional linear accelerator for 9, 12, 15(16), and 18(20) MeV electron energies SO MEDICAL PHYSICS LA English DT Article DE neutron leakage; linear accelerators; electron beams; bubble detectors; track-etch detectors ID DOSIMETRY AB The issue of neutron leakage has recently been raised in connection with dedicated electron-only linear accelerators used for intraoperative radiation therapy (IORT). In particular, concern has been expressed about the degree of neutron production at energies of 10 MeV and higher due to the need for additional, perhaps permanent, shielding in the room in which the device is operated. In particular, three mobile linear accelerators available commercially offer electron energies at or above the neutron threshold, one at 9 MeV, one at 10 MeV, and the third at 12 MeV. To investigate this problem, neutron leakage has been measured around the head of two types of electron accelerators at a distance of 1 m from the target at azimuthal angles of 0 degrees, 45 degrees, 90 degrees, 135 degrees, and 180 degrees. The first is a dedicated electron-only (nonmobile) machine with electron energies of 6 (not used here), 9, 12, 15, and 18 MeV and the second a conventional machine with electron energies of 6 (also not used here), 9, 12, 16, and 20 MeV. Measurements were made using neutron bubble detectors and track-etch detectors. For electron beams from a conventional accelerator, the neutron leakage in the forward direction in Sv/Gy is 2.1x10(-5) at 12 MeV, 1.3x10(-4) at 16 MeV, and 4.2x10(-4) at 20 MeV, assuming a quality factor (RBE) of 10. For azimuthal angles >0 degrees, the leakage is almost angle independent [2x10(-6) at 12 MeV; (0.7-1.6)x10(-5) at 16 MeV, and (1.6-2.9)x10(-5) at 20 MeV]. For the electron-only machine, the neutron leakage was lower than for the conventional linac, but also independent of azimuthal angle for angles >0 degrees: {[0 degrees: 7.7x10(-6) at 12 MeV; 3.0x10(-5) at 15 MeV; 1.0x10(-4) at 18 MeV]; [other angles: (2.6-5.9)x10(-7) at 12 MeV; (1.4-2.2)x10(-6) at 15 MeV; (2.7-4.7)x10(-6) at 18 MeV]}. Using the upper limit of 6x10(-7) Sv/Gy at 12 MeV for the IORT machine for azimuthal angles >0 degrees and assuming a workload of 200 Gy/wk and an inverse square factor of 10, the neutron dose equivalent is calculated to be 0.012 mSv/wk. For the primary beam at 12 MeV (0 degrees), the 10x higher dose would be compensated by the attenuation of a primary beam stopper in a mobile linear accelerator. These neutron radiation levels are below regulatory values (National Council on Radiation Protection and Measurements, "Limitation of exposure to ionizing radiation," NCRP Report No. 116, NCRP Bethesda, MD, 1993). (C) 2008 American Association of Physicists in Medicine. C1 [Jaradat, Adnan K.] Univ Massachusetts, Dept Phys, Lowell, MA 01854 USA. [Biggs, Peter J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jaradat, AK (reprint author), Univ Massachusetts, Dept Phys, Lowell, MA 01854 USA. EM pjbiggs@partners.org NR 15 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2008 VL 35 IS 5 BP 1711 EP 1717 DI 10.1118/1.2898144 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 295DZ UT WOS:000255456500011 PM 18561646 ER PT J AU Trofimov, A Vrancic, C Chan, TCY Sharp, GC Bortfeld, T AF Trofimov, Alexei Vrancic, Christian Chan, Timothy C. Y. Sharp, Gregory C. Bortfeld, Thomas TI Tumor trailing strategy for intensity-modulated radiation therapy of moving targets SO MEDICAL PHYSICS LA English DT Article DE intensity-modulated radiation therapy (IMRT); intrafractional target motion; motion correction strategies; adaptive radiotherapy treatment planning; robust 4D planning ID RESPIRATORY-GATED RADIOTHERAPY; INCORPORATING ORGAN MOVEMENTS; FLUENCE-CONVOLUTION METHOD; INTRA-FRACTION-MOTION; 3D DOSE CALCULATIONS; RESIDUAL MOTION; INTRAFRACTIONAL MOTION; IMRT OPTIMIZATION; BEAM RADIOTHERAPY; PROSTATE-CANCER AB Internal organ motion during the course of radiation therapy of cancer affects the distribution of the delivered dose and, generally, reduces its conformality to the targeted volume. Previously proposed approaches aimed at mitigating the effect of internal motion in intensity-modulated radiation therapy (IMRT) included expansion of the target margins, motion-correlated delivery (e.g., respiratory gating, tumor tracking), and adaptive treatment plan optimization employing a probabilistic description of motion. We describe and test the tumor trailing strategy, which utilizes the synergy of motion-adaptive treatment planning and delivery methods. We regard the (rigid) target motion as a superposition of a relatively fast cyclic component (e.g., respiratory) and slow aperiodic trends (e.g., the drift of exhalation baseline). In the trailing approach, these two components of motion are decoupled and dealt with separately. Real-time motion monitoring is employed to identify the "slow" shifts, which are then corrected by applying setup adjustments. The delivery does not track the target position exactly, but trails the systematic trend due to the delay between the time a shift occurs, is reliably detected, and, subsequently, corrected. The "fast" cyclic motion is accounted for with a robust motion-adaptive treatment planning, which allows for variability in motion parameters (e.g., mean and extrema of the tidal volume, variable period of respiration, and expiratory duration). Motion-surrogate data from gated IMRT treatments were used to provide probability distribution data for motion-adaptive planning and to test algorithms that identified systematic trends in the character of motion. Sample IMRT fields were delivered on a clinical linear accelerator to a programmable moving phantom. Dose measurements were performed with a commercial two-dimensional ion-chamber array. The results indicate that by reducing intrafractional motion variability, the trailing strategy enhances relevance and applicability of motion-adaptive planning methods, and improves conformality of the delivered dose to the target in the presence of irregular motion. Trailing strategy can be applied to respiratory-gated treatments, in which the correction for the slow motion can increase the duty cycle, while robust probabilistic planning can improve management of the residual motion within the gate window. Similarly, trailing may improve the dose conformality in treatment of patients who exhibit detectable target motion of low amplitude, which is considered insufficient to provide a clinical indication for the use of respiratory-gated treatment (e.g., peak-to-peak motion of less than 10 mm). The mechanical limitations of implementing tumor trailing are less rigorous than those of real-time tracking, and the same technology could be used for both. (C) 2008 American Association of Physicists in Medicine. C1 [Trofimov, Alexei; Sharp, Gregory C.; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Vrancic, Christian] Univ Heidelberg, Klinikum Mannheim, Dept Radiat Oncol, D-69120 Heidelberg, Germany. [Chan, Timothy C. Y.] MIT, Ctr Operat Res, Cambridge, MA 02139 USA. RP Trofimov, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM atrofimov@partners.org FU NCI NIH HHS [R01 CA103904, R01-CA103904] NR 58 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2008 VL 35 IS 5 BP 1718 EP 1733 DI 10.1118/1.2900108 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 295DZ UT WOS:000255456500012 PM 18561647 ER PT J AU Court, LE Wagar, M Ionascu, D Berbeco, R Chin, L AF Court, Laurence E. Wagar, Matthew Ionascu, Dan Berbeco, Ross Chin, Lee TI Management of the interplay effect when using dynamic MLC sequences to treat moving targets SO MEDICAL PHYSICS LA English DT Article DE respiratory motion; IMRT; interplay effect ID ORGAN MOTION; INTRAFRACTION MOTION; INTENSITY MODULATION; RESPIRATORY MOTION; IMRT TREATMENTS; DOSE DELIVERY; LUNG; RADIOTHERAPY AB Interplay between organ motion and leaf motion has been shown to generally have a small dosimetric impact for most clinical intensity-modulated radiation therapy treatments. However, it has also been shown that for some MLC sequences there can be large daily variations in the delivered dose, depending on details of patient motion or the number of fractions. This study investigates guidelines for dynamic MLC sequences that will keep daily dose variations due to the interplay between organ motion and leaf motion within 10%. Dose distributions for a range of MLC separations (0.2-5.0 cm) and displacements between adjacent MLCs (0-1.5 cm) were exported from ECLIPSE to purpose-written software, which simulated the dose distribution delivered to a moving target. Target motion parallel and perpendicular to the MLC motion was investigated for a range of amplitudes (0.5-4.0 cm), periods (1.5-10 s), and MLC speeds (0.1-3.0 cm/s) with target motions modeled as sin(6). Results were confirmed experimentally by measuring the dose delivered to an ion chamber array in a moving phantom for different MLC sequences. The simulation results were used to identify MLC sequences that kept dose variations within 10% compared to the dose delivered with no motion. The maximum allowable MLC speed, when target motion is parallel to the MLC motion, was found to be a simple function of target period and MLC separation. When the target motion is perpendicular to MLC motion, the maximum allowable MLC speed can be described as a function of MLC separation and the displacement of adjacent MLCs. These guidelines were successfully applied to two-dimensional motion, and a simple program was written to import MLC sequence files and evaluate whether the maximum daily dose discrepancy caused by the interplay effect will be larger than 10%. This software was experimentally evaluated, and found to conservatively predict whether a given MLC sequence could give large daily dose discrepancies. (C) 2008 American Association of Physicists in Medicine. C1 [Court, Laurence E.; Wagar, Matthew; Ionascu, Dan; Berbeco, Ross; Chin, Lee] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Court, LE (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. EM lcourt@lroc.harvard.edu NR 17 TC 25 Z9 26 U1 2 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 MAY PY 2008 VL 35 IS 5 BP 1926 EP 1931 DI 10.1118/1.2896083 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 295DZ UT WOS:000255456500033 PM 18561668 ER PT J AU Cohen, B Hooks, RB Elghanayan, JB Abolian, AM Figoni, SF AF Cohen, Babak Hooks, Roy B., Jr. Elghanayan, Jeanousse B. Abolian, Anna M. Figoni, Stephen F. TI Rates of Improvement during Treadmill and Calf Exercise Training in Peripheral Arterial Disease SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Cohen, Babak] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM babak2060@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2008 VL 40 IS 5 SU S BP S159 EP S159 DI 10.1249/01.mss.0000322154.27112.d8 PG 1 WC Sport Sciences SC Sport Sciences GA V19KI UT WOS:000208070901581 ER PT J AU Ellingson, LD McLoughlin, MJ Stegner, AJ Cook, DB AF Ellingson, Laura D. McLoughlin, Michael J. Stegner, Aaron J. Cook, Dane B. TI Imaging the Relationship Between Physical Activity and Cognition in Women with Fibromyalgia SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Ellingson, Laura D.; McLoughlin, Michael J.; Stegner, Aaron J.] Univ Wisconsin, Madison, WI USA. [Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. EM lellingson@wisc.edu NR 0 TC 0 Z9 0 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2008 VL 40 IS 5 SU S BP S364 EP S364 DI 10.1249/01.mss.0000323456.52618.db PG 1 WC Sport Sciences SC Sport Sciences GA V19KI UT WOS:000208070903136 ER PT J AU Figoni, SF Kunkel, CF Scremin, AME Scremin, OU AF Figoni, Stephen F. Kunkel, Charles F. Scremin, A. M. Erika Scremin, Oscar U. TI Calf Muscle Oxygenation during Treadmill and Calf Exercise and Recovery in Peripheral Arterial Disease SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Figoni, Stephen F.; Kunkel, Charles F.; Scremin, A. M. Erika; Scremin, Oscar U.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. EM stephen.figoni@va.gov 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2008 VL 40 IS 5 SU S BP S158 EP S158 DI 10.1249/01.mss.0000322153.19489.c2 PG 1 WC Sport Sciences SC Sport Sciences GA V19KI UT WOS:000208070901580 ER PT J AU Sakamoto, K Bouskila, M Hirshman, MF Goodyear, LJ Jensen, J AF Sakamoto, Kei Bouskila, Michale Hirshman, Michael F. Goodyear, Laurie J. Jensen, Jorgen TI Allosteric Regulation Plays a Key Role in Muscle Glycogen Synthesis SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Sakamoto, Kei; Bouskila, Michale] Univ Dundee, Dundee, Scotland. [Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Jensen, Jorgen] Natl Inst Occupa Hlth, Oslo, Norway. EM k.sakamoto@dundee.ac.uk RI Jensen, Jorgen/O-2245-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2008 VL 40 IS 5 SU S BP S191 EP S191 DI 10.1249/01.mss.0000322288.08793.03 PG 1 WC Sport Sciences SC Sport Sciences GA V19KI UT WOS:000208070902091 ER PT J AU Suyematsu, ME Whiteley, J Bond, K AF Suyematsu, Megan E. Whiteley, Jessica Bond, Katrina TI Genes versus behavior: Relationships among health attitudes and physical activity SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Suyematsu, Megan E.; Whiteley, Jessica] Univ Massachusetts, Boston, MA 02125 USA. [Bond, Katrina] Dana Farber Canc Inst, Boston, MA 02115 USA. EM Megan_suyematsu@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2008 VL 40 IS 5 SU S BP S359 EP S359 DI 10.1249/01.mss.0000323437.20338.65 PG 1 WC Sport Sciences SC Sport Sciences GA V19KI UT WOS:000208070903117 ER PT J AU DiGirolamo, CM Feldman, ER Toth, TL AF DiGirolamo, Carla M. Feldman, Ellen R. Toth, Thomas L. TI The menopausal experience - confounding factors SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID HORMONE REPLACEMENT THERAPY; INFERTILITY; SYMPTOMS; WOMEN; AGE C1 [DiGirolamo, Carla M.; Feldman, Ellen R.; Toth, Thomas L.] Massachusetts Gen Hosp, Fertil Ctr, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP DiGirolamo, CM (reprint author), Massachusetts Gen Hosp, Fertil Ctr, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY-JUN PY 2008 VL 15 IS 3 BP 410 EP 411 DI 10.1097/gme.0b013e318166865f PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298MU UT WOS:000255692600004 PM 18277304 ER PT J AU Penson, RT AF Penson, Richard T. TI Cycles within cycles SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID DEPENDENT KINASE INHIBITORS; COLORECTAL-CANCER; COLON-CANCER; PATHWAYS; TARGETS; THERAPY; GENES; WOMEN C1 Massachusetts Gen Hosp, Gillette Ctr Womens Canc Gynecol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc Gynecol Oncol, Boston, MA 02114 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY-JUN PY 2008 VL 15 IS 3 BP 412 EP 413 DI 10.1097/gme.0b013e31816f70bd PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 298MU UT WOS:000255692600005 PM 18391835 ER PT J AU Lesheru, O Kashino, SS Goncalves, RB Suzuki, N Onodera, M Fujimura, A Sasaki, H Stashenko, P Campos-Neto, A AF Lesheru, Onir Kashino, Suely S. Goncalves, Reginaldo B. Suzuki, Noriyuki Onodera, Masao Fujimura, Akira Sasaki, Hajime Stashenko, Philip Campos-Neto, Antonio TI Th1 biased response to a novel Porphyromonas gingivalis protein aggravates bone resorption caused by this oral pathogen SO MICROBES AND INFECTION LA English DT Article DE Prophyromonas gingivalis; Th1 response; bone resorption ID EARLY-ONSET PERIODONTITIS; CELL-EXPRESSION CLONING; CYTOKINE PROFILES; DISEASE; INFECTION; ANTIGEN; INTERLEUKIN-12; IMMUNIZATION; LYMPHOCYTES; PROTECTION AB In previous studies we showed that biasing the immune response to Porphyromonas gingivalis antigens to the Th1 phenotype increases inflammatory bone resorption caused by this organism. Using a T cell screening strategy we identified eight P. gingivalis genes coding for proteins that appear to be involved in T-helper cell responses. In the present study, we characterized the protein encoded by the PG_1841 gene and evaluated its relevance in the bone resorption caused by P. gingivalis because subcutaneous infection of mice with this organism resulted in the induction of Th1 biased response to the recombinant PG1841 antigen molecule. Using an immunization regime that strongly biases toward the Th1 phenotype followed by challenge with P. gingivalis in dental pulp tissue, we demonstrate that mice pre-immunized with rPG1841 developed severe bone loss compared with control immunized mice. Pre-immunization of mice with the antigen using a Th2 biasing regime resulted in no exacerbation of the disease. These results support the notion that selected antigens of P. gingivalis are involved in a biased Th1 host response that leads to the severe bone loss caused by this oral pathogen. (C) 2008 Elsevier Masson SAS. All rights reserved. C1 [Lesheru, Onir; Kashino, Suely S.; Sasaki, Hajime; Stashenko, Philip; Campos-Neto, Antonio] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Lesheru, Onir; Campos-Neto, Antonio] Boston Univ, Sch Dent Med, Dept Oral Biol, Boston, MA 02215 USA. [Goncalves, Reginaldo B.] Univ Estadual Campinas, Piracicaba Sch Dent, Sao Paulo, Brazil. [Suzuki, Noriyuki] Tokyo Med & Dent Univ, Grad Sch, Tokyo, Japan. [Onodera, Masao; Fujimura, Akira] Iwate Med Univ, Sch Dent, Dept Oral Anat 1, Morioka, Iwate 020, Japan. RP Campos-Neto, A (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM acampos@forsyth.org RI Kashino, Suely/F-4171-2012 FU NIDCR NIH HHS [R01 DE009018, R01 DE009018-15, R01-DE-09018, T32 DE007327, T32 DE007327-07, T32-DE-007327] NR 28 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAY PY 2008 VL 10 IS 6 BP 664 EP 672 DI 10.1016/j.micinf.2008.03.003 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 322IH UT WOS:000257367900013 PM 18457976 ER PT J AU Beckham, JC Becker, ME Hamlett-Berry, KW Drury, PD Kang, HK Wiley, MT Calhoun, PS Moore, SD Bright, MA McFall, ME AF Beckham, Jean C. Becker, Mary E. Hamlett-Berry, Kim W. Drury, Pamela D. Kang, Han K. Wiley, Matthew T. Calhoun, Patrick S. Moore, Scott D. Bright, Mary Anne McFall, Miles E. TI Preliminary findings from a clinical demonstration project for veterans returning from Iraq or Afghanistan SO MILITARY MEDICINE LA English DT Article ID NICOTINE REPLACEMENT THERAPY; SMOKING-CESSATION; CIGARETTE-SMOKING; UNITED-STATES; TOBACCO USE; INTERVENTIONS; PERSONNEL; QUITLINE; ACCESS; DEATH AB Military veterans are at high risk for nicotine dependence. This clinical demonstration project used invitational letters, referral to the National Cancer Institute's Smoking Quitline, and local Veteran Affairs prescriptions for tobacco cessation to evaluate whether this low-cost method would potentially reduce smoking in separated veterans who served in Afghanistan and Iraq. Three cohorts (500 each) of recently separated veterans from Afghanistan and Iraq were contacted by survey letters. Interested veterans received follow-up telephone calls using standardized scripts. They were referred to the National Cancer Institute's Smoking Quitline (1-877-44U-QUIT) and offered local Veteran Affairs pharmacologic treatment for smoking cessation. Forty-three percent of respondents who were smokers were interested in the clinical program; of these, 77% participated. At 2 months follow-up, 38% of participants self-reported maintained smoking abstinence. Results suggested that the intervention was feasible and assisted the small number of veterans who participated. C1 [Beckham, Jean C.; Becker, Mary E.; Drury, Pamela D.; Wiley, Matthew T.; Calhoun, Patrick S.; Moore, Scott D.] Durham Vet Adm Med Ctr, Durham, NC 27705 USA. [Beckham, Jean C.; Calhoun, Patrick S.; Moore, Scott D.] Duke Univ, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC 27710 USA. [Beckham, Jean C.; Calhoun, Patrick S.; Moore, Scott D.] Durham VA Med Ctr, VA Mid Atlant Reg Mental Illness Res Educ & Clin, Durham, NC 27705 USA. [Hamlett-Berry, Kim W.] VA Publ Hlth Strateg, Dept Vet Affairs 13B, Hlth Care Grp, Washington, DC 20420 USA. [Kang, Han K.] Dept Vet Affairs 135, VA Environm Epidemiol Serv, Washington, DC 20422 USA. [Bright, Mary Anne] NCI, Office Canc Informat Serv, Rockville, MD 20852 USA. [McFall, Miles E.] Seattle Vet Adm Med Ctr, Seattle, WA 98108 USA. [McFall, Miles E.] Portland VA Med Ctr, VA Pacific NW Mental Illness Res Educ & Clin Ctr, Portland, OR 97207 USA. RP Beckham, JC (reprint author), Durham Vet Adm Med Ctr, 508 Fulton St,116B, Durham, NC 27705 USA. NR 30 TC 16 Z9 16 U1 1 U2 4 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAY PY 2008 VL 173 IS 5 BP 448 EP 451 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 300SY UT WOS:000255846700010 PM 18543565 ER PT J AU Choi, MY Romer, AI Wang, Y Wu, MP Ito, S Leiter, AB Shivdasani, RA AF Choi, Michael Y. Romer, Anthony I. Wang, Yang Wu, Melissa P. Ito, Susumu Leiter, Andrew B. Shivdasani, Ramesh A. TI Requirement of the tissue-restricted homeodomain transcription factor Nkx6.3 in differentiation of gastrin-producing G cells in the stomach antrum SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; ENDOCRINE CELL; SOMATOSTATIN CELLS; ACID-SECRETION; DEFICIENT MICE; MOUSE; EXPRESSION; GENES; RAT; GUT AB Many homeodomain transcription factors function in organogenesis and cell differentiation. The Nkx family illustrates these functions especially well, and the Nkx6 subfamily controls differentiation in the central nervous system and pancreas. Nkx6.3, a recent addition to this subfamily, overlaps Nkx6.1 and Nkx6.2 in expression in the hindbrain and stomach. Nkx6.3 transcripts localize in the epithelium of the most distal stomach region, the antrum and pylorus; expression in the adult intestine is lower and confined to the proximal duodenum. Nkx6.3(-/-) mice develop and grow normally, with a grossly intact stomach and duodenum. These mice show markedly reduced gastrin mRNA, many fewer gastrin-producing (G) cells in the stomach antrum, hypogastrinemia, and increased stomach luminal pH, with a corresponding increase in somatostatin mRNA levels and antral somatostatin-producing (D) cells. They express normal levels of other transcription factors required for gastric endocrine cell differentiation, Pdx1, Pax6, and Ngn3; conversely, Ngn3(-/-) mice, which also show reduced gastrin levels, express Nkx6.3 normally. These studies implicate Nkx6.3 as a selective regulator of G- and D-cell lineages, which are believed to derive from a common progenitor, and suggest that it operates in parallel with Ngn3. C1 [Choi, Michael Y.; Romer, Anthony I.; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choi, Michael Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Choi, Michael Y.; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wang, Yang] Tufts Univ, Sch Med, Grad Program Genet, Boston, MA 02111 USA. [Wu, Melissa P.] Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA USA. [Ito, Susumu] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Leiter, Andrew B.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu RI Wu, Melissa/D-7032-2012 FU NIDDK NIH HHS [R01DK43673, R01 DK043673, R01 DK061139, R01 DK067166, R01DK61139, R01DK67166] NR 49 TC 12 Z9 12 U1 0 U2 0 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 MAY PY 2008 VL 28 IS 10 BP 3208 EP 3218 DI 10.1128/MCB.01737-07 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 297EV UT WOS:000255600800011 PM 18347062 ER PT J AU Chang, CJ Mulholland, DJ Valamehr, B Mosessian, S Sellers, WR Wu, H AF Chang, Chun-Ju Mulholland, David J. Valamehr, Bahram Mosessian, Sherly Sellers, William R. Wu, Hong TI PTEN nuclear localization is regulated by oxidative stress and mediates p53-dependent tumor suppression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LIPID PHOSPHATASE-ACTIVITY; CYCLIN D1; PROTEIN; P53; PHOSPHORYLATION; CELLS; EXPRESSION; PATHWAY; CANCER; GENE AB The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted on chromosome 10) is frequently mutated or deleted in various human cancers. PTEN localizes predominantly to the cytoplasm and functions as a lipid phosphatase, thereby negatively regulating the phosphatidylinositol 3-kinase-AKT signaling pathway. PTEN can also localize to the nucleus, where it binds and regulates p53 protein level and transcription activity. However, the precise function of nuclear PTEN and the factors that control PTEN nuclear localization are still largely unknown. In this study, we identified oxidative stress as one of the physiological stimuli that regulate the accumulation of nuclear PTEN. Specifically, oxidative stress inhibits PTEN nuclear export, a process depending on phosphorylation of its amino acid residue Ser-380. Nuclear PTEN, independent of its phosphatase activity, leads to p53-mediated G(1) growth arrest, cell death, and reduction of reactive oxygen species production. Using xenografts propagated from human prostate cancer cell lines, we reveal that nuclear PTEN is sufficient to reduce tumor progression in vivo in a p53-dependent manner. The data outlined in this study suggest a unique role of nuclear PTEN to arrest and protect cells upon oxidative damage and to regulate tumorigenesis. Since tumor cells are constantly exposed to oxidative stress, our study elucidates the cooperative roles of nuclear PTEN with p53 in tumor suppression. C1 [Chang, Chun-Ju; Mulholland, David J.; Valamehr, Bahram; Mosessian, Sherly; Wu, Hong] Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Sellers, William R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wu, H (reprint author), Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. EM hwu@mednet.ucla.edu FU NCI NIH HHS [F32 CA112988, CA107166, CA107166:01S1, F32 CA112988-02, P50 CA086306, P50 CA092131, P50 CA86306, R01 CA107166]; PHS HHS [R01] NR 40 TC 67 Z9 71 U1 0 U2 4 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 MAY PY 2008 VL 28 IS 10 BP 3281 EP 3289 DI 10.1128/MCB.00310-08 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 297EV UT WOS:000255600800017 PM 18332125 ER PT J AU Yang, DP Zhang, DP Mak, KS Bonder, DE Pomeroy, SL Kim, HA AF Yang, David P. Zhang, Dan P. Mak, Kimberley S. Bonder, Daniel E. Pomeroy, Scott L. Kim, Haesun A. TI Schwann cell proliferation during Wallerian degeneration is not necessary for regeneration and remyelination of the peripheral nerves: Axon-dependent removal of newly generated Schwann cells by apoptosis SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE schwarm cell; proliferation; cyclin D1; Wallerian degeneration; apoptosis; functional recovery ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; LEUKEMIA INHIBITORY FACTOR; RAT SCIATIC-NERVE; GROWTH-FACTOR; CYCLIN D1; MACROPHAGE RECRUITMENT; DNA FRAGMENTATION; P75 RECEPTOR; MICE LACKING; MOTOR AXONS AB Peripheral nerve injury is followed by a wave of Schwann cell proliferation in the distal nerve stumps. To resolve the role of Schwann cell proliferation during functional recovery of the injured nerves, we used a mouse model in which injury-induced Schwarnn cell mitotic response is ablated via targeted disruption of cyclin D1. In the absence of distal Schwann cell proliferation, axonal regeneration and myelination occur normally in the mutant mice and functional recovery of injured nerves is achieved. This is enabled by pre-existing Schwann cells in the distal stump that persist but do not divide. On the other hand, in the wild type littermates, newly generated Schwann cells of injured nerves are culled by apoptosis. As a result, distal Schwann cell numbers in wild type and cyclin D1 null mice converge to equivalence in regenerated nerves. Therefore, distal Schwann cell proliferation is not required for functional recovery of injured nerves. (C) 2008 Elsevier Inc. All rights reserved. C1 [Yang, David P.; Bonder, Daniel E.; Kim, Haesun A.] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA. [Zhang, Dan P.; Mak, Kimberley S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zhang, Dan P.; Mak, Kimberley S.; Pomeroy, Scott L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bonder, Daniel E.] Drew Univ, Dept Biol, Madison, NJ 07940 USA. [Pomeroy, Scott L.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Kim, HA (reprint author), Rutgers State Univ, Dept Biol Sci, 195 Univ Ave, Newark, NJ 07102 USA. EM haekim@andromeda.rutgers.edu FU NINDS NIH HHS [R01 NS045939, R01 NS045939-04, R01-NS45939-01] NR 49 TC 32 Z9 34 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY PY 2008 VL 38 IS 1 BP 80 EP 88 DI 10.1016/j.mcn.2008.01.017 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 300SO UT WOS:000255845700006 PM 18374600 ER PT J AU Xu, L Shen, SS Hoshida, Y Subramanian, A Ross, K Brunet, JP Wagner, SN Ramaswamy, S Mesirov, JP Hynes, RO AF Xu, Lei Shen, Steven S. Hoshida, Yujin Subramanian, Aravind Ross, Ken Brunet, Jean-Philippe Wagner, Stephan N. Ramaswamy, Sridhar Mesirov, Jill P. Hynes, Richard O. TI Gene expression changes in an animal melanoma model correlate with aggressiveness of human melanoma metastases SO MOLECULAR CANCER RESEARCH LA English DT Article ID BREAST-CANCER METASTASIS; MOLECULAR PORTRAITS; TUMOR-METASTASIS; CARCINOMAS; SIGNATURE; PROFILES; RECEPTOR; GROWTH AB Metastasis is the deadliest phase of cancer progression. Experimental models using immunodeficient mice have been used to gain insights into the mechanisms of metastasis. We report here the identification of a "metastasis aggressiveness gene expression signature" derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model. Comparison with expression data from human melanoma patients shows that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients. Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis. C1 [Xu, Lei; Shen, Steven S.; Hynes, Richard O.] MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Shen, Steven S.] MIT, Biomicro Ctr, Cambridge, MA 02139 USA. [Hoshida, Yujin; Subramanian, Aravind; Ross, Ken; Brunet, Jean-Philippe; Mesirov, Jill P.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Ramaswamy, Sridhar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ramaswamy, Sridhar] Harvard Univ, Sch Med, Boston, MA USA. [Wagner, Stephan N.] Med Univ Vienna, Dept Dermatol, Div Immunol Allergy & Infect Dis, Vienna, Austria. [Wagner, Stephan N.] Austrian Acad Sci, Ctr Mol Med, A-1010 Vienna, Austria. RP Hynes, RO (reprint author), MIT, Ctr Canc Res, Howard Hughes Med Inst, 40 Ames St,E17-227, Cambridge, MA 02139 USA. EM rohynes@mit.edu OI Wagner, Stephan/0000-0003-4941-7029; Shen, Steven/0000-0001-7725-1260 FU Howard Hughes Medical Institute; NCI NIH HHS [U54-CA112967, U54 CA112967-02, U54 CA112967-02S1, R01 CA121941, R01-CA17007, U54 CA112967, R01 CA121941-03, R01 CA017007-26, R01 CA017007] NR 26 TC 84 Z9 87 U1 0 U2 1 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 MAY PY 2008 VL 6 IS 5 BP 760 EP 769 DI 10.1158/1541-7786.MCR-07-0344 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 308VH UT WOS:000256417700010 PM 18505921 ER PT J AU Weisberg, E Wright, RD McMillin, DW Mitsiades, C Ray, A Barrett, R Adamia, S Stone, R Galinsky, I Kung, AL Griffin, JD AF Weisberg, Ellen Wright, Renee D. McMillin, Douglas W. Mitsiades, Constantine Ray, Arghya Barrett, Rosemary Adamia, Sophia Stone, Richard Galinsky, Ilene Kung, Andrew L. Griffin, James D. TI Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BONE-MARROW STROMA; ACUTE MYELOID-LEUKEMIA; ELM ERYTHROLEUKEMIA-CELLS; HEMATOPOIETIC STEM-CELLS; PREVENT APOPTOSIS; B-CELLS; DENDRITIC CELLS; SOLUBLE FACTORS; PROLIFERATION; SURVIVAL AB Clinical studies of patients with chronic myeloid leukemia revealed that a common pattern of response is a dramatic fall in the circulating population of blast cells, with a minimal or delayed decrease in marrow blasts, suggesting a protective environment. These observations suggest that a greater understanding of the interaction of stromal cells with leukemic cells is essential. Here, we present an in vivo system for monitoring relative tumor accumulation in leukemic mice and residual disease in leukemic mice treated with a tyrosine kinase inhibitor and an in vitro system for identifying integral factors involved in stromal-mediated cytoprotection. Using the in vivo model, we observed high tumor burden/residual disease in tissues characterized as significant sources of hematopoiesis-promoting stroma, with bone marrow stroma most frequently showing the highest accumulation of leukemia in untreated and nilotinib-treated mice as well as partial protection of leukemic cells from the inhibitory effects of nilotinib. These studies, which showed a pattern of leukemia distribution consistent with what is observed in imatinib- and nilotinib-treated chronic myeloid leukemia patients, were followed by a more in-depth analysis of stroma-leukemia cell interactions that lead to protection of leukemia cells from nilotinib-induced cytotoxicity. For the latter, we used the human BCR-ABL-positive cell line, KU812F, and the human bone marrow stroma cell line, HS-5, to more closely approximate the bone marrow-associated cytoprotection observed in drug-treated leukemia patients. This in vitro system helped to elucidate stromal-secreted viability factors that may play a role in stromal-mediated cytoprotection of tyrosine kinase inhibitor-treated leukemia cells. C1 [Weisberg, Ellen; McMillin, Douglas W.; Mitsiades, Constantine; Ray, Arghya; Barrett, Rosemary; Adamia, Sophia; Stone, Richard; Galinsky, Ilene; Griffin, James D.] Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, Boston, MA 02115 USA. [Wright, Renee D.; Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Wright, Renee D.; Kung, Andrew L.] Childrens Hosp, Boston, MA 02115 USA. [Stone, Richard] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Weisberg, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, 44 Binney St, Boston, MA 02115 USA. EM Ellen_Weisberg@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [CA36167, CA66996, P01 CA066996, R01 CA036167, R37 CA036167]; NIDDK NIH HHS [P01 DK050654, DK50654] NR 38 TC 35 Z9 35 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2008 VL 7 IS 5 BP 1121 EP 1129 DI 10.1158/1535-7163.MCT-07-2331 PG 9 WC Oncology SC Oncology GA 301RS UT WOS:000255913900013 PM 18445657 ER PT J AU Romero, V Azocar, J Zuniga, J Clavijo, OP Terreros, D Gu, XJ Husain, Z Chung, RT Amos, C Yunis, EJ AF Romero, Viviana Azocar, Jose Zuniga, Joaquin Clavijo, Olga P. Terreros, Daniel Gu, Xiangjun Husain, Zaheed Chung, Raymond T. Amos, Christopher Yunis, Edmond J. TI Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in Hepatitis C virus infection outcome SO MOLECULAR IMMUNOLOGY LA English DT Review DE HCV; KIR; HLA-C; genetic interactions; clinical outcome ID POPULATION STRATIFICATION; VIRAL CLEARANCE; ASSOCIATION; IMMUNOGLOBULIN; FREQUENCY; INNATE; CELLS; PERSISTENCE; DIVERSITY; LIVER AB Natural killer cells are important in innate defense against viral infections. The interplay between stimulatory and inhibitory natural killer cell receptors and their corresponding human leukocyte antigen ligands are known to influence the outcome of acute Hepatitis C virus infection. Frequencies of NK receptor genes (8 inhibitory, 6 activating and 2 pseudogenes) and HLA class II alleles (DRB1, DQB1) were analyzed in 160 Puerto-Rican American drug users with Hepatitis C virus infection; 121 had chronic viremia (CV) and 39 were spontaneous clearance (SC). We further ruled out genetic stratification using short tandem repeats. Interaction between KIR gene receptor 2DL3/2DL3 and its ligand, C1/C1 of HLA-Cw alleles and spontaneous clearance was confirmed (p = 0.03, OR = 3.05). We also found a new interaction between the KIR receptor gene 2DL3 with HLA-DR131*1201 (p = 0.0001, OR = 22) associated with SC, and an association of HLA DQB1*0501 (p = 0.05, OR = 0.30) with CV. Our findings suggested a role for MHC class II alleles in Hepatitis C virus peptide presentation to T cells together with NK ligand interaction involving pathways that will be useful for the development of immunotherapeutic interventions. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Romero, Viviana; Zuniga, Joaquin; Clavijo, Olga P.; Husain, Zaheed; Yunis, Edmond J.] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Romero, Viviana; Zuniga, Joaquin; Clavijo, Olga P.; Husain, Zaheed; Yunis, Edmond J.] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Azocar, Jose] Northgate Med Ctr, Springfield, MA 01103 USA. [Zuniga, Joaquin] Inst Nacl Enfermedades Resp, Secc 16, Mexico City 14080, DF, Mexico. [Gu, Xiangjun; Amos, Christopher] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yunis, Edmond J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02116 USA. [Terreros, Daniel] Texas Tech Hlth Sci Ctr, El Paso, TX 79905 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 724,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org; edmond-yunis@dfci.harvard.edu FU NHLBI NIH HHS [HL59838, HL29583, P01 HL029583, P01 HL029583-130008, R01 HL059838]; NIAID NIH HHS [AI49213, AI69939, R01 AI069939, U24 AI049213] NR 40 TC 66 Z9 69 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 2008 VL 45 IS 9 BP 2429 EP 2436 DI 10.1016/j.molimm.2008.01.002 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 296FH UT WOS:000255528400001 PM 18289678 ER PT J AU Paintlia, AS Paintlia, MK Singh, AK Singh, I AF Paintlia, Ajaib Singh Paintlia, Manjeet Kaur Singh, Avtar Kaur Singh, Inderjit TI Inhibition of Rho family functions by lovastatin promotes myelin repair in ameliorating experimental autoimmune encephalomyelitis SO MOLECULAR PHARMACOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; COA REDUCTASE INHIBITOR; ACTIN STRESS FIBERS; MULTIPLE-SCLEROSIS; OLIGODENDROCYTE PROGENITORS; ENDOTHELIAL-CELLS; T-LYMPHOCYTES; ANIMAL-MODEL; NITRIC-OXIDE; STATINS AB Impaired remyelination is critical to neuroinflammation in multiple sclerosis (MS), which causes chronic and relapsing neurological impairments. Recent studies revealed that immunomodulatory activity of statins in an experimental autoimmune encephalomyelitis (EAE) model of MS are via depletion of isoprenoids (farnesyl-pyrophosphate and geranylgeranyl-pyrophosphate) rather than cholesterol in immune cells. In addition, we previously documented that lovastatin impedes demyelination and promotes myelin repair in treated EAE animals. To this end, we revealed the underlying mechanism of lovastatin-induced myelin repair in EAE using in vitro and in vivo approaches. Survival, proliferation (chondroitin sulfate proteoglycan-NG2(+) and late oligodendrocyte progenitor marker(+)), and terminal-differentiation (myelin basic protein(+)) of OPs was significantly increased in association with induction of a promyelinating milieu by lovastatin in mixed glial cultures stimulated with proinflammatory cytokines. Lovastatin-induced effects were reversed by cotreatment with mevalonolactone or geranylgeranyl-pyrophosphate, but not by farnesyl-pyrophosphate or cholesterol, suggesting that depletion of geranygeranyl-pyrophosphate is more critical than farnesyl-pyrophosphate in glial cells. These effects of lovastatin were mimicked by inhibitors of geranylgeranyl-transferase (geranylgeranyl transferase inhibitor-298) and downstream effectors {i.e., Rho-family functions (C3-exoenzyme) and Rho kinase [Y27632 (N-(4- pyridyl)-4-(1-aminoethyl) cyclohexanecarboxamide dihydrochloride)]} but not by an inhibitor of farnesyl-transferase (farnesyl transferase inhibitor-277). Moreover, activities of Rho/Ras family GTPases were reduced by lovastatin in glial cells. Corresponding with these findings, EAE animals exhibiting demyelination (on peak clinical day; clinical scores >= 3.0) when treated with lovastatin and aforementioned agents validated these in vitro findings. Together, these data provide unprecedented evidence that - like immune cells - geranylgeranyl-pyrophosphate depletion and thus inhibition of Rho family functions in glial cells by lovastatin promotes myelin repair in ameliorating EAE. C1 [Paintlia, Ajaib Singh; Paintlia, Manjeet Kaur; Singh, Inderjit] Med Univ S Carolina, Darby Children Res Inst, Dept Pediat, Charleston, SC 29425 USA. [Singh, Avtar Kaur] Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Darby Children Res Inst, Dept Pediat, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NCRR NIH HHS [C06-RR015455, C06-RR018823, C06 RR015455, C06 RR018823]; NINDS NIH HHS [NS22576, R01 NS034741, R01 NS034741-12, R01 NS037766, R01 NS037766-10, R01 NS040810, R37 NS022576, NS40810, R01 NS022576, R01 NS034741-08, R37 NS022576-24, NS-34741, NS37766] NR 39 TC 40 Z9 42 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 2008 VL 73 IS 5 BP 1381 EP 1393 DI 10.1124/mol.107.044230 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 288VP UT WOS:000255014200008 PM 18239032 ER PT J AU Denoux, C Galletti, R Mammarella, N Gopalan, S Werck, D De Lorenzo, G Ferrari, S Ausubel, FM Dewdney, J AF Denoux, Carine Galletti, Roberta Mammarella, Nicole Gopalan, Suresh Werck, Daniele De Lorenzo, Giulia Ferrari, Simone Ausubel, Frederick M. Dewdney, Julia TI Activation of defense response pathways by OGs and Flg22 elicitors in Arabidopsis seedlings SO MOLECULAR PLANT LA English DT Review ID SYSTEMIC ACQUIRED-RESISTANCE; GENE-EXPRESSION ANALYSIS; SALICYLIC-ACID; TRANSCRIPTION FACTOR; PSEUDOMONAS-SYRINGAE; SIGNAL-TRANSDUCTION; DISEASE RESISTANCE; PLANT DEFENSE; OXIDATIVE BURST; CELL-DEATH AB We carried out transcriptional profiling analysis in 10-d-old Arabidopsis thaliana seedlings treated with oligogalacturonides (OGs), oligosaccharides derived from the plant cell wall, or the bacterial flagellin peptide Flg22, general elicitors of the basal defense response in plants. Although detected by different receptors, both OGs and Flg22 trigger a fast and transient response that is both similar and comprehensive, and characterized by activation of early stages of multiple defense signaling pathways, particularly JA-associated processes. However, the response to Flg22 is stronger in both the number of genes differentially expressed and the amplitude of change. The magnitude of induction of individual genes is in both cases dose-dependent, but, even at very high concentrations, OGs do not induce a response that is as comprehensive as that seen with Flg22. While high doses of either microbe-associated molecular pattern (MAMP) elicit a late response that includes activation of senescence processes, SA-dependent secretory pathway genes and PR1 expression are substantially induced only by Flg22. These results suggest a lower threshold for activation of early responses than for sustained or SA-mediated late defenses. Expression patterns of amino-cyclopropane-carboxylate synthase genes also implicate ethylene biosynthesis in regulation of the late innate immune response. C1 [Denoux, Carine; Mammarella, Nicole; Gopalan, Suresh; Ausubel, Frederick M.; Dewdney, Julia] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Denoux, Carine; Mammarella, Nicole; Gopalan, Suresh; Ausubel, Frederick M.; Dewdney, Julia] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Denoux, Carine; Werck, Daniele] Univ Strasbourg 1, CNRS, Inst Biol Mol Plantes, Strasbourg, France. [Galletti, Roberta; De Lorenzo, Giulia; Ferrari, Simone] Univ Roma La Sapienza, Dipartimento Biol Vegetale, I-00185 Rome, Italy. RP Dewdney, J (reprint author), Harvard Univ, Sch Med, Dept Genet, 185 Cambridge St,Simches 7700, Boston, MA 02114 USA. EM dewdney@molbio.mgh.harvard.edu RI De Lorenzo, Giulia/F-5475-2013; OI De Lorenzo, Giulia/0000-0002-1707-5418; Galletti, Roberta/0000-0001-8299-7649 FU National Science Foundation [DBI-0114783]; National Institutes of Health [GM48707]; European Union [23044]; Ministero dell Universita e della Ricerca (MIUR); Fondo per gli Investimenti della Ricerca di Base 2001 and Cofinanziamento 2002; Giovanni Armenise-Harvard Foundation; Institute Pasteur-Fondazione Cenci Bolognetti FX This work was supported by the National Science Foundation (grant DBI-0114783 to F. M. A.); the National Institutes of Health (grant GM48707 to F. M. A.); the European Union (grant n. 23044 'NutraSnacks' to S. F.); the Ministero dell Universita e della Ricerca (MIUR) Programma di ricerca di Rilevante Interesse Nazionale 2006 (S. F.); Fondo per gli Investimenti della Ricerca di Base 2001 and Cofinanziamento 2002 (G. D. L.); the Giovanni Armenise-Harvard Foundation (G. D. L.); and the Institute Pasteur-Fondazione Cenci Bolognetti (G. D. L.). NR 118 TC 146 Z9 152 U1 4 U2 39 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1674-2052 J9 MOL PLANT JI Mol. Plant. PD MAY PY 2008 VL 1 IS 3 BP 423 EP 445 DI 10.1093/mp/ssn019 PG 23 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 346XX UT WOS:000259104000003 PM 19825551 ER PT J AU Galofre, JC Lomvardias, S Davies, TF AF Galofre, Juan C. Lomvardias, Stylianos Davies, Terry F. TI Evaluation and treatment of thyroid nodules: A clinical guide SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Editorial Material DE benign; diagnosis; malignant; management; multinodular; nodules; thyroid; treatment ID NONTOXIC MULTINODULAR GOITER; FINE-NEEDLE-ASPIRATION; RECOMBINANT HUMAN THYROTROPIN; ROUTINE MEASUREMENT; ENDOCRINE SURGEONS; SERUM CALCITONIN; FOLLOW-UP; MANAGEMENT; CANCER; SOLITARY AB Thyroid nodules are inexplicably frequent and affect approximately one-third of the adult population. The appropriate clinical management is focused primarily oil excluding thyroid cancer and also on evaluating thyroid dysfunction and mechanical obstruction. There remains no evidence that a benign thyroid nodule, once diagnosed appropriately, will progress to a malignant lesion. The initial evaluation should include a complete clinical review, a thyroid sonogram by an experienced sonographer, a laboratory assessment of thyroid function, and, where indicated, a cytological assessment of the nodule(s) by fine needle aspiration under ultrasound guidance. Only patients with suppressed serum thyroid-stimulating hormone levels, indicating hyperthyroidism, may need further evaluation by radioactive iodine uptake and scanning. Optimal treatment depends oil the patient as well as the nodule characteristics. The usual options remain a simple annual follow-up to detect changes in nodule size and thyroid function and surgical removal. Levothyroxine therapy is now seldom indicated because of poor efficacy in nodule suppression and its inability to differentiate benign lesions front thyroid carcinoma. Clinical guidelines have a very arbitrary recommendation of aspiration biopsy in all lesions greater than 1 cm in size, but this proposal has no scientific basis and should always be viewed in the clinical context. C1 [Galofre, Juan C.; Davies, Terry F.] James J Peters VA Med Ctr, Mt Sinai Sch Med, Thyroid Res Unit, New York, NY USA. [Galofre, Juan C.] Univ Navarra, Clin Univ, Dept Endocrinol & Nutr, E-31080 Pamplona, Spain. [Lomvardias, Stylianos] James J Peters VA Med Ctr, Dept Pathol, New York, NY USA. RP Galofre, JC (reprint author), Mt Sinai Med Ctr, Thyroid Res Unit, Miami Beach, FL 33140 USA. EM terry.davies@mssm.edu NR 61 TC 2 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0027-2507 EI 1931-7581 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD MAY-JUN PY 2008 VL 75 IS 3 BP 299 EP 311 DI 10.1002/msj.20040 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 343MT UT WOS:000258858900010 PM 18704984 ER PT J AU Ben-Porath, I Thomson, MW Carey, VJ Ge, R Bell, GW Regev, A Weinberg, RA AF Ben-Porath, Ittai Thomson, Matthew W. Carey, Vincent J. Ge, Ruping Bell, George W. Regev, Aviv Weinberg, Robert A. TI An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors SO NATURE GENETICS LA English DT Article ID INVASIVE BREAST-CARCINOMA; BASAL-LIKE SUBTYPE; C-MYC; HUMAN FIBROBLASTS; CANCER PATIENTS; PROTEIN; METAANALYSIS; SUBCLASSES; PROGNOSIS; PATTERNS AB Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear, however, whether these phenotypic similarities reflect the activity of common molecular pathways. Here, we analyze the enrichment patterns of gene sets associated with embryonic stem ( ES) cell identity in the expression profiles of various human tumor types. We find that histologically poorly differentiated tumors show preferential overexpression of genes normally enriched in ES cells, combined with preferential repression of Polycomb- regulated genes. Moreover, activation targets of Nanog, Oct4, Sox2 and c-Myc are more frequently overexpressed in poorly differentiated tumors than in well-differentiated tumors. In breast cancers, this ES-like signature is associated with high-grade estrogen receptor ( ER)-negative tumors, often of the basal-like subtype, and with poor clinical outcome. The ES signature is also present in poorly differentiated glioblastomas and bladder carcinomas. We identify a subset of ES cell-associated transcription regulators that are highly expressed in poorly differentiated tumors. Our results reveal a previously unknown link between genes associated with ES cell identity and the histopathological traits of tumors and support the possibility that these genes contribute to stem cell-like phenotypes shown by many tumors. C1 [Ben-Porath, Ittai; Thomson, Matthew W.; Regev, Aviv; Weinberg, Robert A.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Ben-Porath, Ittai; Weinberg, Robert A.] MIT, Ludwig Ctr Canc Res, Cambridge, MA 02142 USA. [Thomson, Matthew W.; Regev, Aviv] MIT, Broad Inst Harvard, Cambridge, MA 02142 USA. [Carey, Vincent J.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dana Farber Canc Inst, Boston, MA 02115 USA. [Carey, Vincent J.] Harvard Univ, Sch Med, Dept Med Oncol, Brigham & Womens Hosp,Dana Farber Canc Inst, Boston, MA 02115 USA. [Carey, Vincent J.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Dana Farber Canc Inst, Boston, MA 02115 USA. [Ben-Porath, Ittai; Ge, Ruping; Bell, George W.; Weinberg, Robert A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu FU NCI NIH HHS [R01 CA078461, R01 CA078461-10A1]; NHGRI NIH HHS [P41 HG 004059, P41 HG004059] NR 50 TC 1178 Z9 1220 U1 8 U2 69 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 MAY PY 2008 VL 40 IS 5 BP 499 EP 507 DI 10.1038/ng.127 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 293WS UT WOS:000255366700013 PM 18443585 ER PT J AU Finberg, KE Heeney, MM Campagna, DR Aydinok, Y Pearson, HA Hartman, KR Mayo, MM Samuel, SM Strouse, JJ Markianos, K Andrews, NC Fleming, MD AF Finberg, Karin E. Heeney, Matthew M. Campagna, Dean R. Aydinok, Yesim Pearson, Howard A. Hartman, Kip R. Mayo, Mary M. Samuel, Stewart M. Strouse, John J. Markianos, Kyriacos Andrews, Nancy C. Fleming, Mark D. TI Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA) SO NATURE GENETICS LA English DT Article ID MICROCYTIC ANEMIA; MALABSORPTION; METABOLISM; HEPCIDIN AB Iron deficiency is usually attributed to chronic blood loss or inadequate dietary intake. Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin. These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans. C1 [Finberg, Karin E.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Heeney, Matthew M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Campagna, Dean R.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Aydinok, Yesim] Ege Univ, Fac Med, Dept Pediat Hematol, TR-35100 Izmir, Turkey. [Pearson, Howard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Hartman, Kip R.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Mayo, Mary M.] St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63104 USA. [Samuel, Stewart M.] Pediat Hlth Associates PC, New York, NY 11803 USA. [Strouse, John J.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Hematol, Baltimore, MD 21205 USA. [Markianos, Kyriacos] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Markianos, Kyriacos; Andrews, Nancy C.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Fleming, Mark D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Finberg, Karin E.; Heeney, Matthew M.; Andrews, Nancy C.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. EM Nancy.Andrews@duke.edu; Mark.Fleming@childrens.harvard.edu RI Strouse, John/A-2690-2008; Heeney, Matthew/J-6838-2015; OI Strouse, John/0000-0003-0341-1457; Heeney, Matthew/0000-0002-1104-6843; Andrews, Nancy/0000-0003-0243-4462 FU NCI NIH HHS [T32 CA009216]; NHLBI NIH HHS [K12 HL087164]; NIDDK NIH HHS [R01 DK080011, DK053813, R01 DK053813, R01 DK053813-10, R01 DK066373] NR 9 TC 321 Z9 340 U1 3 U2 8 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 MAY PY 2008 VL 40 IS 5 BP 569 EP 571 DI 10.1038/ng.130 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 293WS UT WOS:000255366700023 PM 18408718 ER PT J AU Lettre, G Jackson, AU Gieger, C Schumacher, FR Berndt, SI Sanna, S Eyheramendy, S Voight, BF Butler, JL Guiducci, C Illig, T Hackett, R Heid, IM Jacobs, KB Lyssenko, V Uda, M Boehnke, M Chanock, SJ Groop, LC Hu, FB Isomaa, B Kraft, P Peltonen, L Salomaa, V Schlessinger, D Hunter, DJ Hayes, RB Abecasis, GR Wichmann, HE Mohlke, KL Hirschhorn, JN AF Lettre, Guillaume Jackson, Anne U. Gieger, Christian Schumacher, Fredrick R. Berndt, Sonja I. Sanna, Serena Eyheramendy, Susana Voight, Benjamin F. Butler, Johannah L. Guiducci, Candace Illig, Thomas Hackett, Rachel Heid, Iris M. Jacobs, Kevin B. Lyssenko, Valeriya Uda, Manuela Boehnke, Michael Chanock, Stephen J. Groop, Leif C. Hu, Frank B. Isomaa, Bo Kraft, Peter Peltonen, Leena Salomaa, Veikko Schlessinger, David Hunter, David J. Hayes, Richard B. Abecasis, Goncalo R. Wichmann, H-Erich Mohlke, Karen L. Hirschhorn, Joel N. CA Diabet Genetics Initiative FUSION KORA Prostate Lung Colorectal Ovarian C Nurses' Hlth Study SardiNIA TI Identification of ten loci associated with height highlights new biological pathways in human growth SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; PROTEIN-KINASE-II; GENETIC ASSOCIATION; COMMON VARIANTS; FTO GENE; RISK; PROLIFERATION; POPULATION; LINKAGE; CANCER AB Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet- undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in 410,000 subjects. Ten newly identified and two previously reported loci were strongly associated with variation in height (P values from 4 x 10(-7) to 8 x 10(-22)). Together, these 12 loci account for similar to 2% of the population variation in height. Individuals with <= 8 height-increasing alleles and >= 16 height-increasing alleles differ in height by similar to 3.5 cm. The newly identified loci, along with several additional loci with strongly suggestive associations, encompass both strong biological candidates and unexpected genes, and highlight several pathways (let-7 targets, chromatin remodeling proteins and Hedgehog signaling) as important regulators of human stature. These results expand the picture of the biological regulation of human height and of the genetic architecture of this classical complex trait. C1 [Lettre, Guillaume; Voight, Benjamin F.; Guiducci, Candace; Hackett, Rachel; Peltonen, Leena; Hunter, David J.; Hirschhorn, Joel N.] MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02142 USA. [Lettre, Guillaume; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. [Lettre, Guillaume; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Jackson, Anne U.; Sanna, Serena; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Gieger, Christian; Eyheramendy, Susana; Illig, Thomas; Heid, Iris M.; Wichmann, H-Erich] GSF Natl Res Ctr Environm & Hlth, Inst Epidemiol, D-85764 Neuherberg, Germany. [Gieger, Christian; Eyheramendy, Susana; Heid, Iris M.; Wichmann, H-Erich] Univ Munich, Dept Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany. [Schumacher, Fredrick R.; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Schumacher, Fredrick R.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schumacher, Fredrick R.; Hu, Frank B.; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA. [Berndt, Sonja I.; Hayes, Richard B.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Sanna, Serena; Uda, Manuela] Cittadella Univ Monserrato, INN, Consiglio Nazl Ric, I-09042 Cagliari, Italy. [Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA. [Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Dept Clin Sci Diabetes & Endocrinol, Malmo Univ Hosp, S-20502 Malmo, Sweden. [Chanock, Stephen J.] NCI, NIH, DHHS, Lab Translat Genom,Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Groop, Leif C.] Univ Helsinki, Dept Med, Helsinki Univ Cent Hosp, Helsinki, Finland. [Groop, Leif C.] Univ Helsinki, Res Program Mol Med, Helsinki, Finland. [Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Isomaa, Bo] Malmska Municipal Hlth Ctr & Hosp, Pietarsaari, Finland. [Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. [Peltonen, Leena] Univ Helsinki, Dept Mol Med, Natl Publ Hlth Inst, FI-00014 Helsinki, Finland. [Peltonen, Leena] Univ Helsinki, Dept Mol Med, Dept Med Genet, FI-00014 Helsinki, Finland. [Salomaa, Veikko] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, FI-00300 Helsinki, Finland. [Schlessinger, David] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Hirschhorn, JN (reprint author), MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02142 USA. EM joelh@broad.mit.edu RI Genetic Epidemiology, Innsbruck Med.Univ./C-2095-2008; Abecasis, Goncalo/B-7840-2010; Voight, Benjamin/F-1775-2011; OI sanna, serena/0000-0002-3768-1749; Abecasis, Goncalo/0000-0003-1509-1825; Gieger, Christian/0000-0001-6986-9554; Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS; NCI NIH HHS [5P01CA087969, 5U01CA098233, CA49449, P01 CA087969, R01 CA049449, U01 CA049449, U01 CA098233]; NHGRI NIH HHS [HG02651, R01 HG002651]; NHLBI NIH HHS [HL084729, U01 HL084729]; NIDDK NIH HHS [5 R01 DK 075787, DK62370, DK72193, R01 DK062370, R01 DK072193, R01 DK075787, R56 DK062370, U01 DK062370]; Wellcome Trust [089061] NR 40 TC 364 Z9 373 U1 3 U2 27 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 MAY PY 2008 VL 40 IS 5 BP 584 EP 591 DI 10.1038/ng.125 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 293WS UT WOS:000255366700026 PM 18391950 ER PT J AU Haigis, KM Kendall, KR Wang, YF Cheung, A Haigis, MC Glickman, JN Niwa-Kawakita, M Sweet-Cordero, A Sebolt-Leopold, J Shannon, KM Settleman, J Giovannini, M Jacks, T AF Haigis, Kevin M. Kendall, Krystle R. Wang, Yufang Cheung, Ann Haigis, Marcia C. Glickman, Jonathan N. Niwa-Kawakita, Michiko Sweet-Cordero, Alejandro Sebolt-Leopold, Judith Shannon, Kevin M. Settleman, Jeffrey Giovannini, Marco Jacks, Tyler TI Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon SO NATURE GENETICS LA English DT Article ID INTESTINAL EPITHELIUM; PROTEIN-KINASE; STEM-CELL; IN-VIVO; H-RAS; CANCER; GROWTH; MOUSE; MICE; IDENTIFICATION AB Kras is commonly mutated in colon cancers, but mutations in Nras are rare. We have used genetically engineered mice to determine whether and how these related oncogenes regulate homeostasis and tumorigenesis in the colon. Expression of K-Ras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek-dependent manner. N-Ras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc-mutant colonic tumor, activation of K-Ras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This K-Ras tumor phenotype was associated with attenuated signaling through the MAPK pathway, and human colon cancer cells expressing mutant K-Ras were hypersensitive to inhibition of Raf, but not Mek. These studies demonstrate clear phenotypic differences between mutant Kras and Nras, and suggest that the oncogenic phenotype of mutant K-Ras might be mediated by noncanonical signaling through Ras effector pathways. C1 [Haigis, Kevin M.; Cheung, Ann; Jacks, Tyler] MIT, Ctr Canc Res, Cambridge, MA 02139 USA. [Haigis, Kevin M.; Cheung, Ann; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA. [Haigis, Kevin M.; Kendall, Krystle R.; Wang, Yufang; Settleman, Jeffrey] Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. [Haigis, Kevin M.; Kendall, Krystle R.; Wang, Yufang; Settleman, Jeffrey] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Haigis, Marcia C.] Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs, Boston, MA 02115 USA. [Glickman, Jonathan N.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Niwa-Kawakita, Michiko; Giovannini, Marco] Ctr Etude Polymorphisme Humain, Fdn Jean Dausset, INSERM, U674, Paris, France. [Niwa-Kawakita, Michiko; Giovannini, Marco] Inst Univ Hematol, Paris, France. [Sweet-Cordero, Alejandro] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [Sweet-Cordero, Alejandro] Stanford Univ, Sch Med, Canc Biol Program, Stanford, CA 94305 USA. [Sebolt-Leopold, Judith] JS Leopold Consulting, Ann Arbor, MI 48105 USA. [Shannon, Kevin M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Jacks, T (reprint author), MIT, Ctr Canc Res, Cambridge, MA 02139 USA. EM tjacks@mit.edu FU Howard Hughes Medical Institute; NCI NIH HHS [K01 CA118425, K01 CA118425-01A1, K01 CA118425-02, K01-CA118425, P30 CA014051, P30 CA014051-33, P30 CA014051-34, P30 CA014051-35, P30 CA014051-36, P30-CA14051, P50 CA127003, P50-CA127003, R01 CA072614, R01 CA072614-03, R01 CA072614-04, R01 CA072614-04S1, R01 CA072614-05, R01 CA072614-05S1, R01 CA072614-06, R01 CA072614-07, R01 CA072614-08, R01 CA072614-09, R01 CA072614-10, R01-CA72614, R37 CA072614, U01 CA084221, U01 CA084221-01, U01 CA084221-02, U01 CA084221-03, U01 CA084221-04, U01 CA084221-05, U01 CA084221-06, U01 CA084221-07, U01 CA084221-08, U01 CA084221-09, U01 CA084306, U01 CA084306-01, U01 CA084306-02, U01 CA084306-03, U01 CA084306-04, U01 CA084306-05, U01-CA84221, U01-CA84306, U54 CA112967, U54 CA112967-010002, U54 CA112967-020002, U54 CA112967-030002, U54 CA112967-040002, U54-CA112967]; NIGMS NIH HHS [R01 GM088827] NR 36 TC 265 Z9 270 U1 2 U2 14 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 MAY PY 2008 VL 40 IS 5 BP 600 EP 608 DI 10.1038/ng.115 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 293WS UT WOS:000255366700028 PM 18372904 ER PT J AU Zeggini, E Scott, LJ Saxena, R Voight, BF Marchini, JL Hu, T de Bakker, PIW Abecasis, GR Almgren, P Andersen, G Ardlie, K Bostroem, KB Bergman, RN Bonnycastle, LL Borch-Johnsen, K Burtt, NP Chen, H Chines, PS Daly, MJ Deodhar, P Ding, CJ Doney, ASF Duren, WL Elliott, KS Erdos, MR Frayling, TM Freathy, RM Gianniny, L Grallert, H Grarup, N Groves, CJ Guiducci, C Hansen, T Herder, C Hitman, GA Hughes, TE Isomaa, B Jackson, AU Jorgensen, T Kong, A Kubalanza, K Kuruvilla, FG Kuusisto, J Langenberg, C Lango, H Lauritzen, T Li, Y Lindgren, CM Lyssenko, V Marvelle, AF Meisinger, C Midthjell, K Mohlke, KL Morken, MA Morris, AD Narisu, N Nilsson, P Owen, KR Palmer, CNA Payne, F Perry, JRB Pettersen, E Platou, C Prokopenko, I Qi, L Qin, L Rayner, NW Rees, M Roix, JJ Sandbaek, A Shields, B Sjogren, M Steinthorsdottir, V Stringham, HM Swift, AJ Thorleifsson, G Thorsteinsdottir, U Timpson, NJ Tuomi, T Tuomilehto, J Walker, M Watanabe, RM Weedon, MN Willer, CJ Illig, T Hveem, K Hu, FB Laakso, M Stefansson, K Pedersen, O Wareham, NJ Barroso, I Hattersley, AT Collins, FS Groop, L McCarthy, MI Boehnke, M Altshuler, D AF Zeggini, Eleftheria Scott, Laura J. Saxena, Richa Voight, Benjamin F. Marchini, Jonathan L. Hu, Tianle de Bakker, Paul I. W. Abecasis, Goncalo R. Almgren, Peter Andersen, Gitte Ardlie, Kristin Bostroem, Kristina Bengtsson Bergman, Richard N. Bonnycastle, Lori L. Borch-Johnsen, Knut Burtt, Noel P. Chen, Hong Chines, Peter S. Daly, Mark J. Deodhar, Parimal Ding, Chia-Jen Doney, Alex S. F. Duren, William L. Elliott, Katherine S. Erdos, Michael R. Frayling, Timothy M. Freathy, Rachel M. Gianniny, Lauren Grallert, Harald Grarup, Niels Groves, Christopher J. Guiducci, Candace Hansen, Torben Herder, Christian Hitman, Graham A. Hughes, Thomas E. Isomaa, Bo Jackson, Anne U. Jorgensen, Torben Kong, Augustine Kubalanza, Kari Kuruvilla, Finny G. Kuusisto, Johanna Langenberg, Claudia Lango, Hana Lauritzen, Torsten Li, Yun Lindgren, Cecilia M. Lyssenko, Valeriya Marvelle, Amanda F. Meisinger, Christa Midthjell, Kristian Mohlke, Karen L. Morken, Mario A. Morris, Andrew D. Narisu, Narisu Nilsson, Peter Owen, Katharine R. Palmer, Colin N. A. Payne, Felicity Perry, John R. B. Pettersen, Elin Platou, Carl Prokopenko, Inga Qi, Lu Qin, Li Rayner, Nigel W. Rees, Matthew Roix, Jeffrey J. Sandbaek, Anelli Shields, Beverley Sjogren, Marketa Steinthorsdottir, Valgerdur Stringham, Heather M. Swift, Amy J. Thorleifsson, Gudmar Thorsteinsdottir, Unnur Timpson, Nicholas J. Tuomi, Tiinamaija Tuomilehto, Jaakko Walker, Mark Watanabe, Richard M. Weedon, Michael N. Willer, Cristen J. Illig, Thomas Hveem, Kristian Hu, Frank B. Laakso, Markku Stefansson, Kari Pedersen, Oluf Wareham, Nicholas J. Barroso, Ines Hattersley, Andrew T. Collins, Francis S. Groop, Leif McCarthy, Mark I. Boehnke, Michael Altshuler, David CA DIAGRAM Consortium Wellcome Trust Case Control Consor TI Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes SO NATURE GENETICS LA English DT Article ID PROSTATE-CANCER; RISK LOCI; VARIANTS; GENES AB Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. C1 [Marchini, Jonathan L.; Elliott, Katherine S.; Lindgren, Cecilia M.; Prokopenko, Inga; Rayner, Nigel W.; Roix, Jeffrey J.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Scott, Laura J.; Hu, Tianle; Andersen, Gitte; Bostroem, Kristina Bengtsson; Ding, Chia-Jen; Duren, William L.; Erdos, Michael R.; Freathy, Rachel M.; Jackson, Anne U.; Li, Yun; Meisinger, Christa; Stringham, Heather M.; Watanabe, Richard M.; Willer, Cristen J.; Barroso, Ines] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Scott, Laura J.; Andersen, Gitte; Bostroem, Kristina Bengtsson; Duren, William L.; Erdos, Michael R.; Jackson, Anne U.; Li, Yun; Meisinger, Christa; Stringham, Heather M.; Watanabe, Richard M.; Willer, Cristen J.; Barroso, Ines] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Saxena, Richa; Voight, Benjamin F.; Ardlie, Kristin; Borch-Johnsen, Knut; Burtt, Noel P.; Deodhar, Parimal; Duren, William L.; Gianniny, Lauren; Guiducci, Candace; Hughes, Thomas E.; Kuruvilla, Finny G.; Lauritzen, Torsten] Broad Inst Harvard, Cambridge, MA 02142 USA. [Saxena, Richa; Voight, Benjamin F.; de Bakker, Paul I. W.; Ardlie, Kristin; Kuruvilla, Finny G.; Altshuler, David] MIT, Cambridge, MA 02142 USA. [Saxena, Richa; Voight, Benjamin F.; Daly, Mark J.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, Richa; Voight, Benjamin F.; Abecasis, Goncalo R.; Daly, Mark J.; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Saxena, Richa; Kuruvilla, Finny G.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Saxena, Richa; Voight, Benjamin F.; de Bakker, Paul I. W.; Daly, Mark J.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Saxena, Richa; Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Marchini, Jonathan L.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [de Bakker, Paul I. W.] Brigham & Womens Hosp, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. [Chines, Peter S.; Lyssenko, Valeriya; Nilsson, Peter; Sjogren, Marketa; Groop, Leif] Lund Univ, Dept Clin Sci, Diabet & Endocrinol Res Unit, Malmo Univ Hosp, S-20502 Malmo, Sweden. [Andersen, Gitte; Borch-Johnsen, Knut; Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Steno Diabet Ctr, DK-2820 Copenhagen, Denmark. [Bostroem, Kristina Bengtsson] Skaraborg Inst, S-54130 Skovde, Sweden. [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Bonnycastle, Lori L.; Chines, Peter S.; Deodhar, Parimal; Erdos, Michael R.; Kubalanza, Kari; Morken, Mario A.; Narisu, Narisu; Rees, Matthew; Swift, Amy J.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Borch-Johnsen, Knut; Sandbaek, Anelli; Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, DK-8000 Aarhus, Denmark. [Chen, Hong; Hughes, Thomas E.; Roix, Jeffrey J.] Novartis Inst Biomed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA. [Doney, Alex S. F.] Ninewells Hosp & Med Sch, Diabet Res Grp, Div Med & Therapeut, Dundee DD1 9SY, Scotland. [Frayling, Timothy M.; Freathy, Rachel M.; Lango, Hana; Perry, John R. B.; Weedon, Michael N.; Hattersley, Andrew T.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England. [Frayling, Timothy M.; Freathy, Rachel M.; Lango, Hana; Perry, John R. B.; Shields, Beverley; Weedon, Michael N.; Hattersley, Andrew T.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England. [Grallert, Harald; Meisinger, Christa; Illig, Thomas] Gesell Strahlenforsch Natl Res Ctr Environm & Hlt, Inst Epidemiol, D-85764 Neuherberg, Germany. [Groves, Christopher J.; Lindgren, Cecilia M.; Owen, Katharine R.; Prokopenko, Inga; Rayner, Nigel W.] Univ Oxford, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LJ, England. [Herder, Christian] Univ Dusseldorf, Inst Clin Diabet Res, German Diabetes Ctr, Leiden Inst, D-40225 Dusseldorf, Germany. [Hitman, Graham A.] Royal London Hosp, Ctr Diabet & Metab Med, London E1 1BB, England. [Isomaa, Bo] Malmska Municipal Hlth Ctr & Hosp, FIN-68601 Pietarsaari, Finland. [Isomaa, Bo] Folkhalsan Res Ctr, FIN-00014 Helsinki, Finland. [Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark. [Kong, Augustine; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Langenberg, Claudia; Wareham, Nicholas J.] Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge CB2 0QQ, England. [Lauritzen, Torsten] Univ Aarhus, Dept Gen Practice, DK-8000 Aarhus, Denmark. [Marvelle, Amanda F.; Mohlke, Karen L.; Qin, Li] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Midthjell, Kristian; Platou, Carl; Hveem, Kristian] Norwegian Univ Sci & Technol, HUNT Res Ctr, Dept Publ Hlth & Gen Practice, Fac Med, N-7650 Verdal, Norway. [Palmer, Colin N. A.] Ninewells Hosp & Med Sch, Populat Pharmacogenet Grp, Biomed Res Ctr, Dundee DD1 9SY, Scotland. [Payne, Felicity; Barroso, Ines] Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge CB10 1SA, England. [Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Qi, Lu] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Qi, Lu; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Timpson, Nicholas J.] Univ Bristol, MRC Ctr Causal Analyses Translat Epidemiol, Bristol BS2 8PR, Avon, England. [Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, Helsinki Univ Hosp, Dept Med, FIN-00300 Helsinki, Finland. [Tuomilehto, Jaakko; Altshuler, David] Natl Publ Hlth Inst, Diabet Unit, Dept Epidemiol & Hlth Promot, SF-00300 Helsinki, Finland. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki 60220, Finland. [Walker, Mark] Univ Newcastle Upon Tyne, Diabet Res Grp, Sch Clin Med Sci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Pettersen, Elin] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7600 Levanger, Norway. RP McCarthy, MI (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM mark.mccarthy@drl.ox.ac.uk; boehnke@umich.edu; altshuler@molbio.mgh.harvard.edu RI Fox, Laura /C-6249-2016; Prokopenko, Inga/H-3241-2014; Grarup, Niels/K-2807-2015; Study, GoDARTS/K-9448-2016; Palmer, Colin/C-7053-2008; Morris, Andrew/C-2837-2009; Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; Lango Allen, Hana/G-9026-2012; Hu, Tianle/H-9105-2012; de Bakker, Paul/B-8730-2009; Meisinger, Christine/B-5358-2014; Grallert, Harald/B-3424-2013 OI Freathy, Rachel/0000-0003-4152-2238; Zeggini, Eleftheria/0000-0003-4238-659X; Tuomi, Tiinamaija/0000-0002-8306-6202; Jorgensen, Torben/0000-0001-9453-2830; Timpson, Nicholas/0000-0002-7141-9189; Payne, Felicity/0000-0003-4228-581X; Prokopenko, Inga/0000-0003-1624-7457; Grarup, Niels/0000-0001-5526-1070; Palmer, Colin/0000-0002-6415-6560; Altshuler, David/0000-0002-7250-4107; Lango Allen, Hana/0000-0002-7803-8688; de Bakker, Paul/0000-0001-7735-7858; FU Department of Health [DHCS/07/07/008]; Intramural NIH HHS; Medical Research Council [G0000649, G0600705, G0601261, MC_U106179471]; NCI NIH HHS [CA87969, P01 CA087969]; NHGRI NIH HHS [HG002651, N01HG65403, R01 HG002651, U01 HG004171, U01 HG004399, Z01 HG000024]; NHLBI NIH HHS [HL084729, U01 HL084729]; NIDA NIH HHS [U54 DA021519]; NIDDK NIH HHS [DK062370, DK072193, DK58845, P30 DK040561, P30 DK040561-12, R01 DK029867, R01 DK058845, R01 DK062370, R01 DK072193, R56 DK062370, U01 DK062370]; Wellcome Trust [076113, 072960, 077016, 079557, 090532, GR072960] NR 27 TC 1141 Z9 1179 U1 8 U2 105 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 MAY PY 2008 VL 40 IS 5 BP 638 EP 645 DI 10.1038/ng.120 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 293WS UT WOS:000255366700033 PM 18372903 ER PT J AU Qiu, W Hu, M Sridhar, A Opeskin, K Fox, S Shipitsin, M Trivett, M Thompson, ER Ramakrishna, M Gorringe, KL Polyak, K Haviv, I Campbell, IG AF Qiu, Wen Hu, Min Sridhar, Anita Opeskin, Ken Fox, Stephen Shipitsin, Michail Trivett, Melanie Thompson, Ella R. Ramakrishna, Manasa Gorringe, Kylie L. Polyak, Kornelia Haviv, Izhak Campbell, Ian G. TI No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas SO NATURE GENETICS LA English DT Article ID STROMAL CELLS; TUMOR STROMA; MUTATIONS; HETEROZYGOSITY; CARCINOGENESIS; INSTABILITY; EPITHELIUM; MICE; PCR AB There is increasing evidence showing that the stromal cells surrounding cancer epithelial cells, rather than being passive bystanders, might have a role in modifying tumor outgrowth. The molecular basis of this aspect of carcinoma etiology is controversial. Some studies have reported a high frequency of genetic aberrations in carcinoma-associated fibroblasts (CAFs), whereas other studies have reported very low or zero mutation rates. Resolution of this contentious area is of critical importance in terms of understanding both the basic biology of cancer as well as the potential clinical implications of CAF somatic alterations. We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis of CAFs derived from breast and ovarian carcinomas using a 500K SNP array platform. Our data show conclusively that LOH and copy number alterations are extremely rare in CAFs and cannot be the basis of the carcinoma-promoting phenotypes of breast and ovarian CAFs. C1 [Qiu, Wen; Sridhar, Anita; Thompson, Ella R.; Ramakrishna, Manasa; Gorringe, Kylie L.; Campbell, Ian G.] Peter MacCallum Canc Ctr, VBCRC Canc Genet Lab, Melbourne, Vic 3002, Australia. [Qiu, Wen; Haviv, Izhak] Univ Melbourne, Dept Biochem, Melbourne, Vic 3010, Australia. [Hu, Min; Shipitsin, Michail; Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hu, Min; Shipitsin, Michail; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Opeskin, Ken] St Vincents Hosp, Dept Pathol, Fitzroy, Vic 3065, Australia. [Opeskin, Ken; Thompson, Ella R.; Ramakrishna, Manasa; Campbell, Ian G.] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Fox, Stephen; Trivett, Melanie] Peter MacCallum Canc Ctr, Dept Pathol, Melbourne, Vic 3002, Australia. [Haviv, Izhak] Peter MacCallum Canc Ctr, Canc Cell Biol Lab, Melbourne, Vic 3002, Australia. RP Campbell, IG (reprint author), Peter MacCallum Canc Ctr, VBCRC Canc Genet Lab, Melbourne, Vic 3002, Australia. EM ian.campbell@petermac.org RI campbell, Ian/F-6006-2011; OI Gorringe, Kylie/0000-0001-5681-2022; Fox, Stephen/0000-0002-7648-8896 FU NCI NIH HHS [P50 CA089393, CA116235, P50 CA089393-080014, R01 CA094074, R01 CA094074-05, R01 CA116235, R01 CA116235-01A1, R01 CA116235-02, R01 CA116235-03] NR 30 TC 143 Z9 145 U1 1 U2 8 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 MAY PY 2008 VL 40 IS 5 BP 650 EP 655 DI 10.1038/ng.117 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 293WS UT WOS:000255366700035 PM 18408720 ER PT J AU Krause, DS Van Etten, RA AF Krause, Daniela S. Van Etten, Richard A. TI Bedside to bench: Interfering with leukemic stem cells SO NATURE MEDICINE LA English DT Editorial Material ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; MOLECULAR RESPONSE RATE; POLYCYTHEMIA-VERA; ALPHA; IMATINIB; THERAPY; PROTEIN AB Kinase inhibitors such as imatinib (Gleevec) have improved the outlook for many people with chronic myeloid leukemia and related blood disorders. But such drugs do not target the leukemia stem cell population and may not be curative. Krause and Van Etten discuss several clinical studies that suggest that interferon-alpha may provide a solution by selectively eliminating leukemic stem cells-although only more basic research will tell us whether this is true and how it may happen. C1 [Krause, Daniela S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Van Etten, Richard A.] Tufts Univ, Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Van Etten, Richard A.] Tufts Univ, Med Ctr, Div Hematol Oncol, Boston, MA 02111 USA. RP Krause, DS (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM rvanetten@tuftsmedicacenter.org FU NCI NIH HHS [R01 CA090576]; NHLBI NIH HHS [R01 HL089747] NR 15 TC 9 Z9 9 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD MAY PY 2008 VL 14 IS 5 BP 494 EP 495 DI 10.1038/nm0508-494 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 298IQ UT WOS:000255681800025 PM 18463658 ER PT J AU Lo, EH AF Lo, Eng H. TI A new penumbra: transitioning from injury into repair after stroke SO NATURE MEDICINE LA English DT Article ID ACUTE ISCHEMIC-STROKE; NITRIC-OXIDE SYNTHASE; TISSUE-PLASMINOGEN ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; N-TERMINAL KINASE; BRAIN-INJURY; MATRIX-METALLOPROTEINASE; FUNCTIONAL RECOVERY; CLINICAL-TRIALS; MICE DEFICIENT AB The penumbra is an area of brain tissue that is damaged but not yet dead after focal ischemia. The existence of a penumbra implies that therapeutic salvage is theoretically possible after stroke. The first decade of penumbral science investigated the ischemic regulation of electrophysiology, cerebral blood flow and metabolism. The second decade advanced our understanding of molecular mechanisms that mediate penumbral cell death. And the third decade saw the rapid development of clinical neuroimaging tools that are now increasingly applied in stroke patients. But how can we look ahead as we move into the fourth decade of penumbra research? This author speculates that a paradigm shift is needed. Most molecular targets for therapy have biphasic roles in stroke pathophysiology. During the acute phase, these targets mediate injury. During the recovery phase, the same mediators contribute to neurovascular remodeling. It is this boundary zone that comprises the new penumbra, and future investigations should dissect where, when and how damaged brain makes the transition from injury into repair. C1 [Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA 02129 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Massachusetts Gen Hosp E 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu NR 50 TC 249 Z9 260 U1 0 U2 23 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 MAY PY 2008 VL 14 IS 5 BP 497 EP 500 DI 10.1038/nm1735 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 298IQ UT WOS:000255681800027 PM 18463660 ER PT J AU Mendez, I Vinuela, A Astradsson, A Mukhida, K Hallett, P Robertson, H Tierney, T Holness, R Dagher, A Trojanowski, JQ Isacson, O AF Mendez, Ivar Vinuela, Angel Astradsson, Arnar Mukhida, Karim Hallett, Penelope Robertson, Harold Tierney, Travis Holness, Renn Dagher, Alain Trojanowski, John Q. Isacson, Ole TI Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years SO NATURE MEDICINE LA English DT Article ID ALPHA-SYNUCLEIN; SUBSTANTIA-NIGRA; LEWY BODIES; STEM-CELLS; TRANSPLANTATION AB Postmortem analysis of five subjects with Parkinson's disease 9-14 years after transplantation of fetal midbrain cell suspensions revealed surviving grafts that included dopamine and serotonin neurons without pathology. These findings are important for the understanding of the etiopathogenesis of midbrain dopamine neuron degeneration and future use of cell replacement therapies. C1 [Vinuela, Angel; Astradsson, Arnar; Hallett, Penelope; Tierney, Travis; Isacson, Ole] Harvard Univ, Belmont, MA 02478 USA. [Vinuela, Angel; Astradsson, Arnar; Hallett, Penelope; Tierney, Travis; Isacson, Ole] McLean Hosp, US Natl Inst Neurol Disorders & Stroke, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. [Mendez, Ivar; Mukhida, Karim; Robertson, Harold; Holness, Renn] Dalhousie Univ, Halifax, NS B3H 3A7, Canada. [Mendez, Ivar; Mukhida, Karim; Robertson, Harold; Holness, Renn] Queen Elizabeth 2 Hlth Sci Ctr, Div Neurosurg, Halifax, NS B3H 3A7, Canada. [Mendez, Ivar; Mukhida, Karim; Robertson, Harold; Holness, Renn] Queen Elizabeth 2 Hlth Sci Ctr, Dept Anat & Neurobiol, Halifax, NS B3H 3A7, Canada. [Mendez, Ivar; Mukhida, Karim; Robertson, Harold; Holness, Renn] Queen Elizabeth 2 Hlth Sci Ctr, Dept Pharmacol, Halifax, NS B3H 3A7, Canada. [Tierney, Travis] Massachusetts Gen Hosp, Neurosci Serv, Boston, MA 02114 USA. [Dagher, Alain] McGill Univ, Montreal, PQ H3A 2B4, Canada. [Dagher, Alain] Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. [Trojanowski, John Q.] Univ Penn, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Inst Aging,NINDS Udall Parkinsons Dis Res Ctr Exc, Philadelphia, PA 19104 USA. RP Isacson, O (reprint author), Harvard Univ, 115 Mill St, Belmont, MA 02478 USA. EM isacson@hms.harvard.edu OI Hallett, Penelope/0000-0002-8858-9096 FU NINDS NIH HHS [NS 053488, P50 NS 39793, P50 NS039793, P50 NS039793-08, P50 NS053488] NR 15 TC 230 Z9 239 U1 1 U2 24 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 MAY PY 2008 VL 14 IS 5 BP 507 EP 509 DI 10.1038/nm1752 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 298IQ UT WOS:000255681800030 PM 18391961 ER PT J AU Li, J Wang, LL Mamon, H Kulke, MH Berbeco, R Makrigiorgos, GM AF Li, Jin Wang, Lilin Mamon, Harvey Kulke, Matthew H. Berbeco, Ross Makrigiorgos, G. Mike TI Replacing PCR with COLD-PCR enriches variant DNA sequences and redefines the sensitivity of genetic testing SO NATURE MEDICINE LA English DT Article ID CELL LUNG-CANCER; SINGLE-NUCLEOTIDE POLYMORPHISMS; GROWTH-FACTOR RECEPTOR; MUTATION DETECTION; PROGNOSTIC-FACTORS; PLASMA DNA; P53; RESISTANCE; GEFITINIB; CARCINOMA AB PCR is widely employed as the initial DNA amplification step for genetic testing. However, a key limitation of PCR-based methods is the inability to selectively amplify low levels of mutations in a wild-type background. As a result, downstream assays are limited in their ability to identify subtle genetic changes that can have a profound impact in clinical decision-making and outcome. Here we describe co-amplification at lower denaturation temperature PCR ( COLD-PCR), a novel form of PCR that amplifies minority alleles selectively from mixtures of wild-type and mutation-containing sequences irrespective of the mutation type or position on the sequence. We replaced regular PCR with COLD-PCR before sequencing or genotyping assays to improve mutation detection sensitivity by up to 100-fold and identified new mutations in the genes encoding p53, KRAS and epidermal growth factor in heterogeneous cancer samples that had been missed by the currently used methods. For clinically relevant microdeletions, COLD-PCR enabled exclusive amplification and isolation of the mutants. COLD-PCR will transform the capabilities of PCR-based genetic testing, including applications in cancer, infectious diseases and prenatal identification of fetal alleles in maternal blood. C1 [Li, Jin; Wang, Lilin; Mamon, Harvey; Berbeco, Ross; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Boston, MA 02115 USA. [Li, Jin; Wang, Lilin; Mamon, Harvey; Berbeco, Ross; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Div Phys, Dept Radiat Oncol, Boston, MA 02115 USA. [Li, Jin; Wang, Lilin; Mamon, Harvey; Berbeco, Ross; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Div Radiat Therapy, Dept Radiat Oncol, Boston, MA 02115 USA. [Kulke, Matthew H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Room JF514,44 Binney St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NCI NIH HHS [5 T32 CA09078, CA111994-01, CA115439-01] NR 27 TC 173 Z9 187 U1 3 U2 33 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 MAY PY 2008 VL 14 IS 5 BP 579 EP 584 DI 10.1038/nm1708 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 298IQ UT WOS:000255681800040 PM 18408729 ER PT J AU Goldstein, DM Gray, NS Zarrinkar, PP AF Goldstein, David M. Gray, Nathanael S. Zarrinkar, Patrick P. TI High-throughput kinase profiling as a platform for drug discovery SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID P38 MAP KINASE; MOLECULAR-MECHANISMS; CANCER THERAPEUTICS; ANTITUMOR-ACTIVITY; TYROSINE KINASES; PROTEIN-KINASES; RECEPTOR KINASE; LUNG-CANCER; TUMOR-CELLS; INHIBITION AB To fully exploit the potential of kinases as drug targets, novel strategies for the efficient discovery of inhibitors are required. In contrast to the traditional, linear process of inhibitor discovery, high-throughput kinase profiling enables a parallel approach by interrogating compounds against hundreds of targets in a single screen. Compound potency and selectivity are determined simultaneously, providing a choice of targets to pursue that is guided by the quality of lead compounds available, rather than by target biology alone. C1 [Zarrinkar, Patrick P.] Ambit Biosci, San Diego, CA 92121 USA. [Goldstein, David M.] Roche Palo Alto, Palo Alto, CA 94304 USA. [Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zarrinkar, PP (reprint author), Ambit Biosci, 4215 Sorrento Valley Blvd, San Diego, CA 92121 USA. EM pzarrinkar@ambitbio.com NR 60 TC 128 Z9 129 U1 0 U2 11 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 MAY PY 2008 VL 7 IS 5 BP 391 EP 397 DI 10.1038/nrd2541 PG 7 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 294QF UT WOS:000255419900013 PM 18404149 ER PT J AU Ansel, KM Pastor, WA Rath, N Lapan, AD Glasmacher, E Wolf, C Smith, LC Papadopoulou, N Lamperti, ED Tahiliani, M Ellwart, JW Shi, Y Kremmer, E Rao, A Heissmeyer, V AF Ansel, K. Mark Pastor, William A. Rath, Nicola Lapan, Ariya D. Glasmacher, Elke Wolf, Christine Smith, Laura C. Papadopoulou, Nikoletta Lamperti, Edward D. Tahiliani, Mamta Ellwart, Joachim W. Shi, Yujiang Kremmer, Elisabeth Rao, Anjana Heissmeyer, Vigo TI Mouse Eri1 interacts with the ribosome and catalyzes 5.8S rRNA processing SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID HISTONE MESSENGER-RNA; HUMAN PM-SCL; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; MICROPROCESSOR COMPLEX; C-ELEGANS; YEAST; MICRORNAS; 3'-EXONUCLEASE; INTERFERENCE AB Eri1 is a 3'-to-5' exoribonuclease conserved from fission yeast to humans. Here we show that Eri1 associates with ribosomes and ribosomal RNA (rRNA). Ribosomes from Eri1-deficient mice contain 5.8S rRNA that is aberrantly extended at its 3' end, and Eri1, but not a catalytically inactive mutant, converts this abnormal 5.8S rRNA to the wild-type form in vitro and in cells. In human and murine cells, Eri1 localizes to the cytoplasm and nucleus, with enrichment in the nucleolus, the site of preribosome biogenesis. RNA binding residues in the Eri1 SAP and linker domains promote stable association with rRNA and thereby facilitate 5.8S rRNA 3' end processing. Taken together, our findings indicate that Eri1 catalyzes the final trimming step in 5.8S rRNA processing, functionally and spatially connecting this regulator of RNAi with the basal translation machinery. C1 [Ansel, K. Mark] Childrens Hosp, Dept Pediat, Boston, MA 01125 USA. [Rath, Nicola; Glasmacher, Elke; Wolf, Christine; Papadopoulou, Nikoletta; Ellwart, Joachim W.; Kremmer, Elisabeth; Heissmeyer, Vigo] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Mol Immunol, D-81377 Munich, Germany. Brigham & Womens Hosp, Dept Med & BCMP, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Rao, Anjana] Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA. [Ansel, K. Mark; Pastor, William A.; Lapan, Ariya D.; Smith, Laura C.; Lamperti, Edward D.; Tahiliani, Mamta; Rao, Anjana] Harvard Med Sch, Immune Dis Inst, Boston, MA 02115 USA. RP Ansel, KM (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, Sandler Asthma Basic Res Ctr, 513 Parnassus Ave,Box 0414, San Francisco, CA 94143 USA. EM mark.ansel@ucsf.edu; vigo.heissmeyer@helmholtz-muenchen.de RI Rath, Nicola/M-6766-2015; Glasmacher, Elke/B-8939-2015 OI Rath, Nicola/0000-0002-2342-6843; Glasmacher, Elke/0000-0003-1265-2543 FU NIAID NIH HHS [R01 AI070788-04, AI44432, AI70788, R01 AI044432, R01 AI044432-06, R01 AI044432-07, R01 AI044432-08, R01 AI044432-09, R01 AI070788, R01 AI070788-03, R01 AI070788-05] NR 34 TC 34 Z9 35 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2008 VL 15 IS 5 BP 523 EP 530 DI 10.1038/nsmb.1417 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 297AO UT WOS:000255587800021 PM 18438418 ER PT J AU Gabel, HW Ruvkun, G AF Gabel, Harrison W. Ruvkun, Gary TI The exonuclease ERI-1 has a conserved dual role in 5.8S rRNA processing and RNAi SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID HISTONE MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; C-ELEGANS; 3'-EXONUCLEASE; PATHWAYS; SUBUNITS; 3'-END; YEAST; BOX AB The exonuclease ERI-1 negatively regulates RNA interference in Caenorhabditis elegans and Schizosaccharomyces pombe, and is required for production of some C. elegans endogenous small interfering RNAs. We show that ERI-1 performs 3' end processing of the 5.8S ribosomal RNA in both C. elegans and S. pombe. In C. elegans, two protein isoforms of ERI-1 are localized to the cytoplasm, and each has distinct functions in ribosomal RNA processing and negative regulation of RNA interference. C1 [Ruvkun, Gary] Harvard Med Sch, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Med Sch, Dept Genet, CPZN7250,185 Cambridge St, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU NIGMS NIH HHS [GM44619, R01 GM044619, R01 GM044619-17] NR 14 TC 39 Z9 42 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2008 VL 15 IS 5 BP 531 EP 533 DI 10.1038/nsmb.1411 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 297AO UT WOS:000255587800022 PM 18438419 ER PT J AU Frye, RE Fisher, JM Witzel, T Ahlfors, SP Swank, P Liederman, J Halgrene, E AF Frye, Richard E. Fisher, Janet McGraw Witzel, Thomas Ahlfors, Seppo P. Swank, Paul Liederman, Jacqueline Halgrene, Eric TI Objective phonological and subjective perceptual characteristics of syllables modulate spatiotemporal patterns of superior temporal gyrus activity SO NEUROIMAGE LA English DT Article DE laterality; magnetoencephalography; syllable perception; voice-onset time ID VOICE ONSET TIME; AUDITORY SENTENCE COMPREHENSION; SURFACE-BASED ANALYSIS; EVENT-RELATED FMRI; SPEECH-PERCEPTION; TOP-DOWN; LANGUAGE COMPREHENSION; SOURCE LOCALIZATION; MAGNETIC-FIELDS; WORKING-MEMORY AB Natural consonant-vowel syllables are reliably classified by most listeners as voiced or voiceless. However, our previous research [Liederman, J., Frye, R., Fisher, J. M., Greenwood, K., Alexander, R., 2005. A temporally dynamic context effect that disrupts voice onset time discrimination of rapidly successive stimuli. Psychon Bull Rev. 12, 380-386] suggests that among synthetic stimuli varying systematically in voice onset time (VOT), syllables that are classified reliably as voiceless are nonetheless perceived differently within and between listeners. This perceptual ambiguity was measured by variation in the accuracy of matching two identical stimuli presented in rapid succession. In the current experiment, we used magnetoencephalography (MEG) to examine the differential contribution of objective (i.e., VOT) and subjective (i.e., perceptual ambiguity) acoustic features on speech processing. Distributed source models estimated cortical activation within two regions of interest in the superior temporal gyrus (STG) and one in the inferior frontal gyrus. These regions were differentially modulated by VOT and perceptual ambiguity. Ambiguity strongly influenced lateralization of activation; however, the influence on lateralization was different in the anterior and middle/posterior portions of the STG. The influence of ambiguity on the relative amplitude of activity in the right and left anterior STG activity depended on VOT, whereas that of middle/posterior portions of the STG did not. These data support the idea that early cortical responses are bilaterally distributed whereas late processes are lateralized to the dominant hemisphere and support a "how/what" dual-stream auditory model. This study helps to clarify the role of the anterior STG, especially in the right hemisphere, in syllable perception. Moreover, our results demonstrate that both objective phonological and subjective perceptual characteristics of syllables independently modulate spatiotemporal patterns of cortical activation. (C) 2008 Elsevier Inc. All rights reserved. C1 [Frye, Richard E.] Univ Texas Houston, Dept Pediat, Div Child & Adolescent Neurol, Ctr Hlth Sci, Houston, TX 77030 USA. [Frye, Richard E.; Swank, Paul] Univ Texas Houston, Childrens Learning Inst, Hlth Sci Ctr, Dept Pediat, Houston, TX 77030 USA. [Fisher, Janet McGraw; Liederman, Jacqueline] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Witzel, Thomas; Ahlfors, Seppo P.] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Fisher, Janet McGraw; Liederman, Jacqueline] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. RP Frye, RE (reprint author), Univ Texas Houston, Dept Pediat, Div Child & Adolescent Neurol, Ctr Hlth Sci, 7000 Fannin UCT 2478, Houston, TX 77030 USA. EM Richard.E.Frye@uth.tmc.edu RI Witzel, Thomas/P-1402-2014; Ahlfors, Seppo/P-3644-2016 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NINDS NIH HHS [F31 NS048778, K23 NS046565, K23 NS046565-03, NS046565, NS048778, NS18741, R01 NS018741] NR 65 TC 9 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2008 VL 40 IS 4 BP 1888 EP 1901 DI 10.1016/j.neuroimage.2008.01.048 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 293PL UT WOS:000255347100045 PM 18356082 ER PT J AU Chen, WL Song, BB Marvizon, JC AF Chen, Wenling Song, Bingbing Marvizon, Juan Carlos G. TI Inhibition of opioid release in the rat spinal cord by alpha(2C) adrenergic receptors SO NEUROPHARMACOLOGY LA English DT Article DE clonidine; dorsal horn; dynorphin; enkephalin; guanfacine; internalization; JP-1302; medetomidine; mu-opioid receptor; norepinephrine; opioid; UK-14304 ID ENKEPHALIN-DEGRADING ENZYMES; DORSAL-HORN NEURONS; NOXIOUS MECHANICAL STIMULI; MEDIAL PREOPTIC NUCLEUS; RECEPTOR INTERNALIZATION; CALCIUM-CHANNELS; MIXED INHIBITOR; SUBSTANCE-P; PRIMARY AFFERENTS; GLUTAMATE RELEASE AB Neurotransmitter receptors that control the release of opioid peptides in the spinal cord may play an important role in pain modulation. Norepinephrine, released by a descending pathway originating in the brainstem, is a powerful inducer of analgesia in the spinal cord. Adrenergic alpha(2C) receptors are present in opioid-containing terminals in the dorsal horn, where they could modulate opioid release. The goal of this study was to investigate this possibility. Opioid release was evoked from rat spinal cord slices by incubating them with the sodium channel opener veratridine in the presence of peptidase inhibitors (actinonin, captopril and thiorphan), and was measured in situ through the internalization of mu-opioid receptors in dorsal horn neurons. Veratridine produced internalization in 70% of these neurons. The alpha(2) receptor agonists clonidine, guanfacine, medetomidine and UK-14304 inhibited the evoked mu-opioid receptor internalization with IC(50)S of 1.7 mu M, 248 nM, 0.3 nM and 22 nM, respectively. However, inhibition by medetomidine was only partial, and inhibition by UK-14304 reversed itself at concentrations higher than 50 nM. None of these agonists inhibited mu-opioid receptor internalization produced by endomorphin-2, showing that they inhibited opioid release and not the internalization itself. The inhibitions produced by clonidine, guanfacine or UK-14304 were completely reversed by the selective alpha(2C) antagonist JP-1203. In contrast, inhibition by guanfacine was not prevented by the alpha(2A) antagonist BRL-44408. These results show that alpha(2C) receptors inhibit the release of opioids in the dorsal horn. This action may serve to shut down the opioid system when the adrenergic system is active. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Chen, Wenling; Song, Bingbing; Marvizon, Juan Carlos G.] Vet Affairs Greater Los Angels Healthcare Syst, Los Angeles, CA 90073 USA. [Chen, Wenling; Song, Bingbing; Marvizon, Juan Carlos G.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurobiol Stress, Los Angeles, CA 90095 USA. [Chen, Wenling; Song, Bingbing; Marvizon, Juan Carlos G.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. RP Marvizon, JC (reprint author), Vet Affairs Greater Los Angels Healthcare Syst, Los Angeles, CA 90073 USA. EM marvizon@ucla.edu FU NIDA NIH HHS [R01 DA012609-06A1, R01 DA012609, 2 R01 DA012609, R01 DA012609-08, R01 DA012609-07] NR 70 TC 15 Z9 17 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAY PY 2008 VL 54 IS 6 BP 944 EP 953 DI 10.1016/j.neuropharm.2008.02.002 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 305TL UT WOS:000256200600005 PM 18343461 ER PT J AU Goldstein, G Allen, DN Minshew, NJ Williams, DL Volkmar, F Klin, A Schultz, RT AF Goldstein, Gerald Allen, Daniel N. Minshew, Nancy J. Williams, Diane L. Volkmar, Fred Klin, Ami Schultz, Robert T. TI The structure of intelligence in children and adults with high functioning autism SO NEUROPSYCHOLOGY LA English DT Article DE autism; intelligence testing; confirmatory factor analysis ID CONFIRMATORY FACTOR-ANALYSIS; DIAGNOSTIC OBSERVATION SCHEDULE; SENTENCE COMPREHENSION; WAIS-R; SCHIZOPHRENIA; INDIVIDUALS; FIT; UNDERCONNECTIVITY; CONNECTIVITY; VALIDATION AB Confirmatory factor analyses of the commonly used 11 subtests of the Wechsler child and adult intelligence scales were accomplished for 137 children and 117 adults with high functioning autism (HFA) and for comparable age groups from the standardization samples contained in the Wechsler manuals. The objectives were to determine whether the structure of intelligence in HFA groups was similar to that found in the normative samples, and whether a separate "social context" factor would emerge that was unique to HFA. Four-factor models incorporating a Social Context factor provided the best fit in both the autism and normative samples, but the subtest intercorrelations were generally lower in the autism samples. Findings suggest similar organization of cognitive abilities in HFA, but with the possibility of underconnectivity or reduced communication among brain regions in autism. C1 [Goldstein, Gerald] VA Pittsburgh Hlth Care Syst, Res Serv 151R, Pittsburgh, PA 15206 USA. [Allen, Daniel N.] Univ Nevada Las Vegas, Dept Psychol, Las Vegas, NV USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. [Williams, Diane L.] Duquesne Univ, Dept Speech Language Pathol, Pittsburgh, PA USA. [Volkmar, Fred; Klin, Ami] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Schultz, Robert T.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA USA. RP Goldstein, G (reprint author), VA Pittsburgh Hlth Care Syst, Res Serv 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM ggold@nb.net RI Williams, Diane/B-4128-2017 FU NICHD NIH HHS [P50 HD055748, U19 HD035469-08, U19 HD035469-06, U19 HD035469-09, U19 HD035469, U19 HD035469-07, U19 HD035469-10] NR 44 TC 30 Z9 32 U1 2 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAY PY 2008 VL 22 IS 3 BP 301 EP 312 DI 10.1037/0894-4105.22.3.301 PG 12 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 294AX UT WOS:000255377600003 PM 18444708 ER PT J AU Bearden, CE Thompson, PM Dutton, RA Frey, BN Peluso, MAM Nicoletti, M Dierschke, N Hayashi, KM Klunder, AD Glahn, DC Brambilla, P Sassi, RB Mallinger, AG Soares, JC AF Bearden, Carrie E. Thompson, Paul M. Dutton, Rebecca A. Frey, Benicio N. Peluso, Marco A. M. Nicoletti, Mark Dierschke, Nicole Hayashi, Kiralee M. Klunder, Andrea D. Glahn, David C. Brambilla, Paolo Sassi, Roberto B. Mallinger, Alan G. Soares, Jair C. TI Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-for-Neuroscience CY OCT 14-18, 2006 CL Atlanta, GA SP Soc Neurosci DE mood disorder; magnetic resonance imaging; hippocampus; medication effects; neurotrophins; brain mapping ID MILD COGNITIVE IMPAIRMENT; MANIC-DEPRESSIVE ILLNESS; N-ACETYL-ASPARTATE; GRAY-MATTER; MOOD DISORDERS; HUMAN BRAIN; IN-VIVO; ALZHEIMERS-DISEASE; PROTEIN BCL-2; SCHIZOPHRENIA AB Declarative memory impairments are common in patients with bipolar illness, suggesting underlying hippocampal pathology. However, hippocampal volume deficits are rarely observed in bipolar disorder. Here we used surface-based anatomic mapping to examine hippocampal anatomy in bipolar patients treated with lithium relative to matched control subjects and unmedicated patients with bipolar disorder. High-resolution brain magnetic resonance images were acquired from 33 patients with bipolar disorder ( 21 treated with lithium and 12 unmedicated), and 62 demographically matched healthy control subjects. Three-dimensional parametric mesh models were created from manual tracings of the hippocampal formation. Total hippocampal volume was significantly larger in lithium-treated bipolar patients compared with healthy controls (by 10.3%; p=0.001) and unmedicated bipolar patients ( by 13.9%; p=0.003). Statistical mapping results, confirmed by permutation testing, revealed localized deficits in the right hippocampus, in regions corresponding primarily to cornu ammonis vertical bar subfields, in unmedicated bipolar patients, as compared to both normal controls (p=0.01), and in lithium-treated bipolar patients (p=0.03). These findings demonstrate the sensitivity of these anatomic mapping methods for detecting subtle alterations in hippocampal structure in bipolar disorder. The observed reduction in subregions of the hippocampus in unmedicated bipolar patients suggests a possible neural correlate for memory deficits frequently reported in this illness. Moreover, increased hippocampal volume in lithium-treated bipolar patients may reflect postulated neurotrophic effects of this agent, a possibility warranting further study in longitudinal investigations. C1 [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Thompson, Paul M.; Dutton, Rebecca A.; Klunder, Andrea D.] Calif State Univ Los Angeles, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90032 USA. [Frey, Benicio N.; Peluso, Marco A. M.; Dierschke, Nicole; Glahn, David C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Frey, Benicio N.] Univ Fed Rio Grande do Sul, Dept Psychiat, Porto Alegre, RS, Brazil. [Frey, Benicio N.] Univ Fed Rio Grande do Sul, Bipolar Disorder Program, Porto Alegre, RS, Brazil. [Peluso, Marco A. M.; Sassi, Roberto B.] Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. [Nicoletti, Mark; Soares, Jair C.] UNC Chapel HilL, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Brambilla, Paolo] IRCCS, Inst Sci, Udine, Italy. [Brambilla, Paolo] Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. [Sassi, Roberto B.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Mallinger, Alan G.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RP Bearden, CE (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Semel Inst Neurosci & Human Behav, 300 Bldg Med Pl,Suite 2265, Los Angeles, CA 90095 USA. EM cbearden@mednet.ucla.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NCRR NIH HHS [RR019771, RR020571]; NIA NIH HHS [AG016570]; NIBIB NIH HHS [EB01651]; NICHD NIH HHS [HD050735]; NIMH NIH HHS [K23 MH074644-01, K23 MH074644, MH 01736, MH 30915] NR 54 TC 71 Z9 71 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2008 VL 33 IS 6 BP 1229 EP 1238 DI 10.1038/sj.npp.1301507 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 287KI UT WOS:000254915600002 PM 17687266 ER PT J AU Peterson, RT Nass, R Boyd, WA Freedman, JH Dong, K Narahashi, T AF Peterson, Randall T. Nass, Richard Boyd, Windy A. Freedman, Jonathan H. Dong, Ke Narahashi, Toshio TI Use of non-mammalian alternative models for neurotoxicological study SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 11th Meeting of the International-Neurotoxicology-Association CY JUN, 2007 CL Pacific Grove, CA SP Int Neurotoxicol Assoc DE C. elegans; Parkinson's; zebrafish; neurotoxicological studies; insects; insecticides ID GATED CHLORIDE CHANNELS; RESISTANT SODIUM-CHANNELS; ROOT GANGLION NEURONS; HUMAN ALPHA-SYNUCLEIN; CAENORHABDITIS-ELEGANS; PARKINSONS-DISEASE; COCKROACH NEURONS; XENOPUS OOCYTES; C-ELEGANS; PYRETHROID INSECTICIDES AB The field of neurotoxicology needs to satisfy two opposing demands: the testing of a growing list of chemicals, and resource limitations and ethical concerns associated with testing using traditional mammalian species. National and international government agencies have defined a need to reduce, refine or replace mammalian species in toxicological testing with alternative testing methods and mammalian models. Toxicological assays using alternative animal models may relieve some of this pressure by allowing testing of more compounds while reducing expense and using fewer mammals. Recent advances in genetic technologies and, the strong conservation between human and non-mammalian genomes allow for the dissection of the molecular pathways involved in neurotoxicological responses and neurological diseases using genetically tractable organisms. In this review, applications of four non-mammalian species, zebrafish, cockroach, Drosophila, and Caenorhabditis elegans, in the investigation of neurotoxicology and neurological diseases are presented. (C) 2008 Elsevier Inc. All rights reserved. C1 [Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Nass, Richard] Indiana Univ, Sch Med, Ctr Environm Hlth, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. [Boyd, Windy A.; Freedman, Jonathan H.] Natl Inst Environm Hlth Sci, NIH, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Boyd, Windy A.; Freedman, Jonathan H.] Natl Inst Environm Hlth Sci, NIH, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Dong, Ke] Michigan State Univ, Pesticide Res Ctr, E Lansing, MI 48824 USA. [Narahashi, Toshio] Northwestern Univ, Feinberg Sch Med, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA. RP Narahashi, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM narahashi@northwestern.edu OI Boyd, Windy/0000-0003-3803-3716 FU NINDS NIH HHS [R01 NS014143-27] NR 99 TC 80 Z9 83 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAY PY 2008 VL 29 IS 3 SI SI BP 546 EP 555 DI 10.1016/j.neuro.2008.04.006 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 317MV UT WOS:000257025200022 PM 18538410 ER PT J AU Carmody, TP Duncan, C Simon, JA Solkowitz, S Huggins, J Lee, S Delucchi, K AF Carmody, Timothy P. Duncan, Carol Simon, Joel A. Solkowitz, Sharon Huggins, Joy Lee, Sharon Delucchi, Kevin TI Hypnosis for smoking cessation: A randomized trial SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SUGGESTIBILITY; PAIN AB The purpose of this study was to determine whether hypnosis would be more effective in helping smokers quit than standard behavioral counseling when both interventions are combined with nicotine patches (NP). A total of 286 current smokers were enrolled in a randomized controlled smoking cessation trial at the San Francisco Veterans Affairs Medical Center. Participants in both treatment conditions were seen for two 60-min sessions, and received three follow-up phone calls and 2 months of NP. At 6 months, 29% of the hypnosis group reported 7-day point-prevalence abstinence compared with 23% of the behavioral counseling group (relative risk [RR]=1.27; 95% confidence interval, CI 0.84-1.92). Based on biochemical or proxy confirmation, 26% of the participants in the hypnosis group were abstinent at 6 months compared with 18% of the behavioral group (RR = 1.44; 95% CI 0.91-2.30). At 12 months, the self-reported 7-day point-prevalence quit rate was 24% for the hypnosis group and 16% for the behavioral group (RR = 1.47; 95% CI 0.90-2.40). Based on biochemical or proxy confirmation, 20% of the participants in the hypnosis group were abstinent at 12 months compared with 14% of the behavioral group (RR=1.40; 95% CI 0.81-2.42). Among participants with a history of depression, hypnosis yielded significantly higher validated point-prevalence quit rates at 6 and 12 months than standard treatment. It was concluded that hypnosis combined with NP compares favorably with standard behavioral counseling in generating long-term quit rates. C1 [Carmody, Timothy P.; Duncan, Carol; Simon, Joel A.; Solkowitz, Sharon; Huggins, Joy; Lee, Sharon; Delucchi, Kevin] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Carmody, TP (reprint author), Vet Affairs Med Ctr, Mental Hlth Serv 116B, 4150 Clement St, San Francisco, CA 94121 USA. EM Timothy.Carmody@ucsf.edu OI Delucchi, Kevin/0000-0003-2195-9627 NR 27 TC 24 Z9 25 U1 3 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD MAY PY 2008 VL 10 IS 5 BP 811 EP 818 DI 10.1080/14622200802023833 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 303QP UT WOS:000256055900006 PM 18569754 ER PT J AU Donelan, K Buerhaus, P DesRoches, C Dittus, R Dutwin, D AF Donelan, Karen Buerhaus, Peter DesRoches, Catherine Dittus, Robert Dutwin, David TI Public perceptions of nursing careers: The influence of the media and nursing shortages SO NURSING ECONOMICS LA English DT Article ID PHYSICIANS; NURSES AB The high public regard for nurses has not necessarily translated into an adequate supply of individuals who are willing to be nurses. The expected future demand for nurse labor challenges us to look more closely at the public's perceptions of nursing and nursing careers, and consider how they are shaped by personal experience, media messages, and socio-demographic factors. As part of ongoing efforts to examine factors shaping the future of the nursing workforce, a national survey of Americans was conducted to probe attitudes toward the nursing profession and their experiences with nurses. The data in this national survey of the public about nursing demonstrate that the nursing profession is highly respected and that the vast majority of the general public would recommend nursing careers to qualified students. If the profession is so well thought of and so highly recommended, why are there persistent concerns that not enough people are becoming RNs to avoid or at least slow down the development of future shortages? A prolonged and persistent effort is needed to educate people about nursing careers, to stimulate the expanded production of nursing faculty, and to bring creative approaches to financing nursing education and workforce improvements to convert the large number of seriously interested candidates into the nursing profession. C1 [Donelan, Karen; DesRoches, Catherine] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Buerhaus, Peter] Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Nashville, TN USA. [Dittus, Robert] Vanderbilt Univ, Med Ctr, Div Gen Internal Med & Publ Hlth, Nashville, TN USA. [Dutwin, David] ICR Commun Res, Media, PA USA. RP Donelan, K (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. NR 16 TC 27 Z9 27 U1 0 U2 4 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD MAY-JUN PY 2008 VL 26 IS 3 BP 143 EP + PG 9 WC Nursing SC Nursing GA 319OV UT WOS:000257174300002 PM 18616051 ER PT J AU Papaliodis, GN Montezuma, SR AF Papaliodis, George Nick Montezuma, Sandra R. TI Pseudo-hypopyon as the presenting feature of recurrent B-cell lymphoma SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE uveitis; iritis; masquerade syndrome; intraocular lymphoma; malignancy ID INTRAOCULAR LYMPHOMA; RELAPSE AB Purpose: To report a case of a pseudo-hypopyon as the presentation for recurrent B-cell lymphoma. Design: Case report. Methods: Case report with anterior segment photograph. Results: A 74-year-old man with past medical history of peripheral B-cell lymphoma developed a hypopyon 3 months after R-CHOP chemotherapy and prophylactic intrathecal chemotherapy. Anterior chamber aspirate was consistent with B-cell lymphoma. Conclusions: Pseudo-hypopyon as a manifestation of recurrent B-cell lymphoma is a rare clinical presentation of an intraocular malignancy. A high index of suspicion along with intraocular fluid analysis are essential to establish the diagnosis. C1 [Papaliodis, George Nick; Montezuma, Sandra R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Papaliodis, George Nick] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Papaliodis, GN (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM gpapaliodis@partners.org NR 6 TC 3 Z9 3 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 MAY-JUN PY 2008 VL 16 IS 3 BP 121 EP 122 DI 10.1080/09273940802026052 PG 2 WC Ophthalmology SC Ophthalmology GA 311EA UT WOS:000256582300012 PM 18569803 ER PT J AU Moy, B AF Moy, Beverly TI Medical integrity up in smoke? Conflicts of interest and the lung cancer screening controversy SO ONCOLOGIST LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Cancers, Boston, MA 02114 USA. RP Moy, B (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Cancers, 55 Fruit St,Lawrence House,LRH 304, Boston, MA 02114 USA. EM bmoy@partners.org NR 13 TC 4 Z9 4 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2008 VL 13 IS 5 BP 474 EP 476 DI 10.1634/theoncologist.2008-0098 PG 3 WC Oncology SC Oncology GA 307KO UT WOS:000256318000001 PM 18515732 ER PT J AU Cashavelly, BJ Donelan, K Binda, KD Mailhot, JR Clair-Hayes, KA Maramaldi, P AF Cashavelly, Barbara J. Donelan, Karen Binda, Kathryn D. Mailhot, Johanna R. Clair-Hayes, Katherine A. Maramaldi, Peter TI The forgotten team member: Meeting the needs of oncology support staff SO ONCOLOGIST LA English DT Article DE patient care team; cancer care unit; Burnout; stress; staff attitude; job satisfaction ID JOB STRESS; CARE; BURNOUT; SATISFACTION; EXPERIENCES; WORKERS; NURSES AB Introduction. The impact of working in an oncology setting has been widely researched for physicians, nurses, social workers, and chaplains. The experiences of nonlicensed support staff in an oncology setting have rarely been acknowledged or addressed. Few studies have addressed support or education initiatives for support staff caring for oncology patients. The intent of this study was to understand the work experiences of oncology support staff. Emotional impact, patient relationships, and team relationships were addressed. These data would help shape the development of an oncology support staff program. Methods. A qualitative and quantitative approach was used to explore the experiences of support staff. Seven focus groups and individual interviews were conducted addressing work life in a cancer center. The quantitative survey collected baseline data on job satisfaction, working relationships, patient relationships, burnout, and support programs. Results. Four predominant themes emerged from the focus groups. These included: relationships with patients and families, coping with death and dying, value and recognition, and balancing function with emotion. The quantitative survey reported the highest satisfaction with patient relationships and the lowest satisfaction with job recognition and supervisor support. High personal accomplishment scores declined with duration of employment. Educational grand rounds were a high interest. Discussion. This study provides insight into the impact of caring for oncology patients on support staff. Burnout and job satisfaction can be costly. Recognizing the challenges inherent in the oncology environment is essential to supporting a successful oncology practice for licensed and nonlicensed support staff. C1 [Cashavelly, Barbara J.; Binda, Kathryn D.; Clair-Hayes, Katherine A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Donelan, Karen; Mailhot, Johanna R.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA USA. [Maramaldi, Peter] Massachusetts Gen Hosp, Simmons Coll, Sch Social Work, Boston, MA 02114 USA. RP Cashavelly, BJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7-7058,55 Fruit St, Boston, MA 02114 USA. EM bcashavelly@partners.org NR 21 TC 14 Z9 16 U1 1 U2 10 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2008 VL 13 IS 5 BP 530 EP 538 DI 10.1634/theoncologist.2008-0023 PG 9 WC Oncology SC Oncology GA 307KO UT WOS:000256318000007 PM 18515738 ER PT J AU Schapira, L Vargas, E Hidalgo, R Brier, M Sanchez, L Hobrecker, K Lynch, T Chabner, B AF Schapira, Lidia Vargas, Erika Hidalgo, Renzo Brier, Marilyn Sanchez, Lourdes Hobrecker, Karin Lynch, Thomas Chabner, Bruce TI Lost in translation: Integrating medical interpreters into the multidisciplinary team SO ONCOLOGIST LA English DT Article DE language; interpreters; communication; cancer ID LIMITED ENGLISH PROFICIENCY; LANGUAGE DIVIDE; HEALTH-CARE; PHYSICIANS; COMMUNICATION; SERVICES; IMPROVE; ERRORS; ROLES AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Professional medical interpreters play a crucial role in mediating language-discordant encounters between cancer patients and oncologists. Trained interpreters allow for timely information exchange that is both accurate and culturally sensitive. Rising numbers of immigrants will increase the demand for interpreters. Medical oncologists need to respond by establishing collaborative practices with interpreters or using remote interpretation services. The article provides specific recommendations for working with medical interpreters and reviews common areas of concern for patients and healthcare professionals facing language and cultural barriers. C1 [Schapira, Lidia; Lynch, Thomas; Chabner, Bruce] Massachusetts Gen Hosp, Ctr Canc, Dept Med Oncol, Gillette Ctr Breast Canc, Boston, MA 02114 USA. [Vargas, Erika; Hidalgo, Renzo; Sanchez, Lourdes; Hobrecker, Karin] Massachusetts Gen Hosp, Ctr Canc, Dept Interpreter Serv, Boston, MA 02114 USA. [Brier, Marilyn] Massachusetts Gen Hosp, Ctr Canc, Dept Social Serv, Boston, MA 02114 USA. RP Schapira, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med Oncol, Gillette Ctr Breast Canc, 55 Fruit St,YAW 9, Boston, MA 02114 USA. EM lschapira@partners.org NR 23 TC 11 Z9 11 U1 5 U2 18 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2008 VL 13 IS 5 BP 586 EP 592 DI 10.1634/theoncologist.2008-0042 PG 7 WC Oncology SC Oncology GA 307KO UT WOS:000256318000012 PM 18515743 ER PT J AU Drapek, L Odette, E AF Drapek, Lorraine Odette, Esther TI Caring for patients receiving chemo/radiation for pancreatic cancer SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Drapek, Lorraine; Odette, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 2630 BP 489 EP 489 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700041 ER PT J AU Bartholomay, M Mannix, C Barton-Burke, M Bilodeau, ML Delaney, R Doherty, C Lewis, M AF Bartholomay, Mimi Mannix, Catherine Barton-Burke, Margaret Bilodeau, Mary Liz Delaney, Robin Doherty, Carol Lewis, Maryellen TI A feasibility study of low-cost patient-administered skin care intervention among head and neck cancer patients receiving chemo-radiation SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Mannix, Catherine; Barton-Burke, Margaret; Bilodeau, Mary Liz; Delaney, Robin; Doherty, Carol; Lewis, Maryellen] Massachusetts Gen Hosp, MGHCC, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 2675 BP 494 EP 494 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700058 ER PT J AU Fonteyn, M Spenser, L Gross, A AF Fonteyn, Marsha Spenser, Leslie Gross, Anne TI Assessment of the challenges of oral chemotherapy adherence in adult oncology patients SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Fonteyn, Marsha; Spenser, Leslie; Gross, Anne] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 2894 BP 524 EP 524 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700156 ER PT J AU Fonteyn, M Suzuki, N Pedulla, LV Gross, A AF Fonteyn, Marsha Suzuki, Naoe Pedulla, Lillian Vitale Gross, Anne TI A coordinated approach to support nurses' dissemination efforts improved the quality and quantity of presentations at professional conferences SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Fonteyn, Marsha; Suzuki, Naoe; Pedulla, Lillian Vitale; Gross, Anne] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 2927 BP 529 EP 529 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700173 ER PT J AU Johnson, E Bartholomay, M Curran, J Finn, S Lyons, H AF Johnson, Elizabeth Bartholomay, Mimi Curran, Judith Finn, Susan Lyons, Hannah TI An integrated education program to support evidence-based oncology nursing practice SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Johnson, Elizabeth; Bartholomay, Mimi; Curran, Judith; Finn, Susan; Lyons, Hannah] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 3006 BP 539 EP 540 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700209 ER PT J AU Johnson, E Caster, C AF Johnson, Elizabeth Caster, Coleen TI Growing pearls: Promoting unit-based quality improvement through communication, negotiation, and critical thinking SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Johnson, Elizabeth; Caster, Coleen] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 3030 BP 544 EP 545 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700225 ER PT J AU Roper, K Cooley, M Powell, M McDermott, K Coakley, C Boyd, K Fawcett, J AF Roper, Kristin Cooley, Mary Powell, Mark McDermott, Kathleen Coakley, Christine Boyd, Kecia Fawcett, Jacqueline TI Health-related quality of life after treatment for Hodgkin disease SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Roper, Kristin; Cooley, Mary; Powell, Mark; McDermott, Kathleen; Coakley, Christine; Boyd, Kecia] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fawcett, Jacqueline] Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 3050 BP 547 EP 548 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700235 ER PT J AU Singer, M Poage, E Armer, J Ridner, S Shellaberger, J Poundall, M AF Singer, Marybeth Poage, Ellen Armer, Jane Ridner, Sheila Shellaberger, Jeanne Poundall, Melanie TI Demystifying lymphedema: Putting evidence into practice SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Poundall, Melanie] Massachusetts Gen Hosp, Yawkey Infus Ctr, Boston, MA 02114 USA. [Poage, Ellen] Lymphedema Practitioner Consultant, Ft Myers, FL USA. [Armer, Jane; Shellaberger, Jeanne] Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. [Ridner, Sheila] ACNP, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 3069 BP 550 EP 551 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700245 ER PT J AU Schulte, K Mazeika, T Tracey, E Spencer, L Gross, A Fonteyn, M AF Schulte, Karen Mazeika, Teresa Tracey, Elizabeth Spencer, Leslie Gross, Anne Fonteyn, Marsha TI Assessment of current nursing practice associated with oral chemotherapy adherence SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 [Schulte, Karen; Mazeika, Teresa; Tracey, Elizabeth; Spencer, Leslie; Gross, Anne; Fonteyn, Marsha] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2008 VL 35 IS 3 MA 3074 BP 551 EP 552 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 298NF UT WOS:000255693700248 ER PT J AU Topuz, O Aydin, C Uzun, O Inan, U Alacam, T Tunca, YM AF Topuz, Ozgur Aydin, Cumhur Uzun, Ozgur Inan, Ugur Alacam, Tayfun Tunca, Yasar M. TI Structural effects of sodium hypochlorite solution on RaCe rotary nickel-titanium instruments: an atomic force microscopy study SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID ENDODONTIC INSTRUMENTS; FRACTURE PROPERTIES; FILES; CORROSION; SURFACES; SEM AB Objective. The aim of this study was to investigate the effect of sodium hypochlorite immersion on the surface characteristics of RaCe rotary nickel-titanium instruments using atomic force microscopy (AFM). Study design. Four new RaCe instruments were used in this study (two 30.06 and two 30.02). One 30.06 and one 30.02 instrument were immersed in sodium hypochlorite solution for 5 min. Surface topography of the instruments was evaluated using the AFM. The instruments were analyzed on 11 points along a 3-mm section. Root mean square (RMS) values were used to compare the topographic deviations. The data were analyzed using Student t test. Results. Mean RMS values for NaOCl measurements were higher than the measurements on new files, and the difference was statistically significant (P <.01). Conclusion. The AFM results show that NaOCl causes deterioration on the surface of RaCe instruments and should be used with care during clinical use because of the risk of unexpected failure. C1 [Topuz, Ozgur; Uzun, Ozgur; Alacam, Tayfun] Gazi Univ, Dept Operat Dent & Endodont, Fac Dent, Ankara, Turkey. [Aydin, Cumhur; Tunca, Yasar M.] Gulhane Mil Med Acad, Dept Endodont & Cconservat Treatment, Ctr Dent Sci, Ankara, Turkey. [Inan, Ugur] Ondokuz Mayis Univ, Dept Endodont & Restorat Dent, Fac Dent, Samsun, Turkey. RP Aydin, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Blossom St Thier 10, Boston, MA 02114 USA. EM oaydin@partners.org NR 25 TC 13 Z9 13 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAY PY 2008 VL 105 IS 5 BP 661 EP 665 DI 10.1016/j.tripleo.2007.11.006 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 293OJ UT WOS:000255344300020 PM 18329912 ER PT J AU Taitsman, LA Altman, DT Hecht, AC Pedlow, FX AF Taitsman, Lisa A. Altman, Daniel T. Hecht, Andrew C. Pedlow, Frank X. TI Complications of cervical halo-vest orthoses in elderly patients SO ORTHOPEDICS LA English DT Article C1 [Taitsman, Lisa A.] Harborview Med Ctr, Dept Orthoped, Seattle, WA 98104 USA. [Altman, Daniel T.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Hecht, Andrew C.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Pedlow, Frank X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taitsman, LA (reprint author), Harborview Med Ctr, Dept Orthoped, 325 9th Ave, Seattle, WA 98104 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD MAY PY 2008 VL 31 IS 5 BP 446 EP 446 PG 1 WC Orthopedics SC Orthopedics GA 302HW UT WOS:000255960400010 PM 19292320 ER PT J AU Morse, L Teng, YD Pham, L Newton, K Yu, D Liao, WL Kohler, T Muller, R Graves, D Stashenko, P Battaglino, R AF Morse, L. Teng, Y. D. Pham, L. Newton, K. Yu, D. Liao, W. -L. Kohler, T. Mueller, R. Graves, D. Stashenko, P. Battaglino, R. TI Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats) SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE bone; osteoclast; osteoporosis; rehabilitation medicine; spinal cord injury ID ACUTE HEMATOGENOUS OSTEOMYELITIS; EXTERNAL URETHRAL SPHINCTER; CHRONIC CENTRAL PAIN; BLADDER DETRUSOR; MINERAL DENSITY; SYMPATHECTOMY; RECOVERY; CELLS; MODEL; COORDINATION AB Spinal cord injury causes severe bone loss. We report osteoclast resorption with severe trabecular and cortical bone loss, decreased bone mineral apposition, and growth plate abnormalities in a rodent model of contusion spinal cord injury. These findings will help elucidate the mechanisms of osteoporosis following neurological trauma. Introduction Limited understanding of the mechanism(s) that underlie spinal cord injury (SCI)-induced bone loss has led to few treatment options. As SCI-induced osteoporosis carries significant morbidity and can worsen already profound disability, there is an urgency to advance knowledge regarding this pathophysiology. Methods A clinically relevant contusion model of experimental spinal cord injury was used to generate severe lower thoracic SCI by weight-drop (10 g x 50 mm) in adolescent male Sprague-Dawley rats. Body weight and gender-matched naive (no surgery) rats served as controls. Bone microarchitecture was determined by micro-computed tomographic imaging. Mature osteoclasts were identified by TRAP staining and bone apposition rate was determined by dynamic histomorphometry. Results At 10 days post-injury we detected a marked 48% decrease in trabecular bone and a 35% decrease in cortical bone at the distal femoral metaphysis by micro-CT. A 330% increase in the number of mature osteoclasts was detected at the growth plate in the injured animals that corresponded with cellular disorganization at the chondro-osseous junction. Appositional growth studies demonstrated decreased new bone formation with a mineralization defect indicative of osteoblast dysfunction. Conclusions Contusion SCI results in a rapid bone loss that is the result of increased bone resorption and decreased bone formation. C1 [Morse, L.; Teng, Y. D.; Liao, W. -L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Morse, L.; Teng, Y. D.; Liao, W. -L.] Spaulding Rehabil Hosp, Boston, MA 02115 USA. [Teng, Y. D.; Newton, K.; Yu, D.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Teng, Y. D.; Newton, K.; Yu, D.] Brigham & Womens Hosp, Childrens Hosp, Boston, MA 02115 USA. [Teng, Y. D.; Newton, K.; Yu, D.; Liao, W. -L.] VA Boston Healthcare Syst, Div Spinal Cord Injury Res, Boston, MA USA. [Kohler, T.; Mueller, R.] ETH, Inst Biomech, Zurich, Switzerland. [Graves, D.] Boston Univ, Sch Dent Med, Boston, MA 02215 USA. [Pham, L.; Stashenko, P.; Battaglino, R.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. RP Morse, L (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, 140 Fenway, Boston, MA 02115 USA. EM lmorse4@partners.org RI Muller, Ralph/A-1198-2008; battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Muller, Ralph/0000-0002-5811-7725; Morse, Leslie/0000-0002-7426-6341 FU NIAMS NIH HHS [L30 AR063489]; NICHD NIH HHS [K12 HD001097-08, K12 HD001097]; NIDCR NIH HHS [DE007378-18, R01 DE007378]; NINDS NIH HHS [R21 NS053935, R21 NS053935-01A1, R21NS53935] NR 46 TC 23 Z9 25 U1 0 U2 2 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2008 VL 19 IS 5 BP 645 EP 652 DI 10.1007/s00198-007-0494-x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 283GR UT WOS:000254625200006 PM 17987335 ER PT J AU Nurgalieva, Z Goodman, KJ Phillips, CV Fischbach, L de La Rosa, JM Gold, BD AF Nurgalieva, Zhannat Goodman, Karen J. Phillips, Carl V. Fischbach, Lori de la Rosa, J. Manuel Gold, Benjamin D. TI Correspondence between Helicobacter pylori antibodies and urea breath test results in a US-Mexico birth cohort SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE Helicobacter pylori infection; serology; urea breath test; methodology ID LINKED-IMMUNOSORBENT-ASSAY; FOLLOW-UP; DIAGNOSTIC-ACCURACY; STOOL SAMPLES; CHILDREN; INFECTION; ERADICATION; ACQUISITION; CHILDHOOD; SEROLOGY AB The uncertain accuracy of methods for detecting Helicobacter pylori infection in young children complicates research on this infection in early life. The aim of the present report was to describe the correspondence between positive serology and positive urea breath test (UBT) in children followed from age 0 to 24 months in the Pasitos Cohort Study, conducted along the US-Mexico border at El Paso and Juarez. Children were recruited before birth during 1998-2000 and examined at target ages of 6, 12, 18 and 24 months. H. pylori infection was detected using an enzyme immunoassay for serum immunoglobulin G antibodies and the C-13-urea breath test corrected for age-dependent variation in CO2 production. Of 472 children, 125 had one or more positive UBT results and 46 had one or more positive serology results. The prevalence of H. pylori infection at target ages of 6, 12, 18 and 24 months was 7%, 14%, 16% and 19%, respectively, by UBT and 8%, 2%, 3% and 3%, respectively, by serology. Few (< 1%) of those tested on both tests were positive on both at any age. Among UBT-positive children, 6% were concurrently seropositive and 6% became seropositive later. Because UBT positivity cut points were selected to minimise false positives, these results suggest that H. pylori infection occurred frequently in this cohort, but rarely produced detectable antibodies. For clinical or epidemiological investigations, serology should not be used as the sole method for detecting H. pylori infection in children aged 2 years or less. C1 [Nurgalieva, Zhannat; Goodman, Karen J.] Univ Texas Hlth Sci Ctr San Antonio, Sch Publ Hlth, Houston, TX USA. [Fischbach, Lori] Univ Texas Hlth Sci Ctr San Antonio, Sch Publ Hlth, Ft Worth, TX USA. [de la Rosa, J. Manuel] Texas Tech Univ, Hlth Sci Ctr, Sch Med, El Paso, TX USA. [Gold, Benjamin D.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Goodman, Karen J.] Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada. [Goodman, Karen J.] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada. RP Nurgalieva, Z (reprint author), Houston VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM zhannatn@bcm.tmc.edu RI Goodman, Karen/D-6823-2013 OI Goodman, Karen/0000-0002-3790-3217 FU NIDDK NIH HHS [DK-53708-07, R01-DK053664] NR 46 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAY PY 2008 VL 22 IS 3 BP 302 EP 312 DI 10.1111/j.1365-3016.2008.00932.x PG 11 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 289NS UT WOS:000255061800011 PM 18426526 ER PT J AU Rathmell, JP Saal, JS Saal, J AF Rathmell, James P. Saal, Joel S. Saal, Jeffrey TI Discography, IDET, percutaneous discectomy, and nucleoplasty: Complications and their prevention SO PAIN MEDICINE LA English DT Article DE complications; discography; intradiscal electrothermal therapy (IDET); nucleoplasty ID INTRADISCAL ELECTROTHERMAL THERAPY; LOW-BACK-PAIN; FOLLOW-UP; CONTROLLED-TRIAL; ANTIBIOTICS; DISCITIS AB Objective. The ability to access the intervertebral disk percutaneously using image guidance has proven to be a safe approach that allows for diagnostic and therapeutic interventions within the nucleus pulposus. Among the most common techniques currently in use are discography, intradiscal electrothermal therapy (IDET), and nucleoplasty; complications have been described but are uncommon. The objective of the current manuscript is to review the available literature regarding complications associated with these intradiscal techniques. Design. This report describes a patient with chronic low back pain associated with lumbar degenerative disc disease who is a typical candidate for diagnostic discography and treatment with intradiscal approaches. In the current manuscript, the available reports detailing complications associated with each of these techniques are reviewed, and recommendations for prevention are outlined. Conclusions. All of these techniques share the common element of introducing a cannula into the nucleus pulposus using a percutaneous approach, and direct trauma to the spinal nerve can occur. Likewise, bleeding and infection can follow the introduction, of the cannula. With any of these intradiscal techniques, discitis is an inherent risk, a delayed and insidious infection within the disk space that can be difficult to diagnose and treat. The thermal wire used to perform IDET is subject to mechanical breakage, and the thermal energy delivered during both IDET and nucleoplasty can cause direct thermal injury to neural elements when incorrectly positioned. With use of prophylactic antibiotics, sterile technique, and disciplined use of image guidance, the incidence of these complications can be minimized. C1 [Rathmell, James P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Ctr Pain Med, Boston, MA 02114 USA. [Saal, Joel S.; Saal, Jeffrey] Physiatry Med Grp, Redwood City, CA USA. RP Rathmell, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Ctr Pain Med, 15 Parkman St,WACC 333, Boston, MA 02114 USA. EM jrathmell@partners.org NR 33 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD MAY-JUN PY 2008 VL 9 SU 1 BP S73 EP S81 DI 10.1111/j.1526-4637.2008.00442.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 311VF UT WOS:000256627800009 ER PT J AU Manchikanti, L Singh, V Derby, R Helm, S Trescot, AM Staats, PS Prager, JP Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Derby, Richard Helm, Standiford, II Trescot, Andrea M. Staats, Peter S. Prager, Joshua P. Hirsch, Joshua A. TI Review of Occupational Medicine Practice Guidelines for Interventional Pain Management and Potential Implications SO PAIN PHYSICIAN LA English DT Review DE Guidelines; ACOEM; ASIPP; interventional pain management; interventional techniques; evidence-based medicine; systematic reviews; guideline development; AHCPR; AHRQ; IOM; AMA; AGREE; workers' compensation; chronic pain guidelines; low back pain guidelines ID CLINICAL-PRACTICE GUIDELINES; SMALL-AREA VARIATIONS; HEALTH-CARE; SYSTEMATIC REVIEWS; CONTROLLED-TRIALS; METHODOLOGICAL QUALITY; ENVIRONMENTAL-MEDICINE; UNITED-STATES; USERS GUIDES; RECOMMENDATIONS AB in the modern day environment, workers' compensation costs continue to be a challenge, with a need to balance costs, benefits, and quality of medical care. The cost of workers' compensation care affects all stakeholders including workers, employers, providers, regulators, legislators, and insurers. Consequently, a continued commitment to quality, accessibility to care, and cost containment will help ensure that workers are afforded accessible, high quality, and cost-effective care. In 2004, workers' compensation programs in all 50 states, the District of Columbia, and federal programs in the United States combined received an income of $87.4 billion while paying out only $56 billion in medical and cash benefits with $31.4 billion or 37% in administrative expenses and profit. Occupational diseases represented only 8% of the workers' compensation claims and 29% of the cost. The American College of Occupational and Environmental Medicine (ACOEM) has published several guidelines, though widely adopted by WCPs, these guidelines evaluate the practice of medicine of multiple specialties without adequate expertise and expert input from the concerned specialties, including interventional pain management. An assessment of the ACOEM guidelines utilizing Appraisal of Guidelines for Research and Evaluation (AGREE) criteria, the criteria developed by the American Medical Association (AMA), the Institute of Medicine (IOM), and other significantly accepted criteria, consistently showed very low scores (< 30%) in most aspects of the these guidelines. The ACOEM recommendations do not appear to have been based on a careful review of the literature, overall quality of evidence, standard of care, or expert consensus, Based on the evaluation utilizing appropriate and current evidence-based medicine (EBM) principles, the evidence ratings for diagnostic techniques of limbar discography;, cervical, thoracic, and lumbar facet joint nerve blocks and sacroiliac joint nerve blocks; therapeutic cervical and lumbar media) branch blocks and radiofrequency neurolysis; cervical interlaminar epidural steroid injections, caudal epidural steroid injections, and lumbar transforaminal epidural injections; caudal percutaneous adhesiolysis; abd spinal cord stimulation were found to be moderate with strong recommendation applying for most patients in most circumstances. The evidence ratings for intradiscal electrothermal therapy (IDET), an automated percutaneous disc decompression and also deserve further scrutiny and analysis. In conclusion, these ACOEM guidelines for interventional pain management have no applicability in modern patient care due to lack of expertise by the developing organization (ACOEM), lack of utilization of appropriate and current EBM principles, and lack of significant involvement of experts in these techniques resulting in a lack of clinical relevance. Thus, they may result in reduced medical quality of care; may severely hinder access to appropriate, medically needed and essential medical care; and finally, they may increase costs for injured workers, third party payors, and the government by transferring the injured worker into a non-productive disability system. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Derby, Richard] Spinal Diagnost & Treatment Ctr, Daly City, CA USA. [Helm, Standiford, II] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA. [Trescot, Andrea M.] Univ Florida, Gainesville, FL USA. [Staats, Peter S.] Metzger Staats Pain Management, Shrewsbury, NJ USA. [Prager, Joshua P.] Ctr Rehabil Pain Syndromes, Los Angeles, CA USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU ASIPP Board of Directors; Editorial Board of Pain Physician FX The authors wish to thank the ASIPP Board of Directors for their support; the Editorial Board of Pain Physician, for review and criticism in improving the manuscript; Tonie M. Hatton and Diane E. Neihoff, Transcriptionists, for their assistance in preparation of this manuscript; and contributors. NR 142 TC 60 Z9 60 U1 2 U2 4 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2008 VL 11 IS 3 BP 271 EP 289 PG 19 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 375GQ UT WOS:000261102500001 PM 18523500 ER PT J AU Manchikanti, L Singh, V Helm, S Trescot, AM Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Helm, Standiford, II Trescot, Andrea M. Hirsch, Joshua A. TI A Critical Appraisal of 2007 American College of Occupational and Environmental Medicine (ACOEM) Practice Guidelines for Interventional Pain Management: An Independent Review Utilizing AGREE, AMA, IOM, and Other Criteria SO PAIN PHYSICIAN LA English DT Review DE Evidence-based medicine; systematic reviews; guideline development; AHCPR; AHRQ; IOM; AMA; AGREE; workers' compensation; guidelines; ACOEM; ASIPP; interventional pain management; interventional techniques; chronic pain guidelines; low back pain guidelines ID CLINICAL-PRACTICE GUIDELINES; CONFLICT-OF-INTEREST; LOW-BACK-PAIN; SYSTEMATIC REVIEWS; METHODOLOGICAL QUALITY; USERS GUIDES; PUBLIC TRUST; RECOMMENDATIONS; STRENGTH; INDUSTRY AB Background: Today, with the growing interest of the medical community and others in practice guidelines, there is greater emphasis on formal procedures and methods for arriving at a widely scrutinized and endorsed consensus than ever before. Conflicts in terminology and technique are notable for the confusion that guidelines create and for what they reflect about differences in values experiences, and interests among different parties. While public and private development activities continue to multiply, the means for coordinating these efforts to resolve inconsistencies, fill in gaps, track applications and results, and asses, the soundness of particular guidelines continue to be limited. In this era of widespread guideline development by private organizations, the American College of Occupational and Environment Medicine (ACOEM) has developed guidelines that evaluate areas of clinical practice well beyond the scope of occupational medicine and yet fail to properly involve physicians expert in these, especially those in the field of interventional pain management. As the field of guidelines suffers from imperfect and incomplete scientific knowledge as well as imperfect and uneven means of applying that knowledge without a single or correct way to develop guidelines, ACOEM guidelines have been alleged to hinder patient care, reduce access to interventional pain management procedures, and transfer patients into a system of disability, Medicare, and Medicaid. Objective: To critically appraise occupational medicine practice guidelines for interventional pain management by an independent review utilizing the Appraisal of Guidelines for Research and Evaluation (AGREE), American Medical Association (AMA), Institute of Medicine (IOM), and other commonly utilized criteria. Methods: Revised chapters of ACOEM guidelines, low back pain and chronic pain, developed in 2007 and 2008 are evaluated, utilizing AGREE, AMA, IOM instruments, and Shaneyfelt et al's criteria, were independently reviewed by 4 appraisers. Results: Critical appraisal utilizing the AGREE instrument found that both chapters scored less than 10% in 3 of the 6 contains, less than 20% in one domain, over 30% in one domain, and over 70% in one domain. Global assessment also scored below 30% with a recommendation from AGREE, "not recommended or suitable for use in practice." Based on AMA key attributes, both chapters of ACOEM guidelines met only one of the 6 key attributes, only 3 of the 8 attributes were met by IOM criteria, and based on the criteria described by Shaneyfelt et al, overall only 28% of criteria were met. Conclusion: Both the low back pain and chronic pain chapters of the ACOEM guidelines may not be ideal for clinical use based on the assessment by the AGREE instrument, AMA attributes, and criteria established by Shaneyfelt et al. They also scored low on IOM criteria (37.5%). These guidelines may not be applicable for clinical use. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Helm, Standiford, II] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA. [Trescot, Andrea M.] Univ Florida, Pain Program, Gainesville, FL USA. [Trescot, Andrea M.] Malcolm Randall VA Med Ctr, Gainesville, FL USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU ASIPP Board of Directors; Editorial Board of Pain Physician FX The authors wish to thank David S. Kloth, MID, Board Member and Past President of the American Society of Interventional Pain Physicians (ASIPP) and Eric Hauth, MA, MS, Executive Director of Neuromodulation Therapy Access Coalition (NTAC) for their constructive criticisms, reviews, support, and suggestions in preparation of this manuscript; ASIPP Board of Directors for their support; the Editorial Board of Pain Physician, for review and criticism in improving the manuscript; and Vidyasagar Pampati, MSc, Statistician, and Tonie M. Hatton and Diane E. Neihoff, Transcriptionists, for their assistance in preparation of this manuscript. NR 95 TC 39 Z9 39 U1 0 U2 5 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAY-JUN PY 2008 VL 11 IS 3 BP 291 EP 310 PG 20 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 375GQ UT WOS:000261102500002 PM 18523501 ER PT J AU Sanlioglu, AD Dirice, E Elpek, O Korcum, AF Balci, MK Omer, A Griffith, TS Sanlioglu, S AF Sanlioglu, Ahter Dilsad Dirice, Ercument Elpek, Ozlem Korcum, Aylin Fidan Balci, Mustafa Kemal Omer, Abdulkadir Griffith, Thomas S. Sanlioglu, Salih TI High levels of endogenous tumor necrosis factor-related apoptosis-inducing ligand expression correlate with increased cell death in human pancreas SO PANCREAS LA English DT Article DE TRAIL; death-decoy receptors; pancreas; Langerhans islets ID PROSTATE CARCINOMA-CELLS; DIABETES-MELLITUS; FACTOR-ALPHA; FAS LIGAND; BETA-CELLS; NOD MICE; TRAIL; TYPE-1; DESTRUCTION; RECEPTORS AB Objectives: Type 1 diabetes (T1D) has been characterized by the T cellYmediated destruction of pancreatic beta cells. Although various members of the tumor necrosis factor (TNF) family, such as Fas ligand or TNF, have recently been implicated in the development of T1D, the lack of TNF-related apoptosis-inducing ligand (TRAIL) expression or function facilitates the onset of T1D. Thus, the goal of the present study was to investigate the expression profiles of TRAIL and its receptors in human pancreas. Methods: Pancreata of 31 patients were analyzed by immunohistochemistry using antibodies developed against TRAIL and its receptors. Apoptosis was confirmed by Annexin V-fluorescein isothiocyanate binding and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling assays. Results: Acinar cells displayed high levels of TRAIL and death receptor 4, but only low levels of death receptor 5. In contrast, only TRAIL and TRAIL decoy receptors (DcR1, DcR2) were detected in ductal cells. Similarly, Langerhans islets expressed only TRAIL and TRAIL decoy receptor. High levels of TRAIL expression in pancreas correlated with increased number of apoptotic cells. Conclusions: Although the expression of TRAIL decoy receptors might be necessary for defense from TRAIL-induced apoptosis, high levels of TRAIL may provide protection for Langerhans islets from the immunological attack of cytotoxic T cells. C1 [Sanlioglu, Ahter Dilsad; Dirice, Ercument; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Human Gene Therapy Unit, TR-07070 Antalya, Turkey. [Sanlioglu, Ahter Dilsad; Dirice, Ercument; Sanlioglu, Salih] Akdeniz Univ, Fac Med, Dept Med Biol & Genet, TR-07070 Antalya, Turkey. [Elpek, Ozlem] Akdeniz Univ, Fac Med, Dept Pathol, TR-07070 Antalya, Turkey. [Korcum, Aylin Fidan] Akdeniz Univ, Fac Med, Dept Radiat Oncol, TR-07070 Antalya, Turkey. [Balci, Mustafa Kemal] Akdeniz Univ, Fac Med, Div Endocrinol & Metab, TR-07070 Antalya, Turkey. [Omer, Abdulkadir] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. [Griffith, Thomas S.] Univ Iowa, Coll Med, Dept Urol, Iowa City, IA 52242 USA. RP Sanlioglu, S (reprint author), Akdeniz Univ, Fac Med, Human Gene Therapy Unit, B Block,1st Floor,Campus, TR-07070 Antalya, Turkey. EM sanlioglu@akdeniz.edu.tr RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Ahter/C-6504-2016; Sanlioglu, Salih/F-9305-2016; Dirice, Ercument/B-2825-2017 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; Sanlioglu, Ahter/0000-0003-4504-0375; NR 31 TC 18 Z9 19 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 2008 VL 36 IS 4 BP 385 EP 393 DI 10.1097/MPA.0b013e318158a4e5 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 294YT UT WOS:000255442900009 PM 18437085 ER PT J AU Sutton, R Petersen, OH Pandol, SJ AF Sutton, Robert Petersen, Ole H. Pandol, Stephen J. TI Pancreatitis and calcium signalling - Report of an international workshop SO PANCREAS LA English DT Editorial Material ID KAPPA-B ACTIVATION; PROTEIN-KINASE-C; MITOCHONDRIAL PERMEABILITY TRANSITION; INOSITOL TRISPHOSPHATE RECEPTORS; ADENINE-NUCLEOTIDE TRANSLOCASE; MEMBRANE NA+/CA2+ EXCHANGER; HUMAN CATIONIC TRYPSINOGEN; LEUKOTRIENE C-4 SECRETION; NECROSIS-FACTOR-ALPHA; ACINAR-CELLS AB Pancreatitis and Calcium Signalling was an international research workshop organized by the authors and held at the Liverpool Medical Institution, Liverpool, United Kingdom, from Sunday 12th to Tuesday 14th November 2006. The overall goal of the workshop was to review progress and explore new opportunities for understanding the mechanisms of acute pancreatitis with an emphasis on the role of pathological calcium signaling. The participants included those with significant interest and expertise in pancreatitis research and others who are in fields outside gastroenterology but with significant expertise in areas of cell biology relevant to pancreatitis. The workshop was designed to enhance interchange of ideas and collaborations, to engage and encourage younger researchers in the field, and promote biomedical research through the participating and supporting organizations and societies. The workshop was divided into 8 topic-oriented sessions. The sessions were: (1) Physiology and pathophysiology of calcium signaling; (2) Interacting signaling mechanisms; (3) Premature digestive enzyme activation; (4) Physiology Society Lecture: Aberrant Ca2+ signaling, bicarbonate secretion, and pancreatitis; (5) NF kappa B, cytokines, and immune mechanisms; (6) Mitochondrial injury; (7) Cell death pathways; and (8) Overview of areas for future research. In each session, speakers presented work appropriate to the topic followed by discussion of the material presented by the group. The publication of these proceedings is intended to provide a platform for enhancing research and therapeutic development for acute pancreatitis. C1 [Sutton, Robert] Univ Liverpool, Div Surg & Oncol, MRC Grp, Liverpool L69 3BX, Merseyside, England. [Petersen, Ole H.] Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. [Pandol, Stephen J.] Univ Calif Los Angeles, USC, Res Ctr Alcohol Liver & Pancreat Dis, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Sutton, R (reprint author), Univ Liverpool, Div Surg & Oncol, Royal Liverpool Univ Hosp, Daulby St, Liverpool L69 3GA, Merseyside, England. EM r.sutton@liverpool.ac.uk RI Sutton, Robert/I-3587-2016 OI Sutton, Robert/0000-0001-6600-562X NR 110 TC 14 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 2008 VL 36 IS 4 BP E1 EP E14 DI 10.1097/MPA.0b013e3181675010 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 294YT UT WOS:000255442900018 PM 18437073 ER PT J AU Kanwar, VS Heath, J Krasner, CN Pearce, JM AF Kanwar, Vikramjit S. Heath, Jessica Krasner, Carolyn N. Pearce, Jennifer M. TI Advanced small cell carcinoma of the ovary in a seventeen-year-old female, successfully treated with surgery and multi-agent chemotherapy SO PEDIATRIC BLOOD & CANCER LA English DT Article DE rare tumors; chemotherapy; pediatric oncology; ovarian cancer ID HYPERCALCEMIC TYPE; SURVIVAL; CANCER; KIT AB Advanced small cell carcinoma of the ovary (FIGO stage III or IV) is a rare and usually lethal tumor seen in adolescents and young women. In pediatric patients with advanced disease, there have been only two case reports of successful therapy, we report a third patient, diagnosed at 17 years of age, with an abdominal mass and metastatic disease to regional and distant lymph nodes, who was successfully treated with surgery and intensive multi-agent chemotherapy. Imatinib, thalidomide, and celecoxib were also administered for up to 24 months following initial chemotherapy. She remains in remission 3 years from diagnosis. C1 [Kanwar, Vikramjit S.; Heath, Jessica; Pearce, Jennifer M.] Albany Med Ctr, Dept Pediat, Albany, NY 12208 USA. [Krasner, Carolyn N.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Kanwar, VS (reprint author), Albany Med Ctr, Dept Pediat, 43 New Scotland Ave MC-24, Albany, NY 12208 USA. EM kanwarv@mail.amc.edu NR 14 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2008 VL 50 IS 5 BP 1060 EP 1062 DI 10.1002/pbc21333 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 283NL UT WOS:000254642900025 PM 17914739 ER PT J AU Albritton, KH Eden, T AF Albritton, Karen H. Eden, Tim TI Access to care SO PEDIATRIC BLOOD & CANCER LA English DT Article; Proceedings Paper CT Symposium on Adolescent and Young Adult Oncology CY 2006 CL Geneva, SWITZERLAND SP SIOP DE access; cancer care ID ACUTE-LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD-CANCER SURVEILLANCE; PEDIATRIC SOLID TUMORS; YOUNG-ADULTS; RETROSPECTIVE ANALYSIS; SINGLE INSTITUTION; SYMPTOM INTERVAL; CONTROL PROGRAM; BREAST-CANCER; DIAGNOSIS AB Rapid diagnosis, timely initiation of optimal treatment and good supportive care should be the gold standard for all patients who develop cancer, irrespective of age and where they live. This article reviews the evidence that teenagers/adolescents and young adults may be disadvantaged with regard to access to care. Delays in diagnosis and the reasons for them (patient and professional), low enrolment into clinical trials, suboptimal treatment strategies and place of care are addressed. We must access the voice of the young, address their needs, and involve them more in decisions concerning their own health. Progress is being made slowly in several countries and international collaboration linking patients, health care professionals, governmental and non-govern mental agencies is essential. Such international collaboration and focus, with specific research goals are suggested in order to make variation in access to optimal care become a thing of the past. C1 [Albritton, Karen H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Eden, Tim] Univ Manchester, Manchester, Lancs, England. [Eden, Tim] Christie Hosp NHS Fdn Trust, Manchester, Lancs, England. RP Albritton, KH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM karen_albritton@dfci.harvard.edu NR 44 TC 15 Z9 16 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2008 VL 50 IS 5 SU S BP 1094 EP 1098 DI 10.1002/pbc.21461 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 286CE UT WOS:000254822200003 PM 18360836 ER PT J AU Hoganson, DM Pryor, HI Vacanti, JP AF Hoganson, David M. Pryor, Howard I., II Vacanti, Joseph P. TI Tissue engineering and organ structure: A vascularized approach to liver and lung SO PEDIATRIC RESEARCH LA English DT Review ID MESENCHYMAL STEM-CELLS; HUMAN ADIPOSE-TISSUE; HEPATOCYTE-LIKE CELLS; HEPATIC OVAL CELLS; BONE-MARROW; IN-VITRO; BIOARTIFICIAL LIVER; RAT HEPATOCYTES; CONTROLLED-TRIAL; STROMAL CELLS AB Over the past two decades, great strides have been made in the field of tissue engineering. Many of the initial attempts to develop an engineered tissue construct were based on the concept of seeding cells onto an avascular scaffold. Using advanced manufacturing technologies, the creation of a preformed vascular scaffold has become a reality. This article discusses some of the issues surrounding the development of such a vascular scaffold. We then examine of the challenges associated with applying this scaffold technology to two vital organ constructs: liver and lung. C1 [Hoganson, David M.; Pryor, Howard I., II; Vacanti, Joseph P.] Harvard Univ, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WRN 11-1151, Boston, MA 02114 USA. EM jvacanti@partners.org FU NIDDK NIH HHS [T32DK07754-09, 1 F32DK076349-01] NR 83 TC 41 Z9 42 U1 2 U2 20 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2008 VL 63 IS 5 BP 520 EP 526 DI 10.1203/01.pdr.0000305879.38476.0c PG 7 WC Pediatrics SC Pediatrics GA 293CH UT WOS:000255311900011 PM 18427297 ER PT J AU Hsu, HW Zytkovicz, TH Comeau, AM Strauss, AW Marsden, D Shih, VE Grady, GF Eaton, RB AF Hsu, Ho-Wen Zytkovicz, Thomas H. Comeau, Anne Marie Strauss, Arnold W. Marsden, Deborah Shih, Vivian E. Grady, George F. Eaton, Roger B. TI Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening SO PEDIATRICS LA English DT Article DE newborn screening; metabolic disorders; fatty acid oxidation defects ID TANDEM MASS-SPECTROMETRY; MCAD DEFICIENCY; BIOCHEMICAL PHENOTYPES; PREVALENT MUTATION; BLOOD SPOTS; IDENTIFICATION; DISORDERS; DIAGNOSIS; ACID; METABOLISM AB OBJECTIVE. Our goal was to describe the clinical spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by routine newborn screening and assess factors associated with elevations of octanoylcarnitine in newborns and characteristics associated with adverse clinical consequences of medium-chain acyl-CoA dehydrogenase deficiency. METHODS. The first 47 medium-chain acyl-CoA dehydrogenase deficiency cases detected by the New England Newborn Screening Program were classified according to initial and follow-up octanoylcarnitine values, octanoylcarnitine-decanoylcarnitine ratios, medium-chain acyl-CoA dehydrogenase genotype, follow-up biochemical parameters, and feeding by breast milk or formula. RESULTS. All 20 patients who were homozygous for 985A -> G had high initial octanoylcarnitine values (7.0-36.8 mu M) and octanoylcarnitine-decanoylcarnitine ratios (7.0-14.5), whereas the 27 patients with 0 to 1 copy of 985A -> G exhibited a wide range of octanoylcarnitine values (0.5-28.6 mu M) and octanoylcarnitine-decanoylcarnitine ratios (0.8-12.7). Initial newborn octanoylcarnitine values decreased by days 5 to 8, but the octanoylcarnitine-decanoylcarnitine ratio generally remained stable. Among 985A -> G homozygotes, breastfed newborns had higher initial octanoylcarnitine values than newborns who received formula. Adverse events occurred in 5 children, 4 985A -> G homozygotes and 1 compound heterozygote with a very high initial octanoylcarnitine: 2 survived severe neonatal hypoglycemia, 1 survived a severe hypoglycemic episode at 15 months of age, and 2 died as a result of medium-chain acyl-CoA dehydrogenase deficiency at ages 11 and 33 months. CONCLUSION. Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency has detected cases with a wide range of genotypes and biochemical abnormalities. Although most children do well, adverse outcomes have not been entirely avoided. Assessment of potential risk and determination of appropriate treatment remain a challenge. C1 [Hsu, Ho-Wen; Zytkovicz, Thomas H.; Comeau, Anne Marie; Grady, George F.; Eaton, Roger B.] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Dept Pediat, Boston, MA 02130 USA. [Strauss, Arnold W.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Marsden, Deborah] Childrens Hosp Boston, Dept Pediat, Boston, MA USA. [Shih, Vivian E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Hsu, HW (reprint author), Univ Massachusetts, Sch Med, New England Newborn Screening Program, Dept Pediat, 305 S St,Jamaica Pl, Boston, MA 02130 USA. EM ho-wen.hsu@umassmed.edu FU PHS HHS [1H46MC00198, U22MC03959] NR 26 TC 20 Z9 20 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2008 VL 121 IS 5 BP E1108 EP E1114 DI 10.1542/peds.2007-1993 PG 7 WC Pediatrics SC Pediatrics GA 295VL UT WOS:000255501900052 PM 18450854 ER PT J AU Levy, JA Noble, VE AF Levy, Jason A. Noble, Vicki E. TI Bedside ultrasound in pediatric emergency medicine SO PEDIATRICS LA English DT Review DE emergency ultrasound; bedside ultrasound; ultrasound; sonography ID BLUNT ABDOMINAL-TRAUMA; INTERNAL JUGULAR-VEIN; INFERIOR VENA-CAVA; CENTRAL VENOUS CANNULATION; TISSUE FOREIGN-BODIES; DIFFICULT INTRAVENOUS ACCESS; SURGEON-DIRECTED ULTRASOUND; ENDOTRACHEAL-TUBE PLACEMENT; CONTROLLED CLINICAL-TRIAL; LANDMARK-GUIDED TECHNIQUE AB Bedside emergency ultrasound has been used by emergency physicians for > 20 years for a variety of conditions. In adult centers, emergency ultrasound is routinely used in the management of victims of blunt abdominal trauma, in patients with abdominal aortic aneurysm and biliary disease, and in women with first-trimester pregnancy complications. Although its use has grown dramatically in the last decade in adult emergency departments, only recently has this tool been embraced by pediatric emergency physicians. As the modality advances and becomes more available, it will be important for primary care pediatricians to understand its uses and limitations and to ensure that pediatric emergency physicians have access to the proper training, equipment, and experience. This article is meant to review the current literature relating to emergency ultrasound in pediatric emergency medicine, as well as to describe potential pediatric applications. C1 [Levy, Jason A.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Levy, Jason A.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Noble, Vicki E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Emergency Med, Boston, MA USA. RP Levy, JA (reprint author), Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM jason.levy@childrens.harvard.edu NR 138 TC 30 Z9 32 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2008 VL 121 IS 5 BP E1404 EP E1412 DI 10.1542/peds.2007-1816 PG 9 WC Pediatrics SC Pediatrics GA 295VL UT WOS:000255501900090 PM 18450883 ER PT J AU Streeck, H Brumme, ZL Anastario, M Cohen, KW Jolin, JS Meier, A Brumme, CJ Rosenberg, ES Alter, G Allen, TM Walker, BD Altfeld, M AF Streeck, Hendrik Brumme, Zabrina L. Anastario, Michael Cohen, Kristin W. Jolin, Jonathan S. Meier, Angela Brumme, Chanson J. Rosenberg, Eric S. Alter, Galit Allen, Todd M. Walker, Bruce D. Altfeld, Marcus TI Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8(+) T cells SO PLOS MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; ACUTE HIV-1 INFECTION; EXPRESS HIGH-LEVELS; DISEASE PROGRESSION; LYMPHOCYTE ESCAPE; EFFECTOR; EXHAUSTION; RESPONSES; NONPROGRESSORS AB Background Virus-specific CD8(+) T lymphocytes play a key role in the initial reduction of peak viremia during acute viral infections, but display signs of increasing dysfunction and exhaustion under conditions of chronic antigen persistence. It has been suggested that virus-specific CD8(+) T cells with a 'polyfunctional'' profile, defined by the capacity to secrete multiple cytokines or chemokines, are most competent in controlling viral replication in chronic HIV-1 infection. We used HIV-1 infection as a model of chronic persistent viral infection to investigate the process of exhaustion and dysfunction of virus-specific CD8(+) T cell responses on the single-epitope level over time, starting in primary HIV-1 infection. Methods and Findings We longitudinally analyzed the polyfunctional epitope-specific CD8(+) T cell responses of 18 patients during primary HIV-1 infection before and after therapy initiation or sequence variation in the targeted epitope. Epitope-specific CD8(+) T cells responded with multiple effector functions to antigenic stimulation during primary HIV-1 infection, but lost their polyfunctional capacity in response to antigen and up-regulated programmed death 1 (PD-1) expression with persistent viremic infection. This exhausted phenotype significantly decreased upon removal of stimulation by antigen, either in response to antiretroviral therapy or by reduction of epitope-specific antigen load in the presence of ongoing viral replication, as a consequence of in vivo selection of cytotoxic T lymphocyte escape mutations in the respective epitopes. Monofunctionality increased in CD8(+) T cell responses directed against conserved epitopes from 49% (95% confidence interval 27%-72%) to 76% (56%-95%) (standard deviation [SD] of the effect size 0.71), while monofunctionality remained stable or slightly decreased for responses directed against escaped epitopes from 61% (47%-75%) to 56% (42%-70%) (SD of the effect size 0.18) (p < 0.05). Conclusion These data suggest that persistence of antigen can be the cause, rather than the consequence, of the functional impairment of virus-specific T cell responses observed during chronic HIV-1 infection, and underscore the importance of evaluating autologous viral sequences in studies aimed at investigating the relationship between virus-specific immunity and associated pathogenesis. C1 [Streeck, Hendrik; Brumme, Zabrina L.; Cohen, Kristin W.; Jolin, Jonathan S.; Meier, Angela; Brumme, Chanson J.; Rosenberg, Eric S.; Alter, Galit; Allen, Todd M.; Walker, Bruce D.; Altfeld, Marcus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit,Partners AIDS Res Ctr, Boston, MA 02115 USA. [Streeck, Hendrik; Brumme, Zabrina L.; Cohen, Kristin W.; Jolin, Jonathan S.; Meier, Angela; Brumme, Chanson J.; Rosenberg, Eric S.; Alter, Galit; Allen, Todd M.; Walker, Bruce D.; Altfeld, Marcus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit,Partners AIDS Res Ctr,Div AIDS, Boston, MA 02115 USA. [Anastario, Michael] Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Ctr Disaster & Humanitarian Assistance Med, Bethesda, MD 20814 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Altfeld, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit,Partners AIDS Res Ctr, Boston, MA 02115 USA. EM maltfeld@partners.org RI Allen, Todd/F-5473-2011; OI Brumme, Chanson/0000-0003-2722-5288 FU NIAID NIH HHS [R01 AI050429, R01 AI50429, U01 AI052403] NR 45 TC 144 Z9 146 U1 1 U2 11 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 MAY PY 2008 VL 5 IS 5 BP 790 EP 804 AR e100 DI 10.1371/journal.pmed.0050100 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 315AL UT WOS:000256850200020 PM 18462013 ER PT J AU Pienta, KJ Abate-Shen, C Agus, DB Attar, RM Chung, LWK Greenberg, NM Hahn, WC Isaacs, JT Navone, NM Peehl, DM Simons, JW Solit, DB Soule, HR VanDyke, TA Weber, MJ Wu, L Vessella, RL AF Pienta, Kenneth J. Abate-Shen, Cory Agus, David B. Attar, Ricardo M. Chung, Leland W. K. Greenberg, Norman M. Hahn, William C. Isaacs, John T. Navone, Nora M. Peehl, Donna M. Simons, Jonathon W. Solit, David B. Soule, Howard R. VanDyke, Terry A. Weber, Michael J. Wu, Lily Vessella, Robert L. TI The current state of preclinical prostate cancer animal models SO PROSTATE LA English DT Article DE mouse; genetically engineered; cell lines ID GENETICALLY-ENGINEERED MICE; CARCINOMA-CELL LINES; TRANSGENIC MOUSE; PROGRESSION; MECHANISMS; EXPRESSION; FUSION; NKX3.1; GENES; ADENOCARCINOMAS AB Prostate cancer continues to be a major cause of morbidity and mortality in men around the world. The field of prostate cancer research continues to be hindered by the lack of relevant preclinical models to study tumorigenesis and to further development of effective prevention and therapeutic strategies. The Prostate Cancer Foundation held a Prostate Cancer Models Working Group (PCMWG) Summit on August 6th and 7th, 2007 to address these issues. The PCMWG reviewed the state of prostate cancer preclinical models and identified the current limitations of cell line, xenograft and genetically engineered mouse models that have hampered the transition of scientific findings from these models to human clinical trials. In addition the PCMWG identified administrative issues that inhibit the exchange of models and impede greater interactions between academic centers and these centers with industry. The PCMWG identified potential solutions for discovery bottlenecks that include: (1) insufficient number of models with insufficient molecular and biologic diversity to reflect human cancer, (2) a lack of understanding of the molecular events that define tumorigenesis, (3) a lack of tools for studying tumor-host interactions, (4) difficulty in accessing model systems across institutions, and (5) addressing why preclinical studies appear not to be predictive of human clinical trials. It should be possible to apply the knowledge gained molecular and epigenetic studies to develop new cell lines and models that mimic progressive and fatal prostate cancer and ultimately improve interventions. C1 [Pienta, Kenneth J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Pienta, Kenneth J.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Abate-Shen, Cory] Columbia Univ, Herbert Irving Canc Ctr, New York, NY USA. [Agus, David B.] Louis Warschaw Prostate Canc Ctr, Los Angeles, CA USA. [Attar, Ricardo M.] Bristol Myers Squibb Co, Princeton, NJ 08540 USA. [Chung, Leland W. K.] Emory Univ, Dept Urol, Atlanta, GA 30322 USA. [Greenberg, Norman M.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Hahn, William C.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Isaacs, John T.] Johns Hopkins Med Sch, Dept Urol, Baltimore, MD USA. [Isaacs, John T.] Johns Hopkins Med Sch, Dept Oncol, Baltimore, MD USA. [Navone, Nora M.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Oncol, Houston, TX 77030 USA. [Peehl, Donna M.] Stanford Univ, Dept Urol, Stanford, CA 94305 USA. [Simons, Jonathon W.; Soule, Howard R.] Prostate Canc Fdn, Santa Monica, CA USA. [Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Genitourinary Oncol, New York, NY 10021 USA. [VanDyke, Terry A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Weber, Michael J.] Univ Virginia, Ctr Canc, Charlottesville, VA 22908 USA. [Weber, Michael J.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. [Wu, Lily] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. [Vessella, Robert L.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. [Vessella, Robert L.] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. RP Pienta, KJ (reprint author), 1500 E Med Ctr Dr,7308 CCC, Ann Arbor, MI 48109 USA. EM kpienta@umich.edu RI Abate-Shen, Cory/O-2520-2014; Pienta, Kenneth/E-7679-2015 OI Abate-Shen, Cory/0000-0002-5021-0570; Pienta, Kenneth/0000-0002-4138-2186 FU NCI NIH HHS [U01 CA084296, 2P50 CA69568, P01 CA093900, P01 CA093900-01A2, P01 CA098912, P01 CA098912-01A1, P01 CA104106, P01 CA104106-05, P01CA093900, P01CA098912, P50 CA069568, P50 CA069568-05, R01 CA101904, R01 CA101904-01, R01 CA105402, R01 CA105402-01, U01 CA084294, U01 CA084296-01, U01 CA84296, U19 CA113317, U19 CA113317-01] NR 43 TC 76 Z9 78 U1 0 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 1 PY 2008 VL 68 IS 6 BP 629 EP 639 DI 10.1002/pros.20726 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 293DI UT WOS:000255314800006 PM 18213636 ER PT J AU Kilbourne, AM Lasky, E Pincus, HA Good, CB Cooley, S Basavaraju, A Greenwald, D Fine, MJ Bauer, MS AF Kilbourne, Amy M. Lasky, Elaine Pincus, Harold Alan Good, C. Bernie Cooley, Susan Basavaraju, Anu Greenwald, Devra Fine, Michael J. Bauer, Mark S. TI The continuous improvement for veterans in care: Mood disorders (CIVIC-MD) study, a VA-academic partnership SO PSYCHIATRIC SERVICES LA English DT Editorial Material AB The Department of Veterans Affairs (VA) provides an ideal opportunity to conduct mental health services research among vulnerable populations, given its extensive data sources, disproportionate number of vulnerable patients (older, often with comorbidities), and quality improvement mission. Although VA facilities are often affiliated with universities, successful VA-academic research partnerships are sometimes elusive. The Continuous Improvement for Veterans in Care: Mood Disorders (CIVIC-MD) study was a partnership with a VA facility that had not been engaged in mood disorders research. This column describes how the partnership formed, key elements of its success, and challenges and opportunities to inform future research partnerships. C1 [Kilbourne, Amy M.] Vet Affairs Natl Serious Mental Illness Treatment, VA SMITREC, Ann Arbor, MI USA. [Kilbourne, Amy M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Lasky, Elaine; Good, C. Bernie; Cooley, Susan; Basavaraju, Anu; Greenwald, Devra; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Pincus, Harold Alan] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Boston, MA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Harvard S Shore Psychiat Residency Training Progr, Boston, MA USA. RP Kilbourne, AM (reprint author), VA Ann Arbor SMITREC 11H, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu NR 8 TC 9 Z9 9 U1 3 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2008 VL 59 IS 5 BP 483 EP 485 DI 10.1176/appi.ps.59.5.483 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 296AQ UT WOS:000255516300004 PM 18451002 ER PT J AU Simon, NM Connor, KM LeBeau, RT Hoge, EA Worthington, JJ Zhang, W Davidson, JRT Pollack, MH AF Simon, Naomi M. Connor, Kathryn M. LeBeau, Richard T. Hoge, Elizabeth A. Worthington, John J., III Zhang, Wei Davidson, Jonathan R. T. Pollack, Mark H. TI Quetiapine augmentation of paroxetine CR for the treatment of refractory generalized anxiety disorder: preliminary findings SO PSYCHOPHARMACOLOGY LA English DT Article DE GAD; refractory; paroxetine; quetiapine; augmentation; anxiety; pharmacotherapy; treatment ID CONTROLLED-RELEASE PAROXETINE; LONG-TERM TREATMENT; OPEN-LABEL TRIAL; QUALITY-OF-LIFE; PHARMACOLOGICAL-TREATMENT; SURVEY REPLICATION; DOUBLE-BLIND; PLACEBO; EFFICACY; TOLERABILITY AB Rationale More data are needed to guide "next step" strategies for patients with generalized anxiety disorder (GAD) remaining symptomatic despite initial pharmacotherapy. Objective This study prospectively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy. Materials and methods Adult outpatients with GAD were recruited from 2004 to 2007 at two academic centers. Phase 1 consisted of 10 weeks of open-label paroxetine CR flexibly dosed to a maximum of 62.5 mg/day. Those remaining symptomatic (Hamilton Anxiety Scale [HAM-A] >= 7) at week 10 were randomized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day. Results For participants receiving paroxetine CR (n = 50), there was a significant reduction in HAM-A scores (baseline mean +/- SD = 22.4 +/- 4.2 to endpoint mean +/- SD = 11.2 +/- 6.9; paired t = 12.1, df = 49, t < 0.0001) with 40% (n = 20) achieving remission. Counter to our hypothesis, we did not find significant benefit for quetiapine augmentation of continued paroxetine CR (HAM-A reduction mean +/- SD = 2.6 +/- 5.8 points quetiapine, 0.3 +/- 5.5 points placebo; t = 0.98, df = 20, p = n.s.) in the randomized sample (n = 22) with relatively minimal additional improvement overall in phase 2. Conclusions Although conclusions are considered preliminary based on the relatively small sample size, our data do not support the addition of quetiapine to continued paroxetine CR for individuals with GAD who remain symptomatic after 10 weeks of prospective antidepressant pharmacotherapy and suggest that further research examining strategies for GAD refractory to antidepressants is needed. C1 [Simon, Naomi M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Simon, Naomi M.; LeBeau, Richard T.; Hoge, Elizabeth A.; Worthington, John J., III; Pollack, Mark H.] Harvard Univ, Sch Med, Boston, MA USA. [Connor, Kathryn M.; Zhang, Wei; Davidson, Jonathan R. T.] Duke Univ, Durham, NC USA. [Connor, Kathryn M.] Merck & Co Inc, Merck Res Labs, Whitehouse Stn, NJ USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA. EM nsimon@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 NR 41 TC 43 Z9 46 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2008 VL 197 IS 4 BP 675 EP 681 DI 10.1007/s00213-008-1087-x PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 285BK UT WOS:000254752100014 PM 18246327 ER PT J AU Pirl, WF Temel, JS Billings, A Dahlin, C Jackson, V Prigerson, HG Greer, J Lynch, TJ AF Pirl, William F. Temel, Jennifer S. Billings, Andrew Dahlin, Constance Jackson, Vicki Prigerson, Holly G. Greer, Joseph Lynch, Thomas J. TI Depression after diagnosis of advanced non-small cell lung cancer and survival: A pilot study SO PSYCHOSOMATICS LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Academy-of-Psychosomatic-Medicine CY NOV 15-19, 2006 CL Tucson, AZ SP Acad Psychosomat Med ID MORTALITY; SYMPTOMS; PREVALENCE; DISORDER; ANXIETY AB Background: Major depressive disorder is estimated to occur in 10%-25% of people with cancer and it has been inconsistently linked to increased mortality. Objective: This pilot study investigates the association of depression and survival in advanced non-small cell lung cancer (NSCLC) patients. Method: Forty-three recently-diagnosed advanced NSCLC patients completed the Hospital Anxiety and Depression Scale and were followed prospectively. Results: Patients with depression had poorer survival. Median survival was four times shorter than those without depression. Controlling for baseline performance status, depression predicted 6-month mortality, but was not significant for overall survival. Conclusion: Although depression after advanced-NSCLC diagnosis was associated with poorer survival at 6 months, this association was not present for overall survival; however, further research with larger samples should be pursued. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM wpirl@partners.org FU NCI NIH HHS [K23 CA115908] NR 29 TC 33 Z9 34 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2008 VL 49 IS 3 BP 218 EP 224 DI 10.1176/appi.psy.49.3.218 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 297DN UT WOS:000255597400006 PM 18448776 ER PT J AU Caplan, JP AF Caplan, Jason P. TI Too much too soon? Refeeding syndrome as an iatrogenic cause of delirium SO PSYCHOSOMATICS LA English DT Article ID INTENSIVE-CARE-UNIT; HYPOPHOSPHATEMIA; PATIENT AB Background: Delirium is a significant and costly complication of medical hospitalization, and it has been shown to be a significant predictor of morbidity and mortality. It is often noted as a symptom in reported cases of refeeding syndrome, which is a potentially fatal complication in the treatment of patients suffering from malnutrition. Objective: A case of delirium due to refeeding syndrome in a 61-year-old man is presented to help clinicians recognize this entity. The pathophysiology of refeeding syndrome and its possible role as an as-yet poorly-identified iatrogenic cause of delirium are discussed. Method: A diagnosis of delirium due to refeeding syndrome was made, and a nutrition consult was requested. Per nutrition recommendations, the patient was placed on a restricted calorie regimen, with aggressive supplementation of magnesium and phosphate. Results: With his new dietary regimen, his mental status gradually improved, with complete resolution of his delirium by the 8th hospital day. He suffered no further episodes of confusion or disorientation. Conclusion: The relationship between refeeding syndrome and delirium may be of particular significance in the elderly, since malnutrition, medical hospitalization, and delirium are prevalent phenomena in this population. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Caplan, JP (reprint author), Massachusetts Gen Hosp, Warren 605,55 Fruit St, Boston, MA 02114 USA. EM jpcaplan@gmail.com NR 15 TC 6 Z9 6 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2008 VL 49 IS 3 BP 249 EP 251 DI 10.1176/appi.psy.49.3.249 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 297DN UT WOS:000255597400011 PM 18448781 ER PT J AU Stevens, JR Freudenreich, O Stern, TA AF Stevens, Jonathan R. Freudenreich, Oliver Stern, Theodore A. TI Elevated clozapine serum level after treatment with amiodarone SO PSYCHOSOMATICS LA English DT Article ID DRUG-DRUG INTERACTIONS; TOXICITY; THERAPY C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Stevens, JR (reprint author), 15 Parkman St,MGH,WACC 812, Boston, MA 02114 USA. EM jrstevens@partners.org NR 14 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2008 VL 49 IS 3 BP 255 EP 257 DI 10.1176/appi.psy.49.3.255 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 297DN UT WOS:000255597400013 PM 18448783 ER PT J AU Berg, C Raminani, S Greer, J Harwood, M Safren, S AF Berg, Carla Raminani, Sudha Greer, Joseph Harwood, Meaghan Safren, Steven TI Participants' perspectives on cognitive-behavioral therapy for adherence and depression in HIV SO PSYCHOTHERAPY RESEARCH LA English DT Article DE cognitive behavior therapy; depression; brief psychotherapy; qualitative research methods ID MEDICATION ADHERENCE; INFECTION; DISEASE; PREVALENCE; PREDICTORS; DISORDERS; OUTCOMES; ANXIETY; TRIAL; CARE AB As part of the process of developing cognitive-behavioral therapy (CBT) for medical adherence and depression (Safren, Gonzalez, & Soroudi, 2007), the authors conducted exit interviews among 14 HIV-infected patients who received the intervention, and transcribed, coded, and analyzed these data. The authors concluded that CBT was structured yet flexible, developed self-awareness emphasized social support, and involved therapist empathy and supportiveness. Limitations included the discomfort of discussing personal information and the impact of feeling ill on attendance and homework completion. Suggestions included more sessions, more flexibility in scheduling appointments, and more realistic and clear expectations regarding homework. These results provide insights about strengths and limitations of this psychotherapy with medically ill patients and may help to maximize intervention effectiveness and client acceptability. C1 [Raminani, Sudha; Harwood, Meaghan; Safren, Steven] Fenway Community Hlth, Res & Evaluat Dept, Boston, MA 02115 USA. [Berg, Carla; Greer, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Berg, Carla; Greer, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Safren, S (reprint author), Fenway Community Hlth, Res & Evaluat Dept, 7 Haviland St, Boston, MA 02115 USA. EM ssafren@partners.org FU NIDA NIH HHS [R01 DA018603]; NIMH NIH HHS [R21 MH066660]; PHS HHS [066660, 018603] NR 36 TC 14 Z9 14 U1 2 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1050-3307 J9 PSYCHOTHER RES JI Psychother. Res. PD MAY PY 2008 VL 18 IS 3 BP 271 EP 280 DI 10.1080/10503300701561537 PG 10 WC Psychology, Clinical SC Psychology GA 308QO UT WOS:000256405300004 PM 18815979 ER PT J AU Corriden, R Chen, Y Inoue, Y Beldi, G Robson, S Insel, P Junger, W AF Corriden, Ross Chen, Yu Inoue, Yoshiaki Beldi, Guido Robson, Simon Insel, Paul Junger, Wolfgang TI E-NTPDase1 and alkaline phosphatase control chemotaxis of human neutrophils by generating adenosine from released ATP SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Chen, Yu; Inoue, Yoshiaki; Junger, Wolfgang] Harvard Univ, Sch Med, BIDMC, Dept Surg, Boston, MA 02215 USA. [Corriden, Ross; Insel, Paul; Junger, Wolfgang] Univ Calif San Diego, Program Biomed Sci, La Jolla, CA 92093 USA. [Corriden, Ross; Insel, Paul] Univ Calif San Diego, Dept Med & Pharmacol, La Jolla, CA 92093 USA. [Beldi, Guido; Robson, Simon] Harvard Univ, Sch Med, BIDMC, Dept Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 J9 PURINERG SIGNAL JI Purinergic Signal. PD MAY PY 2008 VL 4 SU 1 BP S29 EP S29 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 347QU UT WOS:000259156900056 ER PT J AU Dulla, CG Frenguelli, BG Staley, KJ Masino, SA AF Dulla, Chris G. Frenguelli, Bruno G. Staley, Kevin J. Masino, Susan A. TI Intracellular acidification causes adenosine release during states of hyperexcitability in the hippocampus SO PURINERGIC SIGNALLING LA English DT Meeting Abstract C1 [Dulla, Chris G.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Frenguelli, Bruno G.] Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. [Staley, Kevin J.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Masino, Susan A.] Trinity Coll, Neurosci Program, Hartford, CT 06106 USA. [Masino, Susan A.] Trinity Coll, Dept Psychol, Hartford, CT 06106 USA. RI Frenguelli, Bruno/C-5007-2015 OI Frenguelli, Bruno/0000-0001-7214-3172 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1573-9538 J9 PURINERG SIGNAL JI Purinergic Signal. PD MAY PY 2008 VL 4 SU 1 BP S160 EP S161 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 347QU UT WOS:000259156900311 ER PT J AU Pomerantz, SR AF Pomerantz, Stuart R. TI Net assets: Personal technology for productivity in radiology SO RADIOLOGY LA English DT Editorial Material ID SEARCH C1 Harvard Univ, Sch Med, Dept Neuroradiol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pomerantz, SR (reprint author), Harvard Univ, Sch Med, Dept Neuroradiol, Massachusetts Gen Hosp, 55 Fruit St,Gray 2-B285, Boston, MA 02114 USA. EM netassets@rsna.org NR 4 TC 6 Z9 6 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2008 VL 247 IS 2 BP 307 EP 310 DI 10.1148/radiol.2472080187 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 292TT UT WOS:000255289700003 PM 18430870 ER PT J AU Beland, MD Gervais, DA Levis, DA Hahn, PF Arellano, RS Mueller, PR AF Beland, Michael D. Gervais, Debra A. Levis, Diane A. Hahn, Peter F. Arellano, Ronald S. Mueller, Peter R. TI Complex abdominal and pelvic abscesses: Efficacy of adjunctive tissue-type plasminogen activator for drainage SO RADIOLOGY LA English DT Article ID PERCUTANEOUS DRAINAGE; INTRACAVITARY UROKINASE; INTRAABDOMINAL ABSCESS AB Purpose: To retrospectively evaluate the effectiveness and safety of tissue-type plasminogen activator (tPA) for drainage of abdominal and pelvic abscesses refractory to simple catheter drainage. Materials and Methods: This HIPAA-compliant study was approved by the Institutional Review Board; informed consent was waived. Forty-three patients ( 17 men, 26 women; mean age, 46 years; age range, 10-89 years) with a total of 46 abscesses underwent percutaneous drainage with 8.5 -14- F catheters. Etiology was postoperative in 28 abscesses ( 60.9%) and varied in 18 ( 39.1%). Intracavitary tPA was initiated on the basis of viscous contents yielding minimal drainage at initial placement or if follow-up imaging showed a large residual collection despite satisfactory catheter position. A treatment cycle was 4-6 mg of tPA in 0.9% saline administered twice daily for 3 days. Drainage success was defined as evacuation of the abscess without surgery. Safety was evaluated on the basis of complications. Statistical analysis was performed by using the Student t test and Fisher exact test. Results: Forty-six abscesses were initially drained by 51 catheters. Complete evacuation was achieved in 41 (89.1%) abscesses, whereas five (10.9%) required surgical drainage. Three (60%) of these five had a documented fistula, a higher ( P =.02) percentage than in successfully drained abscesses. Three ( 6.5%) of the 46 abscesses recurred ( 12-95 days after catheter removal). There were no tPA-linked bleeding complications despite four patients receiving full systemic anticoagulation and 24 receiving prophylactic anticoagulation. Conclusion: Intracavitary tPA is safe and effective for draining complex fluid collections, with most patients avoiding surgery. C1 [Beland, Michael D.; Gervais, Debra A.; Levis, Diane A.; Hahn, Peter F.; Arellano, Ronald S.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Beland, MD (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM mdbeland@gmail.com NR 12 TC 13 Z9 13 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2008 VL 247 IS 2 BP 567 EP 573 DI 10.1148/radiol.2472070761 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 292TT UT WOS:000255289700032 PM 18372451 ER PT J AU Konya, D Liao, WL Choi, H Yu, D Woodard, MC Newton, KM King, AM Pamir, NM Black, PM Frontera, WR Sabharwal, S Teng, YD AF Konya, Deniz Liao, Wei-Lee Choi, Howard Yu, Dou Woodard, Matthew C. Newton, Kimberly M. King, Allyson M. Pamir, Necmettin M. Black, Peter M. Frontera, Walter R. Sabharwal, Sunil Teng, Yang D. TI Functional recovery in T13-L1 hemisected rats resulting from peripheral nerve rerouting: role of central neuroplasticity SO REGENERATIVE MEDICINE LA English DT Article DE anastomosis; hemisection; neural stem cell; peripheral nervous system; regeneration; rehabilitation; spinal cord injury; synaptophysin ID SPINAL-CORD-INJURY; FIBROBLAST-GROWTH-FACTOR; NEURAL STEM-CELLS; NITRIC-OXIDE; ADULT-RAT; ELECTRICAL-STIMULATION; CONTUSION INJURIES; PHYSICAL-ACTIVITY; PRECURSOR CELLS; MOTOR FUNCTION AB Background: Functional improvements after spinal cord injury (SCI) have been reported anecdotally following neurotization, in other words, rerouting nerves proximal to injured cord segments to distal neuromuscular targets, although the underlying mechanisms remain largely unknown. Aim: To test our hypothesis that neurotization-mediated recovery is primarily attributable to CNS neuroplasticity that therefore manifests optimal response during particular therapeutic windows, we anastomosed the T12 intercostal nerve to the ipsilateral L3 nerve root 1-4 weeks after T13-L1 midline hemisection in rats. Results: While axonal tracing and electromyography revealed limited reinnervation in the target muscles, neurobehavioral function, as assessed by locomotion, extensor postural thrust and sciatic functional index of SCI rats receiving neurotization 7-10 days postinjury (n = 11), recovered to levels close to non-SCI controls with neurcitization only (n = 3), beginning 3-5 weeks postanastomosis. Conversely, hindlimb deficits were unchanged in hemisected controls with sham neurcitization (n = 7) or 4 weeks-delayed neurcitization (n = 3) and in rats that had undergone T13-L1 transection plus bilateral anastomoses (n = 6). Conclusion: Neurotized SCI animals demonstrated multiparameters of neural reorganization in the distal lumbar cord, including enhanced proliferation of endogenous neural stem cells, increased immunoreactivity of serotonin and synaptophysin, and neurite growth/sprouting, suggesting that anastomosing functional nerves with the nerve stump emerging distal to the hemisection stimulates neuroplasticity in the dysfunctional spinal cord. Our conclusion is validated by the fact that severance of the T13-L1 contralateral cord abolished the postanastomosis functional recovery. Neurotization and its neuroplastic sequelae need to be explored further to optimize clinical strategies of post-SCI functional repair. C1 [Konya, Deniz; Yu, Dou; Woodard, Matthew C.; Newton, Kimberly M.; King, Allyson M.; Teng, Yang D.] VA Boston Healthcare Syst, Div SCI Res, Boston, MA 02132 USA. [Konya, Deniz; Liao, Wei-Lee; Choi, Howard; Yu, Dou; Woodard, Matthew C.; Newton, Kimberly M.; King, Allyson M.; Black, Peter M.; Sabharwal, Sunil; Teng, Yang D.] Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Konya, Deniz; Liao, Wei-Lee; Choi, Howard; Yu, Dou; Woodard, Matthew C.; Newton, Kimberly M.; King, Allyson M.; Black, Peter M.; Sabharwal, Sunil; Teng, Yang D.] Childrens Hosp, Boston, MA 02115 USA. [Konya, Deniz; Pamir, Necmettin M.] Marmara Univ, Dept Neurosurg, Istanbul, Turkey. [Liao, Wei-Lee; Choi, Howard; Frontera, Walter R.; Sabharwal, Sunil; Teng, Yang D.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Frontera, Walter R.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. RP Teng, YD (reprint author), VA Boston Healthcare Syst, Div SCI Res, Boston, MA 02132 USA. EM yang_teng@hms.harvard.edu FU NINDS NIH HHS [1R21NS053935, R21 NS053935, R21 NS053935-02] NR 76 TC 11 Z9 12 U1 0 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0751 J9 REGEN MED JI Regen. Med. PD MAY PY 2008 VL 3 IS 3 BP 309 EP 327 DI 10.2217/17460751.3.3.309 PG 19 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA 331EJ UT WOS:000257995200016 PM 18462055 ER PT J AU Cohen, SP Christo, PJ Wang, S Chen, L Stojanovic, MP Shields, CH Brummett, C Mao, J AF Cohen, Steven P. Christo, Paul J. Wang, Shuxing Chen, Lucy Stojanovic, Milan P. Shields, Cynthia H. Brummett, Chad Mao, Jianren TI The effect of opioid dose and treatment duration on the perception of a painful standardized clinical stimulus SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article DE hyperalgesia; nerve block; opioid; pain perception; tolerance ID FACET RADIOFREQUENCY DENERVATION; METHADONE-MAINTENANCE PATIENTS; TOLERANCE; MORPHINE; FAILURE; SUCCESS AB Background and objectives: The concept of opioid-induced hyperalgesia has recently gained prominence as a contributing factor for opioid tolerance and long-term treatment failure. But whereas the preclinical data for this phenomenon are strong, the mixed clinical data derive primarily from experimental pain models conducted in volunteers and heroin addicts, and nonstandardized clinical stimuli, e.g., surgery. The primary objective of this study is to delineate the effect of opioid dose and treatment duration on pain intensity and unpleasantness ratings following a standardized clinical pain stimulus. Methods: Three hundred and fifty-five patients, on a steady regimen of analgesic medications and scheduled for an interventional procedure, received a standardized subcutaneous injection of lidocaine prior to a full dose of local anesthetic. Before and immediately following the injection, subjects were asked to rate pain and unpleasantness intensity on a 0 to 10 numerical rating scale. Subjects were stratified into 6 groups based on opioid dosage. A control group of 27 volunteers who had no pain and were taking no analgesics were also injected. Results: Both opioid dose and duration of treatment directly correlated with pain intensity and unpleasantness scores. Baseline pain intensity was also positively associated with both outcome variables. Gender was found to be associated with pain intensity and unpleasantness, with females scoring higher in both categories than males. Compared with patients not receiving opioid treatment, patients receiving opioid therapy were more likely to rate the standardized pain stimulus as being more unpleasant than painful. Conclusions: The results of this study bolster preclinical and experimental pain models demonstrating enhanced pain perception in subjects receiving opioid therapy. This simple clinical model may provide a useful tool in examining opioid-induced hyperalgesia. C1 [Cohen, Steven P.; Christo, Paul J.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Cohen, Steven P.; Shields, Cynthia H.] Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. [Wang, Shuxing; Chen, Lucy; Stojanovic, Milan P.; Mao, Jianren] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Stojanovic, Milan P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. [Brummett, Chad] Univ Michigan, Sch Med, Dept Anesthesiol, Ann Arbor, MI USA. RP Cohen, SP (reprint author), 550 N Broadway,Suite 301, Baltimore, MD 21029 USA. EM scohen40@jhmi.edu OI Brummett, Chad/0000-0003-0974-7242 NR 19 TC 47 Z9 48 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 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAY-JUN PY 2008 VL 33 IS 3 BP 199 EP 206 DI 10.1016/j.rapm.2007.10.009 PG 8 WC Anesthesiology SC Anesthesiology GA 297LE UT WOS:000255617400002 PM 18433669 ER PT J AU Syrkina, O Jafari, B Hales, CA Quinn, DA AF Syrkina, Olga Jafari, Behrouz Hales, Charles A. Quinn, Deborah A. TI Oxidant stress mediates inflammation and apoptosis in ventilator-induced lung injury SO RESPIROLOGY LA English DT Article DE acute lung injury; apoptosis; cytokine; N-acetylcysteine; neutrophil; oxidant stress ID RESPIRATORY-DISTRESS-SYNDROME; HIGH TIDAL VOLUME; N-ACETYLCYSTEINE; OXIDATIVE STRESS; DOUBLE-BLIND; IN-VIVO; GLUTATHIONE; ENDOTOXIN; CELLS; RATS AB Background and objective: Ventilator-induced lung injury (VILI) leads to airway epithelial cell apoptosis and lung inflammation. High tidal volume ventilation in vivo has been shown to induce MIP-2 production, lung neutrophil sequestration and apoptotic airway cell death. This study aimed to determine the effect of N-acetylcysteine (NAC), a scavenger of oxygen radicals, on lung inflammation and apoptosis in an in vivo model of VILI. Methods: Sprague-Dawley rats (n = 5 per group) were ventilated at low tidal volume (V-T 7 mL/kg) or high tidal volume (V-T 20 mL/kg) with or without administration of 140 mg/kg of intravenous NAC. Animals were ventilated for 30 min, 1 or 2 h, then allowed to recover for 2 h, at which time neutrophil infiltration, MIP-2, TNF-alpha and IL-6 in BAL fluid, as well as the percentage of apoptotic airway epithelial cells, were measured. Results:Ventilation at V-T 20 mL/kg increased oxidant release, as measured by serum isoprostane, and decreased lung glutathione, the major antioxidant in the lung. NAC treatment during ventilation at V-T 20 mL/kg prevented the decrease in lung glutathione and significantly lowered serum isoprostane levels, neutrophil infiltration, cytokines in the BAL and apoptosis in the airways as compared with animals ventilated at V-T 20 mL/kg without NAC (P < 0.05). Conclusions: These data point to an early role of oxidant-induced inflammation and apoptosis in VILI. C1 [Syrkina, Olga; Jafari, Behrouz; Hales, Charles A.; Quinn, Deborah A.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. [Syrkina, Olga; Jafari, Behrouz; Hales, Charles A.; Quinn, Deborah A.] Harvard Univ, Sch Med, Boston, MA USA. RP Syrkina, O (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, 55 Fruit St,Bullfinch 148, Boston, MA 02114 USA. EM osyrkina@partners.org FU NHLBI NIH HHS [HL03920, HL 3915] NR 37 TC 43 Z9 46 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1323-7799 J9 RESPIROLOGY JI Respirology PD MAY PY 2008 VL 13 IS 3 BP 333 EP 340 DI 10.1111/j.1440-1843.2008.01279.x PG 8 WC Respiratory System SC Respiratory System GA 285QV UT WOS:000254792200002 PM 18399853 ER PT J AU Soares, SMTP Oliveira, RARA Franca, SA Rezende, SM Dragosavac, D Kacmarek, RM Carvalho, CRR AF Soares, Silvia M. T. P. Oliveira, Rosmari A. R. A. Franca, Suelene A. Rezende, Silvio M. Dragosavac, Desanka Kacmarek, Robert M. Carvalho, Carlos R. R. TI Continuous positive airway pressure increases inspiratory capacity of COPD patients SO RESPIROLOGY LA English DT Article DE COPD; CPAP; inspiratory capacity; non-invasive mechanical ventilation; pulmonary hyperinflation ID OBSTRUCTIVE PULMONARY-DISEASE; END-EXPIRATORY PRESSURE; FLOW LIMITATION; DYNAMIC HYPERINFLATION; NONINVASIVE VENTILATION; LUNG HYPERINFLATION; EXERCISE; DYSPNEA; VOLUME; REST AB Background and objective: Hyperinflation with a decrease in inspiratory capacity (IC) is a common presentation for both unstable and stable COPD patients. As CPAP can reduce inspiratory load, possibly secondary to a reduction in hyperinflation, this study examined whether CPAP would increase IC in stable COPD patients. Methods: Twenty-one stable COPD patients (nine emphysema, 12 chronic bronchitis) received a trial of CPAP for 5 min at 4, 7 and 11 cmH(2)O. Fast and slow VC (SVC) were measured before and after each CPAP trial. In patients in whom all three CPAP levels resulted in a decreased IC, an additional trial of CPAP at 2 cmH(2)O was conducted. For each patient, a 'best CPAP' level was defined as the one associated with the greatest IC. This pressure was then applied for an additional 10 min followed by spirometry. Results: Following application of the 'best CPAP', the IC and SVC increased in 15 patients (nine emphysema, six chronic bronchitis). The mean change in IC was 159 mL (95% CI: 80-237 mL) and the mean change in SVC was 240 mL (95% CI: 97-386 mL). Among these patients, those with emphysema demonstrated a mean increase in IC of 216 mL (95% CI: 94-337 mL). Six patients (all with chronic bronchitis) did not demonstrate any improvement in IC. Conclusions: The best individualized CPAP can increase inspiratory capacity in patients with stable COPD, especially in those with emphysema. C1 [Franca, Suelene A.; Carvalho, Carlos R. R.] Univ Sao Paulo, Hosp Clin, Resp ICU, Div Pulm, BR-04004002 Sao Paulo, Brazil. [Soares, Silvia M. T. P.; Oliveira, Rosmari A. R. A.] Univ Estadual Campinas, Intens Care Unit, Sao Paulo, Brazil. [Rezende, Silvio M.] Univ Estadual Campinas, Physiol Resp Lab, Sao Paulo, Brazil. [Dragosavac, Desanka] Univ Estadual Campinas, Dept Surg, Sao Paulo, Brazil. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care & Resp Care, Boston, MA 02115 USA. RP Carvalho, CRR (reprint author), Univ Sao Paulo, Hosp Clin, Resp ICU, Div Pulm, Rua Sampaio Viana 509,Apt 21, BR-04004002 Sao Paulo, Brazil. EM crrcarvalho@uol.com.br RI Carvalho, Carlos/H-2161-2011 NR 28 TC 8 Z9 8 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1323-7799 J9 RESPIROLOGY JI Respirology PD MAY PY 2008 VL 13 IS 3 BP 387 EP 393 DI 10.1111/j.1440-1843.2008.01263.x PG 7 WC Respiratory System SC Respiratory System GA 285QV UT WOS:000254792200010 PM 18399861 ER PT J AU Kreher, DA Holcomb, PJ Goff, D Kuperberg, GR AF Kreher, Donna A. Holcomb, Phillip J. Goff, Donald Kuperberg, Gina R. TI Neural evidence for faster and further automatic spreading activation in schizophrenic thought disorder SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; N400; semantic priming ID COMMUNICATION DISORDERS; WORD PRONUNCIATION; SEMANTIC NETWORK; BRAIN POTENTIALS; LANGUAGE; N400; REPETITION; HANDEDNESS; RETRIEVAL; INVENTORY AB It has been proposed that the loose associations characteristic of thought disorder in schizophrenia result from an abnormal increase in the automatic spread of activation through semantic memory. We tested this hypothesis by examining the time course of neural semantic priming using event-related potentials (ERPs). ERPs were recorded to target words that were directly related, indirectly related, and unrelated to their preceding primes, while thought-disordered (TD) and non-TD schizophrenia patients and healthy controls performed an implicit semantic categorization task under experimental conditions that encouraged automatic processing. By 300-400 milliseconds after target word onset, TD patients showed increased indirect semantic priming relative to non-TD patients and healthy controls, while the degree of direct semantic priming was increased in only the most severely TD patients. By 400-500 milliseconds after target word onset, both direct and indirect semantic priming were generally equivalent across the 3 groups. These findings demonstrate for the first time at a neural level that, under automatic conditions, activation across the semantic network spreads further within a shorter period of time in specific association with positive thought disorder in schizophrenia. C1 [Kreher, Donna A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Kreher, Donna A.; Holcomb, Phillip J.; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Goff, Donald; Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. [Goff, Donald; Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Kreher, DA (reprint author), Univ Massachusetts, Dept Psychol, 135 Hicks Way, Amherst, MA 01003 USA. EM dkreher@psych.umass.edu FU NICHD NIH HHS [R01 HD043251, R01 HD025889, R01 HD025889-15, R01 HD025889-16, R01 HD025889-17, R01 HD25889]; NIMH NIH HHS [R01 MH071635] NR 43 TC 45 Z9 45 U1 6 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2008 VL 34 IS 3 BP 473 EP 482 DI 10.1093/schbul/sbm108 PG 10 WC Psychiatry SC Psychiatry GA 290XI UT WOS:000255156500011 PM 17905785 ER PT J AU Rutherford, A Chung, RT AF Rutherford, Anna Chung, Raymond T. TI Acute liver failure: Mechanisms of hepatocyte injury and regeneration SO SEMINARS IN LIVER DISEASE LA English DT Review DE acute liver failure; apoptosis; necrosis; regeneration ID FULMINANT HEPATIC-FAILURE; ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; MITOCHONDRIAL PERMEABILITY TRANSITION; MEDIATED APOPTOSIS; STEM-CELLS; OVAL CELL; ALCOHOLIC HEPATITIS; CASPASE INHIBITOR; ONCOTIC NECROSIS AB Acute liver failure (ALF) occurs when the extent of hepatocyte death exceeds the liver's regenerative capacity. Despite vast differences in causes, the mode of cell death typically follows one of two patterns: necrosis or apoptosis. Necrosis and apoptosis have traditionally been considered separate entities within various etiologies of ALF; however, there is increasing evidence that they are alternative outcomes of the same initiating factors and signaling pathways, a process known as necroapoptosis. Here we review mechanisms of liver cell injury in ALF, including evolving knowledge of pathways leading to apoptosis, necrosis, and necroapoptosis, as well as how these pathways are potential therapeutic targets in ALF. We also discuss hepatic regeneration and the cytokines and growth factors involved in both the replication of differentiated hepatocytes as well as activation of intrahepatic progenitor cells, two pathways of hepatocyte regeneration that are dependent on the type and extent of hepatic insult in ALF. C1 [Rutherford, Anna] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Rutherford, A (reprint author), Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA. EM ARutherford@partners.org NR 67 TC 58 Z9 67 U1 0 U2 13 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 2008 VL 28 IS 2 BP 167 EP 174 DI 10.1055/s-2008-1073116 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296NQ UT WOS:000255553500005 PM 18452116 ER PT J AU Brown, D AF Brown, Dennis TI Aquaporins and vasopressin signaling in kidney health and disease: Introduction SO SEMINARS IN NEPHROLOGY LA English DT Editorial Material C1 [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAY PY 2008 VL 28 IS 3 BP 215 EP 216 DI 10.1016/j.semnephrol.2008.03.001 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 316FJ UT WOS:000256934300001 PM 18519082 ER PT J AU Bouley, R Hasler, U Lu, HAJ Nunes, P Brown, D AF Bouley, Richard Hasler, Udo Lu, Hua A. J. Nunes, Paula Brown, Dennis TI Bypassing vasopressin receptor signaling pathways in nephrogenic diabetes insipidus SO SEMINARS IN NEPHROLOGY LA English DT Review DE vasopressin receptor; AQP2; endocytosis; exocytosis; cGMP ID DUCT PRINCIPAL CELLS; AQUAPORIN-2 WATER CHANNEL; NITRIC-OXIDE SYNTHASE; COA REDUCTASE INHIBITORS; RENAL EPITHELIAL-CELLS; COLLECTING DUCT; RAT-KIDNEY; MEDIATED TRANSLOCATION; MEMBRANE INSERTION; SODIUM-TRANSPORT C1 [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, 185 Cambridge St,Simches Res Bldg,Suite 8202, Boston, MA 02114 USA. EM brown@receptor.mgh.harvard.edu RI Nunes-Hasler, Paula/N-4337-2015 OI Nunes-Hasler, Paula/0000-0002-4598-685X FU NIDDK NIH HHS [DK02114, DK43341, DK57521, K08 DK075940, K08 DK075940-01, P01 DK038452, P01 DK038452-22, P30 DK057521] NR 82 TC 36 Z9 37 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAY PY 2008 VL 28 IS 3 BP 266 EP 278 DI 10.1016/j.semnephrol.2008.03.010 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 316FJ UT WOS:000256934300006 PM 18519087 ER PT J AU Seo, Y Mari, C Hasegawa, BH AF Seo, Youngho Mari, Carina Hasegawa, Bruce H. TI Technological development and advances in single-photon emission computed tomography/computed tomography SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review ID X-RAY CT; MYOCARDIAL-PERFUSION SPECT; LEFT-VENTRICULAR FUNCTION; LOW-DOSE CT; SENTINEL NODE IDENTIFICATION; HEPATIC ARTERIAL INFUSION; SQUAMOUS-CELL CARCINOMA; MEDICAL IMAGING-SYSTEM; NON-HODGKINS-LYMPHOMA; ATTENUATION CORRECTION AB Single-photon emission computed tomography/computed tomography (SPECT/CT) has emerged during the past decade as a means of correlating anatomical information from CT with functional information from SPECT. The integration of SPECT and CT in a single imaging device facilitates anatomical localization of the radiopharmaceutical to differentiate physiological uptake from that associated with disease and patient-specific attenuation correction to improve the visual quality and quantitative accuracy of the SPECT image. The first clinically available SPECT/CT systems performed emission-transmission imaging using a dual-headed SPECT camera and a low-power x-ray CT subsystem. Newer SPECT/CT systems are available with high-power CT subsystems suitable for detailed anatomical diagnosis, including CT coronary angiography and coronary calcification that can be correlated with myocardial perfusion measurements. The high-performance CT capabilities also offer the potential to improve compensation of partial volume errors for more accurate quantitation of radionuclide measurement of myocardial blood flow and other physiological processes and for radiation dosimetry for radionuclide therapy. In addition, new SPECT technologies are being developed that significantly improve the detection efficiency and spatial resolution for radionuclide imaging of small organs including the heart, brain, and breast, and therefore may provide new capabilities for SPECT/CT imaging in these important clinical applications. C1 [Seo, Youngho; Mari, Carina; Hasegawa, Bruce H.] Univ Calif San Francisco, Dept Radiol, Phys Res Lab, San Francisco, CA 94107 USA. [Seo, Youngho; Hasegawa, Bruce H.] Univ Calif San Francisco, Joint Bioengn Grad Grp, San Francisco, CA 94107 USA. [Mari, Carina] San Francisco Vet Adm Med Ctr, Nucl Med Serv, San Francisco, CA USA. [Hasegawa, Bruce H.] Univ Calif Berkeley, Dept Nucl Engn, Berkeley, CA 94720 USA. RP Hasegawa, BH (reprint author), Univ Calif San Francisco, Dept Radiol, Phys Res Lab, 185 Berry St,Suite 350, San Francisco, CA 94107 USA. EM bruce.hasegawa@radiology.ucsf.edu FU NCI NIH HHS [2 R44 CA095936, 5 K25 CA114254, K25 CA114254, K25 CA114254-03, R44 CA095936]; NHLBI NIH HHS [1 R21 HL083073, R21 HL083073]; NIA NIH HHS [1 R41 AG030241, R41 AG030241]; NIBIB NIH HHS [5 R01 EB000288, 4 R44 EB001685, 5 R21 EB006373, R01 EB000288, R21 EB001685, R21 EB006373, R33 EB001685]; NIEHS NIH HHS [2 R44 ES012361, R44 ES012361]; PHS HHS [2 R44 H083494] NR 228 TC 60 Z9 63 U1 0 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 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD MAY PY 2008 VL 38 IS 3 BP 177 EP 198 DI 10.1053/j.semnuclmed.2008.01.001 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 285UO UT WOS:000254801900005 PM 18396178 ER PT J AU Mimiaga, MJ Mayer, KH Reisner, SL Gonzalez, A Dumas, B Vanderwarker, R Novak, DS Bertrand, T AF Mimiaga, Matthew J. Mayer, Kenneth H. Reisner, Sari L. Gonzalez, Alex Dumas, Bill Vanderwarker, Rodney Novak, David S. Bertrand, Thomas TI Asymptomatic gonorrhea and chlamydial infections detected by nucleic acid amplification tests among Boston area men who have sex with men SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; POSITIVE PREDICTIVE-VALUE; NEISSERIA-GONORRHOEAE; LOW-PREVALENCE; HIV-INFECTION; RISK; TRANSMISSION; BEHAVIOR AB Background: The purpose of this project was to determine the prevalence of asymptomatic sexually transmitted diseases (STDs) among men who have sex with men (MSM) in the Boston area who had been sexually active (oral and/or anal sex) with another male within the past year. Methods: Over a 1-month period (March 2007), asymptomatic MSM in care at a Boston community health center (n = 114) were screened for gonorrhea and chlamydia using the BD ProbeTec technique. Deidentified medical record data were analyzed and linked to prevalence monitoring results. Results: Eleven percent of the sample tested positive for one of the 2 STDs (gonorrhea or chlamydia) from at least one mucosal site. Individuals who were infected with an STD were considerably more likely to have a prior history of one or more STD infections when compared with those without an STD history (OR = 3.69; P <0.02). There were no significant differences observed in psychosocial and other behavioral risk factors between patients with or without an STD. Conclusions: Screening asymptomatic MSM using nucleic acid amplification tests (NAATs) revealed a substantial STD burden that might not have been diagnosed using traditional assays. These data are critical for the design of effective public health interventions for this population. C1 [Mimiaga, Matthew J.; Mayer, Kenneth H.; Reisner, Sari L.; Gonzalez, Alex; Vanderwarker, Rodney] Fenway Inst, Res & Evaluat Dept, Boston, MA 02119 USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. [Dumas, Bill; Novak, David S.; Bertrand, Thomas] Massachusetts Dept Publ Hlth, Boston, MA USA. RP Mimiaga, MJ (reprint author), Fenway Inst, Res & Evaluat Dept, Prudential Tower,4th Floor,800 Boylston St, Boston, MA 02119 USA. EM mmimiaga@fenwayhealth.org NR 20 TC 27 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY PY 2008 VL 35 IS 5 BP 495 EP 498 DI 10.1097/OLQ.0b013e31816471ae PG 4 WC Infectious Diseases SC Infectious Diseases GA 295SG UT WOS:000255493600013 PM 18354345 ER PT J AU Bredella, MA Essary, B Torriani, M Ouellette, HA Palmer, WE AF Bredella, Miriam A. Essary, Brendan Torriani, Martin Ouellette, Hugue A. Palmer, William E. TI Use of FDG-PET in differentiating benign from malignant compression fractures SO SKELETAL RADIOLOGY LA English DT Article DE spine; compression fractures; malignant; benign; FDG-PET ID BONE-TUMORS; MRI; DISCRIMINATION; OSTEOPOROSIS; TOMOGRAPHY; METASTASES; LESIONS; MARROW AB Objective The objective was to evaluate the use of fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating benign from malignant compression fractures. Patients and methods In a retrospective analysis, we identified 33 patients with 43 compression fractures who underwent FDG-PET. On FDG-PET the uptake pattern was recorded qualitatively and semiquantitatively and fractures were categorized as benign or malignant. Standardized uptake values (SUV) were obtained. MRI, CT, and biopsy results as well as clinical follow-up for 1-3 years served as standards of reference. The Student's t test was used to determine whether there was a statistically significant difference between the SUV for benign and malignant compression fractures. Results There were 14 malignant and 29 benign compression fractures, including 5 acute benign fractures. On FDG-PET, 5 benign fractures were falsely classified as malignant (false-positive). Three of these patients underwent prior treatment with bone marrow-stimulating agents. There were two false-negative results. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET in differentiating benign from malignant compression fractures were 86%, 83%, 84%, 71%, and 92% respectively. The difference between SUV values of benign and malignant fractures was statistically significant (1.9 +/- 0.97 for benign and 3.9 +/- 1.52 for malignant fractures, p<0.001). SUV of benign acute and chronic fractures were not statistically significant. Conclusion Fluorodeoxyglucose positron emission tomography is useful in differentiating benign from malignant compression fractures. Therapy with bone marrow-stimulating agents can mimic malignant involvement. C1 [Bredella, Miriam A.; Essary, Brendan; Torriani, Martin; Ouellette, Hugue A.; Palmer, William E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org NR 19 TC 10 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAY PY 2008 VL 37 IS 5 BP 405 EP 413 DI 10.1007/s00256-008-0452-5 PG 9 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 278CV UT WOS:000254262000003 PM 18278491 ER PT J AU Gilbertson, L Ahn, SH Teng, PN Studer, RK Niyibizi, C Kang, JD AF Gilbertson, Lars Ahn, Sang-Ho Teng, Pang-Ning Studer, Rebecca K. Niyibizi, Christopher Kang, James D. TI The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells SO SPINE JOURNAL LA English DT Review DE human intervertebral disc; nucleus pulposus cells; annulus fibrosis cells; BMP-2; BMP-12; matrix protein synthesis; gene therapy ID INTERVERTEBRAL DISC CELLS; MEDIATED GENE-TRANSFER; GROWTH-FACTOR; IN-VIVO; EXTRACELLULAR-MATRIX; CULTURE SYSTEM; DEGENERATION; EXPRESSION; THERAPY; RABBIT AB BACKGROUND CONTEXT: Bone morphogenetic proteins (BMPs) are potential therapeutic factors for degenerative discs, and BMP-12 does not have the osteogenic potential of BMP-2, making it better suited for intradiscal injection. However, no reports have compared the actions of BMP-2 and -12 on human annulus fibrosus (AF) and nucleus pulposus (NP) cells nor evaluated adenoviral-mediated gene therapy in human AF cells. PURPOSE: To evaluate and compare the effects of recombinant human (rh) BMP-2, rhBMP-12, and adenoviral BMP-12 (Ad-BMP-12) on nucleus pulposus and annulus fibrosis cell matrix protein synthesis. STUDY DESIGN: In vitro study using rhBMP-2 and -12 and adenoviral BMP-12 with human intervertebral disc (IVD) cells. METHODS: Human NP and AF IVD cells were isolated, maintained in monolayer, and incubated with BMP-2 or - 12 for 2 days. AF and NP cells were transduced with Ad-BMP-12, pellets formed, and incubated for 6 days. Growth factor-treated cells were labelled with either 35-S or 3H-proline to assay matrix protein synthesis. RESULTS: rhBMP-2 increased NP proteoglycan, collagen, and noncollagen protein synthesis to 355%, 388%, and 234% of control. RhBMP-12 increased the same NP matrix proteins' synthesis to 140%, 143%, and 160% of control. Effects on AF matrix protein synthesis were minimal. Ad-BMP-12 significantly increased matrix protein synthesis and DNA content of AF and NP cells in pellet culture. NP synthesis of all matrix proteins and AF synthesis of proteoglycans was increased when the data were normalized to pellet DNA. AF synthesis of noncollagen protein and collagen was not modulated by Ad-BMP-12 if the data are normalized to pellet DNA content. CONCLUSIONS: Both rhBMP-2 and -12 increase human NP cell matrix protein synthesis while having minimal effects on AF cells. However, Ad-BMP-12 did increase matrix protein synthesis in both NP and AF cells, making it a potential therapy for enhancing matrix production in the IVD. These responses plus the proliferative action of Ad-BMP-12 seen in the current studies, and the lack of an osteogenic action noted in other studies justifies future studies to determine if gene therapy with BMP-12 could provide protective and/or reparative actions in degenerating discs. (C) 2008 Elsevier Inc. All rights reserved. C1 [Gilbertson, Lars; Teng, Pang-Ning; Kang, James D.] Univ Pittsburgh, Dept Orthoped Surg, Ferguson Lab, Pittsburgh, PA 15261 USA. [Ahn, Sang-Ho] Yeungnam Univ, Dept Rehabil Med, Taegu, South Korea. [Studer, Rebecca K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Niyibizi, Christopher] Penn State Univ, Coll Med, Dept Orthopaed & Rehabil, Hershey, PA 17033 USA. RP Kang, JD (reprint author), Univ Pittsburgh, Dept Orthoped Surg, Ferguson Lab, E1641 BST,200 Lothrop St, Pittsburgh, PA 15261 USA. EM Kangjd@UPMC.edu NR 43 TC 50 Z9 62 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 J9 SPINE J JI Spine Journal PD MAY-JUN PY 2008 VL 8 IS 3 BP 449 EP 456 DI 10.1016/j.spinee.2006.11.006 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 305MA UT WOS:000256181300005 PM 18455111 ER PT J AU Cohen, SP Stojanovic, MP Crooks, M Kim, P Schmidt, RK Shields, CH Croll, S Hurley, RW AF Cohen, Steven P. Stojanovic, Milan P. Crooks, Matthew Kim, Peter Schmidt, Rolf K. Shields, Cynthia H. Croll, Scott Hurley, Robert W. TI Lumbar zygapophysial (facet) joint radiofrequency denervation success as a function of pain relief during diagnostic medial branch blocks: a multicenter analysis SO SPINE JOURNAL LA English DT Article DE denervation; facet joint; low back pain; medical branch block; predictive value; radiofrequency; zygapophysial joint ID LOW-BACK-PAIN; CHRONIC NECK PAIN; DOUBLE-BLIND; CONTROLLED TRIAL; SINGLE-NEEDLE; NEUROTOMY; EFFICACY; SPECIFICITY; PREVALENCE; INJECTION AB BACKGROUND CONTEXT: The publication of several recent studies showing minimal benefit for radiofrequency (RF) lumbar zygapophysial (1-z) joint denervation have led many investigators to reevaluate selection criteria. One controversial explanation for these findings is that the most commonly used cutoff value for selecting patients for 1-z (facet) joint RF denervation, greater than 50% pain relief after diagnostic blocks, is too low and hence responsible for the high failure rate. PURPOSE: To compare 1-z joint RF denervation success rates between the conventional greater than or equal to 50% pain relief threshold and the more stringently proposed greater than or equal to 80% cutoff for diagnostic medial branch blocks (MBB). STUDY DESIGN/SETTING: Multicenter, retrospective clinical data analysis. PATIENT SAMPLE: Two hundred and sixty-two patients with chronic low back pain who underwent 1-z RF denervation at three pain clinics. OUTCOME MEASURES: Outcome measures were greater than 50% pain relief based on visual analog scale or numerical pain rating score after RF denervation persisting at least 6 months post-procedure, and global perceived effect (GPE), which considered pain relief, satisfaction and functional improvement. METHODS: Data were garnered at three centers on 262 patients who underwent 1-z RF denervation after obtaining greater than or equal to 50% pain relief after diagnostic MBB. Subjects were separated into those who received partial (greater than or equal to 50% but less than 80%) and near-complete (greater than or equal to 80%) pain relief from the MBB. Outcomes between groups were compared with multivariate analysis after controlling for 14 demographic and clinical variables. RESULTS: One hundred and forty-five patients obtained greater than or equal to 50% but less than 80% pain relief after diagnostic MBB, and 117 patients obtained greater than or equal to 80% relief. In the greater than or equal to 50% group, success rates were 52% and 67% based on pain relief and GPE, respectively. Among patients who experienced greater than 80% relief from diagnostic blocks, 56% obtained greater than or equal to 50% relief from RF denervation and 66% had a positive GPE. CONCLUSIONS: Using more stringent pain relief criteria when selecting patients for 1-z joint RF denervation is unlikely to improve success rates, and may lead to misdiagnosis and withholding a potentially valuable treatment from good candidates. (C) 2008 Elsevier Inc. All rights reserved. C1 [Cohen, Steven P.; Crooks, Matthew; Hurley, Robert W.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Pain Management Div, Baltimore, MD 21029 USA. [Cohen, Steven P.; Schmidt, Rolf K.; Shields, Cynthia H.; Croll, Scott] Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. [Stojanovic, Milan P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care,Pain Management Div, Boston, MA 02144 USA. [Kim, Peter] Univ So Calif, Sch Med, Dept Anesthesiol, Los Angeles, CA 90033 USA. RP Cohen, SP (reprint author), Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Pain Management Div, 550 North Broadway,Suite 301, Baltimore, MD 21029 USA. EM scohen40@jhmi.edu NR 41 TC 40 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 J9 SPINE J JI Spine Journal PD MAY-JUN PY 2008 VL 8 IS 3 BP 498 EP 504 DI 10.1016/j.spinee.2007.04.022 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 305MA UT WOS:000256181300011 PM 17662665 ER PT J AU Cai, C Thorne, J Grabel, L AF Cai, Chunyu Thorne, Jeffrey Grabel, Laura TI Hedgehog serves as a mitogen and survival factor during embryonic stem cell neurogenesis SO STEM CELLS LA English DT Article DE Shh; embryonic stem cells; neurogenesis; Sox1; proliferation; apoptosis ID INTERMEDIATE FILAMENT PROTEIN; NEURAL SUBTYPE SPECIFICATION; SONIC-HEDGEHOG; IN-VITRO; ES CELLS; PRECURSOR CELLS; MOUSE EMBRYOS; NEURONS; DIFFERENTIATION; BRAIN AB Hedgehog (Hh) signaling is involved in a wide range of important biological activities. Within the vertebrate central nervous system, Sonic Hedgehog (Shh) can act as a morphogen or mitogen that regulates the patterning, proliferation, and survival of neural stem cells (NSCs). However, its role in embryonic stem cell (ESC) neurogenesis has not been explored in detail. We have previously shown that Hh signaling is required for ESC neurogenesis. In order to elucidate the underlying mechanism, we utilized the Sox1-GFP ESC line, which has a green fluorescent protein (GFP) reporter under the control of the Sox1 gene promoter, providing an easy means of detecting NSCs in live cell culture. We show here that ESC differentiation in adherent culture follows the ESC -> primitive ectoderm -> neurectoderm transitions observed in vivo. Selective death of the Sox1-GFP-negative cells contributes to the enrichment of Sox1-GFP-positive NSCs. Interestingly, Shh is expressed exclusively by the NSCs themselves and elicits distinct downstream gene expression in Sox1-GFP-positive and -negative cells. Suppression of Hh signaling by antagonist treatment leads to different responses from these two populations as well: increased apoptosis in Sox1-GFP-positive NSCs and decreased proliferation in Sox1-GFP-negative primitive ectoderm cells. Hedgehog agonist treatment, in contrast, inhibits apoptosis and promotes proliferation of Sox1-GFP-positive NSCs. These results suggest that Hh acts as a mitogen and survival factor during early ESC neurogenesis, and evidence is presented to support a novel autocrine mechanism for Hh-mediated effects on NSC survival and proliferation. C1 [Cai, Chunyu; Grabel, Laura] Wesleyan Univ, Dept Biol, Middletown, CT 06457 USA. [Thorne, Jeffrey] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Grabel, L (reprint author), Wesleyan Univ, Dept Biol, 52 Lawn Ave, Middletown, CT 06457 USA. EM lgrabel@wesleyan.edu NR 52 TC 46 Z9 53 U1 0 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 2008 VL 26 IS 5 BP 1097 EP 1108 DI 10.1634/stemcells.2007-0684 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 305SB UT WOS:000256197000002 PM 18308949 ER PT J AU Yan, Z Wang, Z Sharova, L Sharov, AA Ling, C Piao, Y Aiba, K Matoba, R Wang, W Ko, MSH AF Yan, Zhijiang Wang, Zhong Sharova, Lioudmila Sharov, Alexei A. Ling, Chen Piao, Yulan Aiba, Kazuhiro Matoba, Ryo Wang, Weidong Ko, Minoru S. H. TI BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells SO STEM CELLS LA English DT Article DE chromatin remodeling; gene targeting; SWI/SNF; embryonic stem cells; DNA microarray; BAF250B; ARID1B ID EXPRESSION; DIFFERENTIATION; MICROARRAY; REVEALS; SUBUNIT; FAMILY; PURIFICATION; SPECIFICITY; DISRUPTION; MUTATION AB Whether SWI/SNF chromatin remodeling complexes play roles in embryonic stem (ES) cells remains unknown. Here we show that SWI/SNF complexes are present in mouse ES cells, and their composition is dynamically regulated upon induction of ES cell differentiation. For example, the SWI/SNF purified from undifferentiated ES cells contains a high level of BAF155 and a low level of BAF170 (both of which are homologs of yeast SWI3 protein), whereas that from differentiated cells contains nearly equal amounts of both. Moreover, the levels of BAF250A and BAF250B decrease during the differentiation of ES cells, whereas that of BRM increases. The altered expression of SWI/SNF components hinted that these complexes could play roles in ES cell maintenance or differentiation. We therefore generated ES cells with biallelic inactivation of BAF250B and found that these cells display a reduced proliferation rate and an abnormal cell cycle. Importantly, these cells are deficient in the self-renewal capacity of undifferentiated ES cells and exhibit certain phenotypes of differentiated cells, including reduced expression of several pluripotency-related genes and increased expression of some differentiation-related genes. These data suggest that the BAF250B-associated SWI/SNF is essential for mouse ES cells to maintain their normal proliferation and pluripotency. The work presented here underscores the importance of SWI/SNF chromatin remodeling complexes in pluripotent stem cells. C1 [Yan, Zhijiang; Ling, Chen; Wang, Weidong] NIA, Genome Instabil & Chromatin Remodeling Sect, Genet Lab, Natl Inst Hlth, Baltimore, MD 21224 USA. [Sharova, Lioudmila; Sharov, Alexei A.; Piao, Yulan; Aiba, Kazuhiro; Matoba, Ryo; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, Natl Inst Hlth, Baltimore, MD 21224 USA. [Wang, Zhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Richard B Simches Res Ctr, Boston, MA USA. RP Wang, W (reprint author), NIA, Genome Instabil & Chromatin Remodeling Sect, Genet Lab, Natl Inst Hlth, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov; kom@mail.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS [Z01 AG000662-07, Z01 AG000650-09] NR 43 TC 87 Z9 89 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 2008 VL 26 IS 5 BP 1155 EP 1165 DI 10.1634/stemcells.2007-0846 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 305SB UT WOS:000256197000008 PM 18323406 ER PT J AU Lo Celso, C Berta, MA Braun, KM Frye, M Lyle, S Zouboulis, CC Watt, FM AF Lo Celso, Cristina Berta, Melanie A. Braun, Kristin M. Frye, Michaela Lyle, Stephen Zouboulis, Christos C. Watt, Fiona M. TI Characterization of bipotential epidermal progenitors derived from human sebaceous gland: Contrasting roles of c-Myc and beta-catenin SO STEM CELLS LA English DT Article DE epidermis; sebaceous glands; cell differentiation; Myc oncogene; beta-catenin ID HAIR FOLLICLE MORPHOGENESIS; MULTIPOTENT STEM-CELLS; ADULT-MOUSE SKIN; TRANSIENT ACTIVATION; DIFFERENTIATION; EXPRESSION; TUMORS; LINEAGE; KERATINOCYTES; HEDGEHOG AB The current belief is that the epidermal sebaceous gland (SG) is maintained by unipotent stem cells that are replenished by multipotent stem cells in the hair follicle (HF) bulge. However, sebocytes can be induced by c-Myc (Myc) activation in interfollicular epidermis (IFE), suggesting the existence of bipotential stem cells. We found that every SZ95 immortalized human sebocyte that underwent clonal growth in culture generated progeny that differentiated into both sebocytes and cells expressing involucrin and cornifin, markers of IFE and HF inner root sheath differentiation. The ability to generate involucrin positive cells was also observed in a new human sebocyte line, Seb-E6E7. SZ95 xenografts differentiated into SG and IFE but not HF. SZ95 cells that expressed involucrin had reduced Myc levels; however, this did not correlate with increased expression of the Myc repressor Blimp1, and Blimp1 expression did not distinguish cells undergoing SG, IFE, or HF differentiation in vivo. Overexpression of Myc stimulated sebocyte differentiation, whereas overexpression of beta-catenin stimulated involucrin and cornifin expression. In transgenic mice simultaneous activation of Myc and beta-catenin revealed mutual antagonism: Myc blocked ectopic HF formation and beta-catenin reduced SG differentiation. Overexpression of the Myc target gene Indian hedgehog did not promote sebocyte differentiation in culture and cyclopamine treatment, while reducing proliferation, did not block Myc induced sebocyte differentiation in vivo. Our studies provide evidence for a bipotential epidermal stem cell population in an in vitro model of human epidermal lineage selection and highlight the importance of Myc as a regulator of sebocyte differentiation. C1 [Berta, Melanie A.; Watt, Fiona M.] CR UK Cambridge Res Inst, La Ka Shing Ctr, Cambridge CB1 ORE, England. [Lo Celso, Cristina] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Braun, Kristin M.] Ctr Cutaneous Res, Inst Cell & Mol Sci, Barts & London Queen Marys Sch Med & Dent, London, England. [Frye, Michaela; Watt, Fiona M.] Wellcome Trust Ctr Stem Cell Res, Cambridge, England. [Lyle, Stephen] Univ Massachusetts, Sch Med, Dept Canc Biol & Pathol, Canc Ctr Tissue Bank, Worcester, MA USA. [Zouboulis, Christos C.] Dessau Med Ctr, Dept Dermatol, Dessau, Germany. [Zouboulis, Christos C.] Dessau Med Ctr, Dept Venereol, Dessau, Germany. [Zouboulis, Christos C.] Dessau Med Ctr, Dept Allergol, Dessau, Germany. [Zouboulis, Christos C.] Dessau Med Ctr, Dept Immunol, Dessau, Germany. RP Watt, FM (reprint author), CR UK Cambridge Res Inst, La Ka Shing Ctr, Robinson Way, Cambridge CB1 ORE, England. EM fiona.watt@cancer.org.uk RI Dr. Zouboulis, Christos/I-4493-2013; OI Dr. Zouboulis, Christos/0000-0003-1646-2608; Lo Celso, Cristina/0000-0002-1163-4207; Watt, Fiona/0000-0001-9151-5154 FU Cancer Research UK; Medical Research Council [G0500502]; NCI NIH HHS [CA-118916] NR 52 TC 54 Z9 56 U1 1 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 2008 VL 26 IS 5 BP 1241 EP 1252 DI 10.1634/stemcells.2007-0651 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 305SB UT WOS:000256197000016 PM 18308950 ER PT J AU Li, N Singh, S Cherukuri, P Li, H Yuan, ZQ Ellisen, LW Wang, BL Robbins, D Direnzo, J AF Li, Na Singh, Samer Cherukuri, Pratima Li, Hua Yuan, Ziqiang Ellisen, Leif W. Wang, Baolin Robbins, David Direnzo, James TI Reciprocal intraepithelial interactions between TP63 and hedgehog signaling regulate quiescence and activation of progenitor elaboration by mammary stem cells SO STEM CELLS LA English DT Article DE mammary stem cells; mammary progenitors; quiescence; TP63; hedgehog; Gli3 ID P53 HOMOLOG; TRANSCRIPTION FACTOR; MYOEPITHELIAL CELLS; P63; GLAND; MOUSE; DIFFERENTIATION; CANCER; LIMB; DELTA-NP63-ALPHA AB TP63 is required for preservation of epithelial regenerative stasis and regulates the activity of diverse genetic pathways; however, specific effector pathways are poorly understood. Data presented here indicate that reciprocal regulatory interactions between hedgehog signaling and TP63 mediate stage-specific effects on proliferation and clonigenicity of separable enriched mammary stem and progenitor fractions. Analysis of Delta N-p63 and TA-p63 indicates segregated expression in mammary stem and progenitor fractions, respectively, demonstrating that differential TP63 promoter selection occurs during elaboration of mammary progenitors by mammary stem cells. This segregation underlies mammary progenitor-specific expression of Indian Hedgehog, identifying it as a binary transcriptional target of TP63. Hedgehog activation in vivo enhances elaboration of mammary progenitors and decreases label retention within mammary stem cell-enriched fractions, suggesting that hedgehog exerts a mitogenic effect on mammary stem cells. Hedgehog signaling promotes differential TP63 promoter usage via disruption of Gli3 or Gli3(R) accumulation, and shRNA-mediated disruption of Gli3 expression was sufficient to alter TP63 promoter usage and enhance clonigenicity of mammary stem cells. Finally, hedgehog signaling is enhanced during pregnancy, where it contributes to expansion of the mammary progenitor compartment. These studies support a model in which hedgehog activates elaboration and differentiation of mammary progenitors via differential TP63 promoter selection and forfeiture of self-renewing capacity. C1 [Li, Na; Singh, Samer; Cherukuri, Pratima; Li, Hua; Yuan, Ziqiang; Robbins, David; Direnzo, James] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. [Ellisen, Leif W.] Massachusetts Gen Hosp, Ctr Canc Res, Dept Med, Boston, MA 02114 USA. [Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Baolin] Weill Cornell Med Coll, Dept Med Genet, New York, NY USA. RP Direnzo, J (reprint author), Dartmouth Med Sch, Dept Pharmacol & Toxicol, 7650 Remsen, Hanover, NH 03755 USA. EM james.direnzo@dartmouth.edu RI Singh, Samer/H-8468-2013 FU NCI NIH HHS [P30 CA023108, R01 CA108539, 5R01CA108539-04)]; NIDCR NIH HHS [R01 DE015945] NR 54 TC 41 Z9 43 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD MAY PY 2008 VL 26 IS 5 BP 1253 EP 1264 DI 10.1634/stemcells.2007-0691 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 305SB UT WOS:000256197000017 PM 18292212 ER PT J AU Parodi, K Bortfeld, T Haberer, T AF Parodi, K. Bortfeld, T. Haberer, T. TI Quantitative comparison between in-beam and offline PET imaging for proton and carbon ion therapeutic irradiation at synchrotron- and cyclotron-based facilities SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 14th Annual Congress of the Deutschen-Gesellschaft-fur-Radioonkologie/25th Annual Conference of the Osterreichischen-Gesellschaft-fur-Radioonkologie-Radiobiologie-und-Mediz inische-Radiophysik CY NOV 15-19, 2006 CL Vienna, AUSTRIA SP Desche Gesell Radioonkol, Osterreich Gesell Radioonkol Radiobiol & Med Radiophys C1 [Parodi, K.; Haberer, T.] Heidelberg Ion Beam Therapy Ctr, Heidelberg, Germany. [Bortfeld, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD MAY PY 2008 VL 184 SU 1 BP 9 EP 9 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 289DH UT WOS:000255034700015 ER PT J AU Schwarte, S Bremer, M Roemermann, D Hoffmann, MW AF Schwarte, S. Bremer, M. Roemermann, D. Hoffmann, M. W. TI Induction of GvHD after allogeneic stem cell transplantation is independent of the dose efficiency: First results of a experimental analysis on mouse model SO STRAHLENTHERAPIE UND ONKOLOGIE LA German DT Meeting Abstract CT 14th Annual Congress of the Deutschen-Gesellschaft-fur-Radioonkologie/25th Annual Conference of the Osterreichischen-Gesellschaft-fur-Radioonkologie-Radiobiologie-und-Mediz inische-Radiophysik CY NOV 15-19, 2006 CL Vienna, AUSTRIA SP Desche Gesell Radioonkol, Osterreich Gesell Radioonkol Radiobiol & Med Radiophys C1 [Schwarte, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Bremer, M.] Hannover Med Sch, Klin Strahlentherapie & Spez, D-30623 Hannover, Germany. [Roemermann, D.; Hoffmann, M. W.] Hannover Med Sch, Viszeral & Transplantat Chirurg Klin, D-30623 Hannover, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD MAY PY 2008 VL 184 SU 1 BP 79 EP 79 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 289DH UT WOS:000255034700206 ER PT J AU Bolling, T Janke, K Glashoerster, M Reinartz, G Ernst, I Wolters, H Brockmann, J Liebsch, NJ Willich, N Konemann, S AF Boelling, T. Janke, K. Glashoerster, M. Reinartz, G. Ernst, I. Wolters, H. Brockmann, J. Liebsch, N. J. Willich, N. Koenemann, S. TI Autologous kidney transplantation for reduction of organ doses of radiotherapy: A case report SO STRAHLENTHERAPIE UND ONKOLOGIE LA German DT Meeting Abstract CT 14th Annual Congress of the Deutschen-Gesellschaft-fur-Radioonkologie/25th Annual Conference of the Osterreichischen-Gesellschaft-fur-Radioonkologie-Radiobiologie-und-Mediz inische-Radiophysik CY NOV 15-19, 2006 CL Vienna, AUSTRIA SP Desche Gesell Radioonkol, Osterreich Gesell Radioonkol Radiobiol & Med Radiophys C1 [Boelling, T.; Janke, K.; Glashoerster, M.; Reinartz, G.; Ernst, I.; Willich, N.; Koenemann, S.] Univ Klinikum Munster, Klin Strahlentherapie, Munster, Germany. [Wolters, H.; Brockmann, J.] Univ Klinikum Munster, Klin Allgemein Chirurg, Munster, Germany. [Liebsch, N. J.] Massachusetts Gen Hosp, Dept Radiotherapy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD MAY PY 2008 VL 184 SU 1 BP 153 EP 154 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 289DH UT WOS:000255034700428 ER PT J AU Ay, H Arsava, EM Rosand, J Furie, KL Singhal, AB Schaefer, PW Wu, O Gonzalez, RG Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, E. Murat Rosand, Jonathan Furie, Karen L. Singhal, Aneesh B. Schaefer, Pamela W. Wu, Ona Gonzalez, R. Gilberto Koroshetz, Walter J. Sorensen, A. Gregory TI Severity of leukoaraiosis and susceptibility to infarct growth in acute stroke SO STROKE LA English DT Article DE acute stroke; cerebral infarct; diffusion-weighted imaging; leukoaraiosis; MRI ID WHITE-MATTER LESIONS; APOLIPOPROTEIN-E POLYMORPHISM; CEREBRAL-ARTERY OCCLUSION; ACUTE ISCHEMIC-STROKE; HYPERINTENSITY VOLUME; BINSWANGERS-DISEASE; INTRACRANIAL VOLUME; KNOCKOUT MICE; FOLLOW-UP; MRI AB Background and Purpose-Leukoaraiosis (LA) is associated with structural and functional vascular changes that may compromise tissue perfusion at the microvascular level. We hypothesized that the volume of LA correlated with the proportion of initially ischemic but eventually infarcted tissue in acute human stroke. Methods-We studied 61 consecutive patients with diffusion-weighted imaging-mean transit time mismatch. All patients were scanned twice within 12 hours of symptom onset and between days 4 and 30. We explored the relationship between the volume of white matter regions with LA on acute images and the proportion of diffusion-weighted imaging-mean transit time mismatch tissue that progressed to infarction (percentage mismatch lost). Results-Bivariate analyses showed a statistically significant correlation between percentage mismatch lost and LA volume (r = 0.33, P<0.01). A linear regression model with percentage mismatch lost as response and LA volume, acute diffusion-weighted imaging and mean transit time volumes, age, admission blood glucose level, admission mean arterial blood pressure, etiologic stroke subtype, time to acute MRI, and time between acute and follow-up imaging as covariates revealed that LA volume was an independent predictor of infarct growth (P = 0.04). The adjusted percentage mismatch lost in the highest quartile of LA volume was 1.9-fold (95% CI: 1.2 to 3.1) greater than the percentage mismatch lost in the lowest quartile. Conclusion-LA volume at the time of acute ischemic stroke is a predictor infarct growth. Because LA is associated with factors that modulate tissue perfusion as well as tissue capacity for handling of ischemia, LA volume appears to be a composite predictive marker for the fate of acutely ischemic tissue. C1 [Ay, Hakan; Arsava, E. Murat; Schaefer, Pamela W.; Wu, Ona; Gonzalez, R. Gilberto; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ay, Hakan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ay, Hakan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke Serv, Charlestown, MA 02129 USA. [Ay, Hakan; Rosand, Jonathan; Furie, Karen L.; Singhal, Aneesh B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Charlestown, MA 02129 USA. [Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02129 USA. [Rosand, Jonathan] Broad Inst MIT, Program Med & Populat Genet, Cambridge, MA USA. [Rosand, Jonathan] Harvard Univ, Cambridge, MA 02138 USA. [Koroshetz, Walter J.] NINDS, NIH, Bethesda, MD 20892 USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013 OI Arsava, Ethem Murat/0000-0002-6527-4139 FU AHRQ HHS [R01-HS11392-02]; NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [R01-NS38477-04] NR 40 TC 75 Z9 82 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2008 VL 39 IS 5 BP 1409 EP 1413 DI 10.1161/STROKEAHA.107.501932 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 294GG UT WOS:000255393100004 PM 18340093 ER PT J AU Shin, HK Nishimura, M Jones, PB Ay, H Boas, DA Moskowitz, MA Ayata, C AF Shin, Hwa Kyoung Nishimura, Masaki Jones, Phillip B. Ay, Hakan Boas, David A. Moskowitz, Michael A. Ayata, Cenk TI Mild induced hypertension improves blood flow and oxygen metabolism in transient focal cerebral ischemia SO STROKE LA English DT Article DE cerebral metabolic rate of oxygen; laser speckle flowmetry; middle cerebral artery occlusion; multispectral reflectance imaging; stroke ID PHENYLEPHRINE-INDUCED HYPERTENSION; LASER SPECKLE FLOWMETRY; ACUTE STROKE; ARTERY OCCLUSION; SUBACUTE STROKE; PERIINFARCT DEPOLARIZATIONS; FUNCTIONAL ACTIVATION; VASCULAR REACTIVITY; BARREL CORTEX; BRAIN EDEMA AB Background and Purpose - In focal ischemic cortex, cerebral blood flow autoregulation is impaired, and perfusion passively follows blood pressure variations. Although it is generally agreed that profound hypotension is harmful in acute stroke, the hemodynamic and metabolic impact of increased blood pressure on the ischemic core and penumbra are less well understood. We, therefore, tested whether pharmacologically induced hypertension improves cerebral blood flow and metabolism and tissue outcome in acute stroke using optical imaging with high spatiotemporal resolution. Methods - Cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen were measured noninvasively using simultaneous multispectral reflectance imaging and laser speckle flowmetry during distal middle cerebral artery occlusion in mice. Hypertension was induced by phenylephrine infusion starting 10 or 60 minutes after ischemia to raise blood pressure by 30% for the duration of ischemia; control groups received saline infusion. Results - Mild induced hypertension rapidly increased cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen in both the core and penumbra and prevented the expansion of cerebral blood flow deficit during 1 hour distal middle cerebral artery occlusion. Induced hypertension also diminished the deleterious effects of periinfarct depolarizations on cerebral blood flow, oxyhemoglobin, and cerebral metabolic rate of oxygen without altering their frequency. Consistent with this, mild induced hypertension reduced infarct volume by 48% without exacerbating tissue swelling when measured 2 days after 1 hour transient distal middle cerebral artery occlusion. Conclusions - Our data suggest that mild induced hypertension increases collateral cerebral blood flow and oxygenation and improves cerebral metabolic rate of oxygen in the core and penumbra, supporting its use as bridging therapy in acute ischemic stroke until arterial recanalization is achieved. C1 [Jones, Phillip B.; Ay, Hakan; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv & Neurosci Intens Care Unit,Dept Neur, Charlestown, MA USA. [Shin, Hwa Kyoung; Nishimura, Masaki; Moskowitz, Michael A.; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Regulat Lab, Charlestown, MA USA. RP Ayata, C (reprint author), Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Moskowitz, Michael/D-9916-2011; OI Jones, Phillip/0000-0003-0525-6323 FU NIBIB NIH HHS [R01EB00790, R01 EB000790-05, R01 EB000790]; NINDS NIH HHS [P01 NS035611, P01 NS035611-14, P01 NS055104, P01 NS055104-03, P01NS055104, P01NS35611, P50 NS010828, P50 NS010828-32, P50NS10828, R01 NS061505] NR 55 TC 57 Z9 59 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2008 VL 39 IS 5 BP 1548 EP 1555 DI 10.1161/STROKEAHA.107.499483 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 294GG UT WOS:000255393100026 PM 18340095 ER PT J AU Wintermark, M Albers, GW Alexandrov, AV Alger, JR Bammer, R Baron, JC Davis, S Demaerschalk, BM Derdeyn, CP Donnan, GA Eastwood, JD Fiebach, JB Fisher, M Furie, KL Goldmakher, GV Hacke, W Kidwell, CS Kloska, SP Kohrmann, M Koroshetz, W Lee, TY Lees, KR Lev, MH Liebeskind, DS Ostergaard, L Powers, WJ Provenzale, J Schellinger, P Silbergleit, R Sorensen, AG Wardlaw, J Warach, S AF Wintermark, Max Albers, Gregory W. Alexandrov, Andrei V. Alger, Jeffry R. Bammer, Roland Baron, Jean-Claude Davis, Stephen Demaerschalk, Bart M. Derdeyn, Colin P. Donnan, Geoffrey A. Eastwood, James D. Fiebach, Jochen B. Fisher, Marc Furie, Karen L. Goldmakher, Gregory V. Hacke, Werner Kidwell, Chelsea S. Kloska, Stephan P. Koehrmann, Martin Koroshetz, Walter Lee, Ting-Yim Lees, Kennedy R. Lev, Michael H. Liebeskind, David S. Ostergaard, Leif Powers, William J. Provenzale, James Schellinger, Peter Silbergleit, Robert Sorensen, Alma Gregory Wardlaw, Joanna Warach, Steven TI Acute stroke imaging research roadmap SO STROKE LA English DT Article DE acute stroke; CT; magnetic resonance; outcomes; thrombolysis; perfusion imaging AB The recent "Advanced Neuroimaging for Acute Stroke Treatment" meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them. C1 [Wintermark, Max] Univ Calif San Francisco, Dept Radiol, Neuroradiol Sect, San Francisco, CA 94143 USA. [Albers, Gregory W.; Bammer, Roland] Stanford Univ, Palo Alto, CA USA. [Alexandrov, Andrei V.] Univ Alabama, Comprehens Stroke Ctr, Birmingham, AL USA. [Alger, Jeffry R.] Univ Calif Los Angeles, Los Angeles, CA USA. [Baron, Jean-Claude] Addenbrookes Hosp, Dept Neurol, Cambridge, England. [Davis, Stephen] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic 3052, Australia. [Demaerschalk, Bart M.] Mayo Clin, Phoenix, AZ USA. [Derdeyn, Colin P.] Washington Univ, St Louis, MO USA. [Donnan, Geoffrey A.] Univ Melbourne, Natl Stroke Res Inst, Parkville, Vic 3052, Australia. [Eastwood, James D.; Provenzale, James] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Fiebach, Jochen B.] Charite Univ Hosp & Berlin, NeuroImaging Ctr BNIC, Berlin, Germany. [Fisher, Marc] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Furie, Karen L.; Goldmakher, Gregory V.; Lev, Michael H.; Sorensen, Alma Gregory] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hacke, Werner] Univ Heidelberg, D-6900 Heidelberg, Germany. [Kidwell, Chelsea S.] Georgetown Univ, Washington Hosp Ctr, Washington, DC USA. [Kloska, Stephan P.] Univ Munster, Dept Clin Radiol, Munster, Germany. [Koehrmann, Martin] Univ Clin, Dept Neurol, Erlangen, Germany. [Koroshetz, Walter; Warach, Steven] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Lees, Kennedy R.] Univ Glasgow, Western Infirm, Univ Dept Med & Therapeut, Glasgow G12 8QQ, Lanark, Scotland. [Liebeskind, David S.] Univ Calif Los Angeles, Los Angeles Stroke Ctr, Los Angeles, CA 90024 USA. [Ostergaard, Leif] Ctr Funct Integrat Neurosci, Dept Neuroradiol, Aarhus, Denmark. [Powers, William J.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Schellinger, Peter] Univ Clin, Dept Neurol, Erlangen, Germany. [Silbergleit, Robert] Univ Michigan, Ann Arbor, MI 48109 USA. [Wardlaw, Joanna] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. RP Wintermark, M (reprint author), Univ Calif San Francisco, Dept Radiol, Neuroradiol Sect, 505 Parnassus Ave,Box 0628, San Francisco, CA 94143 USA. EM Max.Wintermark@radiology.ucsf.edu RI Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008; Lee, Ting-Yim/M-1721-2013; Davis, Stephen/L-5260-2013; OI Derdeyn, Colin/0000-0002-5932-2683; Donnan, Geoffrey/0000-0001-6324-3403; Kaste, Markku/0000-0001-6557-6412; Ostergaard, Leif/0000-0003-2930-6997; Davis, Stephen/0000-0003-0962-2300; Alexandrov, Andrei V/0000-0001-8871-1023; Fiebach, Jochen B./0000-0002-7936-6958; Wintermark, Max/0000-0002-6726-3951; baron, jean-claude/0000-0002-5264-2588 FU NINDS NIH HHS [1R13NS061371-01] NR 0 TC 134 Z9 135 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2008 VL 39 IS 5 BP 1621 EP 1628 DI 10.1161/STROKEAHA.107.512319 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 294GG UT WOS:000255393100043 PM 18403743 ER PT J AU Sogg, S Mori, DL AF Sogg, Stephanie Mori, DeAnna L. TI Revising the Boston Interview: incorporating new knowledge and experience SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Review DE Bariatric surgery; Bariatric psychology; Behavior; Humans; Morbid obesity; Obesity psychology; Obesity surgery; Gastric bypass surgery ID GASTRIC BYPASS-SURGERY; BINGE-EATING DISORDER; QUALITY-OF-LIFE; MORBIDLY OBESE-PATIENTS; WEIGHT-LOSS MAINTENANCE; CHILDHOOD SEXUAL-ABUSE; TERM FOLLOW-UP; BARIATRIC-SURGERY; PSYCHOSOCIAL PREDICTORS; HEALTH-PROFESSIONALS C1 [Sogg, Stephanie] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Mori, DeAnna L.] Boston Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02118 USA. RP Sogg, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Weight Ctr, 50 Staniford Str,4th Floor, Boston, MA 02114 USA. EM ssogg@partners.org NR 113 TC 10 Z9 10 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD MAY-JUN PY 2008 VL 4 IS 3 BP 455 EP 463 DI 10.1016/j.soard.2008.01.007 PG 9 WC Surgery SC Surgery GA 375EV UT WOS:000261097800018 PM 18436484 ER PT J AU Rattner, DW AF Rattner, D. W. TI NOTES: Where have we been and where are we going? SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM drattner@partners.org NR 4 TC 17 Z9 17 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAY PY 2008 VL 22 IS 5 BP 1143 EP 1145 DI 10.1007/s00464-008-9911-2 PG 3 WC Surgery SC Surgery GA 302WD UT WOS:000255999700001 PM 18414948 ER PT J AU Xu, JM Filetti, S Hershman, JM AF Xu, Jimin Filetti, Sebastiano Hershman, Jerome M. TI Expression of hepatocyte nuclear factor-1 alpha mRNA in human anaplastic thyroid cancer cell lines and tumors SO THYROID LA English DT Article ID NICOTINAMIDE N-METHYLTRANSFERASE; GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA; TRANSCRIPTION FACTORS; CLEAR-CELL; HNF-1-ALPHA; HNF-1-BETA; ACTIVATION; INACTIVATION; HETERODIMERS AB Background: Hepatocyte nuclear factor (HNF)-1 alpha and HNF-1 beta are related transcription factors that are mainly expressed in liver cells. Our previous study showed that HNF-1 beta was highly expressed in papillary thyroid cancer cell lines and tumors. HNF-1 alpha mRNA, however, was not detected in differentiated thyroid cancer cell lines. The objective of this study was to determine whether HNF-1 alpha is expressed in dedifferentiated anaplastic thyroid cancer cells. Methods: Total RNA isolated from six anaplastic thyroid cancer cell lines and 38 surgical samples was analyzed for HNF-1 alpha mRNA by conventional reverse-transcription polymerase chain reaction (RT-PCR) or real-time RTPCR. HNF-1 alpha DNA binding activity was measured by gel retardation assay and HNF-1 alpha protein was identified by Western blotting. Results: HNF-1 alpha mRNA was expressed in four of the six anaplastic cell lines. The presence of HNF-1 alpha protein and DNA binding activity was detected in three lines with higher HNF-1 alpha mRNA level. Three cell lines also expressed HNF-1b. HNF-1 alpha transcripts were also detected in five out of six anaplastic tumors, but not in the papillary tumors except one with weak PCR signal. Conclusion: HNF-1 alpha mRNA was detected in high frequency in anaplastic thyroid cancer cell lines and tumors. HNF-1 alpha might play a role in the pathogenesis of anaplastic thyroid cancer. C1 [Hershman, Jerome M.] Univ Calif Los Angeles, Sch Med, Dept Med, Endocrinol & Diabet Div, Los Angeles, CA 90024 USA. [Xu, Jimin] Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. [Filetti, Sebastiano] Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RP Hershman, JM (reprint author), VA Greater Los Angeles Healthcare Syst, Endocrinol Div 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu NR 23 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2008 VL 18 IS 5 BP 533 EP 539 DI 10.1089/thy.2007.0312 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306IF UT WOS:000256240800008 PM 18399756 ER PT J AU Ramaiah, SK Rittling, S AF Ramaiah, Shashi K. Rittling, Susan TI Pathophysiological role of osteopontin in hepatic inflammation, toxicity, and cancer SO TOXICOLOGICAL SCIENCES LA English DT Review DE hepatic injury; hepatic carcinoma; inflammation; neutrophils; osteopontin ID MICE EXPRESSING OSTEOPONTIN; ALCOHOLIC LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; NEUTROPHIL INFILTRATION; KUPFFER CELLS; STRUCTURAL REQUIREMENTS; PROGNOSTIC-SIGNIFICANCE; MACROPHAGE-MIGRATION; BONE SIALOPROTEIN; TUMOR PROGRESSION AB Osteopontin (OPN) is a highly modified integrin-binding extracellular matrix glycophosphoprotein produced by cells of the immune system, epithelial tissue, smooth muscle cells, osteoblasts, and tumor cells. Extensive research has elucidated the pivotal role of OPN in cell signaling that controls inflammation, tumor progression, and metastasis. OPN interaction with the integrin receptors expressed on inflammatory cells through its arginine-glycine-aspartate (RGD) and non-RGD motifs promote migration and adhesion of cells. In the liver, it has been reported that hepatic Kupffer cells secrete OPN facilitating macrophage infiltration into necrotic areas following carbon tetrachloride liver toxicity. Recent work has highlighted the role of OPN in inflammatory liver diseases such as alcoholic and nonalcoholic liver disease and T-cell-mediated hepatitis. The role of OPN in hepatocellular carcinoma (HCC) has also generated significant interest, especially with regards to its role as a prognostic factor. OPN therefore appears to play an important role during liver inflammation and cancer. In this review we will present data to demonstrate the key role played by OPN in mediating hepatic inflammation (neutrophils, monocytes/macrophages, and lymphocytes) and its role in HCC. Greater understanding of the pathophysiologic role of OPN in hepatic inflammation and cancer may enable development of novel inflammation and cancer treatment strategies. C1 [Ramaiah, Shashi K.] Texas A&M Univ, Coll Vet Med, Dept Pathobiol, College Stn, TX 77843 USA. [Rittling, Susan] Forsyth Inst, Boston, MA 02115 USA. RP Ramaiah, SK (reprint author), Texas A&M Univ, Coll Vet Med, Dept Pathobiol, MS 4467, College Stn, TX 77843 USA. EM sramaiah@cvm.tamu.edu FU NIAAA NIH HHS [AA016316]; NIDDK NIH HHS [R01-DK067685] NR 75 TC 80 Z9 89 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2008 VL 103 IS 1 BP 4 EP 13 DI 10.1093/toxsci/kfm246 PG 10 WC Toxicology SC Toxicology GA 287ZH UT WOS:000254955500002 PM 17890765 ER PT J AU Litz, BT Salters-Pedneault, K AF Litz, Brett T. Salters-Pedneault, Kristalyn TI Training Psychologists to Assess, Manage, and Treat Posttraumatic Stress Disorder: An Examination of the National Center for PTSD Behavioral Science Division Training Program SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE training; emotional trauma; stress disorders; posttraumatic AB Most traumatized people do not get the care they need, making the demand for well-trained clinicians, researchers, and supervisors in the trauma field particularly acute. We describe the psychology training program at the Behavioral Science Division of the National Center for PTSD, provide a rationale for the training procedures we employ, and summarize the challenges we face. We suggest that the trauma field needs to establish training guidelines and criterion-based outcomes, and to conduct systematic evaluation of training program efficacy. As a first step toward these goals, we present information about our program and our unique clinical and professional context to assist those who intend to develop training programs and to allow existing training programs to compare and contrast practices. C1 [Litz, Brett T.; Salters-Pedneault, Kristalyn] Natl Ctr PTSD, Boston Dept Vet Affairs Med Ctr, Boston, MA 02130 USA. [Litz, Brett T.; Salters-Pedneault, Kristalyn] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Litz, BT (reprint author), Natl Ctr PTSD, Boston Dept Vet Affairs Med Ctr, 150 South Huntington Ave, Boston, MA 02130 USA. EM brett.litz@va.gov NR 32 TC 4 Z9 4 U1 2 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD MAY PY 2008 VL 2 IS 2 BP 67 EP 74 DI 10.1037/1931-3918.2.2.67 PG 8 WC Psychology, Educational SC Psychology GA V29EC UT WOS:000208730700001 ER PT J AU Darabi, K Makar, RS AF Darabi, Kamran Makar, Robert S. TI Acute hemolysis of transfused A2 red cells by an auto-HI antibody SO TRANSFUSION LA English DT Article ID PREWARMED TESTS; CONTROVERSIES; MEDICINE; IH AB Background: Anti-HI is a common cold autoantibody that complicates serologic testing for underlying alloantibodies and has only rarely been associated with hemolysis. An unusual case of an acute hemolytic transfusion reaction (AHTR) due to an anti-HI autoantibody in a subgroup A1 patient transfused with A2 red blood cells (RBCs) is reported. Case reporot: A 56-year-old man presented to the hospital with anemia and gastrointestinal tract bleeding. His medical history was significant for congestive heart failure, obesity, and pulmonary hypertension. On admission, he was noted to have a hemoglobin level of 7.7 g per dL and therefore transfusion of RBCs was ordered. The patient was group A, D- with a reactive antibody screen due to a cold autoantibody with HI specificity. Further serologic investigation did not detect any alloantibodies. The patient was issued an electronically cross-matched group A, D- unit of RBCs. Several hours after the transfusion, he was found to be producing "Coca-cola"-colored urine with gross hemoglobinemia visible in a posttransfusion specimen, indicating an AHTR. A transfusion reaction investigation excluded mistransfusion or a missed alloantibody and instead revealed that the patient's anti-HI had a high thermal amplitude and that the implicated unit of RBCs was from the A2 subgroup. The patient subsequently tolerated transfusion of a unit of group A1 RBCs through a blood warmer without any signs or symptoms of hemolysis. Conclusion: This case illustrates that anti-HI autoantibodies rarely may behave like alloantibodies and cause AHTRs. Subsequent RBC transfusion with an appropriate ABO group or subgroup through a blood warmer is well tolerated. C1 [Darabi, Kamran; Makar, Robert S.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, 55 Fruit St,GRJ 2-2-6C, Boston, MA 02114 USA. EM rmakar@partners.org NR 21 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2008 VL 48 IS 5 BP 964 EP 968 DI 10.1111/j.1537-2995.2008.01661.x PG 5 WC Hematology SC Hematology GA 295TU UT WOS:000255497600024 PM 18454737 ER PT J AU Saidi, RF Wertheim, JA Ko, DSC Elias, N Martin, H Delmonico, FL Cosimi, AB Kawai, T AF Saidi, R. F. Wertheim, J. A. Ko, D. S. C. Elias, N. Martin, H. Delmonico, F. L. Cosimi, A. B. Kawai, T. TI Impact of donor kidney recovery method on lymphatic complications in kidney transplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 9th Congress of the International-Society-for-Organ-Donatio-and-Procurement/6th Congress of the International-Transplant-Coordinators-Society CY NOV 11-14, 2007 CL Philadelphia, PA SP Int Soc Organ Donat & Procurement, Trnasplant Coordinators Soc ID RENAL-TRANSPLANTATION; LYMPHOCELE AB Introduction. Prolonged lymphatic drainage and lymphocele are undesirable complications following kidney transplantation. We evaluated the impact of kidney recovery methods (deceased donor vs laparoscopic nephrectomy) on the lymphatic complications of the kidney transplant recipients. Method. The incidence of lymphatic complications was retrospectively analyzed in recipients of deceased donor kidneys (DD, n = 62) versus laparoscopically procured kidneys from living donors (LP, n = 61). A drain was placed in the retroperitoneal space in all recipients. The drain was maintained until the output became less than 30 mL/d with no evidence of fluid collection by ultrasound examination. Results. There was no statistically significant difference in the patient demographics (age, gender, and original disease and procedure time) between two groups. The incidence of lymphocele that required therapeutic intervention was comparable in both groups (3.2%). However, the duration of drain placement was significantly longer in the LP group than in the DD group, 8.6 +/- 2.5 days versus 5.4 +/- 2.5 day, respectively (P < .05). Conclusion. The recipients of laparoscopically removed kidneys had a higher incidence of prolonged lymphatic leakage. More meticulous back table preparation may be required in LP kidneys to prevent prolonged lymphatic drainage after kidney transplantation. These observations may indicate that the major source of persistent lymphatic leakage is lymphatics of the allograft rather than severed recipient lymphatics. C1 [Saidi, R. F.; Wertheim, J. A.; Ko, D. S. C.; Elias, N.; Martin, H.; Delmonico, F. L.; Cosimi, A. B.; Kawai, T.] Massachusetts Gen Hosp, Dept Surg, Transplant Ctr, Boston, MA 02214 USA. RP Kawai, T (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplant Ctr, WHT-5-510,55 Fruit St, Boston, MA 02214 USA. EM tkawai@partners.org RI Wertheim, Jason/H-1275-2014 OI Wertheim, Jason/0000-0001-5680-1067 NR 6 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD MAY PY 2008 VL 40 IS 4 BP 1054 EP 1055 DI 10.1016/j.transproceed.2008.04.007 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 316GH UT WOS:000256936900042 PM 18555113 ER PT J AU Besancon, E Guo, SZ Lok, J Tymianski, M Lo, EH AF Besancon, Elaine Guo, Shuzhen Lok, Josephine Tymianski, Michael Lo, Eng H. TI Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID NONSELECTIVE CATION CHANNEL; MEMBRANE NA+/CA2+ EXCHANGER; GAP-JUNCTION HEMICHANNELS; ACUTE ISCHEMIC-STROKE; FOCAL BRAIN ISCHEMIA; ADULT-RAT BRAIN; CEREBRAL-ISCHEMIA; IN-VITRO; HYDROGEN-PEROXIDE; CORTICAL-NEURONS AB The glutamate receptor was one of the most intensely investigated targets for neuroprotection. However, numerous clinical trials of glutamate receptor antagonists for the treatment of stroke were unsuccessful. These failures have led to pessimism in the field. But recent advances could provide hope for the future. This minireview looks beyond the traditional mechanism of glutamate-receptor-driven excitotoxicity to identify other mechanisms of ionic imbalance. These advances include findings implicating sodium-calcium exchangers, hemi-channels, volume-regulated anion channels, acid-sensing channels, transient receptor potential channels, nonselective cation channels and signaling cascades that mediate crosstalk between redundant pathways of cell death. Further in vivo validation of these pathways could ultimately lead us to new therapeutic targets for stroke, trauma and neurodegeneration. C1 [Tymianski, Michael] Univ Toronto, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. [Tymianski, Michael] Univ Toronto, Dept Neurosurg, Toronto, ON M5T 2S8, Canada. [Besancon, Elaine; Guo, Shuzhen; Lok, Josephine; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab, Boston, MA 02129 USA. [Guo, Shuzhen; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. [Guo, Shuzhen; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. [Lok, Josephine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Tymianski, M (reprint author), Univ Toronto, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. EM mike_t@uhnres.utoronto.ca FU NINDS NIH HHS [P50-NS10828, R01-NS37074, R01-NS48422, R01-NS53560, P01-NS55104, R01-NS56458] NR 80 TC 109 Z9 114 U1 1 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2008 VL 29 IS 5 BP 268 EP 275 DI 10.1016/j.tips.2008.02.003 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 312BR UT WOS:000256644600006 PM 18384889 ER PT J AU D'Amico, AV Halabi, S Vollmer, R Loffredo, M McMahon, E Sanford, B Archer, L Vogelzang, NJ Small, EJ Kantoff, PW AF D'Amico, Anthony V. Halabi, Susan Vollmer, Robin Loffredo, Marian McMahon, Elizabeth Sanford, Ben Archer, Laura Vogelzang, Nicholas J. Small, Eric J. Kantoff, Philip W. CA Can Leukemia Grp B TI p53 protein expression status and recurrence in men treated with radiation and androgen suppression therapy for higher-risk prostate cancer: A prospective phase II cancer and leukemia group B study (CALGB 9682) SO UROLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; RADIOTHERAPY; ADENOCARCINOMA; MITOXANTRONE; DEPRIVATION; PREDNISONE; DOCETAXEL; MORTALITY; ADJUVANT AB OBJECTIVES It has been hypothesized that abnormal p53 protein expression is associated with a worse prognosis after radiation (RT) and androgen suppression therapy (AST). This hypothesis was prospectively tested. METHODS Between May 1997 and April 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered on a study evaluating whether the endorectal magnetic resonance imaging (eMRI)-defined change in tumor volume (TV) during neoadjuvant (n) AST was associated with prostate-specific antigen (PSA) outcome. Of these, 141 had sufficient tissue to perform immunohistochemical detection of the p53 protein expression status and 113 had complete eMRI information. Multivariable Cox regression analysis was used to assess whether p53 protein expression status predicted time to PSA failure adjusting for known prognostic factors. RESULTS After a median follow-up of 6.9 years and adjusting for PSA level, Gleason score, clinical stage, and eMRI-defined TV change during nAST, men with abnormal compared with normal p53 expression were at increased risk of PSA failure (hazard ratio [HR]: 2.8; 95% confidence interval [CI]: 1.3-5.9; P = 0.008 for the 141; HR: 2.4; 95% Cl: 1.1-5.4; P = 0.03 for the 113). Adjusted estimates of PSA failure were significantly higher (P = 0.03) in men with abnormal compared with normal p53 expression. At 5 years, these respective estimates were 33% and 18%. CONCLUSIONS Maximizing local control and randomized trials evaluating the impact on survival of adding novel agents to maximal local therapy are warranted in men whose prostate cancer demonstrates abnormal p53 expression. C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Nevada Canc Inst, Las Vegas, NV USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@partners.org FU NCI NIH HHS [CA33601, CA77651, CA77406, CA60138, CA41287, CA03927, CA31946, CA32291] NR 25 TC 13 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2008 VL 71 IS 5 BP 933 EP 937 DI 10.1016/j.urology.2007.11.005 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 302TJ UT WOS:000255992000052 PM 18291508 ER PT J AU Azadzoi, KM Radisavijevic, ZM Siroky, MB AF Azadzoi, Kazern M. Radisavijevic, Ziv M. Siroky, Mike B. TI Effects of ischemia on tachykinin-containing nerves and neurokinin receptors in the rabbit bladder SO UROLOGY LA English DT Article ID GENE-RELATED PEPTIDE; URINARY-BLADDER; IN-VITRO; ACTIVATION; OVERACTIVITY AB OBJECTIVES Our previous studies showed marked changes in efferent nerve structure and reactivity in the ischemic bladder. The goal of this study was to examine the effects of bladder ischemia on tachykinin (TK) containing sensory nerves and neurokinin receptors (NKR) in a rabbit model. METHODS We recorded bladder blood flow and spontaneous contractions in treated animals at week 8 after the induction of iliac arteries atherosclerosis and in age-matched controls. Bladder tissues were processed for Studies of isometric smooth muscle tension in the organ bath, NK2R gene expression using quantitative real-time polymerase chain reaction (PCR), immunohistochemical staining of TK containing nerves and epithelial TK expression, and transmission electron microscopy. RESULTS Atherosclerosis-induced ischemia significantly increased the frequency of spontaneous bladder contractions in vivo. Electrical field stimulation (EFS)-induced smooth muscle contractions were significantly greater in the ischemic tissues. Inhibition of NK1R diminished contractions to low-frequency EFS in control tissues while having no significant effect on the ischemic tissues. In contrast, NK2R inhibition significantly decreased contractions to both low- and high-frequency EFS in the ischemic tissues. Inhibition of NK3R had no significant effect on EFS-induced contractions. Real-time PCR showed a significant increase in NK2R gene expression in the ischemic bladder. The number of TK immunopositive nerves and epithelial TK immunoreactivity were significantly greater in the ischemic bladder. These alterations were associated with marked ultrastructural reactions to bladder ischemia. CONCLUSIONS Alterations of NK2R reactivity and gene expression, increased number of TK immunopositive nerves, and greater epithelial TK immunoreactivity may imply activated bladder afferents to signal ischemic insult. C1 VA Boston Healthcare Syst, Dept Urol, Boston, MA USA. Boston Univ, Sch Med, Dept Urol & Pathol, Boston, MA 02118 USA. RP Azadzoi, KM (reprint author), Bldg 1A,Room 315,150 S Huntington Ave, Boston, MA 02130 USA. EM kazadzoi@bu.edu NR 25 TC 12 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 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2008 VL 71 IS 5 BP 979 EP 983 DI 10.1016/j.urology.2007.11.012 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 302TJ UT WOS:000255992000063 PM 18314167 ER PT J AU Gelfand, JM Kimball, AB Mostow, EN Chiou, CF Patel, V Xia, HA Freundlich, B Stevens, SR AF Gelfand, Joel M. Kimball, Alexa B. Mostow, Eliot N. Chiou, Chiun-Fang Patel, Vaishali Xia, H. Amy Freundlich, Bruce Stevens, Seth R. TI Patient-reported outcomes and health-care resource utilization in patients with psoriasis treated with etanercept: Continuous versus interrupted treatment SO VALUE IN HEALTH LA English DT Article DE clinical trial; etanercept; health-care resource utilization; psoriasis; quality of life; tumor necrosis factor ID QUALITY-OF-LIFE; PHASE-III TRIAL; ATOPIC-DERMATITIS; PLAQUE PSORIASIS; DOUBLE-BLIND; DEPRESSION; THERAPY; MONOTHERAPY; ARTHRITIS; EFFICACY AB Objective: The 24-week Etanercept Assessment of Safety and Effectiveness (EASE) study evaluated the effectiveness and tolerability of continuous versus interrupted etanercept treatment in patients with moderate to severe plaque psoriasis. The objective of this analysis was to assess patient-reported outcomes (PROs) and health-care resource utilization (HRU) data from the EASE study. Methods: Patients received open-label etanercept 50 mg twice weekly for 12 weeks and then received either continued or interrupted (single round of discontinuation and re-treatment with etanercept) etanercept 50 mg once weekly for the second 12 weeks. PROs included the following: 1) the patient global assessments of psoriasis, joint pain, and itching scores; 2) the Dermatology Life Quality Index; 3) the Medical Outcomes Study Short Form 36 vitality domain; 4) the Beck Depression Inventory; 5) the European Quality-of-Life Group Feeling Thermometer; and 6) a patient satisfactionsurvey. HRU was evaluated using the Economic Implications of Psoriasis patient questionnaire. Results: Continuous treatment with etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks produced sustained and clinically important improvements in PROs and reductions in HRU. Reductions in some outcome measures after treatment discontinuation at week 12 were observed in the interrupted group; however, most changes did not revert to baseline levels, consistent with some residual clinical effect, and re-treatment produced improvements similar to week 12 levels. Conclusions: Continuous etanercept treatment provided greater sustained improvements in PROs than interrupted therapy; however, interrupting etanercept therapy, if needed, has predictable and manageable effects. C1 [Chiou, Chiun-Fang; Patel, Vaishali; Xia, H. Amy; Stevens, Seth R.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Gelfand, Joel M.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Gelfand, Joel M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mostow, Eliot N.] Case Western Reserve Univ, Coll Med, Cleveland, OH 44106 USA. [Mostow, Eliot N.] Northeastern Ohio Univ Coll Med & Pharm, Rootstown, OH 44272 USA. [Freundlich, Bruce] Wyeth Pharmaceut, Collegeville, PA USA. RP Stevens, SR (reprint author), Amgen Inc, 1 Amgen Ctr Dr,MS 27-1-D, Thousand Oaks, CA 91320 USA. EM sstevens@amgen.com NR 28 TC 33 Z9 33 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP 400 EP 407 DI 10.1111/j.1524-4733.2007.00251.x PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400006 PM 18489665 ER PT J AU Campbell, R Cooper, GS Gilkeson, GS AF Campbell, R., Jr. Cooper, G. S. Gilkeson, G. S. TI The economic burden of systemic lupus erythematosus among patients of the carolina lupus study early in the course of disease SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Campbell, R., Jr.] Med Univ S Carolina, Charleston, SC 29425 USA. [Cooper, G. S.] US EPA, Washington, DC 20460 USA. [Gilkeson, G. S.] Med Univ S Carolina, Ralph Johnson Med Ctr, Charleston, SC 29425 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A154 EP A154 DI 10.1016/S1098-3015(10)70489-7 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400488 ER PT J AU Cipriano, LE Barth, WH Zaric, GS AF Cipriano, L. E. Barth, W. H. Zaric, G. S. TI The cost-effectiveness of routine screening for vasa previa at 18-20 weeks gestation in Ontario SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Cipriano, L. E.; Barth, W. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zaric, G. S.] Univ Western Ontario, London, ON, Canada. RI Zaric, Gregory/B-7665-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A248 EP A248 DI 10.1016/S1098-3015(10)70784-1 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400783 ER PT J AU Farwell, WR Lawler, E Boulanger, L Cincotta, AH Scranton, RE AF Farwell, W. R. Lawler, E. Boulanger, L. Cincotta, A. H. Scranton, R. E. TI Assessment of safety for bromocriptine: Comparisons of reporting systems and a retrospective cohort study SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Farwell, W. R.; Cincotta, A. H.; Scranton, R. E.] VeroSci LLC, Tiverton, RI USA. [Lawler, E.] VA Boston Healthcare Syst, Boston, MA USA. Abt Associates Inc, Lexington, 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A192 EP A193 DI 10.1016/S1098-3015(10)70612-4 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400611 ER PT J AU Fournier, AA Duh, MS Moyneur, E Dial, E Neary, MP Oh, WK AF Fournier, A. A. Duh, M. S. Moyneur, E. Dial, E. Neary, M. P. Oh, W. K. TI Cost implications of intravenous (IV) bevacizumab treatment in patients with renal cell carcinoma (RCC) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Anal Grp, Boston, MA USA. Anal Grp Inc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. GlaxoSmithKline Inc, Collegeville, PA USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A304 EP A305 DI 10.1016/S1098-3015(10)70960-8 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400959 ER PT J AU Hankin, C Knispel, J Dunn, JD Levin, A Culpepper, L Dougherty, D Koran, L Hollander, E Sheehan, D Black, D Bronstone, A Wang, Z AF Hankin, C. Knispel, J. Dunn, J. D. Levin, A. Culpepper, L. Dougherty, D. Koran, L. Hollander, E. Sheehan, D. Black, D. Bronstone, A. Wang, Z. TI Health care use and costs of patients with "Pure Obsessive-Compulsive Disorder" versus "Pure Depression": 9-year (1997-2006), large-scale, retrospective claims analysis of florida medicaid adult enrollees SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Black, D.] Univ Iowa, Iowa City, IA USA. [Sheehan, D.] Univ S Florida, Coll Med, Tampa, FL USA. [Hollander, E.] Mt Sinai Sch Med, New York, NY USA. [Koran, L.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Dougherty, D.] Massachusetts Gen Hosp, Charlestown, MA USA. [Culpepper, L.] Boston Univ, Med Ctr, Boston, MA USA. [Levin, A.] Hlth Plus, Bronx, NY USA. [Dunn, J. D.] SelectHlth, Salt Lake City, UT USA. [Knispel, J.] Humana, Singer Isl, FL USA. [Hankin, C.; Bronstone, A.; Wang, Z.] BioMedEcon, Moss Beach, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A116 EP A116 DI 10.1016/S1098-3015(10)70374-0 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400373 ER PT J AU Harding, G Roberts, L Spiegel, BM Mody, RR Revicki, D Kahrilas, PJ Camilleri, ML Walter, K AF Harding, G. Roberts, L. Spiegel, B. M. Mody, R. R. Revicki, D. Kahrilas, P. J. Camilleri, M. L. Walter, K. TI Validation of a nocturnal gastroesophageal reflux disease (GERD) symptom severity and impact instrument SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Harding, G.; Roberts, L.; Revicki, D.; Walter, K.] United BioSource Corp, Bethesda, MD USA. [Spiegel, B. M.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Spiegel, B. M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mody, R. R.] TAP Pharmaceut Prod Inc, Lake Forest, IL USA. [Kahrilas, P. J.] Northwestern Univ, Chicago, IL 60611 USA. [Camilleri, M. L.] Mayo Clin, Rochester, MN 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A90 EP A90 DI 10.1016/S1098-3015(10)70293-X PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400292 ER PT J AU Miksad, R Woo, SB Dodson, T Treister, NS Maytal, G August, M Akinyemi, O Bihrle, MM Swan, JS AF Miksad, R. Woo, S. B. Dodson, T. Treister, N. S. Maytal, G. August, M. Akinyemi, O. Bihrle, M. M. Swan, J. S. TI Methods for assessing quality of life in cancer patients experiencing complications: Osteonecrosis of the Jaw pilot study SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Miksad, R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Inst Technol Assessment, Boston, MA 02215 USA. [Woo, S. B.; Treister, N. S.] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [Bihrle, M. M.] Harvard Univ, Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RI Miksad, Rebecca/B-8066-2009 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A78 EP A78 DI 10.1016/S1098-3015(10)70255-2 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400254 ER PT J AU Parikh, NM Singh, H Ashton, C Sharma, M Yadav, R Walder, A Johnson, M AF Parikh, N. M. Singh, H. Ashton, C. Sharma, M. Yadav, R. Walder, A. Johnson, M. TI Patterns of diuretic use in multi-drug anti-hypertensive regimens in the post ALLHAT era SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Parikh, N. M.; Sharma, M.; Yadav, R.] Univ Houston, Houston, TX USA. [Singh, H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Walder, A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Johnson, M.] Univ Houston, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Ashton, C.] Univ Alabama, Birmingham, AL 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A212 EP A212 DI 10.1016/S1098-3015(10)70672-0 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400671 ER PT J AU Reddy, P Fiumara, K Yeh, YC Clapp, M Churchill, W Blackwell, AD AF Reddy, P. Fiumara, K. Yeh, Y. C. Clapp, M. Churchill, W. Blackwell, A. D. TI Effect of bisphosphonates on fractures in postmeopausal women: A systematic literature review SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Reddy, P.; Yeh, Y. C.] Partners Healthcare, Charlestown, MA USA. [Fiumara, K.; Churchill, W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Clapp, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blackwell, A. D.] Global Hlth Ourtcomes, Smayrna, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A254 EP A254 DI 10.1016/S1098-3015(10)70803-2 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400802 ER PT J AU Reddy, P Yeh, YC Clapp, M Churchill, W AF Reddy, P. Yeh, Y. C. Clapp, M. Churchill, W. TI Systematic review of nicardipine in neurovascular conditions SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Reddy, P.; Yeh, Y. C.] Partners Healthcare, Charlestown, MA USA. [Clapp, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Churchill, W.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A186 EP A186 DI 10.1016/S1098-3015(10)70591-X PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400590 ER PT J AU Reddy, P Yeh, Y Clapp, M Churchill, W AF Reddy, P. Yeh, Y. Clapp, M. Churchill, W. TI The Center for Drug Policy: Partners Healthcare SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Reddy, P.; Yeh, Y.] Partners Healthcare, Charlestown, MA USA. [Clapp, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Churchill, W.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A8 EP A9 DI 10.1016/S1098-3015(10)70042-5 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400041 ER PT J AU Sharma, M Deswal, A Henderson, L Desai, R Chitnis, A Petersen, N Ashton, C Johnson, M AF Sharma, M. Deswal, A. Henderson, L. Desai, R. Chitnis, A. Petersen, N. Ashton, C. Johnson, M. TI Effectiveness of combined beta-blocker and ACEI or ARB therapy in chronic heart failure SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Sharma, M.; Desai, R.; Chitnis, A.] Univ Houston, Houston, TX USA. [Deswal, A.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Deswal, A.; Petersen, N.; Johnson, M.] Univ Houston, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Henderson, L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ashton, C.] Univ Alabama, Birmingham, AL 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A16 EP A16 DI 10.1016/S1098-3015(10)70064-4 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400063 ER PT J AU Spiegel, BM Patel, V Chiou, CF Esrailian, E AF Spiegel, B. M. Patel, V Chiou, C. F. Esrailian, E. TI Using cost-utility analysis to assess the budget impact of biologics for the treatment of psoriasis (PSO) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Spiegel, B. M.; Esrailian, E.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Spiegel, B. M.; Esrailian, E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Patel, V; Chiou, C. F.] Amgen Inc, Thousand Oaks, CA 91320 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A292 EP A292 DI 10.1016/S1098-3015(10)70921-9 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400920 ER PT J AU Wright, DR Wittenberg, E Swan, JS Miksad, R Prosser, L AF Wright, D. R. Wittenberg, E. Swan, J. S. Miksad, R. Prosser, L. TI A review and critique of methods for measuring temporary health states in cost-utility analyses SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Wright, D. R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wright, D. R.] Brandeis Univ, Waltham, MA USA. [Swan, J. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miksad, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Prosser, L.] Harvard Univ, Sch Med, Boston, MA USA. RI Miksad, Rebecca/B-8066-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A177 EP A178 DI 10.1016/S1098-3015(10)70564-7 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400563 ER PT J AU Yeh, YC Reddy, P Clapp, M Churchill, W AF Yeh, Y. C. Reddy, P. Clapp, M. Churchill, W. TI Systematic review of palonosetron in chemotherapy-induced nausea and vomiting SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Yeh, Y. C.; Reddy, P.] Partners Healthcare, Charlestown, MA USA. [Clapp, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Churchill, W.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2008 VL 11 IS 3 BP A54 EP A55 DI 10.1016/S1098-3015(10)70182-0 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 302CC UT WOS:000255945400181 ER PT J AU Seelig, MD Yano, EM Bean-Mayberry, B Lanto, AB Washington, DL AF Seelig, Michelle D. Yano, Elizabeth M. Bean-Mayberry, Bevanne Lanto, Andy B. Washington, Donna L. TI Availability of gynecologic services in the department of veterans affairs SO WOMENS HEALTH ISSUES LA English DT Article ID WOMENS HEALTH-CARE; NATIONAL CENTERS; MEDICAL-CENTER; CLINICS; SATISFACTION; ORGANIZATION; EXCELLENCE; DELIVERY AB Purpose. The optimum approach to providing the Congressionally mandated gender-specific services for which women veterans are eligible is unknown. We evaluated onsite availability of gynecologic services, clinic type and staffing arrangements, and the impact of having a gynecology clinic (GYN) and/or an obstetrician gynecologist (OBGYN) routinely available. Methods. We analyzed data from the 2001 national VHA Survey of Women Veterans Health Programs and Practices (n = 136 sites; response rate, 83%). We assessed availability of gynecologic services, and evaluated differences in availability by clinic type (designated women's health provider in primary care [PC], separate women's health clinic for primary care [WHC], and/or separate GYN) and staffing arrangements (OBGYN routinely involved versus not). Main Findings. Out of 133 sites, 77 sites (58%) offered services through a GYN and 56 sites (42%) did not have GYN. Seventy-two (54%) sites had a WHC. More sites with an OBGYN provided endometrial biopsies (91% vs. 20%), IUD insertion (85% vs. 14%), infertility evaluation (56% vs. 23%), infertility treatment (25% vs. none), gynecologic surgery (65 vs. 28%), p < .01. In comparison to sites without WHC, those with WHC were more likely to offer services onsite: endometrial biopsy odds ratio (OR) 6.0 (95% confidence interval [CI], 2.0-18.1); IUD insertion 4.4 (1.6-12.2); infertility evaluation 2.8 (1.2-6.3); and gynecologic surgery 2.3 (1.0-5.4). Conclusion. As the VA develops strategic plans for accommodating the growing number of women veterans, leaders should consider focusing on establishing WHC for primary care and routine availability of OBGYN or other qualified clinicians, rather than establishing separate GYN. C1 [Seelig, Michelle D.] HSR&D Ctr Excellence, Dept Vet Affairs Puget Sound Healthcare System, Seattle, WA USA. [Yano, Elizabeth M.; Bean-Mayberry, Bevanne; Lanto, Andy B.; Washington, Donna L.] Ctr Study Healthcare Provider Behav, VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. [Bean-Mayberry, Bevanne; Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Seelig, MD (reprint author), Puget Sound Hlth Alliance, 2003 Western Ave,Suite 600, Seattle, WA 98105 USA. EM seelip@mac.com NR 19 TC 19 Z9 19 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 2008 VL 18 IS 3 BP 167 EP 173 DI 10.1016/j.whi.2007.1.2.006 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 303GK UT WOS:000256028800003 PM 18329895 ER PT J AU Jacobson, M Fufa, D Abreu, EL Kevy, S Murray, MM AF Jacobson, May Fufa, Duretti Abreu, Eduardo L. Kevy, Sherwin Murray, Martha M. TI Platelets, but not erythrocytes, significantly affect cytokine release and scaffold contraction in a provisional scaffold model SO WOUND REPAIR AND REGENERATION LA English DT Article ID GROWTH-FACTOR-BETA; ANTERIOR CRUCIATE LIGAMENT; RED-BLOOD-CELLS; FIBROBLAST-MEDIATED CONTRACTION; IN-VITRO; RICH PLASMA; PERIODONTAL-LIGAMENT; BIOMECHANICAL RESPONSE; COLLATERAL LIGAMENT; COLLAGEN GELS AB Platelets and erythrocytes are major components of wound provisional scaffolding. In this study, we hypothesized that the concentration of platelets and erythrocytes would significantly affect fibroblast-mediated contraction of three-dimensional scaffolds or the release of cytokines from the scaffold. To test this hypothesis, human anterior cruciate ligament fibroblasts were cultured in one of four scaffolds: a collagen matrix, a collagen-fibrin matrix containing the same concentration of platelets as whole blood, a collagen-fibrin matrix containing a high platelet concentration, and a collagen-fibrin matrix containing a high platelet concentration and red blood cells. Cytokine release from the four groups of gels and gel contraction were measured over a 10-day period. The results of these assays supported greater cytokine release, fibroblast proliferation, and gel contraction in scaffolds with higher platelet concentration. In contrast, the addition of erythrocytes did not significantly stimulate or suppress scaffold contraction or growth factor release from the provisional scaffolds. We concluded that while platelet concentration can significantly impact cytokine release and scaffold retraction in a provisional scaffold, the inclusion of erythrocytes does not have a significant effect on these same behaviors. Therefore, while platelets may be an important regulator of repair processes after injury, it is less likely that erythrocytes have a similar function. C1 [Fufa, Duretti; Abreu, Eduardo L.; Murray, Martha M.] Harvard Univ, Sch Med, Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Jacobson, May; Kevy, Sherwin] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Murray, MM (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Orthopaed Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM Martha.murray@childrens.harvard.edu FU NIAMS NIH HHS [R01AR054099, K02 AR049346, R01 AR054099] NR 40 TC 24 Z9 24 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAY-JUN PY 2008 VL 16 IS 3 BP 370 EP 378 DI 10.1111/j.1524-475X.2008.00376.x PG 9 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 298DL UT WOS:000255666500007 PM 18471255 ER PT J AU Burkatovskaya, M Castano, AP Demidova-Rice, TN Tegos, GP Hamblin, MR AF Burkatovskaya, Marina Castano, Ana P. Demidova-Rice, Tatiana N. Tegos, George P. Hamblin, Michael R. TI Effect of chitosan acetate bandage on wound healing in infected and noninfected wounds in mice SO WOUND REPAIR AND REGENERATION LA English DT Article ID TARGETED PHOTODYNAMIC THERAPY; IN-VIVO; SILVER; MANAGEMENT; MEMBRANE; IODINE; CHITIN AB HemCon(R) bandage is an engineered chitosan acetate preparation designed as a hemostatic dressing, and is under investigation as a topical antimicrobial dressing. We studied its effects on healing of excisional wounds that were or were not infected with Staphylococcus aureus, in normal mice or mice previously pretreated with cyclophosphamide (CY). CY significantly suppressed wound healing in both the early and later stages, while S. aureus alone significantly stimulated wound healing in the early stages by preventing the initial wound expansion. CY plus S. aureus showed an advantage in early stages by preventing expansion, but a significant slowing of wound healing in later stages. In order to study the conflicting clamping and stimulating effects of chitosan acetate bandage on normal wounds, we removed the bandage from wounds at times after application ranging from 1 hour to 9 days. Three days application gave the earliest wound closure, and all application times gave a faster healing slope after removal compared with control wounds. Chitosan acetate bandage reduced the number of inflammatory cells in the wound at days 2 and 4, and had an overall beneficial effect on wound healing especially during the early period where its antimicrobial effect is most important. C1 [Burkatovskaya, Marina; Castano, Ana P.; Demidova-Rice, Tatiana N.; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Castano, Ana P.; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Demidova-Rice, Tatiana N.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Grad Program Cell Mol & Dev Biol, Medford, MA 02155 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-05A1] NR 32 TC 43 Z9 46 U1 0 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAY-JUN PY 2008 VL 16 IS 3 BP 425 EP 431 DI 10.1111/j.1524-475X.2008.00382.x PG 7 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 298DL UT WOS:000255666500013 PM 18471261 ER PT J AU Veves, A AF Veves, Aristidis TI Biology and treatment of diabetic foot ulcers SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Editorial Material C1 [Veves, Aristidis] Harvard Univ, Sch Med, Boston, MA USA. [Veves, Aristidis] Joslin Beth Israel Deaconess Foot Ctr, Boston, MA USA. [Veves, Aristidis] Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. RP Veves, A (reprint author), Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@caregroup.har-vard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD MAY PY 2008 VL 20 IS 5 BP 110 EP 110 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 304PM UT WOS:000256121400001 ER PT J AU Doupis, J Veves, A AF Doupis, John Veves, Aristidis TI Classification, diagnosis, and treatment of diabetic foot ulcers SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Review ID WOUND BED PREPARATION; PLANTAR ULCERS; CLINICAL-TRIAL; MAGGOT THERAPY; DEBRIDEMENT; INFECTIONS; MANAGEMENT; ULCERATION; DRESSINGS; MELLITUS AB The diabetic foot is one of the most significant complications of diabetes and is considered to be a major medical, social, and economic power worldwide. The risk for foot ulceration in patients with diabetes is close to 25% and is also closely related to risk of limb amputation. Diabetic neuropathy, limited joint mobility, micro- and macroangiopathy, and higher plantar pressures have been described as the main risk factors for diabetic foot ulceration. Proper diagnosis and adequate therapeutic treatment are considered the cornerstones to prevention of the limb amputation and preservation of quality of life in patients with diabetes. The following review focuses on the classification, diagnosis, and current trends in the treatment of diabetic foot ulceration. C1 [Veves, Aristidis] Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. [Veves, Aristidis] Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA USA. RP Veves, A (reprint author), Joslin Beth Israel Deaconess Foot Ctr, Palmer 321 A,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu NR 44 TC 7 Z9 8 U1 0 U2 2 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD MAY PY 2008 VL 20 IS 5 BP 117 EP 126 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 304PM UT WOS:000256121400003 PM 25942412 ER PT J AU Dinh, T Veves, A AF Dinh, Thanh Veves, Aristidis TI The influence of gender as a risk factor in diabetic foot ulceration SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article ID LIMITED JOINT MOBILITY; PERIPHERAL NEUROPATHY; MELLITUS; ULCERS; MULTICENTER; THRESHOLDS; PRESSURE; PEOPLE AB Objective. In a previous large, prospective trial, 29% of all patients with diabetes were shown to ulcerate over a 30-month period. The influence of gender on foot ulcers has been controversial, with some studies demonstrating male gender as a risk factor, while other studies have shown no difference. The authors hypothesized that gender may pose a significant risk factor for the development of diabetic i foot ulcers. Methods. A total of 248 patients with diabetes were enrolled in a 30-month, multicenter, prospective study. There were 124 men (M) and 124 women (W). There were no differences between M and W in age (59 +/- 12 years [mean +/- SDI) versus 57 +/- 13), duration of diabetes mellitus (15 +/- 11 years versus 13 +/- 11), or body mass index (BMI) (30.0 +/- 7.7 versus 31.3 +/- 6.2). The following known risk factors for diabetic foot ulceration were measured in both groups: Neuropathy Disability Score (NDS), Vibration Perception Threshold (VPT), Semmes Weinstein Monofilament (SWM), plantar peak foot pressures, and subtalar joint (STJ) and first metatarsal joint (MTPJ mobility. Results. Men had higher NDS (13 +/- 8 versus 8 +/- 7, P < 0.0001), VPT (36 +/- 17 V versus 23 +/- 16, P < 0.0001), SWM (5.9 +/- 1.4 versus 5.9 +/- 1.3, P < 0.0001), and plantar peak foot pressures (6.4 +/- 3.4 kg/cml versus 5.0 +/- 2.3, P < 0.0001), while women had higher MTPJ mobility (69 +/- 24 degrees versus 77 +/- 23, P< 0.0001) and STJ mobility (22 +/- 10 degrees versus 26 +/- 8, P < 0.0001). Plantar-foot ulceration developed in 49 (40%) men compared to 24 (19%) women (P < 0.00011). However, when men and women were analyzed separately univariate logistical regression analysis yielded similar odds ration (OR) in both groups for high NDS (>= 5, M 6. 1, W 8.3), high VPT (>= 25 V, M 6.0, W 8.9), SWM (M 6.6, W 3.7), high foot pressures (>= 6 kg/cm(2), M 2.7, W 3.0), and MTPJ mobility (M 0.96, W 0.97). Conclusiom, While women have a lower risk than men for foot ulceration this appears to be the result of less severe neuropathy, increased joint mobility, and lower foot pressures. However, once neuropathy or other risk factors are present, women were found to have the same risk of developing a foot ulceration as men. Therefore, women with risk factors for foot ulceration should be considered to be at equal risk as men for developing future problems. C1 [Dinh, Thanh; Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Boston, MA 02215 USA. [Veves, Aristidis] Joslin Beth Israel Deaconess Foot Ctr, Boston, MA USA. RP Veves, A (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Microcirculat Lab, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@caregroup.harvard.edu NR 27 TC 5 Z9 5 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD MAY PY 2008 VL 20 IS 5 BP 127 EP 131 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 304PM UT WOS:000256121400004 PM 25942414 ER PT J AU Doupis, J Grigoropoulou, P Voulgari, C Stylianou, A Georga, A Thomakos, P Xiromeritis, K Koliaki, X Katsilambros, N Tentolouris, N AF Doupis, John Grigoropoulou, Penelope Voulgari, Christina Stylianou, Andreas Georga, Anna Thomakos, Petros Xiromeritis, Konstantinos Koliaki, Xrysi Katsilambros, Nicholas Tentolouris, Nicholas TI High rates of comorbid conditions in patients with type 2 diabetes and foot ulcers SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article ID QUALITY-OF-LIFE; CHRONIC KIDNEY-DISEASE; LOWER-EXTREMITY; RISK-FACTORS; CARDIOVASCULAR-DISEASE; ARTERIAL-DISEASE; MORTALITY; ULCERATION; HEALTH; ASSOCIATION AB Background/Aim. Foot ulceration is one of the most important diabetic complications that results in major medical, social, and economic consequences for patients, their families, and society as a whole. Previous studies have shown increased mortality in patients with diabetes with foot ulcers; however, the reason for the high mortality in this group of patients is not known. The aim of this cross-sectional study was to investigate prevalence rates of comorbid condition in patients with diabetes and foot ulcers. Methods. A total of 742 patients with type 2 diabetes (234 with foot ulcers and 508 with out ulcers), consecutively attending the outpatient diabetes and diabetic foot clinics of the authors' hospital were reviewed. Clinical examination was performed to classify ulcers as neuropathic or neuroischemic, microvascular and macrovascular complications, as well as laboratory tests that were reviewed from medical records. Results. Patients with diabetes with and without foot ulcers did not differ significantly in terms of age, sex, smoking habits, glycemic control, and prevalence rates of hypertension, dyslipidemia, and cerebrovascular disease. Known duration of diabetes was longer (P < 0.001), while the values of body mass index (P = 0.03) and creatinine clearance (P = 0.003) were lower in the patients with foot ulcers than in those without ulcers. In addition, prevalence rates of coronary artery disease (P = 0.005), lower extremity arterial disease (P < 0.001), retinopathy (P < 0.001), and nephropathy (P = 0.04), were higher in the patients with foot ulcers compared to those without ulcers. Additionally, duration of diabetes was longer and the prevalence rates of microvascular and macrovascuiar complications as well as hypertension, dyslipidemia, and smoking were much higher in the patients with neuroischemic ulcers in comparison to those with neuropathic ulcers. Conclusion. The high mortality rates in patients with diabetes and foot ulcers may be due to the high prevalence rates of comorbid conditions, especially coronary artery disease and nephropathy. C1 [Doupis, John; Grigoropoulou, Penelope; Voulgari, Christina; Stylianou, Andreas; Georga, Anna; Thomakos, Petros; Xiromeritis, Konstantinos; Koliaki, Xrysi; Katsilambros, Nicholas; Tentolouris, Nicholas] Univ Athens, Sch Med, Laiko Gen Hosp, Dept Propaedeut Med 1, GR-11527 Athens, Greece. RP Doupis, J (reprint author), Harvard Univ, Sch Med, Dept Clin Res, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM john.doupis@joslin.har-vard.edu NR 48 TC 4 Z9 4 U1 1 U2 2 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD MAY PY 2008 VL 20 IS 5 BP 132 EP 138 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 304PM UT WOS:000256121400005 PM 25942413 ER PT J AU Duska, LR Russell, AH AF Duska, Linda R. Russell, Anthony H. TI Treatment of gynecologic cancers: From Halsted to the 21st century SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 [Duska, Linda R.] Massachusetts Gen Hosp, Ctr Canc, Dept Gynecol & Obstet, Boston, MA 02114 USA. [Russell, Anthony H.] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Gynecol & Obstet, Boston, MA 02114 USA. NR 0 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 APR 30 PY 2008 VL 22 IS 5 BP 542 EP 543 PG 2 WC Oncology SC Oncology GA 333SJ UT WOS:000258172400007 ER PT J AU Wang, J Levasseur, DN Orkin, SH AF Wang, Jianlong Levasseur, Dana N. Orkin, Stuart H. TI Requirement of Nanog dimerization for stem cell self-renewal and pluripotency SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryonic stem cells; homeoprotein ID SUSTAINING FACTOR; MOUSE EMBRYOS; ES CELLS; EXPRESSION; TRANSCRIPTION; PROTEIN; HETERODIMERIZATION; DIFFERENTIATION; IDENTIFICATION; HOMEOPROTEIN AB Pluripotency of embryonic stem (ES) cells is maintained by transcription factors that form a highly interconnected protein interaction network surrounding the homeobox protein Nanog. Enforced expression of Nanog in mouse ES (mES) cells promotes self-renewal and alleviates their requirement for leukemia inhibitory factor (LIF). Understanding molecular mechanisms by which Nanog functions should illuminate fundamental properties of stem cells and the process of cellular reprogramming. Previously, we showed that Nanog forms multiple protein complexes in mES cells. Here, we demonstrate that Nanog dimerizes through its C-terminal domain rather than the homeodomain. Dimerization is required for interaction with other pluripotency network proteins. We also show that enforced expression of the Nanog dimer, but not the monomer, functionally replaces wild-type Nanog to sustain LIF-independent self-renewal of ES cells. Our results demonstrate that Nanog-Nanog homodimerization is a critical aspect of its function promoting stem cell pluripotency. C1 [Wang, Jianlong; Levasseur, Dana N.; Orkin, Stuart H.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Childrens Hosp,Div Hematol Oncol, Boston, MA 02115 USA. [Wang, Jianlong; Levasseur, Dana N.; Orkin, Stuart H.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Childrens Hosp,Div Hematol Oncol, Boston, MA 02115 USA. EM orkin@bioodgroup.tch.harvard.edu FU Howard Hughes Medical Institute NR 37 TC 71 Z9 73 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 APR 29 PY 2008 VL 105 IS 17 BP 6326 EP 6331 DI 10.1073/pnas.0802288105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296HM UT WOS:000255534100022 PM 18436640 ER PT J AU Tiwari, S Sharma, N Gill, PS Igarashi, P Kahn, CR Wade, JB Ecelbarger, CMA AF Tiwari, Swasti Sharma, Nikhil Gill, Pritmohinder S. Igarashi, Peter Kahn, C. Ronald Wade, James B. Ecelbarger, Carolyn M. A. TI Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diabetes; metabolic syndrome; natriuresis; volume expansion ID OBESE ZUCKER RATS; KIDNEY-SPECIFIC CADHERIN; VASOPRESSIN ESCAPE; KSP-CADHERIN; COLLECTING DUCT; RABBIT KIDNEY; GENE PROMOTER; HYPERINSULINEMIA; HYPERTENSION; TRANSPORT AB Renal tubule epithelial cells express the insulin receptor (IR); however, their value has not been firmly established. We generated mice with renal epithelial cell-specific knockout of the IR by Cre-recombinase-IoxP recombination using a kidney-specific (Ksp) cadherin promoter. KO mice expressed significantly lower levels of IR mRNA and protein in kidney cortex (49-56% of the WT) and medulla (32-47%) homogenates. Immunofluorescence showed the greatest relative reduction in the thick ascending limb and collecting duct cell types. Body weight, kidney weight, and food and water intakes were not different from WT littermates. However, KO mice had significantly increased basal systolic blood pressure (1313, 15 mm Hg higher) as measured by radiotelemetry. In response to a volume load by gavage (20 ml/kg of body weight, 0.9% NaCl, 15% dextrose), KO mice had impaired natriuresis (37 10 versus 99 +/- 9 mmol of Na+ per 2 h in WT). Furthermore, volume load led to a sustained increase in BP in KO mice only. In contrast, insulin administration i.p. (0.5 units/kg of body weight) resulted in a significant fall in BP in WT, but not in KO mice. To test the role of reduced renal nitric oxide (NO) production in these responses, basal urinary nitrates plus nitrites excretion (UNOx) was measured and found to be 61% lower in KO vs. WT mice. Furthermore, acute insulin increased UNOx by 202% in the WT, relative to a significantly blunted rise (67%) in KO animals. These results illuminate a previously uncharacterized role for renal IR to reduce BP and facilitate sodium and water excretion, possibly via NO production. C1 [Tiwari, Swasti; Sharma, Nikhil; Gill, Pritmohinder S.; Ecelbarger, Carolyn M. A.] Georgetown Univ, Dept Med, Washington, DC 20057 USA. Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Wade, James B.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Tiwari, S (reprint author), Georgetown Univ, Dept Med, Box 571412, Washington, DC 20057 USA. EM st285@georgetown.edu OI Igarashi, Peter/0000-0001-8698-1185 FU NHLBI NIH HHS [HL073193, HL074142, R01 HL073193, R01 HL074142]; NIDDK NIH HHS [DK064872, R21 DK064872, R37 DK042921]; PHS HHS [P3ODKO79328] NR 54 TC 37 Z9 37 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2008 VL 105 IS 17 BP 6469 EP 6474 DI 10.1073/pnas.0711283105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296HM UT WOS:000255534100046 PM 18424559 ER PT J AU Huang, AJ Grady, D Jacoby, VL Blackwell, TL Bauer, DC Sawaya, GF AF Huang, Alison J. Grady, Deborah Jacoby, Vanessa L. Blackwell, Terri L. Bauer, Douglas C. Sawaya, George F. TI Persistent hot flushes in older postmenopausal women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HORMONE REPLACEMENT THERAPY; MENOPAUSAL SYMPTOMS; SERUM-LIPIDS; POPULATION; TRANSITION; FLASHES; STRESS; TRIAL; RISK; AGE AB Objective: To examine the prevalence, natural history, and predictors of hot flushes in older postmenopausal women. Methods:.Prevalence, severity, and 3-year change in severity of hot flushes were assessed by questionnaire in 3167 older postmenopausal women with osteoporosis. Logistic regression was used to identify characteristics associated with symptoms at baseline and after 3 years of follow-up. Results: At baseline, 375 women (11.8%) reported bothersome hot flushes. Women were more likely to have baseline symptoms if they were less educated (odds ratio [ OR], 1.28; 95% confidence interval [CI], 1.06-1.53 per 4-year decrease), more recently menopausal (OR, 1.44; 95% Cl, 1.34-1.56 per 5-year decrease), had previously used estrogen (OR, 1.57; 95% Cl, 1.23-2.00), or had. undergone hysterectomy (OR, 1.51; 95% Cl, 1.14-1.99). Hot flushes were also associated with higher body rnass index (OR, 1.22; 95% Cl, 1.08-1.38 per 1 SD) higher follicle-stimulating hormone levels (OR, 1.34; 95% Cl, 1.20-1. 51 per I SD), lower high-density lipoprotein levels (OR, 1. 17; 95% Cl, 1.03-1.34 per 1SD decrease), vaginal dryness (OR, 1.52; 95% Cl, 1.19-1.93), and trouble sleeping (OR., 2.48; 95% Cl, 1.94-3.16), but not estradiol levels. Of the 375 women with baseline symptoms, 278 contributed 3-year data, and 157 (56.5%) of these women reported persistent symptoms after 3 years. Fewer years since menopause (OR, 1.15; 95% Cl, 1.01-1.32 per 5-year decrease) and trouble sleeping (OR, 1.97; 95% Cl, 1. 19-3.26) were associated with symptom persistence. Conclusions: For a substantial minority of women, hot flushes are a persistent source of discomfort into the late postmenopausal years. Identification of risk factors for hot flushes may help guide evaluation and treatment in this population. C1 [Huang, Alison J.; Grady, Deborah; Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Grady, Deborah; Bauer, Douglas C.; Sawaya, George F.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Jacoby, Vanessa L.; Sawaya, George F.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Grady, Deborah] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Blackwell, Terri L.] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA. RP Huang, AJ (reprint author), 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA. EM ahuang@ucsfmed.org FU NCRR NIH HHS [KL2 RR024130]; NICHD NIH HHS [K12 HD001262] NR 34 TC 41 Z9 42 U1 0 U2 0 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 APR 28 PY 2008 VL 168 IS 8 BP 840 EP 846 DI 10.1001/archinte.168.8.840 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 292EI UT WOS:000255248900010 PM 18443259 ER PT J AU Laios, A O'Toole, S Flavin, R Martin, C Kelly, L Ring, M Finn, SP Barrett, C Loda, M Gleeson, N D'Arcy, T McGuinness, E Sheils, O Sheppard, B Leary, JO AF Laios, Alexandros O'Toole, Sharon Flavin, Richard Martin, Cara Kelly, Lynne Ring, Martina Finn, Stephen P. Barrett, Ciara Loda, Massimo Gleeson, Noreen D'Arcy, Tom McGuinness, Eamonn Sheils, Orla Sheppard, Brian Leary, John O' TI Potential role of miR-9 and miR-223 in recurrent ovarian cancer SO MOLECULAR CANCER LA English DT Article ID MICRORNA EXPRESSION; GENE; TRANSCRIPTION; CELLS; DEREGULATION; SIGNATURES; SURVIVAL; TARGETS; TUMORS; MODEL AB Background: MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease. Results: Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6) in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18) and FFPE serous ovarian tumours (n = 22). Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry. Conclusion: We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer. C1 [Laios, Alexandros; O'Toole, Sharon; Kelly, Lynne; Gleeson, Noreen; D'Arcy, Tom; McGuinness, Eamonn; Sheppard, Brian] Trinity Coll Dublin, St James Hosp, Dept Obstet & Gynaecol, Trinity Ctr Hlth Sci, Dublin 8, Ireland. [Flavin, Richard; Martin, Cara; Ring, Martina; Barrett, Ciara; Sheils, Orla; Leary, John O'] Trinity Coll Dublin, St James Hosp, Dept Histopathol, Trinity Ctr Hlth Sci, Dublin 8, Ireland. [Finn, Stephen P.; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP O'Toole, S (reprint author), Trinity Coll Dublin, St James Hosp, Dept Obstet & Gynaecol, Trinity Ctr Hlth Sci, Dublin 8, Ireland. EM alxlaios2000@yahoo.com; shotoole@tcd.ie; flavinr@tcd.ie; cmartin2@tcd.ie; kellyly@tcd.ie; mring@coombe.ie; finnstev@gmail.com; cbarret@tcd.ie; Massimo_Loda@dfci.harvard.edu; noreengleeson@eircom.net; tsdarcy@indigo.ie; gynaesec@stjames.ie; osheils@tcd.ie; bshepprd@tcd.ie; olearyjj@tcd.ie RI Sheils, Orla Sheils/B-8461-2015; OI Sheils, Orla Sheils/0000-0002-4493-9496; Finn, Stephen/0000-0002-8628-5814; o toole, sharon/0000-0002-9260-3225 NR 45 TC 180 Z9 194 U1 4 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD APR 28 PY 2008 VL 7 AR 35 DI 10.1186/1476-4598-7-35 PG 14 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 305AU UT WOS:000256151000002 PM 18442408 ER PT J AU Denham, S Koppelman, GH Blakey, J Wjst, M Ferreira, MA Hall, IP Sayers, I AF Denham, Samuel Koppelman, Gerard H. Blakey, John Wjst, Matthias Ferreira, Manuel A. Hall, Ian P. Sayers, Ian TI Meta-analysis of genome-wide linkage studies of asthma and related traits SO RESPIRATORY RESEARCH LA English DT Article ID IMMUNOGLOBULIN-E LEVELS; BRONCHIAL HYPERRESPONSIVENESS; SUSCEPTIBILITY ALLELES; POSITIONAL CLONING; SMOKING EXPOSURE; EGEA FAMILIES; FRENCH EGEA; GENE; SCREEN; SEARCH AB Background: Asthma and allergy are complex multifactorial disorders, with both genetic and environmental components determining disease expression. The use of molecular genetics holds great promise for the identification of novel drug targets for the treatment of asthma and allergy. Genome-wide linkage studies have identified a number of potential disease susceptibility loci but replication remains inconsistent. The aim of the current study was to complete a meta-analysis of data from genome-wide linkage studies of asthma and related phenotypes and provide inferences about the consistency of results and to identify novel regions for future gene discovery. Methods: The rank based genome-scan meta-analysis (GSMA) method was used to combine linkage data for asthma and related traits; bronchial hyper-responsiveness (BHR), allergen positive skin prick test (SPT) and total serum Immunoglobulin E (IgE) from nine Caucasian asthma populations. Results: Significant evidence for susceptibility loci was identified for quantitative traits including; BHR (989 pedigrees, n = 4,294) 2p12-q22.1, 6p22.3-p21.1 and 11q24.1-qter, allergen SPT (1,093 pedigrees, n = 4,746) 3p22.1-q22.1, 17p12-q24.3 and total IgE (729 pedigrees, n = 3,224) 5q11.2-q14.3 and 6pter-p22.3. Analysis of the asthma phenotype (1,267 pedigrees, n = 5,832) did not identify any region showing genome-wide significance. Conclusion: This study represents the first linkage meta-analysis to determine the relative contribution of chromosomal regions to the risk of developing asthma and atopy. Several significant results were obtained for quantitative traits but not for asthma confirming the increased phenotype and genetic heterogeneity in asthma. These analyses support the contribution of regions that contain previously identified asthma susceptibility genes and provide the first evidence for susceptibility loci on 5q11.2-q14.3 and 11q24.1-qter. C1 [Denham, Samuel; Blakey, John; Hall, Ian P.; Sayers, Ian] Univ Nottingham Hosp, Div Therapeut & Mol Med, Nottingham NG7 2UH, England. [Koppelman, Gerard H.] Univ Groningen, Univ Med Ctr Groningen, Beatrix Children Hosp, NL-9700 AB Groningen, Netherlands. [Wjst, Matthias] Inst Epidemiol, D-85764 Neuherberg, Germany. [Ferreira, Manuel A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Sayers, I (reprint author), Univ Nottingham Hosp, Div Therapeut & Mol Med, Nottingham NG7 2UH, England. EM mzyysnd@exmail.nottingham.ac.uk; g.h.koppelman@bkk.umcg.nl; John.Blakey@nottingham.ac.uk; m@wjst.de; mferreira@chgr.mgh.harvard.edu; Ian.Hall@nottingham.ac.uk; ian.sayers@nottingham.ac.uk RI Ferreira, Manuel/D-3609-2013; OI Hall, Ian/0000-0001-9933-3216 FU Medical Research Council NR 38 TC 38 Z9 41 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-9921 J9 RESP RES JI Respir. Res. PD APR 28 PY 2008 VL 9 AR 38 DI 10.1186/1465-9921-9-38 PG 12 WC Respiratory System SC Respiratory System GA 305AJ UT WOS:000256149900001 PM 18442398 ER PT J AU Gergely, J AF Gergely, John TI Key events in the history of calcium regulation of striated muscle SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Editorial Material ID TROPONIN-C; SKELETAL-MUSCLE; CONFORMATIONAL TRANSITION; THIN FILAMENT; CONTRACTION; RESOLUTION; PROTEINS; TROPOMYOSIN; COMPLEX; CARP C1 [Gergely, John] Boston Biomed Res Inst, Watertown, MA USA. [Gergely, John] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Gergely, John] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gergely, J (reprint author), Boston Biomed Res Inst, Watertown, MA USA. EM gergely@bbri.org NR 34 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 25 PY 2008 VL 369 IS 1 BP 49 EP 51 DI 10.1016/j.bbre.2007.11.184 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 281DV UT WOS:000254478000008 PM 18157939 ER PT J AU Haasl, RJ Ahmadi, MR Meethal, SV Gleason, CE Johnson, SC Asthana, S Bowen, RL Atwood, CS AF Haasl, Ryan J. Ahmadi, M. Reza Meethal, Sivan Vadakkadath Gleason, Carey E. Johnson, Sterling C. Asthana, Sanjay Bowen, Richard L. Atwood, Craig S. TI A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer's disease in males carrying an apolipoprotein E epsilon 4 allele SO BMC MEDICAL GENETICS LA English DT Article ID MULTIFACTOR-DIMENSIONALITY REDUCTION; GENE-GENE INTERACTIONS; LOGISTIC-REGRESSION; BREAST-CANCER; BETA-SUBUNIT; GONADOTROPIN; MUTATIONS; PROTEIN; PEPTIDE; WOMEN AB Genetic and biochemical studies support the apolipoprotein E (APOE) epsilon 4 allele as a major risk factor for late-onset Alzheimer's disease (AD), though similar to 50% of AD patients do not carry the allele. APOE transports cholesterol for luteinizing hormone (LH)-regulated steroidogenesis, and both LH and neurosteroids have been implicated in the etiology of AD. Since polymorphisms of LH beta-subunit (LHB) and its receptor (LHCGR) have not been tested for their association with AD, we scored AD and age-matched control samples for APOE genotype and 14 polymorphisms of LHB and LHCGR. Thirteen gene-gene interactions between the loci of LHB, LHCGR, and APOE were associated with AD. The most strongly supported of these interactions was between an LHCGR intronic polymorphism (rs4073366; lhcgr2) and APOE in males, which was detected using all three interaction analyses: linkage disequilibrium, multi-dimensionality reduction, and logistic regression. While the APOE e4 allele carried significant risk of AD in males [p = 0.007, odds ratio (OR) = 3.08(95% confidence interval: 1.37, 6.91)], epsilon 4-positive males carrying 1 or 2 C-alleles at lhcgr2 exhibited significantly decreased risk of AD [OR = 0.06(0.01, 0.38); p = 0.003]. This suggests that the lhcgr2 C-allele or a closely linked locus greatly reduces the risk of AD in males carrying an APOE e4 allele. The reversal of risk embodied in this interaction powerfully supports the importance of considering the role gene-gene interactions play in the etiology of complex biological diseases and demonstrates the importance of using multiple analytic methods to detect well-supported gene-gene interactions. C1 [Haasl, Ryan J.; Ahmadi, M. Reza; Meethal, Sivan Vadakkadath; Gleason, Carey E.; Johnson, Sterling C.; Asthana, Sanjay; Atwood, Craig S.] Univ Wisconsin, Sch Med & Publ Hlth, Sect Geriatr & Gerontol, Dept Med, Madison, WI 53705 USA. [Haasl, Ryan J.; Meethal, Sivan Vadakkadath; Gleason, Carey E.; Johnson, Sterling C.; Asthana, Sanjay; Atwood, Craig S.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Bowen, Richard L.] OTB Res, Charleston, SC 29464 USA. [Atwood, Craig S.] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Joondalup, WA 6027, Australia. RP Atwood, CS (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Sect Geriatr & Gerontol, Dept Med, Madison, WI 53705 USA. EM haasl@wisc.edu; mrahmadi@wisc.edu; svm@medicine.wisc.edu; ceg@medicine.wisc.edu; scj@medicine.wisc.edu; sa@medicine.wisc.edu; richard.bowen@yahoo.com; csa@medicine.wisc.edu FU NIA NIH HHS [U24 AG021886] NR 60 TC 10 Z9 11 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD APR 25 PY 2008 VL 9 AR 37 DI 10.1186/1471-2350-9-37 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 307EK UT WOS:000256300600001 PM 18439297 ER PT J AU Belsley, NA Pitman, MB Lauwers, GY Brugge, WR Deshpande, V AF Belsley, Nicole A. Pitman, Martha B. Lauwers, Gregory Y. Brugge, William R. Deshpande, Vikram TI Serous cystadenoma of the pancreas - Limitations and pitfalls of endoscopic ultrasound-guided fine-needle aspiration biopsy SO CANCER CYTOPATHOLOGY LA English DT Article DE serous cystadenoma; pancreatic cyst; fine-needle aspiration biopsy; endoscopic ultrasound; cytology ID CYST FLUID ANALYSIS; LESIONS; EUS; DIAGNOSIS; NEOPLASMS; TUMOR; CT AB BACKGROUND. Expectant management of serous cystadenoma (SCA) of the pancreas requires an accurate preoperative diagnosis. Previously published cytologic diagnostic sensitivities have ranged widely, from 10% to 100%. In the current study, the authors evaluated the diagnostic sensitivity of endoscopic ultrasound (EUS)-guided fine-needle aspiration biopsy (FNAB) and cross-sectional imaging for SCA. METHODS. Group I consisted of 21 histologically confirmed SCAs. Group II (n = 7 lesions) lacked histologic confirmation and was defined by EUS findings that were consistent with SCA and a cyst fluid carcinoembryonic antigen (CEA) level <5 ng/mL. Group III was comprised of 2 nonserous and potentially malignant cysts of the pancreas for which a preoperative diagnosis of SCA was considered. Cross-sectional imaging data were recorded. The smears were evaluated for the presence of serous lining epithelium, gastrointestinal-contaminating epithelium, and inflammatory cells including hemosiderin-laden macrophages. The authors also evaluated the presence of hemosiderin-laden macrophages in a series of 110 FNA specimens from histologically confirmed neoplastic mucinous cysts of the pancreas and 45 pseudocysts of the pancreas. RESULTS. Prospectively among Group I lesions, the appearance on computed tomography (CT) was considered definitive for SCA in 3 of 12 cases (25%). The histologically confirmed SCA cases had CEA levels of <5 ng/mL, except for 1 case for which the CEA level was 176.5 ng/mL. A cytologic diagnosis of SCA was made prospectively in only 1 CT-guided case. Retrospectively, 3 intraoperative FNAs and 1 additional CT-guided aspirate contained rare epithelial cells of a SCA. None of the EUS-guided aspirates demonstrated serous epithelium. Among Group II aspiration specimens, only 1 contained serous epithelial cells. Approximately 52% of the EUS-guided aspirates demonstrated gastrointestinal contamination. This glandular epithelium was categorized as atypical in 2 cases. Hemosiderin-laden macrophages were identified in 43% of the SCAs. Conversely, only 2% of neoplastic mucinous cysts and 9% of pseudocysts produced hemosiderin-laden macrophages in aspirate fluid. CONCLUSIONS. in the current study, serous epithelial cells were identified in <20% of cases. Gastrointestinal-contaminating epithelium, often observed in EUS-guided aspirates, further contributes to difficulties in interpretation. The presence of hemosiderin-laden macrophages as a surrogate marker for SCA requires further study. A preoperative diagnosis of SCA remains a challenge, and an EUS-guided FNAB is unlikely to provide the high level of diagnostic accuracy necessary to permit a nonoperative approach. C1 [Belsley, Nicole A.; Pitman, Martha B.; Lauwers, Gregory Y.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brugge, William R.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 20 TC 62 Z9 63 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2008 VL 114 IS 2 BP 102 EP 110 DI 10.1002/cncr.23346 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 288XI UT WOS:000255019000008 PM 18260088 ER PT J AU Shen, XR Li, HM Ou, Y Tao, WB Dong, A Kong, JL Ji, CN Yu, SN AF Shen, Xianrong Li, Huiming Ou, Yan Tao, Wenbing Dong, Aichun Kong, Jilie Ji, Chaoneng Yu, Shaoning TI The secondary structure of calcineurin regulatory region and conformational change induced by calcium/calmodulin binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMP RECEPTOR PROTEIN; AUTOINHIBITORY DOMAIN; PHOSPHATASE-ACTIVITY; ESCHERICHIA-COLI; CALMODULIN; CALCIUM; NFAT; COMPLEX; FAMILY AB The protein serine/threonine phosphatase calcineurin (CN) is activated by calmodulin (CaM) in response to intracellular calcium mobilization. A widely accepted model for CN activation involves displacement of the CN autoinhibitory peptide (CN467-486) from the active site upon binding of CaM. However, CN activation requires calcium binding both to the low affinity sites of CNB and to CaM, and previous studies did not dissect the individual contributions of CNB and CaM to displacement of the autoinhibitory peptide from the active site. In this work we have produced separate CN fragments corresponding to the CNA regulatory region (CNRR381-521, residues 381-521), the CNA catalytic domain truncated at residue 341, and the CNA-CNB heterodimer with CNA truncated at residue 380 immediately after the CNB binding helix. We show that the separately expressed regulatory region retains its ability to inhibit CN phosphatase activity of the truncated CN341 and CN380 and that the inhibition can be reversed by calcium/CaM binding. Tryptophan fluorescence quenching measurements further indicate that the isolated regulatory region inhibits CN activity by occluding the catalytic site and that CaM binding exposes the catalytic site. The results provide new support for a model in which calcium binding to CNB enables CaM binding to the CNA regulatory region, and CaM binding then instructs an activating conformational change of the regulatory region that does not depend further on CNB. Moreover, the secondary structural content of the CNRR381-521 was tentatively addressed by Fourier transform infrared spectroscopy. The results indicate that the secondary structure of CNRR381-521 fragment is predominantly random coil, but with significant amount of beta-strand and alpha-helix structures. C1 [Shen, Xianrong; Ou, Yan; Tao, Wenbing; Kong, Jilie; Yu, Shaoning] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China. [Shen, Xianrong; Ou, Yan; Tao, Wenbing; Kong, Jilie; Yu, Shaoning] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. [Ji, Chaoneng] Fudan Univ, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China. [Li, Huiming] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Dong, Aichun] Univ No Colorado, Dept Chem & Biochem, Greeley, CO 80639 USA. RP Yu, SN (reprint author), Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China. EM yushaoning@fudan.edu.cn NR 21 TC 18 Z9 19 U1 9 U2 16 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 25 PY 2008 VL 283 IS 17 BP 11407 EP 11413 DI 10.1074/jbc.M708513200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 289PW UT WOS:000255067400038 PM 18296442 ER PT J AU Thaler, JP Cummings, DE AF Thaler, Joshua P. Cummings, David E. TI Metabolism - Food alert SO NATURE LA English DT Editorial Material ID GLUCOSE-HOMEOSTASIS C1 [Thaler, Joshua P.; Cummings, David E.] Univ Washington, Harborview Med Ctr, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. [Thaler, Joshua P.; Cummings, David E.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Thaler, JP (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu NR 11 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 24 PY 2008 VL 452 IS 7190 BP 941 EP 942 DI 10.1038/452941a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291PF UT WOS:000255208600023 PM 18432230 ER PT J AU Munshi, NC Digumarthy, S Rahemtullah, A Taqueti, V Harris, NL Weinger, RS Bazari, H Murali, MR AF Munshi, Nikhil C. Digumarthy, Subba Rahemtullah, Aliyah Taqueti, Viviany Harris, Nancy Lee Weinger, Ronald S. Bazari, Hasan Murali, Mandakolathur R. TI A man with rheumatoid arthritis and lymphadenopathy - Gamma heavy-chain disease and rheumatoid arthritis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MODEL; GENE C1 [Munshi, Nikhil C.] Dana Farber Canc Inst, Boston Vet Affairs Healthcare Syst, Boston, MA 02115 USA. [Munshi, Nikhil C.] Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma, Boston, MA 02115 USA. [Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Rahemtullah, Aliyah] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Digumarthy, Subba] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Rahemtullah, Aliyah] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Boston Vet Affairs Healthcare Syst, Boston, MA 02115 USA. NR 16 TC 12 Z9 12 U1 0 U2 2 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 APR 24 PY 2008 VL 358 IS 17 BP 1838 EP 1848 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 291PL UT WOS:000255209200012 PM 18434654 ER PT J AU Mandinova, A Lefort, K di Vignano, AT Stonely, W Ostano, P Chiorino, G Iwaki, H Nakanishi, J Dotto, GP AF Mandinova, Anna Lefort, Karine di Vignano, Alice Tommasi Stonely, Wesley Ostano, Paola Chiorino, Giovanna Iwaki, Haruhi Nakanishi, Jotaro Dotto, G. Paolo TI The FoxO3a gene is a key negative target of canonical Notch signalling in the keratinocyte UVB response SO EMBO JOURNAL LA English DT Article DE apoptosis; FoxO3a; Notch; p53; UVB ID FORKHEAD TRANSCRIPTION FACTOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; RBP-J-KAPPA; INDUCED APOPTOSIS; TUMOR SUPPRESSION; EPITHELIAL-CELLS; FACTOR RECEPTOR; GROWTH ARREST; HUMAN HOMOLOG; DIFFERENTIATION AB Notch signalling has an important role in skin homeostasis, promoting keratinocyte differentiation and suppressing tumorigenesis. Here we show that this pathway also has an essential anti-apoptotic function in the keratinocyte UVB response. Notch1 expression and activity are significantly induced, in a p53-dependent manner, by UVB exposure of primary keratinocytes as well as intact epidermis of both mouse and human origin. The apoptotic response to UVB is increased by deletion of the Notch1 gene or down-modulation of Notch signalling by pharmacological inhibition or genetic suppression of ' canonical' Notch/CSL/MAML1-dependent transcription. Conversely, Notch activation protects keratinocytes against apoptosis through a mechanism that is not linked to Notch-induced cell cycle withdrawal or NF-kappa B activation. Rather, transcription of FoxO3a, a key pro-apoptotic gene, is under direct negative control of Notch/HERP transcription in keratinocytes, and upregulation of this gene accounts for the increased susceptibility to UVB of cells with suppressed Notch signalling. Thus, the canonical Notch/HERP pathway functions as a protective anti-apoptotic mechanism in keratinocytes through negative control of FoxO3a expression. C1 [Lefort, Karine; Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Mandinova, Anna; di Vignano, Alice Tommasi; Stonely, Wesley; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lefort, Karine; Dotto, G. Paolo] Lab Canc Pharmacogenom, Biella, Italy. [Iwaki, Haruhi; Nakanishi, Jotaro] Shiseido Life Sci Res Ctr, Kanazawa Ku, Yokohama, Kanagawa, Japan. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, Chemin Boveresses 155, CH-1066 Epalinges, Switzerland. EM Gian-Paolo.Dotto@unil.ch RI Chiorino, Giovanna/K-5037-2016 OI Chiorino, Giovanna/0000-0002-9502-6400 FU NCI NIH HHS [CA16038, CA73796, P01 CA016038, R01 CA073796]; NIAMS NIH HHS [AR39190, R01 AR039190] NR 69 TC 44 Z9 45 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 23 PY 2008 VL 27 IS 8 BP 1243 EP 1254 DI 10.1038/emboj.2008.45 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292UL UT WOS:000255291500006 PM 18388864 ER PT J AU Ajani, JA Winter, KA Gunderson, LL Pedersen, J Benson, AB Thomas, CR Mayer, RJ Haddock, MG Rich, TA Willett, C AF Ajani, Jaffer A. Winter, Kathryn A. Gunderson, Leonard L. Pedersen, John Benson, Al B., III Thomas, Charles R., Jr. Mayer, Robert J. Haddock, Michael G. Rich, Tyvin A. Willett, Christopher TI Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; DOSE RADIATION-THERAPY; EPIDERMOID CARCINOMA; CHEMORADIATION THERAPY; EUROPEAN-ORGANIZATION; CLINICAL-TRIALS; ONCOLOGY-GROUP; PHASE-II; CANCER; 5-FLUOROURACIL AB Context Chemoradiation as definitive therapy is the preferred primary therapy for patients with anal canal carcinoma; however, the 5- year disease- free survival rate from concurrent fluorouracil/ mitomycin and radiation is only approximately 65%. Objective To compare the efficacy of cisplatin- based ( experimental) therapy vs mitomycin-based ( standard) therapy in treatment of anal canal carcinoma. Design, Setting, and Participants US Gastrointestinal Intergroup trial RTOG 9811, a multicenter, phase 3, randomized controlled trial comparing treatment with fluorouracil plus mitomycin and radiotherapy vs treatment with fluorouracil plus cisplatin and radiotherapy in 682 patients with anal canal carcinoma enrolled between October 31, 1998, and June 27, 2005. Stratifications included sex, clinical nodal status, and tumor diameter. Intervention Participants were randomly assigned to 1 of 2 intervention groups: ( 1) the mitomycin- based group ( n= 341), who received fluorouracil ( 1000 mg/ m(2) on days 1- 4 and 29- 32) plus mitomycin ( 10 mg/ m2 on days 1 and 29) and radiotherapy ( 45- 59 Gy) or ( 2) the cisplatin- based group ( n= 341), who received fluorouracil ( 1000 mg/ m2 on days 1- 4, 29- 32, 57- 60, and 85- 88) plus cisplatin ( 75 mg/ m2 on days 1, 29, 57, and 85) and radiotherapy ( 45- 59 Gy; start day= day 57). Main Outcome Measures The primary end point was 5- year disease- free survival; secondary end points were overall survival and time to relapse. Results A total of 644 patients were assessable. The median follow- up for all patients was 2.51 years. Median age was 55 years, 69% were women, 27% had a tumor diameter greater than 5 cm, and 26% had clinically positive nodes. The 5- year disease- free survival rate was 60% ( 95% confidence interval [ CI], 53%- 67%) in the mitomycin- based group and 54% ( 95% CI, 46%- 60%) in the cisplatin- based group ( P=. 17). The 5- year overall survival rate was75%( 95% CI, 67%- 81%) in the mitomycin-based group and 70% ( 95% CI, 63%- 76%) in the cisplatin- based group ( P=. 10). The 5- year local- regional recurrence and distant metastasis rates were 25% ( 95% CI, 20%-30%) and 15% ( 95% CI, 10%- 20%), respectively, for mitomycin- based treatment and 33%( 95% CI, 27%- 40%) and 19%( 95% CI, 14%- 24%), respectively, for cisplatin-based treatment. The cumulative rate of colostomy was significantly better for mitomycin-based than cisplatin- based treatment ( 10% vs 19%; P=. 02). Severe hematologic toxicity was worse with mitomycin- based treatment ( P <. 001). Conclusions In this population of patients with anal canal carcinoma, cisplatin-based therapy failed to improve disease- free- survival compared with mitomycinbased therapy, but cisplatin- based therapy resulted in a significantly worse colostomy rate. These findings do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma. Trial Registration clinicaltrials. gov Identifier: NCT00003596. C1 [Ajani, Jaffer A.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Winter, Kathryn A.] Radiat Therapy Oncol Grp, Philadelphia, PA USA. [Gunderson, Leonard L.] Mayo Clin, Scottsdale, AZ USA. [Pedersen, John] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Benson, Al B., III] Northwestern Univ, Chicago, IL 60611 USA. [Thomas, Charles R., Jr.] Univ Oregon, Portland, OR USA. [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haddock, Michael G.] Mayo Clin, Rochester, MN USA. [Rich, Tyvin A.] Univ Virginia, Charlottesville, VA USA. [Willett, Christopher] Duke Univ, Durham, NC USA. RP Ajani, JA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd,Mail Stop 426, Houston, TX 77030 USA. EM jajani@mdanderson.org FU NCI NIH HHS [U10 CA37422, U10 CA21661, U10 CA32115] NR 34 TC 330 Z9 335 U1 0 U2 11 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 APR 23 PY 2008 VL 299 IS 16 BP 1914 EP 1921 DI 10.1001/jama.299.16.1914 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 291AD UT WOS:000255163800025 PM 18430910 ER PT J AU Solomon, SD Wittes, J Finn, PV Fowler, R Viner, J Bertagnolli, MM Arber, N Levin, B Meinert, CL Martin, B Pater, JL Goss, PE Lance, P Obara, S Chew, EY Kim, J Arndt, G Hawk, E AF Solomon, Scott D. Wittes, Janet Finn, Peter V. Fowler, Robert Viner, Jaye Bertagnolli, Monica M. Arber, Nadir Levin, Bernard Meinert, Curtis L. Martin, Barbara Pater, Joseph L. Goss, Paul E. Lance, Peter Obara, Stefanie Chew, Emily Y. Kim, Jonghyeon Arndt, Gretchen Hawk, Ernest CA Cross Trial Safety Assessment Grp TI Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials - The cross trial safety analysis SO CIRCULATION LA English DT Article DE drugs; cardiovascular diseases; cyclooxygenase 2 inhibitors ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACUTE MYOCARDIAL-INFARCTION; CYCLOOXYGENASE-2 INHIBITORS; SELECTIVE INHIBITORS; COLORECTAL ADENOMAS; COX-2; PREVENTION; EVENTS; PREDICTION; DISEASE AB Background-Observational studies and randomized trials have reported increased cardiovascular risk associated with cyclooxygenase-2 inhibitors. Prior placebo-controlled randomized studies had limited ability to assess the relationship of either celecoxib dose or pretreatment cardiovascular status to risk associated with celecoxib. Our aim was to assess the cardiovascular risk associated with celecoxib in 3 dose regimens and to assess the relationship between baseline cardiovascular risk and effect of celecoxib on cardiovascular events. Methods and Results-We performed a patient-level pooled analysis of adjudicated data from 7950 patients in 6 placebo-controlled trials comparing celecoxib with placebo for conditions other than arthritis with a planned follow-up of at least 3 years. Patients were administered celecoxib in 3 dose regimens: 400 mg QD, 200 mg BID, or 400 mg BID. From the pooled data, we calculated a hazard ratio for all dose regimens combined and individual hazard ratios for each dose regimen and examined whether celecoxib-related risk was associated with baseline cardiovascular risk. The primary end point was the combination of cardiovascular death, myocardial infarction, stroke, heart failure, or thromboembolic event. With 16 070 patient-years of follow-up, the hazard ratio for the composite end point combining the tested doses was 1.6 (95% CI, 1.1 to 2.3). The risk, which increased with dose regimen (P=0.0005), was lowest for the 400-mg-QD dose (hazard ratio, 1.1; 95% CI, 0.6 to 2.0), intermediate for the 200-mg-BID dose (hazard ratio, 1.8; 95% CI, 1.1 to 3.1), and highest for the 400-mg-BID dose (hazard ratio, 3.1; 95% CI, 1.5 to 6.1). Patients at highest baseline risk demonstrated disproportionately greater risk of celecoxib-related adverse events (P for interaction=0.034). Conclusions-We observed evidence of differential cardiovascular risk as a function of celecoxib dose regimen and baseline cardiovascular risk. By further clarifying the extent of celecoxib-related cardiovascular risk, these findings may help guide treatment decisions for patients who derive clinical benefit from selective cyclooxygenase-2 inhibition. C1 [Solomon, Scott D.; Finn, Peter V.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wittes, Janet; Fowler, Robert; Arndt, Gretchen] Stat Collaborat Inc, Washington, DC USA. [Viner, Jaye; Hawk, Ernest] NCI, Bethesda, MD 20892 USA. [Levin, Bernard] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Houston, TX USA. [Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. [Meinert, Curtis L.; Martin, Barbara] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lance, Peter; Obara, Stefanie] Arizona Canc Ctr, Tucson, AZ USA. [Kim, Jonghyeon] EMMES Corp, Rockville, MD USA. [Pater, Joseph L.] Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. [Arber, Nadir] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Solomon, Scott/I-5789-2013 FU Intramural NIH HHS [Z99 EY999999] NR 30 TC 210 Z9 215 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 22 PY 2008 VL 117 IS 16 BP 2104 EP 2113 DI 10.1161/CIRCULATIONAHA.108.764530 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 291UR UT WOS:000255222900009 PM 18378608 ER PT J AU Bowman, CC Sobo, EJ Asch, SM Gifford, AL AF Bowman, Candice C. Sobo, Elisa J. Asch, Steven M. Gifford, Allen L. CA Hiv Hepatitis Quality Enhancement TI Measuring persistence of implementation: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE; QUALITY-IMPROVEMENT; ADOLESCENT HEALTH; PROGRAMS; SUSTAINABILITY; INNOVATIONS; PREVENTION; INTERVENTION; SERVICES AB As more quality improvement programs are implemented to achieve gains in performance, the need to evaluate their lasting effects has become increasingly evident. However, such long-term follow-up evaluations are scarce in healthcare implementation science, being largely relegated to the "need for further research" section of most project write-ups. This article explores the variety of conceptualizations of implementation sustainability, as well as behavioral and organizational factors that influence the maintenance of gains. It highlights the finer points of design considerations and draws on our own experiences with measuring sustainability, framed within the rich theoretical and empirical contributions of others. In addition, recommendations are made for designing sustainability analyses. This article is one in a Series of articles documenting implementation science frameworks and approaches developed by the U. S. Department of Veterans Affairs Quality Enhancement Research Initiative (QUERI). C1 [Bowman, Candice C.] VA San Diego Healthcare Syst, Hlth Serv Res & Dev, San Diego, CA USA. [Sobo, Elisa J.] San Diego State Univ, Dept Anthropol, San Diego, CA 92182 USA. [Asch, Steven M.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Gifford, Allen L.] VA New England Healthcare Syst, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Bowman, CC (reprint author), VA San Diego Healthcare Syst, Hlth Serv Res & Dev, San Diego, CA USA. EM candybowman@gmail.com; esobo@mail.sdsu.edu; steven.asch@va.gov; agifford@bu.edu FU VA Health Services Research and Development [01-090] FX The authors would like to acknowledge all the members of the QUERI-HIV/Hepatitis project team who contributed to the many aspects of both the main project and the supplemental evaluation. This project was funded by a VA Health Services Research and Development grant (HIT 01-090, Improving HIV Care Quality). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 55 TC 34 Z9 34 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD APR 22 PY 2008 VL 3 AR 21 DI 10.1186/1748-5908-3-21 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QW UT WOS:000265150200002 PM 18430200 ER PT J AU Smith, MW Barnett, PG AF Smith, Mark W. Barnett, Paul G. TI The role of economics in the QUERI program: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID COST-EFFECTIVENESS ANALYSIS; CARE DECISION-MAKING; ISPOR TASK-FORCE; GUIDELINE IMPLEMENTATION; INFLUENZA VACCINATION; HEALTH-PROFESSIONALS; VETERANS; STRATEGIES; RECOMMENDATIONS; INTERVENTIONS AB Background: The United States (U. S.) Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has implemented economic analyses in single-site and multi-site clinical trials. To date, no one has reviewed whether the QUERI Centers are taking an optimal approach to doing so. Consistent with the continuous learning culture of the QUERI Program, this paper provides such a reflection. Methods: We present a case study of QUERI as an example of how economic considerations can and should be integrated into implementation research within both single and multi-site studies. We review theoretical and applied cost research in implementation studies outside and within VA. We also present a critique of the use of economic research within the QUERI program. Results: Economic evaluation is a key element of implementation research. QUERI has contributed many developments in the field of implementation but has only recently begun multisite implementation trials across multiple regions within the national VA healthcare system. These trials are unusual in their emphasis on developing detailed costs of implementation, as well as in the use of business case analyses (budget impact analyses). Conclusion: Economics appears to play an important role in QUERI implementation studies, only after implementation has reached the stage of multi-site trials. Economic analysis could better inform the choice of which clinical best practices to implement and the choice of implementation interventions to employ. QUERI economics also would benefit from research on costing methods and development of widely accepted international standards for implementation economics. C1 [Smith, Mark W.; Barnett, Paul G.] US Dept Vet Affairs, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Smith, Mark W.; Barnett, Paul G.] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA. [Barnett, Paul G.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. RP Smith, MW (reprint author), US Dept Vet Affairs, Hlth Econ Resource Ctr, Menlo Pk, CA USA. EM mark.smith9@va.gov; paul.barnett@va.gov RI Smith, Mark/G-1522-2012 OI Smith, Mark/0000-0002-4582-9088 FU VA Health Services Research and Development Service [TRA 05-081] FX The QUERI Program of the VA Health Services Research and Development Service funded this research through grant TRA 05-081. We gratefully acknowledge comments from the editors and referees, and the research assistance of Andrea Shane. The findings and conclusions in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 51 TC 7 Z9 7 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD APR 22 PY 2008 VL 3 AR 20 DI 10.1186/1748-5908-3-20 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QW UT WOS:000265150200001 PM 18430199 ER PT J AU Wallace, CM Legro, MW AF Wallace, Carolyn M. Legro, Marcia W. TI Using formative evaluation in an implementation project to increase vaccination rates in high-risk veterans: QUERI Series SO IMPLEMENTATION SCIENCE LA English DT Article ID INFLUENZA VACCINATION; QUALITY AB Background: Implementation of research into practice in health care systems is a challenging and often unsuccessful endeavor. The United States Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) research teams include formative evaluations (FE) in their action-oriented VA implementation projects to identify critical information about the processes of implementation that can guide adjustments to project activities, in order to better meet project goals. This article describes the development and use of FE in an action-oriented implementation research project. Methods: This two-year action-oriented implementation research project was conducted at 23 VA Spinal Cord Injury (SCI) Centers, and targeted patients, staff and the system of care, such as administration and information technology. Data for FE were collected by electronic and paper surveys, semi-structured and open-ended interviews, notes during conference calls, and exchange of e-mail messages. Specific questions were developed for each intervention (designed to improve vaccination rates for influenza in veterans with spinal cord injury and disorder); informants were selected for their knowledge of interventions and their use in SCI Centers. Results: Data from FE were compiled separately for each intervention to describe barriers to progress and guide adjustments to implementation activities. These data addressed the processes of implementing the interventions, problem-solving activities and the status of interventions at SCI Centers. Conclusion: Formative evaluations provided the project team with a broad view of the processes of implementing multi-targeted interventions as well as the evolving status of the related best practice. Using FE was useful, although the challenges of conducting FE for non-field researchers should be addressed. Work is needed to develop methods for conducting FE across multiple sites, as well as acknowledging variations in local contexts that affect implementation of interventions. C1 [Wallace, Carolyn M.; Legro, Marcia W.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. RP Wallace, CM (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. EM Carolyn.Wallace1@va.gov; mwlegro@msn.com FU Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service (HSRD) [SCT 01-169]; U. S. Department of Veterans Affairs FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (HSR&D), SCT 01-169. The authors' salaries were supported by the Department of Veterans Affairs during this project. The findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily represent the views of the U. S. Department of Veterans Affairs. NR 10 TC 6 Z9 6 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD APR 22 PY 2008 VL 3 AR 22 DI 10.1186/1748-5908-3-22 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 432QW UT WOS:000265150200003 PM 18430201 ER PT J AU Haddad, GE Saunders, LJ Crosby, SD Carles, M del Monte, F King, K Bristow, MR Spinale, FG Macgillivray, TE Semigran, MJ Dec, GW Williams, SA Hajjar, RJ Gwathmey, JK AF Haddad, Georges E. Saunders, Lori J. Crosby, Seth D. Carles, Maria del Monte, Federica King, Kindra Bristow, Michael R. Spinale, Francis G. Macgillivray, Thomas E. Semigran, Marc J. Dec, G. William Williams, Steven A. Hajjar, Roger J. Gwathmey, Judith K. TI Human cardiac-specific cDNA array for idiopathic dilated cardiomyopathy: sex-related differences SO PHYSIOLOGICAL GENOMICS LA English DT Article DE gene expression; heart failure; IDCM markers ID CONGESTIVE-HEART-FAILURE; DENSITY OLIGONUCLEOTIDE ARRAYS; GENE-EXPRESSION ANALYSIS; MYOCARDIAL-INFARCTION; CREATINE-KINASE; ENERGY RESERVE; MICE LACKING; HUMAN ATRIAL; MICROARRAYS; METABOLISM AB Idiopathic dilated cardiomyopathy (IDCM) constitutes a large portion of patients with heart failure of unknown etiology. Up to 50% of all transplant recipients carry this clinical diagnosis. Female-specific gene expression in IDCM has not been explored. We report sex-related differences in the gene expression profile of ventricular myocardium from patients undergoing cardiac transplantation. We produced and sequenced subtractive cDNA libraries, using human left ventricular myocardium obtained from male transplant recipients with IDCM and nonfailing human heart donors. With the resulting sequence data, we generated a custom human heart failure microarray for IDCM containing 1,145 cardiac-specific oligonucleotide probes. This array was used to characterize RNA samples from female IDCM transplant recipients. We identified a female gene expression pattern that consists of 37 upregulated genes and 18 downregulated genes associated with IDCM. Upon functional analysis of the gene expression pattern, deregulated genes unique to female IDCM were those that are involved in energy metabolism and regulation of transcription and translation. For male patients we found deregulation of genes related to muscular contraction. These data suggest that 1) the gene expression pattern we have detected for IDCM may be specific for this disease and 2) there is a sex-specific profile to IDCM. Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men. C1 [Gwathmey, Judith K.] Boston Univ, Sch Med, Cambridge, MA 02138 USA. [Haddad, Georges E.] Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. [Saunders, Lori J.; Carles, Maria; King, Kindra; Gwathmey, Judith K.] Gwathmey Inc, Cambridge, MA USA. [Crosby, Seth D.] Washington Univ, Sch Med, Microarray Core Facil, St Louis, MO USA. [del Monte, Federica] Beth Israel Deaconess Med Ctr, Cardiovasc Res Ctr, Boston, MA 02215 USA. [Bristow, Michael R.] Univ Colorado, Hlth Sci Ctr, Sch Med, Div Cardiol, Denver, CO 80262 USA. [Spinale, Francis G.] Med Univ S Carolina, Charleston, SC 29425 USA. [Semigran, Marc J.; Dec, G. William] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Williams, Steven A.] Smith Coll, Dept Sci Biol, Northampton, MA 01063 USA. [Hajjar, Roger J.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY USA. RP Gwathmey, JK (reprint author), Boston Univ, Sch Med, 763 Concord Ave,Bldg E, Cambridge, MA 02138 USA. EM gwathmey@earthlink.net RI bristow, michael/G-7850-2011 FU NHLBI NIH HHS [R43-HL-67516, R44-HL-67516]; NIAAA NIH HHS [R43-AA-066758, R44-AA-066758]; NIGMS NIH HHS [S06 GM008016] NR 71 TC 21 Z9 22 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR 22 PY 2008 VL 33 IS 2 BP 267 EP 277 DI 10.1152/physiolgenomics.00265.2007 PG 11 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 314OP UT WOS:000256819000013 PM 18303083 ER PT J AU Kim, C Wilcox-Adelman, S Sano, Y Tang, WJ Collier, RJ Park, JM AF Kim, Chun Wilcox-Adelman, Sarah Sano, Yasuyo Tang, Wei-Jen Collier, R. John Park, Jin Mo TI Inflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE edema toxin; macrophage; Bacillus anthracis ID PROTECTIVE ANTIGEN; DENDRITIC CELLS; CONNEXIN43 EXPRESSION; LETHAL TOXIN; MACROPHAGE; RESOLUTION; CHEMOTAXIS; MICE; DISSEMINATION; TRANSLOCATION AB Bacillus anthracis, the etiologic agent of anthrax, avoids immune surveillance and commandeers host macrophages as a vehicle for lymphatic spreading. Here, we show that B. anthracis edema toxin (ET), via its adenylyl cyclase activity, dramatically increases the motility of infected macrophages and the expression of vascular endothelial growth factor. The transcription factor CREB and the syndecan-1 gene, a CREB target, play crucial roles in ET-induced macrophage migration. These molecular and cellular responses occur in macrophages engaged in antiinflammatory G protein-coupled receptor activation, thus illustrating a common signaling circuitry controlling resolution of inflammation and host cell hijacking by B. anthracis. C1 [Kim, Chun; Sano, Yasuyo; Park, Jin Mo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. [Wilcox-Adelman, Sarah] Boston Biomed Res Inst, Watertown, MA 02472 USA. [Tang, Wei-Jen] Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. [Collier, R. John] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Park, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. EM jmpark@cbrc2.mgh.harvard.edu FU NICHD NIH HHS [HD037490, R01 HD037490]; NIGMS NIH HHS [GM62548, R01 GM062548, R01 GM062548-07] NR 37 TC 35 Z9 37 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 22 PY 2008 VL 105 IS 16 BP 6150 EP 6155 DI 10.1073/pnas.0800105105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293SW UT WOS:000255356000037 PM 18427110 ER PT J AU Manoussaki, D Chadwick, RS Ketten, DR Arruda, J Dimitriadis, EK O'Malley, JT AF Manoussaki, Daphne Chadwick, Richard S. Ketten, Darlene R. Arruda, Julie Dimitriadis, Emilios K. O'Malley, Jen T. TI The influence of cochlear shape on low-frequency hearing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE inner ear; function; mammalian evolution; spiral ID MONGOLIAN GERBIL; SENSITIVITY; RANGE; RAT; THRESHOLDS; ABSOLUTE; COILING; MAMMALS; MICE AB The conventional theory about the snail shell shape of the mammalian cochlea is that it evolved essentially and perhaps solely to conserve space inside the skull. Recently, a theory proposed that the spiral's graded curvature enhances the cochlea's mechanical response to low frequencies. This article provides a multispecies analysis of cochlear shape to test this theory and demonstrates that the ratio of the radii of curvature from the outermost and innermost turns of the cochlear spiral is a significant cochlear feature that correlates strongly with low-frequency hearing limits. The ratio, which is a measure of curvature gradient, is a reflection of the ability of cochlear curvature to focus acoustic energy at the outer wall of the cochlear canal as the wave propagates toward the apex of the cochlea. C1 [Chadwick, Richard S.; Ketten, Darlene R.] Natl Inst Deafness & Other Commun Disorders, NIH, Auditory Mech Sect, Bethesda, MD 20892 USA. [Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, NIH, Lab Bioengn & Phys Sci, Bethesda, MD 20892 USA. [Manoussaki, Daphne] Vanderbilt Univ, Dept Math, Nashville, TN 37240 USA. [Manoussaki, Daphne] Tech Univ Crete, Dept Sci, Hania 73100, Greece. [Ketten, Darlene R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Ketten, Darlene R.; Arruda, Julie] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. [Arruda, Julie; O'Malley, Jen T.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chadwick, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Auditory Mech Sect, Bethesda, MD 20892 USA. EM chadwick@helix.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [Z01 DC000033] NR 40 TC 52 Z9 53 U1 4 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 22 PY 2008 VL 105 IS 16 BP 6162 EP 6166 DI 10.1073/pnas.0710037105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293SW UT WOS:000255356000039 PM 18413615 ER PT J AU Taoufik, E Petit, E Divoux, D Tseveleki, V Mengozzi, M Roberts, ML Valable, S Ghezzi, P Quackenbush, J Brines, M Cerami, A Probert, L AF Taoufik, Era Petit, Edwige Divoux, Didier Tseveleki, Vivian Mengozzi, Manuela Roberts, Michael L. Valable, Samuel Ghezzi, Pietro Quackenbush, John Brines, Michael Cerami, Anthony Probert, Lesley TI TNF receptor I sensitizes neurons to erythropoietin- and VEGF-mediated neuroprotection after ischemic and excitotoxic injury SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cDNA microarray; cytokine signaling; neuron death; transgenic mice; epilepsy ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; FOCAL CEREBRAL-ISCHEMIA; CELL-DEATH; PROTECTS NEURONS; MICE LACKING; BRAIN-INJURY; FACTOR-ALPHA; MOTONEURON DEGENERATION AB CNS neurons use robust cytoprotective mechanisms to ensure survival and functioning under conditions of injury. These involve pathways induced by endogenous neuroprotective cytokines such as erythropoietin (EPO). Recently, in contrast to its well known deleterious roles, TNF has also been shown to exhibit neuroprotective properties. In the present study, we investigated the molecular mechanisms by which TNF receptor (TNFR)I mediates neuroprotection by comparing the gene expression profiles of lesioned cortex from WT and TNFRI KO mice after permanent middle cerebral artery occlusion. Several known neuroprotective molecules were identified as TNFRI targets, notably members of the Bcl-2 family, DNA repair machinery and cell cycle, developmental, and differentiation factors, neurotransmitters and growth factors, as well as their receptors, including EPO receptor (EPOR), VEGF, colony-stimulating factor receptor 1, insulin-like growth factor (IGF), and nerve growth factor (NGF). Further analysis showed that induction of EPOR and VEGF expression in primary cortical neurons after glucose deprivation (GD) largely depended on TNFRI and was further up-regulated by TNF. Also, EPO- and VEGF-induced neuroprotection against GD, oxygen-glucose deprivation, and NMDA excitotoxicity depended significantly on TNFRI presence. Finally, EPO prevented neuronal damage induced by kainic acid in WT but not TNFRI KO mice. Our results identify cross-talk between tissue protective cytokines, specifically that TNFRI is necessary for constitutive and GD-induced expression of EFOR and VEGF and for EIPO-mediated neuroprotection. C1 [Taoufik, Era; Tseveleki, Vivian; Probert, Lesley] Hellen Pastuer Inst, Lab Mol Genet, Athens 11521, Greece. [Petit, Edwige; Divoux, Didier; Valable, Samuel] Univ Paris 05, Univ Caen Basse Normandie,CNRS, Ctr CYCERON,Ctr Imaging Neurosci & Applicat Patho, CERVOxy Team Hypoxia & Cerebrovasc Pathophysiol, F-14074 Caen, France. [Mengozzi, Manuela; Ghezzi, Pietro] Mario Negri Inst Pharmacol Res, Lab Neuroimmunol, I-20157 Milan, Italy. [Roberts, Michael L.] Regulon Inc, Athens 17455, Greece. [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Lab Computat Biol & Funct Genom, Boston, MA 02115 USA. [Brines, Michael; Cerami, Anthony] Warren Pharmaceut, Ossining, NY 10562 USA. RP Probert, L (reprint author), Hellen Pastuer Inst, Lab Mol Genet, Athens 11521, Greece. EM acerami@warrenpharma.com; lesley.probert@pasteur.gr RI Ghezzi, Pietro/A-4995-2010; PETIT, Edwige/C-1896-2008; valable, samuel/B-7578-2008 OI Roberts, Michael/0000-0001-7387-1155; Brines, Michael/0000-0003-4151-4449; Ghezzi, Pietro/0000-0003-0911-8358; valable, samuel/0000-0003-0355-0270 NR 56 TC 66 Z9 70 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 22 PY 2008 VL 105 IS 16 BP 6185 EP 6190 DI 10.1073/pnas.0801447105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293SW UT WOS:000255356000043 PM 18413601 ER PT J AU Li, C Beroukhim, R Weir, BA Winckler, W Garraway, LA Sellers, WR Meyerson, M AF Li, Cheng Beroukhim, Rameen Weir, Barbara A. Winckler, Wendy Garraway, Levi A. Sellers, William R. Meyerson, Matthew TI Major copy proportion analysis of tumor samples using SNP arrays SO BMC BIOINFORMATICS LA English DT Article ID LOSS-OF-HETEROZYGOSITY; NUCLEOTIDE POLYMORPHISM ARRAYS; HIDDEN MARKOV MODEL; OLIGONUCLEOTIDE ARRAYS; GENOTYPING MICROARRAYS; CANCER GENOME; NUMBER; DNA; ALGORITHMS AB Background: Single nucleotide polymorphisms (SNPs) are the most common genetic variations in the human genome and are useful as genomic markers. Oligonucleotide SNP microarrays have been developed for high-throughput genotyping of up to 900,000 human SNPs and have been used widely in linkage and cancer genomics studies. We have previously used Hidden Markov Models (HMM) to analyze SNP array data for inferring copy numbers and loss-of-heterozygosity (LOH) from paired normal and tumor samples and unpaired tumor samples. Results: We proposed and implemented major copy proportion (MCP) analysis of oligonucleotide SNP array data. A HMM was constructed to infer unobserved MCP states from observed allele-specific signals through emission and transition distributions. We used 10 K, 100 K and 250 K SNP array datasets to compare MCP analysis with LOH and copy number analysis, and showed that MCP performs better than LOH analysis for allelic-imbalanced chromosome regions and normal contaminated samples. The major and minor copy alleles can also be inferred from allelic-imbalanced regions by MCP analysis. Conclusion: MCP extends tumor LOH analysis to allelic imbalance analysis and supplies complementary information to total copy numbers. MCP analysis of mixing normal and tumor samples suggests the utility of MCP analysis of normal-contaminated tumor samples. The described analysis and visualization methods are readily available in the user-friendly dChip software. C1 [Li, Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Dept Biostat & Computat Biol, Sch Publ Hlth, Boston, MA 02115 USA. [Beroukhim, Rameen; Weir, Barbara A.; Winckler, Wendy; Garraway, Levi A.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen; Weir, Barbara A.; Winckler, Wendy; Garraway, Levi A.; Meyerson, Matthew] Harvard Univ, Dept Med Oncol, Sch Med, Boston, MA 02115 USA. [Beroukhim, Rameen; Weir, Barbara A.; Winckler, Wendy; Garraway, Levi A.; Meyerson, Matthew] Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. [Beroukhim, Rameen; Weir, Barbara A.; Winckler, Wendy; Garraway, Levi A.; Meyerson, Matthew] MIT, Cambridge, MA 02141 USA. [Sellers, William R.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Li, C (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 3 Blackfan Circle, Boston, MA 02115 USA. EM cli@hsph.harvard.edu; rameen@broad.mit.edu; bweir@broad.mit.edu; wendy_winckler@dfci.harvard.edu; Levi_Garraway@dfci.harvard.edu; William.Sellers@novartis.com; matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [1P50 CA090578, K08 CA122833, K08 CA122833-01A1, P50 CA090578]; NHGRI NIH HHS [5R01 HG002341, R01 HG002341] NR 37 TC 28 Z9 29 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD APR 21 PY 2008 VL 9 AR 204 DI 10.1186/1471-2105-9-204 PG 16 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 303JP UT WOS:000256037100002 PM 18426588 ER PT J AU Seed, B Xavier, R AF Seed, Brian Xavier, Ramnik TI Spinophilin and the immune synapse SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material ID IMMUNOLOGICAL SYNAPSE; DENDRITIC SPINES; BINDING-PROTEIN; ACTIVATION; CELLS AB Extensive alterations in cellular organization are known to accompany the responses of sensitized T cells to target cells presenting an antigen of interest. Now, equally if not more dramatic changes are found to take place in cells presenting an antigen. With the help of a spinophilin-GFP fusion protein, Bloom et al. (Bloom, O.,J.J. Unternaehrer, A. Jiang, J.-S. Shin, L. Delamarre, P. Allen, and I. Mellman. 2008. J. Cell Biol. 181: 203-211) have captured a remarkable polarization of the cellular architecture of dendritic cells presenting an antigen to T cells. C1 [Seed, Brian] Massachusetts Gen Hosp, Dept Pediat, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik] Massachusetts Gen Hosp, Dept Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Pediat, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM bseed@ccib.mgh.harvard.edu NR 15 TC 1 Z9 1 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 21 PY 2008 VL 181 IS 2 BP 181 EP 183 DI 10.1083/jcb.200803120 PG 3 WC Cell Biology SC Cell Biology GA 294MO UT WOS:000255410300002 PM 18411314 ER PT J AU Canellos, GP AF Canellos, George P. TI What constitutes "Improved Prognosis"? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID B-CELL LYMPHOMA; DIFFUSE HISTIOCYTIC LYMPHOMA; NON-HODGKINS-LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; HIGH-DOSE METHOTREXATE; COMBINATION CHEMOTHERAPY; AGGRESSIVE LYMPHOMA; CHOP CHEMOTHERAPY; YOUNG-PATIENTS; M-BACOD C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2008 VL 26 IS 12 BP 1913 EP 1914 DI 10.1200/JCO.2007.13.8172 PG 2 WC Oncology SC Oncology GA 289KZ UT WOS:000255054700001 PM 18421041 ER PT J AU Lin, NU Winer, EP AF Lin, Nancy U. Winer, Eric P. TI Optimizing endocrine therapy for estrogen receptor-positive breast cancer: Treating the right patients for the right length of time SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID SURGICAL ADJUVANT BREAST; POSTMENOPAUSAL WOMEN; GENE-EXPRESSION; RANDOMIZED-TRIAL; UPDATED FINDINGS; TAMOXIFEN; LETROZOLE; SURVIVAL; EFFICACY; INTERVENTION C1 [Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 30 TC 6 Z9 6 U1 0 U2 0 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 APR 20 PY 2008 VL 26 IS 12 BP 1919 EP 1921 DI 10.1200/JCO.2007.14.7744 PG 3 WC Oncology SC Oncology GA 289KZ UT WOS:000255054700004 PM 18332468 ER PT J AU Goss, PE Ingle, JN Pater, JL Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Shepherd, LE Pritchard, KI Livingston, RB Davidson, NE Norton, L Perez, EA Abrams, JS Cameron, DA Palmer, MJ Tu, DS AF Goss, Paul E. Ingle, James N. Pater, Joseph L. Martino, Silvana Robert, Nicholas J. Muss, Hyman B. Piccart, Martine J. Castiglione, Monica Shepherd, Lois E. Pritchard, Kathleen I. Livingston, Robert B. Davidson, Nancy E. Norton, Larry Perez, Edith A. Abrams, Jeffrey S. Cameron, David A. Palmer, Michael J. Tu, Dongsheng TI Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ONCOLOGY-TECHNOLOGY-ASSESSMENT; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; AMERICAN-SOCIETY; UPDATED FINDINGS; THERAPY; SURVIVAL; ESTROGEN AB Purpose The National Cancer Institute of Canada Clinical Trials Group MA. 17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET. Patients and Methods This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding. Results There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [ HR], 0.37; 95% CI, 0.23 to 0.61; P <.0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P =.004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P =.02). Conclusion Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen. C1 [Goss, Paul E.; Ingle, James N.; Pater, Joseph L.; Martino, Silvana; Robert, Nicholas J.; Muss, Hyman B.; Piccart, Martine J.; Castiglione, Monica; Shepherd, Lois E.; Pritchard, Kathleen I.; Livingston, Robert B.; Davidson, Nancy E.; Norton, Larry; Perez, Edith A.; Abrams, Jeffrey S.; Cameron, David A.; Palmer, Michael J.; Tu, Dongsheng] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Angeles Clin, Los Angeles, CA USA. Res Inst, Los Angeles, CA USA. Inova Fairfax Hosp, Falls Church, VA USA. Univ Vermont, Burlington, VT USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Natl Canc Inst, Clin Trials Grp, Kingston, ON, Canada. Univ Toronto, Toronto Sunnybrook Odette Canc Ctr, Toronto, ON M5S 1A1, Canada. Univ Washington, Seattle, WA 98195 USA. Sidney Kimmel Copmrehens Canc Ctr, Baltimore, MD USA. NCI, Canc Therapy Evaluat Program, Clin Invest Branch, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Jacksonville, FL 32224 USA. Western Gen Hosp, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LHR-302, Boston, MA 02114 USA. EM pgoss@partners.org OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA38926, CA21115, CA25224, CA31946, CA32102] NR 18 TC 116 Z9 123 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 APR 20 PY 2008 VL 26 IS 12 BP 1948 EP 1955 DI 10.1200/JCO.2007.11.6798 PG 8 WC Oncology SC Oncology GA 289KZ UT WOS:000255054700010 PM 18332475 ER PT J AU Muss, HB Tu, D Ingle, JN Martino, S Robert, NJ Pater, JL Whelan, TJ Palmer, MJ Piccart, MJ Shepherd, LE Pritchard, KI He, Z Goss, PE AF Muss, Hyman B. Tu, Dongsheng Ingle, James N. Martino, Silvana Robert, Nicholas J. Pater, Joseph L. Whelan, Timothy J. Palmer, Michael J. Piccart, Martine J. Shepherd, Lois E. Pritchard, Kathleen I. He, Zhi Goss, Paul E. TI Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCICCTG intergroup trial MA.17 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; ADJUVANT TAMOXIFEN; ELDERLY-WOMEN; BONE HEALTH; THERAPY; SURVIVAL; DATABASE; AGE AB Purpose National Cancer Institute of Canada Clinical Trials Group trial MA. 17 randomly assigned 5,187 postmenopausal, hormone-receptor-positive patients with early breast cancer who completed 5 years of tamoxifen to receive either letrozole or placebo. At 30 months median follow-up, letrozole significantly improved disease-free survival (DFS) in all patients and overall survival (OS) in node-positive patients. Breast cancer incidence increases with age and more than 1,300 women age 70 years or older were enrolled onto MA. 17, making it ideal to explore the benefits, toxicities, and quality of life (QOL) impact of letrozole on older women. Patients and Methods In this study, 5,169 randomly assigned patients were divided into three age groups: younger than 60 years (n = 2,152), 60 to 69 years (n = 1,694), and >= 70 years (n = 1,323). Log-rank test was used to compare differences in DFS, distant-disease-free survival, and OS between age and treatment groups, and Cox models were used to estimate hazard ratios and associated 95% CIs. QOL was measured using the Medical Outcomes Short Form-36 and the Menopause-Specific Quality-of-Life questionnaire. Results At 4 years, DFS demonstrated statistically significant differences favoring letrozole only in patients age younger than 60 years (hazard ratio = 0.46; P =.0004); there was no interaction between age and treatment, indicating a similar effect of letrozole among all age groups. There was no difference in toxicity or QOL at 24 months among letrozole- and placebo-treated patients age >= 70 years. Conclusion Healthy patients age 70 years and older completing 5 years of tamoxifen should be considered for extended adjuvant therapy with letrozole. C1 [Muss, Hyman B.; Tu, Dongsheng; Ingle, James N.; Martino, Silvana; Robert, Nicholas J.; Pater, Joseph L.; Whelan, Timothy J.; Palmer, Michael J.; Piccart, Martine J.; Shepherd, Lois E.; Pritchard, Kathleen I.; He, Zhi; Goss, Paul E.] Univ Vermont, Coll Med, Ctr Canc, Burlington, VT 05401 USA. Queens Univ, Natl Canc Inst, Clin Trials Grp, Kingston, ON, Canada. McMaster Univ, Hamilton, ON L8S 4L8, Canada. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Univ Toronto, Toronto, ON, Canada. Mayo Clin, Ctr Canc, Rochester, MN USA. Angeles Clin, Santa Monica, CA USA. Res Inst, Santa Monica, CA USA. Inova Fairfax Hosp, Fairfax, VA USA. Jules Bordet Canc Inst, Brussels, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Muss, HB (reprint author), Univ Vermont, Coll Med, Ctr Canc, 1 S Prospect St,St Joseph 3400, Burlington, VT 05401 USA. EM hyman.muss@uvm.edu RI Whelan, Timothy/D-3185-2017; Pritchard, Kathleen/I-2184-2014 OI Pritchard, Kathleen/0000-0003-0758-9666 NR 26 TC 81 Z9 83 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2008 VL 26 IS 12 BP 1956 EP 1964 DI 10.1200/JCO.2007.12.6334 PG 9 WC Oncology SC Oncology GA 289KZ UT WOS:000255054700011 PM 18332474 ER PT J AU Crivellari, D Sun, Z Coates, AS Price, KN Thurlimann, B Mouridsen, H Mauriac, L Forbes, JF Paridaens, RJ Castiglione-Gertsch, M Gelber, RD Colleoni, M Lang, I Del Mastro, L Gladieff, L Rabaglio, M Smith, IE Chirgwin, JH Goldhirsch, A AF Crivellari, Diana Sun, Zhuoxin Coates, Alan S. Price, Karen N. Thuerlimann, Beat Mouridsen, Henning Mauriac, Louis Forbes, John F. Paridaens, Robert J. Castiglione-Gertsch, Monica Gelber, Richard D. Colleoni, Marco Lang, Istvan Del Mastro, Lucia Gladieff, Laurence Rabaglio, Manuela Smith, Ian E. Chirgwin, Jacquie H. Goldhirsch, Aron TI Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: The BIG 1-98 trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; ADJUVANT TAMOXIFEN; AROMATASE INHIBITORS; AMERICAN-SOCIETY; RANDOMIZED TRIAL; HEART-DISEASE; PHASE-III; THERAPY; MORBIDITY AB Purpose To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial. Methods This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were defined: "younger postmenopausal" patients were younger than 65 years (n = 3,127), "older" patients were 65 to 74 years old (n = 1,500), and "elderly" patients were 75 years of age or older (n = 295). Results Efficacy results for subpopulations defined by age were similar to the overall trial results: Letrozole significantly improved disease-free survival (DFS), the primary end point, compared with tamoxifen. Elderly patients were less likely to complete trial treatment, but at rates that were similar in the two treatment groups. The incidence of bone fractures, observed more often in the letrozole group, did not differ by age. In elderly patients, letrozole had a significantly higher incidence of any grade 3 to 5 protocol-specified non-fracture AE compared with tamoxifen (P = .002), but differences were not significant for thromboembolic or cardiac AEs. Conclusion Adjuvant treatment with letrozole had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy. C1 [Crivellari, Diana; Sun, Zhuoxin; Coates, Alan S.; Price, Karen N.; Thuerlimann, Beat; Mouridsen, Henning; Mauriac, Louis; Forbes, John F.; Paridaens, Robert J.; Castiglione-Gertsch, Monica; Gelber, Richard D.; Colleoni, Marco; Lang, Istvan; Del Mastro, Lucia; Gladieff, Laurence; Rabaglio, Manuela; Smith, Ian E.; Chirgwin, Jacquie H.; Goldhirsch, Aron] IBCSG, Coordinating Ctr, CH-3008 Bern, Switzerland. Ctr Riferimento Oncol, I-33081 Aviano, Italy. European Inst Oncol, Dept Med, Milan, Italy. Natl Inst Canc Res, Genoa, Italy. IBCSG, Ctr Stat, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Univ Sydney, Sydney, NSW 2006, Australia. Univ Newcastle, Australian New Zealand Breast Canc Trails Grp, Newcastle, NSW 2308, Australia. Box Hill & Meroondah Hosp, Melbourne, Vic, Australia. Kantonsspital, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. Oncol Inst So Switzerland, Bellinzona, Switzerland. Rigshosp, Danish Breast Canc Cooperat Grp, DK-2100 Copenhagen, Denmark. Fed Natl Ctr Lutte Contre Canc, Inst Bergonie, Bordeaux, France. Inst Claudius Regaud, Toulouse, France. Catholic Univ Louvain, Hosp Gasthuisberg, Dept Med Oncol, B-3000 Louvain, Belgium. Natl Inst Oncol, Budapest, Hungary. Royal Marsden Hosp, London SW3 6JJ, England. RP Crivellari, D (reprint author), IBCSG, Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM dcrivellari@cro.it RI GLADIEFF, Laurence/O-5129-2014; OI GLADIEFF, Laurence/0000-0002-6980-9719; Del Mastro, Lucia/0000-0002-9546-5841 FU NCI NIH HHS [CA-75362, U24 CA075362] NR 40 TC 75 Z9 83 U1 0 U2 2 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 APR 20 PY 2008 VL 26 IS 12 BP 1972 EP 1979 DI 10.1200/JCO.2007.14.0459 PG 8 WC Oncology SC Oncology GA 289KZ UT WOS:000255054700013 PM 18332471 ER PT J AU Lin, NU Carey, LA Liu, MC Younger, J Come, SE Ewend, M Harris, GJ Bullitt, E Van den Abbeele, AD Henson, JW Li, XC Gelman, R Burstein, HJ Kasparian, E Kirsch, DG Crawford, A Hochberg, F Winer, EP AF Lin, Nancy U. Carey, Lisa A. Liu, Minetta C. Younger, Jerry Come, Steven E. Ewend, Matthew Harris, Gordon J. Bullitt, Elizabeth Van den Abbeele, Annick D. Henson, John W. Li, Xiaochun Gelman, Rebecca Burstein, Harold J. Kasparian, Elizabeth Kirsch, David G. Crawford, Ann Hochberg, Fred Winer, Eric P. TI Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID CELL LUNG-CANCER; PLATINUM CONCENTRATIONS; 1ST-LINE TREATMENT; ANTITUMOR-ACTIVITY; CLINICAL-TRIALS; SINGLE-AGENT; TRASTUZUMAB; GEFITINIB; CHEMOTHERAPY; CARCINOMA AB Purpose One third of women with advanced human epidermal growth factor receptor 2 (HER-2)-positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2-positive brain metastases. Patients and Methods Patients had HER-2-positive breast cancer, progressive brain metastases, prior trastuzumab treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included objective response in non-CNS sites, time to progression, overall survival, and toxicity. Results Thirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%). Conclusion The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2-positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point. C1 [Lin, Nancy U.; Carey, Lisa A.; Liu, Minetta C.; Younger, Jerry; Come, Steven E.; Ewend, Matthew; Harris, Gordon J.; Bullitt, Elizabeth; Van den Abbeele, Annick D.; Henson, John W.; Li, Xiaochun; Gelman, Rebecca; Burstein, Harold J.; Kasparian, Elizabeth; Kirsch, David G.; Crawford, Ann; Hochberg, Fred; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ewiner@partners.org FU NCI NIH HHS [CA89393, P30 CA006516, P50 CA058223, P50 CA089393, CA58223]; NCRR NIH HHS [M01 RR000046, M01RR00046]; NIBIB NIH HHS [R01 EB000219, R01 EB000219-09, R01EB000219] NR 35 TC 223 Z9 228 U1 1 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2008 VL 26 IS 12 BP 1993 EP 1999 DI 10.1200/JCO.2007.12.3588 PG 7 WC Oncology SC Oncology GA 289KZ UT WOS:000255054700016 PM 18421051 ER PT J AU Hodi, FS Friedlander, P Corless, CL Heinrich, MC Mac Rae, S Kruse, A Jagannathan, J Van den Abbeele, AD Velazquez, EF Demetri, GD Fisher, DE AF Hodi, F. Stephen Friedlander, Philip Corless, Christopher L. Heinrich, Michael C. Mac Rae, Suzanne Kruse, Andrea Jagannathan, Jyothi Van den Abbeele, Annick D. Velazquez, Elsa F. Demetri, George D. Fisher, David E. TI Major response to imatinib mesylate in KIT-mutated melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; ABL TYROSINE KINASE; HIGH-DOSE IMATINIB; PHASE-II TRIAL; METASTATIC MELANOMA; MALIGNANT-MELANOMA; CLINICAL-EFFICACY; MUTATIONS; SAFETY; INHIBITOR C1 [Hodi, F. Stephen; Friedlander, Philip] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Melanoma Program, Boston, MA 02115 USA. [Corless, Christopher L.; Heinrich, Michael C.] Oregon Hlth & Sci Univ, Div Hematol & Oncol, Portland, OR USA. [Jagannathan, Jyothi; Van den Abbeele, Annick D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. [Velazquez, Elsa F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ludwig Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Fisher, David E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Melanoma Program, Boston, MA 02115 USA. RP Hodi, FS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Melanoma Program, Boston, MA 02115 USA. NR 20 TC 261 Z9 270 U1 1 U2 11 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2008 VL 26 IS 12 BP 2046 EP 2051 DI 10.1200/JCO.2007.14.0707 PG 7 WC Oncology SC Oncology GA 289KZ UT WOS:000255054700025 PM 18421059 ER PT J AU Streeck, H Cohen, KW Jolin, JS Brockman, MA Meier, A Power, KA Waring, MT Alter, G Altfeld, M AF Streeck, Hendrik Cohen, Kristin W. Jolin, Jonathan S. Brockman, Mark A. Meier, Angela Power, Karen A. Waring, Michael T. Alter, Galit Altfeld, Marcus TI Rapid ex vivo isolation and long-term culture of human Th17 cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Th17 cells; isolation; capture assay; long-term culture; ROR gamma t ID INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; CYTOKINE MILIEU; INTERLEUKIN-17; EXPRESSION; T(H)17; DIFFERENTIATION; LYMPHOCYTES; INFECTION; RESPONSES AB T helper (Th) 17 cells are a distinct lineage of CD4+ T cells mediating tissue inflammation through the secretion of IL-17. In addition, it has been shown that the expression of the transcriptional factor ROR gamma t is responsible for the induction and maintenance of this cell line. Th 17 cells are believed to be involved in a variety of autoimmune disorders, but may also play an important role in host defense. Here we describe a novel technique to reproducibly isolate viable Th17 cells based on their IL-17 secreting ability. We confirmed Th17 cell enrichment by quantitative PCR analysis and demonstrate that positively selected cells using this technique express significantly increased mRNA levels of ROR gamma t, IL-23 receptor and CCR4 when compared to negatively selected cells. Furthermore, we show that purified Th 17 cells can be maintained in long-term culture and expand in vitro. In conclusion, this technique will allow for the first time the direct, ex vivo analysis of phenotypic and functional properties of Th17 cells. (C) 2008 Elsevier B.V. All rights reserved. C1 [Streeck, Hendrik; Cohen, Kristin W.; Jolin, Jonathan S.; Brockman, Mark A.; Meier, Angela; Power, Karen A.; Waring, Michael T.; Alter, Galit; Altfeld, Marcus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr,Div Infect Dis, Charlestown, MA 02129 USA. RP Streeck, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr,Div Infect Dis, Bldg 149,13th St,6th Floor, Charlestown, MA 02129 USA. EM hstreeck@partners.org OI Brockman, Mark/0000-0001-6432-1426 NR 26 TC 30 Z9 31 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 20 PY 2008 VL 333 IS 1-2 BP 115 EP 125 DI 10.1016/j.jim.2008.01.018 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 299CX UT WOS:000255734500011 PM 18314131 ER PT J AU Wiviott, SD Braunwald, E McCabe, CH Horvath, I Keltai, M Herrman, JPR Van de Werf, F Downey, WE Scirica, BM Murphy, SA Antman, EM AF Wiviott, Stephen D. Braunwald, Eugene McCabe, Carolyn H. Horvath, Ivan Keltai, Matyas Herrman, Jean-Paul R. Van de Werf, Frans Downey, William E. Scirica, Benjamin M. Murphy, Sabina A. Antman, Elliott M. CA TRITON TIMI 38 Investigators TI Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial SO LANCET LA English DT Article ID DRUG-ELUTING STENTS; ACUTE MYOCARDIAL-INFARCTION; BARE-METAL STENTS; ARTERY-DISEASE; PLATELET INHIBITION; OFF-LABEL; BALLOON ANGIOPLASTY; CLINICAL-OUTCOMES; UNCOATED STENTS; INCREASED RISK AB Background Intracoronary stenting can improve procedural success and reduce restenosis compared with balloon angioplasty in patients with acute coronary syndromes, but can also increase the rate of thrombotic complications including stent thrombosis. The TRITON-TIMI 38 trial has shown that prasugrel-a novel, potent thienopyridine-can reduce ischaemic events compared with standard clopidogrel therapy. We assessed the rate, outcomes, and prevention of ischaemic events in patients treated with prasugrel or clopidogrel with stents in the TRITON-TIMI 38 study. Methods patients with moderate-risk to high-risk coronary syndromes ware included in our analysis if they had received at least one coronary stent at the time of the index procedure following randomisation in TRITON-TIMI 38, and were further subdivided by type of stent received. Patients were randomly assigned in a 1 to 1 fashion to receive a loading dose of study drug (prasugrel 60 mg or clopidogrel 300 mg) as soon as possible after randomisation, followed by daily maintenance therapy (prasugrel 10 mg or clopidogrel 75 mg). All patients were to receive aspirin therapy. Treatment was to be continued for a minimum of 6 months and a maximum of 15 months. Randomisation was not stratified by stents used or stent type. The primary endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Stent thrombosis was assessed using Academic Research Consortium definitions, and analysis was by intention to treat. TRITON-TIMI 38 is registered with ClinicalTrials.gov, number NCT 00097591. Findings 12 844 patients received at least one coronary stent; 5743 received only drug-eluting stents, and 6461 received only bare-metal stents. Prasugrel compared with clopidogrel reduced the primary endpoint (9.7 vs 11.9%, HR 0.81, p=0.0001) in the stented cohort, in patients with only drug-eluting stents (9.0 vs 11.1%, HR 0.82, p=0.019), and in pateints with only bare-metal stents (10.0 vs 12.2%, HR 0.80, p=0.003). Stent thrombosis was associated with death or myocardial infarction in 89% (186/210) of patients. Stent thrombosis was reduced with prasugrel overall (1.13 vs 2.35%, HR 0.48, p<0.0001), in patients with drug-eluting stents only (0.84 vs 2.31%, HR 0.36, p<0.0001), and in those with bare-metal stents only (1.27 vs 2.41%, HR 0.52, p=0.0009). Interpretation Intensive antiplatelet therapy with prasugrel resulted in fewer ischaemic outcomes including stent thrombosis than with standard clopidogrel. These findings were statistically robust irrespective of stent type, and the data affirm the importance of intensive platelet inhibition in patients with intracoronary stents. Funding TRITON-TIMI 38 was supported by research grants from Daiichi Sankyo and Eli Lilly. C1 [Wiviott, Stephen D.; Braunwald, Eugene; McCabe, Carolyn H.; Scirica, Benjamin M.; Murphy, Sabina A.; Antman, Elliott M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Wiviott, Stephen D.; Braunwald, Eugene; McCabe, Carolyn H.; Scirica, Benjamin M.; Murphy, Sabina A.; Antman, Elliott M.] Harvard Univ, Sch Med, Boston, MA USA. [Horvath, Ivan] Univ Pecs, Inst Heart, Pecs, Hungary. [Keltai, Matyas] Semmelweis Univ, Hungarian Inst Cardiol, H-1085 Budapest, Hungary. [Herrman, Jean-Paul R.] Onze Lieve Vrouw Hosp, Dept Cardiol, Amsterdam, Netherlands. [Van de Werf, Frans] Univ Louvain, Dept Cardiovasc Dis, Louvain, Belgium. [Downey, William E.] LeBauer Cardiovasc Res Fdn, Greensboro, NC USA. [Downey, William E.] Moses Cone Heart & Vasc Ctr, Greensboro, NC USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. EM swiviott@partners.org NR 50 TC 281 Z9 299 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 19 PY 2008 VL 371 IS 9621 BP 1353 EP 1363 DI 10.1016/S0140-6736(08)60422-5 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 291PE UT WOS:000255208500026 PM 18377975 ER PT J AU Martin, TR Wurfel, MM AF Martin, Thomas R. Wurfel, Mark M. TI A TRIFfic perspective on acute lung injury SO CELL LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME AB Acute lung injury (ALI) is a leading cause of death in people infected with H5N1 avian influenza virus or the SARS-coronavirus. Imai et al. (2008) now report that ALI is triggered by the signaling of oxidized phospholipids through Toll-like receptor 4 (TLR4) and the adaptor protein TRIF. These findings provide insight into the molecular pathogenesis of ALI, a condition for which treatment options are currently very limited. C1 [Martin, Thomas R.; Wurfel, Mark M.] Univ Washington, Med Res Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Martin, Thomas R.; Wurfel, Mark M.] Univ Washington, Div Pulm & Crit Care Med, Dept Med, Seattle, WA 98108 USA. RP Martin, TR (reprint author), Univ Washington, Med Res Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM trmartin@u.washington.edu FU NHLBI NIH HHS [HL073996, HL629063, HL081764] NR 11 TC 13 Z9 16 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 18 PY 2008 VL 133 IS 2 BP 208 EP 210 DI 10.1016/j.cell.2008.04.006 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 289JY UT WOS:000255052000009 PM 18423191 ER PT J AU Ramachandran, B Yu, GS Li, SG Zhu, B Gulick, T AF Ramachandran, Bindu Yu, Gengsheng Li, Shiguang Zhu, Bangmin Gulick, Tod TI Myocyte enhancer factor 2A is transcriptionally autoregulated SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE DIFFERENTIATION; SIGNAL-REGULATED KINASE-5; MEF2 PROTEIN FAMILY; GENE-EXPRESSION; MADS-BOX; HISTONE DEACETYLASES; MOUSE EMBRYOGENESIS; NEURONAL SURVIVAL; STRIATED-MUSCLE; NERVOUS-SYSTEM AB MEF2 (myocyte enhancer factor 2) proteins are a small family of transcription factors that play pivotal roles in striated muscle differentiation, development, and metabolism, in neuron survival and synaptic formation, and in lymphocyte selection and activation. Products of the four mammalian MEF2 genes, MEF2A, MEF2B, MEF2C, and MEF2D, are expressed with overlapping but distinct temporospatial patterns. Toward analysis of MEF2A functions and the determinants of its regulated expression, we have mapped and begun studies of the transcriptional control regions of this gene. Heterogeneous 5'-untranslated regions of MEF2A mRNAs result from use of alternative promoters and splicing patterns. The two closely approximated TATA-less promoters are similar to 65 kb upstream of the exon containing the sole initiation codon. Ribonuclease protection and primer extension assays show that each promoter is active in various adult tissues. A canonical MEF2 site overlies the major promoter 1 transcription start site. This element specifically binds MEF2 factors, including endogenous nuclear MEF2A according to chromatin immunoprecipitation studies, and is critical to MEF2A transcription in myocytes. The site exerts reciprocal control of the alternative promoters, silencing promoter 1 and activating promoter 2 under some conditions. Erk5 and p38 MAPK signaling stimulate MEF2A expression by activating both promoters from the MEF2 element. MEF2A transcription is therefore subject to positive or negative regulation by its protein products, depending on signaling activities that influence MEF2 factor trans-activity. The sole MEF2 gene of the cephalochordate amphioxus has a similar regulatory region structure, suggesting that this mode of autoregulatory control is conserved among higher metazoan MEF2 genes. C1 [Ramachandran, Bindu; Yu, Gengsheng; Li, Shiguang; Zhu, Bangmin; Gulick, Tod] Massachusetts Gen Hosp, Diabet Res Lab, Dept Med, Charlestown, MA 02129 USA. [Yu, Gengsheng; Zhu, Bangmin; Gulick, Tod] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gulick, T (reprint author), Massachusetts Gen Hosp, Diabet Res Lab, Dept Med, CNY 149 8219, Charlestown, MA 02129 USA. EM gulick@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL72713]; NIDDK NIH HHS [DK55875, DK02461, P30-DK40561] NR 83 TC 19 Z9 20 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 18 PY 2008 VL 283 IS 16 BP 10318 EP 10329 DI 10.1074/jbc.M707623200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 287CQ UT WOS:000254894700012 PM 18073218 ER PT J AU Yang, L Clinton, JM Blackburn, ML Zhang, Q Zou, JH Zielinska-Kwiatkowska, A Tang, BL Chansky, HA AF Yang, Liu Clinton, Jeremiah M. Blackburn, Michael L. Zhang, Qi Zou, Junhui Zielinska-Kwiatkowska, Anna Tang, Bor Luen Chansky, Howard A. TI Rab23 regulates differentiation of ATDC5 chondroprogenitor cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AUTOSOMAL SEX REVERSAL; SRY-RELATED GENE; CAMPOMELIC DYSPLASIA; NEGATIVE REGULATOR; GROWTH-PLATE; NEURAL-TUBE; OPEN BRAIN; MOUSE; SOX9; MUTATIONS AB Insulin treatment of mouse ATDC5 chondroprogenitors induces these cells to differentiate into mature chondrocytes. To identify novel factors that are involved in this process, we carried out mutagenesis of ATDC5 cells through retroviral insertion and isolated two mutant clones incapable of differentiation. Inverse PCR analysis of these clones revealed that the retroviral DNA was inserted into the promoter region of the Rab23 gene, resulting in increased Rab23 expression. To investigate whether an elevated level of Rab23 protein led to inhibition of chondrogenic differentiation, we characterized ATDC5 cells that either overexpress endogenous Rab23 or stably express ectopic Rab23. Our results revealed that up-regulation of Rab23 can indeed inhibit chondrogenic differentiation with a concomitant down-regulation of matrix genes such as type II collagen and aggrecan. In addition, stable small interfering RNA knockdown of Rab23 also resulted in inhibition of chondrogenic differentiation as well as down-regulation of Sox9, a master regulator of chondrogenesis. Interestingly, Sox9 expression has recently been linked to Gli1, and we found that Rab23 knockdown decreased Gli1 expression in chondrocytes. Because the phenotypes of Rab23 mutations in mice and humans include defects in cartilage and bone development, our study suggests that Rab23 is involved in the control of Sox9 expression via Gli1 protein. C1 [Yang, Liu; Clinton, Jeremiah M.; Zhang, Qi; Zou, Junhui; Zielinska-Kwiatkowska, Anna; Chansky, Howard A.] Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98195 USA. [Yang, Liu; Blackburn, Michael L.; Chansky, Howard A.] Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. [Tang, Bor Luen] Natl Univ Singapore, Dept Biochem, Singapore 117597, Singapore. RP Yang, L (reprint author), Univ Washington, Dept Orthoped, 1660 S Columbian Way,GMR 151, Seattle, WA 98108 USA. EM lyang@u.washington.edu RI Tang, Bor Luen/E-4548-2012 OI Tang, Bor Luen/0000-0002-1925-636X FU NIAMS NIH HHS [R01 AR051455] NR 27 TC 13 Z9 15 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 18 PY 2008 VL 283 IS 16 BP 10649 EP 10657 DI 10.1074/jbc.M706795200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 287CQ UT WOS:000254894700047 PM 18218620 ER PT J AU Taylor, AB Hu, G Hart, PJ McAlister-Henn, L AF Taylor, Alexander B. Hu, Gang Hart, P. John McAlister-Henn, Lee TI Allosteric motions in structures of yeast NAD(+)-specific isocitrate dehydrogenase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCES; SACCHAROMYCES-CEREVISIAE; ANOMALOUS DIFFRACTION; BINDING-SITES; 3-DIMENSIONAL STRUCTURE; THERMUS-THERMOPHILUS; COMPARATIVE GENOMICS; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; KINETIC-ANALYSIS AB Mitochondrial NAD(+)-specific isocitrate dehydrogenases (IDHs) are key regulators of flux through biosynthetic and oxidative pathways in response to cellular energy levels. Here we present the first structures of a eukaryotic member of this enzyme family, the allosteric, hetero-octameric, NAD(+)-specific IDH from yeast in three forms: 1) without ligands, 2) with bound analog citrate, and 3) with bound citrate + AMP. The structures reveal the molecular basis for ligand binding to homologous but distinct regulatory and catalytic sites positioned at the interfaces between IDH1 and IDH2 subunits and define pathways of communication between heterodimers and heterotetramers in the hetero-octamer. Disulfide bonds observed at the heterotetrameric interfaces in the unliganded IDH hetero-octamer are reduced in the ligand-bound forms, suggesting a redox regulatory mechanism that may be analogous to the "on-off" regulation of non-allosteric bacterial IDHs via phosphorylation. The results strongly suggest that eukaryotic IDH enzymes are exquisitely tuned to ensure that allosteric activation occurs only when concentrations of isocitrate are elevated. C1 [Taylor, Alexander B.; Hu, Gang; Hart, P. John; McAlister-Henn, Lee] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Taylor, Alexander B.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA. [Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Hart, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM pjhart@biochem.uthscsa.edu; henn@uthscsa.edu FU NIGMS NIH HHS [5R01GM051256] NR 47 TC 27 Z9 27 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 18 PY 2008 VL 283 IS 16 BP 10872 EP 10880 DI 10.1074/jbc.M708719200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 287CQ UT WOS:000254894700069 PM 18256028 ER PT J AU Redline, RW Sagar, P King, ME Krishnamoorthy, KS Grabowski, EF Roberts, DJ Harris, NL AF Redline, Raymond W. Sagar, Pallavi King, Mary Etta Krishnamoorthy, Kalpathy S. Grabowski, Eric F. Roberts, Drucilla J. Harris, Nancy Lee TI A newborn infant with intermittent apnea and seizures - Severe acute chorioamnionitis with umbilical-cord phlebitis and intense chorionic-plate vasculitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FETAL INFLAMMATORY RESPONSE; PLACENTAL REACTION PATTERNS; NEUROLOGIC IMPAIRMENT; ARTERIAL STROKE; TERM INFANTS; INFECTION; CHILDREN; REPRODUCIBILITY; VASCULOPATHY; NOSOLOGY C1 [Redline, Raymond W.] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH USA. [Sagar, Pallavi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [King, Mary Etta] Massachusetts Gen Hosp, Dept Pediat Cardiol, Boston, MA 02114 USA. [Krishnamoorthy, Kalpathy S.] Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02114 USA. [Grabowski, Eric F.] Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. [Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Redline, Raymond W.] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA. [Sagar, Pallavi] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [King, Mary Etta; Krishnamoorthy, Kalpathy S.; Grabowski, Eric F.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Roberts, Drucilla J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Redline, RW (reprint author), Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH USA. NR 17 TC 10 Z9 10 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 APR 17 PY 2008 VL 358 IS 16 BP 1713 EP 1723 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 288DO UT WOS:000254966600011 PM 18420504 ER PT J AU Goldstein, NE Genden, E Morrison, RS AF Goldstein, Nathan E. Genden, Eric Morrison, R. Sean TI Palliative care for patients with head and neck cancer - "I would like a quick return to a normal lifestyle" SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-LIFE; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; RADIATION-INDUCED XEROSTOMIA; SQUAMOUS-CELL CARCINOMA; INDUCED ORAL MUCOSITIS; HUMAN-PAPILLOMAVIRUS; PROGNOSTIC-FACTORS; LARYNGEAL-CANCER; PHASE-III; MANAGEMENT AB Head and neck cancers constitute a diverse group of diseases including malignancies of the oral cavity, oropharynx, larynx, sinuses, and skull base. Treatment of these cancers includes a combination of surgical resection, chemotherapy, and radiation. Due to both the patterns of disease recurrence and the adverse effects of treatments, patients with head and neck cancer often have a complex and prolonged course of illness that is marked by periods of freedom from disease and symptoms interspersed with bouts of serious illness, debility, and numerous physical and psychological symptoms including pain, dysphagia, weight loss, disfigurement, depression, and xerostomia. Thus, management of this disease is best provided by an interdisciplinary team that includes individuals from the disciplines of otolaryngology, palliative care, radiation oncology, oncology, nutrition, speech, and physical and occupational therapy. Using the case of Mr K, we describe the symptoms encountered by patients with head and neck cancer and suggest options for management. We discuss the psychological aspects that affect these patients, including issues such as changes in body image, quality of life, anxiety, and guilt. Finally, we discuss the importance of the interdisciplinary team in the care of these patients and outline the roles of each team member. By providing comprehensive care to patients with malignancies of the head and neck, clinicians can increase the likelihood that patients and their families will be able to obtain the best possible outcomes and quality of life. C1 [Goldstein, Nathan E.; Morrison, R. Sean] Mt Sinai Sch Med, Hertzberg Palliat Care Inst, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. [Genden, Eric] Mt Sinai Sch Med, Dept Otolaryngol, New York, NY 10029 USA. [Goldstein, Nathan E.; Morrison, R. Sean] James J Peters VA Med Ctr, Bronx, NY USA. RP Goldstein, NE (reprint author), Mt Sinai Sch Med, Dept Geriatr, Box 1070,1 Gustave Levy Pl, New York, NY 10029 USA. EM nathan.goldstein@mssm.edu FU NIA NIH HHS [K23AG025933, K24AG22345] NR 81 TC 23 Z9 23 U1 6 U2 9 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 APR 16 PY 2008 VL 299 IS 15 BP 1818 EP 1825 DI 10.1001/jama.299.15.1818 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 287ZA UT WOS:000254954800026 PM 18413876 ER PT J AU Firestein, R Blander, G Michan, S Oberdoerffer, P Ogino, S Campbell, J Bhimavarapu, A Luikenhuis, S de Cabo, R Fuchs, C Hahn, WC Guarente, LP Sinclair, DA AF Firestein, Ron Blander, Gil Michan, Shaday Oberdoerffer, Philipp Ogino, Shuji Campbell, Jennifer Bhimavarapu, Anupama Luikenhuis, Sandra de Cabo, Rafael Fuchs, Charles Hahn, William C. Guarente, Leonard P. Sinclair, David A. TI The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth SO PLOS ONE LA English DT Article AB Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD(+)-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR), a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a beta-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates beta-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of beta-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of beta-catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in beta-catenin-driven malignancies. C1 [Firestein, Ron; Michan, Shaday; Oberdoerffer, Philipp; Campbell, Jennifer; Luikenhuis, Sandra; Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. [Blander, Gil; Bhimavarapu, Anupama; Guarente, Leonard P.] Massachusetts Inst Technol, Dept Biol, Cambridge, MA USA. [Firestein, Ron; Ogino, Shuji] Brigham & Womens Hospital, Harvard Med Sch, Dept Pathol, Boston, MA USA. [Firestein, Ron; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [de Cabo, Rafael] NIH, NIA, Lab Expt Gerontol, Bethesda, MD USA. [Firestein, Ron; Fuchs, Charles; Hahn, William C.] Massachusetts Inst Technol, Broad Inst Harvard, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Sinclair, DA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. EM david_sinclair@hms.harvard.edu RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Sinclair, David/0000-0002-9936-436X; , rafael/0000-0003-2830-5693 FU NIH [T32]; Estee Lauder [postdoctoral fellowship]; National Space Biomedical Research Institute; Intramural Research Program of the NIH/NIA; Paul F. Glenn Foundation FX RF was supported by the NIH T32 Grant. GB by an Estee Lauder postdoctoral fellowship. PO by a National Space Biomedical Research Institute Grant. DAS, SO, CSF and LG by grants from NIH; RD in part by the Intramural Research Program of the NIH/NIA. DS is also supported by a gift from the Paul F. Glenn Foundation. NR 33 TC 318 Z9 337 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 16 PY 2008 VL 3 IS 4 AR e2020 DI 10.1371/journal.pone.0002020 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 371XZ UT WOS:000260867300029 PM 18414679 ER PT J AU Cavusoglu, E Chopra, V Battala, V Ruwende, C Yanarnadala, S Eng, C Pinsky, DJ Marmur, JD AF Cavusoglu, Erdal Chopra, Vineet Battala, Venkata Ruwende, Cyril Yanarnadala, Sunitha Eng, Calvin Pinsky, David J. Marmur, Jonathan D. TI Baseline plasma adiponectin levels as a predictor of left ventricular systolic dysfunction in patients referred for coronary angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; MYOCARDIAL-INFARCTION; MORTALITY; PROTEIN AB The objective of the present study was to determine the association between plasma adiponectin and left ventricular (LV) systolic function. Baseline plasma adiponectin was measured in 389 patients undergoing coronary angiography for a variety of indications at a Veterans Affairs Medical Center. Detailed demographic, clinical, laboratory, and angiographic data were available for patients. LV systolic function was assessed using ventriculography, and patients were grouped into those with normal or mild dysfunction (ejection fraction >= 45%) versus those with moderate to severe systolic dysfunction (ejection fraction <45%). After adjusting for a variety of clinically relevant covariates known to affect LV systolic function, adiponectin was independently associated with LV systolic function in the entire cohort of patients (p = 0.0002) using multivariate linear regression analysis. In addition, using multivariate logistic regression analysis, adiponectin was an independent predictor of the presence of moderate to severe LV dysfunction (odds ratio 1.54, 95% confidence interval 1.21 to 1.97, p = 0.0005). Moreover, baseline adiponectin was also independently associated with LV function in both the myocardial infarction (MI) and non-MI subpopulations of patients (p = 0.0401 and p = 0.0023, respectively). Finally, in the non-MI subpopulation, baseline adiponectin was an independent predictor of moderate to severe LV systolic dysfunction (odds ratio 1.52, 95% confidence interval 1.15 to 2.02, p = 0.0034). In conclusion, baseline plasma adiponectin was an independent predictor of LV systolic dysfunction in a population of patients referred for coronary angiography. (C) 2008 Elsevier Inc. All rights reserved. C1 [Cavusoglu, Erdal; Battala, Venkata; Marmur, Jonathan D.] SUNY Hlth Sci Ctr, Dept Med, Div Cardiol, Brooklyn, NY 11203 USA. [Cavusoglu, Erdal; Chopra, Vineet; Eng, Calvin] Bronx Vet Affairs Med Ctr, Dept Med, Div Cardiol, Bronx, NY USA. [Ruwende, Cyril; Yanarnadala, Sunitha; Pinsky, David J.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Cavusoglu, E (reprint author), SUNY Hlth Sci Ctr, Dept Med, Div Cardiol, 450 Clarkson Ave, Brooklyn, NY 11203 USA. EM ecavusoglu@aol.com NR 14 TC 15 Z9 17 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2008 VL 101 IS 8 BP 1073 EP 1078 DI 10.1016/j.amjcird.2007.12.008 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 288XT UT WOS:000255020200001 PM 18394435 ER PT J AU Butler, J Mooyaart, EAQ Dannemann, N Bamberg, F Shapiro, MD Ferencik, M Brady, TJ Hoffmann, U AF Butler, Javed Mooyaart, Eline A. Q. Dannemann, Nina Bamberg, Fabian Shapiro, Michael D. Ferencik, Maros Brady, Thomas J. Hoffmann, Udo TI Relation of the metabolic syndrome to quantity of coronary atherosclerotic plaque SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; CHOLESTEROL EDUCATION-PROGRAM; CARDIOVASCULAR-DISEASE; SUBCLINICAL ATHEROSCLEROSIS; INTRAVASCULAR ULTRASOUND; UNITED-STATES; ADULTS; PROGRESSION; PREVALENCE; MORTALITY AB Although metabolic syndrome (MS) is associated with adverse cardiovascular outcomes, its association with the presence and extent of coronary atherosclerotic plaques is not well described. To assess this relation, multidetector computed tomography-based patterns of coronary plaque were assessed in 77 patients enrolled in the ROMICAT study (age 54 +/- 12 years; 79% Caucasians, and 36% women) and compared betwen those who did (n = 35; 45%) and did not (n = 42; 55%) have MS. The presence of any, calcified, and noncalcified plaque was significantly higher in patients with than without MS (91%, 74%, and 77% vs 46%, 45%, and 40% segments with plaque, respectively; all p <0.01). The overall number of segments with plaques was also higher in patients with MS (5.8 +/- 3.7 vs 2.1 +/- 3.3; p <0.001). MS was independently associated with both the presence and extent of overall plaques after adjusting for the Framingham risk score (odds ratio 6.7, 95% confidence interval 1.6 to 28.8, p <0.01 for presence, beta coefficient = 3.59 +/- 0.88 [SE], p = 0.009 for extent) and individual risk factors, including age, gender, smoking, body mass index, hypertension, diabetes, hyperlipidemia, and clinical coronary disease (odds ratio 8.4, 95% confidence interval 1.7 to 42.5, p = 0.008 for presence, beta coefficient = 2.35 +/- 0.86 [SE], p = 0.007 for extent). Similarly, MS was independently associated with calcified and non- calcified plaques individually. In conclusion, MS was independently associated with the presence and extent of both calcified and noncalcified coronary atherosclerotic plaques detected using multidetector computed tomography. These data may explain the higher cardiovascular risk in these patients and may lay the foundation for studies to determine whether such information may improve risk stratification. (C) 2008 Elsevier Inc. All rights reserved. C1 [Butler, Javed; Mooyaart, Eline A. Q.; Dannemann, Nina; Bamberg, Fabian; Shapiro, Michael D.; Ferencik, Maros; Brady, Thomas J.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02115 USA. [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02115 USA. EM uhoffmann@partners.org FU NHLBI NIH HHS [R01 HL080053, R01 HL080053-01A1, R01 HL080053-03, R01 HL080053-02] NR 24 TC 12 Z9 13 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2008 VL 101 IS 8 BP 1127 EP 1130 DI 10.1016/j.amjcard.2007.12.012 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 288XT UT WOS:000255020200011 PM 18394445 ER PT J AU Camtbell, R Cooper, GS Gilkeson, GS AF Camtbell, Robert, Jr. Cooper, Glinda S. Gilkeson, Gary S. TI Two aspects of the clinical and humanistic burden of systemic lupus erythematosus: Mortality risk and quality of life early in the course of disease SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID STAGE RENAL-DISEASE; HEALTH-STATUS; DEATH; IMPACT; RACE; AGE; POPULATION; PREDICTORS; PROGNOSIS; OUTCOMES AB Objective. To evaluate mortality risk and predictors among recently diagnosed systemic lupus erythematosus (SLE) patients. Methods. The vital status of 265 SLE patients and 355 controls enrolled in the Carolina Lupus Study (median time since diagnosis 13 months) was determined similar to 5 years after enrollment. We also assessed the utility of an 8-item quality of life instrument, derived from the standard 36-item Medical Outcomes Study Short Form 36, as an additional measure of disease impact. Results. Five years after diagnosis, 9.7% of patients compared with 0.3% of controls had died (P < 0.0001). Increased mortality risk was seen among older patients (adjusted hazard ratio [HR] 1.03, 95% confidence interval [95% CI] 1.01-1.06 per 1-year increment in age) and among men, African Americans, patients with lupus nephritis, and patients with anti-double-stranded DNA antibodies (adjusted HR similar to 2.0 for each of these factors). In addition, patients who did not provide a blood sample at study enrollment experienced increased mortality risk (age-, sex-, and race-adjusted HR 3.7, 95% CI 1.5-9.1). Similar results were seen in analyses limited to time from study enrollment. Physical component scores of the quality of life measure were 7.7 points lower (P < 0.0001) and mental component scores were 1.8 points lower (P = 0.07) in patients compared with controls. Conclusion. The mortality risk among SLE patients is significant, particularly among African Americans, even early in the disease process and even with currently available treatments. Differences between cases and controls in health-related quality of life using the Short Form 8 also demonstrate the multidimensional burden of SLE. C1 [Camtbell, Robert, Jr.; Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Cooper, Glinda S.] US EPA, Washington, DC 20460 USA. [Gilkeson, Gary S.] Ralph H. Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Camtbell, R (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. FU Intramural NIH HHS; NIAMS NIH HHS [1T32-AR050958, 2R01-AR045476, P60-AR049459] NR 28 TC 6 Z9 8 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2008 VL 59 IS 4 BP 458 EP 464 DI 10.1002/art.23539 PG 7 WC Rheumatology SC Rheumatology GA 288JT UT WOS:000254983400002 PM 18383420 ER PT J AU Krystal, JH Carter, CS Geschwind, D Manji, HK March, JS Nestler, EJ Zubieta, JK Charney, DS Goldman, D Gur, RE Lieberman, JA Roy-Byrne, P Rubinow, DR Anderson, SA Barondes, S Berman, KF Blair, J Braff, DL Brown, ES Calabrese, JR Carlezon, WA Cook, EH Davidson, RJ Davis, M Desimone, R Drevets, WC Duman, RS Essock, SM Faraone, SV Freedman, R Friston, KJ Gelernter, J Geller, B Gill, M Gould, E Grace, AA Grillon, C Gueorguieva, R Hariri, AR Innis, RB Jones, EG Kleinman, JE Koob, GF Krystal, AD Leibenluft, E Levinson, DF Levitt, PR Lewis, DA Liberzon, I Lipska, BK Marder, SR Markou, A Mason, GF McDougle, CJ McEwen, BS McMahon, FJ Meaney, MJ Meltzer, HY Merikangas, KR Meyer-Lindenberg, A Mirnics, K Monteggia, LM Neumeister, A O'Brien, CP Owen, MJ Pine, DS Rapoport, JL Rauch, SL Robbins, TW Rosenbaum, JF Rosenberg, DR Ross, CA Rush, AJ Sackeim, HA Sanacora, G Schatzberg, AF Shaham, Y Siever, LJ Sunderland, T Tecott, LH Thase, ME Todd, RD Weissman, MM Yehuda, R Yoshikawa, T Young, EA McCandless, R AF Krystal, John H. Carter, Cameron S. Geschwind, Daniel Manji, Husseini K. March, John S. Nestler, Eric J. Zubieta, Jon-Kar Charney, Dennis S. Goldman, David Gur, Raquel E. Lieberman, Jeffrey A. Roy-Byrne, Peter Rubinow, David R. Anderson, Stewart A. Barondes, Samuel Berman, Karen F. Blair, James Braff, David L. Brown, E. Sherwood Calabrese, Joseph R. Carlezon, William A., Jr. Cook, Edwin H., Jr. Davidson, Richard J. Davis, Michael Desimone, Robert Drevets, Wayne C. Duman, Ronald S. Essock, Susan M. Faraone, Stephen V. Freedman, Robert Friston, Karl J. Gelernter, Joel Geller, Barbara Gill, Michael Gould, Elizabeth Grace, Anthony A. Grillon, Christian Gueorguieva, Ralitza Hariri, Ahmad R. Innis, Robert B. Jones, Edward G. Kleinman, Joel E. Koob, George F. Krystal, Andrew D. Leibenluft, Ellen Levinson, Douglas F. Levitt, Pat R. Lewis, David A. Liberzon, Israel Lipska, Barbara K. Marder, Stephen R. Markou, Athina Mason, Graeme F. McDougle, Christopher J. McEwen, Bruce S. McMahon, Francis J. Meaney, Michael J. Meltzer, Herbert Y. Merikangas, Kathleen R. Meyer-Lindenberg, Andreas Mirnics, Karoly Monteggia, Lisa M. Neumeister, Alexander O'Brien, Charles P. Owen, Michael J. Pine, Daniel S. Rapoport, Judith L. Rauch, Scott L. Robbins, Trevor W. Rosenbaum, Jerrold F. Rosenberg, David R. Ross, Christopher A. Rush, A. John Sackeim, Harold A. Sanacora, Gerard Schatzberg, Alan F. Shaham, Yavin Siever, Larry J. Sunderland, Trey Tecott, Laurence H. Thase, Michael E. Todd, Richard D. Weissman, Myrna M. Yehuda, Rachel Yoshikawa, Takeo Young, Elizabeth A. McCandless, R. TI It is time to take a stand for medical research and against terrorism targeting medical scientists SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 [Krystal, John H.; Duman, Ronald S.; Gelernter, Joel; Mason, Graeme F.; Neumeister, Alexander; Sanacora, Gerard] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Krystal, John H.; Duman, Ronald S.; Gelernter, Joel; Mason, Graeme F.; Neumeister, Alexander; Sanacora, Gerard] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. [Duman, Ronald S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT USA. [Duman, Ronald S.] Yale Univ, Sch Med, Interdept Neurosci Program, New Haven, CT USA. [Gelernter, Joel] VA Connecticut Hlthcare Syst, West Haven, CT USA. [Nestler, Eric J.; Brown, E. Sherwood; Monteggia, Lisa M.; Rush, A. John; McCandless, R.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Nestler, Eric J.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Braff, David L.; Markou, Athina] Univ Calif San Diego, Dept Psychiat, Sch Med, San Diego, CA 92103 USA. [Braff, David L.; Markou, Athina] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Carter, Cameron S.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Carter, Cameron S.] Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. [Jones, Edward G.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Geschwind, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Geschwind, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Marder, Stephen R.] 22 Mental Illness Res Educ & Clin Ctr, VA Vet Integrated Serv Networks, Los Angeles, CA USA. [Barondes, Samuel] Univ Calif San Francisco, Ctr Neurobiol & Psychiat, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. [Tecott, Laurence H.] Univ Calif San Francisco, Ctr Neurobiol & Psychiat, Dept Psychiat, San Francisco, CA 94143 USA. [Levinson, Douglas F.] Stanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94304 USA. [Schatzberg, Alan F.] Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94304 USA. [Grace, Anthony A.; Hariri, Ahmad R.; Lewis, David A.; Thase, Michael E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Grace, Anthony A.; Lewis, David A.] Univ Pittsburgh, Sch Med, Dept Neurosci, Pittsburgh, PA USA. [Grace, Anthony A.] Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA USA. [Hariri, Ahmad R.] Univ Pittsburgh, Sch Med, Ctr Neural Basis Cognit, Pittsburgh, PA USA. [O'Brien, Charles P.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Sch Med, Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Sch Med, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Sch Med, Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [O'Brien, Charles P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Manji, Husseini K.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Lab Mol Pathophysiol & Exp, Bethesda, MD 20892 USA. [McMahon, Francis J.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Genet Basis Mood & Anxiety, Bethesda, MD 20892 USA. [Grillon, Christian] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Unit Affect Psychophysiol, Bethesda, MD 20892 USA. [Leibenluft, Ellen] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Unit Affect Disorders, Bethesda, MD 20892 USA. [Blair, James] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Unit Affect Cognit Neurosc, Bethesda, MD 20892 USA. [Pine, Daniel S.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Sect Dev & Affect Neurosc, Bethesda, MD 20892 USA. [Drevets, Wayne C.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Sect Neuroimaging, Bethesda, MD 20892 USA. [Kleinman, Joel E.; Lipska, Barbara K.] NIMH, NIH, Dept Hlth & Human Serv,Sect Neuropathol, Intramural Res Program,Mood & Anxiety Disorders P, Bethesda, MD 20892 USA. [Berman, Karen F.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. [Shaham, Yavin] NIMH, NIH, Dept Hlth & Human Serv,Behav Neurosci Branch, Intramural Res Program,Clin Brain Disorders Branc, Bethesda, MD 20892 USA. [Innis, Robert B.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Mol Imaging Branch, Bethesda, MD 20892 USA. [Rapoport, Judith L.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Child Psychiat Branch, Bethesda, MD 20892 USA. [Rubinow, David R.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Behav Endocrinol Branch, Bethesda, MD 20892 USA. [Goldman, David] NIAAA, NIH, Neurogenet Lab, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Behav Sci, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Rosenbaum, Jerrold F.] Massachusetts Gen Hosp, Dept Psychiat, Belmont, MA USA. [Carlezon, William A., Jr.] McLean Hosp, Mailman Res Ctr, Belmont, MA 02178 USA. [Carlezon, William A., Jr.; Rauch, Scott L.; Rosenbaum, Jerrold F.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Desimone, Robert] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Rubinow, David R.] Emory Univ, Dept Psychiat, Yerkes Natl Primate Ctr, Atlanta, GA 30322 USA. Univ N Carolina, Dept Psychiat & Behav Sci, Chapel Hill, NC USA. [March, John S.; Krystal, Andrew D.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Zubieta, Jon-Kar; Young, Elizabeth A.] Univ Michigan, Dept Psychiat, Med Ctr, Ann Arbor, MI 48109 USA. [Zubieta, Jon-Kar; Liberzon, Israel; Young, Elizabeth A.] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Rosenberg, David R.] Wayne State Univ, Sch Med, Dept Psychiat, Detroit, MI USA. [McDougle, Christopher J.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenille Res, Chicago, IL 60612 USA. [Davidson, Richard J.] Univ Wisconsin, WM Key Lab Funct Brain Imaging & Behav, Madison, WI USA. [Sackeim, Harold A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Sackeim, Harold A.] Columbia Univ, Mailman Sch Publ Hlth, Dept Radiol, Coll Phys & Surg, New York, NY 10027 USA. [Weissman, Myrna M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. [Charney, Dennis S.; Siever, Larry J.; Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [McEwen, Bruce S.] Rockefeller Univ, Harold & Margaret Milliken Hatch Lab Neuroendocri, Neuroendocrinol Lab, New York, NY 10021 USA. [Siever, Larry J.; Yehuda, Rachel] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA. [Freedman, Robert] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Boulder, CO 80309 USA. [Freedman, Robert] Denver VA Med Ctr, MIRECC, VISN19, Denver, CO USA. [Meltzer, Herbert Y.; Mirnics, Karoly] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Levitt, Pat R.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. [Levitt, Pat R.] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN USA. [Roy-Byrne, Peter] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Roy-Byrne, Peter] Harborview Med Ctr, Harborview Ctr Hlthcare Improvement Addict, Seattle, WA USA. [Geller, Barbara; Todd, Richard D.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Calabrese, Joseph R.] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr,Dept Psychiat, Bipolar Disorder Res Ctr,Mood Disorders Program, Cleveland, Qld, Australia. [Gould, Elizabeth] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. [Meaney, Michael J.] McGill Univ, Dept Psychiat, Montreal Neurol Inst, Montreal, PQ, Canada. [Meaney, Michael J.] McGill Univ, Doughlas Hosp Res Ctr, Ctr Studies Humnan Stress, Montreal, PQ, Canada. [Gill, Michael] Univ Dublin Trinity Coll, Inst Mol Med, Dublin 2, Ireland. [Gill, Michael] Univ Dublin Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [Yoshikawa, Takeo] RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama, Japan. [Friston, Karl J.] UCL, Inst Neurol, Wellcome Trust Ctr Neuroimaging, London WC1E 6BT, England. [Robbins, Trevor W.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 1TN, England. [Owen, Michael J.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, Wales. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychiat, D-6800 Mannheim, Germany. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychotherapy, D-6800 Mannheim, Germany. RP Krystal, JH (reprint author), VA Connecticut Hlth Syst, Psychiat Serv 116 A, 950 Campbell Ave, West Haven, CT 06516 USA. EM john.krystal@yale.edu RI Hariri, Ahmad/D-5761-2011; Mirnics, Karoly/E-6730-2010; Krystal, Andrew/J-7109-2013; McMahon, Francis/A-7290-2009; Friston, Karl/D-9230-2011; turton, miranda/F-4682-2011; shaham, yavin/G-1306-2014; Lewis, David/G-4053-2014; Meltzer, Herbert/E-8131-2013; Goldman, David/F-9772-2010; koob, george/P-8791-2016; Meyer-Lindenberg, Andreas/H-1076-2011; OI Rush, Augustus/0000-0003-2004-2382; Weissman, Myrna/0000-0003-3490-3075; McMahon, Francis/0000-0002-9469-305X; Gueorguieva, Ralitza/0000-0003-0944-5973; Faraone, Stephen/0000-0002-9217-3982; Mirnics, Karoly/0000-0002-5521-0254; Krystal, Andrew/0000-0002-6702-781X; Friston, Karl/0000-0001-7984-8909; Lewis, David/0000-0002-3225-6778; Goldman, David/0000-0002-1724-5405; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Gill, Michael/0000-0003-0206-5337 FU Medical Research Council [G0001354] NR 3 TC 6 Z9 6 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2008 VL 63 IS 8 BP 725 EP 727 DI 10.1016/j.biopsych.2008.03-005 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 286AJ UT WOS:000254817100001 PM 18371494 ER PT J AU Tonomura, N Habiro, K Shimizu, A Sykes, M Yang, YG AF Tonomura, Noriko Habiro, Katsuyoshi Shimizu, Akira Sykes, Megan Yang, Yong-Guang TI Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model SO BLOOD LA English DT Article ID FOLLICULAR DENDRITIC CELLS; SCID-HU MOUSE; HIV-1 INFECTION; IMMUNE-SYSTEM; MICE; LYMPHOCYTES; BLOOD; RECONSTITUTION; IGG AB Humanized mice with a functional human immune system would be very useful for in vivo studies of human immunobiology. We have previously shown that cotransplantation of human fetal thymus/liver tissues and CD34(+) fetal liver cells into immunodeficient nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice leads to the development of multiple lineages of human lymphohematopoietic cells and formation of secondary lymphoid organs with normal architecture. Here, we evaluated the ability of these humanized mice to develop antigen-specific, T cell-dependent antibody responses after in vivo immunization with T-dependent antigen, 2,4-dinitrophenyl hapten-keyhole limpet hemocyanin (DNP23-KLH). Human T cells from DNP23-KLH-immunized mice showed strong proliferation in response to KLH in vitro. Furthermore, T cell-dependent production of DNP-specific human antibodies (mainly IgG1 and IgG2) was detected in all immunized mice. These results confirm that a functional human immune system can be established in immunodeficient mice through cotransplantation of human fetal thymus/liver tissues and CD34(+) hematopoietic stem/progenitor cells. C1 [Tonomura, Noriko; Habiro, Katsuyoshi; Shimizu, Akira; Sykes, Megan; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Yang, YG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH East,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU NIAID NIH HHS [P30 AI060354, P01 AI 045897, P01 AI045897, P30 AI 060354] NR 20 TC 59 Z9 63 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2008 VL 111 IS 8 BP 4293 EP 4296 DI 10.1182/blood-2007-11-121319 PG 4 WC Hematology SC Hematology GA 290PM UT WOS:000255134700053 PM 18270327 ER PT J AU Dayyani, F Wang, JF Yeh, JRJ Ahn, EY Tobey, E Zhang, DE Bernstein, ID Peterson, RT Sweetser, DA AF Dayyani, Farshid Wang, Jianfeng Yeh, Jing-Ruey J. Ahn, Eun-Young Tobey, Erica Zhang, Dong-Er Bernstein, Irwin D. Peterson, Randall T. Sweetser, David A. TI Loss of TLE1 and TLE4 from the del(9q) commonly deleted region in AML cooperates with AML1-ETO to affect myeloid cell proliferation and survival SO BLOOD LA English DT Article ID FACTOR-KAPPA-B; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; HEMATOPOIETIC STEM-CELLS; PEDIATRIC-ONCOLOGY-GROUP; TRANSGENIC MOUSE MODEL; WNT SIGNALING PATHWAY; TUMOR-SUPPRESSOR; GENE-EXPRESSION; FUSION PROTEIN AB Deletions on chromosome 9q are seen in a subset of acute myeloid leukemia (AML) cases and are specifically associated with t(8;21) AML. We previously defined the commonly deleted region in del(9q) AML and characterized the genes in this interval. To determine the critical lost gene(s) that might cooperate with the AML1-ETO fusion gene produced by t(8;21), we developed a set of shRNAs directed against each gene in this region. Within this library, shRNAs to TLE1 and TLE4 were the only shRNAs capable of rescuing AML1-ETO expressing U937T-A/E cells from AML1-ETO-induced cell-cycle arrest and apoptosis. Knockdown of TLE1 or TLE4 levels increased the rate of cell division of the AML1-ETO-expressing Kasumi-1 cell line, whereas forced expression of either TLE1 or TLE4 caused apoptosis and cell death. Knockdown of Gro3, a TLE homolog in zebrafish, cooperated with AML1-ETO to cause an accumulation of noncirculating hematopoietic blast cells. Our data are consistent with a model in which haploinsufficiency of these TLEs overcomes the negative survival and antiproliferative effects of AML1-ETO on myeloid progenitors, allowing preleukemic stem cells to expand into AML. This study is the first to implicate the TLEs as potential tumor suppressor genes in myelold leukemia. C1 [Dayyani, Farshid; Wang, Jianfeng; Tobey, Erica; Sweetser, David A.] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02114 USA. [Yeh, Jing-Ruey J.; Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Yeh, Jing-Ruey J.; Peterson, Randall T.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ahn, Eun-Young; Zhang, Dong-Er] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Bernstein, Irwin D.; Sweetser, David A.] Childrens Oncol Grp, Arcadia, CA USA. [Bernstein, Irwin D.] Fred Hutchinson Canc Res Ctr, Dept Pediat Oncol, Seattle, WA 98104 USA. [Yeh, Jing-Ruey J.; Peterson, Randall T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sweetser, DA (reprint author), Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, 55 Fruit St,Jackson 904, Boston, MA 02114 USA. EM dsweetser@partners.org FU NCI NIH HHS [CA118498, R01 CA118498, 5T32CA71345-09, U24 CA114766, CA96735, U10CA98543, U10 CA098543, 1R01CA115772, T32 CA071345, CA98543, R01 CA115772, R01 CA096735]; NHLBI NIH HHS [R01 HL079267, HL079267] NR 74 TC 41 Z9 42 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2008 VL 111 IS 8 BP 4338 EP 4347 DI 10.1182/blood-2007-07-103291 PG 10 WC Hematology SC Hematology GA 290PM UT WOS:000255134700058 PM 18258796 ER PT J AU Dall'Era, MA Cooperberg, MR Chan, JM Davies, BJ Albertsen, PC Klotz, LH Warlick, CA Holmberg, L Bailey, DE Wallace, ME Kantoff, PW Carroll, PR AF Dall'Era, Marc A. Cooperberg, Matthew R. Chan, June M. Davies, Benjamin J. Albertsen, Peter C. Klotz, Laurence H. Warlick, Christopher A. Holmberg, Lars Bailey, Donald E., Jr. Wallace, Meredith E. Kantoff, Philip W. Carroll, Peter R. TI Active surveillance for early-stage prostate cancer - Review of the current literature SO CANCER LA English DT Review DE prostate cancer; active surveillance; review; risk stratification ID QUALITY-OF-LIFE; SELECTIVE DELAYED INTERVENTION; PSA DOUBLING TIME; RADICAL PROSTATECTOMY; ANTIGEN ERA; CONSERVATIVE MANAGEMENT; DEFINITIVE THERAPY; DISEASE RECURRENCE; NATURAL-HISTORY; CURATIVE INTENT AB The natural history of prostate cancer is remarkably heterogeneous and, at this time, not completely understood. The widespread adoption and application of prostate-specific antigen (PSA) screening has led to a dramatic shift toward the diagnosis of low-volume, nonpalpable, early-stage rumors. Autopsy and early observational studies have shown that approximately I in 3 men aged >50 years has histologic evidence of prostate cancer, with a significant portion of tumors being small and possibly clinically insignificant. Utilizing the power of improved contemporary risk stratification schema to better identify patients with a low risk of cancer progression, several centers are gaining considerable experience with active surveillance and delayed, selective, and curative therapy. A literature review was performed to evaluate the rationale behind active surveillance for prostate cancer and to describe the early experiences from surveillance protocols. It appears that a limited number of men on active surveillance have required treatment, with the majority of such men having good outcomes after delayed selective intervention for progressive disease. The best candidates for active surveillance are being defined, as are predictors of active treatment. The psychosocial ramifications of surveillance for prostate cancer can be profound and future needs and unmet goals will be discussed. C1 [Dall'Era, Marc A.; Cooperberg, Matthew R.; Chan, June M.; Davies, Benjamin J.; Carroll, Peter R.] Univ Calif San Francisco, Dept Urol, Francisco Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Albertsen, Peter C.] Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA. [Klotz, Laurence H.] Univ Toronto, Div Urol, Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto, ON, Canada. [Warlick, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Holmberg, Lars] Kings Coll London, Div Canc Studies, London WC2R 2LS, England. [Bailey, Donald E., Jr.] Duke Univ, Sch Nursing, Durham, NC USA. [Wallace, Meredith E.] Fairfield Univ, Sch Nursing, Fairfield, CT 06430 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Dall'Era, MA (reprint author), Univ Calif San Francisco, Dept Urol, Francisco Comprehens Canc Ctr, 1600 Divisadero,Box 1695, San Francisco, CA 94143 USA. EM mdallera@urology.ucsf.edu RI Cooperberg, Matthew/B-3867-2008 NR 69 TC 180 Z9 185 U1 2 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2008 VL 112 IS 8 BP 1650 EP 1659 DI 10.1002/cncr23373 PG 10 WC Oncology SC Oncology GA 288XH UT WOS:000255018900003 PM 18306379 ER PT J AU Zhang, JM Smolen, GA Haber, DA AF Zhang, Jianmin Smolen, Gromoslaw A. Haber, Daniel A. TI Negative regulation of YAP by LATS1 underscores evolutionary conservation of the Drosophila Hippo pathway SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; CANCER CELL-LINES; PROMOTES APOPTOSIS; BANTAM MICRORNA; PROTEIN-KINASE; SIZE-CONTROL; CYCLE EXIT; ORGAN SIZE; PROLIFERATION AB The Hippo pathway defines a novel signaling cascade regulating cell proliferation and survival in Drosophila, which involves the negative regulation of the transcriptional coactivator Yorkie by the kinases Hippo and Warts. We have recently shown that the human ortholog of Yorkie, YAP, maps to a minimal amplification locus in mouse and human cancers, and that it mediates dramatic transforming activity in MCF10A primary mammary epithelial cells. Here, we show that LATS proteins (mammalian orthologs of Warts) interact directly with YAP in mammalian cells and that ectopic expression of LATS1, but not LATS2, effectively suppresses the YAP phenotypes. Furthermore, shRNA-mediated knockdown of LATS1 phenocopies YAP overexpression. Because this effect can be suppressed by simultaneous YAP knockdown, it suggests that YAP is the primary target of LATS1 in mammalian cells. Expression profiling of genes induced by ectopic expression of YAP or by knockdown of LATS I reveals a subset of potential Hippo pathway targets implicated in epithelial-to-mesenchymal transition, suggesting that this is a key feature of YAP signaling in mammalian cells. C1 [Zhang, Jianmin; Smolen, Gromoslaw A.; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Bldg149,13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu FU NCI NIH HHS [F32 CA117737]; PHS HHS [P01 95281] NR 36 TC 135 Z9 145 U1 3 U2 17 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 APR 15 PY 2008 VL 68 IS 8 BP 2789 EP 2794 DI 10.1158/0008-5472.CAN-07-6205 PG 6 WC Oncology SC Oncology GA 290CM UT WOS:000255100500030 PM 18413746 ER PT J AU Ahmad, R Raina, D Meyer, C Kufe, D AF Ahmad, Rehan Raina, Deepak Meyer, Colin Kufe, Donald TI Triterpenoid CDDO-methyl ester inhibits the janus-activated kinase-1 (JAK1)-> Signal transducer and activator of transcription-3 (STAT3) pathway by direct inhibition of JAK1 and STAT3 SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; ACUTE MYELOGENOUS LEUKEMIA; TUMOR-NECROSIS-FACTOR; KAPPA-B-KINASE; SIGNAL TRANSDUCER; INDUCE APOPTOSIS; COVALENT MODIFICATION; PROTEIN TARGETS; ACID; MECHANISM AB The C-28 methyl ester of the oleane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO-Me) induces apoptosis of human cancer cells by disrupting redox balance and is in clinical trials. CDDO-Me contains alpha,beta-unsaturated carbonyl groups that form reversible adducts with thiol nucleophiles. The present studies show that CDDO-Me blocks interleukin-6 (IL-6)-induced and constitutive activation of the Janus-activated kinase 1 (JAK1) in cells. In support of a direct mechanism, CDDO-Me forms adducts with JAK1 at Cys(1077) in the kinase domain and inhibits JAK1 activity. In concert with these results, CDDO-Me blocked IL-6-induced and constitutive activation of signal transducer and activator of transcription 3 (STAT3). Moreover, we show that CDDO-Me (a) binds directly to STAT3 by a mechanism dependent on the alkylation of Cys(259) and (b) inhibits the formation of STAT3 dimers. These findings indicate that CDDO-Me inhibits activation of the JAK1-->STAT3 pathway by forming adducts with both JAK1 and STAT3. C1 [Ahmad, Rehan; Raina, Deepak; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Meyer, Colin] Reata Pharmaceut Inc, Dallas, TX USA. RP Kufe, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [P50 CA100707-01, CA42802, P50 CA100707, R01 CA042802-13, R01 CA098628, R01 CA098628-01, CA100707, CA98628, R01 CA042802] NR 46 TC 61 Z9 61 U1 1 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 APR 15 PY 2008 VL 68 IS 8 BP 2920 EP 2926 DI 10.1158/0008-5472.CAN-07-3036 PG 7 WC Oncology SC Oncology GA 290CM UT WOS:000255100500045 PM 18413761 ER PT J AU Epardaud, M Elpek, KG Rubinstein, MP Yonekura, AR Bellemare-Pelletier, A Bronson, R Hamerman, JA Goldrath, AW Turley, SJ AF Epardaud, Mathieu Elpek, Kutlu G. Rubinstein, Mark P. Yonekura, Ai-ris Bellemare-Pelletier, Angelique Bronson, Roderick Hamerman, Jessica A. Goldrath, Ananda W. Turley, Shannon J. TI Lnterleukin-15/interieukin-15R alpha complexes promote destruction of established tumors by reviving tumor-resident CD8(+) T cells SO CANCER RESEARCH LA English DT Article ID IN-VIVO; ADOPTIVE IMMUNOTHERAPY; CANCER-IMMUNOTHERAPY; ANTITUMOR LYMPHOCYTES; TRANSGENIC MICE; IL-15; IMMUNITY; NK; THERAPY; INTERLEUKIN-15 AB Tumors often escape immune-mediated destruction by suppressing lymphocyte infiltration or effector function. New approaches are needed that overcome this suppression and thereby augment the tumoricidal capacity of tumor-reactive lymphocytes. The cytokine interleukin-15 (IL-15) promotes proliferation and effector capacity of CD8(+) T cells, natural killer (NK) cells, and NKT cells; however, it has a short half-life and high doses are needed to achieve functional responses in vivo. The biological activity of IL-15 can be dramatically increased by complexing this cytokine to its soluble receptor, IL-15R alpha. Here, we report that in vivo delivery of IL-15/IL-15R alpha complexes triggers rapid and significant regression of established solid tumors in two murine models. Despite a marked expansion of IL-2/IL-15R beta(+) cells in lymphoid organs and peripheral blood following treatment with IL-15/IL-15R alpha complexes, the destruction of solid tumors was orchestrated by tumor-resident rather than newly infiltrating CD8(+) T cells. Our data provide novel insights into the use of IL-15/IL-15R alpha complexes to relieve tumor-resident T cells from functional suppression by the tumor microenvironment and have significant implications for cancer immunotherapy and treatment of chronic infections. C1 [Epardaud, Mathieu; Elpek, Kutlu G.; Yonekura, Ai-ris; Bellemare-Pelletier, Angelique; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Yonekura, Ai-ris] Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. [Bronson, Roderick; Turley, Shannon J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Epardaud, Mathieu] INRA, Dept Virol & Immunol Mol UR892, Jouy En Josas, France. [Rubinstein, Mark P.; Goldrath, Ananda W.] Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA. [Hamerman, Jessica A.] Benaroya Res Inst, Program Immunol, Seattle, WA USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,D1440A, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu FU NIAID NIH HHS [R01 AI067545] NR 51 TC 86 Z9 86 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 APR 15 PY 2008 VL 68 IS 8 BP 2972 EP 2983 DI 10.1158/0008-5472.CAN-08-0045 PG 12 WC Oncology SC Oncology GA 290CM UT WOS:000255100500051 PM 18413767 ER PT J AU Kobayashi, N Barnard, RJ Said, J Hong-Gonzalez, J Corman, DM Ku, M Doan, NB Gui, D Elashoff, D Cohen, P Aronson, WJ AF Kobayashi, Naoko Barnard, R. James Said, Jonathan Hong-Gonzalez, Jenny Corman, Dan M. Ku, Melvin Doan, Ngan Bao Gui, Dorina Elashoff, David Cohen, Pinchas Aronson, William J. TI Effect of low-fat diet on development of prostate cancer and Akt phosphorylation in the Hi-Myc transgenic mouse model SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-I; INTRAEPITHELIAL NEOPLASIA; CYCLIN D1; C-MYC; BINDING PROTEIN-1; CELL-GROWTH; NOBLE RAT; IGF-I; RISK; PROGRESSION AB This study evaluated the effect of dietary fat on prostate cancer development by using the Hi-Myc mouse transgenic prostate cancer model. Hi-Myc mice develop marine prostatic intraepithelial neoplasia (mPIN) as early as 2 to 4 weeks and invasive adenocarcinoma between 6 and 9 months due to the overexpression of human c-Myc in the mouse prostate. Three-week-old male Hi-Myc mice were placed on high-fat (HF; 42% Kcal) or low-fat (LF; 12% Kcal) diets, and equal caloric intake was maintained until euthanasia at 7 months. The number of mice that developed invasive adenocarcinoma at 7 months was 27% less in the LF diet group (12/28) compared with the HF diet group (23/33, P < 0.05). Epithelial cells in mPIN lesions in the LF group had a significantly lower proliferative index compared with epithelial cells in the HF group (21.7% versus 28.9%, P < 0.05). During the mPIN phase of carcinogenesis (4 months), the LF group had higher serum insulin-like growth factor (IGF) binding protein-1 levels (21.0 +/- 8.9 ng/mL versus 3.2 +/- 0.8 ng/mL, P < 0.05) relative to the HF group. Akt (Ser(473)) phosphorylation, Akt kinase activity, and phosphorylation of downstream targets of Akt in prostates were significantly reduced in the LF diet group compared with the HF group. We conclude that dietary fat reduction delays transition from mPIN to invasive cancer in this Myc-driven transgenic mouse model, possibly through suppression of the IGF-Akt pathway and decreased proliferation of mPIN epithelial cells. C1 [Kobayashi, Naoko; Aronson, William J.] Univ Calif Los Angeles, Dept Urol, Ctr Hlth Sci 66 124, Los Angeles, CA 90095 USA. [Elashoff, David] Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA USA. [Barnard, R. James; Hong-Gonzalez, Jenny; Corman, Dan M.; Ku, Melvin] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA USA. [Said, Jonathan; Doan, Ngan Bao; Gui, Dorina] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. [Cohen, Pinchas] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Cohen, Pinchas] Univ Calif Los Angeles, Div Pediat Endocrinol, Los Angeles, CA USA. [Aronson, William J.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Dept Urol, Ctr Hlth Sci 66 124, Box 951738, Los Angeles, CA 90095 USA. EM waronson@ucla.edu FU NCI NIH HHS [P50 CA092131-01A10005, P50 CA092131, 1R01CA100938, P50 CA92131-01A1, R01 CA100938, R01 CA100938-04] NR 50 TC 43 Z9 44 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 APR 15 PY 2008 VL 68 IS 8 BP 3066 EP 3073 DI 10.1158/0008-5472.CAN-07-5616 PG 8 WC Oncology SC Oncology GA 290CM UT WOS:000255100500062 PM 18413778 ER PT J AU Goldfine, AB Beckman, JA AF Goldfine, Allison B. Beckman, Joshua A. TI Life and death in Denmark: Lessons about diabetes and coronary heart disease SO CIRCULATION LA English DT Editorial Material DE editorials; diabetes mellitus; heart disease ID PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RISK; CHOLESTEROL; MORTALITY; PEOPLE; ATHEROSCLEROSIS; PREVENTION; MEN C1 [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Goldfine, Allison B.; Beckman, Joshua A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goldfine, Allison B.; Beckman, Joshua A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Allison.Goldfine@Joslin.Harvard.Edu OI Beckman, Joshua/0000-0001-8332-8439 NR 19 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 15 PY 2008 VL 117 IS 15 BP 1914 EP 1917 DI 10.1161/CIRCULATIONAHA.108.767681 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 288DK UT WOS:000254966200002 PM 18413508 ER PT J AU Sabatine, MS Morrow, DA Higgins, LJ MacGillivray, C Guo, W Bode, C Rifai, N Cannon, CP Gerszten, RE Lee, RT AF Sabatine, Marc S. Morrow, David A. Higgins, Luke J. MacGillivray, Catherine Guo, Wei Bode, Christophe Rifai, Nader Cannon, Christopher P. Gerszten, Robert E. Lee, Richard T. TI Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction SO CIRCULATION LA English DT Article DE myocardial infarction; natriuretic peptides; prognosis ID ACUTE CORONARY SYNDROMES; SEGMENT ELEVATION; PROGNOSTIC VALUE; MORTALITY; CLOPIDOGREL; THERAPY; PROTEIN; PREDICT; TRIAL; IL-33 AB Background - ST2 is a member of the interleukin-1 receptor family with a soluble form that is markedly upregulated on application of biomechanical strain to cardiac myocytes. Circulating ST2 levels are elevated in the setting of acute myocardial infarction, but the predictive value of ST2 independent of traditional clinical factors and of an established biomarker of biomechanical strain, N-terminal prohormone B-type natriuretic peptide ( NT-proBNP), has not been established. Methods and Results - We measured ST2 at baseline in 1239 patients with ST-elevation myocardial infarction from the CLopidogrel as Adjunctive ReperfusIon TherapY - Thrombolysis in Myocardial Infarction 28 ( CLARITY- TIMI 28) trial. Per trial protocol, patients were to undergo coronary angiography after 2 to 8 days and were followed up for 30 days for clinical events. In contrast to NT- proBNP, ST2 levels were independent of clinical factors potentially related to chronic increased left ventricular wall stress, including age, hypertension, prior myocardial infarction, and prior heart failure; levels also were only modestly correlated with NT- proBNP ( r = 0.14). After adjustment for baseline characteristics and NT- proBNP levels, an ST2 level above the median was associated with a significantly greater risk of cardiovascular death or heart failure ( third quartile: adjusted odds ratio, 1.42; 95% confidence interval, 0.68 to 3.57; fourth quartile: adjusted odds ratio, 3.57; 95% confidence interval, 1.87 to 6.81; P < 0.0001 for trend). When both ST2 and NT- proBNP were added to a model containing traditional clinical predictors, the c statistic significantly improved from 0.82 ( 95% confidence interval, 0.77 to 0.87) to 0.86 ( 95% confidence interval, 0.81 to 0.90) ( P = 0.017). Conclusions - In ST- elevation myocardial infarction, high baseline ST2 levels are a significant predictor of cardiovascular death and heart failure independently of baseline characteristics and NT- proBNP, and the combination of ST2 and NT- proBNP significantly improves risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers of biomechanical strain in ST- elevation myocardial infarction. C1 [Sabatine, Marc S.; Morrow, David A.; Cannon, Christopher P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Dept Med, Boston, MA 02115 USA. [Sabatine, Marc S.; Morrow, David A.; Higgins, Luke J.; MacGillivray, Catherine; Cannon, Christopher P.; Lee, Richard T.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Guo, Wei] Harvard Clin Res Inst, Boston, MA USA. [Bode, Christophe] Univ Freiburg, Freiburg, Germany. [Rifai, Nader] Childrens Hosp, Dept Lab Med & Pathol, Boston, MA 02115 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org FU NHLBI NIH HHS [U01 HL081341, U01 HL083-1341] NR 19 TC 139 Z9 146 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 15 PY 2008 VL 117 IS 15 BP 1936 EP 1944 DI 10.1161/CIRCULATIONAHA.107.728022 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 288DK UT WOS:000254966200005 PM 18378613 ER PT J AU Shahian, DM Normand, SLT AF Shahian, David M. Normand, Sharon-Lise T. TI Comparison of "risk-adjusted" hospital outcomes SO CIRCULATION LA English DT Article DE health care quality assessment; outcomes research; risk; statistics ID 30-DAY MORTALITY-RATES; CAUSAL INFERENCE; PROPENSITY SCORE; POTENTIAL OUTCOMES; LOGISTIC-REGRESSION; PERFORMANCE; MODEL; CARE; DESIGN; ISSUES AB Background - A frequent challenge in outcomes research is the comparison of rates from different populations. One common example with substantial health policy implications involves the determination and comparison of hospital outcomes. The concept of " risk- adjusted" outcomes is frequently misunderstood, particularly when it is used to justify the direct comparison of performance at 2 specific institutions. Methods and Results - Data from 14 Massachusetts hospitals were analyzed for 4393 adults undergoing isolated coronary artery bypass graft surgery in 2003. Mortality estimates were adjusted using clinical data prospectively collected by hospital personnel and submitted to a data coordinating center designated by the state. The primary outcome was hospital- specific, risk- standardized, 30- day all- cause mortality after surgery. Propensity scores were used to assess the comparability of case mix ( covariate balance) for each Massachusetts hospital relative to the pool of patients undergoing coronary artery bypass grafting surgery at the remaining hospitals and for selected pairwise comparisons. Using hierarchical logistic regression, we indirectly standardized the mortality rate of each hospital using its expected rate. Predictive cross- validation was used to avoid underidentification of true outlying hospitals. Overall, there was sufficient overlap between the case mix of each hospital and that of all other Massachusetts hospitals to justify comparison of individual hospital performance with that of the remaining hospitals. As expected, some pairwise hospital comparisons indicated lack of comparability. This finding illustrates the fallacy of assuming that risk adjustment per se is sufficient to permit direct side- by- side comparison of healthcare providers. In some instances, such analyses may be facilitated by the use of propensity scores to improve covariate balance between institutions and to justify such comparisons. Conclusions - Risk- adjusted outcomes, commonly the focus of public report cards, have a specific interpretation. Using indirect standardization, these outcomes reflect a provider's performance for its specific case mix relative to the expected performance of an average provider for that same case mix. Unless study design or post hoc adjustments have resulted in reasonable overlap of case- mix distributions, such risk- adjusted outcomes should not be used to directly compare one institution with another. C1 [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Shahian, David M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shahian, David M.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Ctr Qual & Safety, Boston, MA 02114 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Normand, SLT (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM Sharon@hcp.med.harvard.edu NR 51 TC 75 Z9 77 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 15 PY 2008 VL 117 IS 15 BP 1955 EP 1963 DI 10.1161/CIRCULATIONAHA.107.747873 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 288DK UT WOS:000254966200007 PM 18391106 ER PT J AU Yu, B Raher, MJ Volpato, GP Bloch, KD Ichinose, F Zapol, WM AF Yu, Binglan Raher, Michael J. Volpato, Gian Paolo Bloch, Kenneth D. Ichinose, Fumito Zapol, Warren M. TI Inhaled nitric oxide enables artificial blood transfusion without hypertension SO CIRCULATION LA English DT Article DE endothelium; hemoglobin; hypertension; nitric oxide; vasoconstriction ID CELL-FREE HEMOGLOBIN; PULMONARY-HYPERTENSION; ISCHEMIA-REPERFUSION; NO; DISEASE; VASOCONSTRICTION; HEMOLYSIS; INJURY; MICE; FLOW AB Background - One of the major obstacles hindering the clinical development of a cell-free, hemoglobin- based oxygen carrier ( HBOC) is systemic vasoconstriction. Methods and Results - Experiments were performed in healthy mice and lambs by infusion of either murine tetrameric hemoglobin ( 0.48 g/kg) or glutaraldehyde- polymerized bovine hemoglobin ( HBOC- 201, 1.44 g/kg). We observed that intravenous infusion of either murine tetrameric hemoglobin or HBOC- 201 induced prolonged systemic vasoconstriction in wild-type mice but not in mice congenitally deficient in endothelial nitric oxide ( NO) synthase ( NOS3). Treatment of wild-type mice by breathing NO at 80 ppm in air for 15 or 60 minutes or with 200 ppm NO for 7 minutes prevented the systemic hypertension induced by subsequent intravenous administration of murine tetrameric hemoglobin or HBOC- 201 and did not result in conversion of plasma hemoglobin to methemoglobin. Intravenous administration of sodium nitrite ( 48 nmol) 5 minutes before infusion of murine tetrameric hemoglobin also prevented the development of systemic hypertension. In awake lambs, breathing NO at 80 ppm for 1 hour prevented the systemic hypertension caused by subsequent infusion of HBOC- 201. Conclusions - These findings demonstrate that HBOC can cause systemic vasoconstriction by scavenging NO produced by NOS3. Moreover, in 2 species, inhaled NO administered before the intravenous infusion of HBOC can prevent systemic vasoconstriction without causing methemoglobinemia. C1 [Yu, Binglan; Raher, Michael J.; Volpato, Gian Paolo; Bloch, Kenneth D.; Ichinose, Fumito; Zapol, Warren M.] Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Med Sch,Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Bloch, Kenneth D.; Ichinose, Fumito] Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med,Med Sch, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Med Sch,Anesthesia Ctr Crit Care Res, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@partners.org FU NHLBI NIH HHS [R01 HL042397, HL-42397, R01 HL042397-18] NR 33 TC 71 Z9 71 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 15 PY 2008 VL 117 IS 15 BP 1982 EP 1990 DI 10.1161/CIRCULATIONAHA.107.729137 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 288DK UT WOS:000254966200010 PM 18391111 ER PT J AU Jia, L Liu, YJ Yi, XF Miron, A Crum, CP Kong, B Zheng, WX AF Jia, Lin Liu, Yongjuan Yi, Xiaofang Miron, Alexander Crum, Christopher P. Kong, Beihua Zheng, Wenxin TI Endometrial glandular dysplasia with frequent p53 gene mutation: A genetic evidence supporting its precancer nature for endometrial serous carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID INTRAEPITHELIAL CARCINOMA; PRECURSOR LESION; CLONAL ORIGIN; PATHWAYS; FEATURES; CANCER; OVEREXPRESSION; DISEASE AB Purpose: Endometrial glandular dysplasia (EmGD) has been recently proposed to be a putative precursor to endometrial serous carcinoma (ESC). The purpose of this study is to determine if EmGD is genetically linked to ESC and if it can be used for early detection. Experimental Design: The tumor suppressor p53 gene was sequenced from serial samples of benign and neoplastic endometrial with serous differentiation. The study group contained 15 neoplastic uteri and the control group had 12 age-matched benign uteri. A total of 139 informative samples were obtained, including 55 resting endometrium, 37 EmGD, 25 serous endometrial intraepithelial carcinoma (EIC), and 22 ESC. At least one representative section from each uterus was used for p53 immunohistochemical staining to correlate p53 overexpression with gene mutation status. Results: The mutations of p53 were detected in 0%, 43%, 72%, and 96% in resting endometrium, EmGD, serous EIC, and ESC, respectively. More than 50% of the neoplastic uteri showed at least one identical p53 gene mutant among lesions of EmGD, serous EIC, and/or ESC. The majority of lesions showed overexpression of p53 protein, which was significantly correlated with p53 gene mutation (P < 0.01). Conclusions: This genetic evidence strongly supports that EmGD represents the precancer of ESC or serous EIC. Mutation of p53 gene is probably one of the most important factors to initiate the enclometrial serous carcinogenesis. Correct identification of EmGD will provide us an opportunity of early diagnosis and a potentially effective therapeutic modality to control ESC. C1 [Jia, Lin; Zheng, Wenxin] Univ Arizona, Dept Pathol, Coll Med, Tucson, AZ 85724 USA. [Jia, Lin; Yi, Xiaofang; Zheng, Wenxin] Univ Arizona, Dept Obstet & Gynecol, Coll Med, Tucson, AZ 85724 USA. [Yi, Xiaofang] Univ Arizona, Coll Med, Arizona Canc Ctr, Tucson, AZ 85724 USA. [Jia, Lin; Kong, Beihua] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Shandong, Peoples R China. [Liu, Yongjuan; Zheng, Wenxin] Fudan Univ, Shanghai Med Coll, Dept Pathol, Shanghai 200433, Peoples R China. [Yi, Xiaofang] Fudan Univ, Hosp Obstet & Gynecol, Shanghai 200433, Peoples R China. [Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Crum, Christopher P.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zheng, WX (reprint author), Univ Arizona, Dept Pathol, Coll Med, 1501 N Campbell Ave,5224A, Tucson, AZ 85724 USA. EM kongbeihua@sdu.edu.cn FU NCI NIH HHS [P30 CA23074] NR 33 TC 48 Z9 56 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2008 VL 14 IS 8 BP 2263 EP 2269 DI 10.1158/1078-0432.CCR-07-4837 PG 7 WC Oncology SC Oncology GA 287VC UT WOS:000254943600003 PM 18369088 ER PT J AU Marsit, CJ Black, CC Posner, MR Kelsey, KT AF Marsit, Carmen J. Black, Candice C. Posner, Marshall R. Kelsey, Karl T. TI A genotype-phenotype examination of cyclin D1 on risk and outcome of squamous cell carcinoma of the head and neck SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN-PAPILLOMAVIRUS; MOLECULAR EPIDEMIOLOGY; CANCER; POLYMORPHISM; GENE; SUSCEPTIBILITY; PHARYNGEAL; EXPRESSION; ALCOHOL; TOBACCO AB Purpose: The variant allele of CCND1 G870A encodes a splice variant of the cyclin D1 protein, which possesses an increased half-life. To confirm the phenotypic effect of the variant allele, we examined the immunohistochemical staining pattern of the protein in tumors from a case population of head and neck squamous cell carcinoma (HNSCC) and compared it with the genotype of these individuals. We also examined how this genotype was associated with the risk of HNSCC and if this genotype-phenotype association was related to patient outcome. Experimental Design: In a population-based case-control study of 698 cases and 777 controls, we both genotyped all participants for the CCND1 gene and did immunohistochemical staining of the cyclin D1 protein in the HNSCC tumors. Results: The variant AA genotype was significantly associated with positive immunohistochemical staining (P < 0.02), and this variant genotype was associated with a significantly elevated odds ratio of 1.5 (95% confidence interval, 1.1-2.0) for HNSCC overall, with risk greatest in oral and laryngeal sites. Positive immunohistochemical staining was inversely related to human papillomavirus 16 DNA present in the tumor (P < 0.03). The AA genotype and superpositive immunohistochemical staining for cyclin D1 also had independent and significant effects on patient survival. Conclusions: These results strongly suggest that this splice variant, when present in two copies, is a significant predictor of both the occurrence of HNSCC as well as patient survival after treatment. These data further indicate that this variant protein is an important determinant of individual response to therapy for this disease. C1 [Marsit, Carmen J.] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Kelsey, Karl T.] Brown Univ, Ctr Environm Hlth & Technol, Providence, RI 02912 USA. [Black, Candice C.] Dartmouth Med Sch, Dept Pathol, Hanover, NH USA. [Posner, Marshall R.] Dana Farber Canc Inst, Dept Med Oncol, Head & Neck Canc Program, Boston, MA 02115 USA. RP Marsit, CJ (reprint author), Brown Univ, Dept Pathol & Lab Med, Box G-E537, Providence, RI 02912 USA. EM carmen-marsit@brown.edu RI Kelsey, Karl/I-1252-2014; OI Marsit, Carmen/0000-0003-4566-150X FU NCI NIH HHS [R01 CA100679, R01 CA078609, R01 CA100679-05, R01CA078609, R01CA100679, R01 CA078609-09] NR 27 TC 24 Z9 24 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 APR 15 PY 2008 VL 14 IS 8 BP 2371 EP 2377 DI 10.1158/1078-0432.CCR-07-4368 PG 7 WC Oncology SC Oncology GA 287VC UT WOS:000254943600017 PM 18413827 ER PT J AU Raje, N Woo, SB Hande, K Yap, JT Richardson, PG Vallet, S Treister, N Hideshima, T Sheehy, N Chhetri, S Connell, B Xie, W Tai, YT Szot-Barnes, A Tian, M Schlossman, RL Weller, E Munshi, NC Van Den Abbeele, AD Anderson, KC AF Raje, Noopur Woo, Sook-Bin Hande, Karen Yap, Jeffrey T. Richardson, Paul G. Vallet, Sonia Treister, Nathaniel Hideshima, Teru Sheehy, Niall Chhetri, Shweta Connell, Brendan Xie, Wanling Tai, Yu-Tzu Szot-Barnes, Agnieszka Tian, Mei Schlossman, Robert L. Weller, Edie Munshi, Nikhil C. Van Den Abbeele, Annick D. Anderson, Kenneth C. TI Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw SO CLINICAL CANCER RESEARCH LA English DT Article ID BISPHOSPHONATE-ASSOCIATED OSTEONECROSIS; ZOLEDRONIC ACID; AMERICAN-SOCIETY; BONE METASTASES; BREAST-CANCER; RISK-FACTORS; DOUBLE-BLIND; OSTEOPOROSIS; INHIBITION; EXPERIENCE AB Purpose: Osteonecrosis of the jaw (ONJ) has been reported in patients with a history of aminobisphosphonate use. This study was conducted in order to define ONJ clinically and radiographically and gain insights into its pathophysiology. Experimental Design: Eleven multiple myeloma (MM) patients with ONJ were included in the study. Patients underwent clinical, biochemical, radiographic, and molecular profiling. Ten MM patients on aminobisphosphonates without ONJ and five healthy volunteers were used as controls for biochemical and molecular studies. Results: MM patients with ONJ were treated with either pamidronate (n = 3), zoledronate (n = 4), or both agents sequentially (n = 4) for a mean of 38.7 months. Radiographic studies showed bone sclerosis and fragmentation on plain films and computerized tomography. Quantitative regional analysis of NaF-PET and FDG-PET scans confirmed an increased standardized uptake value (SUVmax) in areas of ONJI. The target to background ratio of SUVmax was significantly greater for NaF-PET compared with FDG-PET scan. Biochemical bone marker data and transcriptional profiling studies showed that genes and proteins involved in osteoblast and osteoclast signaling cascades were significantly down-regulated in patients with ONJ. Conclusions: ONJ was associated with a mean duration of 38.7 months of aminobisphosphonate exposure. Radiographic and functional imaging confirmed sites of clinically established ONJ. Gene and protein studies are consistent with altered bone remodeling, evidenced by suppression of both bone resorption and formation. C1 [Raje, Noopur] Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. [Raje, Noopur; Hande, Karen; Yap, Jeffrey T.; Richardson, Paul G.; Vallet, Sonia; Hideshima, Teru; Sheehy, Niall; Chhetri, Shweta; Connell, Brendan; Xie, Wanling; Tai, Yu-Tzu; Szot-Barnes, Agnieszka; Tian, Mei; Schlossman, Robert L.; Weller, Edie; Munshi, Nikhil C.; Van Den Abbeele, Annick D.; Anderson, Kenneth C.] Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. [Woo, Sook-Bin; Treister, Nathaniel] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Raje, N (reprint author), Massachusetts Gen Hosp, Dana Farber Canc Inst, POB 218,55 Furit St, Boston, MA 02114 USA. EM nraie@partners.org RI Tian, Mei/E-3751-2012 FU NCI NIH HHS [R0-1 CA 50947, IP50 CA10070-01]; PHS HHS [P0-1 78378] NR 35 TC 72 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2008 VL 14 IS 8 BP 2387 EP 2395 DI 10.1158/1078-0432.CCR-07-1430 PG 9 WC Oncology SC Oncology GA 287VC UT WOS:000254943600019 PM 18413829 ER PT J AU Longworth, MS Herr, A Ji, JY Dyson, NJ AF Longworth, Michelle S. Herr, Anabel Ji, Jun-Yuan Dyson, Nicholas J. TI RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3 SO GENES & DEVELOPMENT LA English DT Article DE RBF1; RB; CAP-D3; chromatin; condensation; condensin II ID RETINOBLASTOMA TUMOR-SUPPRESSOR; E2F TARGET GENES; CHROMOSOME CONDENSATION; HISTONE DEACETYLASE; REPRESS TRANSCRIPTION; SISTER CHROMATIDS; POCKET PROTEINS; DROSOPHILA; COMPLEX; HETEROCHROMATIN AB The Drosophila retinoblastoma family of proteins (RBF1 and RBF2) and their mammalian homologs (pRB, p130, and p107) are best known for their regulation of the G1/S transition via the repression of E2F-dependent transcription. However, RB family members also possess additional functions. Here, we report that rbf1 mutant larvae have extensive defects in chromatin condensation during mitosis. We describe a novel interaction between RBF1 and dCAP-D3, a non-SMC component of the Condensin II complex that links RBF1 to the regulation of chromosome structure. RBF1 physically interacts with dCAP-D3, RBF1 and dCAP-D3 partially colocalize on polytene chromosomes, and RBF1 is required for efficient association of dCAP-D3 with chromatin. dCap-D3 mutants also exhibit chromatin condensation defects, and mutant alleles of dCap-D3 suppress cellular and developmental phenotypes induced by the overexpression of RBF1. Interestingly, this interaction is conserved between flies and humans. The re-expression of pRB into a pRB-deficient human tumor cell line promotes chromatin association of hCAP-D3 in a manner that depends on the LXCXE-binding cleft of pRB. These results uncover an unexpected link between pRB/RBF1 and chromatin condensation, providing a mechanism by which the functional inactivation of RB family members in human tumor cells may contribute to genome instability. C1 [Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA064402-15, CA64402, R01 CA064402, R01 CA064402-12, R01 CA064402-13, R01 CA064402-14]; NIGMS NIH HHS [GM53203, R01 GM053203, R01 GM053203-13, R01 GM053203-14] NR 58 TC 61 Z9 61 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2008 VL 22 IS 8 BP 1011 EP 1024 DI 10.1101/gad.1631508 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 288AT UT WOS:000254959300009 PM 18367646 ER PT J AU Edberg, JC Wu, JM Langefeld, CD Brown, EE Marion, MC McGwin, G Petri, M Ramsey-Goldman, R Reveille, JD Frank, SG Kaufman, KM Harley, JB Alarcon, GS Kimberly, RP AF Edberg, Jeffrey C. Wu, Jianming Langefeld, Carl D. Brown, Elizabeth E. Marion, Miranda C. McGwin, Gerald, Jr. Petri, Michelle Ramsey-Goldman, Rosalind Reveille, John D. Frank, Summer G. Kaufman, Kenneth M. Harley, John B. Alarcon, Graciela S. Kimberly, Robert P. TI Genetic variation in the CRP promoter: association with systemic lupus erythematosus SO HUMAN MOLECULAR GENETICS LA English DT Article ID C-REACTIVE PROTEIN; CARDIOVASCULAR EVENTS; REVISED CRITERIA; POLYMORPHISMS; MICE; COMPLEMENT; DISEASE; RISK; SLE; AUTOIMMUNITY AB The pentraxin C-reactive protein (CRP), an innate immune system opsonin which binds nuclear debris and apoptotic bodies, may protect against autoimmunity. A relative deficiency of CRP levels in patients with systemic lupus erythematosus (SLE) might contribute to altered handling of self-antigens. We report that the proximal 5' promoter region of CRP contains several polymorphisms that exhibit association with SLE in multiple populations. Strongest association was observed at the proximal promoter single nucleotide polymorphism (SNP) rs3093061 (CRP-707) (P = 6.41 x 10(-7) and P = 2.13 x 10(-6) in African-American and Caucasian case-control samples respectively). This association remains after adjustment for admixture. Linkage disequilibrium exists between SNPs in the proximal promoter and association of functional haplotypes containing rs3091244/rs3093062 (CRP-409/-390) appear to be driven by the rs3093061 (CRP-707) association. These data demonstrate that rs3093061 at the -707 site within the CRP gene is an SLE susceptibility locus. C1 [Edberg, Jeffrey C.; Wu, Jianming; Alarcon, Graciela S.; Kimberly, Robert P.] Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. [McGwin, Gerald, Jr.] Univ Alabama, Dept Surg, Sect Trauma Burns & Crit Care, Birmingham, AL 35294 USA. [Langefeld, Carl D.] Wake Forest Univ, Dept Biostat Sci, Div Publ Hlth Sci, Sect Stat Genet & Bioinformat, Winston Salem, NC 27109 USA. [Petri, Michelle] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA. [Reveille, John D.] Univ Texas Houston, Hlth Sci Ctr, Dept Med, Div Rheumatol, Houston, TX USA. [Frank, Summer G.; Kaufman, Kenneth M.; Harley, John B.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Kaufman, Kenneth M.; Harley, John B.] US Dept Vet Affairs, Oklahoma City, OK USA. [Kaufman, Kenneth M.; Harley, John B.] Univ Oklahoma, Dept Med, Oklahoma City, OK USA. RP Edberg, JC (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, SHEL207,1825 Univ Blvd, Birmingham, AL 35294 USA. EM jedberg@uab.edu OI Kimberly, Robert/0000-0002-5330-3086; Frank, Summer/0000-0003-0779-4926 FU NCRR NIH HHS [M01 RR000048, M01-RR00032, M01-RR00048, M01-RR00052, M01-RR02558, RR020143]; NIAID NIH HHS [AI24717]; NIAMS NIH HHS [P30 AR053483, AR048940, AR42460, AR43727, K24 AR002138, P01 AR49084, P60 AR048098] NR 45 TC 41 Z9 43 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2008 VL 17 IS 8 BP 1147 EP 1155 DI 10.1093/hmg/ddn004 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 284LP UT WOS:000254708200009 PM 18182444 ER PT J AU Chen, LY Daley, GQ AF Chen, Lingyi Daley, George Q. TI Molecular basis of pluripotency SO HUMAN MOLECULAR GENETICS LA English DT Review ID EMBRYONIC STEM-CELLS; HUMAN SOMATIC-CELLS; SELF-RENEWAL; DEVELOPMENTAL REGULATORS; DEFINED FACTORS; MOUSE EMBRYOS; NANOG; MICRORNAS; DIFFERENTIATION; NETWORK AB Embryonic stem (ES) cells are pluripotent and capable of self-renewal, thus holding promise for regenerative medicine. Recent studies have begun to provide insights into the molecular mechanisms underlying pluripotency and self-renewal. In this article, we discuss the roles of transcriptional regulation, epigenetic regulation and miRNAs in the maintenance of pluripotency and the differentiation of ES cells. C1 [Chen, Lingyi; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Chen, Lingyi; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI Chen, Lingyi/G-6309-2013 FU Howard Hughes Medical Institute NR 44 TC 70 Z9 73 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2008 VL 17 SI 1 BP R23 EP R27 DI 10.1093/hmg/ddn050 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 334ZW UT WOS:000258261600005 PM 18632692 ER PT J AU Geijsen, N Jones, DL AF Geijsen, Niels Jones, D. Leanne TI Seminal discoveries in regenerative medicine: contributions of the male germ line to understanding pluripotency SO HUMAN MOLECULAR GENETICS LA English DT Review ID EMBRYONIC STEM-CELLS; LONG-TERM PROLIFERATION; HUMAN SOMATIC-CELLS; MOUSE TESTIS; SELF-RENEWAL; DROSOPHILA SPERMATOGENESIS; IN-VITRO; UNDIFFERENTIATED SPERMATOGONIA; DEVELOPMENTAL REGULATORS; TERATOCARCINOMA CELLS AB Germ cells are highly specialized cells that form gametes (sperm and eggs), and they are the only cells within an organism that contribute genes to offspring. Due to the fact that the genetic information contained within germ cells is passed from generation to generation, the germ line is often thought of as immortal. Studies have revealed that germ cells are remarkably similar to pluripotent embryonic stem cells (ESCs). For example, there is a significant overlap in the gene expression profile between ESCs and primordial germ cells (PGCs), the founders of the germ cell lineage. In addition, pluripotent embryonic germ (EG) cell lines have been derived from mammalian PGCs. Secondly, a subset of testicular germ cell tumors, known as non-seminomas, often contain differentiated cells representative of all three germ layers, a definitive test of pluripotency. Lastly, recent results have demonstrated the ability of spermatogonial stem cells (SSCs) to de-differentiate into pluripotent ES-like cells, underscoring a unique relationship between the germ line and pluripotent cells that are present during the earliest stages of embryonic development. Here, we will review the factors that regulate the self-renewal and maintenance of male germline stem cells (GSCs) and discuss how these factors may allow us to manipulate the germ line to create pluripotent cells that could serve as a critical tool in cell replacement therapies and regenerative medicine. C1 [Jones, D. Leanne] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. [Geijsen, Niels] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. RP Jones, DL (reprint author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM ljones@salk.edu FU NICHD NIH HHS [R01 HD048769] NR 72 TC 5 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2008 VL 17 SI 1 BP R16 EP R22 DI 10.1093/hmg/ddn084 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 334ZW UT WOS:000258261600004 PM 18632691 ER PT J AU Mundel, TM Yliniemi, AM Maeshima, Y Sugimoto, H Kieran, M Kalluri, R AF Mundel, Thomas M. Yliniemi, Anna-Maija Maeshima, Yohei Sugimoto, Hikaru Kieran, Mark Kalluri, Raghu TI Type IV collagen alpha 6 chain-derived noncollagenous domain 1 (alpha 6(IV)NC1) inhibits angiogenesis and tumor growth SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE alpha 6 chain; endogenous angiogenesis inhibitor; Hexastatin; NC1 domain; noncollagenous; tumor; type IV Collagen ID BASEMENT-MEMBRANE COLLAGEN; LINKED ALPORT SYNDROME; ALPHA(V)BETA(3) INTEGRIN; ENDOGENOUS INHIBITORS; ENDOTHELIAL-CELLS; X-CHROMOSOME; NC1 DOMAIN; IN-VIVO; TUMSTATIN; GENE AB Type IV collagen is a major component of vascular basement membranes. The noncollagenous (NC1) domains of several alpha-chains of type IV collagen reveal a capacity to inhibit angiogenesis and tumor growth. Here, we demonstrate that the NC1 domain of the alpha 6 chain of type IV collagen (alpha 6NC1) is an endogenous inhibitor of angiogenesis and tumor growth. Recombinant alpha 6NC1 inhibits human endothelial cell proliferation and neovascularization of Matrigel plugs in mice. The alpha 6NC1 suppresses the growth of subcutaneously transplanted Lewis lung carcinoma and also spontaneous pancreatic insulomas that develop in the Rip1Tag2 mice. Inhibition of tumor growth is associated with significantly diminished microvascular density. Collectively, our results demonstrate that alpha 6NC1 is an endogenous inhibitor of angiogenesis and tumor growth. (c) 2007 Wiley-Liss, Inc. C1 [Mundel, Thomas M.; Yliniemi, Anna-Maija; Maeshima, Yohei; Sugimoto, Hikaru; Kalluri, Raghu] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Matrix Biol,Dept Med, Boston, MA 02215 USA. [Kieran, Mark] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kalluri, Raghu] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Kalluri, Raghu] Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. RP Kalluri, R (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Matrix Biol,Dept Med, 330 Brookline Ave,DANA 514, Boston, MA 02215 USA. EM rkalluri@bidmc.harvard.edu RI Peng, Chunwei/F-6788-2010; Kalluri, Raghu/E-2677-2015 OI Kalluri, Raghu/0000-0002-2190-547X FU NIAAA NIH HHS [AA53194]; NIDDK NIH HHS [DK55001, DK61688, DK62987] NR 59 TC 21 Z9 25 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2008 VL 122 IS 8 BP 1738 EP 1744 DI 10.1002/ijc.23269 PG 7 WC Oncology SC Oncology GA 275JS UT WOS:000254068300010 PM 18074349 ER PT J AU McGlynn, KA Gridley, G Mellemkjaer, L Brinton, LA Anderson, KC Caporaso, NE Landgren, O Olsen, JH AF McGlynn, Katherine A. Gridley, Gloria Mellemkjaer, Lene Brinton, Louise A. Anderson, Kenneth C. Caporaso, Neil E. Landgren, Ola Olsen, Jorgen H. TI Risks of cancer among a cohort of 23,935 men and women with osteophorosis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE osteoporosis; age; breast cancer; endometrial cancer; prostate cancer; colorectal cancer; smoking; alcohol ID BONE-MINERAL DENSITY; MULTIPLE-MYELOMA CELLS; BREAST-CANCER; ENDOMETRIAL CANCER; PROSTATE-CANCER; POSTMENOPAUSAL WOMEN; HIP-FRACTURES; REDUCED RISK; OSTEOPOROTIC FRACTURES; CIGARETTE-SMOKING AB Low hormone levels among persons with osteoporosis may decrease risk of some cancers. Other osteoporosis risk factors, such as smoking and alcohol consumption, however, may increase risk. As these deleterious factors are more often associated with osteoporosis diagnosed prior to age 70 years, cancer risk may be higher in these younger persons than in the general population. To examine this hypothesis, a cohort study of 23,935 persons with osteoporosis was conducted in Denmark. Patients hospitalized with osteoporosis between 1978 and 1993 were identified in the Danish Inpatient Register. Linkage to the Danish Cancer Registry identified all cancer outcomes through 2003. Standardized incidence ratios (SIR) and 95% confidence intervals (95%CI) were calculated to compare cancer incidence in the cohort with that in the general population. Persons diagnosed prior to age 70 years were at increased cancer risk (women: SIR = 1.11, 95%CI = 1.04-1.19; men: SIR = 1.31, 95%CI = 1.13-1.50) due, in part, to increased risks of cancers of the buccal cavity, esophagus, liver, pancreas and lung. Persons diagnosed at ages 70 and older were at decreased risk (women: SIR = 0.91, 95%CI = 0.87-0.96; men: SIR = 0.89, 0.77-1.01) due, in part, to decreased risks of breast, endometrial, colon, rectal and brain cancers in women and prostate cancer in men. These results suggest that risk factors associated with earlier onset osteoporosis may be associated with increased risk of cancer. Conversely, factors associated with later onset osteoporosis may be related to a decreased risk of cancer. (c) 2007 Wiley-Liss, Inc. C1 [Mellemkjaer, Lene; Olsen, Jorgen H.] Inst Canc Epidemiol, Danish Canc Soc, Copenhagen, Denmark. [Anderson, Kenneth C.] Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, EPS Suite 550 6120 Execut Blvd, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 48 TC 15 Z9 15 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2008 VL 122 IS 8 BP 1879 EP 1884 DI 10.1002/ijc.23290 PG 6 WC Oncology SC Oncology GA 275JS UT WOS:000254068300029 PM 18074348 ER PT J AU Seach, N Ueno, T Fletcher, AL Lowen, T Mattesich, M Engwerda, CR Scott, HS Ware, CF Chidgey, AP Gray, DHD Boyd, RL AF Seach, Natalie Ueno, Tomoo Fletcher, Anne L. Lowen, Tamara Mattesich, Monika Engwerda, Christian R. Scott, Hamish S. Ware, Carl F. Chidgey, Ann P. Gray, Daniel H. D. Boyd, Richard L. TI The lymphotoxin pathway regulates Aire-independent expression of ectopic genes and chemokines in thymic stromal cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL TOLERANCE; EPITHELIAL-CELLS; BETA-RECEPTOR; SIGNALING PATHWAYS; MEDULLA MIGRATION; AUTOIMMUNITY; MICROENVIRONMENTS; DIFFERENTIATION; THYMOCYTES; MESENCHYME AB Medullary thymic epithelial cells (mTEC) play an important and unique role in central tolerance, expressing tissue-restricted Ags (TRA) which delete thymocytes autoreactive to peripheral organs. Since deficiencies in this cell type or activity can lead to devastating autoimmune diseases, it is important to understand the factors which regulate mTEC differentiation and function. Lymphotoxin (LT) ligands and the LT beta R have been recently shown to be important regulators of mTEC biology; however, the precise role of this pathway in the thymus is not clear. In this study, we have investigated the impact of this signaling pathway in greater detail, focusing not only on mTEC but also on other thymic stromal cell subsets. LT beta R expression was found in all TEC subsets, but the highest levels were detected in MTS-15(+) thymic fibroblasts. Rather than directing the expression of the autoimmune regulator Aire in mTEC, we found LT beta R signals were important for TRA expression in a distinct population of mTEC characterized by low levels of MHC class II (mTEC(low)), as well as maintenance of MTS-15(+) fibroblasts. In addition, thymic stromal cell subsets from LT-deficient mice exhibit defects in chemokine production similar to that found in peripheral lymphoid organs of Lta(-/-) and Ltbr(-/-) mice. Thus, we propose a broader role for LT alpha 1 beta 2-LT beta R signaling in the maintenance of the thymic microenvironments, specifically by regulating TRA and chemokine expression in mTEC(low) for efficient induction of central tolerance. C1 [Boyd, Richard L.] Monash Univ, Monash Immunol & Stem Cell Ctr, Monash Immunol & Stem Cell Labs, Clayton, Vic 3800, Australia. [Mattesich, Monika] Bernard OBrien Inst Microsurg, Fitzroy, Vic, Australia. [Scott, Hamish S.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Mol Med, Parkville, Vic 3050, Australia. [Engwerda, Christian R.] Queensland Inst Med Res, Herston, Qld 4006, Australia. [Ware, Carl F.] La Jolla Inst Allergy & Immunol, Div Mol Immunol, La Jolla, CA 92037 USA. [Gray, Daniel H. D.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Boyd, RL (reprint author), Monash Univ, Monash Immunol & Stem Cell Ctr, Monash Immunol & Stem Cell Labs, Wellington Rd, Clayton, Vic 3800, Australia. EM richard.boyd@med.monash.edu.au RI Scott, Hamish/B-2122-2009; Gray, Daniel/A-3293-2013; Fletcher, Anne/A-1590-2011; Engwerda, Christian/I-3072-2015 OI Scott, Hamish/0000-0002-5813-631X; Gray, Daniel/0000-0002-8457-8242; FU NIAID NIH HHS [R37 AI033068, R37 AI033068-12, R37 AI033068-13] NR 36 TC 60 Z9 62 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2008 VL 180 IS 8 BP 5384 EP 5392 PG 9 WC Immunology SC Immunology GA 324GU UT WOS:000257506900026 PM 18390720 ER PT J AU Akbari, O Stock, P Meyer, EH Freeman, GJ Sharpe, AH Umetsu, DT DeKruyff, RH AF Akbari, Omid Stock, Philippe Meyer, Everett H. Freeman, Gordon J. Sharpe, Arlene H. Umetsu, Dale T. DeKruyff, Rosemarie H. TI ICOS/ICOSL interaction is required for CD4(+) invariant NKT cell function and homeostatic survival SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KILLER T-CELLS; INDUCED AIRWAY HYPERREACTIVITY; COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; DENDRITIC CELLS; IN-VIVO; ICOS; ACTIVATION; ANTIGEN; ALLERGEN AB The development of airway hyperreactivity (AHR), a cardinal feature of asthma, requires the presence of invariant NKT (iNKT) cells. In a mouse model of asthma, we demonstrated that the induction of AHR required ICOS costimulation of iNKT cells. ICOS was highly expressed on both naive and activated iNKT cells, and expression of ICOS was greater on the CD4(+) iNKT than on CD4(-) iNKT cells. Furthermore, the number of CD4(+) iNKT cells was significantly lower in spleens and livers of ICOS-/- and ICOSL-/- mice, and the remaining iNKT cells in ICOS-/- mice were dysfunctional and failed to reconstitute AHR when adoptively transferred into iNKT cell-deficient J alpha 18(-/-) mice. In addition, direct activation of iNKT cells with alpha-GalCer, which induced AHR in wild-type mice, failed to induce AHR in ICOS-/- mice. The failure of ICOS-/- iNKT cells to induce AHR was due in part to an inability of the ICOS-/- iNKT cells to produce IL-4 and IL-13 on activation. Moreover, survival of wild-type iNKT cells transferred into ICOSL-/- mice was greatly reduced due to the induction of apoptosis. These results indicate that ICOS costimulation plays a major role in induction of AHR by iNKT cells and is required for CD4(+) iNKT cell function, homeostasis, and survival in the periphery. C1 [Akbari, Omid] Harvard Univ, Childrens Hosp, Karp Res Labs, Sch Med,Div Immunol, Boston, MA 02115 USA. [Stock, Philippe] Univ Hosp Charite, Dept Pediat Pneumol & Immunol, Berlin, Germany. [Meyer, Everett H.] Stanford Univ, Program Immunol, Stanford, CA 94305 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Akbari, O (reprint author), Harvard Univ, Childrens Hosp, Karp Res Labs, Sch Med,Div Immunol, 1 Blackfan Circle, Boston, MA 02115 USA. EM omid.akbari@childrens.harvard.edu FU NHLBI NIH HHS [R01 HL069507]; NIAID NIH HHS [P01 AI056299, P01 AI56299, R01 AI066020-01A2, R01 AI066020-02, R01 AI066020-04, R01 AI066020-03, R01 AI066020, T32 AI007290] NR 44 TC 42 Z9 42 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2008 VL 180 IS 8 BP 5448 EP 5456 PG 9 WC Immunology SC Immunology GA 324GU UT WOS:000257506900033 PM 18390727 ER PT J AU Johnson, SW AF Johnson, Steven W. TI Rebound bursts following inhibition: how dopamine modifies firing pattern in subthalamic neurons SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID NUCLEUS NEURONS; BASAL GANGLIA; IN-VITRO C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. EM johnsost@ohsu.edu NR 9 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 15 PY 2008 VL 586 IS 8 BP 2033 EP 2033 DI 10.1113/jphysiol.2008.153643 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 288PM UT WOS:000254998300002 PM 18413336 ER PT J AU Hudson, LA Rollins, YD Anderson, CA Johnston-Brooks, C Tyler, KL Filley, CM AF Hudson, Lynsee A. Rollins, Yvonne D. Anderson, C. Alan Johnston-Brooks, Catharine Tyler, Kenneth L. Filley, Christopher M. TI Reduplicative paramnesia in Morvan's syndrome SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE reduplicative paramnesia; encephalopathy; VGKC antibodies; myokymia; myoclonus ID POTASSIUM CHANNEL ANTIBODY; CENTRAL-NERVOUS-SYSTEM; LIMBIC ENCEPHALITIS; MISIDENTIFICATION SYNDROMES; ENCEPHALOPATHY; LOCALIZATION; DISORDERS AB Background: Morvan's syndrome is characterized by peripheral nervous system hyperexcitibility (myokymia and neuromyotonia), hyperhydrosis, sleep disorder, limb paresthesias, and encephalopathy. Voltage gated potassium channel antibodies (VGKC abs) are frequently present. Reduplicative paramnesia (RP) has not been reported with this disorder. Objective: To describe a patient with Morvan's syndrome presenting with R-P. Design: Single case study. Patient: A 64-year-old man with several years of myokymia and myoclonus with escalating parasomnia and confusion developed the delusion that a replica of his house and its contents existed 40 mi away. Results: Serum VGKC ab titer was elevated. Neuropsychological testing disclosed executive function and memory deficits. Electromyography demonstrated diffuse myokymia. Treatment with intravenous immunoglobulin and prednisone produced improvement of RP and myoclonus, but not myokymia. Conclusion: RP may occur in patients with VGKC ab-associated Morvan's syndrome. Both RP and nervous system hyperexcitability may respond to immunotherapy including intravenous immunoglobulin and corticosteroids. (C) 2007 Elsevier B.V. All rights reserved. C1 [Hudson, Lynsee A.; Rollins, Yvonne D.; Anderson, C. Alan; Tyler, Kenneth L.; Filley, Christopher M.] Univ Colorado, Sch Med, Dept Neurol, Colorado Springs, CO 80907 USA. [Anderson, C. Alan; Filley, Christopher M.] Univ Colorado, Sch Med, Dept Psychiat, Colorado Springs, CO 80907 USA. [Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Med, Colorado Springs, CO 80907 USA. [Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Microbiol, Colorado Springs, CO 80907 USA. [Rollins, Yvonne D.; Anderson, C. Alan; Johnston-Brooks, Catharine; Tyler, Kenneth L.; Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Filley, CM (reprint author), UCHSC B-183,4200 E 9th Ave, Denver, CO 80262 USA. EM christopher.filley@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 NR 29 TC 7 Z9 8 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 APR 15 PY 2008 VL 267 IS 1-2 BP 154 EP 157 DI 10.1016/j.jns.2007.09.030 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 276YW UT WOS:000254180600025 PM 17928004 ER PT J AU Boas, DA Jones, SR Devor, A Huppert, TJ Dale, AM AF Boas, David A. Jones, Stephanie R. Devor, Anna Huppert, Theodore J. Dale, Anders M. TI Avascular anatomical network model of the spatio-temporal response to brain activation SO NEUROIMAGE LA English DT Article ID CEREBRAL-BLOOD-FLOW; RODENT BARREL CORTEX; HEMODYNAMIC-RESPONSE; OXIDATIVE-METABOLISM; OXYGEN-METABOLISM; NEURONAL-ACTIVITY; RAT-BRAIN; BOLD FMRI; SOMATOSENSORY STIMULATION; INTRACRANIAL-PRESSURE AB Neuronal activity-induced changes in vascular tone and oxygen consumption result in a dynamic evolution of blood flow, volume, and oxygenation. Functional neuroimaging techniques, such as functional magnetic resonance imaging, optical imaging, and PET, provide indirect measures of the neural-induced vascular dynamics driving the blood parameters. Models connecting changes in vascular tone and oxygen consumption to observed changes in the blood parameters are needed to guide more quantitative physiological interpretation of these functional neuroimaging modalities. Effective lumped-parameter vascular balloon and Windkessel models have been developed for this purpose, but the lumping of the complex vascular network into a series of arterioles, capillaries, and venules allows only qualitative interpretation. We have therefore developed a parallel vascular anatomical network (VAN) model based on microscopically measurable properties to improve quantitative interpretation of the vascular response. The model, derived from measured physical properties, predicts baseline blood pressure and oxygen saturation distributions and dynamic responses consistent with literature. Furthermore, the VAN model allows investigation of spatial features of the dynamic vascular and oxygen response to neuronal activity. We find that a passive surround negative vascular response ("negative BOLD") is predicted, but that it underestimates recently observed surround negativity suggesting that additional active surround vasoconstriction is required to explain the experimental data. (C) 2008 Elsevier Inc. All rights reserved. C1 [Boas, David A.; Jones, Stephanie R.; Devor, Anna; Huppert, Theodore J.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med, Charlestown, MA USA. [Devor, Anna; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Huppert, Theodore J.] Harvard Univ, Grad Programs Biophys, Boston, MA 02115 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. RP Boas, DA (reprint author), 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM dboas@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NIBIB NIH HHS [R01EB000790, R01 EB000790, R01 EB000790-05, R01 EB002482, R01 EB002482-05, R01EB002482]; NINDS NIH HHS [R01 NS051188, R01 NS051188-04, R01 NS057476, R01 NS057476-01A1, R01NS051188, R01NS057476] NR 77 TC 99 Z9 99 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2008 VL 40 IS 3 BP 1116 EP 1129 DI 10.1016/j.neuroimage.2007.12.061 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 284TH UT WOS:000254728200011 PM 18289880 ER PT J AU Drappatz, J Akar, S Fisher, DC Samuels, MA Kesari, S AF Drappatz, J. Akar, S. Fisher, D. C. Samuels, M. A. Kesari, S. TI Imaging of Bing-Neel syndrome SO NEUROLOGY LA English DT Editorial Material C1 [Drappatz, J.; Akar, S.; Fisher, D. C.; Samuels, M. A.; Kesari, S.] Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kesari, S (reprint author), Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Canc Inst, SW460,44 Binney St, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 1 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 15 PY 2008 VL 70 IS 16 BP 1364 EP 1364 DI 10.1212/01.wnl.0000309212.22661.84 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 312XV UT WOS:000256706600013 PM 18413593 ER PT J AU Driver, JA Kurth, T Buring, JE Gaziano, JM Logroscino, G AF Driver, J. A. Kurth, T. Buring, J. E. Gaziano, J. M. Logroscino, G. TI Parkinson disease and risk of mortality - A prospective comorbidity-matched cohort study SO NEUROLOGY LA English DT Article ID FOLLOW-UP; CARDIOVASCULAR-DISEASE; PHYSICIANS HEALTH; DOPAMINE AGONISTS; RANDOMIZED-TRIAL; CANCER INCIDENCE; OLMSTED COUNTY; BETA-CAROTENE; SURVIVAL; POPULATION AB Objective: To evaluate the association between Parkinson disease (PD) and mortality after adjustment for comorbidities. Methods: We conducted a matched cohort analysis among 22,071 participants in the Physicians' Health Study. Five hundred sixty incident PD cases were identified by self-report. We used a modified Charlson Comorbidity Index to calculate a comorbidity score. Each PD case was matched by age to a comparator who was alive and had an identical comorbidity score at the time of PD diagnosis of the case. Both cohorts were followed for all-cause mortality. We used proportional hazards models to calculate hazard ratios (HRs) for mortality. Results: A total of 330 participants died over a median follow-up of 5.8 years, 200 (35.7%) in the PD group and 130 (23.2%) in the reference group. After adjustment for smoking and age at PD onset, the HR for mortality was 2.32 (95% CI 1.85-2.92). The mortality risk remained significant with increasing age at onset, even in those aged >= 80 years (HR = 2.10; 95% CI 1.44-3.00). The increased risk was apparent for short PD duration (<2 years) and remained stable with increasing duration. We found no different risk of mortality associated with PD according to smoking status. Conclusions: In this large prospective cohort of men and after matching on comorbidities, we found that Parkinson disease patients had an increased risk of all-cause mortality. Mortality was increased regardless of disease duration, did not diminish with increasing age at onset, and was not influenced by smoking status. C1 [Driver, J. A.; Kurth, T.; Buring, J. E.; Gaziano, J. M.; Logroscino, G.] Harvard Univ, Brigham & Womens Hosp, Div Aging, Sch Med,Dept Med, Boston, MA 02120 USA. [Driver, J. A.; Buring, J. E.; Gaziano, J. M.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med,Dept Med, Boston, MA 02120 USA. [Kurth, T.; Buring, J. E.; Logroscino, G.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02120 USA. [Buring, J. E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02120 USA. [Gaziano, J. M.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Kurth, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Aging, Sch Med,Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012; LOGROSCINO, GIANCARLO/K-5148-2016 OI Kurth, Tobias/0000-0001-7169-2620; LOGROSCINO, GIANCARLO/0000-0003-0423-3242 FU NCI NIH HHS [CA 34944, CA 40360]; NHLBI NIH HHS [HL-26490, HL-34595] NR 50 TC 65 Z9 67 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 15 PY 2008 VL 70 IS 16 BP 1423 EP 1430 DI 10.1212/01.wnl.0000310414.85144.ee PN 2 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 312XW UT WOS:000256706700010 PM 18413567 ER PT J AU Haugarvoll, K Rademakers, R Kachergus, JM Nuytemans, K Ross, OA Gibson, JM Tan, EK Gaig, C Tolosa, E Goldwurm, S Guidi, M Riboldazzi, G Brown, L Walter, U Benecke, R Berg, D Gasser, T Theuns, J Pals, P Cras, P De Deyn, PP Engelborghs, S Pickut, B Uitti, RJ Foroud, T Nichols, WC Hagenah, J Klein, C Samii, A Zabetian, CP Bonifati, V Van Broeckhoven, C Farrer, MJ Wszolek, ZK AF Haugarvoll, K. Rademakers, R. Kachergus, J. M. Nuytemans, K. Ross, O. A. Gibson, J. M. Tan, E. -K. Gaig, C. Tolosa, E. Goldwurm, S. Guidi, M. Riboldazzi, G. Brown, L. Walter, U. Benecke, R. Berg, D. Gasser, T. Theuns, J. Pals, P. Cras, P. De Deyn, P. Paul Engelborghs, S. Pickut, B. Uitti, R. J. Foroud, T. Nichols, W. C. Hagenah, J. Klein, C. Samii, A. Zabetian, C. P. Bonifati, V. Van Broeckhoven, C. Farrer, M. J. Wszolek, Z. K. TI Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease SO NEUROLOGY LA English DT Article ID AUTOSOMAL-DOMINANT PARKINSONISM; KINASE-ACTIVITY; RISK-FACTOR; MUTATIONS; G2019S; POPULATION; VARIANT; GENE; PENETRANCE; GLY2385ARG AB Objective: Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson disease (PD). Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein. Herein, we characterize the clinical and genetic features associated with Lrrk2 p. R1441C. Methods: We identified 33 affected and 15 unaffected LRRK2 c. 4321C>T (p. R1441C) mutation carriers through an international consortium originating from three continents. The age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. Results: The clinical presentation of Lrrk2 p.R1441C carriers was similar to sporadic PD and Lrrk2 p.G2019S parkinsonism. The mean age at onset for parkinsonism was 60 years, range 30-79 years; fewer than 20% of the patients had symptoms before the age 50 years, while by 75 years >90% of them had developed symptoms. Haplotype analysis suggests four independent founders for the p. R1441C mutation. Conclusions: The distribution in age at onset and clinical features in Lrrk2 p.R1441C patients are similar to idiopathic and Lrrk2 p.G2019S parkinsonism. Several independent founders of the p.R1441C substitution suggest this site is prone to recurrent mutagenesis. C1 [Haugarvoll, K.; Rademakers, R.; Kachergus, J. M.; Ross, O. A.; Brown, L.; Uitti, R. J.; Farrer, M. J.; Wszolek, Z. K.] Mayo Clin, Coll Med, Dept Neurol, Jacksonville, FL 32224 USA. [Haugarvoll, K.; Rademakers, R.; Kachergus, J. M.; Ross, O. A.; Brown, L.; Uitti, R. J.; Farrer, M. J.; Wszolek, Z. K.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. [Haugarvoll, K.] NTNU Norwegian Univ Sci & Technol, Dept Neurosci, Trondheim, Norway. [Rademakers, R.; Nuytemans, K.; Theuns, J.; Van Broeckhoven, C.] Inst Born Bunge, Neurodegenerat Brain Dis Grp, Antwerp, Belgium. [Rademakers, R.; Nuytemans, K.; Theuns, J.; Van Broeckhoven, C.] Inst Born Bunge, Dept Mol Genet, VIB, Neurogenet Lab, Antwerp, Belgium. [Rademakers, R.; Nuytemans, K.; Theuns, J.; Pals, P.; Cras, P.; De Deyn, P. Paul; Engelborghs, S.; Van Broeckhoven, C.] Univ Antwerp, B-2020 Antwerp, Belgium. [Gibson, J. M.] Royal Victoria Hosp, Dept Neurol, Belfast BT12 6BA, Antrim, North Ireland. [Tan, E. -K.] Singapore Gen Hosp, Singapore 0316, Singapore. [Gaig, C.; Tolosa, E.] Univ Barcelona, Parkinsons Dis & Movement Disorders Unit, E-08007 Barcelona, Spain. Univ Barcelona, Inst Clin Neurociencies, E-08007 Barcelona, Spain. [Gaig, C.; Tolosa, E.] Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08007 Barcelona, Spain. [Goldwurm, S.] Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy. [Guidi, M.] INRCA Inst, Div Neurol, Ancona, Italy. [Riboldazzi, G.] Univ Insubria, Dept Neurol, Varese, Italy. [Walter, U.; Benecke, R.] Univ Rostock, Dept Neurol, D-2500 Rostock 1, Germany. [Berg, D.; Gasser, T.] Hertie Inst Clin Brain Res, Tubingen, Germany. [Pals, P.; Cras, P.] Univ Antwerp Hosp, Div Neurol, Antwerp, Belgium. [Pals, P.; Cras, P.] Inst Born Bunge, Neurobiol Lab, Antwerp, Belgium. [De Deyn, P. Paul; Engelborghs, S.] Inst Born Bunge, Lab Neurochem & Behav, Antwerp, Belgium. [De Deyn, P. Paul; Engelborghs, S.; Pickut, B.] ZNA Middelheim Antwerp, Div Neurol, Antwerp, Belgium. [Foroud, T.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Nichols, W. C.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Nichols, W. C.] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. [Hagenah, J.; Klein, C.] Uni Lubeck, Dept Neurol & Human Genet, Lubeck, Germany. [Samii, A.; Zabetian, C. P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Bonifati, V.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. RP Wszolek, ZK (reprint author), Mayo Clin, Coll Med, Dept Neurol, Cannady Bldg 2E,4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM wszolek.zbigniew@mayo.edu RI Ross, Owen/D-7573-2013; Nuytemans, Karen/F-4797-2012; Haugarvoll, Kristoffer/L-1486-2015; Goldwurm, Stefano/Q-8978-2016 OI Haugarvoll, Kristoffer/0000-0001-9381-1109; Goldwurm, Stefano/0000-0002-1651-567X FU NINDS NIH HHS [R01 NS037167, K08 NS044138, P50 NS040256, P50 NS40256, R01 NS37167]; Telethon [GTB07001] NR 30 TC 67 Z9 67 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 15 PY 2008 VL 70 IS 16 BP 1456 EP 1460 DI 10.1212/01.wnl.0000304044.22253.03 PN 2 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 312XW UT WOS:000256706700015 PM 18337586 ER PT J AU Scharf, JM Moorjani, P Fagerness, J Platko, JV Illmann, C Galloway, B Jenike, E Stewart, SE Pauls, DL AF Scharf, J. M. Moorjani, P. Fagerness, J. Platko, J. V. Illmann, C. Galloway, B. Jenike, E. Stewart, S. E. Pauls, D. L. CA Tourette Syndrome Int Consortium G TI Lack of association between SLITRK1 var321 and Tourette syndrome in a large family-based sample SO NEUROLOGY LA English DT Editorial Material ID VARIANTS; DISORDER C1 [Scharf, J. M.; Moorjani, P.; Fagerness, J.; Platko, J. V.; Illmann, C.; Galloway, B.; Jenike, E.; Stewart, S. E.; Pauls, D. L.] Massachusetts Gen Hosp, Psychiat Neurodev Genet Unit, Ctr Human Genet Res, Dept Psychiat, Boston, MA 02114 USA. [Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Scharf, J. M.] Harvard Univ, Brigham & Womens Hosp, Brigham Behav Neurol Grp, Dept Neurol, Boston, MA 02115 USA. RP Pauls, DL (reprint author), Massachusetts Gen Hosp, Psychiat Neurodev Genet Unit, Ctr Human Genet Res, Dept Psychiat, Richard B Simches Res Bldg,185 Cambridge St,6th F, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu OI Barr, Cathy/0000-0003-0361-0106; Stewart, S. Evelyn/0000-0002-0994-6383 FU NINDS NIH HHS [R01 NS040024, NS 40024, U01 NS040024] NR 7 TC 50 Z9 51 U1 0 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 APR 15 PY 2008 VL 70 IS 16 BP 1495 EP 1496 DI 10.1212/01.wnl.0000296833.25484.bb PN 2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 312XW UT WOS:000256706700022 PM 18413575 ER PT J AU Ruan, PK Gray, RJ AF Ruan, Ping K. Gray, Robert J. TI Sensitivity analysis of progression-free survival with dependent withdrawal SO STATISTICS IN MEDICINE LA English DT Article DE bootstrap variance estimation; dependent censoring; EM algorithm; log-rank test; sensitivity analysis; survival analysis ID END-POINTS; TIME DATA; FAILURE; MODEL AB We develop a sensitivity analysis method for comparing treatment-specific distributions where the endpoint is progression-free survival (PFS). The censoring process may be informative due to selective patient withdrawal, which occurs whenever disease evaluation has been discontinued without progression being documented. The sensitivity analysis explores the effects of the dependence between patient withdrawal and progression time using a conditional probability model which incorporates a set of sensitivity parameters. We propose an EM algorithm for estimation of PFS under the model for dependence and construct log-rank-type score statistics from the estimated distributions. Bootstrap procedures are used to estimate the variance of the score statistic. We also extend the methodology to incorporate additional survival information, which may be available on the cases who were withdrawn. An Eastern Cooperative Oncology Group (ECOG) advanced lung cancer clinical trial (E1594) is used to illustrate the methodology. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 [Ruan, Ping K.] Harvard Univ, Ctr Biostat AIDS Res, Dept Biostat, Boston, MA 02115 USA. [Gray, Robert J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Ruan, PK (reprint author), Harvard Univ, Ctr Biostat AIDS Res, Dept Biostat, Boston, MA 02115 USA. EM pruan@hsph.harvard.edu NR 14 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD APR 15 PY 2008 VL 27 IS 8 BP 1180 EP 1198 DI 10.1002/sim.3015 PG 19 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 291QA UT WOS:000255210700003 PM 17768718 ER PT J AU Fiorina, P Jurewicz, M Vergani, A Augello, A Paez, J Ricchiuti, V Tchipachvili, V Sayegh, MH Abdi, R AF Fiorina, Paolo Jurewicz, Mollie Vergani, Andrea Augello, Andrea Paez, Jesus Ricchiuti, Vincent Tchipachvili, Vaja Sayegh, Mohamed H. Abdi, Reza TI Phenotypic and functional differences between wild-type and CCR2(-/-) dendritic cells: Implications for islet transplantation SO TRANSPLANTATION LA English DT Article DE dendritic cells; chemokines; transplantation; regulatory cells; islet transplantation ID REGULATORY T-CELLS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; ALLOGRAFT-REJECTION; CHEMOKINE RECEPTOR; IN-VITRO; BACTERIAL-INFECTION; ADHESION MECHANISMS; BONE-MARROW; TOLERANCE; CCR2 AB Background. Trafficking of dendritic cells (DC), the primary regulators of alloimmune responses, is controlled by chemokines. Here, we provide evidence that lack of CCR2 could lead to the generation of functionally and phenotypically different DC, which in part could explain the benefits observed in transplanting islets in CCR2(-/-) recipients. Methods and Results. We show that, in contrast to the in vitro DC maturation model, in vivo DC maturation is accompanied by an increase in the expression of CCR2. Compared with wild-type (WT), DC generated in vitro from CCR2(-/-) mice, and DC extracted from CCR2(-/-) naive mice or from CCR2(-/-) recipients of islet allografts, display lesser allostimulatory capacity. Compared with WT DC, CCR2(-/-) DC produce more IL-4 and induce more IL-4-producing T cells. CCR2(-/-) DC also promote the generation of regulatory T cells that more efficiently suppress T cell proliferative responses by mixed leukocyte reaction. Similarly, the percentage of CD4(+)CD25(+)FoxP3(+) cells were found to be higher in CCR2(-/-) recipients of islet allografts than in WT recipients. Conclusions. In summary, lack of CCR2 interferes with the allostimulatory capacity of DC and promotes the generation of regulatory T cells. This is the first demonstration of a mechanistic link between targeting a specific chemokine pathway and the DC-regulatory T cell axis in alloimmunity. C1 [Fiorina, Paolo; Jurewicz, Mollie; Vergani, Andrea; Augello, Andrea; Paez, Jesus; Sayegh, Mohamed H.; Abdi, Reza] Harvard Univ, Sch Med, Childrens Hosp, Transplant Res Ctr, Boston, MA 02115 USA. [Fiorina, Paolo; Jurewicz, Mollie; Vergani, Andrea; Augello, Andrea; Paez, Jesus; Sayegh, Mohamed H.; Abdi, Reza] Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplant Res Ctr, Boston, MA 02115 USA. [Fiorina, Paolo; Vergani, Andrea] Ist Sci San Raffaele, I-20132 Milan, Italy. [Ricchiuti, Vincent] Harvard Univ, Sch Med, Brigham & Womens Hosp, Endocrinol Core Lab, Boston, MA USA. [Tchipachvili, Vaja] Harvard Univ, Sch Med, Joslin Diabet Ctr,JDRF Islet Transplantat Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA USA. RP Abdi, R (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Transplant Res Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM rabdi@rics.bwh.harvard.edu RI Augello, Andrea/C-7321-2013 OI Augello, Andrea/0000-0001-5959-7989 NR 52 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2008 VL 85 IS 7 BP 1030 EP 1038 DI 10.1097/TP.0b013e31816843a0 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 288TQ UT WOS:000255009100018 PM 18408585 ER PT J AU Gasser, O Berger, C Zenhaeusern, G Elsasser, H Oehri, I Schaub, S Hess, C AF Gasser, Olivier Berger, Christoph Zenhaeusern, Gabriela Elsaesser, Hanno Oehri, Ineke Schaub, Stefan Hess, Christoph TI Testing the "Cytokine-ome" theory: A longitudinal pilot study in renal transplant recipients (vol 85, Pg 491, 2008) SO TRANSPLANTATION LA English DT Correction C1 [Gasser, Olivier] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Berger, Christoph; Zenhaeusern, Gabriela; Oehri, Ineke; Hess, Christoph] Univ Basel, Immunobiol Lab, Basel, Switzerland. [Elsaesser, Hanno; Oehri, Ineke; Schaub, Stefan; Hess, Christoph] Univ Basel Hosp, Clin Transplantat Immunol & Nephrol, CH-4031 Basel, Switzerland. RP Gasser, O (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. RI Gasser, Olivier/I-3663-2013 NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2008 VL 85 IS 7 BP 1066 EP 1066 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 288TQ UT WOS:000255009100025 ER PT J AU Aujesky, D Stone, RA Kim, S Crick, EJ Fine, MJ AF Aujesky, Drahomir Stone, Roslyn A. Kim, Sunghee Crick, Elsa J. Fine, Michael J. TI Length of hospital stay and postdischarge mortality in patients with pulmonary embolism SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEEP VENOUS THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; OUTPATIENT TREATMENT; ANTICOAGULATION THERAPY; THROMBOEMBOLISM; OUTCOMES; VALIDATION; MODEL AB Background: The optimal length of stay (LOS) for patients with pulmonary embolism (PE) is unknown. Although reducing LOS is likely to save costs, the effects on patient safety are unclear. We sought to identify patient and hospital factors associated with LOS and assess whether LOS was associated with postdischarge mortality. Methods: We evaluated patients discharged with a primary diagnosis of PE from 186 acute care hospitals in Pennsylvania (January 2000 through November 2002). We used discrete survival models to examine the association between (1) patient and hospital factors and the time to discharge and (2) LOS and postdischarge mortality within 30 days of presentation, adjusting for patient and hospital factors. Results: Among 15 531 patient discharges with PE, the median LOS was 6 days, and postdischarge mortality rate was 33%. In multivariate analysis, patients from Philadelphia were less likely to be discharged on a given day (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.730.93), as were black patients (OR, 0.88; 95% CI, 0.820.94). The odds of discharge decreased notably with greater patient severity of illness and in patients without private health insurance. Adjusted postdischarge mortality was significantly higher for patients with an LOS of 4 days or less (OR, 1.55; 95% CI, 1.21-2.00) relative to those with an LOS of 5 to 6 days. Conclusions: Several hospital and patient factors were independently associated with LOS. Patients with a very short LOS had greater postdischarge mortality relative to patients with a typical LOS, suggesting that physicians may inappropriately select patients with PE for early discharge who are at increased risk of complications. C1 [Aujesky, Drahomir] Univ Lausanne, Div Internal Med, Lausanne, Switzerland. [Kim, Sunghee; Crick, Elsa J.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Stone, Roslyn A.; Kim, Sunghee] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Fine, Michael J.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA. RP Aujesky, D (reprint author), CHU Vaudois, Serv Med Interne, BH 10-622, CH-1011 Lausanne, Switzerland. EM drahomir.aujesky@chuv.ch FU NHLBI NIH HHS [1 R21 HL075521-01A1] NR 24 TC 36 Z9 36 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 14 PY 2008 VL 168 IS 7 BP 706 EP 712 DI 10.1001/archinte.168.7.706 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 286HC UT WOS:000254836000005 PM 18413552 ER PT J AU Green, SM Martinez-Rumayor, A Gregory, SA Baggish, AL O'Donoghue, ML Green, JA Lewandrowski, KB Januzzi, JL AF Green, Sandy M. Martinez-Rumayor, Abelardo Gregory, Shawn A. Baggish, Aaron L. O'Donoghue, Michelle L. Green, Jamie A. Lewandrowski, Kent B. Januzzi, James L., Jr. TI Clinical uncertainty, diagnostic accuracy, and outcomes in emergency department patients presenting with dyspnea SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BRAIN NATRIURETIC PEPTIDE; CONGESTIVE-HEART-FAILURE; COST-EFFECTIVENESS; PULMONARY-DISEASE; HOSPITAL LENGTH; MANAGEMENT; UTILITY; READMISSION; POPULATION; PROGNOSIS AB Background: Dyspnea is a common complaint in the emergency department (ED) and may be a diagnostic challenge. We hypothesized that diagnostic uncertainty in this setting is associated with adverse outcomes, and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) testing would improve diagnostic accuracy and reduce diagnostic uncertainty. Methods: A total of 592 dyspneic patients were evaluated from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Managing physicians were asked to provide estimates from 0% to 100% of the likelihood of acutely destabilized heart failure (ADHF). A certainty estimate of either 20% or lower or 80% or higher was classified as clinical certainty, while estimates between 21% and 79% were defined as clinical uncertainty. Associations between clinical uncertainty, hospital length of stay, morbidity, and mortality were examined. The diagnostic value of clinical judgment vs NT-proBNP measurement was compared across categories of clinical certainty. Results: Clinical uncertainty was present in 185 patients (31%), 103 (56%) of whom had ADHF. Patients judged with clinical uncertainty had longer hospital length of stay and increased morbidity and mortality, especially those with ADHF. Receiver operating characteristic analysis of clinical judgment yielded an area under the curve (AUC) of 0.88 in the clinical certainty group and 0.76 in the uncertainty group (P <.001); NTproBNP testing alone in these same groups had AUCs of 0.96 and 0.91, respectively. The combination of clinical judgment with NT-proBNP testing yielded improvements in AUC. Conclusions: Among dyspneic patients in the ED, clinical uncertainty is associated with increased morbidity and mortality, especially in those with ADHF. The addition of NT-proBNP testing to clinical judgment may reduce diagnostic uncertainty in this setting. C1 [Gregory, Shawn A.; Baggish, Aaron L.; O'Donoghue, Michelle L.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Green, Sandy M.; Martinez-Rumayor, Abelardo; Green, Jamie A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM JJanuzzi@Partners.org NR 24 TC 33 Z9 34 U1 0 U2 0 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 APR 14 PY 2008 VL 168 IS 7 BP 741 EP 748 DI 10.1001/archinte.168.7.741 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 286HC UT WOS:000254836000010 PM 18413557 ER PT J AU Kobelt, P Wisser, AS Stengel, A Goebel, M Inhoff, T Noetzel, S Veh, RW Bannert, N van der Voort, I Wiedenmann, B Klapp, BF Tache, Y Monnikes, H AF Kobelt, Peter Wisser, Anna-Sophia Stengel, Andreas Goebel, Miriam Inhoff, Tobias Noetzel, Steffen Veh, Ruediger W. Bannert, Norbert van der Voort, Iva Wiedenmann, Bertram Klapp, Burghard F. Tache, Yvette Moennikes, Hubert TI Peripheral injection of ghrelin induces Fos expression in the dorsomedial hypothalamic nucleus in rats SO BRAIN RESEARCH LA English DT Article DE ghrelin; dorsomedial hypothalamic nucleus; Fos; brain; rat; food intake ID GROWTH-HORMONE-SECRETION; AGOUTI-RELATED PROTEIN; ARCUATE NUCLEUS; NEUROPEPTIDE-Y; FOOD-INTAKE; C-FOS; PARAVENTRICULAR NUCLEUS; FEEDING-BEHAVIOR; ACYLATED PEPTIDE; MESSENGER-RNA AB Peripheral ghrelin has been shown to act as a gut-brain peptide exerting a potent orexigenic effect on food intake. The dorsomedial nucleus of the hypothalamus (DMH) is innervated by projections from other brain areas being part of the network of nuclei controlling energy homeostasis, among others NPY/AgRP-positive fibers arising from the arcuate nucleus (ARC). The aim of the study was to determine if peripherally administered ghrelin affects neuronal activity in the DMH, as assessed by Fos expression. The number of Fos positive neurons was determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), ARC, ventromedial hypothalamic nucleus (VMH), nucleus of the solitary tract (NTS) and in the area postrema (AP) in non-fasted Sprague-Dawley rats in response to intraperitoneally (ip) injected ghrelin (3 nmol/rat) or vehicle (0.15 M NaCI). Peripheral ghrelin induced a significant increase in the number of Fos-ir positive neurons/section compared with vehicle in the ARC (mean SEM: 49 +/- 2 us. 23 +/- 2 neurons/section, p = 0.001), PVN (69 +/- 5 us. 34 +/- 3, p = 0.001), and DMH (142 +/- 5 us. 83 5, p<0.001). Fos-ir positive neurons were mainly localized within the ventral part of the DMH. No change in Fos expression was observed in the VMH (53 +/- 8 vs.48 +/- 6,p = 0.581), NTS (42 +/- 2 vs. 40 +/- 3,p = 0.603), and in the AP (7 +/- 1 vs. 5 +/- 1, p = 0.096). Additional double-labelling with anti-Fos and anti-AgRP revealed that Fos positive neurons in the DMH were encircled by a network of AgRP-ir positive fibers. These data indicate that peripheral ghrelin activates DMH neurons and that NPY-/AgRP-positive fibers may be involved in the response. (C) 2008 Elsevier B.V. All rights reserved. C1 [Kobelt, Peter; Wisser, Anna-Sophia; Stengel, Andreas; Goebel, Miriam; Inhoff, Tobias; Noetzel, Steffen; van der Voort, Iva; Wiedenmann, Bertram; Moennikes, Hubert] Acad Training Inst Charite Univmed Berlin, Martin Luther Hosp, Dept Med, D-14133 Berlin, Germany. [Moennikes, Hubert] Acad Training Inst Charite Univmed Berlin, Martin Luther Hosp, Inst Neurogastroenterol, D-14133 Berlin, Germany. [Kobelt, Peter; Klapp, Burghard F.] Univmed Berlin, Div Psychosomat Med & Psychotherapy, Dept Med, Berlin, Germany. [Bannert, Norbert] Robert Koch Inst, D-1000 Berlin, Germany. [Tache, Yvette] Vet Affairs Greater Los Angeles Hlthcare Syst, Los Angeles, CA USA. [Tache, Yvette] Univ Calif Los Angeles, CURE Digest Res Ctr, Div Digest Dis, Dept Med, Los Angeles, CA USA. [Tache, Yvette] Univ Calif Los Angeles, Ctr Neurovisceral Sci, Los Angeles, CA USA. [Moennikes, Hubert] Martin Luther Hosp, Dept Med, Berlin, Germany. [Moennikes, Hubert] Martin Luther Hosp, Inst Neurogasteroenterol, Berlin, Germany. RP Monnikes, H (reprint author), Acad Training Inst Charite Univmed Berlin, Martin Luther Hosp, Dept Med, Casper Theyss Str 27-31, D-14133 Berlin, Germany. EM moennikes@web.de FU NIDDK NIH HHS [R01 DK033061-22, DK R01 33061, R01 DK033061] NR 45 TC 22 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 14 PY 2008 VL 1204 BP 77 EP 86 DI 10.1016/j.brainres.2008.01.054 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 296SV UT WOS:000255567000008 PM 18329635 ER PT J AU Diaz-Griffero, F Taube, R Muehlbauer, SM Brojatsch, J AF Diaz-Griffero, Felipe Taube, Ran Muehlbauer, Stefan M. Brojatsch, Jurgen TI Efficient production of HIV-1 viral-like particles in mouse cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE human immunodeficiency virus; gag processing; maturation; assembly; infectivity; mouse model; murine restrictions ID MESSENGER-RNA; MURINE CELLS; SUBGROUP-B; PROTEIN; EXPRESSION; VIRUSES; REPLICATION; RECEPTORS; SEQUENCES; DISTINCT AB Previous efforts to develop a mouse model for HIV/AIDS have been impaired by multiple blocks to HIV replication, including barriers to viral entry, proviral transcription, and assembly. Expression of human cofactors in murine cells overcomes early restrictions, but does not lead to the production of infectious HIV particles. Here we show that stable expression of a codon-optimized synthetic HIV-1 Gag-Pol construct (sGP) in murine cell lines results in efficient Gag production and viral-like particle (VLP) release. Stable expression of the sGP construct in murine cells such as NIH3T3 and A9 improved Gag processing resulting in efficient VLP release comparable to that found in human cells. Using highly efficient transient transfection procedures, we increased Gag expression, and were able to produce infectious HIV particles in NIH3T3 cells. However, the infectivity of VLPs produced in murine cells was significantly below that generated in 293T cells. Reduced infectivity of VLPs produced in murine cells correlated with lower HIV reporter RNA levels in these cells. Taken together, improving the expression of HIV-1 Gag-Pol by using the sGP construct overcomes, at least in part, late restrictions in murine cells. (c) 2008 Published by Elsevier Inc. C1 [Muehlbauer, Stefan M.; Brojatsch, Jurgen] Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Diaz-Griffero, Felipe; Taube, Ran] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Brojatsch, J (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave,Golding 404, Bronx, NY 10461 USA. EM brojatsc@aecom.yu.edu OI brojatsch, jurgen/0000-0002-7424-365X FU NIAID NIH HHS [AI49104-01, AI286]; NIGMS NIH HHS [T32GM007288]; NIMH NIH HHS [K99 MH086162] NR 25 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 11 PY 2008 VL 368 IS 3 BP 463 EP 469 DI 10.1016/j.bbrc.2007.12.195 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 273JJ UT WOS:000253925900003 PM 18241668 ER PT J AU Stanojevic, V Habener, JF Holz, GG Leech, CA AF Stanojevic, Violeta Habener, Joel F. Holz, George G. Leech, Colin A. TI Cytosolic adenylate kinases regulate K-ATP channel activity in human beta-cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE adenylate kinase; K-ATP channel; diadenosine pentaphosphate; expression; glucose; beta-cell; Islet ID GLUCOSE; GENE; EXPRESSION; RAT AB The role of adenylate kinase (AK) as a determinant of K-ATP channel activity in human pancreatic beta-cells was investigated. We have identified that two cytosolic isoforms of AK, AK1 and AK5 are expressed in human islets and INS-1 cells. Elevated concentrations of glucose inhibit AK1 expression and AK1 immunoprecipitates with the Kir6.2 subunit of K-ATP. AK activation by ATP + AMP stimulates K-ATP channel activity and this stimulation is abolished by AK inhibitors. We propose that glucose stimulation of beta-cells inhibits AK through glycolysis and also through the elevation of diadenosine polyphosphate levels. Glucose-dependent inhibition of AK increases the ATP/ADP ratio in the microenvironment of the K-ATP channel promoting channel closure and insulin secretion. The down-regulation of AK1 expression by hyperglycemia may contribute to the defective coupling of glucose metabolism to K-ATP channel activity in type 2 diabetes. (c) 2008 Published by Elsevier Inc. C1 [Holz, George G.; Leech, Colin A.] NYU, Sch Med, Dept Physiol & Neurosci, MSB449, New York, NY 10016 USA. [Stanojevic, Violeta; Habener, Joel F.; Leech, Colin A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA USA. RP Leech, CA (reprint author), NYU, Sch Med, Dept Physiol & Neurosci, MSB449, 550 1st Ave, New York, NY 10016 USA. EM colin.leech@med.nyu.edu RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [R01 DK045817-13, R01 DK069575, R01 DK045817, R01 DK045817-14] NR 22 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 11 PY 2008 VL 368 IS 3 BP 614 EP 619 DI 10.1016/j.bbrc.2008.01.109 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 273JJ UT WOS:000253925900026 PM 18243136 ER PT J AU Romeo, GR Kazlauskas, A AF Romeo, Giulio R. Kazlauskas, Andrius TI Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-PROTEIN; INSULIN-RESISTANCE; RECEPTOR; ATHEROSCLEROSIS; TRANSCRIPTION; INFLAMMATION; DYSFUNCTION; LDL; GENERATION; INHIBITION AB Endothelial dysfunction plays a central role in diabetic vascular disease, but its molecular bases are not completely defined. We showed previously that the actin-binding protein proflin-1 was increased in the diabetic endothelium and that attenuated expression of profilin-1 protected against atherosclerosis. Also 7-ketocholesterol up-regulated profilin-1 in endothelial cells via transcriptional mechanisms. The present study addressed the pathways responsible for profilin-1 gene expression in 7-ketocholesterol-stimulated endothelial cells and in the diabetic aorta. In luciferase reporter assays, the response to 7-ketocholesterol within the 5'-flanking region of profilin-1 was dependent on a single STAT response element. In aortic endothelial cells, 7-ketocholesterol enhanced STAT3 activation, which required JAK2 and tyrosine 394 phosphorylation of oxysterol-binding protein-1. These changes were recapitulated in the aorta of diabetic rats. Also 7-ketocholesterol in cultured endothelial cells and diabetes in the aorta elicited the recruitment of STAT3 and relevant coregulatory factors to the oxysterol-responsive region of the profilin-1 promoter. These events were required for profilin-1 up-regulation. These studies identify a previously unrecognized oxysterol-binding protein-mediated mode of activation of STAT3 that controls the expression of the proatherogenic protein profilin-1 in response to 7-ketocholesterol and the diabetic milieu. C1 [Romeo, Giulio R.; Kazlauskas, Andrius] Harvard Univ, Sch Med, Eye Res Inst, Boston, MA 02114 USA. RP Romeo, GR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA. EM giulio.romeo@joslin.harvard.edu NR 43 TC 26 Z9 30 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 11 PY 2008 VL 283 IS 15 BP 9595 EP 9605 DI 10.1074/jbc.M710092200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 283YE UT WOS:000254671600013 PM 18230613 ER PT J AU Taylor, EB An, D Kramer, HF Yu, H Fujii, NL Roeckl, KSC Bowles, N Hirshman, MF Xie, JX Feener, EP Goodyear, LJ AF Taylor, Eric B. An, Ding Kramer, Henning F. Yu, Haiyan Fujii, Nobuharu L. Roeckl, Katja S. C. Bowles, Nicole Hirshman, Michael F. Xie, Jianxin Feener, Edward P. Goodyear, Laurie J. TI Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING-PROTEIN; GLUT4 TRANSLOCATION; AKT SUBSTRATE; PHOSPHORYLATION ANALYSIS; GLUCOSE-TRANSPORT; AS160 PHOSPHORYLATION; RABGAP AS160; BINDING; KINASE; DOMAIN AB The Akt substrate of 160 kDa (AS160) is phosphorylated on Akt substrate (PAS) motifs in response to insulin and contraction in skeletal muscle, regulating glucose uptake. Here we discovered a dissociation between AS160 protein expression and apparent AS160 PAS phosphorylation among soleus, tibialis anterior, and extensor digitorum longus muscles. Immuno-depletion of AS160 in tibialis anterior muscle lysates resulted in minimal depletion of the PAS band at 160 kDa, suggesting the presence of an additional PAS immunoreactive protein. By immunoprecipitation and mass spectrometry, we identified this protein as the AS160 paralog TBC1D1, an obesity candidate gene regulating GLUT4 translocation in adipocytes. TBC1D1 expression was severalfold higher in skeletal muscles compared with all other tissues and was the dominant protein detected by the anti-PAS antibody at 160 kDa in tibialis anterior and extensor digitorum longus but not soleus muscles. In vivo stimulation by insulin, contraction, and the AMP-activated protein kinase (AMPK) activator AICAR increased TBC1D1 PAS phosphorylation. Using mass spectrometry on TBC1D1 from mouse skeletal muscle, we identified several novel phosphorylation sites on TBC1D1 and found the majority were consensus or near consensus sites for AMPK. Semiquantitative analysis of spectra suggested that AICAR caused greater overall phosphorylation of TBC1D1 sites compared with insulin. Purified Akt and AMPK phosphorylated TBC1D1 in vitro, and AMPK, but not Akt, reduced TBC1D1 electrophoretic mobility. TBC1D1 is a major PAS immunoreactive protein in skeletal muscle that is phosphorylated in vivo by insulin, AICAR, and contraction. Both Akt and AMPK phosphorylate TBC1D1, but AMPK may be the more robust regulator. C1 [Taylor, Eric B.; An, Ding; Kramer, Henning F.; Yu, Haiyan; Fujii, Nobuharu L.; Roeckl, Katja S. C.; Bowles, Nicole; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. [Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Proteom Core, Boston, MA 02215 USA. [Xie, Jianxin] Cell Signaling Technol Inc, Danvers, MA 01923 USA. RP Goodyear, LJ (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR 45670, R01 AR042238, AR 42238, R01 AR045670]; NIDDK NIH HHS [F32 DK 075851, F32 DK075851, P30 DK036836, DK 36836] NR 41 TC 121 Z9 123 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 11 PY 2008 VL 283 IS 15 BP 9787 EP 9796 DI 10.1074/jbc.M708839200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 283YE UT WOS:000254671600033 PM 18276596 ER PT J AU Burstein, HJ Elias, AD Rugo, HS Cobleigh, MA Wolff, AC Eisenberg, PD Lehman, M Adams, BJ Bello, CL DePrimo, SE Baum, CM Miller, KD AF Burstein, Harold J. Elias, Anthony D. Rugo, Hope S. Cobleigh, Melody A. Wolff, Antonio C. Eisenberg, Peter D. Lehman, Mary Adams, Bonne J. Bello, Carlo L. DePrimo, Samuel E. Baum, Charles M. Miller, Kathy D. TI Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; FACTOR RECEPTOR; ANGIOGENIC FACTORS; TUMOR-GROWTH; FACTOR PDGF; EXPRESSION; SU11248; VEGF; KIT AB Purpose Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor ( KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC). Patients and Methods Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis. Results Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for >= 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during >= 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions. Conclusion Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted. C1 [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Pfizer Inc, La Jolla, CA USA. TRACON Pharmaceut Inc, San Diego, CA USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Sidney Kimmel Canc Ctr Johns Hop, Baltimore, MD USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org OI Wolff, Antonio/0000-0003-3734-1063 NR 32 TC 336 Z9 347 U1 2 U2 19 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 APR 10 PY 2008 VL 26 IS 11 BP 1810 EP 1816 DI 10.1200/JCO.2007.14.5375 PG 7 WC Oncology SC Oncology GA 289KY UT WOS:000255054600009 PM 18347007 ER PT J AU Smith, MR Malkowicz, SB Chu, F Forrest, J Sieber, P Barnette, KG Rodriquez, D Steiner, MS AF Smith, Matthew R. Malkowicz, S. Bruce Chu, Franklin Forrest, John Sieber, Paul Barnette, K. Gary Rodriquez, Domingo Steiner, Mitchell S. TI Toremifene improves lipid profiles in men receiving androgen-deprivation therapy for prostate cancer: Interim analysis of a multicenter phase III study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MINERAL DENSITY; BREAST-CANCER; POSTMENOPAUSAL WOMEN; ARTERIAL STIFFNESS; BODY-COMPOSITION; SERUM-LIPIDS; RALOXIFENE; TAMOXIFEN; HEALTHY; TRIAL AB Purpose Androgen-deprivation therapy (ADT) is associated with greater risk of incident coronary heart disease and hospital admission for myocardial infarction; treatment-related increases in serum lipids may contribute to greater cardiovascular disease risk. We evaluated the effects of toremifene, a selective estrogen-receptor modulator, on fasting serum lipid levels in men receiving ADT for prostate cancer. Patients and Methods In an ongoing, multicenter, double-blind, placebo-controlled phase III fracture-prevention study, 1,389 men receiving ADT for prostate cancer were randomly assigned to receive toremifene (80 mg/d) or placebo. In this interim analysis of 188 patients, changes in fasting serum lipids from baseline to month 12 were compared between the placebo and toremifene groups. Results Changes in serum lipids differed significantly between the groups. Mean (+/- SE) total cholesterol decreased by 1.0% +/- 1.7% from baseline to month 12 in the placebo group and decreased by 8.1% +/- 1.4% in the toremifene group (P = .001 for between group comparison). Low-density lipoprotein (LDL) cholesterol increased by 0.8% +/- 2.5% in the placebo group and decreased by 8.2% +/- 2.5% in the toremifene group (P = .003). In contrast, high-density lipoprotein (HDL) cholesterol decreased by 4.9% +/- 1.2% in the placebo group and increased by 0.5% +/- 2.2% in the toremifene group (P = .018). Triglycerides increased by 6.9% +/- 4.2% in the placebo group and decreased by 13.2% +/- 3.6% in the toremifene group (P = .003). Conclusion Toremifene significantly decreased total cholesterol, LDL cholesterol, and triglycerides, and increased HDL cholesterol in men receiving ADT for prostate cancer. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. Urol Associates Lancaster, Lancaster, PA USA. San Bernadino Urol Associates, San Bernardino, CA USA. Urol Specialists Oklahoma, Tulsa, OK USA. GTx Inc, Memphis, TN USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7038,55 Fruit St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu FU NCI NIH HHS [K24 CA121990, K24 CA121990-02, K24 CA121990-03, K24 CA121990-04] NR 23 TC 44 Z9 46 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2008 VL 26 IS 11 BP 1824 EP 1829 DI 10.1200/JCO.2007.13.5517 PG 6 WC Oncology SC Oncology GA 289KY UT WOS:000255054600011 PM 18398147 ER PT J AU Pagan, JA Asch, DA Brown, CJ Guerra, CE Armstrong, K AF Pagan, Jose A. Asch, David A. Brown, Cynthia J. Guerra, Carmen E. Armstrong, Katrina TI Lack of community insurance and mammography screening rates among insured and uninsured women SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEALTH-INSURANCE; INCOME INEQUALITY; UNITED-STATES; MANAGED CARE; SELF-REPORT; CANCER; ACCURACY; ADULTS; NEEDS AB Purpose To evaluate whether the proportion of the local population without health insurance coverage is related to whether women undergo mammography screening. Methods Survey data on 12,595 women 40 to 69 years of age from the 2000 to 2001 Community Tracking Study Household Survey were used to analyze the relation between community lack of insurance and whether the respondent had a mammogram within the past year. Results Women age 40 to 69 were less likely to report that they had a mammogram within the last year if they resided in communities with a relatively high uninsurance rate, even after adjusting for other factors. After adjusting for individual insurance and other factors, a 10-percentage-point decrease in the proportion of the local insured population is associated with a 17% (95% CI, 13% to 21%) decrease in the odds that a woman age 40 to 69 years will undergo mammography screening within a year. Conclusion Women living in communities with high uninsurance are substantially less likely to undergo mammography screening. These results are consistent with the view that the negative impact of uninsurance extends to everyone in the community regardless of individual health insurance status. C1 [Pagan, Jose A.] Univ Texas Pan Amer, Dept Econ & Finance, Coll Business Adm, Edinburg, TX 78539 USA. Univ Texas Pan Amer, Inst Populat Hlth Policy, Coll Business Adm, Edinburg, TX 78541 USA. Univ Penn, Sch Med, Davis Inst Hlth Econ, Div Gen Internal Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Pagan, JA (reprint author), Univ Texas Pan Amer, Dept Econ & Finance, Coll Business Adm, 1201 W Univ Dr, Edinburg, TX 78539 USA. EM jpagan@utpa.edu OI Asch, David/0000-0002-7970-286X NR 32 TC 9 Z9 9 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 APR 10 PY 2008 VL 26 IS 11 BP 1865 EP 1870 DI 10.1200/JCO.2007.14.5664 PG 6 WC Oncology SC Oncology GA 289KY UT WOS:000255054600017 PM 18398151 ER PT J AU Lim, J Crespo-Barreto, J Jafar-Nejad, P Bowman, AB Richman, R Hill, DE Orr, HT Zoghbi, HY AF Lim, Janghoo Crespo-Barreto, Juan Jafar-Nejad, Paymaan Bowman, Aaron B. Richman, Ronald Hill, David E. Orr, Harry T. Zoghbi, Huda Y. TI Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1 SO NATURE LA English DT Article ID BULBAR MUSCULAR-ATROPHY; MOTOR-NEURON DEGENERATION; TRANSGENIC MOUSE MODEL; HUNTINGTONS-DISEASE; MUTANT HUNTINGTIN; IN-VIVO; TRINUCLEOTIDE REPEAT; INTERACTION NETWORK; MICE; ATAXIN-1 AB Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by expansion of a glutamine-encoding repeat in ataxin 1 (ATXN1). In all known polyglutamine diseases, the glutamine expansion confers toxic functions onto the protein; however, the mechanism by which this occurs remains enigmatic, in light of the fact that the mutant protein apparently maintains interactions with its usual partners. Here we show that the expanded polyglutamine tract differentially affects the function of the host protein in the context of different endogenous protein complexes. Polyglutamine expansion in ATXN1 favours the formation of a particular protein complex containing RBM17, contributing to SCA1 neuropathology by means of a gain-of-function mechanism. Concomitantly, polyglutamine expansion attenuates the formation and function of another protein complex containing ATXN1 and capicua, contributing to SCA1 through a partial loss-of-function mechanism. This model provides mechanistic insight into the molecular pathogenesis of SCA1 as well as other polyglutamine diseases. C1 [Lim, Janghoo; Jafar-Nejad, Paymaan; Bowman, Aaron B.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Crespo-Barreto, Juan; Zoghbi, Huda Y.] Baylor Coll Med, Interdept Program Cell & Mol Biol, Houston, TX 77030 USA. [Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Richman, Ronald; Zoghbi, Huda Y.] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. [Hill, David E.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Hill, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Orr, Harry T.] Univ Minnesota, Inst Human Genet, Dept Biochem Biophys & Mol Biol, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Zoghbi, HY (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM hzoghbi@bcm.tmc.edu RI Hill, David/B-6617-2011; OI Bowman, Aaron/0000-0001-8728-3346 FU Howard Hughes Medical Institute; NICHD NIH HHS [P30 HD024064-19, P30 HD024064]; NINDS NIH HHS [R01 NS027699, R01 NS027699-19] NR 43 TC 168 Z9 170 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 10 PY 2008 VL 452 IS 7188 BP 713 EP U1 DI 10.1038/nature06731 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285QY UT WOS:000254792500037 PM 18337722 ER PT J AU Ma, YC Song, MR Park, JP Ho, HYH Hu, L Kurtev, MV Zieg, J Ma, QF Pfaff, SL Greenberg, ME AF Ma, Yong-Chao Song, Mi-Ryoung Park, Jin P. Ho, Hsin-Yi Henry Hu, Linda Kurtev, Martin V. Zieg, Janine Ma, Qiufu Pfaff, Samuel L. Greenberg, Michael E. TI Regulation of motor neuron specification by phosphorylation of neurogenin 2 SO NEURON LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; HOMEODOMAIN PROTEINS; TRANSCRIPTIONAL CODES; CUBITUS INTERRUPTUS; SPINAL-CORD; IDENTITY; BHLH; LIM; GENES; DIFFERENTIATION AB The mechanisms by which proneural basic helix-loop-helix (bHLH) factors control neurogenesis have been characterized, but it is not known how they specify neuronal cell-type identity. Here, we provide evidence that two conserved serine residues on the bHLH factor neurogenin 2 (Ngn2), S231 and S234, are phosphorylated during motor neuron differentiation., In knockin mice in which S231 and S234 of Ngn2 were mutated to alanines, neurogenesis occurs normally, but motor neuron specification is impaired. The phosphorylation of Ngn2 at S231 and S234 facilitates the interaction of Ngn2 with LIM homeodomain transcription factors to specify motor neuron identity. The phosphorylation-dependent cooperativity between Ngn2 and homeodomain transcription factors may be a general mechanism by which the activities of bHLH and homeodomain proteins are temporally and spatially integrated to generate the wide diversity of cell types that are a hallmark of the nervous system. C1 [Ma, Yong-Chao; Park, Jin P.; Ho, Hsin-Yi Henry; Hu, Linda; Kurtev, Martin V.; Zieg, Janine; Greenberg, Michael E.] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Ma, Yong-Chao; Park, Jin P.; Ho, Hsin-Yi Henry; Hu, Linda; Kurtev, Martin V.; Zieg, Janine; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Ma, Yong-Chao; Park, Jin P.; Ho, Hsin-Yi Henry; Hu, Linda; Kurtev, Martin V.; Zieg, Janine; Ma, Qiufu; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Song, Mi-Ryoung; Pfaff, Samuel L.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. [Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Greenberg, ME (reprint author), Childrens Hosp, FM Kirby Neurobiol Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM michael.greenberg@childrens.harvard.edu FU NICHD NIH HHS [HD18655, P30 HD018655, P30 HD018655-25, P30 HD018655-26]; NIGMS NIH HHS [T32 GM007753]; NINDS NIH HHS [P01NS047572, P01 NS047572, P01 NS047572-01A10001, P01 NS047572-020001, P01 NS047572-030001, P01 NS047572-040001, R37 NS037116, R37NS037116, T32 NS007473, T32 NS007473-03, T32 NS007473-04] NR 61 TC 67 Z9 67 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 10 PY 2008 VL 58 IS 1 BP 65 EP 77 DI 10.1016/j.neuron.2008.01.037 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 287WC UT WOS:000254946200011 PM 18400164 ER PT J AU Fishman, JA Gonzalez, RG Branda, JA Rosenberg, ES AF Fishman, Jay A. Gonzalez, R. Gilberto Branda, John A. Rosenberg, Eric S. TI A man with changes in mental status after liver transplantation - Disseminated cryptococcosis with cryptococcal meningitis in a liver-allograft recipient SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VISCERAL LEISHMANIASIS; ORGAN DONOR; NEOFORMANS INFECTION; TRANSMISSION; VIRUS; THERAPY; MANAGEMENT; DISEASE; IMPACT; AGENTS C1 [Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Host Pro, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fishman, Jay A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Branda, John A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 35 TC 11 Z9 11 U1 2 U2 2 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 APR 10 PY 2008 VL 358 IS 15 BP 1604 EP 1613 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 285NK UT WOS:000254783300011 PM 18403769 ER PT J AU Melrose, RJ Tinaz, S Castelo, JMB Courtney, MG Stern, CE AF Melrose, Rebecca J. Tinaz, Sule Castelo, J. Mirni Boer Courtney, Maureen G. Stern, Chantal E. TI Compromised fronto-striatal functioning in HIV: An fMRI investigation of semantic event sequencing SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE HIV; executive functioning; basal ganglia; caudate; prefrontal cortex ID IMMUNODEFICIENCY-VIRUS-INFECTION; CEREBRAL VOLUME LOSS; BASAL-GANGLIA; PREFRONTAL CORTEX; MORPHOMETRIC ANALYSIS; WORKING-MEMORY; HUMAN BRAIN; ATTENTION; ACTIVATION; NETWORK AB The human immunodeficiency virus (HIV) damages fronto-striatal regions, and is associated with deficits in executive functioning. We recently developed a semantic event sequencing task based on the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale-III for use with functional magnetic resonance imaging (fMRI) and found recruitment of dorsolateral prefrontal cortex and basal ganglia in healthy participants. To assess the impact of HIV on the functioning of the basal ganglia and prefrontal cortex, we administered this task to 11 HIV+ and 11 Control participants inatched for age and education. Neuropsychological evaluation demonstrated that the HIV+ group had mild impairment in memory retrieval and motor functioning, but was not demented. Morphometric measurements suggested no atrophy in basal ganglia regions. The results of the fMRI analysis revealed hypoactivation of the left caudate, left dorsolateral prefrontal cortex, and bilateral ventral prefrontal cortex in the HIV+ group. Functional connectivity analysis demonstrated less functional connectivity between the caudate and prefrontal cortex and basal ganglia regions in the HIV+ group. In contrast, the HIV+ group demonstrated increased activation of right postcentral/supramarginal gyrus, and greater connectivity between the caudate and this same anterior parietal region. The results of this study extend previous investigations by demonstrating compromised function of the caudate and connected prefrontal regions in HIV during cognition. This disruption of fronto-striatal circuitry likely precedes the development of cognitive impairment in HIV. (C) 2007 Elsevier B.V. All rights reserved. C1 [Melrose, Rebecca J.; Tinaz, Sule; Castelo, J. Mirni Boer; Courtney, Maureen G.; Stern, Chantal E.] Boston Univ, Cognit Neuroimaging Lab, Ctr Mem & Brain, Boston, MA 02215 USA. [Melrose, Rebecca J.; Tinaz, Sule; Castelo, J. Mirni Boer; Courtney, Maureen G.; Stern, Chantal E.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Stern, Chantal E.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Melrose, RJ (reprint author), Boston Univ, Cognit Neuroimaging Lab, Ctr Mem & Brain, 2 Cummington St, Boston, MA 02215 USA. EM melrose@mind.bu.edu FU NCRR NIH HHS [P41 RR 14075]; NIMH NIH HHS [P50 MH 071702]; NINDS NIH HHS [F31 NS 054570, F31 NS 052126, R01 NS 40239, R01 NS040239] NR 52 TC 68 Z9 69 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR 9 PY 2008 VL 188 IS 2 BP 337 EP 347 DI 10.1016/j.bbr.2007.11.021 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 277MT UT WOS:000254217700014 PM 18242723 ER PT J AU Zhu, AX Abou-Alfa, GK AF Zhu, Andrew X. Abou-Alfa, Ghassan K. TI Expanding the treatment options for hepatocellular carcinoma - Combining transarterial chemoembolization with radiofrequency ablation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; LIPIODOL CHEMOEMBOLIZATION; ARTERIAL CHEMOEMBOLIZATION; SYMPTOMATIC TREATMENT; ETHANOL INJECTION; UNITED-STATES; THERAPY; COMBINATION; MANAGEMENT C1 [Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Zhu, Andrew X.] Harvard Univ, Sch Med, Boston, MA USA. [Abou-Alfa, Ghassan K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lawrence House,POB 232,55 Fruit St, Boston, MA 02114 USA. EM azhu@partners.org NR 23 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 9 PY 2008 VL 299 IS 14 BP 1716 EP 1718 DI 10.1001/jama.299.14.1716 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 285AL UT WOS:000254749600029 PM 18398085 ER PT J AU Kim, MO Chawla, P Overland, RP Xia, E Sadri-Vakili, G Cha, JHJ AF Kim, Mee-Ohk Chawla, Prianka Overland, Ryan P. Xia, Eva Sadri-Vakili, Ghazaleh Cha, Jang-Ho J. TI Altered histone monoubiquitylation mediated by mutant Huntingtin induces transcriptional dysregulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE histone monoubiquitylation; huntingtin; Bmi-1; histone methylation; transcription; histone code ID ACETYLTRANSFERASE-CONTAINING COMPLEXES; GENE-EXPRESSION; MOUSE MODEL; H2B UBIQUITYLATION; UBIQUITIN LIGASE; TRANSGENIC MICE; STRIATAL CELLS; LYSINE 9; DISEASE; METHYLATION AB Although transcriptional dysregulation is a critical pathogenic mechanism in Huntington's disease (HD), it is still not known how mutant huntingtin causes it. Here we show that alteration of histone monoubiquitylation is a key mechanism. Disrupted interaction of huntingtin with Bmi-1, a component of the hPRC1L E3 ubiquitin ligase complex, increases monoubiquityl histone H2A (uH2A) levels in a cell culture model of HD. Genes with expression that is repressed in transgenic R6/2 mouse brain have increased uH2A and decreased uH2B at their promoters, whereas actively transcribed genes show the opposite pattern. Reduction in uH2A reverses transcriptional repression and inhibits methylation of histone H3 at lysine 9 in cell culture. In contrast, reduction in uH2B induces transcriptional repression and inhibits methylation of histone H3 at lysine 4. This is the first report to demonstrate hPRC1L as a huntingtin-interacting histone modifying complex and a crucial role for histone monoubiquitylation in mammalian brain gene expression, which broadens our understanding of histone code. These findings also provide a rationale for targeting histone monoubiquitylation for therapy in HD. C1 [Kim, Mee-Ohk; Chawla, Prianka; Overland, Ryan P.; Xia, Eva; Sadri-Vakili, Ghazaleh; Cha, Jang-Ho J.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM cha@helix.mgh.harvard.edu FU NINDS NIH HHS [P01 NS045242, NS38106, NS45242, P01 NS045242-030004, R01 NS038106, R01 NS038106-06] NR 50 TC 44 Z9 46 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 9 PY 2008 VL 28 IS 15 BP 3947 EP 3957 DI 10.1523/JNEUROSCI.5667-07.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 288UX UT WOS:000255012400014 PM 18400894 ER PT J AU Xu, Y Lopes, C Qian, Y Liu, Y Cheng, LP Goulding, M Turner, EE Lima, D Ma, QF AF Xu, Yi Lopes, Claudia Qian, Ying Liu, Ying Cheng, Leping Goulding, Martyn Turner, Eric E. Lima, Deolinda Ma, Qiufu TI Tlx1 and Tlx3 coordinate specification of dorsal horn pain-modulatory peptidergic neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dorsal spinal cord; peptidergic neurons; Tlx3; cell fate specification; transcriptional regulation; pain ID RAT SPINAL-CORD; LAMINAE-I-III; SENSORY NEURONS; NEUROPATHIC PAIN; GENE-EXPRESSION; MARGINAL ZONE; CELL FATE; INTERNEURONS; PHENOTYPE; GLUTAMATE AB The dorsal spinal cord synthesizes a variety of neuropeptides that modulate the transmission of nociceptive sensory information. Here, we used genetic fate mapping to show that Tlx3(+) spinal cord neurons and their derivatives represent a heterogeneous population of neurons, marked by partially overlapping expression of a set of neuropeptide genes, including those encoding the anti-opioid peptide cholecystokinin, pronociceptive Substance P (SP), Neurokinin B, and a late wave of somatostatin. Mutations of Tlx3 and Tlx1 result in a loss of expression of these peptide genes. Brn3a, a homeobox transcription factor, the expression of which is partly dependent on Tlx3, is required specifically for the early wave of SP expression. These studies suggest that Tlx1 and Tlx3 operate high in the regulatory hierarchy that coordinates specification of dorsal horn pain-modulatory peptidergic neurons. C1 [Xu, Yi; Lopes, Claudia; Ma, Qiufu] Dana Farber Canc Inst, Boston, MA 02115 USA. [Xu, Yi; Lopes, Claudia; Qian, Ying; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Lopes, Claudia; Lima, Deolinda] Univ Porto, Mol Cell Biol Lab, P-4100 Oporto, Portugal. [Turner, Eric E.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Liu, Ying; Turner, Eric E.] Vet Affairs San Diego Healthcare Syst, La Jolla, CA 92093 USA. [Cheng, Leping] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. [Goulding, Martyn] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA. RP Ma, QF (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM Qiufu_Ma@dfci.harvard.edu RI Liu, Ying/C-2734-2008; Turner, Eric/K-3556-2015; OI Turner, Eric/0000-0001-5499-6788; Lima, Deolinda/0000-0002-5723-0777 FU NINDS NIH HHS [R01 NS047710-02, P01 NS047572, P01 NS047572-01A10003, P01 NS047572-020003, P01 NS047572-030003, P01 NS047572-040003, P01 NS047572-050003, P01NS047572, R01 NS047710, R01 NS047710-01, R01 NS047710-03, R01 NS047710-04, R01 NS047710-05, R01NS47710] NR 51 TC 34 Z9 34 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 9 PY 2008 VL 28 IS 15 BP 4037 EP 4046 DI 10.1523/JNEUROSCI.4126-07.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 288UX UT WOS:000255012400023 PM 18400903 ER PT J AU Sachidanandan, C Yeh, JRJ Peterson, QP Peterson, RT AF Sachidanandan, Chetana Yeh, Jing-Ruey J. Peterson, Quinn P. Peterson, Randall T. TI Identification of a Novel Retinoid by Small Molecule Screening with Zebrafish Embryos SO PLOS ONE LA English DT Article ID HEDGEHOG SIGNALING PATHWAY; ACID RECEPTORS; CANCER; HINDBRAIN; GENETICS; PATTERN; TARGET; GENES; DIFFERENTIATION; SPECIFICATION AB Small molecules have played an important role in delineating molecular pathways involved in embryonic development and disease pathology. The need for novel small molecule modulators of biological processes has driven a number of targeted screens on large diverse libraries. However, due to the specific focus of such screens, the majority of the bioactive potential of these libraries remains unharnessed. In order to identify a higher proportion of compounds with interesting biological activities, we screened a diverse synthetic library for compounds that perturb the development of any of the multiple organs in zebrafish embryos. We identified small molecules that affect the development of a variety of structures such as heart, vasculature, brain, and body-axis. We utilized the previously known role of retinoic acid in anterior-posterior (A-P) patterning to identify the target of DTAB, a compound that caused A-P axis shortening in the zebrafish embryo. We show that DTAB is a retinoid with selective activity towards retinoic acid receptors gamma and beta. Thus, conducting zebrafish developmental screens using small molecules will not only enable the identification of compounds with diverse biological activities in a large chemical library but may also facilitate the identification of the target pathways of these biologically active molecules. C1 [Sachidanandan, Chetana; Yeh, Jing-Ruey J.; Peterson, Quinn P.; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Peterson, RT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. EM peterson@cvrc.mgh.harvard.edu FU Novartis Institutes for Biomedical Research NIH - NHLBI [HL079267]; Postdoctoral Fellowship from Massachusetts General Hospital Fund for Medical Discovery; Tosteson Fellowship from the Massachusetts Biomedical Research Corporation FX Funding for R.T.P. from Sponsored Research Agreement from Novartis Institutes for Biomedical Research NIH - NHLBI HL079267. C.S. was supported by Postdoctoral Fellowship from Massachusetts General Hospital Fund for Medical Discovery. J.-R.J.Y. was supported by a Tosteson Fellowship from the Massachusetts Biomedical Research Corporation. None of the funders played any role in the conduct, interpretation, preparation, or approval of the manuscript. NR 41 TC 42 Z9 43 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2008 VL 3 IS 4 AR e1947 DI 10.1371/journal.pone.0001947 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 370XD UT WOS:000260795500022 PM 18398471 ER PT J AU Raitt, MH AF Raitt, Merritt H. TI Implantable cardioverter-defibrillator shocks SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID CONGESTIVE-HEART-FAILURE; HOSPITALIZATION; DEPRESSION; ATTITUDES; ANXIETY; TRIAL; DEATH C1 [Raitt, Merritt H.] Portland VA Med Ctr, Div Cardiol, Portland, OR USA. RP Raitt, MH (reprint author), 3710 SW US Vet Rd, Portland, OR 97239 USA. EM merritt.raitt@va.gov NR 20 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 8 PY 2008 VL 51 IS 14 BP 1366 EP 1368 DI 10.1016/j.jacc.2007.12.032 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 284AL UT WOS:000254677500006 PM 18387437 ER PT J AU Wang, BB Yanaz, A Novina, CD AF Wang, Bingbing Yanaz, Adrienne Novina, Carl D. TI MicroRNA-repressed mRNAs contain 40S but not 60S components SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE argonaute; translation; ribosome ID EUKARYOTIC INITIATION FACTOR-6; TRANSLATION INITIATION; IN-VITRO; CAENORHABDITIS-ELEGANS; PROTEIN-SYNTHESIS; LET-7 MICRORNA; BINDING; CELLS; PURIFICATION; INHIBITION AB MicroRNAs (miRNAs) are small noncoding RNAs that may target more than one-third of human genes, yet the mechanisms used by miRNAs to repress translation of target mRNAs are obscure. Using a recently described cell-free assay of miRNA function, we observe that miRNA-targeted mRNAs are enriched for 40S but not 60S ribosome components. Additionally, toeprinting analysis of miRNA-targeted mRNAs demonstrates that approximate to 18 nt 3' relative to the initiating AUG are protected, consistent with 40S ribosome subunits positioned at the AUG codon. Our results suggest that miRNAs repress translation initiation by preventing 60S subunit joining to miRNA-targeted mRNAs. C1 [Wang, Bingbing; Yanaz, Adrienne; Novina, Carl D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Wang, Bingbing; Yanaz, Adrienne; Novina, Carl D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Novina, Carl D.] MIT, Cambridge, MA 02141 USA. [Novina, Carl D.] Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. RP Novina, CD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM carl_novina@dfci.harvard.edu FU NIGMS NIH HHS [GM07266, F31 GM087947, T32 GM007266] NR 28 TC 69 Z9 69 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 8 PY 2008 VL 105 IS 14 BP 5343 EP 5348 DI 10.1073/pnas.0801102105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 287CG UT WOS:000254893600013 PM 18390669 ER PT J AU Wu, XD Yamada-Mabuchi, M Morris, EJ Tanwar, PS Dobens, L Gluderer, S Khan, S Cao, J Stocker, H Hafen, E Dysont, NJ Raftery, LA AF Wu, Xiaodong Yamada-Mabuchi, Megumu Morris, Erick J. Tanwar, Pradeep Singh Dobens, Leonard Gluderer, Silvia Khan, Sabina Cao, Jing Stocker, Hugo Hafen, Ernst Dysont, Nick J. Raftery, Laurel A. TI The Drosophila homolog of human tumor suppressor TSC-22 promotes cellular growth, proliferation, and survival SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bunched; follicle cells; oogenesis ID BETA-STIMULATED CLONE-22; SALIVARY-GLAND CANCER; LEUCINE-ZIPPER STRUCTURE; OVARIAN-FOLLICLE CELLS; DOWN-REGULATION; DIFFERENTIAL DISPLAY; EYE DEVELOPMENT; IN-VIVO; GENE; NOTCH AB TSC22D1, which encodes transforming growth factor beta-stimulated clone 22 (TSC-22), is thought to be a tumor suppressor because its expression is lost in many glioblastoma, salivary gland, and prostate cancers. TSC-22 is the founding member of the TSC-22/DIP/Bun family of leucine zipper transcription factors; its functions have not been investigated in a multicellular environment. Genetic studies in the model organism Drosophila melanogaster often provide fundamental insights into mechanisms disrupted in carcinogenesis, because of the strong evolutionary conservation of molecular mechanisms between flies and humans. Whereas humans and mice have four TSC-22 domain genes with numerous isoforms, Drosophila has only one TSC-22 domain gene, bunched (bun), which encodes both large and small protein isoforms. Surprisingly, Drosophila Bun proteins promote cellular growth and proliferation in ovarian follicle cells. Loss of both large isoforms has the strongest phenotypes, including increased apoptosis. Cultured S2 cells depleted for large Bun isoforms show increased apoptosis and less frequent cell division, with decreased cell size. Altogether, these data indicate that Drosophila TSC-22/DIP/Bun proteins are necessary for cellular growth, proliferation, and survival both in culture and in an epithelial context. Previous work demonstrated that bun prevents recruitment of epithelial cells to a migratory fate and, thus, maintains epithelial organization. We speculate that reduced TSC22D1 expression generally reduces cellular fitness and only contributes to carcinogenesis in specific tissue environments. C1 [Wu, Xiaodong; Yamada-Mabuchi, Megumu; Tanwar, Pradeep Singh; Dobens, Leonard; Khan, Sabina; Cao, Jing; Raftery, Laurel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Morris, Erick J.; Dysont, Nick J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Gluderer, Silvia; Stocker, Hugo; Hafen, Ernst] ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland. RP Raftery, LA (reprint author), Massachusetts Gen Hosp East, 3rd Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. EM laurel.raftery@cbrc2.mgh.harvard.edu RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NIGMS NIH HHS [R01 GM053203, R01GM53203, R01 GM060501, 2R01-GM60501] NR 65 TC 13 Z9 16 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 8 PY 2008 VL 105 IS 14 BP 5414 EP 5419 DI 10.1073/pnas.0800945105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 287CG UT WOS:000254893600025 PM 18375761 ER PT J AU Castano, AP Mroz, P Wu, MX Hamblin, MR AF Castano, Ana P. Mroz, Pawel Wu, Mei X. Hamblin, Michael R. TI Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunosuppression; cytotoxic T lymphocytes; benzoporphyrin derivative; regulatory T cells; tumor-associated antigen ID REGULATORY T-CELLS; FACILITATED ADOPTIVE IMMUNOTHERAPY; TUMOR-IMMUNITY; LASER IMMUNOTHERAPY; MEDIATED-IMMUNITY; CANCER VACCINES; SOLID TUMORS; DEPLETION; MICE; POPULATIONS AB Photodynamic therapy (PDT) is a modality for the treatment of cancer involving excitation of nontoxic photosensitizers with harmless visible light-producing cytotoxic reactive oxygen species. PDT causes apoptosis and necrosis of tumor cells, destruction of the tumor blood supply, and activation of the immune system. The objective of this study was to compare in an animal model of metastatic cancer PDT alone and PDT combined with low-dose cyclophosphamide (CY) a treatment that has been proposed to deplete regulatory T cells (T-regs) and increase the immune response to some tumors. We used J774 tumors (a highly metastatic reticulum cell sarcoma line) and PDT with benzoporphyrin derivative monoacid ring A, verteporfin for injection (BPD; 1-mg/kg injected i.v. followed after 15 min by 150 J/cm(2) of 690-nm light). CY (50 or 150 mg/kg i.p.) was injected 48 h before light delivery. PDT alone led to tumor regressions and a survival advantage but no permanent cures were obtained. BPD-PDT in combination with low-dose CY (but not high-dose CY) led to 70% permanent cures. Low-dose CY alone gave no permanent cures but did provide a survival advantage and was shown to reduce CD4+FoxP3+ T-regs in lymph nodes, whereas high-dose CY reduced other lymphocyte classes as well. Cured animals were rechallenged with J774 cells, and the tumors were rejected in 71% of mice. Cured mice had tumor-specific T cells in spleens as determined by a Cr-51 release assay. We conclude that low-dose CY depletes T-regs and potentiates BPD-PDT, leading to tumor cures and memory immunity. C1 [Castano, Ana P.; Mroz, Pawel; Wu, Mei X.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Castano, Ana P.; Mroz, Pawel; Wu, Mei X.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Wu, Mei X.; Hamblin, Michael R.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882, R01 CA083882-03]; NIAID NIH HHS [R01 AI050875, R01 AI050875-06, R01-CA/AI838801] NR 56 TC 87 Z9 92 U1 3 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 8 PY 2008 VL 105 IS 14 BP 5495 EP 5500 DI 10.1073/pnas.0709256105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 287CG UT WOS:000254893600039 PM 18378905 ER PT J AU Hadj-Bouziane, F Bell, AH Knusten, TA Ungerleider, LG Tootell, RBH AF Hadj-Bouziane, Fadila Bell, Andrew H. Knusten, Tamara A. Ungerleider, Leslie G. Tootell, Roger B. H. TI Perception of emotional expressions is independent of face selectivity in monkey inferior temporal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amygdala; emotion; valence; fMRl ID SURFACE-BASED ANALYSIS; FACIAL EXPRESSIONS; VISUAL-CORTEX; CONTRAST AGENT; HUMAN AMYGDALA; RESPONSES; NEURONS; MACAQUE; IDENTITY; COMMUNICATION AB The ability to perceive and differentiate facial expressions is vital for social communication. Numerous functional MRI (fMR1) studies in humans have shown enhanced responses to faces with different emotional valence, in both the amygdala and the visual cortex. However, relatively few studies have examined how valence influences neural responses in monkeys, thereby limiting the ability to draw comparisons across species and thus understand the underlying neural mechanisms. Here we tested the effects of macaque facial expressions on neural activation within these two regions using fMR1 in three awake, behaving monkeys. Monkeys maintained central fixation while blocks of different monkey facial expressions were presented. Four different facial expressions were tested: (i) neutral, (it) aggressive (open-mouthed threat), (fil) fearful (fear grin), and (iv) submissive (lip smack). Our results confirmed that both the amygdala and the inferior temporal cortex in monkeys are modulated by facial expressions. As in human fMR1, fearful expressions evoked the greatest response in monkeys-even though fearful expressions are physically dissimilar in humans and macaques. Furthermore, we found that valence effects were not uniformly distributed over the inferior temporal cortex. Surprisingly, these valence maps were independent of two related functional maps: (i) the map of -"face-selective" regions (faces versus non-face objects) and (it) the map of "face-responsive" regions (faces versus scrambled images). Thus, the neural mechanisms underlyingface perception and valence perception appear to be distinct. C1 [Hadj-Bouziane, Fadila; Bell, Andrew H.; Ungerleider, Leslie G.; Tootell, Roger B. H.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Knusten, Tamara A.; Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Hadj-Bouziane, F (reprint author), NIMH, Lab Brain & Cognit, NIH, 49 Convent Dr,Bldg 49-1B80, Bethesda, MD 20892 USA. EM hadjf@mail.nih.gov; ungerlel@mail.nih.gov RI Hadj-Bouziane, Fadila/A-1180-2013; OI Bell, Andrew/0000-0001-8420-4622 FU Intramural NIH HHS; NEI NIH HHS [R01 EY017081, R01 EY017081-01A1, R01 EY017081-02, R01 EY017081-03]; NIMH NIH HHS [R01 MH67529, R01 MH067529] NR 42 TC 50 Z9 50 U1 2 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 APR 8 PY 2008 VL 105 IS 14 BP 5591 EP 5596 DI 10.1073/pnas.0800489105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 287CG UT WOS:000254893600055 PM 18375769 ER PT J AU Estiu, G Wiest, O Greenberg, E Mazitschek, R Bradner, J AF Estiu, Guillermina Wiest, Olaf Greenberg, Edward Mazitschek, Ralph Bradner, James TI COMP 227-Histone deacetylase inhibitors: Reasons for isoform selectivity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Estiu, Guillermina; Wiest, Olaf] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Greenberg, Edward; Mazitschek, Ralph] Harvard Univ & MIT, Broad Inst, Boston, MA 02115 USA. [Bradner, James] Dana Farber Canc Inst, Boston, MA 02115 USA. EM gestiu@nd.edu; owiest@nd.edu; ralph@broad.harvard.edu; James_Bradner@dfci.harvard.edu RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 227-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104099 ER PT J AU Janorkar, AV King, KR Megeed, Z Yarmush, M AF Janorkar, Amol V. King, Kevin R. Megeed, Zak Yarmush, Martin TI BIOL 142-Effect of steatosis and TNF on NFkB response of hepatocyte-derived reporter cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Janorkar, Amol V.] Univ Mississippi, Med Ctr, Dept Biomed Mat Sci, Jackson, MS 39216 USA. [King, Kevin R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [King, Kevin R.] Shriners Hosp Children, Boston, MA 02114 USA. [Megeed, Zak] Shriners Burns Hosp, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02129 USA. [Megeed, Zak] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Yarmush, Martin] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. EM ajanorkar@sod.umsmed.edu; krking@mit.edu; zmegeed@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 142-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100641 ER PT J AU Whetstine, JR AF Whetstine, Johnathan R. TI MEDI 170-Histone demethylases: From enzyme discovery to biological impact SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Whetstine, Johnathan R.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Whetstine, Johnathan R.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM jwhetstine@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 170-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107324 ER PT J AU Liu, ZH Meng, JH Sun, X AF Liu, Zhihua Meng, Jihong Sun, Xiao TI A novel feature-based method for whole genome phylogenetic analysis without alignment: Application to HEV genotyping and subtyping SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE whole genome phylogeny; alignment-free; hepatitis E virus; base-base correlation ID HEPATITIS-E VIRUS; MULTIPLE SEQUENCE ALIGNMENT; CLUSTAL-X; CONSTRUCTION; ORGANISMS; EVOLUTION; PAKISTAN; DISTINCT; TREE; DNA AB Traditional phylogenetic analysis is based on multiple sequence alignment. With the development of worldwide genome sequencing project, more and more completely sequenced genomes become available. However, traditional sequence alignment tools are impossible to deal with large-scale genome sequence. So, the development of new algorithms to infer phylogenetic relationship without alignment from whole genome information represents a new direction of phylogenetic study in the post-genome era. In the present study, a novel algorithm based on BBC (base-base correlation) is proposed to analyze the phylogenetic relationships of HEV (Hepatitis E virus). When 48 HEV genome sequences are analyzed, the phylogenetic tree that is constructed based on BBC algorithm is well consistent with that of previous study. When compared with methods of sequence alignment, the merit of BBC algorithm appears to be more rapid in calculating evolutionary distances of whole genome sequence and not requires any human intervention, such as gene identification, parameter selection. BBC algorithm can serve as an alternative to rapidly construct phylogenetic trees and infer evolutionary relationships. (C) 2008 Elsevier Inc. All rights reserved. C1 [Liu, Zhihua; Sun, Xiao] Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Peoples R China. [Liu, Zhihua] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, Zhihua] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Meng, Jihong] Southeast Univ, Sch Med, Dept Microbiol & Immunol, Nanjing 210009, Peoples R China. RP Liu, ZH (reprint author), Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Peoples R China. EM zhliu@jimmy.harvard.edu; zhliu@seu.edu.cn; xsun@seu.edu.cn NR 40 TC 34 Z9 36 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 4 PY 2008 VL 368 IS 2 BP 223 EP 230 DI 10.1016/j.bbrc.2008.01.070 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 269SC UT WOS:000253669500008 PM 18230342 ER PT J AU Tao, Y Ferrer, JL Ljung, K Pojer, F Hong, FX Long, JA Li, L Moreno, JE Bowman, ME Ivans, LJ Cheng, YF Lim, J Zhao, YD Ballare, CL Sandberg, G Noel, JP Chory, J AF Tao, Yi Ferrer, Jean-Luc Ljung, Karin Pojer, Florence Hong, Fangxin Long, Jeff A. Li, Lin Moreno, Javier E. Bowman, Marianne E. Ivans, Lauren J. Cheng, Youfa Lim, Jason Zhao, Yunde Ballare, Carlos L. Sandberg, Goeran Noel, Joseph P. Chory, Joanne TI Rapid synthesis of auxin via a new tryptophan-dependent pathway is required for shade avoidance in plants SO CELL LA English DT Article ID AMINO-ACID AMINOTRANSFERASES; ENTEROBACTER-CLOACAE; INDOLE-3-ACETIC-ACID BIOSYNTHESIS; INDOLEPYRUVATE DECARBOXYLASE; INDOLE-3-PYRUVIC ACID; ARABIDOPSIS-THALIANA; REACTION SPECIFICITY; INDOLEACETIC-ACID; LIGHT QUALITY; PHYTOCHROME-B AB Plants grown at high densities perceive a decrease in the red to far-red (R:FR) ratio of incoming light, resulting from absorption of red light by canopy leaves and reflection of far-red light from neighboring plants. These changes in light quality trigger a series of responses known collectively as the shade avoidance syndrome. During shade avoidance, stems elongate at the expense of leaf and storage organ expansion, branching is inhibited, and flowering is accelerated. We identified several loci in Arabidopsis, mutations in which lead to plants defective in multiple shade avoidance responses. Here we describe TAA1, an aminotransferase, and show that TAA1 catalyzes the formation of indole-3-pyruvic acid (IPA) from L-tryptophan (L-Trp), the first step in a previously proposed, but uncharacterized, auxin biosynthetic pathway. This pathway is rapidly deployed to synthesize auxin at the high levels required to initiate the multiple changes in body plan associated with shade avoidance. C1 [Tao, Yi; Pojer, Florence; Hong, Fangxin; Bowman, Marianne E.; Lim, Jason; Noel, Joseph P.; Chory, Joanne] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. [Tao, Yi; Hong, Fangxin; Long, Jeff A.; Li, Lin; Ivans, Lauren J.; Lim, Jason; Chory, Joanne] Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA. [Ferrer, Jean-Luc] UJF, CNRS, CEA, Inst Biol Struct,Lab Cristallog & Cristallogenese, F-38027 Grenoble, France. [Ferrer, Jean-Luc; Pojer, Florence; Bowman, Marianne E.; Noel, Joseph P.] Salk Inst Biol Studies, Jack H Skirball Ctr Chem Biol & Proteom, La Jolla, CA 92037 USA. [Ljung, Karin] Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, SE-90183 Umea, Sweden. [Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Moreno, Javier E.; Ballare, Carlos L.] Consejo Nacl Invest Cient & Tecn, Inst Invest Fisiol & Ecol Vinculadas Agr, Buenos Aires, DF, Argentina. [Moreno, Javier E.; Ballare, Carlos L.] Univ Buenos Aires, Buenos Aires, DF, Argentina. [Ivans, Lauren J.; Cheng, Youfa; Zhao, Yunde] Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol Sci, La Jolla, CA 92093 USA. [Sandberg, Goeran] Umea Univ, Dept Plant Physiol, Umea Plant Sci Ctr, SE-90187 Umea, Sweden. RP Chory, J (reprint author), Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA. EM chory@salk.edu RI Ballare, Carlos/F-5141-2011; Tao, Yi/B-7718-2012; Cheng, Youfa/E-4187-2012; OI Ballare, Carlos/0000-0001-9129-4531; Tao, Yi/0000-0002-7460-7927 FU Howard Hughes Medical Institute; NIGMS NIH HHS [GM52413, R01 GM052413, R01 GM052413-13] NR 52 TC 412 Z9 437 U1 18 U2 109 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 4 PY 2008 VL 133 IS 1 BP 164 EP 176 DI 10.1016/j.cell.2008.01.049 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 283MW UT WOS:000254641300017 PM 18394996 ER PT J AU Viswanathan, SR Daley, GQ Gregory, RI AF Viswanathan, Srinivas R. Daley, George Q. Gregory, Richard I. TI Selective blockade of MicroRNA processing by Lin28 SO SCIENCE LA English DT Article ID EMBRYONIC STEM-CELLS; POSTTRANSCRIPTIONAL REGULATION; MICROPROCESSOR COMPLEX; LET-7 MICRORNA; SELF-RENEWAL; EXPRESSION; RNA; TRANSFORMATION; BIOGENESIS; PROFILE AB MicroRNAs ( miRNAs) play critical roles in development, and dysregulation of miRNA expression has been observed in human malignancies. Recent evidence suggests that the processing of several primary miRNA transcripts (pri- miRNAs) is blocked posttranscriptionally in embryonic stem cells, embryonal carcinoma cells, and primary tumors. Here we show that Lin28, a developmentally regulated RNA binding protein, selectively blocks the processing of pri- let- 7 miRNAs in embryonic cells. Using in vitro and in vivo studies, we found that Lin28 is necessary and sufficient for blocking Microprocessor- mediated cleavage of pri- let- 7 miRNAs. Our results identify Lin28 as a negative regulator of miRNA biogenesis and suggest that Lin28 may play a central role in blocking miRNA-mediated differentiation in stem cells and in certain cancers. C1 [Viswanathan, Srinivas R.; Daley, George Q.; Gregory, Richard I.] Harvard Univ, Childrens Hosp Boston, Dept Biol Chem & Mol Pharmacol, Stem Cell Program,Sch Med,Harvard Stem Cell Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Pediat Hematol Oncol, Childrens Hosp Boston, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Howard Hughes Med Inst, Div Hematol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Harvard Univ, Childrens Hosp Boston, Dept Biol Chem & Mol Pharmacol, Stem Cell Program,Sch Med,Harvard Stem Cell Inst, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu; rgregory@enders.tch.harvard.edu FU Howard Hughes Medical Institute; NIDDK NIH HHS [DK70055]; NIH HHS [DP1 OD000256] NR 22 TC 848 Z9 885 U1 5 U2 57 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 4 PY 2008 VL 320 IS 5872 BP 97 EP 100 DI 10.1126/science.1154040 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 283JR UT WOS:000254633000039 PM 18292307 ER PT J AU Chin, L Gray, JW AF Chin, Lynda Gray, Joe W. TI Translating insights from the cancer genome into clinical practice SO NATURE LA English DT Review ID CELL LUNG-CANCER; BREAST-CANCER; SUSCEPTIBILITY GENE; TYROSINE KINASE; NEU ONCOGENE; BCR-ABL; TARGETED THERAPIES; PROSTATE-CANCER; OVARIAN-CANCER; RECEPTOR GENE AB Cancer cells have diverse biological capabilities that are conferred by numerous genetic aberrations and epigenetic modifications. Today's powerful technologies are enabling these changes to the genome to be catalogued in detail. Tomorrow is likely to bring a complete atlas of the reversible and irreversible alterations that occur in individual cancers. The challenge now is to work out which molecular abnormalities contribute to cancer and which are simply 'noise' at the genomic and epigenomic levels. Distinguishing between these will aid in understanding how the aberrations in a cancer cell collaborate to drive pathophysiology. Past successes in converting information from genomic discoveries into clinical tools provide valuable lessons to guide the translation of emerging insights from the genome into clinical end points that can affect the practice of cancer medicine. C1 [Chin, Lynda] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gray, Joe W.] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM lynda_chin@dfci.harvard.edu FU NCI NIH HHS [U54 CA112970, U54 CA112970-05] NR 93 TC 176 Z9 182 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 3 PY 2008 VL 452 IS 7187 BP 553 EP 563 DI 10.1038/nature06914 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282KR UT WOS:000254567200033 PM 18385729 ER PT J AU Weissleder, R Pittet, MJ AF Weissleder, Ralph Pittet, Mikael J. TI Imaging in the era of molecular oncology SO NATURE LA English DT Review ID CIRCULATING TUMOR-CELLS; REGULATORY T-CELLS; PROTEIN-PROTEIN INTERACTIONS; BREAST-CANCER METASTASIS; IN-VIVO; LIVING CELLS; LUNG-CANCER; CARCINOEMBRYONIC ANTIGEN; GENE-EXPRESSION; FLOW-CYTOMETRY AB New technologies for imaging molecules, particularly optical technologies, are increasingly being used to understand the complexity, diversity and in vivo behaviour of cancers. 'Omic' approaches are providing comprehensive 'snapshots' of biological indicators, or biomarkers, of cancer, but imaging can take this information a step further, showing the activity of these markers in vivo and how their location changes over time. Advances in experimental and clinical imaging are likely to improve how cancer is understood at a systems level and, ultimately, should enable doctors not only to locate tumours but also to assess the activity of the biological processes within these tumours and to provide 'on the spot' treatment. C1 [Weissleder, Ralph; Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NCI NIH HHS [P01 CA069246, P01 CA069246-070006, P50 CA086355, P50 CA086355-01, U24 CA092782, U24 CA092782-07] NR 100 TC 1154 Z9 1196 U1 48 U2 443 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 3 PY 2008 VL 452 IS 7187 BP 580 EP 589 DI 10.1038/nature06917 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282KR UT WOS:000254567200036 PM 18385732 ER PT J AU Thakur, JK Arthanari, H Yang, FJ Pan, SJ Fan, XC Breger, J Frueh, DP Gulshan, K Li, DK Mylonakis, E Struhl, K Moye-Rowley, WS Cormack, BP Wagner, G Naar, AM AF Thakur, Jitendra K. Arthanari, Haribabu Yang, Fajun Pan, Shih-Jung Fan, Xiaochun Breger, Julia Frueh, Dominique P. Gulshan, Kailash Li, Darrick K. Mylonakis, Eleftherios Struhl, Kevin Moye-Rowley, W. Scott Cormack, Brendan P. Wagner, Gerhard Naar, Anders M. TI A nuclear receptor-like pathway regulating multidrug resistance in fungi SO NATURE LA English DT Article ID TRANSCRIPTION-FACTOR-BINDING; SACCHAROMYCES-CEREVISIAE; DRUG-RESISTANCE; CANDIDA-GLABRATA; KIX DOMAIN; TRANSACTIVATION DOMAIN; COACTIVATOR COMPLEXES; CASSETTE TRANSPORTER; SECONDARY STRUCTURE; NMR-SPECTROSCOPY AB Multidrug resistance ( MDR) is a serious complication during treatment of opportunistic fungal infections that frequently afflict immunocompromised individuals, such as transplant recipients and cancer patients undergoing cytotoxic chemotherapy. Improved knowledge of the molecular pathways controlling MDR in pathogenic fungi should facilitate the development of novel therapies to combat these intransigent infections. MDR is often caused by upregulation of drug efflux pumps by members of the fungal zinc- cluster transcription- factor family ( for example Pdr1p orthologues). However, the molecular mechanisms are poorly understood. Here we show that Pdr1p family members in Saccharomyces cerevisiae and the human pathogen Candida glabrata directly bind to structurally diverse drugs and xenobiotics, resulting in stimulated expression of drug efflux pumps and induction of MDR. Notably, this is mechanistically similar to regulation of MDR in vertebrates by the PXR nuclear receptor, revealing an unexpected functional analogy of fungal and metazoan regulators of MDR. We have also uncovered a critical and specific role of the Gal11p/ MED15 subunit of the Mediator co- activator and its activator- targeted KIX domain in antifungal/ xenobiotic- dependent regulation of MDR. This detailed mechanistic understanding of a fungal nuclear receptor- like gene regulatory pathway provides novel therapeutic targets for the treatment of multidrug- resistant fungal infections. C1 [Thakur, Jitendra K.; Yang, Fajun; Li, Darrick K.; Naar, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Thakur, Jitendra K.; Yang, Fajun; Naar, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Arthanari, Haribabu; Fan, Xiaochun; Frueh, Dominique P.; Struhl, Kevin; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Pan, Shih-Jung; Cormack, Brendan P.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. [Breger, Julia; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Gulshan, Kailash; Moye-Rowley, W. Scott] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA. RP Naar, AM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM naar@helix.mgh.harvard.edu RI Frueh, Dominique/A-6462-2008; OI Frueh, Dominique/0000-0003-4605-3776; Moye-Rowley, Scott/0000-0002-7163-1120 FU NCI NIH HHS [CA127990, R01 CA127990]; NIBIB NIH HHS [EB2026]; NIGMS NIH HHS [GM30186, GM071449, GM47467, GM49825]; PHS HHS [A1046223] NR 60 TC 141 Z9 153 U1 1 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD APR 3 PY 2008 VL 452 IS 7187 BP 604 EP U4 DI 10.1038/nature06836 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282KR UT WOS:000254567200039 PM 18385733 ER PT J AU Nissen, SE Nicholls, SJ Wolski, K Rodes-Cabau, J Cannon, CP Deanfield, JE Despres, JP Kastelein, JJP Steinhubl, SR Kapadia, S Yasin, M Ruzyllo, W Gaudin, C Job, B Hu, B Bhatt, DL Lincoff, AM Tuzcu, EM AF Nissen, Steven E. Nicholls, Stephen J. Wolski, Kathy Rodes-Cabau, Josep Cannon, Christopher P. Deanfield, John E. Despres, Jean-Pierre Kastelein, John J. P. Steinhubl, Steven R. Kapadia, Samir Yasin, Muhammad Ruzyllo, Witold Gaudin, Christophe Job, Bernard Hu, Bo Bhatt, Deepak L. Lincoff, A. Michael Tuzcu, E. Murat CA STRADIVARIUS Investigators TI Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease - The STRADIVARIUS randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 57th Annual Scientific Session of the American-College-of-Cardiology CY MAR 29-APR 01, 2008 CL Chicago, IL SP Amer Coll Cardiol ID CANNABINOID-1 RECEPTOR BLOCKER; INTRAVASCULAR ULTRASOUND; CARDIOVASCULAR-DISEASE; RISK-FACTORS; OVERWEIGHT PATIENTS; STATIN THERAPY; HEART-DISEASE; UNITED-STATES; WEIGHT; PARTICIPANTS AB Context Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow progression of coronary disease. Objective To determine whether weight loss and metabolic effects of the selective cannabinoid type 1 receptor antagonist rimonabant reduces progression of coronary disease in patients with abdominal obesity and the metabolic syndrome. Design, Setting, and Patients Randomized, double- blinded, placebo- controlled, 2- group, parallel- group trial ( enrollment December 2004- December 2005) comparing rimonabant with placebo in 839 patients at 112 centers in North America, Europe, and Australia. Interventions Patients received dietary counseling, were randomized to receive rimonabant ( 20 mg daily) or matching placebo, and underwent coronary intravascular ultrasonography at baseline ( n= 839) and study completion ( n= 676). Main Outcome Measures The primary efficacy parameter was change in percent atheroma volume ( PAV); the secondary efficacy parameter was change in normalized total atheroma volume ( TAV). Results In the rimonabant vs placebo groups, PAV ( 95% confidence interval [ CI]) increased 0.25% (- 0.04% to 0.54%) vs 0.51% ( 0.22% to 0.80%) ( P=. 22), respectively, and TAV decreased 2.2 mm(3) (- 4.09 to - 0.24) vs an increase of 0.88 mm(3) (- 1.03 to 2.79) ( P=. 03). In the rimonabant vs placebo groups, imputingresultsbasedonbaselinecharacteristics for patients not completing the trial, PAV increased 0.25% (- 0.04% to 0.55%) vs 0.57% ( 0.29% to 0.84%) ( P=. 13), and TAV decreased 1.95 mm(3) (- 3.8 to - 0.10) vs an increase of 1.19 mm(3) (- 0.73 to 3.12) ( P=. 02). Rimonabant- treated patients had a larger reduction in body weight ( 4.3 kg [- 5.1 to - 3.5] vs 0.5 kg [- 1.3 to 0.3]) and greater decrease in waist circumference ( 4.5 cm [- 5.4 to - 3.7] vs 1.0 cm [- 1.9 to - 0.2]) ( P <. 001 for both comparisons). In the rimonabant vs placebo groups, high- density lipoprotein cholesterol levels increased 5.8 mg/dL( 4.9 to 6.8) ( 22.4%) vs 1.8 mg/ dL( 0.9 to 2.7) ( 6.9%) ( P <. 001), and median triglyceride levels decreased 24.8mg/ dL(- 35.4 to - 17.3) ( 20.5%) vs 8.9 mg/ dL (- 14.2 to - 1.8) ( 6.2%) ( P <. 001). Rimonabant- treated patients had greater decreases in high- sensitivity C- reactive protein ( 1.3 mg/ dL[- 1.7 to - 1.2] [ 50.3%] vs 0.9 mg/ dL[- 1.4 to - 0.5][ 30.9%]) and less increase in glycated hemoglobin levels( 0.11%[ 0.02% to 0.20%] vs 0.40% [ 0.31% to 0.49%]) ( P <. 001 for both comparisons). Psychiatric adverse effects were more common in the rimonabant group ( 43.4% vs 28.4%, P <. 001). Conclusions After 18 months of treatment, the study failed to show an effect for rimonabant on disease progression for the primary end point ( PAV) but showed a favorable effect on the secondary end point ( TAV). Determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials, which are currently under way. Trial Registration clinicaltrials. gov Identifier: NCT00124332. C1 [Nissen, Steven E.; Nicholls, Stephen J.; Wolski, Kathy; Kapadia, Samir; Bhatt, Deepak L.; Lincoff, A. Michael; Tuzcu, E. Murat] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Nissen, Steven E.; Nicholls, Stephen J.; Wolski, Kathy; Kapadia, Samir; Bhatt, Deepak L.; Lincoff, A. Michael; Tuzcu, E. Murat] Cleveland Clin, Lerner Sch Med, Cleveland, OH 44106 USA. [Hu, Bo] Cleveland Clin, Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Rodes-Cabau, Josep; Despres, Jean-Pierre] Laval Hosp, Quebec City, PQ, Canada. [Rodes-Cabau, Josep; Despres, Jean-Pierre] Quebec Heart Inst, Quebec City, PQ, Canada. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Deanfield, John E.] UCL, London, England. [Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Steinhubl, Steven R.] Univ Kentucky, Lexington, KY USA. [Yasin, Muhammad] SW Cardiol, Oklahoma City, OK USA. [Ruzyllo, Witold] Inst Kardiol Klin Warsaw 1, Warsaw, Poland. [Gaudin, Christophe; Job, Bernard] Sanofi Aventis, Paris, France. RP Nissen, SE (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM nissens@ccf.org RI Deanfield, John/C-5178-2008; Marroquin, Oscar/F-2214-2015; Colquhoun, David/F-9078-2013 OI Marroquin, Oscar/0000-0002-0909-0319; NR 39 TC 250 Z9 255 U1 3 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 2 PY 2008 VL 299 IS 13 BP 1547 EP 1560 DI 10.1001/jama.299.13.1547 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 281RZ UT WOS:000254517900022 PM 18387931 ER PT J AU Rumsfeld, JS Nallamothu, BK AF Rumsfeld, John S. Nallamothu, Brahmajee K. TI The hope and fear of Rimonabant SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; CORONARY ATHEROSCLEROSIS; RISK-FACTORS; OVERWEIGHT; OBESITY; PROGRESSION; DISEASE; WEIGHT C1 [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Sect Cardiol 111B, Denver, CO 80220 USA. [Rumsfeld, John S.] Univ Colorado Denver, Dept Med, Aurora, CO USA. [Nallamothu, Brahmajee K.] Ann Arbor Vet Affairs Med Ctr, Cardiol Sect, Ann Arbor, MI USA. [Nallamothu, Brahmajee K.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP Rumsfeld, JS (reprint author), Denver Vet Affairs Med Ctr, Sect Cardiol 111B, 1055 Clermont St, Denver, CO 80220 USA. EM john.rumsfeld@va.gov NR 14 TC 18 Z9 19 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 2 PY 2008 VL 299 IS 13 BP 1601 EP 1602 DI 10.1001/jama.299.13.1601 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 281RZ UT WOS:000254517900028 PM 18387935 ER PT J AU Shim, SY Wang, J Asada, N Neumayer, G Tran, HC Ishiguro, K Sanada, K Nakatani, Y Nguyen, MD AF Shim, Su Yeon Wang, Jian Asada, Naoyuki Neumayer, Gernot Tran, Hong Chi Ishiguro, Kei-ichiro Sanada, Kamon Nakatani, Yoshihiro Nguyen, Minh Dang TI Protein 600 is a microtubule/endoplasmic reticulum-associated protein in CNS neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cytoarchitecture; cytoskeleton; development; differentiation; migration; neurite ID EARLY EMBRYONIC LETHALITY; DOUBLECORTIN-LIKE-KINASE; ENDOPLASMIC-RETICULUM; MIGRATION DEFECTS; MICROTUBULES; DYNAMICS; PHOSPHORYLATION; P600; TRANSPORT; OUTGROWTH AB There is an increasing body of literature pointing to cytoskeletal proteins as spatial organizers and interactors of organelles. In this study, we identified protein 600 ( p600) as a novel microtubule- associated protein ( MAP) developmentally regulated in neurons. p600 exhibits the unique feature to interact with the endoplasmic reticulum ( ER). Silencing of p600 by RNA interference ( RNAi) destabilizes neuronal processes in young primary neurons undergoing neurite extension and containing scarce staining of the ER marker Bip. Furthermore, in utero electroporation of p600 RNAi alters neuronal migration, a process that depends on synergistic actions of microtubule dynamics and ER functions. p600- depleted migrating neurons display thin, crooked, and "zigzag" leading process with very few ER membranes. Thus, p600 constitutes the only known MAP to associate with the ER in neurons, and this interaction may impact on multiple cellular processes ranging from neuronal development to neuronal maturation and plasticity. C1 [Shim, Su Yeon; Wang, Jian; Neumayer, Gernot; Tran, Hong Chi; Nguyen, Minh Dang] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB T2N 4N1, Canada. [Shim, Su Yeon; Wang, Jian; Neumayer, Gernot; Tran, Hong Chi; Nguyen, Minh Dang] Univ Calgary, Hotchkiss Brain Inst, Dept Cell Biol & Anat, Calgary, AB T2N 4N1, Canada. [Shim, Su Yeon; Wang, Jian; Neumayer, Gernot; Tran, Hong Chi; Nguyen, Minh Dang] Univ Calgary, Hotchkiss Brain Inst, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. [Ishiguro, Kei-ichiro; Nakatani, Yoshihiro] Dana Farber Canc Inst, Boston, MA 02115 USA. [Asada, Naoyuki; Sanada, Kamon] Osaka Univ, Grad Sch Med, Japan Sci & Technol Agcy, Suita, Osaka 5650871, Japan. [Asada, Naoyuki; Sanada, Kamon] Osaka Univ, Grad Sch Med, Dept Dev Neurosci, Suita, Osaka 5650871, Japan. RP Nguyen, MD (reprint author), Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, 3330 Hosp Dr NW,Heritage Med Res Bldg,Room 151, Calgary, AB T2N 4N1, Canada. EM mdnguyen@ucalgary.ca RI SANADA, YOSHIKADO/G-5014-2014 NR 42 TC 29 Z9 29 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 2 PY 2008 VL 28 IS 14 BP 3604 EP 3614 DI 10.1523/JNEUROSCI.5278-07.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 283GA UT WOS:000254623500010 PM 18385319 ER PT J AU LoPresti, ML Schon, K Tricarico, MD Swisher, JD Celone, KA Stern, CE AF LoPresti, Matthew L. Schon, Karin Tricarico, Marisa D. Swisher, Jascha D. Celone, Kim A. Stern, Chantal E. TI Working memory for social cues recruits orbitofrontal cortex and amygdala: A functional magnetic resonance imaging study of delayed matching to sample for emotional expressions SO JOURNAL OF NEUROSCIENCE LA English DT Article DE social cognition; prefrontal cortex; hippocampus; parahippocampal cortex; active maintenance; faces ID EVENT-RELATED FMRI; PRIMATE PREFRONTAL CORTEX; DISTRIBUTED NEURAL SYSTEM; FUSIFORM FACE AREA; LONG-TERM-MEMORY; FACIAL EXPRESSIONS; RHESUS-MONKEY; TEMPORAL-LOBE; PARAHIPPOCAMPAL REGION; HIPPOCAMPAL-FORMATION AB During everyday interactions, we continuously monitor and maintain information about different individuals and their changing emotions in memory. Yet to date, working memory ( WM) studies have primarily focused on mechanisms for maintaining face identity, but not emotional expression, and studies investigating the neural basis of emotion have focused on transient activity, not delay related activity. The goal of this functional magnetic resonance imaging study was to investigate WM for two critical social cues: identity and emotion. Subjects performed a delayed match- to- sample task that required them to match either the emotional expression or the identity of a face after a 10 s delay. Neuroanatomically, our predictions focused on the orbitofrontal cortex ( OFC) and the amygdala, as these regions have previously been implicated in emotional processing and long- term memory, and studies have demonstrated sustained OFC and medial temporal lobe activity during visual WM. Consistent with previous studies, transient activity during the sample period representing emotion and identity was found in the superior temporal sulcus and inferior occipital cortex, respectively. Sustained delay- period activity was evident in OFC, amygdala, and hippocampus, for both emotion and identity trials. These results suggest that, although initial processing of emotion and identity is accomplished in anatomically segregated temporal and occipital regions, sustained delay related memory for these two critical features is held by the OFC, amygdala and hippocampus. These regions share rich connections, and have been shown previously to be necessary for binding features together in long- term memory. Our results suggest a role for these regions in active maintenance as well. C1 [LoPresti, Matthew L.; Schon, Karin; Tricarico, Marisa D.; Celone, Kim A.; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [LoPresti, Matthew L.; Swisher, Jascha D.; Stern, Chantal E.] Boston Univ, Program Neurosci, Boston, MA 02215 USA. [Schon, Karin; Celone, Kim A.; Stern, Chantal E.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Stern, Chantal E.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Stern, Chantal E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP LoPresti, ML (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St, Boston, MA 02215 USA. EM mattlo@bu.edu OI Schon, Karin/0000-0003-2963-8449 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIMH NIH HHS [P50 MH071702-020001, P50 MH071702-01A2, P50 MH071702, P50 MH071702-01A20001, P50 MH071702-02] NR 86 TC 37 Z9 38 U1 5 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 2 PY 2008 VL 28 IS 14 BP 3718 EP 3728 DI 10.1523/JNEUROSCI.0464-08.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 283GA UT WOS:000254623500021 PM 18385330 ER PT J AU Shelton, RC Papakostas, GI AF Shelton, Richard C. Papakostas, George I. TI Augmentation of antidepressants with atypical antipsychotics for treatment-resistant major depressive disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE major depressive disorder; antidepressants; atypical antipsychotics; treatment resistant; augmentation ID SEROTONIN REUPTAKE INHIBITORS; STAR-ASTERISK-D; VENTRAL TEGMENTAL AREA; DOUBLE-BLIND; OLANZAPINE/FLUOXETINE COMBINATION; ARIPIPRAZOLE AUGMENTATION; RISPERIDONE AUGMENTATION; DOPAMINERGIC-NEURONS; OPEN-LABEL; OLANZAPINE AB Objective: Atypical antipsychotics (AAPs) have been hypothesized to be beneficial in treatment-resistant depression (TRD). This paper will review a biochemical rationale and will summarize the data regarding the effectiveness of AAPs in TRD. Method: Studies were identified using searches of Pubmed/Medline, EMBase and the Cochrane databases by cross-referencing the term 'depression' with each of the six AAPs. Results: After initial positive, short case reports and clinical trials, larger studies failed to show the effectiveness of AAPs combined with antidepressants for TRD. More recently, larger scale clinical trials have supported the effectiveness of at least some of these medications. While AAPs have gained in popularity for TRD, there are nagging concerns regarding risks such as metabolic syndrome and tardive dyskinesia. Conclusion: The existing research provides some support for the beneficial effects of AAPs when combined with SSRI's in TRD. These medications pose significant risks that must be considered in their use. C1 [Shelton, Richard C.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Shelton, RC (reprint author), 1500 21st Ave S,Suite 2200, Nashville, TN 37212 USA. EM richard.shelton@vanderbilt.edu RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629, K24 MH01741] NR 49 TC 60 Z9 61 U1 3 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 2008 VL 117 IS 4 BP 253 EP 259 DI 10.1111/j.1600-0447.2007.01130.x PG 7 WC Psychiatry SC Psychiatry GA 270YV UT WOS:000253757000003 PM 18190674 ER PT J AU Iosifescu, DV Greenwald, S Devlin, P Perlis, RH Denninger, JW Alpert, JE Fava, M AF Iosifescu, D. V. Greenwald, S. Devlin, P. Perlis, R. H. Denninger, J. W. Alpert, J. E. Fava, M. TI Pretreatment frontal EEG and changes in suicidal ideation during SSRI treatment in major depressive disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE major depressive disorder; quantitative electroencephalography; suicidal ideation; selective serotonin reuptake inhibitors ID ALPHA ASYMMETRY; RISK; ANTIDEPRESSANT; PLACEBO; ANXIETY; CONUNDRUMS; RESPONDERS; EMOTION; TRIALS AB Objective: We investigated frontal quantitative EEG (QEEG) as predictor of changes in suicidal ideation (SI) during SSRI treatment in major depressive disorder (MDD). Method: Eighty-two subjects meeting DSM-IV criteria for MDD entered an 8-week, prospective, open-label treatment with flexible dose SSRIs and completed at least 4 weeks of treatment. We assessed MDD severity with the 17-item Hamilton Depression Rating Scale (HAM-D-17); change in SI was measured with HAM-D item no. 3. We recorded four-channel EEGs (F7-Fpz, F8-Fpz, A1-Fpz, A2-Fpz) before treatment. Results: During the first 4 weeks of treatment 9 (11%) subjects experienced worsening SI. Left-right asymmetry of combined theta + alpha power correlated significantly with change in SI from baseline, even when adjusting for changes in depression severity (HAM-D-17) and for the SSRI utilized. Conclusion: Frontal QEEG parameters before treatment may predict worsening SI during SSRI treatment in MDD. C1 [Iosifescu, D. V.; Perlis, R. H.; Denninger, J. W.; Alpert, J. E.; Fava, M.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Iosifescu, D. V.; Perlis, R. H.; Denninger, J. W.; Alpert, J. E.; Fava, M.] Harvard Univ, Sch Med, Boston, MA USA. [Greenwald, S.; Devlin, P.] Aspect Med Syst Inc, Norwood, MA USA. RP Iosifescu, DV (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org OI Alpert, Jonathan/0000-0002-4332-908X NR 31 TC 10 Z9 12 U1 7 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 2008 VL 117 IS 4 BP 271 EP 276 DI 10.1111/j.1600-0447.2008.01156.x PG 6 WC Psychiatry SC Psychiatry GA 270YV UT WOS:000253757000005 PM 18307587 ER PT J AU Ingelfinger, JR AF Ingelfinger, Julie R. TI Disparities in renal endowment: Causes and consequences SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE nephrogenesis; hyperfiltration; renal endowment ID INTRAUTERINE GROWTH-RETARDATION; CHRONIC KIDNEY-DISEASE; GLOMERULAR NUMBER; BIRTH-WEIGHT; BLOOD-PRESSURE; ADULT HYPERTENSION; NEPHRON NUMBER; AUSTRALIAN ABORIGINES; PROTEIN RESTRICTION; INCREASED APOPTOSIS AB In humans, nephrogenesis is completed by 36 weeks of gestation. Thus, human kidney development is complete at the time of birth in full-term infants. Those infants born before 36 weeks of gestation are still undergoing nephrogenesis for several weeks after their preterm birth and, accordingly, may be exposed to medications that impact the kidney during its final stages of renal development. The ultimate nephron number (nephron endowment) may influence future response to kidney injury, should it occur. The concept that nephron number may strongly influence blood pressure as well as susceptibility to kidney disease in later life developed in parallel with that of perinatal programming, which holds that the perinatal milieu causes changes that permanently alter organ structure and function, preordaining adult physiology to some extent. Both concepts together may help elucidate, at least in part, the pathogenesis of not only primary but secondary hypertension. This article summarizes human data on nephron number and its evaluation and considers the circumstances, implication, and management of persons born with or acquiring a decreased complement of nephrons early in life. Insufficient data exist to predict outcome or guide management. However, a common-sense approach of avoiding nephrotoxins and minimizing renal stress is indicated. (c) 2008 by the National Kidney Foundation, Inc. C1 [Ingelfinger, Julie R.] Massachusetts Gen Hosp, MassGen Hosp Children, Pediat Nephrol Unit, Boston, MA 02114 USA. [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ingelfinger, JR (reprint author), Pediat Nephrol Yawkey 6C,55 Fruit St, Boston, MA 02114 USA. EM jingelfinger@nejm.org NR 76 TC 18 Z9 19 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 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD APR PY 2008 VL 15 IS 2 BP 107 EP 114 DI 10.1053/j.ackd.2008.01.003 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 280HO UT WOS:000254416800004 PM 18334234 ER PT J AU Vranceanu, AM Safren, SA Lu, M Coady, WM Skolnik, PR Rogers, WH Wilson, IB AF Vranceanu, Ana Maria Safren, Steven A. Lu, Minyi Coady, William M. Skolnik, Paul R. Rogers, William H. Wilson, Ira B. TI The relationship of post-traumatic stress disorder and depression to antiretroviral medication adherence in persons with HIV SO AIDS PATIENT CARE AND STDS LA English DT Article ID OUTPATIENT CLINICS; INFECTED WOMEN; PRIMARY-CARE; THERAPY; IMPACT; POPULATION; STRATEGIES; SYMPTOMS; HIV/AIDS; BARRIERS AB In HIV/AIDS, symptoms of depression or post-traumatic stress may interfere with important self-care behaviors such as the ability to adhere to one's medical treatment regimen. However, these problems may frequently go undetected in HIV care settings. The present study used brief self-report screening measures of depression and post-traumatic stress disorder (PTSD) in the HIV/AIDS care settings to examine (1) frequency of positive screens for these diagnoses; (2) the degree to which those with a positive screen were prescribed antidepressant treatment; and (3) the association of continuous PTSD and depression symptom scores, and categorical (screening positive or negative) PTSD and depression screening status, to each other and to ART adherence as assessed by the Medication Event Monitoring System, regardless of antidepressant treatment. Participants were 164 HIV-infected individuals who took part in a multisite adherence intervention study in HIV treatment settings in Massachusetts. Available data from 5 time points was used, yielding 444 data points. Participants screened positive for PTSD at 20% of visits, and depression at 22% of visits. At visits when participants screened positive for both depression and PTSD, 53.6% of the time they were on an antidepressant. Those who screened positive for PTSD were more likely to also screen positive for depression. In multiple regression analyses that included both continuous and dichotomous PTSD and depression and controlled for shared variance due to clustering of multiple observations, only depression contributed significant unique variance, suggesting the primary role of depression and the secondary role of PTSD in poor adherence in individuals with HIV. C1 [Vranceanu, Ana Maria; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychol, Boston, MA USA. [Vranceanu, Ana Maria; Safren, Steven A.] Fenway Community Hlth Ctr, Boston, MA USA. [Lu, Minyi; Coady, William M.; Rogers, William H.; Wilson, Ira B.] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA. [Lu, Minyi; Coady, William M.; Rogers, William H.; Wilson, Ira B.] Tufts Univ New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Skolnik, Paul R.] Boston Univ, Med Ctr, Ctr HIV AIDS Care & Res, Boston, MA USA. RP Wilson, IB (reprint author), Tufts New England Med Ctr 345, 750 Washington St, Boston, MA 02111 USA. EM iwilson@tufts-nemc.org RI Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X FU NCRR NIH HHS [K24 RR020300]; NIAID NIH HHS [5P30AI042853]; NIDA NIH HHS [5R01DA015679] NR 31 TC 52 Z9 52 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD APR PY 2008 VL 22 IS 4 BP 313 EP 321 DI 10.1089/apc.2007.0069 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 296AG UT WOS:000255515300006 PM 18338960 ER PT J AU Diem, K Nickle, DC Motoshige, A Fox, A Ross, S Mullins, JI Corey, L Coombs, RW Krieger, JN AF Diem, Kurt Nickle, David C. Motoshige, Alexis Fox, Alan Ross, Susan Mullins, James I. Corey, Lawrence Coombs, Robert W. Krieger, John N. TI Male genital tract compartmentalization of human immunodeficiency virus type 1 (HIV) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article; Proceedings Paper CT 44th Interscience Conference on Antimicrobial Agents and Chemotherapy CY OCT 30-NOV 02, 2004 CL Washington, DC ID N-LINKED GLYCOSYLATION; V3 LOOP; BLOOD; SEMEN; INFECTION; CELLS; RESERVOIRS; ENV AB We present phylogenetic evidence supporting viral compartmentalization between the blood ( peripheral blood mononuclear cells or plasma) and multiple genitourinary sites in HIV-infected men. Four of the five subjects evaluated demonstrated compartmentalization of viral sequences between urogenital tract specimens ( tissue or fluid) and at least one blood category. HIV sequence migration from blood to urogenital tract was detected in four of five men, with migration from urogenital tract to blood in the fifth, and cross migration between both compartments noted in one man. These observations add 5 additional cases to the 27 total reported cases in which male urogenital tract compartmentalization has been studied, investigate surgical samples/specimens that have not been evaluated previously, and provide further evidence for restricted flow of HIV between the blood and the genital tract. As such, our study findings are important for understanding the long-term response to antiretroviral therapy, the design of vaccines, and the sexual transmission of HIV. C1 [Ross, Susan; Krieger, John N.] Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Diem, Kurt; Motoshige, Alexis; Fox, Alan; Corey, Lawrence; Coombs, Robert W.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Nickle, David C.; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Krieger, JN (reprint author), Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Box 358280,Room 6B-127,GU-112, Seattle, WA 98195 USA. EM jkrieger@u.washington.edu FU NIAID NIH HHS [AI-27664, AI-27757, AI-38858, AI-57005]; NICHD NIH HHS [HD-40540]; NIDDK NIH HHS [DK-49477] NR 25 TC 36 Z9 36 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2008 VL 24 IS 4 BP 561 EP 571 DI 10.1089/aid.2007.0115 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 294GV UT WOS:000255394900006 PM 18426336 ER PT J AU Mak, KM Ren, CL Ponomarenko, A Cao, Q Lieber, CS AF Mak, Ki M. Ren, Chaoling Ponomarenko, Anatoly Cao, Qi Lieber, Charles S. TI Adipose differentiation-related protein is a reliable lipid droplet marker in alcoholic fatty liver of rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE adipose differentiation-related protein; immunohistochemistry; lipid droplet marker; alcoholic fatty liver; medium-chain triglycerides ID MEDIUM-CHAIN TRIGLYCERIDES; DIMINISHED DEPOSITION; ACCUMULATION; ADIPOPHILIN; HEPATOCYTES; METABOLISM; STORAGE; LONG; DIET AB Background: Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that coats cytoplasmic lipid droplets. The present study evaluated whether alcohol feeding enhances ADRP expression and whether ADRP is a lipid droplet marker in alcoholic fatty liver of rats. Because medium-chain triglycerides (MCT) reduce alcoholic hepatosteatosis, their effects on ADRP were also evaluated. Methods: Fatty liver was induced in rats by the consumption of the Lieber-DeCarli alcohol liquid diet with or without replacement of long-chain triglycerides (LCT) by MCT (32% of calories). Immunohistochemical staining for ADRP was performed in formalin-fixed, paraffin-embedded liver sections. ADRP immunostaining was quantified by image analysis. Triacylglycerol was measured chemically. ADRP mRNA and protein were analyzed by real-time polymerase chain reaction and western blot, respectively. Double staining technique was performed to distinguish ADRP from glycogen in hepatocytes. Results: Alcohol feeding for 21 days increased ADRP staining in the centrilobular and mid zonal regions of the liver lobules coincident with fat deposition in the liver. Replacing LCT in the alcohol diet with MCT diminished ADRP immunostaining in parallel with reduced steatosis. MCT also attenuated the up-regulation of ADRP mRNA and protein after alcohol. In steatotic hepatocytes ADRP selectively stained the surface of macrovesicular and microvesicular lipid droplets. ADRP immunostaining quantitatively correlated with hepatic triacylglycerol levels, validating ADRP as a reliable lipid droplet marker. Compared with hematoxylin and eosin stains, ADRP was more sensitive in detecting microvesicular lipid droplets. ADRP immunostaining also distinguished lipid droplets from glycogen, as demonstrated by double staining for ADRP and glycogen. Conclusions: Alcohol induction of fatty liver enhances ADRP expression and MCT oppose the alcohol effects. ADRP is a reliable and sensitive marker for lipid droplets in alcoholic fatty liver. ADRP immunostaining permits quantification of fatty change in hepatocytes and can be used as an ancillary technique in assessing the efficacy of diets or drugs against hepatosteatosis. C1 [Ponomarenko, Anatoly; Lieber, Charles S.] James J VA Med Ctr, Bronx, NY 10468 USA. [Mak, Ki M.; Ren, Chaoling; Cao, Qi; Lieber, Charles S.] Mt Sinai Sch Med, New York, NY USA. RP Lieber, CS (reprint author), James J VA Med Ctr, 130 W Kingsbridge Rd 151-2, Bronx, NY 10468 USA. EM liebercs@aol.com FU NIAAA NIH HHS [R01 AA012867] NR 24 TC 26 Z9 29 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2008 VL 32 IS 4 BP 683 EP 689 DI 10.1111/j.1530-0277.2008.00624.x PG 7 WC Substance Abuse SC Substance Abuse GA 278FV UT WOS:000254271200015 PM 18341646 ER PT J AU Rinaldi, MJ Kirtane, AJ Piana, RN Caputo, RP Gordon, PC Lopez, JJ Dauerman, HL Ryan, TJ Kiernan, FJ Cutlip, DE Ho, KKL Gibson, CM Murphy, SA Cohen, DJ AF Rinaldi, Michael J. Kirtane, Ajay J. Piana, Robert N. Caputo, Ronald P. Gordon, Paul C. Lopez, John J. Dauerman, Harold L. Ryan, Thomas J., Jr. Kiernan, Francis J. Cutlip, Donald E. Ho, Kalon K. L. Gibson, C. Michael Murphy, Sabina A. Cohen, David J. TI Clinical, procedural, and pharmacologic correlates of acute and subacute stent thrombosis: Results of a multicenter case-control study with 145 thrombosis events SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY STENTS; ELUTING STENTS; BARE-METAL; CLOPIDOGREL; IMPLANTATION; TICLOPIDINE; PREDICTORS; ANTIPLATELET; PLACEMENT; SIROLIMUS AB Objectives The aim of this study was to determine correlates of acute/subacute coronary stent thrombosis among unselected patients treated in the era of routine dual antiplatelet therapy and specifically to investigate the influence of prophylactic administration of glycoprotein IIb/IIIa (GpIIb-IIIa) inhibitors and use of clopidogrel versus ticlopidine on the development of coronary stent thrombosis (ST). Background Because of a relative infrequency of ST events and relatively uniform practice patterns within randomized trials, previous studies have had a limited ability to address whether the use of different antiplatelet regimens at the time of coronary stenting is associated with differences in ST. Methods We performed a multicenter, case-control study to evaluate clinical, angiographic, and pharmacologic/ procedural correlates of ST. Between 1996 and 2000, all cases of angiographically-confirmed ST (n = 145) among patients receiving dual antiplatelet therapy were identified from 10 participating clinical sites and were matched with a control without ST randomly selected from the same institution. Results Multivariable conditional logistic regression identified higher pre-procedure platelet count, stenting for acute myocardial infarction, use of a coil or self-expanding stent, and overt angiographic thrombus prior to the procedure, as independent predictors of ST (all P <.05). After adjusting for these factors, the use of clopidogrel (vs ticlopidine) was independently associated with an increased risk of ST (OR 2.1, 95% CI 1.0-4. 1, P=.04). The use of prophylactic glycoprotein IIb/IIIa inhibitors was not associated with reduced ST in the overall analysis, but appeared to confer some protection against ST within the first 24 hours post procedure (OR 0.5 [95% CI 0.2-1.1] for ST during first day, OR 1.7 [95% CI 0.7-4.3] for ST on subsequent days). Conclusion Both biologic and pharmacologic factors are independently associated with acute/subacute ST. The association between clopidogrel use (vs ticlopidine) and increased ST in this analysis requires confirmation in adequately powered clinical trials and suggests a potential role for newer and more potent antiplatelet agents. C1 [Cohen, David J.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Rinaldi, Michael J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kirtane, Ajay J.; Cutlip, Donald E.; Ho, Kalon K. L.; Gibson, C. Michael; Cohen, David J.] Sanger Clin PA, Charlotte, NC USA. [Piana, Robert N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Caputo, Ronald P.] St Josephs Hosp, Syracuse, NY USA. [Gordon, Paul C.] Miriam Hosp, Providence, RI 02906 USA. [Lopez, John J.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Dauerman, Harold L.] Univ Vermont, Coll Med, Burlington, VT USA. [Ryan, Thomas J., Jr.] Maine Med Ctr, Portland, ME 04102 USA. [Kiernan, Francis J.] Hartford Hosp, Hartford, CT 06115 USA. [Cutlip, Donald E.; Ho, Kalon K. L.; Cohen, David J.] Harvard Clin Res Inst, Boston, MA USA. [Gibson, C. Michael; Murphy, Sabina A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Cohen, DJ (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 4401 Wornali Rd, Kansas City, MO 64111 USA. EM dcohen@saint-lukes.org OI Lopez, John/0000-0002-6727-3623 NR 22 TC 19 Z9 22 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2008 VL 155 IS 4 BP 654 EP 660 DI 10.1016/j.ahj.2007.11.028 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 285WY UT WOS:000254808100010 PM 18371472 ER PT J AU Takasu, J Katz, R Nasir, K Carr, JJ Wong, N Detrano, R Budoff, MJ AF Takasu, Junichiro Katz, Ronit Nasir, Khurram Carr, J. Jeffrey Wong, Nathan Detrano, Robert Budoff, Matthew J. TI Relationships of thoracic aortic wall calcification to cardiovascular risk factors: The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; OSTEOPONTIN MESSENGER-RNA; COMPUTED-TOMOGRAPHY; PLAQUES; ASSOCIATION; EXPRESSION; CT; OSTEOPOROSIS; PREDICTOR; COMMITTEE AB Background The aim of this article is to determine the relationships between aortic wall calcification (AWC) including ascending and descending thoracic aortic calcification and sex, race/ethnicity, age, and traditional risk factors. Allison et al (Arterioscier Thromb Vasc Biol. 2004;24:331-336) previously described the relationship of noted risk factors and AWC as detected by computed tomography (CT) in smaller cohorts. We performed a cross-sectional study to determine which of these variables are independently associated with thoracic calcium. Methods The MESA population included a population-based sample of 4 ethnic groups (12 % Chinese, 38% white, 22 % Hispanic, and 28% black) of 6814 women and men aged 45 to 84 years. Computed tomographic scans were performed for all participants. We quantified AWC, which ranged from the lower edge of the pulmonary artery bifurcation to the cardiac apex. Multivariable logistic regression was used to evaluate relationships between AWC and measured cardiovascular risk factors. Resuits Overall prevalence of AWC was 28.0%. In the ethnic groups, prevalence of AWC was 32.4% Chinese, 32.4 % white, 24.9% Hispanic, and 22.4 % black. All age categories of females had a higher prevalence of thoracic calcification than males (total age prevalence 29.1 % and 26.8 %, respectively). Aortic wall calcifications were most strongly associated with hypertension and current smoking. In addition, diabetes, hypercholesterolemia, high level of low-density lipoprotein, low level of high-density lipoprotein, family history of myocardial infarction, and high C-reactive protein were all associated with increased AWC. Overall P value for difference between sexes for prevalence of AWC is 0.037. Overall P value for difference between race for prevalence of AWC is <.001. The only significant sex differences distributed by race were for Chinese (P =.035) and Hispanic (P =.042) participants. Conclusions Risk factors for aortic calcification were similar to cardiovascular risk factors in a large population-based cohort. Surprisingly, AWC was similar for the Chinese and white populations despite the fact that MESA demonstrated that coronary calcium was more prevalent in the white population. Further studies are needed to investigate whether aortic calcification is a risk factor for coronary disease, independent of coronary calcification. C1 [Takasu, Junichiro; Budoff, Matthew J.] Harbor UCLA Med Ctr, Div Cardiol, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Katz, Ronit] Univ Washington, Seattle, WA 98195 USA. [Nasir, Khurram] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Carr, J. Jeffrey] Wake Forest Sch Med, Dept Radiol, Winston Salem, NC USA. [Wong, Nathan; Detrano, Robert] Univ Calif Irvine, Irvine, CA 92717 USA. RP Budoff, MJ (reprint author), Harbor UCLA Med Ctr, Div Cardiol, Los Angeles Biomed Res Inst, 1124 W Carson St,RB2, Torrance, CA 90502 USA. EM budoff@ucla.edu RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 FU NHLBI NIH HHS [N01-HC-95164, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95165, N01-HC-95169, N01HC95159, N01HC95165, N01HC95169, R01 HL063963, R01 HL071739, R01 HL071739-01, R01 HL071739-02, R01 HL071739-03, R01 HL071739-04, R01-HL-071739] NR 32 TC 47 Z9 47 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2008 VL 155 IS 4 BP 765 EP 771 DI 10.1016/j.ahj.2007.11.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 285WY UT WOS:000254808100029 PM 18371491 ER PT J AU Ho, PM Magid, DJ Shetterly, SM Olson, KL Maddox, TM Peterson, PN Masoudi, FA Rumsfeld, JS AF Ho, P. Michael Magid, David J. Shetterly, Susan M. Olson, Kari L. Maddox, Thomas M. Peterson, Pamela N. Masoudi, Frederick A. Rumsfeld, John S. TI Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease SO AMERICAN HEART JOURNAL LA English DT Article ID CONVERTING ENZYME-INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; HEALTH MAINTENANCE ORGANIZATION; RANDOMIZED CONTROLLED-TRIAL; BETA-BLOCKERS; SECONDARY PREVENTION; ELDERLY PATIENTS; STATIN THERAPY; BLOOD-PRESSURE; DRUG-THERAPY AB Background Little is known about the effect of nonadherence among patients with coronary artery disease (CAD) on a broad spectrum of outcomes including cardiovascular mortality, cardiovascular hospitalizations, and revascularization procedures. Methods This was a retrospective cohort study of 15767 patients with CAD. Medication adherence was calculated as proportion of days covered for filled prescriptions of)beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statin medications. Multivariable Cox regression assessed the association between medication nonadherence as a time-varying covariate and a broad range of outcomes, adjusting for demographics and clinical characteristics. Median follow-up was 4.1 years. Results Rates of medication nonadherence were 28.8% for beta-blockers, 21.6% for ACE inhibitors, and 26.0% for statins. In unadjusted analysis, nonadherence to each class of medication was associated with higher all-cause and cardiovascular mortality. In multivariable analysis, nonadherence remained significantly associated with increased all-cause mortality risk for (beta-blockers (hazard ratio [HR] 1.50, 95 % CI 1.33-1.71), ACE inhibitors (HR 1.74, 95 % CI 1.52-1.98), and statins (HR 1.85, 95 % CI 1.63-2.09). In addition, nonadherence remained significantly associated with higher risk of cardiovascular mortality for (beta-blockers (HR 1.53, 95% CI 1.16-2.01), ACE inhibitors (HR 1.66, 95% CI 1.26-2.20), and statins (HR 1.62, 95 % CI 1.124-2.13). The findings of increased risk associated with nonadherence were consistent for cardiovascular hospitalization and revascularization procedures. Conclusions Nonadherence to cardioprotective medications is common in clinical practice and associated with a broad range of adverse outcomes. These findings suggest that medication nonadherence should be a target for quality improvement interventions to maximize the outcomes of patients with CAD. C1 [Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.] Denver VA Med Ctr, Cardiol Sect, Denver, CO USA. [Ho, P. Michael; Magid, David J.; Olson, Kari L.; Maddox, Thomas M.; Peterson, Pamela N.; Masoudi, Frederick A.; Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Ho, P. Michael; Magid, David J.; Shetterly, Susan M.; Maddox, Thomas M.; Peterson, Pamela N.; Masoudi, Frederick A.; Rumsfeld, John S.] Kaiser Permanente Colorado, Clin Res Unit, Aurora, CO USA. [Olson, Kari L.] Kaiser Permanente Colorado, Dept Pharm & Clin Pharm, Cardiac Risk Serv, Aurora, CO USA. [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Dept Med, Denver, CO USA. RP Ho, PM (reprint author), 1055 Clermont St 111B, Denver, CO 80220 USA. EM michael.ho@uchsc.edu NR 26 TC 231 Z9 238 U1 1 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2008 VL 155 IS 4 BP 772 EP 779 DI 10.1016/j.ahj.2007.12.011 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 285WY UT WOS:000254808100030 PM 18371492 ER PT J AU Orakzai, RH Nasir, K Orakzai, SH Kalia, N Gopal, A Musunuru, K Blumenthal, RS Budoff, MJ AF Orakzai, Raza H. Nasir, Khurram Orakzai, Sarwar H. Kalia, Nove Gopal, Ambarish Musunuru, Kiran Blumenthal, Roger S. Budoff, Mathew J. TI Effect of patient visualization of coronary calcium by electron beam computed tomography on changes in beneficial lifestyle behaviors SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ADHERENCE AB Despite convincing data demonstrating the benefits of aspirin (ASA), exercise, and dietary changes for both primary and secondary prevention of coronary heart disease, they remain underused. In this study, we assess whether higher coronary artery calcium (CAC) scores determined by electron beam computed tomography (EBCT) are associated with beneficial lifestyle behaviors in asymptomatic individuals. A total of 980 asymptomatic patients referred for EBCT risk assessment by their primary physician were sent a survey questioning them about health behaviors. We evaluated long-term ASA utilization, exercise, and dietary changes based on CAC using multivariable analysis. The study population consisted of 980 individuals (78% men, mean age 60 +/- 8 years) who were followed for a mean of 3 +/- 2 years after an initial EBCT scan. Overall, ASA initiation was lowest (29%) among those with CAC = 0, and gradually increased with higher CAC scores (1 to 99, 55%; 100 to 399, 61%; >= 400, 63%; p < 0.001 for trend). Similarly, dietary changes and exercise were lowest (33% and 44%, respectively) among those with CAC = 0 and gradually increased with higher CAC scores (1 to 99, 40%; 100 to 399, 58%; >= 400, 56%; p < 0.001 for trend for dietary changes; and 1 to 99, 62%; 100 to 399,63%; >= 400, 67%; p < 0.001 for trend for exercise). In multivariable analysis, greater baseline CAC was strongly associated with initiation of ASA therapy, dietary changes, and increased exercise. In conclusion, in addition to risk stratification of asymptomatic individuals, determination of CAC may also improve utilization of ASA therapy and behavioral modification. (C) 2008 Elsevier Inc. C1 [Orakzai, Raza H.] Cedars Sinai Med Ctr, Div Cardiol, Los Angeles, CA 90048 USA. [Nasir, Khurram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI PET CT Program, Boston, MA USA. [Orakzai, Sarwar H.] St Lukes Episcopal Hosp, Texas Heart Inst, Div Cardiol, Houston, TX USA. [Kalia, Nove] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Gopal, Ambarish; Budoff, Mathew J.] Univ Calif Los Angeles, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA USA. [Musunuru, Kiran; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. RP Budoff, MJ (reprint author), Cedars Sinai Med Ctr, Div Cardiol, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM mbudoff@labiomed.org NR 14 TC 52 Z9 52 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2008 VL 101 IS 7 BP 999 EP 1002 DI 10.1016/j.amjcard.2007.11.059 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 283TE UT WOS:000254658600015 PM 18359321 ER PT J AU Jiang, R Camargo, CA Varraso, R Paik, DC Willett, WC Barr, RG AF Jiang, Rui Camargo, Carlos A., Jr. Varraso, Raphaelle Paik, David C. Willett, Walter C. Barr, R. Graham TI Consumption of cured meats and prospective risk of chronic obstructive pulmonary disease in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID NITRIC-OXIDE; NITROGEN; COHORT; NITRATION; PATHOGENESIS; POPULATION; VALIDATION; INHALATION; MECHANISM; EMPHYSEMA AB Background: Most cured meats contain nitrites. Nitrites generate oxidative-nitrative stress and were shown in animal models to cause emphysema. Prospective epidemiologic data on cured meats and chronic obstructive pulmonary disease (COPD), however, are sparse. Objective: We examined the relation between cured meat consumption and the prospective risk of newly diagnosed COPD in women. Design: This was a prospective cohort study of 71531 women from the Nurses' Health Study who completed a validated dietary questionnaire at baseline in 1984 and had no baseline COPD or a report of asthma. Participants were aged 38-63 y in 1984 and were followed for 16 y. Results: A total of 750 new cases of COPD were documented during the follow-up. Cured meat consumption was positively associated with COPD risk after adjustment for age, smoking, and multiple other potential confounders. The adjusted relative risks of COPD across categories of cured meat consumption (never or almost never, 1-3 servings/mo, 1 serving/wk, 2-3 servings/wk, and 4 servings/wk) were 1.0, 1.14 (95% CI: 0.78, 1.66), 1.15 (95% CI: 0.79, 1.69), 1.40 (95% CI: 0.96, 2.05), and 1.51 (95% CI: 1.00, 2.27), respectively, (P for trend = 0.005). This positive association was present among both past (P for trend = 0.02) and current (P for trend = 0.03) smokers. No association was observed among never smokers, probably because of the small number of COPD cases in these women. Conclusion: Frequent cured meat consumption was associated with an increased risk of newly diagnosed COPD, among women who smoke. C1 [Jiang, Rui; Barr, R. Graham] Columbia Univ, Med Ctr, Dept Med, Coll Phys & Surg, New York, NY 10032 USA. [Camargo, Carlos A., Jr.; Willett, Walter C.; Barr, R. Graham] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Varraso, Raphaelle; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Emergency Med, Massachusetts Gen Hosp, Boston, MA USA. [Paik, David C.] Columbia Univ, Coll Phys & Surg, Dept Ophthalmol, New York, NY 10032 USA. [Barr, R. Graham] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. RP Barr, RG (reprint author), Columbia Univ, Med Ctr, Dept Med, Coll Phys & Surg, 622 W 168th St,PH 9 E,Room 105, New York, NY 10032 USA. EM rgb9@columbia.edu RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 FU NCI NIH HHS [CA87969, P01 CA087969]; NHLBI NIH HHS [HL63841, HL60712, HL75476, HL77612, R01 HL060712, R01 HL075476, R01 HL075476-01, R01 HL077612, R01 HL077612-04]; NIAID NIH HHS [AI52338, R21 AI052338] NR 42 TC 23 Z9 24 U1 3 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2008 VL 87 IS 4 BP 1002 EP 1008 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 288UT UT WOS:000255012000028 PM 18400725 ER PT J AU Zhang, J Sokal, I Peskind, ER Quinn, JF Jankovic, J Kenney, C Chung, KA Millard, SP Nutt, JG Montine, TJ AF Zhang, Jing Sokal, Izabela Peskind, Elaine R. Quinn, Joseph F. Jankovic, Joseph Kenney, Christopher Chung, Kathryn A. Millard, Steven P. Nutt, John G. Montine, Thomas J. TI CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE cerebrospinal fluid; Alzheimer disease; Parkinson disease; biomarkers; analyte profile; random forest algorithm ID MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID; DIAGNOSTIC-CRITERIA; TASK-FORCE; BIOMARKERS; PROTEOMICS AB The therapeutic imperative for Alzheimer disease (AD) and Parkinson disease (PD) calls for discovery and validation of biomarkers. Increased cerebrospinal fluid (CSF) tau and decreased amyloid (A) beta(42) have been validated as biomarkers of AD. In contrast, there is no validated CSF biomarker for PD. We validated our proteomics-discovered multianalyte profile (MAP) in CSF from 95 control subjects, 48 patients with probable AD, and 40 patients with probable PD. An optimal 8-member MAP agreed with expert diagnosis for 90 control subjects (95%), 36 patients with probable AD (75%), and 38 patients with probable PD (95%). This MAP consisted of the following (in decreasing order of contribution): tau, brain-derived neurotrophic factor, interleukin 8, A beta(42), beta(2)-microglobulin, vitamin D binding protein, apolipoprotein (apo) AII, and apoE. This first large-scale validation of a proteomic-discovered MAP suggests a panel of 8 CSF proteins that are highly effective at identifying PD and moderately effective at identifying AD. C1 [Zhang, Jing; Sokal, Izabela; Montine, Thomas J.] Univ Washington, Harborview Med Ctr, Dept Pathol, Sch Med, Seattle, WA 98104 USA. [Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Peskind, Elaine R.; Millard, Steven P.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Quinn, Joseph F.; Chung, Kathryn A.; Nutt, John G.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Jankovic, Joseph; Kenney, Christopher] Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA. [Jankovic, Joseph; Kenney, Christopher] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA. RP Montine, TJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Pathol, Sch Med, 300 9th Ave, Seattle, WA 98104 USA. FU NIA NIH HHS [P50 AG005136-25, P50 AG005136, AG05136] NR 18 TC 146 Z9 157 U1 1 U2 8 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 2008 VL 129 IS 4 BP 526 EP 529 DI 10.1309/W01Y0B808EMEH12L PG 4 WC Pathology SC Pathology GA 276FV UT WOS:000254127600002 PM 18343778 ER PT J AU Lee, HS Berg, JH Garcia-Godoy, F Jang, KT AF Lee, Hyeok-Sang Berg, Joel H. Garcia-Godoy, Franklin Jang, Ki-Taeg TI Long-term evaluation of the remineralization of interproximal caries-like lesions adjacent to glass-ionomer restorations: A micro-CT study SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID FLUORIDE RELEASE; CEMENT; ENAMEL; TOMOGRAPHY; COMPOSITES AB Purpose: To compare the remineralization of incipient artificial interproximal caries in the presence of three glass-ionomer cements (highly-filled glass-ionomer cement, compomer, resin-modified glass-ionomer cement) and a resin composite (control). Methods: Proximal restorations were simulated by placing tooth specimens and the various glass-ionomer cements in closed containers with artificial saliva at 37 degrees C and pH 7.0 for 30 days with constant circulation. Tomographic images were obtained with a micro CT scanner at 90, 180, and 270 days, and density-measuring software was used to calculate the micro-density of artificial caries lesions in the specimens. The mean density changes were compared between groups in order to evaluate the effects of remineralization. All data were analyzed using one-way ANOVA and the post-hoc Tukey multiple comparison test at P<0.05. Results: While the density of artificial caries lesions increased for all treatments, the increases for the three glass-ionomer groups were significantly higher than that for the resin group in each 3-month period. As time increased, the amount of density also increased for the glass-ionomer groups, and significant differences were found between the remineralization effects of the glass-ionomer groups. The micro CT proved to be an effective evaluation method. C1 [Lee, Hyeok-Sang; Jang, Ki-Taeg] Seoul Natl Univ, Inst Dent Res, Seoul 110744, South Korea. [Lee, Hyeok-Sang; Jang, Ki-Taeg] Seoul Natl Univ, Coll Dent, Dept Pediat Dent, Seoul 110744, South Korea. [Berg, Joel H.] Univ Washington, Dept Pediat Dent, Sch Dent, Lloyd & Kay Chair Oral Hlth, Seattle, WA 98195 USA. [Garcia-Godoy, Franklin] Nova SE Univ, Biosci Res Ctr, Coll Dent Med, Ft Lauderdale, FL 33314 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. RP Jang, KT (reprint author), Seoul Natl Univ, Inst Dent Res, 28-2,Yeongun Dong, Seoul 110744, South Korea. EM jangkt@snu.ac.kr NR 24 TC 17 Z9 17 U1 0 U2 2 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD APR PY 2008 VL 21 IS 2 BP 129 EP 132 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 297EJ UT WOS:000255599600014 PM 18578183 ER EF