FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Velmahos, GC Jurkovich, GJ AF Velmahos, George C. Jurkovich, Gregory J. TI The concept of acute care surgery: A vision for the not-so-distant future SO SURGERY LA English DT Editorial Material ID TRAUMA CARE; GENERAL-SURGERY; COVERAGE; MODEL C1 Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. RP Velmahos, GC (reprint author), Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 18 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2007 VL 141 IS 3 BP 288 EP 290 DI 10.1016/j.surg.2006.12.017 PG 3 WC Surgery SC Surgery GA 150ZL UT WOS:000245258000002 PM 17349831 ER PT J AU Reilly, PM Schwab, CW AF Reilly, Patrick M. Schwab, C. William TI Acute care surgery: The academic hospital's perspective SO SURGERY LA English DT Editorial Material ID EMERGENCY GENERAL-SURGERY; TRAUMA SURGEONS; SERVICE; FUTURE; MODEL C1 Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. RP Reilly, PM (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 9 TC 17 Z9 17 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2007 VL 141 IS 3 BP 299 EP 301 DI 10.1016/j.surg.2007.01.007 PG 3 WC Surgery SC Surgery GA 150ZL UT WOS:000245258000006 PM 17349835 ER PT J AU Gamelli, RL AF Gamelli, Richard L. TI Organisation of faculty practice and resident training in acute care surgery in an academic medical center SO SURGERY LA English DT Editorial Material C1 Loyola Univ, Ctr Med, Dept Surg, Maywood, IL 60153 USA. RP Gamelli, RL (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2007 VL 141 IS 3 BP 302 EP 303 DI 10.1016/j/surg.2007.01.005 PG 2 WC Surgery SC Surgery GA 150ZL UT WOS:000245258000007 PM 17349836 ER PT J AU Vrahas, MS AF Vrahas, Mark S. TI Acute care surgery from the orthopedic surgeon's perspective: A lost opportunity SO SURGERY LA English DT Editorial Material ID EXTREMITIES; FRACTURES; TRAUMA C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthoped, Div Orthoped Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP Vrahas, MS (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthoped, Div Orthoped Trauma, 32 Fruit St,YAW 3-3C, Boston, MA 02114 USA. EM mvrahas@partners.org NR 9 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2007 VL 141 IS 3 BP 317 EP 320 DI 10.1016/j.surg.2007.01.003 PG 4 WC Surgery SC Surgery GA 150ZL UT WOS:000245258000011 PM 17349840 ER PT J AU Valadka, AB Ellenbogen, RG Wirth, FP Laws, ER AF Valadka, Alex B. Ellenbogen, Richard G. Wirth, Fremont P., Jr. Laws, Edward R., Jr. TI Acute care surgery: Challenges and opportunities from the neurosurgical perspective SO SURGERY LA English DT Editorial Material ID DECOMPRESSIVE SURGERY; TRAUMA; FUTURE C1 Univ Texas, Dept Neurosurg, Sch Med, Houston, TX USA. Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. Neurol Inst, Savannah, GA USA. Univ Virginia, Dept Neurol Surg, Charlottesville, VA USA. RP Valadka, AB (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2007 VL 141 IS 3 BP 321 EP 323 DI 10.1016/j.surg.2007.01.009 PG 3 WC Surgery SC Surgery GA 150ZL UT WOS:000245258000012 PM 17349841 ER PT J AU Malangoni, MA AF Malangoni, Mark A. TI Acute care surgery: The general surgeon's perspective SO SURGERY LA English DT Editorial Material C1 Metrohlth Med Ctr, Dept Surg, Cleveland, OH 44109 USA. RP Malangoni, MA (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 2 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2007 VL 141 IS 3 BP 324 EP 326 DI 10.1016/j.surg.2007.01.008 PG 3 WC Surgery SC Surgery GA 150ZL UT WOS:000245258000013 PM 17349842 ER PT J AU Wall, E AF Wall, Eva TI Surgical hospitalism: A perspective from the community hospital SO SURGERY LA English DT Editorial Material ID MORTALITY C1 Everett Clin, Dept Surg, Washington, DC USA. RP Wall, E (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2007 VL 141 IS 3 BP 327 EP 329 DI 10.1016/j.surg.2007.01.011 PG 3 WC Surgery SC Surgery GA 150ZL UT WOS:000245258000014 PM 17349843 ER PT J AU Cummings, DE Overduin, J Foster-Schubert, KE Carlson, MJ AF Cummings, David E. Overduin, Joost Foster-Schubert, Karen E. Carlson, Molly J. TI Role of the bypassed proximal intestine in the anti-diabetic effects of bariatric surgery SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Editorial Material ID GLUCAGON-LIKE PEPTIDE-1; MORBIDLY OBESE SUBJECTS; ROUX-EN-Y; INDUCED WEIGHT-LOSS; GASTRIC-BYPASS; ILEAL TRANSPOSITION; JEJUNOILEAL BYPASS; GUT HORMONE; FOOD-INTAKE; ILEOJEJUNAL TRANSPOSITION C1 [Cummings, David E.; Overduin, Joost; Foster-Schubert, Karen E.; Carlson, Molly J.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,S-111-Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu FU NIDDK NIH HHS [DK68384, P01 DK068384, P01 DK068384-040002, R01 DK061516, R01 DK061516-06, R01 DK61516] NR 56 TC 77 Z9 87 U1 1 U2 5 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 MAR-APR PY 2007 VL 3 IS 2 BP 109 EP 115 DI 10.1016/j.soard.2007.02.003 PG 7 WC Surgery SC Surgery GA 375EO UT WOS:000261097100001 PM 17386391 ER PT J AU Collins, J Mattar, S Qureshi, F Warman, J Ramanathan, R Schauer, P Eid, G AF Collins, Joy Mattar, Samer Qureshi, Faisal Warman, Juanita Ramanathan, Ramesh Schauer, Philip Eid, George TI Initial outcomes of laparoscopic Roux-en-Y gastric bypass in morbidly obese adolescents SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Morbid obesity; Adolescent obesity; Bariatric surgery; Gastric bypass; Quality of life ID POLYCYSTIC-OVARY-SYNDROME; TYPE-2 DIABETES-MELLITUS; INSULIN-RESISTANCE; CHILDHOOD OBESITY; US CHILDREN; BODY-MASS; SURGERY; OVERWEIGHT; ASSOCIATION; PREVALENCE AB Background: Adolescent obesity is an epidemic in the United States, leading to significant morbidity. Because the impact of laparoscopic bariatric surgery in this Population is not as well delineated as in adults, we examined the short-term outcome of adolescents undergoing laparoscopic Roux-en-Y gastric bypass at our institution. Methods: The medical records of patients <= 18 years of age who had undergone laparoscopic Roux-en-Y gastric bypass for morbid obesity from 1999 to June 2005 were reviewed. The outcome variables examined included preoperative body mass index, percent of excess weight lost for those with at least 3 months Of follow-up, length of hospital stay, postoperative morbidity and mortality, changes in cornorbid conditions, and effects Of Surgical weight loss on quality of life. Data are presented as the mean +/- standard error of the mean. Results: Eleven patients (seven girls and four boys) had undergone laparoscopic Roux-en-Y gastric bypass. The mean follow-up was 11.5 +/- 2.8 months (range 3-32). The average patient age was 16.5 +/- 0.2 years, and the average body mass index was 50.5 +/- 2.0 kg/m(2). The average number of comorbidities was 5.3, 70% of which improved or resolved postoperatively. No mortalities resulted. of the 11 patients, 1 had early postoperative bleeding and 2 developed a marginal ulcer. The quality-of-life, Surveys obtained from 9 patients, reflected an overall improvement in self-esteem, social functioning, and productivity in school or the workplace. Conclusions: The initial data suggest that laparoscopic gastric bypass is an effective weight loss treatment for morbidly obese adolescents. (Surg Obes Relat Dis 2007;3:147-152.) (C) 2007 American Society for Bariatric Surgery. All rights reserved. C1 [Collins, Joy; Mattar, Samer; Qureshi, Faisal; Warman, Juanita; Ramanathan, Ramesh; Eid, George] Univ Pittsburgh, Med Ctr, Div Minimally Invas Surg, Pittsburgh, PA USA. [Schauer, Philip] Cleveland Clin Fdn, Div Minimally Invas Surg, Cleveland, OH 44195 USA. [Eid, George] Vet Affairs Pittsburg Healthcare Syst, Pittsburgh, PA USA. RP Eid, G (reprint author), Minimally Invas Surg Ctr, 3380 Blvd Allies,Suite 390, Pittsburgh, PA 15213 USA. EM eidgm@upmc.edu OI Qureshi, Faisal/0000-0002-7986-720X FU Ethicon Endosurgery, Inc. (Johnson Johnson, Inc.); Stryker, Inc.; W.L. Gore, Inc. FX Dr. Schauer is on the speakers' bureau and a consultant and the recipient of an educational grant from Ethicon Endosurgery, Inc. (Johnson & Johnson, Inc.), a consultant for and recipient of an educational grant from Stryker, Inc., a recipient at the time of this study of an educational grant from U.S. Surgical, Inc. (Tyco Health, Inc.), and a consultant for and recipient of a research grant from W.L. Gore, Inc. NR 28 TC 38 Z9 38 U1 0 U2 4 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 MAR-APR PY 2007 VL 3 IS 2 BP 147 EP 152 DI 10.1016/j.soard.2006.12.002 PG 6 WC Surgery SC Surgery GA 375EO UT WOS:000261097100008 PM 17324636 ER PT J AU O'Rourke, RW Kim, CY Chang, EY Hunter, JG Jobe, BA AF O'Rourke, Robert W. Kim, Charles Y. Chang, Eugene Y. Hunter, John G. Jobe, Blair A. TI Incorporation of Nissen fundoplication in a rat model of duodenoesophageal reflux SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Barrett's esophagus; esophageal adenocarcinoma; gastroesophageal reflux disease; rat ID BARRETTS-ESOPHAGUS; ANTIREFLUX SURGERY; ENDOSCOPIC SURVEILLANCE; GASTROESOPHAGEAL-REFLUX; ADENOCARCINOMA; EFFICACY; ANTERIOR AB Background: Few in vivo models of esophageal reflux and fundoplication suitable for the study of the pathogenesis of Barrett's esophagus and esophageal cancer exist. We describe a modification of a rat model of duodenoesophageal reflux that incorporates Nissen fundoplication and uses it to study the role of fundoplication in ameliorating esophageal reflux. Methods: A previously described rat model of duodenoesophageal reflux was modified to include Nissen fundoplication. Reflux threshold (RT), defined as the gastric pressure required to cause gastroesophageal reflux during transgastric instillation of saline, was measured in 12 Sprague-Dawley rats at baseline, after cardiomyotomy with esophagogastroduodenal anastomosis (EGDA), after subsequent Nissen fundoplication, and, finally, after takedown of Nissen fundoplication (NF). Results: Cardiomyotomy with EGDA induced no significant change in RT compared with baseline (mean RT SD: 4.0 +/- 1.9 mmHg and 6.0 +/- 2.5 mmHg, respectively, p = 0.741). Nissen fundoplication led to a 14-fold increase in RT (56.4 +/- 18.2 mmHg) compared with cardiomyotomy. RT pressure reverted to baseline levels after NF takedown (4.7 +/- 2.9 mmHg,p < 0.001). Antegrade esophageal flow was demonstrated without an increase in distal esophageal pressure after NF. Conclusions: Nissen fundoplication creates a one-way antireflux mechanism that eliminates gastroesophageal reflux in this rat model. This modification of an in vivo model of duodenoesophageal reflux represents a unique opportunity to investigate the effect of NF on cardiomyotomy-induced reflux and distal esophageal exposure to duodenogastric refluxate, and could be useful in the study of the role of NF in preventing progression to BE and ECA. C1 Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Jobe, BA (reprint author), Oregon Hlth Sci Univ, Dept Surg, 3181 SW Sam Jackson Pk Rd,L-233A, Portland, OR 97239 USA. NR 21 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAR PY 2007 VL 21 IS 3 BP 467 EP 470 DI 10.1007/s00464-006-9044-4 PG 4 WC Surgery SC Surgery GA 145DK UT WOS:000244845300022 PM 17103272 ER PT J AU Egan, MT Sandberg, WS AF Egan, Marie T. Sandberg, Warren S. TI Auto identification technology and its impact on patient safety in the operating room of the future SO SURGICAL INNOVATION LA English DT Article DE auto-ID; Operating Room of the Future; operating room efficiency; radio frequency identification; patient safety; data integration; operating room supply management; perioperative systems design AB Automatic identification technologies, such as bar coding and radio frequency identification, are ubiquitous in everyday life but virtually nonexistent in the operating room. User expectations, based on everyday experience with automatic identification technologies, have generated much anticipation that these systems will improve readiness, workflow, and safety in the operating room, with minimal training requirements. We report, in narrative form, a multi-year experience with various automatic identification technologies in the Operating Room of the Future Project at Massachusetts General Hospital. In each case, the additional human labor required to make these 'labor-saving' technologies function in the medical environment has proved to be their undoing. We conclude that while automatic identification technologies show promise, significant barriers to realizing their potential still exist. Nevertheless, overcoming these obstacles is necessary if the vision of an operating room of the future in which all processes are monitored, controlled, and optimized is to be achieved. C1 Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Egan, MT (reprint author), Massachusetts Gen Hosp, Dept Nursing, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM mtegan@partners.org FU NCRR NIH HHS [R43 RR018076-01] NR 12 TC 13 Z9 13 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1553-3506 J9 SURG INNOV JI Surg. Innov. PD MAR PY 2007 VL 14 IS 1 BP 41 EP 50 DI 10.1177/1553350606298971 PG 10 WC Surgery SC Surgery GA 151WZ UT WOS:000245323000008 PM 17442879 ER PT J AU Maia, AL Dupuis, J Manning, A Liu, CY Meigs, JB Cupples, LA Larsen, PR Fox, CS AF Maia, Ana Luiza Dupuis, Josee Manning, Alisa Liu, Chunyu Meigs, James B. Cupples, L. Adrienne Larsen, P. Reed Fox, Caroline S. TI The type 2 deiodinase (DIO2) A/G polymorphism is not associated with glycemic traits: The Framingham Heart Study SO THYROID LA English DT Article ID INSULIN-RESISTANCE; THR92ALA POLYMORPHISM; INDEXES; VARIANT; ROLES AB Background: Type 2 deiodinase plays a critical role in thyroid hormone homeostasis. A single nucleotide polymorphism in DIO2 gene (A/G) in humans has been associated with a similar to 20% lower glucose disposal rate and greater insulin resistance in type 2 diabetes (DM2) patients. Objective: This study was designed to test whether homozygosity for the DIO2 A/G polymorphism would be associated with risk of DM2 or elevated levels of diabetes intermediate traits. Design and setting: Community-based, longitudinal study. Participants were withdrawn from a subset of unrelated individuals from the Offspring Cohort of the Framingham Heart Study who had DNA collected between 1995 and 1998. Methods: DNA samples from 1633 participants (mean age, 62 years) underwent genotyping of the DIO2 A/G polymorphism. Incident DM2 and diabetes-related traits (fasting plasma glucose, mean fasting plasma glucose, 2-hour glucose, hemoglobin A(1c), fasting insulin, insulin resistance) were measured. Results: The minor allele (G) frequency was 0.37. Using multivariable regression for intermediate traits and Cox proportional hazards regression for DM2, p values were calculated for two models: Model 1: age, age-squared, sex, and smoking; Model 2: Model 1+ body mass index. There were no significant associations (all p > 0.20) for any trait examined. For DM2 risk, the hazard ratios associated with A/G or G/G relative to the A/A genotype were 1.0 (95% confidence interval [CI] 0.7-1.3) and 1.2 (95% CI 0.7-1.9), respectively. Conclusions: Our results indicate that in this community-based sample, there is no association of the DIO2 A/G polymorphism with diabetes intermediate trait levels or DM2 risk. C1 Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Div Endocrine, BR-90035003 Porto Alegre, RS, Brazil. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study Genet Lab, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Gen Div, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, NHLBIs Framingham Heart Study, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Sch Med, Boston, MA 02115 USA. RP Maia, AL (reprint author), Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Div Endocrine, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. EM almaia@ufrgs.br RI Maia, Ana Luiza/F-9201-2012; OI Maia, Ana Luiza/0000-0002-4186-5532; Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603 FU NHLBI NIH HHS [N01-HC-25195]; NIDDK NIH HHS [DK 36256] NR 14 TC 19 Z9 19 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 MAR PY 2007 VL 17 IS 3 BP 199 EP 202 DI 10.1089/thy.2006.0298 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 152XP UT WOS:000245395900002 PM 17381351 ER PT J AU Dzik, S AF Dzik, Sunny TI How I do it: platelet support for refractory patients SO TRANSFUSION LA English DT Article ID HLA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Dzik, S (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org NR 12 TC 8 Z9 8 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 MAR PY 2007 VL 47 IS 3 BP 374 EP 378 DI 10.1111/j.1537-2995.2007.01126.x PG 5 WC Hematology SC Hematology GA 145LJ UT WOS:000244866300006 PM 17319815 ER PT J AU Babic, AM Josefsson, EC Bergmeier, W Wagner, DD Kaufman, RM Silberstein, LE Stossel, TP Hartwig, JH Hoffmeister, KM AF Babic, Aleksandar M. Josefsson, Emma C. Bergmeier, Wolfgang Wagner, Denisa D. Kaufman, Richard M. Silberstein, Leslie E. Stossel, Thomas P. Hartwig, John H. Hoffmeister, Karin M. TI In vitro function and phagocytosis of galactosylated platelet concentrates after long-term refrigeration SO TRANSFUSION LA English DT Article ID CHILLED BLOOD-PLATELETS; BACTERIAL-CONTAMINATION; P-SELECTIN; UNITED-STATES; TRANSFUSION; SURVIVAL; MAINTENANCE; ASSOCIATION; CLEARANCE; APOPTOSIS AB BACKGROUND: Short-term refrigeration of platelets (PLTs) in the absence of plasma results in their rapid clearance after transfusion. Blocking beta-N-acetylglucosamine (beta-GlcNAc) residues of glycoprotein lb alpha (GPlb alpha) with galactose prevents binding of refrigerated human and mouse PLTs to macrophages and prolongs the circulation times of refrigerated mouse PLTs. PLT-associated galactosyltransferase efficiently galactosylates chilled PLTs in the presence of its substrate UDP-galactose is added to PLT-rich plasma. STUDY DESIGN AND METHODS: To characterize the hemostatic function of refrigerated and galactosylated human PLTs processed in the blood bank, PLT aggregation was studied in vitro under static and flow conditions and expression of integrin beta 3 (CD61), CD62P (P-selectin), GPlb alpha (CD42b), annexin V binding, and integrin all 3 activation with flow cytometry. Affinity of macrophages for galactosylated refrigerated PLTs was evaluated with THP-1 cells, which recognize and phagocytize refrigerated PLTs. RESULTS: PLTs refrigerated and galactosylated for 14 days 1) maintained their ability to aggregate when exposed to agonists in a standard aggregometry assay, 2) showed less pronounced changes in surface expression of GPlb alpha compared with room temperature (RT)stored PLTs, 3) increased P-selectin expression, and 4) were poorly phagocytized by differentiated THP-1 cells in vitro. In addition, it is shown that refrigeration of PLTs does not affect their adhesive properties under in vitro flow conditions. CONCLUSION: It is shown that refrigerated human PLTs retain in vitro function better than RT PLTs during storage and demonstrate that galactosylation prevents recognition of stored refrigerated PLTs by macrophages in vitro. C1 Brigham & Womens Hosp, Dept Pathol, Div Translat Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Translat Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Joint Program Transfus Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hoffmeister, KM (reprint author), Brigham & Womens Hosp, Div Hematol, 75 Francis St,CHRB 6TH Floor, Boston, MA 02115 USA. EM khoffmeister@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL56949, P01 HL056949] NR 19 TC 25 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2007 VL 47 IS 3 BP 442 EP 451 DI 10.1111/j.1537-2995.2007.01134.x PG 10 WC Hematology SC Hematology GA 145LJ UT WOS:000244866300015 PM 17319824 ER PT J AU Philips, JA Marty, FM Stone, RM Koplan, BA Katz, JT Baden, LR AF Philips, J. A. Marty, F. M. Stone, R. M. Koplan, B. A. Katz, J. T. Baden, L. R. TI Torsades de pointes associated with voriconazole use SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE voriconazole; torsades de pointes; arrhythmia; aspergillosis ID INVASIVE FUNGAL-INFECTIONS; FEMALE GENDER; RISK FACTOR; LONG QT; ASPERGILLOSIS; THERAPY; PROLONGATION AB We describe 2 patients who developed prolonged QTc interval on electrocardiogram while being treated with voriconazole. The first patient had undergone induction chemotherapy for acute myelogenous leukemia, and her course had been complicated by invasive aspergillosis and an acute cardiomyopathy. She developed torsades de pointes 3 weeks after starting voriconazole therapy. She was re-challenged with voriconazole without recurrent QTc prolongation or cardiac dysfunction. The second patient had a significantly prolonged QTc interval while on voriconazole therapy We recommend careful monitoring for QTc prolongation and arrhythmia in patients who are receiving voriconazole, particularly those who have significant electrolyte disturbances, are on concomitant QT prolonging medications, have heart failure such as from a dilated cardiomyopathy, or have recently received anthracycline-based chemotherapy. The potential for synergistic cardiotoxicity must be carefully considered. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Baden, LR (reprint author), Brigham & Womens Hosp, Div Infect Dis, PBB-A4,75 Francis St, Boston, MA 02115 USA. EM lbaden@partners.org NR 16 TC 29 Z9 31 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD MAR PY 2007 VL 9 IS 1 BP 33 EP 36 DI 10.1111/j.1399-3062.2006.00160.x PG 4 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 146TJ UT WOS:000244957300007 PM 17313469 ER PT J AU Boerma, M Fiser, WP Hoyt, G Berry, GJ Joseph, L Joseph, J Wang, J Crew, MD Robbins, RC Hauer-Jensen, M AF Boerma, Marjan Fiser, William P. Hoyt, Grant Berry, Gerald J. Joseph, Lija Joseph, Jacob Wang, Junru Crew, Mark D. Robbins, Robert C. Hauer-Jensen, Martin TI Influence of mast cells on outcome after heterotopic cardiac transplantation in rats SO TRANSPLANT INTERNATIONAL LA English DT Article DE animal models; cardiac transplantation; graft survival; mast cells ID DELAYED RADIATION-INJURY; GROWTH-FACTOR; ENDOTHELIN-1 IMPROVES; HEART-TRANSPLANTS; CHRONIC REJECTION; GENE-TRANSFER; T-CELLS; C-KIT; EXPRESSION; RECEPTOR AB Correlative data suggest that mast cells adversely affect cardiac transplantation. This study uses a mast cell-deficient rat model to directly address the role of mast cells in cardiac allotransplantation. Standardized cardiac heterotopic transplantation with cyclosporine immunosuppression was performed in mast cell-deficient and mast cell-competent rats. Rejection, ischemia, fibrosis, fibrin deposition, numbers of T-cell receptor alpha/beta positive cells, expression of transforming growth factor-beta (TGF-beta), and of endothelin-1 (ET-1) and its receptors ETA and ETB were assessed. Differences in baseline cardiac gene expression were quantified by real-time PCR in a separate group of untransplanted animals. Baseline cardiac gene expression levels of all investigated growth factors, cytokines, ET-1, ETA, and ETB were similar in mast cell-deficient and mast cell-competent rats. Surprisingly, upon heterotopic transplantation, donor heart survival was significantly reduced in mast cell-deficient rats. Moreover, in mast cell-deficient donor hearts rejection was more severe, although nonsignificant, and extracellular matrix associated TGF-beta immunoreactivity was significantly lower than in mast cell-competent donor hearts. Fibrin immunoreactive area, on the other hand, was only increased in mast cell-deficient donor hearts, but not in mast cell-competent donor hearts. Histopathological changes in all donor hearts were accompanied by increased immunoreactivity for ET-1. In conclusion, this study shows that mast cells play a protective role after cardiac transplantation. C1 Univ Arkansas Med Sci, Dept Surg, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Surg, Little Rock, AR USA. Stanford Univ, Sch Med, Falk Res Ctr, Dept Cardiothorac Surg, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. VA Boston Healthcare Syst, Div Cardiol, Med Serv, Boston, MA USA. Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. RP Boerma, M (reprint author), Univ Arkansas Med Sci, Dept Surg, 4301 W Markham,Slot 522-3, Little Rock, AR 72205 USA. EM mboerma@uams.edu FU NCI NIH HHS [CA71382] NR 49 TC 22 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD MAR PY 2007 VL 20 IS 3 BP 256 EP 265 DI 10.1111/j.1432-2277.2006.00420.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 132XF UT WOS:000243975500006 PM 17291219 ER PT J AU Garbe, AI von Boehmer, H AF Garbe, Annette I. von Boehmer, Harald TI TCR and Notch synergize in alpha beta versus gamma delta lineage choice SO TRENDS IN IMMUNOLOGY LA English DT Review ID T-CELL-RECEPTOR; ADAPTER PROTEIN SLP-76; PRE-TCR; THYMOCYTE DEVELOPMENT; BETA/GAMMA-DELTA; C-MYC; LYMPHOCYTE DEVELOPMENT; GENE REARRANGEMENT; PT-ALPHA; EXPRESSION AB At two checkpoints, T cell development is controlled by T cell receptor (TCR) signaling, which determines survival and lineage commitment. At the first of these checkpoints, signaling by the pre-TCR, the gamma delta TCR or the alpha beta TCR has a major but nonexclusive impact on whether cells will become CD4(-)CD8(-) gamma delta or CD4(+)CD8(+) alpha beta lineage cells. Pre-TCR signals synergize with moderate Notch signals to generate up lineage cells. Relatively strong signals by the gamma delta TCR (or early expressed alpha beta TCR) in the absence of Notch signaling are sufficient to yield gamma delta lineage cells. However, relatively weak signals of the latter two receptors combined with strong Notch signaling result in the formation of alpha beta lineage cells that generate a diverse alpha beta TCR repertoire in pre-TCR-deficient mice. It remains to be determined whether TCR and/or Notch signals instruct or confirm predetermined lineage fate. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Garbe, Annette/A-4824-2014 FU NCI NIH HHS [P01 CA 109901]; NIAID NIH HHS [R01 AI 47281, R01 AI 45846] NR 66 TC 22 Z9 22 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD MAR PY 2007 VL 28 IS 3 BP 124 EP 131 DI 10.1016/j.it.2007.01.004 PG 8 WC Immunology SC Immunology GA 149UA UT WOS:000245171100005 PM 17261380 ER PT J AU Freedland, SJ Kane, CJ Amling, CL Aronson, WJ Terris, MK Presti, JC AF Freedland, Stephen J. Kane, Christopher J. Amling, Christopher L. Aronson, William J. Terris, Martha K. Presti, Joseph C., Jr. CA SEARCH Database Study Grp TI Upgrading and downgrading of prostate needle biopsy specimens: Risk factors and clinical implications SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; GLEASON SCORES; CANCER; GRADE; OBESITY; MORTALITY; ACCURACY; IMPROVES; DATABASE; SCHEME AB OBJECTIVES The prostate biopsy Gleason grade frequently differs from the radical prostatectomy (RP) grade. Given the critical role that needle biopsy plays in treatment decisions, we sought to determine the risk factors for upgrading and downgrading the prostate biopsy specimen. METHODS We determined the significant predictors of upgrading (worse RP grade than biopsy grade) and downgrading (better RP grade than biopsy grade) among 1113 men treated with RP from 1996 to 2005 within the Shared Equal Access Regional Cancer Hospital (SEARCH) database who had undergone at least sextant biopsy. The Gleason sum was examined as a categorical variable of 2 to 6, 3+4, and 4+3 or greater. RESULTS Overall, the disease of 299 men (27%) was upgraded and 123 (11%) was downgraded, and 691 men (62%) had identical biopsy and pathologic Gleason sum groups. Upgrading was associated with adverse pathologic features (P <= 0.001) and the risk of biochemical progression (P = 0.001). Downgrading was associated with more favorable pathologic features (P <= 0.01) and a decreased risk of progression (P = 0.04). On multivariate analysis, greater prostate-specific antigen levels (P < 0.001), more biopsy cores with cancer (P = 0.001), and obesity (P = 0.003) were all significantly and positively associated with upgrading. In contrast, biopsy Gleason sum 3+4 (P = 0.001) and obtaining eight or more biopsy cores (P = 0.01) were associated with a lower likelihood of upgrading. CONCLUSIONS Men whose disease was upgraded were at a greater risk of adverse pathologic features and biochemical progression. Men with "high-risk" cancer (greater prostate-specific antigen levels, more positive cores, and obese) were more likely to have their disease category upgraded, and obtaining more biopsy cores reduced the likelihood of upgrading. C1 Durham Vet Affairs Med Ctr, Dept Surg, Durham, NC USA. Duke Univ, Sch Med, Div Urol Surg, Dept Surg, Durham, NC USA. Duke Univ, Sch Med, Div Urol Surg, Dept Pathol, Durham, NC USA. Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC USA. San Francisco VA Med Ctr, Dept Surg, Urol Sect, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Univ Alabama, Dept Urol, Birmingham, AL USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. Med Coll Georgia, Augusta Vet Affairs Med Ctr, Dept Surg, Augusta, GA 30912 USA. Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. Vet Affairs Palo Alto Healthcare Syst, Dept Surg, Urol Sect, Palo Alto, CA USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, Div Urol, DUMC, Box 3850, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50 CA92131-01A1, P50 CA092131, P50 CA092131-01A10005, R01 CA100938, R01CA100938]; NCRR NIH HHS [M01 RR000865, M01 RR000865-310710] NR 19 TC 86 Z9 89 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 MAR PY 2007 VL 69 IS 3 BP 495 EP 499 DI 10.1016/j.urology.2006.10.036 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 155GS UT WOS:000245566500020 PM 17382152 ER PT J AU Gruber, A Chalmers, AS Rasmussen, RA Ong, H Popov, S Andersen, J Hu, SL Ruprecht, RM AF Gruber, Andreas Chalmers, Alistair S. Rasmussen, Robert A. Ong, Helena Popov, Sergei Andersen, Janet Hu, Shiu-Lok Ruprecht, Ruth M. TI Dendritic cell-based vaccine strategy against human immunodeficiency virus clade C: Skewing the immune response toward a helper T cell type 2 profile SO VIRAL IMMUNOLOGY LA English DT Article ID APOPTOTIC TUMOR-CELLS; IN-VITRO; HIV-1; EXPRESSION; CD4(+); IMMUNOGENICITY; TRANSCRIPTION; INDUCTION; PROTEINS; ANTIGEN AB Given the continued spread of human immunodeficiency virus (HIV)-1 worldwide, developing efficient vaccine strategies against HIV-1 is a key task. We tested the safety and immunogenicity of a multicomponent, cell-based vaccine that consisted of antigen-expressing apoptotic bodies with or without autologous dendritic cells (DCs). The vaccine strategy involved transfection of human 293T cells with codon-optimized DNA vectors expressing env of HIV1084i, a newly transmitted pediatric HIV-1 clade C strain; SHIV89.6P tat; and SIV mac239 gag-protease. Apoptotic bodies were generated by heat shock and ultraviolet irradiation and mixed either with mouse DCs (DC-cell vaccine) or given directly (cell-only vaccine) to BALB/c mice for initial priming; boosts consisted of apoptotic bodies only. The immunogens were well tolerated with or without DCs. Compared with the cell-only vaccine, the DC-cell vaccine induced higher antibody titers against all three antigens, whereas virus-specific cytotoxic T lymphocyte responses were equally strong in both groups. Isotype analysis of viral antigen-specific antibodies revealed a skewing toward helper T type 2 responses induced by the DC-cell vaccine but not by the cell-only vaccine. In summary, both vaccine strategies were safe and induced cellular as well as Immoral antiviral immunity; the DC-based approach had the advantage of significantly stronger antibody responses. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB-809, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NIAID NIH HHS [P01 AI48240, R01 AI43839] NR 35 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD SPR PY 2007 VL 20 IS 1 BP 160 EP 169 DI 10.1089/vim.2006.0052 PG 10 WC Immunology; Virology SC Immunology; Virology GA 157HU UT WOS:000245710300016 PM 17425430 ER PT J AU Yao, M Bujold, K Redmond, R Kochevar, I AF Yao, Min Bujold, Kenneth Redmond, Robert Kochevar, Irene TI Wound healing after photochemical tissue bonding SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr Photomed, Sch Med, 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 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2007 VL 15 IS 2 MA 102 BP A41 EP A41 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 143RM UT WOS:000244741900118 ER PT J AU Yamada, K Griesemer, A Sykes, M Sachs, DH AF Yamada, Kazuhiko Griesemer, Adam Sykes, Megan Sachs, David H. TI Transplantation of vascularized thymus and kidney from GaIT-KO pigs to baboons SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Satellite Symposium on Xenotransplantation CY JUL 22-27, 2006 CL Boston, MA ID MINIATURE SWINE; T-CELL; COMPOSITE THYMOKIDNEYS; LOBE TRANSPLANTATION; MISMATCHED BARRIERS; NUCLEAR TRANSFER; MIXED CHIMERISM; KNOCKOUT PIGS; TOLERANCE; INDUCTION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. EM kaz.yamada@tbrc.mgh.harvard.edu NR 23 TC 5 Z9 7 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAR PY 2007 VL 14 IS 2 BP 186 EP 189 DI 10.1111/j.1399-3089.2007.00386_9.x PG 4 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 157VR UT WOS:000245750000020 ER PT J AU George, RE Attiyeh, EF Li, SL Moreau, LA Neuberg, D Li, C Fox, EA Meyerson, M Diller, L Fortina, P Look, AT Maris, JM AF George, Rani E. Attiyeh, Edward F. Li, Shuli Moreau, Lisa A. Neuberg, Donna Li, Cheng Fox, Edward A. Meyerson, Matthew Diller, Lisa Fortina, Paolo Look, A. Thomas Maris, John M. TI Genome-Wide Analysis of Neuroblastomas using High-Density Single Nucleotide Polymorphism Arrays SO PLOS ONE LA English DT Article AB Background. Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH) and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP) array. Findings. Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%). Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016). Chromosome 1p LOH was seen in one-third of cases. LOH events on chromosomes 11q and 1p were generally accompanied by copy number loss, indicating hemizygous deletion within these regions. The one exception was on chromosome 11p, where LOH in all four cases was accompanied by normal copy number or diploidy, implying uniparental disomy. Gain of copy number was most frequently observed on chromosome arm 17q (21/22 samples; 95%) and was associated with allelic imbalance in six samples. Amplification of MYCN was also noted, and also amplification of a second gene, ALK, in a single case. Conclusions. This analysis demonstrates the power of SNP arrays for high-resolution determination of LOH and DNA copy number change in neuroblastoma, a tumor in which specific allelic changes drive clinical outcome and selection of therapy. C1 [George, Rani E.; Moreau, Lisa A.; Diller, Lisa; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Attiyeh, Edward F.; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Oncol, Philadelphia, PA 19104 USA. [Li, Shuli; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fox, Edward A.] Dana Farber Canc Inst, Microarray Core Facil, Boston, MA 02115 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fortina, Paolo] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA. RP George, RE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM rani_george@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NIH/NINDS [K08NS047983]; Young Investigator Awards; American Society of Clinical Oncology; Children's Oncology Group; NIH [R01 CA104605, R33-CA83220, R01-CA87847, U01-CA98543] FX This work was supported by NIH/NINDS Grant K08NS047983 (to R. E. G.), Young Investigator Awards, American Society of Clinical Oncology and Children's Oncology Group (to R. E. G.), NIH R01 CA104605 (A. T. L.), R33-CA83220 (to P. F., J.M.M.), R01-CA87847 (to J.M.M.) and U01-CA98543 (to the Children's Oncology Group). NR 33 TC 68 Z9 68 U1 1 U2 1 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 FEB 28 PY 2007 VL 2 IS 2 AR e255 DI 10.1371/journal.pone.0000255 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DL UT WOS:000207444600015 PM 17327916 ER PT J AU Kaipainen, A Kieran, MW Huang, S Butterfield, C Bielenberg, D Mostoslavsky, G Mulligan, R Folkman, J Panigrahy, D AF Kaipainen, Arja Kieran, Mark W. Huang, Sui Butterfield, Catherine Bielenberg, Diane Mostoslavsky, Gustavo Mulligan, Richard Folkman, Judah Panigrahy, Dipak TI PPAR alpha Deficiency in Inflammatory Cells Suppresses Tumor Growth SO PLOS ONE LA English DT Article AB Inflammation in the tumor bed can either promote or inhibit tumor growth. Peroxisome proliferator-activated receptor (PPAR)alpha is a central transcriptional suppressor of inflammation, and may therefore modulate tumor growth. Here we show that PPAR alpha deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of the endogenous angiogenesis inhibitor thrombospondin-1 and prevents tumor growth. Bone marrow transplantation and granulocyte depletion show that PPAR alpha expressing granulocytes are necessary for tumor growth. Neutralization of thrombospondin-1 restores tumor growth in PPAR alpha-deficient mice. These findings suggest that the absence of PPAR alpha activity renders inflammatory infiltrates tumor suppressive and, thus, may provide a target for inhibiting tumor growth by modulating stromal processes, such as angiogenesis. C1 [Kaipainen, Arja; Kieran, Mark W.; Huang, Sui; Butterfield, Catherine; Bielenberg, Diane; Folkman, Judah; Panigrahy, Dipak] Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. [Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Mostoslavsky, Gustavo; Mulligan, Richard] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Panigrahy, D (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Vasc Biol Program, Boston, MA 02115 USA. EM dipak.panigrahy@childrens.harvard.edu FU Stop & Shop Pediatric Brain Tumor Fund; C.J. Buckley Pediatric Brain Tumor Research Fund; Department of Defense Innovator Award [W81XWH-04-1-0316]; private philanthropic funds FX This study was supported by the Stop & Shop Pediatric Brain Tumor Fund and the C.J. Buckley Pediatric Brain Tumor Research Fund ( M. K.) and Department of Defense Innovator Award #W81XWH-04-1-0316 and private philanthropic funds (J.F.). NR 67 TC 41 Z9 42 U1 0 U2 0 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 FEB 28 PY 2007 VL 2 IS 2 AR e260 DI 10.1371/journal.pone.0000260 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DL UT WOS:000207444600020 PM 17327920 ER PT J AU AhnAllen, CG Nestor, PG McCarley, RW Shenton, ME AF AhnAllen, Christopher G. Nestor, Paul G. McCarley, Robert W. Shenton, Martha E. TI The role of retrieval inhibition in the associative memory impairment of schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE retrieval-induced forgetting; recognition memory; categorical dominance ID MODEL; INTERFERENCE; RECALL AB To examine retrieval-induced forgetting (RIF) in schizophrenia, subjects studied category-exemplar words taken from either strong or weak categories, and then practiced retrieval by completing category word-sterns on half of the word pairs. Patients had reduced recall and recognition, but showed the expected RIF effect of better recall of unpracticed items from unpracticed categories than for unpracticed items front practiced categories. By contrast, patients and controls showed differing RIF for recognition as a function of categorical dominance: whereas controls showed RIF only for dominant category exemplar word pairs, patients showed RIF for both dominant and weak categories. Different patterns of baseline practiced retrieval for weak associate pairs in schizophrenia may explain this finding. The results failed to support faulty RIF in the associative memory impairment of schizophrenia. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Harvard Univ, Sch Med,Brockton Div, Dept Psychiat,VA Boston Healthcare Syst, Clin Neurosci Div,Lab Neurosci, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp,Surg Planning Lab, Dept Radiol,MRI Div, Boston, MA 02115 USA. RP Nestor, PG (reprint author), Brockton VAMC, Psychiat 116A,940 Belmont St, Brockton, MA 02301 USA. EM paul.nestor@umb.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [R01 MH 40799, R01 MH 50740, R01 MH040799, R01 MH050740] NR 28 TC 10 Z9 11 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB 28 PY 2007 VL 150 IS 1 BP 43 EP 50 DI 10.1016/j.psychres.2006.07.001 PG 8 WC Psychiatry SC Psychiatry GA 149RX UT WOS:000245165400005 PM 17188366 ER PT J AU Morrow, DA de Lemos, JA AF Morrow, David A. de Lemos, James A. TI Benchmarks for the assessment of novel cardiovascular biomarkers SO CIRCULATION LA English DT Editorial Material ID C-REACTIVE PROTEIN; ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; PREDICTION; TROPONIN; STRATEGY; THERAPY; DISEASE; FUTURE C1 Harvard Univ, Dept Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75230 USA. RP Morrow, DA (reprint author), Harvard Univ, Dept Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp,Med Sch, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 14 TC 221 Z9 223 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP 949 EP 952 DI 10.1161/CIRCULATIONAHA.106.683110 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200005 PM 17325253 ER PT J AU Ross, JS Ho, VV Wang, YF Cha, SS Epstein, AJ Masoudi, FA Nallamothu, BK Krumholz, HM AF Ross, Joseph S. Ho, Vivian Wang, Yongfei Cha, Stephen S. Epstein, Andrew J. Masoudi, Frederick A. Nallamothu, Brahmajee K. Krumholz, Harlan M. TI Certificate of need regulation and cardiac catheterization appropriateness after acute myocardial infarction SO CIRCULATION LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 27-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med DE angioplasty; myocardial infarction; certificate of need; quality of health care; government regulation ID PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; QUALITY-OF-CARE; HEALTH-CARE; AMERICAN-COLLEGE; UNITED-STATES; MEDICARE BENEFICIARIES; CORONARY-ANGIOGRAPHY; ACC/AHA GUIDELINES; MORTALITY AB Background - Certificate of need (CON) regulation was introduced to control healthcare costs and improve quality of care in part by limiting the number of facilities providing complex medical care. Our objective was to examine whether rates of appropriate cardiac catheterization after admission for acute myocardial infarction varied between states with and without CON regulation of cardiac catheterization. Methods and Results - We performed a retrospective analysis of chart-abstracted data for 137 279 Medicare patients admitted for acute myocardial infarction between 1994 and 1996 at 4179 US acute-care hospitals. Using 3-level hierarchical generalized linear modeling adjusted for patient sociodemographic and clinical characteristics and physician and hospital characteristics, we compared catheterization rates within 60 days of admission for states ( and the District of Columbia) with (n = 32) and without (n = 19) CON regulation in the full cohort and stratified by catheterization appropriateness. Appropriateness was categorized as strongly, equivocally, or weakly indicated. We found CON regulation was associated with a borderline-significant lower rate of catheterization overall (45.8% versus 46.5%; adjusted risk ratio [RR] 0.91, 95% confidence interval 0.82 to 1.00, P = 0.06). After stratification by appropriateness, CON regulation was not associated with a significantly lower rate of catheterization among 63 823 patients with strong indications (49.9% versus 50.3%; adjusted RR 0.94, 95% confidence interval 0.86 to 1.02, P = 0.17). However, CON regulation was associated with significantly lower rates of catheterization among 65 077 patients with equivocal indication (45.0% versus 46.0%; adjusted RR 0.88, 95% confidence interval 0.78 to 1.00, P = 0.05) and among 8379 patients with weak indications (19.8% versus 21.8%; adjusted RR 0.84, 95% confidence interval 0.71 to 0.98, P = 0.04). Associations were weakened substantially after adjustment for hospital coronary artery bypass graft surgery or cardiac catheterization capability. Conclusions - CON regulation was associated with modestly lower rates of equivocally and weakly indicated cardiac catheterization after admission for acute myocardial infarction, but no significant differences existed in rates of strongly indicated catheterization. C1 CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. Rice Univ, Baker Inst Publ Policy, Houston, TX 77251 USA. Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Med, New Haven, CT USA. Yale Univ, Sch Med, Sect Hlth Policy & Adm, Dept Epidemiol & Publ Hlth, New Haven, CT USA. Univ Colorado, Denver Hlth Sci Ctr, Sect Cardiovasc Med, Dept Med,Denver Hlth Med Ctr, Denver, CO USA. Univ Colorado, Denver Hlth Sci Ctr, Colorado Hlth Outcomes Program, Dept Med, Denver, CO USA. Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. Ann Arbor VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Ross, JS (reprint author), CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM joseph.ross@mssm.edu FU NCI NIH HHS [OK0412SC]; NHLBI NIH HHS [R01 HL073825] NR 41 TC 19 Z9 19 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 FEB 27 PY 2007 VL 115 IS 8 BP 1012 EP 1019 DI 10.1161/CIRCULATIONAHA.106.658377 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200013 PM 17283258 ER PT J AU Brouwer, IA Raitt, MH Dullemeijer, C Kraemer, DF Zock, PL Morris, C Katan, MB Connor, WE Schouten, EG McAnulty, J AF Brouwer, Ingeborg A. Raitt, Merritt H. Dullemeijer, Carla Kraemer, Dale F. Zock, Peter L. Morris, Cynthia Katan, Martijn B. Connor, William E. Schouten, Evert G. McAnulty, John TI Effect of fish oil on ventricular tachyarrhythmia in patients with implantable defibrillators: A pooled analysis SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Wageningen Ctr Food Sci, Wageningen, Netherlands. Portland VA Med Ctr, Portland, OR USA. Oregon State Univ, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Vrije Univ Amsterdam, Inst Hlth Sci, Amsterdam, Netherlands. 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E274 EP E274 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200302 ER PT J AU Dublin, S Glazer, NL Smith, NL Psaty, BM Lumley, T Wiggins, KL Page, RL Heckbert, SR AF Dublin, Sascha Glazer, Nicole L. Smith, Nicholas L. Psaty, Bruce M. Lumley, Thomas Wiggins, Kerri L. Page, Richard L. Heckbert, Susan R. TI Diabetes mellitus is a risk factor for new-onset atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RI Page, Richard/L-5501-2014 OI Page, Richard/0000-0001-5603-1330 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E227 EP E227 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200078 ER PT J AU Fox, CS Hwang, SJ Massaro, JM Pou, KM Larson, MG Hoffmann, U O'Donnell, CJ AF Fox, Caroline S. Hwang, Shih-Jen Massaro, Joseph M. Pou, Karla M. Larson, Martin G. Hoffmann, Udo O'Donnell, Christopher J. TI Subcutaneous and visceral adipose tissue and their association with coronary and aortic artery calcification: The Framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E241 EP E241 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200143 ER PT J AU Hwang, SJ Yang, Q Larson, MG Benjamin, EJ Vasan, RS Meigs, JB Parikh, NI O'Donnell, CJ Levy, D Fox, CS AF Hwang, Shih-Jen Yang, Qiong Larson, Martin G. Benjamin, Emelia J. Vasan, Ramachandran S. Meigs, James B. Parikh, Nisha I. O'Donnell, Christopher J. Levy, Daniel Fox, Caroline S. TI Genome-wide association with renal function traits in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RI Yang, Qiong/G-5438-2014 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E223 EP E223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200061 ER PT J AU Ingelsson, E Sullivan, LM Murabito, JM Fox, CS Benjamin, EJ Polak, JF Meigs, JB Keyes, MJ Levy, D O'Donnell, CJ Wang, TJ D'Agostino, RB Wolf, PA Vasan, RS AF Ingelsson, Erik Sullivan, Lisa M. Murabito, Joanne M. Fox, Caroline S. Benjamin, Emelia J. Polak, Joseph F. Meigs, James B. Keyes, Michelle J. Levy, Daniel O'Donnell, Christopher J. Wang, Thomas J. D'Agostino, Ralph B. Wolf, Philip A. Vasan, Ramachandran S. TI Prevalence and prognostic significance of subclinical cardiovascular disease in individuals with the metabolic syndrome SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E218 EP E218 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200036 ER PT J AU O'Donnell, CJ Demissie, S Murabito, JM Fox, CS Hwang, SJ Wang, TJ Cupples, LA AF O'Donnell, Christopher J. Demissie, Serkalem Murabito, Joanne M. Fox, Caroline S. Hwang, Shih-Jen Wang, Thomas J. Cupples, L. Adrienne TI Deciphering genetic determinants for subclinical atherosclerosis in multiple arterial beds: Genome-wide association study in the NHLBI framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 NHLBI Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E294 EP E294 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200397 ER PT J AU Parashar, S Rumsfeld, JS Reid, KJ Spertus, JA Buchanan, D Wenger, NK Dawood, N Khizer, S Khan, BV Decker, C Garavalia, L Krumholz, HM Lichtman, JH Champney, K Bazari, RN Vaccarino, V AF Parashar, Susmita Rumsfeld, John S. Reid, Kimberly J. Spertus, John A. Buchanan, Donna Wenger, Nanette K. Dawood, Nazeera Khizer, Saadia Khan, Bobby V. Decker, Carole Garavalia, Linda Krumholz, Harlan M. Lichtman, Judith H. Champney, Kimberly Bazari, Rasha N. Vaccarino, Viola TI Women, depression, and outcome of myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Emory Univ, Atlanta, GA USA. Denver VA Med Ctr, Denver, CO USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Emory Univ, Atlanta, GA 30322 USA. Yale Univ, Sch Med, New Haven, CT USA. Henry Ford Hlth Syst, Detroit, MI 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E216 EP E217 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200031 ER PT J AU Parikh, NI Keyes, MJ Pou, KM Hamburg, N Larson, MG Vita, JA O'Donnell, CJ Vasan, RS Mitchell, GF Hoffmann, U Fox, CS Benjamin, EJ AF Parikh, Nisha I. Keyes, Michelle J. Pou, Karla M. Hamburg, Naomi Larson, Martin G. Vita, Joseph A. O'Donnell, Christopher J. Vasan, Ramachandran S. Mitchell, Gary F. Hoffmann, Udo Fox, Caroline S. Benjamin, Emelia J. TI Adiposity-related traits and endothelial function in the framingham offspring cohort SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst C1 Boston Univ, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E219 EP E219 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200040 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Fox, CS Manders, ES Murabito, J Massaro, JM Hoffmann, U O'Donnell, CJ AF Parikh, Nisha I. Hwang, Shih-Jen Larson, Martin G. Fox, Caroline S. Manders, Emily S. Murabito, Joanne Massaro, Joseph M. Hoffmann, Udo O'Donnell, Christopher J. TI Validated parental history of premature cardiovascular disease as a risk factor for coronary artery calcification in the framingham third-generation cohort SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Boston Univ, Sch Med, NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, NHLBI, Framingham Heart Study, Framingham, 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E217 EP E217 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200034 ER PT J AU Safford, MM Halanych, J Beall, J Durant, R Prineas, R Cushman, M Howard, G AF Safford, Monika M. Halanych, Jewell Beall, Jennifer Durant, Raegan Prineas, Ron Cushman, Mary Howard, George TI Medication adherence does not explain disparities in blood pressure control: The reasons for geographic and racial differences in stroke (REGARDS) study SO CIRCULATION LA English DT Meeting Abstract CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst C1 Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Samford Coll Pharm, Birmingham, AL USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Vermont, Burlington, VT USA. 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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 27 PY 2007 VL 115 IS 8 BP E288 EP E288 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 140CY UT WOS:000244482200368 ER PT J AU Dombi, E Solomon, J Gillespie, AJ Fox, E Balis, FM Patronas, N Korf, BR Babovic-Vuksanovic, D Packer, RJ Belasco, J Goldman, S Jakacki, R Kieran, M Steinberg, SM Widemann, BC AF Dombi, E. Solomon, J. Gillespie, A. J. Fox, E. Balis, F. M. Patronas, N. Korf, B. R. Babovic-Vuksanovic, D. Packer, R. J. Belasco, J. Goldman, S. Jakacki, R. Kieran, M. Steinberg, S. M. Widemann, B. C. TI NF1 plexiform neurofibroma growth rate by volumetric MRI - Relationship to age and body weight SO NEUROLOGY LA English DT Article ID SOLID TUMORS; PHASE-I AB Objective: To longitudinally analyze changes in plexiform neurofibroma (PN) volume in relation to age and body growth in children and young adults with neurofibromatosis type 1 and inoperable, symptomatic, or progressive PNs, using a sensitive, automated method of volumetric MRI analysis. Methods: We included patients 25 years of age and younger with PNs entered in a natural history study or in treatment trials who had volumetric MRI over >= 16 months. Results: We studied 49 patients (median age 8.3 years) with 61 PNs and a median evaluation period of 34 months (range 18 to 70). The PN growth rates varied among patients, but were constant within patients. Thirty-four patients (69%) experienced >= 20% increase in PN volume during the observation period. PN volume increased more rapidly than body weight over time (p = 0.026). Younger patients had the most rapid PN growth rate. Conclusions: Volume increase of plexiform neurofibromas is a realistic and meaningful trial endpoint. In most patients plexiform neurofibroma growth rate exceeded body growth rate. The youngest patients had the fastest plexiform neurofibroma growth rate, and clinical drug development should be directed toward this population. Age stratification for clinical trials for plexiform neurofibromas should be considered. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Med Numer Inc, Sterling, VA USA. NIH, Diagnost Radiol Dept, Ctr Clin, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Mayo Clin, Rochester, MN USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Biostat & Data Management Sect, CCR, Bethesda, MD 20892 USA. RP Dombi, E (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-5750,MSC 1101, Bethesda, MD 20892 USA. EM dombie@mail.nih.gov OI Kieran, Mark/0000-0003-2184-7692 FU Intramural NIH HHS NR 13 TC 54 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 27 PY 2007 VL 68 IS 9 BP 643 EP 647 DI 10.1212/01.wnl.0000250332.89420.e6 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 140DA UT WOS:000244482400004 PM 17215493 ER PT J AU Smith, EE Abdullah, AR Amirfarzan, H Schwamm, LH AF Smith, Eric E. Abdullah, Abdul R. Amirfarzan, Houman Schwamm, Lee H. TI Serum lipid profile on admission for ischemic stroke - Failure to meet national cholesterol education program adult treatment panel (NCEP-ATPIII) guidelines SO NEUROLOGY LA English DT Article ID OF-NEUROLOGY AFFIRMS; ATRIAL-FIBRILLATION; BLOOD-PRESSURE; PREVENTION; STATINS; ATTACK; ASSOCIATION; DISEASE; PREDICTION; ADHERENCE AB Objective: To determine the characteristics of patients with stroke/TIA whose admission low-density lipoprotein (LDL) levels were above goals defined by National Cholesterol Education Program Adult Treatment Panel (NCEP-ATPIII) guidelines. Methods: From January 1, 2003, to June 30, 2005, there were 1,212 discharges (1,033 stroke, 179 TIA), of whom 1,040/1,212 (86%) had lipid measurement. The preadmission individual LDL goal was determined using 2001 NCEP-ATPIII guidelines. Results: There were 284/1,040 (27%) whose measured LDL was greater than the individual preadmission LDL goal. Failure to be at goal was common even among those with previously diagnosed dyslipidemia (159/527, 30%) and those taking lipid- lowering agents (LLA) (71/370, 19%). LLA would have been indicated in 121/213 (57%) of those above LDL goal who were not already taking LLA, with optional consideration in 77/213 (36%). Lower LDL therapeutic targets were the strongest predictor, in a multivariable model, of failure to be at goal. Compared to LDL target < 160 (reference), the OR for LDL target < 130 was 6.4 (95% CI 3.4 to 12.0, p < 0.0001) and for LDL target < 100 was 26.2 (95% CI 13.3 to 51.5, p < 0.0001). An increased likelihood of being at goal was associated with preadmission LLA (OR 4.2, 95% CI 2.9 to 6.2, p < 0.0001) and increasing calendar time (OR 1.09 per 3-month period, 95% CI 1.03 to 1.15, p = 0.004). Conclusions: Many patients hospitalized with ischemic stroke/TIA, including those with known dyslipidemia and those taking lipid lowering agents, have measured low-density lipoprotein (LDL) that is higher than recommended by national guidelines. Patients at the greatest risk of cardiovascular events are the least likely to be at guideline-recommended LDL levels. C1 Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Stroke Serv, VBK 802,55 Fruit St, Boston, MA 02114 USA. EM eesmith@partners.org RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145 FU NINDS NIH HHS [K23 NS46327] NR 32 TC 20 Z9 23 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 FEB 27 PY 2007 VL 68 IS 9 BP 660 EP 665 DI 10.1212/01.wnl.0000255941.03761.dc PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 140DA UT WOS:000244482400007 PM 17325272 ER PT J AU Polo, JM Juszczynski, P Monti, S Cerchietti, L Ye, K Greally, JM Shipp, M Melnick, A AF Polo, Jose M. Juszczynski, Przemyslaw Monti, Stefano Cerchietti, Leandro Ye, Kenny Greally, John M. Shipp, Margaret Melnick, Ari TI Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE targeted therapy; transcriptional repression; ChIP on ChIP; integrative analysis; gene expression profiling ID GERMINAL-CENTER FORMATION; FALSE DISCOVERY RATE; LYMPHOCYTE DIFFERENTIATION; INFLAMMATION; PROMOTES; GENOME; MTA3 AB Diffuse large B cell lymphomas (DLBCLs) often express BCL6, a transcriptional repressor required for the formation of normal germinal centers. In a subset of DLBCLs, BCL6 is deregulated by chromosomal translocations or aberrant somatic hypermutation; in other tumors, BCL6 expression may simply reflect germinal center lineage. DLBCLs dependent on BCL6-regulated pathways should exhibit differential regulation of BCL6 target genes. Genomic array ChIP-on-chip was used to identify the cohort of direct BCL6 target genes. This set of genes was enriched in modulators of transcription, chromatin structure, protein ubiquitylation, cell cycle, and DNA damage responses. In primary DLBCLs classified on the basis of gene expression profiles, these BCL6 target genes were clearly differentially regulated in "BCR" tumors, a subset of DLBCLs with increased BCL6 expression and more frequent BCL6 translocations. In a panel of DLBCL cell lines analyzed by expression arrays and classified according to their gene expression profiles, only BCR tumors were highly sensitive to the BCL6 peptide inhibitor, BPI. These studies identify a discrete subset of DLBCLs that are reliant on BCL6 signaling and uniquely sensitive to BCL6 inhibitors. More broadly, these data show how genome-wide identification of direct target genes can identify tumors dependent on oncogenic transcription factors and amenable to targeted therapeutics. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Biostat, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med Genet, Bronx, NY 10461 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Broad Inst, Cambridge, MA 02141 USA. RP Shipp, M (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM margaret_shipp@dfci.harvard.edu; amelnick@aecom.yu.edu OI Monti, Stefano/0000-0002-9376-0660; Cerchietti, Leandro/0000-0003-0608-1350; Greally, John/0000-0001-6069-7960 FU NCI NIH HHS [P01 CA092625, R01 CA104348, P01CA092625] NR 29 TC 81 Z9 85 U1 1 U2 7 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 FEB 27 PY 2007 VL 104 IS 9 BP 3207 EP 3212 DI 10.1073/pnas.0611399104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142PG UT WOS:000244661400035 PM 17360630 ER PT J AU McLaughlin, ME Kruger, GM Slocum, KL Crowley, D Michaud, NA Huang, J Magendantz, M Jacks, T AF McLaughlin, Margaret E. Kruger, Genevieve M. Slocum, Kelly L. Crowley, Denise Michaud, Norman A. Huang, Jennifer Magendantz, Margaret Jacks, Tyler TI The Nf2 tumor suppressor reulates cell-cell adhesion during tissue fusion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neurofibromatosis type 2 ID NEURAL-TUBE CLOSURE; NEUROFIBROMATOSIS-2 GENE; TIGHT JUNCTIONS; MOUSE; MEMBRANE; SURVIVAL; MERLIN; PROLIFERATION; TUMORIGENESIS; LOCALIZATION AB Tissue fusion, the morphogenic process by which epithelial sheets are drawn together and sealed, has been extensively studied in Drosophila. However, there are unique features of mammalian tissue fusion that remain poorly understood. Notably, detachment and apoptosis occur at the leading front in mammals but not in invertebrates. We found that in the mouse embryo, expression of the Nf2 tumor suppressor, merlin, is dynamically regulated during tissue fusion: NO expression is low at the leading front before fusion and high across the fused tissue bridge. Mosaic Nf2 mutants exhibit a global defect in tissue fusion characterized by ectopic detachment and increased detachment-induced apoptosis (anoikis). By contrast with core components of the junctional complex, we find that merlin is required specifically for the assembly but not the maintenance of the junctional complex. Our work reveals that regulation of Nf2 expression is a previously unrecognized means of controlling adhesion at the leading front, thereby ensuring successful tissue fusion. C1 MIT, Ctr Canc Res, Boston, MA 02130 USA. MIT, Dept Biol, Boston, MA 02130 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Jacks, T (reprint author), MIT, Ctr Canc Res, 40 Ames St,E17-517, Boston, MA 02130 USA. EM tjacks@mit.edu NR 40 TC 30 Z9 30 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 FEB 27 PY 2007 VL 104 IS 9 BP 3261 EP 3266 DI 10.1073/pnas.0700044104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 142PG UT WOS:000244661400044 PM 17360635 ER PT J AU Herbert, KE Walkley, CR Winkler, IG Hendy, J Olsen, GH Yuan, YD Chandraratna, RAS Prince, HM Levesque, JP Purton, LE AF Herbert, Kirsten E. Walkley, Carl R. Winkler, Ingrid G. Hendy, Jean Olsen, Gernma Haines Yuan, Yang-Dar Chandraratna, Roshantha A. S. Prince, H. Miles Levesque, Jean-Pierre Purton, Louise E. TI Granulocyte colony-stimulating factor and an RARa specific agonist, VTP195183, synergize to enhance the mobilization of hematopoietic progenitor cells SO TRANSPLANTATION LA English DT Article DE retinoids; stem cell mobilization; granulocyte colony-stimulating factor; stem cell transplantation ID TRANS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; BLOOD STEM-CELLS; PERIPHERAL-BLOOD; BONE-MARROW; G-CSF; ALLOGENEIC TRANSPLANTATION; MYELOID PROGENITOR; RAPID MOBILIZATION; MULTIPLE-MYELOMA AB Background. Failure to mobilize adequate numbers of hematopoietic stem and progenitor cells (HSPC) is an important clinical problem. Since bone marrow (BM) neutrophils play a central role in HSPC mobilization, we hypothesized that granulocyte colony-stimulating factor (G-CSF)-mediated mobilization would be enhanced by further expanding the size of the BM granulocyte pool. Methods. We tested the potential of the retinoic acid receptor alpha (RAR alpha) specific agonist VTP195183, and the pan-RAR agonist all-trans retinoic acid (ATRA), to enhance G-CSF-mediated mobilization of HSPC, in two mouse strains. Results. Pretreatment of mice with VTP195183 significantly increased the number of leukocytes, colony-forming cells, and early engrafting hematopoietic stem cells (HSC) mobilized in the blood in response to G-CSF. In contrast, ATRA had only a marginal effect on G-CSF-induced mobilization. HSPC mobilization synergy between VTP195183 and G-CSF occurred only when mice were preconditioned with VTP195183 prior to G-CSF. This preconditioning was shown to increase the numbers of granulocyte/macrophage progenitors in the BM. Treatment with VTP195183 and G-CSF was accompanied by enhanced levels of active neutrophil proteases in the BM extracellular fluid compared to G-CSF treatment alone. Conclusions. VTP195183 treatment increases the numbers of immature granulocyte progenitors in BM and subsequently synergizes to enhance G-CSF-mediated mobilization of HSPC. These data demonstrate a novel approach to improve G-CSF-induced mobilization by accelerating granulocyte maturation in the BM. These findings are currently being tested in a clinical trial of VTP195183 plus G-CSF for mobilization of HSPC in human patients. C1 Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Univ Melbourne, Dept Med, Melbourne, Vic, Australia. Vitae Pharmaceut, Irvine, CA USA. RP Purton, LE (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, CPZN 4265A,185 Cambridge St, Boston, MA 02114 USA. EM lpurton@partners.org RI Levesque, Jean-Pierre/C-5426-2011; Winkler, Ingrid/F-3263-2011 OI Levesque, Jean-Pierre/0000-0002-7299-6025; Winkler, Ingrid/0000-0001-6026-3572 NR 55 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 27 PY 2007 VL 83 IS 4 BP 375 EP 384 DI 10.1097/01.tp.0000251376.75347.b4 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 140VU UT WOS:000244535600003 PM 17318068 ER PT J AU Jagsi, R Butterton, JR Starr, R Tarbell, NJ AF Jagsi, Reshma Butterton, Joan R. Starr, Rebecca Tarbell, Nancy J. TI A targeted intervention for the career development of women in academic medicine SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID COMPENSATION; PHYSICIANS; INSIGHTS; FACULTY; GENDER C1 Massachusetts Gen Hosp, Ctr Fac Dev & Partners Off Womens Careers, Boston, MA 02114 USA. RP Tarbell, NJ (reprint author), Massachusetts Gen Hosp, Ctr Fac Dev & Partners Off Womens Careers, 370 Bulfinch, Boston, MA 02114 USA. EM ntarbell@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 14 TC 11 Z9 11 U1 1 U2 6 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 FEB 26 PY 2007 VL 167 IS 4 BP 343 EP 345 DI 10.1001/archinte.167.4.343 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 139XU UT WOS:000244467000008 PM 17325295 ER PT J AU Bayes-Genis, A Lloyd-Jones, DM van Kimmenade, RRJ Lainchbury, JG Richards, AM Ordonez-Llanos, J Santalo, M Pinto, YM Januzzi, JL AF Bayes-Genis, Antoni Lloyd-Jones, Donald M. van Kimmenade, Roland R. J. Lainchbury, John G. Richards, A. Mark Ordonez-Llanos, Jordi Santalo, Miquel Pinto, Yigal M. Januzzi, James L., Jr. TI Effect of body mass index on diagnostic and prognostic usefulness of amino-terminal pro-brain natriuretic peptide in patients with acute dyspnea SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHRONIC HEART-FAILURE; EMERGENCY-DEPARTMENT; OBESE-PATIENTS; MORTALITY; HYPERTENSION; PARADOX; IMPACT AB Background: Amino (N)-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnostic and prognostic evaluation in patients with dyspnea. An inverse relationship between body mass index (BMI); (calculated as weight in kilograms divided by height in meters squared) and NT-proBNP concentrations has been described. Methods: One thousand one hundred three patients presenting to the emergency department with acute dyspnea underwent analysis. Patients were classified into the following 3 BMI categories: lean (< 25.0), overweight (25.0-29.9), and obese (>= 30.0). Results: The NT-proBNP concentrations in the overweight and obese groups were significantly lower than in the lean patients, regardless of the presence of acute heart failure (P <. 001). The positive likelihood ratio for an NT-proBNP-based diagnosis of acute heart failure was 5.3 for a BMI lower than 25.0, 13.3 for a BMI of 25.0 to 29.9, and 7.5 for a BMI of 30.0 or higher. A cut point of 300 ng/L had very low negative likelihood ratios in all 3 BMI categories (0.02, 0.03, and 0.08, respectively). Among decedents, the NT-proBNP concentrations were lower in the overweight and obese patients compared with the lean subjects (P <.001). Nonetheless, a single cut point of 986 ng/L strongly predicted 1-year mortality across the 3 BMI strata, regardless of the presence of acute heart failure (hazard ratios, 2.22, 3.06, and 3.69 for BMIs of < 25.0, 25.0-29.9, and >= 30.0, respectively; all P <. 004); the risk associated with a high NT-proBNP concentration was detected early and was sustained to a year after baseline in all 3 BMI strata (all P <.001). Conclusions: In patients with and without acute heart failure, the NT-proBNP concentrations are relatively lower in overweight and obese patients with acute dyspnea. Despite this, the NT-proBNP concentration retains its diagnostic and prognostic capacity across all BMI categories. C1 Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Christchurch Sch Med & Hlth Sci, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand. Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. Northwestern Univ, Dept Prevent Med, Div Cardiol, Chicago, IL 60611 USA. Northwestern Univ, Bluhm Cardiovasc Inst, Chicago, IL 60611 USA. Univ Autonoma Barcelona, Dept Cardiol, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain. Univ Autonoma Barcelona, Dept Biochem & Mol Biol, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain. Univ Autonoma Barcelona, Dept Emergency Med, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Lloyd-Jones, Donald/C-5899-2009; Ordonez-Llanos, Jorge/A-9335-2010; Ordonez-Llanos, Jordi/B-4961-2011; Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; Bayes-Genis, Antoni/0000-0002-3044-197X; NR 25 TC 57 Z9 57 U1 0 U2 2 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 FEB 26 PY 2007 VL 167 IS 4 BP 400 EP 407 DI 10.1001/archinte.167.4.400 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 139XU UT WOS:000244467000019 PM 17325303 ER PT J AU Deshpande, V Lauwers, GY AF Deshpande, Vikram Lauwers, Gregory Y. TI Cystic pancreatic endocrine tumor - A variant commonly confused with cystic adenocarcinoma SO CANCER CYTOPATHOLOGY LA English DT Article DE pancreatic endocrine tumor; cystic pancreatic neoplasm; fine-needle aspiration biopsy; endoscopic ultrasound; cytology ID FINE-NEEDLE-ASPIRATION; ISLET-CELL TUMOR; CYTOLOGIC FEATURES; NEOPLASMS; DIAGNOSIS AB BACKGROUND. Most cystic pancreatic neoplasms are Currently evaluated by all endoscopic Ultrasound-guided fine-needle aspiration biopsy (FNAB). In the authors' experience, FNAB of cystic pancreatic endocrine tumors (PETs) frequently causes diagnostic difficulties, partly because of unexpected overlapping features with cystic ductal adenocarcinomas. METHODS. The authors identified 5 histologically confirmed cystic PETs that were evaluated by FNAB and compared their cytomorphologic features to cystic ductal adenocarcinomas (n = 5) and solid PETs (n = 39) of the pancreas. RESULTS. Cytologically, 2 of the aspirates of cystic PETs were devoid of tumor cells whereas the other 3 were variably cellular and composed of cohesive aggregates of monomorphic cellular elements with variably coarse chromatin. Tumor necrosis and unclear membrane irregularities were not identified in cystic PETs. Alternatively, in contrast to PETs, cystic ductal adenocarcinomas were characterized by nuclear pleomorphism, nuclear membrane irregularities, and tumor necrosis. CONCLUSIONS. Given the clinical implications, awareness of cystic PETs and their deceptive cytologic features would assist in distinguishing these lesions from cystic ductal adenocarcinomas. C1 Massachusetts Gen Hosp, Dept Pathol, Cytol & Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Cytol & Gastrointestinal Pathol Serv, Warren 831B,55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 24 TC 13 Z9 13 U1 0 U2 0 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 FEB 25 PY 2007 VL 111 IS 1 BP 47 EP 53 DI 10.1002/cncr.22422 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 138BX UT WOS:000244338700006 PM 17173321 ER PT J AU Weingart, SN Flug, J Brouillard, D Morwayl, L Partridge, A Bartel, S Shulman, LN Connor, M AF Weingart, Saul N. Flug, Jonathan Brouillard, Daniela Morway, Laurinda Partridge, Ann Bartel, Sylvia Shulman, Lawrence N. Connor, Maureen TI Oral chemotherapy safety practices at US cancer centres: questionnaire survey SO BRITISH MEDICAL JOURNAL LA English DT Article AB Objective To characterise current safety practices forth e use of oral chemotherapy. Design Written questionnaire survey of pharmacy directors of cancer centres. Setting Comprehensive cancer centres in the United States. Results Respondents from 42 (78%) of 54 eligible centres completed the survey, after consulting with 89 colleagues. Clinicians at 29 centres used handwritten prescriptions, two used preprinted paper prescriptions, and six used electronic systems for most oral chemotherapy prescribing. For six commonly used oral chemotherapies, on average 10 centres required a diagnosis on the prescription, 11 required the protocol number, four required the cycle number, nine required double checking by a second clinician, 14 required a calculation of body surface area, and 14 required a calculation of dose per square metre of body surface area. Only a third of centres requested patients' written informed consent when oral chemotherapy was given off protocol. Nearly a quarter (10) of centres had no formal process for monitoring patients' adherence. In the past year respondents at 10 centres reported at least one serious adverse drug event related to oral chemotherapy, and respondents at 13 centres reported a serious near miss. Conclusion Few of the safeguards routinely used for infusion chemotherapy have been adopted for oral chemotherapy at US cancer centres. There is currently no consensus at these centres about safe medication practices for oral chemotherapy. C1 Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. EM saul_weingart@dfci.harvard.edu FU AHRQ HHS [1 K08 HS 11644] NR 11 TC 42 Z9 42 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD FEB 24 PY 2007 VL 334 IS 7590 BP 407 EP 409 DI 10.1136/bmj.39069.489757.55 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 142MQ UT WOS:000244654400032 PM 17223629 ER PT J AU Griffin, WC Middaugh, LD Tyor, WR AF Griffin, W. C., III Middaugh, L. D. Tyor, W. R. TI Chronic cocaine exposure in the SCID mouse model of HIV encephalitis SO BRAIN RESEARCH LA English DT Article DE AIDS; dementia; HIV-associated dementia; animal model; drug abuse ID IMMUNODEFICIENCY-VIRUS ENCEPHALITIS; MONONUCLEAR CELL COCULTURES; C57BL/6J MICE; ANTIRETROVIRAL THERAPY; LOCOMOTOR STIMULATION; DRUG USE; REPLICATION; DEPENDENCE; INFECTION; SENSITIZATION AB Clinical and preclinical evidence suggests that cocaine exposure hastens progression of the HIV disease process. An established active, euphoric dose of cocaine (20 mg/kg) was administered to SCID mice according to a regimen consistent with exposure to the drug by cocaine-abusing HIV-infected patients to determine the effects of cocaine on four previously established pathological characteristics of HIV encephalitis: cognitive deficits, fatigue, astrogliosis, and microgliosis. Mice were intracranially inoculated with either HIV-infected, or uninfected macrophages and then injected with either cocaine or saline in a 2 (Infection)x2 (Cocaine) factorial design. Cognition was assessed by acquisition and retention of a spatially cued learning task. Fatigue was assessed by monitoring motor activity following a 2 min forced swim. Mice were then sacrificed to determine the extent of astrogliosis and microgliosis in the four groups. Results indicated that in comparison to uninfected controls, HIV positive mice had increased astrogliosis and microgliosis, cognitive deficits, and recovered more slowly from fatigue. However, despite evidence that the cocaine exposure regimen activated the central nervous system and had long-term CNS effects, the drug did not alter the behavioral or the neuropathological deficits noted in HIV-infected SCID mice. (c) 2006 Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Tyor, WR (reprint author), Ralph H Johnson VAMC, Neurol Serv, 109 Bee St, Charleston, SC 29401 USA. EM tyorwr@musc.edu FU BLRD VA [I01 BX001506]; NIDA NIH HHS [T32 DA07288, R01 DA11870, T32 DA007288] NR 35 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 23 PY 2007 VL 1134 IS 1 BP 214 EP 219 DI 10.1016/j.brainres.2006.11.059 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 142GZ UT WOS:000244638700025 PM 17189621 ER PT J AU Bernstein, BE Meissner, A Lander, ES AF Bernstein, Bradley E. Meissner, Alexander Lander, Eric S. TI The mammalian epigenome SO CELL LA English DT Review ID EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; NON-CPG METHYLATION; DNA METHYLATION; EPIGENETIC CONTROL; GENE-EXPRESSION; DEVELOPMENTAL REGULATORS; DROSOPHILA-MELANOGASTER; COMPREHENSIVE ANALYSIS; HISTONE MODIFICATION C1 Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM bbernstein@partners.org RI jia, xu/A-8386-2016 NR 97 TC 1071 Z9 1128 U1 17 U2 176 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD FEB 23 PY 2007 VL 128 IS 4 BP 669 EP 681 DI 10.1016/j.cell.2007.01.033 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148TX UT WOS:000245098600010 PM 17320505 ER PT J AU Hellman, A Chess, A AF Hellman, Asaf Chess, Andrew TI Gene body-specific methylation on the active X chromosome SO SCIENCE LA English DT Article ID DNA METHYLATION; HPRT GENE; INACTIVATION; CELLS; SITES; WIDE; ARABIDOPSIS AB Differential DNA methylation is important for the epigenetic regulation of gene expression. Allele-specific methylation of the inactive X chromosome has been demonstrated at promoter CpG islands, but the overall pattern of methylation on the active X (Xa) and inactive X ( Xi) chromosomes is unknown. We performed allele-specific analysis of more than 1000 informative loci along the human X chromosome. The Xa displays more than two times as much allele-specific methylation as Xi. This methylation is concentrated at gene bodies, affecting multiple neighboring CpGs. Before X inactivation, all of these Xa gene body-methylated sites are biallelically methylated. Thus, a bipartite methylation-demethylation program results in Xa-specific hypomethylation at gene promoters and hypermethylation at gene bodies. These results suggest a relationship between global methylation and expression potentiality. C1 Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Hellman, A (reprint author), Harvard Univ, Sch Med, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM hellman@chgr.mgh.harvard.edu; chess@chgr.mgh.harvard.edu NR 24 TC 359 Z9 372 U1 5 U2 30 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 23 PY 2007 VL 315 IS 5815 BP 1141 EP 1143 DI 10.1126/science.1136352 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138UA UT WOS:000244387600041 PM 17322062 ER PT J AU Lin, JY Fisher, DE AF Lin, Jennifer Y. Fisher, David E. TI Melanocyte biology and skin pigmentation SO NATURE LA English DT Review ID INDUCED DNA-DAMAGE; HUMAN MELANOCORTIN-1 RECEPTOR; RANDOMIZED CONTROLLED-TRIAL; SUNSCREEN USE; C-KIT; STIMULATING HORMONE; MALIGNANT-MELANOMA; STEM-CELL; CUTANEOUS MELANOMA; MASTER REGULATOR AB Melanocytes are phenotypically prominent but histologically inconspicuous skin cells. They are responsible for the pigmentation of skin and hair, and thereby contribute to the appearance of skin and provide protection from damage by ultraviolet radiation. Pigmentation mutants in various species are highly informative about basic genetic and developmental pathways, and provide important clues to the processes of photoprotection, cancer predisposition and even human evolution. Skin is the most common site of cancer in humans. Continued understanding of melanocyte contributions to skin biology will hopefully provide new opportunities for the prevention and treatment of skin diseases. C1 Childrens Hosp Boston, Dana Farber Canc Inst, Melanoma Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Combined Program Dermatol, Boston, MA 02115 USA. Childrens Hosp Boston, Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Childrens Hosp Boston, Dana Farber Canc Inst, Melanoma Program, 44 Binney St, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu NR 100 TC 345 Z9 370 U1 12 U2 90 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 22 PY 2007 VL 445 IS 7130 BP 843 EP 850 DI 10.1038/nature05660 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138CR UT WOS:000244341200034 PM 17314970 ER PT J AU Stanger, BZ Tanaka, AJ Melton, DA AF Stanger, Ben Z. Tanaka, Akemi J. Melton, Douglas A. TI Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver SO NATURE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; GENE-EXPRESSION; TRANSGENIC MICE; BETA-CATENIN; GROWTH; DIFFERENTIATION; COMPLEMENTATION; EPITHELIUM; LINEAGE; FGF10 AB The determinants of vertebrate organ size are poorly understood, but the process is thought to depend heavily on growth factors and other environmental cues. In the blood and central nervous system, for example, organ mass is determined primarily by growth-factor-regulated cell proliferation and apoptosis to achieve a final target size. Here, we report that the size of the mouse pancreas is constrained by an intrinsic programme established early in development, one that is essentially not subject to growth compensation. Specifically, final pancreas size is limited by the size of the progenitor cell pool that is set aside in the developing pancreatic bud. By contrast, the size of the liver is not constrained by reductions in the progenitor cell pool. These findings show that progenitor cell number, independently of regulation by growth factors, can be a key determinant of organ size. C1 Harvard Univ, Stem Cell Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Howard Hughes Med Inst, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Melton, DA (reprint author), Harvard Univ, Stem Cell Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM bstanger@mail.med.upenn.edu; dmelton@harvard.edu NR 42 TC 195 Z9 197 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 22 PY 2007 VL 445 IS 7130 BP 886 EP 891 DI 10.1038/nature05537 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138CR UT WOS:000244341200042 PM 17259975 ER PT J AU Marson, A Kretschmer, K Frampton, GM Jacobsen, ES Polansky, JK Maclsaac, KD Levine, SS Fraenkel, E von Boehmer, H Young, RA AF Marson, Alexander Kretschmer, Karsten Frampton, Garrett M. Jacobsen, Elizabeth S. Polansky, Julia K. Maclsaac, Kenzie D. Levine, Stuart S. Fraenkel, Ernest von Boehmer, Harald Young, Richard A. TI Foxp3 occupancy and regulation of key target genes during T-cell stimulation SO NATURE LA English DT Article ID LYMPHOID TYROSINE PHOSPHATASE; TRANSCRIPTION FACTOR FOXP3; AUTOIMMUNE-DISEASES; SCURFIN; ENTEROPATHY; EXPRESSION; RECEPTOR; ANTIGEN; PROTEIN; VARIANT AB Foxp3(+) CD4(+) CD25(+) regulatory T (T-reg) cells are essential for the prevention of autoimmunity(1,2). T-reg cells have an attenuated cytokine response to T-cell receptor stimulation, and can suppress the proliferation and effector function of neighbouring T cells(3,4). The forkhead transcription factor Foxp3 ( forkhead box P3) is selectively expressed in T-reg cells, is required for T-reg development and function, and is sufficient to induce a Treg phenotype in conventional CD4(+) CD25(-) T cells(5-8). Mutations in Foxp3 cause severe, multi-organ autoimmunity in both human and mouse(9-11). FOXP3 can cooperate in a DNA-binding complex with NFAT ( nuclear factor of activated T cells) to regulate the transcription of several known target genes(12). However, the global set of genes regulated directly by Foxp3 is not known and consequently, how this transcription factor controls the gene expression programme for T-reg function is not understood. Here we identify Foxp3 target genes and report that many of these are key modulators of T-cell activation and function. Remarkably, the predominant, although not exclusive, effect of Foxp3 occupancy is to suppress the activation of target genes on T-cell stimulation. Foxp3 suppression of its targets appears to be crucial for the normal function of T-reg cells, because overactive variants of some target genes are known to be associated with autoimmune disease. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM Harald_von_Boehmer@dfci.harvard.edu; young@wi.mit.edu RI Kretschmer, Karsten/E-8174-2010; Young, Richard/F-6495-2012; OI Young, Richard/0000-0001-8855-8647; Polansky, Julia K./0000-0003-4727-2540; Fraenkel, Ernest/0000-0001-9249-8181 FU NCI NIH HHS [P01 CA109901, P01 CA109901-067138]; NHGRI NIH HHS [R01 HG002668, R01 HG002668-04A1] NR 30 TC 408 Z9 441 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 22 PY 2007 VL 445 IS 7130 BP 931 EP 935 DI 10.1038/nature05478 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 138CR UT WOS:000244341200053 PM 17237765 ER PT J AU Hinson, JT Fantin, VR Schonberger, J Breivik, N Siem, G McDonough, B Sharma, P Keogh, I Godinho, R Santos, F Esparza, A Nicolau, Y Selvaag, E Cohen, BH Hoppel, CL Tranebjaerg, L Eavey, RD Seidman, JG Seidman, CE AF Hinson, J. Travis Fantin, Valeria R. Schoenberger, Jost Breivik, Noralv Siem, Geir McDonough, Barbara Sharma, Pankaj Keogh, Ivan Godinho, Ricardo Santos, Felipe Esparza, Alfonso Nicolau, Yamileth Selvaag, Edgar Cohen, Bruce H. Hoppel, Charles L. Tranebjaerg, Lisbeth Eavey, Roland D. Seidman, J. G. Seidman, Christine E. TI Missense mutations in the BCS1L gene as a cause of the Bjornstad syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MITOCHONDRIAL RESPIRATORY-CHAIN; SENSORINEURAL HEARING-LOSS; LETHAL METABOLIC-DISORDER; PILI TORTI; GRACILE SYNDROME; IRON OVERLOAD; PROTEIN; COMPLEX; MEMBRANE; DISEASE AB Background: The Bjornstad syndrome, an autosomal recessive disorder associated with sensorineural hearing loss and pili torti, is caused by mutation of a previously unidentified gene on chromosome 2q34-36. Methods: Refined genetic mapping and DNA sequencing of 44 genes between D2S2210 and D2S2244 revealed BCS1L mutations. Functional analyses elucidated how BCS1L mutations cause the Bjornstad syndrome. Results: BCS1L encodes a member of the AAA family of ATPases that is necessary for the assembly of complex III in the mitochondria. In addition to the Bjornstad syndrome, BCS1L mutations cause complex III deficiency and the GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders. Patients with the Bjornstad syndrome have mutations that alter residues involved in protein-protein interactions, whereas mutations in patients with complex III deficiency alter ATP-binding residues, as deduced from the crystal structure of a related AAA-family ATPase. Biochemical studies provided evidence to support this model: complex III deficiency mutations prevented ATP-dependent assembly of BCS1L-associated complexes. All mutant BCS1L proteins disrupted the assembly of complex III, reduced the activity of the mitochondrial electron-transport chain, and increased the production of reactive oxygen species. However, only mutations associated with complex III deficiency increased mitochondrial content, which further increased the production of reactive oxygen species. Conclusions: BCS1L mutations cause disease phenotypes ranging from highly restricted pili torti and sensorineural hearing loss (the Bjornstad syndrome) to profound multisystem organ failure (complex III deficiency and the GRACILE syndrome). All BCS1L mutations disrupted the assembly of mitochondrial respirasomes (the basic unit for respiration in human mitochondria), but the clinical expression of the mutations was correlated with the production of reactive oxygen species. Mutations that cause the Bjornstad syndrome illustrate the exquisite sensitivity of ear and hair tissues to mitochondrial function, particularly to the production of reactive oxygen species. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Hosp Wurzburg, Wurzburg, Germany. Inst Clin Biochem & Pathobiochem, Wurzburg, Germany. Aalesund Hosp, Alesund, Norway. Hammersmith Hosp, London, England. Univ London Imperial Coll Sci Technol & Med, London, England. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Pontificia Univ Catholica Minas Gerais, Belo Horizonte, MG, Brazil. Univ Washington, Seattle, WA 98195 USA. Bispebjerg Hosp, DK-2400 Copenhagen, Denmark. Cleveland Clin, Brain Tumor Inst, Cleveland, OH 44106 USA. Louis Stokes Vet Affairs Med Ctr, Cleveland, OH USA. Univ Copenhagen, Inst Med Biochem & Genet, Copenhagen, Denmark. Univ Tromso Hosp, N-9012 Tromso, Norway. RP Seidman, CE (reprint author), Harvard Univ, Sch Med, Dept Genet, Room 256 NRB,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cseidman@genetics.med.harvard.edu RI KEOGH, IVAN/M-2704-2016; OI KEOGH, IVAN/0000-0001-6358-6377; Santos, Felipe/0000-0002-3523-665X NR 33 TC 90 Z9 96 U1 1 U2 4 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 FEB 22 PY 2007 VL 356 IS 8 BP 809 EP 819 DI 10.1056/NEJMoa055262 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 137XQ UT WOS:000244326700007 PM 17314340 ER PT J AU Kaufman, DS Saksena, MA Young, RH Tabatabaei, S AF Kaufman, Donald S. Saksena, Mansi A. Young, Robert H. Tabatabaei, Shahin TI A 28-year-old man with a mass in the testis - Mixed germ-cell tumor (embryonal carcinoma, teratoma, and scant yolk-sac tumor). SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LYMPH-NODE DISSECTION; LONG-TERM SURVIVORS; TESTICULAR CANCER; CLINICAL STAGE; CHEMOTHERAPY; RISK; DIAGNOSIS; TOXICITY; SURVEILLANCE; IMPACT C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Urol, Cambridge, MA 02138 USA. RP Kaufman, DS (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. NR 23 TC 1 Z9 1 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 FEB 22 PY 2007 VL 356 IS 8 BP 842 EP 849 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 137XQ UT WOS:000244326700012 PM 17314344 ER PT J AU Moza, B Varma, AK Buonpane, RA Zhu, P Herfst, CA Nicholson, MJ Wilbuer, AK Seth, NP Wucherpfennig, KW McCormick, JK Kranz, DM Sundberg, EJ AF Moza, Beenu Varma, Ashok K. Buonpane, Rebecca A. Zhu, Penny Herfst, Christine A. Nicholson, Melissa J. Wilbuer, Anne-Kathrin Seth, Nilufer P. Wucherpfennig, Kai W. McCormick, John K. Kranz, David M. Sundberg, Eric J. TI Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1 SO EMBO JOURNAL LA English DT Article DE protein-protein interaction; superantigen; surface plasmon resonance; T-cell activity; X-ray crystallography ID TOXIC-SHOCK-SYNDROME; STAPHYLOCOCCAL-ENTEROTOXIN-B; RECEPTOR-BETA-CHAIN; MHC CLASS-II; AFFINITY MATURATION; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; SIGNALING COMPLEXES; ANTIBODY-RESPONSE; COMBINING SITE AB Superantigens (SAGs) bind simultaneously to major histocompatibility complex (MHC) and T-cell receptor (TCR) molecules, resulting in the massive release of inflammatory cytokines that can lead to toxic shock syndrome (TSS) and death. A major causative agent of TSS is toxic shock syndrome toxin-1 (TSST-1), which is unique relative to other bacterial SAGs owing to its structural divergence and its stringent TCR specificity. Here, we report the crystal structure of TSST-1 in complex with an affinity-matured variant of its wild-type TCR ligand, human T-cell receptor beta chain variable domain 2.1. From this structure and a model of the wild-type complex, we show that TSST-1 engages TCR ligands in a markedly different way than do other SAGs. We provide a structural basis for the high TCR specificity of TSST-1 and present a model of the TSST-1-dependent MHC-SAG-TCR T-cell signaling complex that is structurally and energetically unique relative to those formed by other SAGs. Our data also suggest that protein plasticity plays an exceptionally significant role in this affinity maturation process that results in more than a 3000-fold increase in affinity. C1 Boston Biomed Res Inst, Watertown, MA 02472 USA. Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. Univ Western Ontario, Lawson Hlth Res Inst, Dept Immunol & Microbiol, London, ON N6A 3K7, Canada. Harvard Univ, Sch Med, Dana Farber Canc Res Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Sundberg, EJ (reprint author), Boston Biomed Res Inst, 64 Grove St, Watertown, MA 02472 USA. EM sundberg@bbri.org RI McCormick, John/E-4232-2015; OI MOZA JALALI, Beenu/0000-0003-0954-3485; McCormick, John/0000-0003-3742-7289 FU NIAID NIH HHS [AI55882, AI064177, R01 AI064177, R21 AI055882, R01 AI064611, AI064611]; NIGMS NIH HHS [T32 GM 07283, T32 GM007283] NR 48 TC 35 Z9 35 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 21 PY 2007 VL 26 IS 4 BP 1187 EP 1197 DI 10.1038/sj.emboj.7601531 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 138TZ UT WOS:000244387500025 PM 17268555 ER PT J AU Mitchell, GF Vasan, RS Keyes, MJ Parise, H Wang, TJ Larson, MG D'Agostino, RB Kannel, WB Levy, D Benjamin, EJ AF Mitchell, Gary F. Vasan, Ramachandran S. Keyes, Michelle J. Parise, Helen Wang, Thomas J. Larson, Martin G. D'Agostino, Ralph B., Sr. Kannel, William B. Levy, Daniel Benjamin, Emelia J. TI Pulse pressure and risk of new-onset atrial fibrillation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NATRIURETIC PEPTIDE LEVELS; SYSTOLIC HYPERTENSION; DIASTOLIC DYSFUNCTION; BLOOD-PRESSURE; HEART-FAILURE; HEALTHY-MEN; FRAMINGHAM; POPULATION; ADULTS; AGE AB Context Atrial fibrillation (AF) is responsible for considerable morbidity and mortality, making identification of modifiable risk factors a priority. Increased pulse pressure, a reflection of aortic stiffness, increases cardiac load and may increase AF risk. Objective To examine relations between pulse pressure and incident AF. Design, Setting, and Participants Prospective, community-based observational cohort in Framingham, Mass, including 5331 Framingham Heart Study participants aged 35 years and older and initially free from AF (median age, 57 years; 55% women). Main Outcome Measures Incident AF. Results AF developed in 698 participants (13.1%) a median of 12 years after pulse pressure assessment. Cumulative 20-year AF incidence rates were 5.6% for pulse pressure of 40 mm Hg or less (25th percentile) and 23.3% for pulse pressure greater than 61 mm Hg (75th percentile). In models adjusted for age, sex, baseline and time-dependent change in mean arterial pressure, and clinical risk factors for AF (body mass index, smoking, valvular disease, diabetes, electrocardiographic left ventricular hypertrophy, hypertension treatment, and prevalent myocardial infarction or heart failure), pulse pressure was associated with increased risk for AF (adjusted hazard ratio [HR], 1.26 per 20-mm Hg increment; 95% confidence interval [CI], 1.12-1.43; P < .001). In contrast, mean arterial pressure was unrelated to incident AF (adjusted HR, 0.96 per 10-mm Hg increment; 95% CI, 0.88-1.05; P = .39). Systolic pressure was related to AF (HR, 1.14 per 20-mm Hg increment; 95% CI, 1.04-1.25; P = .006); however, if diastolic pressure was added, model fit improved and the diastolic relation was inverse (adjusted HR, 0.87 per 10-mm Hg increment; 95% CI, 0.78-0.96; P = .01), consistent with a pulse pressure effect. Among patients with interpretable echocardiographic images, the association between pulse pressure and AF persisted in models that adjusted for baseline left atrial dimension, left ventricular mass, and left ventricular fractional shortening (adjusted HR, 1.23; 95% CI, 1.09-1.39; P = .001). Conclusion Pulse pressure is an important risk factor for incident AF in a community-based sample. Further research is needed to determine whether interventions that reduce pulse pressure will limit the growing incidence of AF. C1 Cardiovasc Engn Inc, Waltham, MA 02453 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Natl Heart Lung & Blood Inst Framingham Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 51 Sawyer Rd,Suite 100, Waltham, MA 02453 USA. EM garyfmitchell@mindspring.com OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K24-HL-04334, N01-HC-25195, R01-HL60040, R01-HL70100] NR 42 TC 154 Z9 160 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 FEB 21 PY 2007 VL 297 IS 7 BP 709 EP 715 DI 10.1001/jama.297.7.709 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 137KI UT WOS:000244291100022 PM 17312290 ER PT J AU Maciejewski, PK Zhang, BH Block, SD Prigerson, HG AF Maciejewski, Paul K. Zhang, Baohui Block, Susan D. Prigerson, Holly G. TI An empirical examination of the stage theory of grief SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SPOUSAL BEREAVEMENT; DEPRESSION; DEATH; SCALE AB Context The stage theory of grief remains a widely accepted model of bereavement adjustment still taught in medical schools, espoused by physicians, and applied in diverse contexts. Nevertheless, the stage theory of grief has previously not been tested empirically. Objective To examine the relative magnitudes and patterns of change over time post-loss of 5 grief indicators for consistency with the stage theory of grief. Design, Setting, and Participants Longitudinal cohort study (Yale Bereavement Study) of 233 bereaved individuals living in Connecticut, with data collected between January 2000 and January 2003. Main Outcome Measures Five rater-administered items assessing disbelief, yearning, anger, depression, and acceptance of the death from 1 to 24 months postloss. Results Counter to stage theory, disbelief was not the initial, dominant grief indicator. Acceptance was the most frequently endorsed item and yearning was the dominant negative grief indicator from 1 to 24 months postloss. In models that take into account the rise and fall of psychological responses, once rescaled, disbelief decreased from an initial high at 1 month postloss, yearning peaked at 4 months postloss, anger peaked at 5 months postloss, and depression peaked at 6 months postloss. Acceptance increased throughout the study observation period. The 5 grief indicators achieved their respective maximum values in the sequence (disbelief, yearning, anger, depression, and acceptance) predicted by the stage theory of grief. Conclusions Identification of the normal stages of grief following a death from natural causes enhances understanding of how the average person cognitively and emotionally processes the loss of a family member. Given that the negative grief indicators all peak within approximately 6 months postloss, those who score high on these indicators beyond 6 months postloss might benefit from further evaluation. C1 Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Psychiat, Womens Hlth Res & Magnet Resonance Res Ctr, New Haven, CT USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St SW,G440A, Boston, MA 02115 USA. EM holly_prigerson@dfci.harvard.edu FU NCI NIH HHS [CA106370, R01 CA106370]; NIMH NIH HHS [MH56529, MH63892]; NINDS NIH HHS [NS044316] NR 30 TC 167 Z9 172 U1 10 U2 60 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 FEB 21 PY 2007 VL 297 IS 7 BP 716 EP 723 DI 10.1001/jama.297.7.716 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 137KI UT WOS:000244291100023 PM 17312291 ER PT J AU Prada, CM Garcia-Alloza, M Betensky, RA Zhang-Nunes, SX Greenberg, SM Bacskai, BJ Frosch, MP AF Prada, Claudia M. Garcia-Alloza, Monica Betensky, Rebecca A. Zhang-Nunes, Sandy X. Greenberg, Steven M. Bacskai, Brian J. Frosch, Matthew P. TI Antibody-mediated clearance of amyloid-beta peptide from cerebral amyloid angiopathy revealed by quantitative in vivo imaging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE immunotherapy; CAA; neurodegeneration; in vivo imaging; Alzheimer's disease; amyloid ID TRANSGENIC MOUSE MODEL; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; IMMUNIZATION; MICE; IMMUNOTHERAPY; MICROHEMORRHAGE; NEUROPATHOLOGY; PROGRESSION; PATHOLOGY AB Cerebral amyloid angiopathy (CAA) is the accumulation of amyloid-beta peptide (A beta) in the vessel wall of arteries in the brain. Because CAA is commonly associated with Alzheimer's disease (AD), characterized by parenchymal deposition of the same peptide in the form of senile plaques, there is considerable interest in the relationship of the two deposits in generating human disease. The study of CAA is of particular importance for immunotherapeutic approaches to AD, because reports of anti-A beta immunotherapy in mice and humans have suggested that, whereas CAA appeared resistant to clearance, its response to this treatment promoted potential adverse effects, including meningoencephalitis. We used multiphoton microscopy and longitudinal imaging to monitor CAA in a mouse model of amyloid deposition to evaluate the effects of anti-A beta passive immunotherapy. We found detectable clearance of CAA deposits within 1 week after a single administration of antibody directly to the brain, an effect that was short-lived. Chronic administration of antibody over 2 weeks led to more robust clearance without evidence of hemorrhage or other destructive changes. We found that the progressive clearance of A beta from vessels follows distinct kinetics from what has been previously reported for clearance of plaques (parenchymal deposits of A beta). This quantitative in vivo imaging approach directly demonstrates that CAA in a transgenic mouse model can be cleared with an optimized immunotherapy. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Unit, 114 16th St,2850, Charlestown, MA 02129 USA. EM bbacskai@partners.org FU NIA NIH HHS [AG020570, AG21084]; NIBIB NIH HHS [EB00768] NR 28 TC 45 Z9 47 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 21 PY 2007 VL 27 IS 8 BP 1973 EP 1980 DI 10.1523/JNEUROSCI.5426-06.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 138SA UT WOS:000244381400018 PM 17314293 ER PT J AU Henderson, TO Whitton, J Stovall, M Mertens, AC Mitby, P Friedman, D Strong, LC Hammond, S Neglia, JP Meadows, AT Robison, L Diller, L AF Henderson, Tara O. Whitton, John Stovall, Marilyn Mertens, Ann C. Mitby, Pauline Friedman, Debra Strong, Louise C. Hammond, Sue Neglia, Joseph P. Meadows, Anna T. Robison, Leslie Diller, Lisa TI Secondary sarcomas in childhood cancer survivors: A report from the childhood cancer survivor study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID 2ND MALIGNANT NEOPLASMS; BONE SARCOMAS; ADOLESCENT CANCER; 5-YEAR SURVIVORS; PRIMARY TUMORS; SOFT-TISSUE; RISK; CHEMOTHERAPY; OSTEOSARCOMA; RADIATION AB Background Childhood cancer survivors are at increased risk for the development of secondary sarcomas. Exposure to radiation therapy is a known risk factor for the development of these sarcomas. Other risk factors for secondary sarcomas have not been well described for childhood cancer survivors. We analyzed a large cohort of childhood cancer survivors to determine the true incidence of secondary sarcomas and to examine factors associated with the risk of developing secondary sarcomas, Methods The history of secondary sarcomas in 14372 participants in the Childhood Cancer Survivor Study was determined from self-reports in three questionnaires. Risk of secondary sarcoma was evaluated by use of standardized incidence ratios (SIRs) and excess absolute risks (EARs) as calculated by use of data from the Surveillance, Epidemiology, and End Results Program. Cox regression models were used to estimate hazard ratios of developing subsequent sarcomas. Hazard ratios were reported as relative risks (RRs). Results We identified 108 patients with sarcomas that were diagnosed a median of 11 years after the diagnosis of childhood cancer. The risk of sarcoma was more than ninefold higher among childhood cancer survivors than among the general population (SIR = 9.02, 95% confidence interval [Cl] = 7.44 to 10.93). The excess absolute risk of secondary sarcoma was 32.5 per 100000 person-years (95% Cl = 26.1 to 40.3 per 100000 person-years). Higher standardized incidence ratios and excess absolute risks were associated with young age at primary diagnosis, primary sarcoma diagnosis, and a family history of cancer. In a multivariable model, increased risk of secondary sarcoma was associated with radiation therapy (RR = 3.1, 95% Cl = 1.5 to 6.2), with a primary diagnosis of sarcoma (RR = 10.1, 95% Cl = 4.7 to 21.8), with a history of other secondary neoplasms (FIR = 2.2, 95% Cl = 1.1 to 4.5), and with treatment with higher doses of anthracyclines (RR = 2.3, 95% Cl = 1.2 to 4.3) or alkylating agents (RR = 2.2, 95% Cl = 1.1 to 4.6). Conclusion Childhood cancer survivors appear to be at increased risk for secondary sarcomas compared with general population rates. C1 Univ Chicago, Dept Pediat, Hematol Oncol Sect, Pritzker Sch Med, Chicago, IL 60637 USA. Fred Hutchinson Canc Res Ctr, Dept Biostat, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Childrens Hosp, Dept Lab Med, Columbus, OH 43205 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Henderson, TO (reprint author), Univ Chicago, Dept Pediat, Hematol Oncol Sect, Pritzker Sch Med, 5841 S Maryland Ave,MC 4060, Chicago, IL 60637 USA. EM thenderson@uchicago.edu FU NCI NIH HHS [U24 CA55727] NR 30 TC 96 Z9 98 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 21 PY 2007 VL 99 IS 4 BP 300 EP 308 DI 10.1093/jnci/djk052 PG 9 WC Oncology SC Oncology GA 140RL UT WOS:000244523800010 PM 17312307 ER PT J AU Najt, P Nicoletti, M Chen, HH Hatch, JP Caetano, SC Sassie, RB Axelson, D Brambilla, P Keshavan, MS Ryan, ND Birmaher, B Soares, JC AF Najt, Pablo Nicoletti, Mark Chen, Hua Hsuan Hatch, John P. Caetano, Sheila C. Sassie, Roberto B. Axelson, David Brambilla, Paolo Keshavan, Macheri S. Ryan, Neal D. Birmaher, Boris Soares, Jair C. TI Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder SO NEUROSCIENCE LETTERS LA English DT Article DE orbitofrontal cortex; adolescents; bipolar disorder; MRI; mood disorders ID MOOD DISORDERS; MAJOR DEPRESSION; ESTROGEN; GENDER; SCHIZOPHRENIA; RELIABILITY; VALIDITY; VOLUME AB Imaging studies indicate smaller orbitofrontal cortex (OFC) volume in mood disorder patients compared with healthy subjects. We sought to determine whether child and adolescent patients with bipolar disorder have smaller OFC volumes than healthy controls. Fourteen children and adolescents meeting DSM-IV criteria for bipolar disorder (six males and eight females with a mean age +/- S.D. = 15.5 +/- 3.2 years) and 20 healthy controls (11 males and nine females with mean age +/- S.D. = 16.9 +/- 3.8 years) were studied. Orbitofrontal cortex volume was measured using magnetic resonance imaging. Male bipolar patients had smaller gray matter volumes in medial (p = 0.044), right medial (0.037) and right (p = 0.032) lateral OFC subdivisions compared to male controls. In contrast, female patients had larger gray matter volumes in left (p = 0.03), lateral (p = 0.012), left lateral (p = 0.007), and trends for larger volumes in right lateral and left medial OFC subdivisions compared with female controls. Male patients exhibit smaller gray matter volumes, while female patients exhibit larger volumes in some OFC sub-regions. Gender differences in OFC abnormalities may be involved in illness pathophysiology among young bipolar patients. (c) 2007 Published by Elsevier Ireland Ltd. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat MC 7792, Div Mood & Anxiety Disorders,MOOD CNS Program, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78284 USA. Univ Sao Paulo, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat MC 7792, Div Mood & Anxiety Disorders,MOOD CNS Program, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010; Caetano, Sheila/H-5010-2012 OI brambilla, paolo/0000-0002-4021-8456; Caetano, Sheila/0000-0001-8403-7078 FU NCRR NIH HHS [RR02057]; NIMH NIH HHS [K23 MH001736, MH 01736, MH 069774, MH 30915, MH 59929, P30 MH030915, P30 MH055123, R01 MH059929, R01 MH069774] NR 21 TC 40 Z9 40 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 21 PY 2007 VL 413 IS 3 BP 183 EP 186 DI 10.1016/j.neulet.2006.10.016 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 143ZB UT WOS:000244763800001 PM 17276600 ER PT J AU Mori, S Kanematsu, N Asakura, H Endo, M AF Mori, Shinichiro Kanematsu, Nobuyuki Asakura, Hiroshi Endo, Masahiro TI Projection-data based temporal maximum attenuation computed tomography: determination of internal target volume for lung cancer against intra-fraction motion SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID CT SCANS; TUMOR MOTION; PERFORMANCE EVALUATION; RADIATION-THERAPY; REAL-TIME; RADIOTHERAPY; RECONSTRUCTION; ARTIFACTS; TRACKING; PRECISE AB The concept of internal target volume (ITV) is highly significant in radiotherapy for the lung, an organ which is hampered by organ motion. To date, different methods to obtain the ITV have been published and are therefore available. To define ITV, we developed a new method by adapting a time filter to the four-dimensional CT scan technique (4DCT) which is projection-data processing (4D projection data maximum attenuation (4DPM)), and compared it with reconstructed image processing (4D image maximum intensity projection (4DIM)) using a phantom and clinical evaluations. 4DIM and 4DPM captured accurate maximum intensity volume (MIV), that is tumour encompassing volume, easily. Although 4DIM increased the CT number 1.8 times higher than 4DPM, 4DPM provided the original tumour CT number for MIV via a reconstruction algorithm. In the patient with lung fibrosis honeycomb, the MIV with 4DIM is 0.7 cm larger than that for cine imaging in the cranio-caudal direction. 4DPM therefore provided an accurate MIV independent of patient characteristics and reconstruction conditions. These findings indicate the usefulness of 4DPM in determining ITV in radiotherapy. C1 Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 2638555, Japan. Accelerator Engn Corp, Inage Ku, Chiba 2630043, Japan. Natl Inst Radiol Sci, Dept Planning & Management, Inage Ku, Chiba 2638555, Japan. RP Mori, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX 3, Boston, MA 02114 USA. EM smori1@partners.org RI Kanematsu, Nobuyuki/B-9130-2008; OI Kanematsu, Nobuyuki/0000-0002-2534-9933; Mori, Shinichiro/0000-0002-0412-4399 NR 32 TC 5 Z9 5 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD FEB 21 PY 2007 VL 52 IS 4 BP 1027 EP 1038 DI 10.1088/0031-9155/52/4/011 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 143IN UT WOS:000244714100011 PM 17264368 ER PT J AU Koizumi, A Zeck, G Ben, YX Masland, RH Jakobs, TC AF Koizumi, Amane Zeck, Guenther Ben, Yixin Masland, Richard H. Jakobs, Tatjana C. TI Organotypic Culture of Physiologically Functional Adult Mammalian Retinas SO PLOS ONE LA English DT Article AB Background. The adult mammalian retina is an important model in research on the central nervous system. Many experiments require the combined use of genetic manipulation, imaging, and electrophysiological recording, which make it desirable to use an in vitro preparation. Unfortunately, the tissue culture of the adult mammalian retina is difficult, mainly because of the high energy consumption of photoreceptors. Methods and Findings. We describe an interphase culture system for adult mammalian retina that allows for the expression of genes delivered to retinal neurons by particle-mediated transfer. The retinas retain their morphology and function for up to six days-long enough for the expression of many genes of interest-so that effects upon responses to light and receptive fields could be measured by patch recording or multielectrode array recording. We show that a variety of genes encoding pre- and post-synaptic marker proteins are localized correctly in ganglion and amacrine cells. Conclusions. In this system the effects on neuronal function of one or several introduced exogenous genes can be studied within intact neural circuitry of adult mammalian retina. This system is flexible enough to be compatible with genetic manipulation, imaging, cell transfection, pharmacological assay, and electrophysiological recordings. C1 [Koizumi, Amane; Masland, Richard H.; Jakobs, Tatjana C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Zeck, Guenther] Max Planck Inst Neurobiol, Martinsried, Germany. [Ben, Yixin] Burke Inst, White Plains, NY USA. RP Jakobs, TC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM Jakobs@helix.mgh.harvard.edu RI Koizumi, Amane/E-7771-2011; Zeck, Gunther/H-7419-2013; OI Zeck, Gunther/0000-0003-3998-9883; Jakobs, Tatjana/0000-0002-8104-9206 FU NIH [RO1-017169] FX Supported by NIH grant RO1-017169. RHM is a Senior Investigator of Research to Prevent Blindness. The funding institution had no part in the design of the study, data collection, or the preparation of the manuscript. NR 40 TC 33 Z9 34 U1 0 U2 4 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 FEB 21 PY 2007 VL 2 IS 2 AR e221 DI 10.1371/journal.pone.0000221 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DK UT WOS:000207444500002 PM 17311097 ER PT J AU Linden, HM Haskell, CM Green, SJ Osborne, CK Sledge, GW Shapiro, CL Ingle, JN Lew, D Hutchins, LF Livingston, RB Martino, S AF Linden, Hannah M. Haskell, Charles M. Green, Stephanie J. Osborne, C. Kent Sledge, George W., Jr. Shapiro, Charles L. Ingle, James N. Lew, Danika Hutchins, Laura F. Livingston, Robert B. Martino, Silvana TI Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: Final analysis from INT-0137 (S9313) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL ADJUVANT BREAST; CHEMOTHERAPY; DOXORUBICIN; EPIRUBICIN; LEUKEMIA; TRIAL; FLUOROURACIL; THERAPY AB Purpose We conducted a phase III randomized study of two adjuvant treatment schedules of doxorubicin ( A) and cyclophosphamide ( C) in early-stage breast cancer to determine if administration of sequential single agents (A --> C) results in superior disease-free survival (DFS) and overall survival ( OS) versus the same total dose given in combination (AC). Patients and Methods High-risk node-negative or low-risk node-positive breast cancer patients received AC given: (arm I) concurrently (AC) doxorubicin 54 mg/m(2) and cyclophosphamide 1.2 g/m(2) intravenously (IV) every 3 weeks for six cycles; or ( arm II) in sequence ( A --> C) doxorubicin 40.5 mg/m(2) IV days 1 and 2 every 3 weeks for four cyles followed by cyclophosphamide 2.4 gm/m(2) IV every 2 weeks for three cycles. Total dose and duration were identical, but the intensity of each drug was increased on A --> C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics. All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy. Results Between 1994 and 1997, 3,176 patients were randomly assigned. Arms were well balanced; 48% of eligible patients were node-negative and 48% were estrogen receptor - positive. No significant differences in OS or DFS were observed; 5-year estimates of OS (95% CI) were 88% (87% to 90%) on AC and 89% (87% to 91%) on A --> C. Grade 4 hematologic toxicity was greater on A --> C, but nonhematological grade 4 was similar. Conclusion The overall result does not support superiority of dose-intense sequenced single agents. The greater toxicity of higher doses of single agents does not support their sequential use. C1 SW Oncol Grp, Ctr Stat, Puget Sound Oncol Consortium, Seattle, WA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Angeles Clin & Res Inst, Santa Monica, CA USA. RP Linden, HM (reprint author), SW Oncol Grp SWOG9313, Operat Off, 14980 Omicron Dr, San Antonio, TX 78245 USA. FU NCI NIH HHS [CA35090, CA32291, CA31946, CA27057, CA25224, CA20319, CA76447, CA76429, CA74647, CA68183, CA67575, CA63845, CA58861, CA58658, CA58416, CA52654, CA49883, CA46282, CA45560, CA45450, CA45377, CA38926, CA37981, CA35431, CA35192, CA32102, CA22433, CA21115, CA04919, CA04920, CA12644, CA13612, CA14028, CA16385, CA76462, CA76132, CA63844, CA58686, CA58415, CA46441, CA46368, CA46113, CA42777, CA35261, CA35119] NR 25 TC 23 Z9 23 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 FEB 20 PY 2007 VL 25 IS 6 BP 656 EP 661 DI 10.1200/JCO.2006.07.0847 PG 6 WC Oncology SC Oncology GA 138SY UT WOS:000244384000009 PM 17308269 ER PT J AU Ryan, TD Rothstein, EC Aban, I Tallaj, JA Husain, A Lucchesi, PA Dell'Italia, LJ AF Ryan, Thomas D. Rothstein, Emily C. Aban, Inmaculada Tallaj, Jose A. Husain, Ahsan Lucchesi, Pamela A. Dell'Italia, Louis J. TI Left ventricular eccentric remodeling and matrix loss are mediated by bradykinin and precede cardiomyocyte elongation in rats with volume overload SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MITRAL-REGURGITATION; METALLOPROTEINASE ACTIVITY; HEART-FAILURE; DOG; HYPERTROPHY; ACTIVATION; CHYMASE; CELLS; ALPHA AB Objectives We hypothesized that left ventricular (LV) remodeling and matrix loss in volume overload (VO) are mediated by bradykinin (BK) and exacerbated by chronic angiotensin-converting enzyme (ACE) inhibition. Background Chronic ACE inhibition increases anti-fibrotic BK and does not attenuate LV remodeling in pure VO. The relative contribution of changes in extracellular matrix versus cardiomyocyte elongation in acute and chronic LV chamber remodeling during VO is unknown. Methods Echocardiography, LV collagen content, and isolated cardiomyocytes were studied in rats after aortocaval fistula (ACF) of 12 h, 2 and 5 days, and 4, 8, and 15 weeks. We also studied ACF rats after BK2 receptor (BK2R) blockade (2 days) or ACE inhibition (4 weeks). Results At 2 days after ACF, LV end-diastolic dimension (LVEDD)/wall thickness was increased, and LV interstitial collagen was decreased by 50% without cardiornyocyte elongation. The BK2R blockade prevented collagen loss and normalized LVEDD/wall thickness. From 4 to 15 weeks after ACF, interstitial collagen decreased by 30% and left ventricular end-systolic (LVES) dimension increased despite normal LVES pressure and isolated cardiomyocyte function. The ACE inhibition did not decrease LVEDD/wall thickness, further decreased LV interstitial collagen, and did not improve LV fractional shortening despite decreased LVES pressure. Conclusions Immediately after ACF induction, eccentric LV remodeling is mediated by interstitial collagen loss without cardiomyocyte elongation. Acute BK2R blockade prevents eccentric LV remodeling and improves function. Chronic ACE inhibition does not prevent eccentric LV remodeling or improve function. These findings suggest that ACE inhibitor-mediated increase in LV BK exacerbates matrix loss and explains why ACE inhibition is ineffective in VO. C1 Univ Alabama, Ctr Heart Failure Res, Dept Physiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Biophys, Birmingham, AL 35294 USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Dell'Italia, LJ (reprint author), Univ Alabama, Ctr Heart Failure Res, Dept Physiol, 432 BMR2,901 19th St S, Birmingham, AL 35294 USA. EM loudell@uab.edu RI Lucchesi, Pamela/E-3558-2011; Husain, Ahsan/J-6861-2012 OI Husain, Ahsan/0000-0003-3426-3469 FU NHLBI NIH HHS [5T32HL07918-05, P50HL077100, R01HL063318, R01HL54816, R01HL60707] NR 23 TC 59 Z9 62 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 20 PY 2007 VL 49 IS 7 BP 811 EP 821 DI 10.1016/j.jacc.2006.06.083 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 137VE UT WOS:000244319900011 PM 17306712 ER PT J AU Kurth, T Everett, BM Buring, JE Kase, CS Ridker, PM Gaziano, JM AF Kurth, T. Everett, B. M. Buring, J. E. Kase, C. S. Ridker, P. M. Gaziano, J. M. TI Lipid levels and the risk of ischemic stroke in women SO NEUROLOGY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; SERUM-CHOLESTEROL; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; APOLIPOPROTEIN-B AB Objective: To evaluate the association between total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol to HDL-C ratio, and non-HDL-C with the risk of ischemic stroke in a large cohort of apparently healthy women. Methods: Prospective cohort study among 27,937 US women aged >= 45 years participating in the Women's Health Study who provided baseline blood samples. Stroke occurrence was self-reported and confirmed by medical record review. We categorized plasma lipid measurements into quintiles. We used Cox proportional hazards models to evaluate the association between lipids and risk of ischemic stroke. Results: During 11 years of follow-up, 282 ischemic strokes occurred. All lipid levels were strongly associated with increased risk of ischemic stroke in age-adjusted models. The association attenuated particularly for HDL-C after adjustment for potential confounders. For the comparison of the highest to the lowest quintile, the multivariable-adjusted hazard ratios (95% CI; p for trend across mean quintile values) of ischemic stroke were 2.27 (1.43, 3.60; p(trend) < 0.001) for total cholesterol; 1.74 (1.14, 2.66; ptrend = 0.003) for LDL-C; 0.78 (0.52, 1.17; p(trend) = 0.27) for HDL-C; 1.65 (1.06, 2.58; p(trend) = 0.02) for the total cholesterol to HDL-C ratio; and 2.45 (1.54, 3.91; p(trend) < 0.001) for non-HDL-C. Conclusions: In this large cohort of apparently healthy women, total cholesterol, low-density lipoprotein cholesterol, the total cholesterol to high-density lipoprotein cholesterol ratio, and non-high-density lipoprotein cholesterol were significantly associated with increased risk of ischemic stroke. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Ctr Cardiovasc Dis Prevent, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Donald W Reynolds Ctr Cardiovasc Res, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02215 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. RP Kurth, T (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [CA-47988, R01 CA047988]; NHLBI NIH HHS [R01 HL043851] NR 40 TC 83 Z9 94 U1 0 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 FEB 20 PY 2007 VL 68 IS 8 BP 556 EP 562 DI 10.1212/01.wnl.0000254472.41810.0d PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 137DT UT WOS:000244273900005 PM 17310025 ER PT J AU Shedlock, AM Botka, CW Zhao, SY Shetty, J Zhang, TT Liu, JS Deschavanne, PJ Edward, SV AF Shedlock, Andrew M. Botka, Christopher W. Zhao, Shaying Shetty, Jyoti Zhang, Tingting Liu, Jun S. Deschavanne, Patrick J. Edward, Scott V. TI Phylogenomics of nonavian reptiles and the structure of the ancestral amniote genorne SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BAC; Reptilia; retroelement; isochore; intron ID EVOLUTIONARY DYNAMICS; VERTEBRATE EVOLUTION; MOLECULAR PHYLOGENY; AVIAN GENOME; SEQUENCE; TURTLES; SIZE; CR-1; MICROSATELLITES; MITOCHONDRIAL AB We report results of a megabase-scale phylogenomic analysis of the Reptilia, the sister group of mammals. Large-scale end-sequence scanning of genomic clones of a turtle, alligator, and lizard reveals diverse, mammal-like landscapes of retroelements and simple sequence repeats (SSRs) not found in the chicken. Several global genomic traits, including distinctive phylogenetic lineages of CR1-like long interspersed elements (LINEs) and a paucity of A-T rich SSRs, characterize turtles and archosaur genomes, whereas higher frequencies of tandem repeats and a lower global GC content reveal mammal-like features in Anolis. Nonavian reptile genomes also possess a high frequency of diverse and novel 50-bp unit tandem duplications not found in chicken or mammals. The frequency distributions of approximate to 65,000 8-meroligonucleotides suggest that rates of DNA-word frequency change are an order of magnitude slower in reptiles than in mammals. These results suggest a diverse array of interspersed and SSRs in the common ancestor of amniotes and a genomic conservatism and gradual loss of retroelements in reptiles that culminated in the minimalist chicken genome. C1 Harvard Univ, Dept Organism & Evolutionary Biol, Museum Comparat Zool, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Inst Genom Res, Rockville, MD 20850 USA. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. INSERM, Equipe Bioinformat Genom & Mol, F-75005 Paris, France. RP Shedlock, AM (reprint author), Harvard Univ, Dept Organism & Evolutionary Biol, Museum Comparat Zool, 26 Oxford St, Cambridge, MA 02138 USA. EM shedlock@oeb.harvard.edu OI Edwards, Scott/0000-0003-2535-6217 NR 43 TC 86 Z9 90 U1 0 U2 9 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 FEB 20 PY 2007 VL 104 IS 8 BP 2767 EP 2772 DI 10.1073/pnas.0606204104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 140NC UT WOS:000244511200038 PM 17307883 ER PT J AU Stone, KE Chiquette, E Chilton, RJ AF Stone, Kenneth E. Chiquette, Elaine Chilton, Robert J. TI Diabetic endovascular disease: Role of coronary artery revascularization SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DRUG-ELUTING STENTS; MYOCARDIAL-INFARCTION; CONTROLLED-TRIALS; GLYCEMIC CONTROL; BLOOD-INSTITUTE; RISK-FACTORS; MELLITUS; IMPLANTATION; RESTENOSIS; ATHEROSCLEROSIS AB This century brings a pandemic of diabetes mellitus, with marked increases in early-accelerated atherosclerosis. When asymptomatic patients with diabetes present for evaluation, they have more extensive coronary atherosclerosis, lower ejection fractions, higher rates of previous cardiac events, and more silent ischemia than the normal population. The challenge faced by clinicians is to accurately identify asymptomatic patients with diabetes who have significant coronary ischemia that would benefit from revascularization. Diabetic endovascular disease has all the high-risk features to promote atherosclerosis and coronary occlusion: hyperglycemia-induced endothelial dysfunction, impaired fibrinolysis, increased platelet aggregation, plaque instability, dysfunctional arterial remodeling, and fibrotic and calcified coronary arteries. The optimal revascularization strategy for patients with diabetes is an ongoing debate. The advent of drug-eluting stents has changed the landscape, and some have suggested that the current role of coronary artery bypass grafting may be reduced by as much as 46%. Unfortunately, there is limited evidence from randomized, controlled trials that reflects current practice and could guide clinicians in making the best choices for patients with diabetes and coronary disease. It is hoped that ongoing trials-including Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D), Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM), and Coronary Artery Revascularisation in Diabetes (CARDia)-will answer many of the remaining questions. Still, the best treatment includes lifestyle modification and early prevention strategies with global risk reduction. (c) 2007 Elsevier Inc. All rights reserved. C1 Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. RP Chilton, RJ (reprint author), S Texas Vet Hlth Care Syst, 7400 Merton Minter Dr, San Antonio, TX 78229 USA. EM Chilton@uthscsa.edu NR 55 TC 11 Z9 15 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 19 PY 2007 VL 99 IS 4A SU S BP 105B EP 112B DI 10.1016/j.amjcard.2006.11.024 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 143FR UT WOS:000244705900012 PM 17307063 ER PT J AU Maillard, MH Cotta-De-Almeida, V Takeshima, F Nguyen, DD Michetti, P Nagler, C Bhan, AK Snapper, SB AF Maillard, Michel H. Cotta-de-Almeida, Vinicius Takeshima, Fuminao Nguyen, Deanna D. Michetti, Pierre Nagler, Cathryn Bhan, Atul K. Snapper, Scott B. TI The Wiskott-Aldrich syndrome protein is required for the function of CD4(+)CD25(+)Foxp3(+) regulatory T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; INTESTINAL INFLAMMATION; IMMUNOLOGICAL SYNAPSE; IN-VITRO; SUPPRESSOR FUNCTION; DEFICIENCY LEADS; CUTTING EDGE; ACTIVATION; MICE; ANTIGEN AB The Wiskott-Aldrich syndrome, a primary human immunodeficiency, results from defective expression of the hematopoietic-specific cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASP). Because CD4(+)CD25(+)Foxp3(+) naturally occurring regulatory T (nTreg) cells control autoimmunity, we asked whether colitis in WASP knockout (WKO) mice is associated with aberrant development/function of nTreg cells. We show that WKO mice have decreased numbers of CD4(+)CD25(+)Foxp3(+) nTreg cells in both the thymus and peripheral lymphoid organs. Moreover, we demonstrate that WKO nTreg cells are markedly defective in both their ability to ameliorate the colitis induced by the transfer of CD45RB(hi) T cells and in functional suppression assays in vitro. Compared with wild-type (WT) nTreg cells, WKO nTreg cells show significantly impaired homing to both mucosal (mesenteric) and peripheral sites upon adoptive transfer into WT recipient mice. Suppression defects may be independent of antigen receptor-mediated actin rearrangement because both WT and WKO nTreg cells remodeled their actin cytoskeleton inefficiently upon T cell receptor stimulation. Preincubation of WKO nTreg cells with exogenous interleukin (IL)-2, combined with antigen receptor-mediated activation, substantially rescues the suppression defects. WKO nTreg cells are also defective in the secretion of the immunomodulatory cytokine IL-10. Overall, our data reveal a critical role for WASP in nTreg cell function and implicate nTreg cell dysfunction in the autoimmunity associated with WASP deficiency. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Rheumatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Univ Lausanne Hosp, Dept Med, Div Gastroenterol & Hepatol, CH-1005 Lausanne, Switzerland. Fundacao Oswaldo Cruz, Oswaldo Cruz Inst, Dept Ultrastruct & Cell Biol, BR-21040360 Rio De Janeiro, Brazil. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM ssnapper@hms.harvard.edu RI Cotta-de-Almeida, Vinicius/G-3939-2012 FU NHLBI NIH HHS [HL59561, P01 HL059561]; NIAID NIH HHS [AI50950, R01 AI050950, R56 AI050950]; NIDDK NIH HHS [DK47677, P30 DK043351, R01 DK047677, DK43351] NR 51 TC 112 Z9 114 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 19 PY 2007 VL 204 IS 2 BP 381 EP 391 DI 10.1084/jem.2006.1338 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 140KP UT WOS:000244504100017 PM 17296786 ER PT J AU Alcaide, P Jones, TG Lord, GM Glimcher, LH Hallgren, J Arinobu, Y Akashi, K Paterson, AM Gurish, MA Luscinskas, FW AF Alcaide, Pilar Jones, Tatiana G. Lord, Graham M. Glimcher, Laurie H. Hallgren, Jenny Arinobu, Yojiro Akashi, Koichi Paterson, Alison M. Gurish, Michael A. Luscinskas, Francis W. TI Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; V-ALPHA-14I NKT CELLS; TRICHINELLA-SPIRALIS; IFN-GAMMA; PROTECTIVE IMMUNITY; BONE-MARROW; TRANSENDOTHELIAL MIGRATION; HELMINTH INFECTION; LINEAGE COMMITMENT; FLOW CONDITIONS AB The transcription factor T-bet was identified in CD4(+) T cells, and it controls interferon gamma production and T helper type 1 cell differentiation. T-bet is expressed in certain other leukocytes, and we recently showed (Lord, G.M., R.M. Rao, H. Choe, B.M. Sullivan, A.H. Lichtman, F.W. Luscinskas, and L.H. Glimcher. 2005. Blood. 106:3432-3439) that it regulates T cell trafficking. We examined whether T-bet influences homing of mast cell progenitors (MCp) to peripheral tissues. Surprisingly, we found that MCp homing to the lung or small intestine in T-bet(-/-) mice is reduced. This is reproduced in adhesion studies using bone marrow-derived MCs (BMMCs) from T-bet(-/-) mice, which showed diminished adhesion to mucosal addresin cellular adhesion molecule-1 (MAdCAM-1) and vascular cell adhesion molecule-1 (VCAM-1), endothelial ligands required for MCp intestinal homing. MCp, their precursors, and BMMCs do not express T-bet, suggesting that T-bet plays an indirect role in homing. However, adoptive transfer experiments revealed that T-bet expression by BM cells is required for MCp homing to the intestine. Furthermore, transfer of WT BM-derived dendritic cells (DCs) to T-bet(-/-) mice restores normal MCp intestinal homing in vivo and MCp adhesion to MAdCAM-1 and VCAM-1 in vitro. Nonetheless, T-bet(-/-) mice respond vigorously to intestinal infection with Trichinella spiralis, eliminating a role for T-bet in MC recruitment to sites of infection and their activation and function. Therefore, remarkably, T-bet expression by DCs indirectly controls MCp homing to mucosal tissues. C1 Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Luscinskas, FW (reprint author), Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM fluscinskas@rics.bwh.harvard.edu RI Lord, Graham/B-3797-2011 FU Medical Research Council [G108/380]; NCI NIH HHS [R01 CA112663, CA112663]; NHLBI NIH HHS [HL 036110, HL36028, HL53993, HL56985, P01 HL036028, P01 HL036110, P50 HL056985, R01 HL053993]; NIAID NIH HHS [AI 031599, AI56296, P01 AI031599, P01 AI056296, U19 AI031599] NR 44 TC 27 Z9 30 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 19 PY 2007 VL 204 IS 2 BP 431 EP 439 DI 10.1084/jem.2006.0626 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 140KP UT WOS:000244504100021 PM 17296784 ER PT J AU Wang, L Albrecht, MA Wurtman, RJ AF Wang, Lei Albrecht, Meredith A. Wurtman, Richard J. TI Dietary supplementation with uridine-5'-monophosphate (UMP), a membrane phosphatide precursor, increases acetylcholine level and release in striatum of aged rat SO BRAIN RESEARCH LA English DT Article DE acetylcholine; microdialysis; uridine; phosphatidylcholine; CDP-choline; aged rat ID FATTY-ACID; DOCOSAHEXAENOIC ACID; NEURITE OUTGROWTH; CDP-CHOLINE; BRAIN; CYTIDINE; URIDINE; PHOSPHOLIPIDS; BIOSYNTHESIS; STIMULATION AB The biosynthesis of brain membrane phosphatides, e.g., phosphatidylcholine (PtdCho), may utilize three circulating compounds: choline, uridine (a precursor for UTP, CTP, and CDPcholine), and a PUFA (e.g., docosahexaenoic acid); moreover, oral administration of the uridine source uridine-5'-monophosphate (UMP) can significantly increase levels of the phosphatides throughout the rodent brain. Since PtdCho can provide choline for acetylcholine (ACh) synthesis, we determined whether UMP administration also affects ACh levels in striatum and striatal extracellular fluid, in aged and young rats. Among aged animals consuming a UMP-containing diet (2.5%, w/w) for 1 or 6 weeks, baseline ACh levels in striatal dialysates rose from 73 fmol/min to 148 or 197 fmol/min (P < 0.05). Consuming a lower dose (0.5%) for 1 week produced a smaller but still significant increase (from 75 to 92 fmol/min, P < 0.05), and elevated striatal ACh content (by 16%; P < 0.05). Dietary UMP (0.5%, 1 week) also amplified the increase in ACh caused by giving atropine (10 mu M in the aCSF); atropine alone increased ACh concentrations from 81 to 386 fmol/min in control rats and from 137 to 680 fmol/min in those consuming UMP (P < 0.05). Young rats eating the UMPcontaining diet exhibited similar increases in basal ECF ACh (from 105 to 118 fmol/min) and in the increase produced by atropine (from 489 to 560 fmol/min; P < 0.05). These data suggest that giving a uridine source may enhance some cholinergic functions, perhaps by increasing brain phosphatide levels. (c) 2006 Elsevier B.V. All rights reserved. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Wurtman, RJ (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM dick@mit.edu FU NIMH NIH HHS [R01 MH028783, R01 MH028783-30, 2 R01 MH028783-30] NR 39 TC 28 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 16 PY 2007 VL 1133 IS 1 BP 42 EP 48 DI 10.1016/j.brainres.2006.11.048 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 138NA UT WOS:000244368100006 PM 17184749 ER PT J AU Xie, ZC Dong, YL Maeda, U Xia, WM Tanzi, RE AF Xie, Zhongcong Dong, Yuanlin Maeda, Uta Xia, Weiming Tanzi, Rudolph E. TI RNA interference silencing of the adaptor molecules ShcC and Fe65 differentially affect amyloid precursor protein processing and A beta generation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE; SECRETASE; CLEAVAGE; X11-ALPHA; GAMMA; APP; PHOSPHORYLATION; METABOLISM; MECHANISMS; BRAIN AB The amyloid precursor protein (APP) and its pathogenic by-product amyloid-beta protein (A beta) play central roles in Alzheimer disease (AD) neuropathogenesis. APP can be cleaved by beta-secretase (BACE) and alpha-secretase to produce APP-C99 and APP-C83. These C-terminal fragments can then be cleaved by gamma-secretase to produce A beta and p3, respectively. p3 has been reported to promote apoptosis, and A beta is the key component of senile plaques in AD brain. APP adaptor proteins with phosphotyrosine-binding domains, including ShcA (SHC1), ShcC (SHC3), and Fe65 (APBB1), can bind to and interact with the conserved YENPTY motif in the APP-C terminus. Here we have described for the first time the effects of RNA interference (RNAi) silencing of ShcA, ShcC, and Fe65 expression on APP processing and A beta production. RNAi silencing of ShcC led to reductions in the levels of APP-C-terminal fragments (APP-CTFs) and A beta in H4 human neuroglioma cells stably overexpressing full-length APP (H4-FL-APP cells) but not in those expressing APP-C99 (H4-APP-C99 cells). RNAi silencing of ShcC also led to reductions in BACE levels in H4-FL-APP cells. In contrast, RNAi silencing of the homologue ShcA had no effect on APP processing or A beta levels. RNAi silencing of Fe65 increased APP-CTF levels, although also decreasing A beta levels in H4-FL-APP cells. These findings suggest that pharmacologically blocking interaction of APP with ShcC and Fe65 may provide novel therapeutic strategies against AD. C1 Harvard Univ, Massachusetts Gen Hosp, Med Sch, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Med Sch, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Inst Med, Ctr Neurol Dis, Boston, MA 02115 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Med Sch, Genet & Aging Res Unit, 114 16th St,C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI xia, weiming/E-5465-2016 OI xia, weiming/0000-0002-7463-3295 FU NIA NIH HHS [K12 AG 000294-17, P60 AG 008812-15, R01 AG 014713-07]; NIMH NIH HHS [R01 MH 60009-03]; NINDS NIH HHS [K08 NS 048140-01] NR 33 TC 32 Z9 35 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 16 PY 2007 VL 282 IS 7 BP 4318 EP 4325 DI 10.1074/jbc.M609293200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 140CX UT WOS:000244482000011 PM 17170108 ER PT J AU Boswell, SA Ongusaha, PP Nghiem, P Lee, SW AF Boswell, Sarah A. Ongusaha, Pat P. Nghiem, Paul Lee, Sam W. TI The protective role of a small GTPase RhoE against UVB-induced DNA damage in keratinocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; HUMAN IMMORTALIZED KERATINOCYTES; RADIATION-INDUCED APOPTOSIS; EPIDERMAL-GROWTH-FACTOR; CELL-CYCLE PROGRESSION; MAP KINASES; ROCK-I; WAVELENGTH DEPENDENCE; MEDIATED APOPTOSIS; SIGNALING PATHWAY AB RhoE, a p53 target gene, was identified as a critical factor for the survival of human keratinocytes in response to UVB. The Rho family of GTPases regulates many aspects of cellular behavior through alterations to the actin cytoskeleton, acting as molecular switches cycling between the active, GTP-bound and the inactive, GDP-bound conformations. Unlike typical Rho family proteins, RhoE (also known as Rnd3) is GTPase-deficient and thus expected to be constitutively active. In this study, we investigated the response of cultured human keratinocyte cells to UVB irradiation. RhoE protein levels increase upon exposure to UVB, and ablation of RhoE induction through small interfering RNA resulted in a significant increase in apoptosis and a reduction in the levels of the pro-survival targets p21, Cox-2, and cyclin D1, as well as an increase of reactive oxygen species levels when compared with control cells. These data indicate that RhoE is a pro-survival factor acting upstream of p38, JNK, p21, and cyclin D1. HaCat cells expressing small interfering RNA to p53 indicate that RhoE functions independently of its known associates, p53 and Rho-associated kinase I (ROCK I). Targeted expression of RhoE in epidermis using skin-specific transgenic mouse model resulted in a significant reduction in the number of apoptotic cells following UVB irradiation. Thus, RhoE induction counteracts UVB-induced apoptosis and may serve as a novel target for the prevention of UVB-induced photodamage regardless of p53 status. C1 Massachusetts Gen Hosp, CBRC, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Washington, Dermatol Div, Seattle, WA 98109 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, CBRC, Charlestown, MA 02129 USA. EM sam.lee@cbrc2.mgh.harvard.edu RI Nghiem, Paul/A-9210-2011; OI Nghiem, Paul/0000-0003-2784-963X; Boswell, Sarah/0000-0002-3118-3378 FU NCI NIH HHS [CA097216, CA127247, CA80058]; NIAMS NIH HHS [AR007098-31] NR 74 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 16 PY 2007 VL 282 IS 7 BP 4850 EP 4858 DI 10.1074/jbc.M610532200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 140CX UT WOS:000244482000067 PM 17170105 ER PT J AU Ghosh-Choudhury, N Mandal, CC Choudhury, GG AF Ghosh-Choudhury, Nandini Mandal, Chandi Charan Choudhury, Goutam Ghosh TI Statin-induced Ras activation integrates the phosphatidylinositol 3-kinase signal to Akt and MAPK for bone morphogenetic protein-2 expression in osteoblast differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COA REDUCTASE INHIBITORS; NF-KAPPA-B; BMP-2 GENE-TRANSCRIPTION; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR PTEN; MESANGIAL CELLS; RETINOBLASTOMA PROTEIN; TRANSDUCTION PATHWAY; MC3T3-E1 CELLS; DNA-SYNTHESIS AB Lovastatin promotes osteoblast differentiation by increasing bone morphogenetic protein-2 (BMP-2) expression. We demonstrate that lovastatin stimulates tyrosine phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K), leading to an increase in its kinase activity in osteoblast cells. Inhibition of PI3K ameliorated expression of the osteogenic markers alkaline phosphatase, type I collagen, osteopontin, and BMP-2. Expression of dominant-negative PI3K and PTEN, an inhibitor of PI3K signaling, significantly attenuated lovastatin-induced transcription of BMP-2. Akt kinase was also activated in a PI3K-dependent manner. However, our data suggest involvement of an additional signaling pathway. Lovastatin-induced Erk1/2 activity contributed to BMP-2 transcription. Inhibition of PI3K abrogated Erk1/2 activity in response to lovastatin, indicating the presence of a signal relay between them. We provide, as a mechanism of this cross-talk, the first evidence that lovastatin stimulates rapid activation of Ras, which associates with and activates PI3K in the plasma membrane, which in turn regulates Akt and Erk1/2 to induce BMP-2 expression for osteoblast differentiation. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Ghosh-Choudhury, N (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhury@uthscsa.edu FU NIAMS NIH HHS [R01 AR52425] NR 51 TC 83 Z9 87 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 16 PY 2007 VL 282 IS 7 BP 4983 EP 4993 DI 10.1074/jbc.M606706200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 140CX UT WOS:000244482000081 PM 17179158 ER PT J AU Sharafkhaneh, A Babb, TG Officer, TM Hanania, NA Sharafkhaneh, H Boriek, AM AF Sharafkhaneh, Arnir Babb, Tony G. Officer, Todd M. Hanania, Nicholas A. Sharafkhaneh, Hossein Boriek, Aladin M. TI The confounding effects of thoracic gas compression on measurement of acute bronchodilator response SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE FEV1; chronic obstructive pulmonary disease; asthma; lung mechanics; albuterol ID EXPIRATORY FLOW; AIRWAY-OBSTRUCTION; VOLUME; PRESSURE; HYPERINFLATION; LIMITATION; RESISTANCE; DYNAMICS; LUNGS; PEAK AB Rationale: Improvement in FEV1 is a main endpoint in clinical trials assessing the efficacy of bronchodilators. However, the effect of bronchodilators on maximal expiratory flow may be confounded by thoracic gas compression (TGC). Objective: To determine whether TGC confounds effect of albuterol on FEV1. Methods: We evaluated the response to albuterol inhalation in 10 healthy subjects, 9 subjects with asthma, and 15 subjects with chronic obstructive pulmonary disease (COPD) with mean (SD) age in years of 38 (SD, 11), 45 (SD, 11), and 64 (SD, 8), respectively. Lung mechanics were measured at baseline and 20 minutes after inhalation of 180 mu g of albuterol. We then applied a novel method to calculate FEV1 corrected for the effect of TGC (NFEV1). Results: Prior to albuterol administration, NFEV1 was significantly higher than FEV1. However, post-albuterol inhalation, FEV1 increased more than NFEV1 because of reduced TGC. In multiple regression analysis, the changes in TGC, inspiratory lung resistance, and ratio of residual volume to total lung capacity postalbuterol predicted more than 75% of FEV1 improvement in patients with COPD. Conclusion: Improvements in FEV1 after albuterol in patients with COPD are due to reduction of lung resistance, hyperinflation, and TGC. The latter is negligible during tidal breathing. Thus, although reduction of lung resistance and hyperinflation may result in improved dyspnea with a bronchodilator, the contribution of TGC reduction to improvement of FEV1 may not exert any meaningful clinical effect during tidal breathing. This fact has to be taken into consideration when assessing the efficacy of new bronchodilators. C1 Baylor Coll Med, VAMC, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Univ Texas, SW Med Ctr, Dallas, TX USA. RP Sharafkhaneh, A (reprint author), Baylor Coll Med, VAMC, Bldg 100 111i,2002 Holcombe Blvd, Houston, TX 77030 USA. EM amirs@bcm.tmc.edu FU NHLBI NIH HHS [HL-072839] NR 24 TC 17 Z9 17 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 15 PY 2007 VL 175 IS 4 BP 330 EP 335 DI 10.1164/rccm.200602-255OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 136ZW UT WOS:000244263600008 PM 17110648 ER PT J AU Singh, P Camazine, B Jadhav, Y Gupta, R Mukhopadhyay, P Khan, A Reddy, R Zheng, Q Smith, DD Khodel, R Bhatt, B Bhat, S Yaqub, Y Shah, RS Sharma, A Sikkal, P Erickson, RA AF Singh, Pankaj Camazine, Brian Jadhav, Yashodeep Gupta, Rahul Mukhopadhyay, Phaiguni Khan, Ahmed Reddy, Rama Zheng, Qi Smith, David D. Khodel, Renu Bhatt, Bankim Bhat, Sanjay Yaqub, Yasir Shah, Rajnikant S. Sharma, Ashish Sikkal, Pawan Erickson, Richard A. TI Endoscopic ultrasound as a first test for diagnosis and staging of lung cancer - A prospective study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lung cancer; non-small cell lung cancer; celiac lymph nodes; endoscopic ultrasound-guided fine needle aspiration; survival ID POSITRON-EMISSION-TOMOGRAPHY; FINE-NEEDLE-ASPIRATION; MEDIASTINAL LYMPH-NODE; EUS-GUIDED FNA; SQUAMOUS-CELL CARCINOMA; LEFT ADRENAL-GLAND; COMPUTED-TOMOGRAPHY; ESOPHAGEAL CANCER; FDG PET; NONDIAGNOSTIC BRONCHOSCOPY AB Rationale: Multiple tests are required for the management of lung cancer. Objectives: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was evaluated as a single test for the diagnosis and staging (thoracic and extrathoracic) of lung cancer. Methods: Consecutive subjects with computed tomography (CT) findings of a lung mass were enrolled for EUS and results were compared with those from CT and positron emission tomography scans. Results: Of 113 subjects with lung cancer, EUS was performed as a first test (after CT scan) for diagnosis in 93 (82%) of them. EUS-FNA established tissue diagnosis in 70% of cases. EUS-FNA, CT, and positron emission tomography detected metastases to the mediastinal lymph nodes with accuracies of 93, 81, and 83%, respectively. EUS-FNA was significantly better than CT at detecting distant metastases (accuracies of 97 and 89%, respectively; p = 0.02). Metastases to lymph nodes at the celiac axis (CLNs) were observed in 11% of cases. The diagnostic yields of EUS-FNA and CT for detection of metastases to the CLNs were 100 and 50%, respectively (p < 0.05). EUS was able to detect small metastases (less than 1 cm) often missed by CT. Metastasis to the CLNs was a predictor of poor survival of subjects with non-small cell lung cancer, irrespective of the size of the CLNs. Of 44 cases with resectable tumor on CT scan, EUS-FNA avoided thoracotomy in 14% of cases. Conclusions: EUS-FNA as a first test (after CT) has high diagnostic yield and accuracy for detecting lung cancer metastases to the mediastinum and distant sites. Metastasis to the CLNs is associated with poor prognosis. EUS-FNA is able to detect occult metastasis to the CLNs and thus avoids thoracotomy. C1 Cent Texas Vet Hlth Care Syst, Div Gastroenterol, Temple, TX 76504 USA. Cent Texas Vet Hlth Care Syst, Dept Radiol, Temple, TX 76504 USA. Cent Texas Vet Hlth Care Syst, Dept Internal Med, Temple, TX 76504 USA. Cent Texas Vet Hlth Care Syst, Div Pulm & Crit Care, Temple, TX 76504 USA. Cent Texas Vet Hlth Care Syst, Div Oncol, Temple, TX 76504 USA. Henderson Mem Hosp, Dept Surg, Henderson, TX USA. Texas A&M Univ, Sch Rural & Publ Hlth, Dept Epidemiol & Biostat, College Stn, TX USA. City Hope Natl Med Ctr, Dept Biostat, Duarte, CA 91010 USA. VA Boston Healthcare Syst, Div Gastroenterol, Boston, MA USA. Scott & White Mem Hosp & Clin, Div Gastroenterol & Hepatol, Temple, TX 76508 USA. RP Singh, P (reprint author), Cent Texas Vet Hlth Care Syst, Div Gastroenterol, 1901 S 1st St, Temple, TX 76504 USA. EM pankaj1110@hotmail.com OI Smith, David/0000-0001-9644-2353 NR 61 TC 30 Z9 32 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 15 PY 2007 VL 175 IS 4 BP 345 EP 354 DI 10.1164/rccm.200606-851OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 136ZW UT WOS:000244263600010 PM 17068326 ER PT J AU Guzman-Clark, JRS Fang, MA Sehl, ME Traylor, L Hahn, TJ AF Guzman-Clark, Jenice Ria S. Fang, Meika A. Sehl, Mary E. Traylor, Laural Hahn, Theodore J. TI Barriers in the management of glucocorticoid-induced osteoporosis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE glucocorticoids; osteoporosis; veterans ID PRIMARY-CARE; CONTROLLED-TRIAL; OLDER PATIENTS; PREVENTION; FRACTURE; RECOMMENDATIONS; GUIDELINES; RISK AB Objective. To determine present practice for the management of glucocorticoid-induced osteoporosis (GIOP) in veterans; to characterize provider knowledge, beliefs, and practice behaviors regarding management of GIOP; and to identify potential barriers and interventions in the management of GIOP. Methods. To characterize current management of GIOP in an academic veterans administration medical center, we conducted a retrospective chart review of 100 patients who were prescribed a 90-day supply of prednisone. To assess clinicians' knowledge of GIOP clinical guidelines and perceptions of GIOP management, primary care clinicians and subspecialists completed a questionnaire and participated in focus groups. Results. Chart review revealed that only 32 of 100 patients receiving long-term glucocorticoid treatment underwent bone mineral density testing, and only 32 patients were prescribed the recommended calcium supplements. Of the 23 providers who completed the questionnaire and participated in the focus groups, 4 correctly identified both the dose and duration of glucocorticoid use at which GIOP prevention measures should be instituted. Common GIOP management barriers cited by participants were lack of knowledge, having limited time during the clinic visit to address all problems, patient nonadherence, and system problems. The most commonly mentioned potential interventions were the use of computerized clinical reminders and patient education. Conclusion. Clinicians frequently do not follow recommended guidelines for the management of GIOP. Improving the management of GIOP will likely require a fundamental redesigning of care processes for this disorder in order to overcome provider, patient-related, and system barriers. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Guzman-Clark, JRS (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jenice.guzman@med.va.gov NR 35 TC 23 Z9 23 U1 0 U2 6 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 FEB 15 PY 2007 VL 57 IS 1 BP 140 EP 146 DI 10.1002/art.22462 PG 7 WC Rheumatology SC Rheumatology GA 135EY UT WOS:000244138100020 PM 17266078 ER PT J AU Thermenos, HW Seidman, LJ Poldrack, RA Peace, NK Koch, JK Faraone, SV Tsuang, MT AF Thermenos, Heidi W. Seidman, Larry J. Poldrack, Russell A. Peace, Nicole K. Koch, Jennifer K. Faraone, Stephen V. Tsuang, Ming T. TI Elaborative verbal encoding and altered anterior parahippocampal activation in adolescents and young adults at genetic risk for schizophrenia using fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Review DE elaborative verbal encoding; functional MRI; genetics; parahippocampus; schizophrenia ID MEDIAL TEMPORAL-LOBE; DORSOLATERAL PREFRONTAL CORTEX; AMYGDALA-HIPPOCAMPAL VOLUME; ENTORHINAL CORTEX; BRAIN ACTIVITY; NONPSYCHOTIC RELATIVES; WORKING-MEMORY; NEUROPSYCHOLOGICAL FUNCTION; VULNERABILITY INDICATOR; FRONTOTEMPORAL ACTIVITY AB Background: First-degree relatives of persons with schizophrenia are at elevated risk for the illness, demonstrate deficits in verbal memory, and exhibit structural abnormalities in the medial temporal lobe (MTL). We used functional magnetic resonance imaging (fMRI) to assess brain activity in the MTL during novel and repeated word-pair encoding. Methods: Participants were 21 non-psychotic, first-degree relatives of persons with schizophrenia and 26 matched healthy controls (ages 13-28). fMRI signal change was measured using a Siemens 1.5T MR scanner, and data were analyzed using SPM-2. Verbal memory was assessed using the Miller Selfridge (MS) Context Memory test prior to scanning. Results: The groups were comparable on demographics, intelligence and post-scan word recognition. Relatives at genetic risk (GR) bad significantly more psychopathology than controls and worse performance on the MS test (p < .05). GR participants exhibited greater repetition suppression of activation in the left and right anterior parahippocampus (PHA, in the region of the entorhinal cortex region), after controlling for possible cor founders. Controls and GR participants with above-median MS performance showed significantly greater repetition suppression of activation in left inferior frontal gyrus than those scoring below the median. Conclusions: This is the first study to demonstrate an alteration of brain activity in the PHA in persons at GR for schizophrenia. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Div Publ Psychiat,Dept Psychiat,Beth Israel Deaco, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol,MIT, Massachusetts Gen Hosp,artinos Ctr Biomed Imagin, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. RP Thermenos, HW (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,2nd floor, Charlestown, MA 02129 USA. EM heidi@nmr.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [MH 63951, MH-43518, MH65562, R25 MH 60485] NR 123 TC 32 Z9 32 U1 1 U2 2 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 FEB 15 PY 2007 VL 61 IS 4 BP 564 EP 574 DI 10.1016/j.biopsych.2006.04.044 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 138DX UT WOS:000244344400019 PM 17276751 ER PT J AU Fukumura, D Jain, RK AF Fukumura, Dai Jain, Rakesh K. TI Novel function of RANKL: eNOS activator SO BLOOD LA English DT Editorial Material ID ENDOTHELIAL-CELLS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Fukumura, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2007 VL 109 IS 4 BP 1339 EP 1340 DI 10.1182/blood-2006-11-059642 PG 2 WC Hematology SC Hematology GA 136JW UT WOS:000244219400001 ER PT J AU Mullally, A Ritz, J AF Mullally, Ann Ritz, Jerome TI Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Review ID VERSUS-HOST-DISEASE; MINOR HISTOCOMPATIBILITY ANTIGEN; BONE-MARROW-TRANSPLANTATION; COPY NUMBER POLYMORPHISM; CYTOTOXIC T-LYMPHOCYTES; MANNOSE-BINDING LECTIN; METHYLENETETRAHYDROFOLATE REDUCTASE; RISK-FACTOR; PROGNOSTIC-SIGNIFICANCE; SEGMENTAL DUPLICATIONS AB The last 2 years have seen much excitement in the field of genetics with the identification of a formerly unappreciated level of "structural variation" within the normal human genome. Genetic structural variants include deletions, duplications, and inversions in addition to the recently discovered, copy number variants. Single nucleotide polymorphisms are the most extensively evaluated variant within the genome to date. Combining our knowledge from these studies with our rapidly accumulating understanding of structural variants, it is apparent that the extent of genetic dissimilarity between any 2 individuals is considerable and much greater than that which was previously recognized. Clearly, this more diverse view of the genome has significant implications for allogeneic hematopoietic stem cell transplantation, not least in the generation of transplant antigens but also in terms of individual susceptibility to transplant-related toxicities. With advances in DNA sequencing technology we now have the capacity to perform genome-wide analysis in a high throughput fashion, permitting a detailed genetic analysis of patient and donor prior to transplantation. Understanding the significance of this additional genetic information and applying it in a clinically meaningful way will be one of the challenges faced by transplant clinicians in the future. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu NR 101 TC 70 Z9 76 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2007 VL 109 IS 4 BP 1355 EP 1362 DI 10.1182/blood-2006-06-030858 PG 8 WC Hematology SC Hematology GA 136JW UT WOS:000244219400009 PM 17008540 ER PT J AU Chen, Z Hu, M Shivdasani, RA AF Chen, Zhao Hu, Michael Shivdasani, Ramesh A. TI Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2 SO BLOOD LA English DT Article ID DEMARCATION MEMBRANE SYSTEM; GENE-EXPRESSION; PLATELET PRODUCTION; BLOOD-PLATELETS; CELL-MATRIX; MUTATION; THROMBOCYTOPENIA; LINEAGE; GATA-1; THROMBOPOIESIS AB Megakaryocyte (MK) differentiation is well described in morphologic terms but its molecular counterparts and the basis for platelet release are incompletely understood. We profiled mRNA expression in populations of primary mouse MKs representing successive differentiation stages. Genes associated with DNA replication are highly expressed in young MKs, in parallel with endomitosis. Intermediate stages are characterized by disproportionate expression of genes associated with the cytoskeleton, cell migration, and G-protein signaling, whereas terminally mature MKs accumulate hemostatic factors, including many membrane proteins. We used these expression profiles to extract a reliable panel of molecular markers for MKs of early, intermediate, or advanced differentiation and establish the value of this marker panel using mouse models of defective thrombopoiesis resulting from absence of GATA1, NF-E2, or tubulin beta 1. Computational analysis of the promoters of late-expressed MK genes identified new candidate targets for NFE2, a critical transcriptional regulator of platelet release. One such gene encodes the kinase adaptor protein LIMS1/PINCH1, which is highly expressed in MKs and platelets and significantly reduced in NF-E2-deficient cells. Transactivation studies and chromatin immunoprecipitation implicate Lims1 as a direct target of NF-E2 regulation. Attribution of stage-specific genes, in combination with various applications, thus constitutes a powerful way to study MK differentiation and platelet biogenesis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NHLBI NIH HHS [R01 HL063143, R01HL63143] NR 51 TC 32 Z9 33 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2007 VL 109 IS 4 BP 1451 EP 1459 DI 10.1182/blood-2006-08-038901 PG 9 WC Hematology SC Hematology GA 136JW UT WOS:000244219400021 PM 17047147 ER PT J AU Ghinassi, B Sanchez, M Martelli, F Amabile, G Vannucchi, AM Migliaccio, G Orkin, SH Migliaccio, AR AF Ghinassi, Barbara Sanchez, Massimo Martelli, Fabrizio Amabile, Giovanni Vannucchi, Alessandro Maria Migliaccio, Giovanni Orkin, Stuart H. Migliaccio, Anna Rita TI The hypomorphic Gata1(low) mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; X-LINKED THROMBOCYTOPENIA; GENE-EXPRESSION; DOWN-SYNDROME; MAST-CELLS; MEGAKARYOBLASTIC LEUKEMIA; INHERITED MUTATION; STEM-CELL; IN-VIVO; LINEAGE AB Recent evidence suggests that mutations in the Gata1 gene may alter the proliferation/differentiation potential of hemopoletic progenitors. By single-cell cloning and sequential replating experiments of prospectively isolated progenitor cells, we demonstrate here that the hypomorphic Gata1(low) mutation increases the proliferation potential of a unique class of progenitor cells, similar in phenotype to adult common erythrold/megakaryocytic progenitors (MEPs), but with the "unique" capacity to generate erythroblasts, megakaryocytes, and mast cells in vitro. Conversely, progenitor cells phenotypically similar to mast cell progenitors (MCPs) are not detectable in the marrow from these mutants. At the single-cell level, about 11% of Gata1(low) progenitor cells, including MEPs, generate cells that will continue to proliferate in cultures for up to 4 months. In agreement with these results, trilineage (erythrold, megakaryocytic, and mastocytic) cell lines are consistently isolated from bone marrow and spleen cells of Gata1(low) mice. These results confirm the crucial role played by Gata1 in hematopoietic commitment and identify, as a new target for the Gata1 action, the restriction point at which common myeloid progenitors become either MEPs or MCPs. C1 Ist Super Sanita, Dept Hematol Oncol & Mol Med, I-00161 Rome, Italy. Univ G Dannunzio, Dept Biomorphol, Chieti, Italy. Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. Univ Florence, Dept Hematol & Oncol, Florence, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Illinois, Dept Med, Chicago, IL USA. Univ Illinois, Myeloproliferat Dis Res Consortium Pathol, Chicago, IL USA. RP Migliaccio, AR (reprint author), Ist Super Sanita, Dept Hematol Oncol & Mol Med, Viale Regina Elena 299, I-00161 Rome, Italy. EM migliar@iss.it RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NCI NIH HHS [P01-CA108671-01A2] NR 62 TC 37 Z9 38 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2007 VL 109 IS 4 BP 1460 EP 1471 DI 10.1182/blood-2006-07-030726 PG 12 WC Hematology SC Hematology GA 136JW UT WOS:000244219400022 PM 17038527 ER PT J AU Takeda, Y Kazarov, AR Butterfield, CE Hopkins, BD Benjamin, LE Kaipainen, A Hemler, ME AF Takeda, Yoshito Kazarov, Alexander R. Butterfield, Catherine E. Hopkins, Benjamin D. Benjamin, Laura E. Kaipainen, Arja Hemler, Martin E. TI Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro SO BLOOD LA English DT Article ID TRANSMEMBRANE 4 SUPERFAMILY; PROTEIN-KINASE-C; ENDOTHELIAL-CELLS; EXTRACELLULAR MATRICES; PROMOTES ANGIOGENESIS; BASEMENT-MEMBRANES; TUMOR ANGIOGENESIS; INDUCED APOPTOSIS; GROWTH-FACTOR; MEMBER CD151 AB Tetraspanin protein CD151 is abundant on endothelial cells. To determine whether CD151 affects angiogenesis, Cd151-null mice were prepared. Cd151-null mice showed no vascular defects during normal development or during neonatal oxygen-induced retinopathy. However, Cd151-null mice showed impaired pathologic angiogenesis in other in vivo assays (Matrigel plug, corneal micropocket, tumor implantation) and in the ex vivo aortic ring assay. Cd151-null mouse lung endothelial cells (MLECs) showed normal adhesion and proliferation, but marked alterations in vitro, in assays relevant to angiogenesis (migration, spreading, invasion, Matrigel contraction, tube and cable formation, spheroid sprouting). Consistent with these functional impairments, and with the close, preferential association of CD151 with laminin-binding integrins, Cd151-null MLECs also showed selective signaling defects, particularly on laminin substrate. Adhesion-dependent activation of PKB/c-Akt, e-NOS, Rac, and Cdc42 was diminished, but Raf, ERK, p38 MAP kinase, FAK, and Src were unaltered. In Cd151-null MLECs, connections were disrupted between laminin-binding integrins and at least 5 other proteins. In conclusion, CD151 modulates molecular organization of laminin-binding integrins, thereby supporting secondary (ie, after cell adhesion) functions of endothelial cells, which are needed for some types of pathologic angiogenesis in vivo. Selective effects of CD151 on pathologic angiogenesis make it a potentially useful target for anticancer therapy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Med Ctr, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM martin_hemler@dfci.harvard.edu FU NCI NIH HHS [R01 CA042368, CA42368, R01 CA109086-04, R01 CA109086]; NHLBI NIH HHS [R01 HL071049-04, R01 HL071049] NR 79 TC 106 Z9 120 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 FEB 15 PY 2007 VL 109 IS 4 BP 1524 EP 1532 DI 10.1182/blood-2006-08-041970 PG 9 WC Hematology SC Hematology GA 136JW UT WOS:000244219400030 PM 17023588 ER PT J AU Podar, K Raab, MS Zhang, J McMillin, D Breitkreutz, I Tai, YT Lin, BK Munshi, N Hideshima, T Chauhan, D Anderson, KC AF Podar, Klaus Raab, Marc S. Zhang, Jing McMillin, Douglas Breitkreutz, Iris Tai, Yu-Tzu Lin, Boris K. Munshi, Nikhil Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. TI Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl) SO BLOOD LA English DT Article ID PROTEIN-KINASE-C; PROMOTING PHORBOL ESTERS; B-CELL LYMPHOMA; SIGNAL TRANSDUCTION; BETA INHIBITOR; AKT PATHWAY; EXPRESSION; APOPTOSIS; GROWTH; ACTIVATION AB In multiple myeloma (MM) protein kinase C (PKC) signaling pathways have been implicated in cell proliferation, survival, and migration. Here we investigated the novel, orally available PKC-inhibitor enzastaurin for its anti-MM activity. Enzastaurin specifically inhibits phorbol ester-induced activation of PKC isoforms, as well as phosphorylation of downstream signaling molecules MARCKS and PKC mu. Importantly, it also inhibits PKC activation triggered by growth factors and cytokines secreted by bone marrow stromal cells (BMSCs), costimulation with fibronectin, vascular enclothelial growth factor (VEGF), or interleukin-6 (IL-6), as well as MM patient serum. Consequently, enzastaurin inhibits proliferation, survival, and migration of MM cell lines and MM cells isolated from multidrug-resistant patients and overcomes MM-cell growth triggered by binding to BMSCs and enclothelial cells. Importantly, strong synergistic cytotoxicity is observed when enzastaurin is combined with bortezomib and moderate synergistic or additive effects when combined with melphalan or lenaliclomide. Finally, tumor growth, survival, and angiogenesis are abrogated by enzastaurin in an in vivo xenograft model of human MM. Our results therefore demonstrate in vitro and in vivo efficacy of the orally available PKC inhibitor enzastaurin in MM and strongly support its clinical evaluation, alone or in combination therapies, to improve outcome in patients with MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. Univ Heidelberg, Dept Internal Med 5, D-6900 Heidelberg, Germany. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [P0-1 CA78378, R0 CA50947, R01 CA050947, P01 CA078378, P50 CA100707] NR 47 TC 91 Z9 94 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 2007 VL 109 IS 4 BP 1669 EP 1677 DI 10.1182/blood-2006-08-042747 PG 9 WC Hematology SC Hematology GA 136JW UT WOS:000244219400047 PM 17023575 ER PT J AU Shimizu, I Kawahara, T Haspot, F Bardwell, PD Carroll, MC Sykes, M AF Shimizu, Ichiro Kawahara, Toshiyasu Haspot, Fabienne Bardwell, Philip D. Carroll, Michael C. Sykes, Megan TI B-cell extrinsic CR1/CR2 promotes natural antibody production and tolerance induction of anti-alpha GAL-producing B-1 cells SO BLOOD LA English DT Article ID FOLLICULAR DENDRITIC CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; BONE-MARROW-TRANSPLANTATION; COMPLEMENT RECEPTORS 1; T-DEPENDENT ANTIGEN; GENE-KNOCKOUT PIGS; MIXED CHIMERISM; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; MARGINAL ZONE; GAL-ALPHA-1,3GAL EPITOPES AB B-1b cells produce IgM natural antibodies against alpha 1-3Gal beta 1-4GlcNAc (alpha Gal). These can be tolerized by nonmyeloablative induction of mixed chimerism using alpha Gal-positive (alpha Gal+) donor marrow. We assessed the role of CR1/2 in this model for induction of tolerance of B-1b cells. Mixed hematopoietic chimerism was induced in alpha 1-3galactosyltransferase (GalT(-/-)) and GalT(-/-)Cr2(-/-) mice with alpha Gal+ BALB/c marrow donors. Anti-alpha Gal Ab and anti-alpha Gal Ab-producing B cells became undetectable in GalT(-/-) chimeras, whereas they persisted in chimeric GalT(-/-)Cr2(-/-) mice. To determine whether CR1/2 expression on stromal cells and/or hematopoietic cells was critical for B-1-cell tolerance, we generated GalT(-/-) radiation chimeras in which CR1/CR2 was expressed on either stromal cells, hematopoietic cells, neither, or both. After induction of mixed chimerism from alpha Gal(+) allogeneic bone marrow (BM) donors, anti-alpha Gal-producing B cells were rendered tolerant in reconstituted recipients expressing only stromal CR1/CR2. Our results suggest a possible role for follicular dendritic cells that pick up immune complexes via CR1/CR2 receptors in the tolerization of B-1b cells. (Blood. 2007;109:1773-1781). (c) 2007 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplanta, MGH E,Bldg 149-5102,13th St, Boston, MA USA. EM megan.sykes@tbrc.mgh.harvard.edu RI Bardwell, Philip/H-2219-2014 OI Bardwell, Philip/0000-0002-3835-255X FU NHLBI NIH HHS [P01 HL018646, P01 HL 018646] NR 67 TC 6 Z9 7 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 FEB 15 PY 2007 VL 109 IS 4 BP 1773 EP 1781 DI 10.1182/blood-2006-02-002386 PG 9 WC Hematology SC Hematology GA 136JW UT WOS:000244219400060 PM 17023586 ER PT J AU Podar, K Raab, MS Tonon, G Sattler, M Barila, D Zhang, J Tai, YT Yasui, H Raje, N DePinho, RA Hideshima, T Chauhan, D Anderson, KC AF Podar, Klaus Raab, Marc S. Tonon, Giovanni Sattler, Martin Barila, Daniela Zhang, Jing Tai, Yu-Tzu Yasui, Hiroshi Raje, Noopur DePinho, Ronald A. Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. TI Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION PATTERNS; CHRONIC MYELOGENOUS LEUKEMIA; CELLS IN-VITRO; TYROSINE KINASE; OLIGONUCLEOTIDE ARRAYS; IMATINIB MESYLATE; OXIDATIVE STRESS; MM CELLS; INDUCTION; NSC-680410 AB Here we show the antimyeloma cytotoxicity of adaphostin and carried out expression profiling of adaphostin-treated multiple myeloma (MM) cells to identify its molecular targets. Surprisingly, c-Jun was the most up-regulated gene even at the earliest point of analysis (2 h). We also observed adaphostin-induced c-Abl cleavage in immunoblot analysis. Proteasome inhibitor bortezomib, but not melphalan or dexamethasone, induced similar effects, indicating unique agent-dependent mechanisms. Using caspase inhibitors, as well as caspase-resistant mutants of c-AbI (TM-c-Abl and D565A-Abl), we then showed that c-AbI cleavage in MM cells requires caspase activity. Importantly, both overexpression of the c-AbI fragment or c-Jun and knockdown of c-AbI and c-Jun expression by small interfering RNA confirmed that adaphostin-induced c-Jun up-regulation triggers downstream caspase-mediated c-AbI cleavage, inhibition of MM cell growth, and induction of apoptosis. Finally, our data suggest that this mechanism may not only be restricted to MM but may also be important in a broad range of malignancies including erythroleukemia and solid tumors. C1 Harvard Univ, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Roma Tor Vergata, Lab Cell Signalling, I-00173 Rome, Italy. Dulbecco Telethon Inst, Lab Cell Signalling, Rome, Italy. RP Podar, K (reprint author), Harvard Univ, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Med Sch, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu RI Barila, Daniela/K-8506-2016 OI Barila, Daniela/0000-0002-6192-1562 FU PHS HHS [R0 50947, P01 78378]; Telethon [TCP00061] NR 50 TC 41 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 FEB 15 PY 2007 VL 67 IS 4 BP 1680 EP 1688 DI 10.1158/0008-5472.CAN-06-1863 PG 9 WC Oncology SC Oncology GA 137JP UT WOS:000244289200035 PM 17308109 ER PT J AU Hansen, JE Fischer, LK Chan, G Chang, SS Baldwin, SW Aragon, RJ Carter, JJ Lilly, M Nishimura, RN Weisbart, RH Reeves, ME AF Hansen, James E. Fischer, Laurice K. Chan, Grace Chang, Sophia S. Baldwin, Scott W. Aragon, Robert J. Carter, Jacqueline J. Lilly, Michael Nishimura, Robert N. Weisbart, Richard H. Reeves, Mark E. TI Antibody-mediated p53 protein therapy prevents liver metastasis in vivo SO CANCER RESEARCH LA English DT Article ID CANCER-CELLS; HIV-1 TAT; TRANSDUCTION; DELIVERY; IMMUNOGLOBULIN; INDUCTION; TOLERANCE; PEPTIDE; NEURONS; BRAIN AB To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and I week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed I week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 +/- 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 +/- 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intraceflular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Loma Linda Vet Affairs Med Ctr, Loma Linda, CA USA. Loma Linda Univ, Loma Linda, CA 92350 USA. Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Weisbart, RH (reprint author), Vet Affairs Med Ctr, 111S,16111 Plummer St, Sepulveda, CA 91343 USA. EM rweisbar@ucla.edu NR 20 TC 25 Z9 27 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2007 VL 67 IS 4 BP 1769 EP 1774 DI 10.1158/0008-5472.CAN-06-3783 PG 6 WC Oncology SC Oncology GA 137JP UT WOS:000244289200045 PM 17308119 ER PT J AU Wei, XL Xu, H Kufe, D AF Wei, Xiaolong Xu, Hai Kufe, Donald TI Human mucin 1 oncoprotein represses transcription of the p53 tumor suppressor gene SO CANCER RESEARCH LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; GROWTH-FACTOR RECEPTOR; MUC1 ONCOPROTEIN; BETA-CATENIN; APOPTOTIC RESPONSE; OXIDATIVE STRESS; BREAST-CANCER; DNA-DAMAGE; PROTEIN; ACTIVATION AB The mucin 1 (MUC1) heterodimeric protein is aberrantly overexpressed in human breast cancers and induces transformation. The MUC1 COOH-terminal subunit (MUC1-C) is targeted to the nucleus of transformed cells, where it interacts with p53 and regulates p53-mediated transcription. The present studies show that MUC1 represses activation of the p53 gene and that MUC1-C occupies the PE21 element in the p53 proximal promoter. Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element. Our results show that MUC1-C binds constitutively to KLF4, occupies PE21 with KLF4, and enhances the KLF4 occupancy of PE21. The results also show that MUC1-C increases the recruitment of historic deacetylases 1/3, deacetylation of core histones, and repression of p53 transcription. These findings indicate that overexpression of MUC1, as found in human breast cancer cells, is of functional importance to repression of the p53 gene. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Pharmacol, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA 97098, CA 29431] NR 40 TC 58 Z9 65 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2007 VL 67 IS 4 BP 1853 EP 1858 DI 10.1158/0008-5472.CAN-06-3063 PG 6 WC Oncology SC Oncology GA 137JP UT WOS:000244289200054 PM 17308127 ER PT J AU Harris, LN You, FL Schnitt, SJ Witkiewicz, A Lu, X Sgroi, D Ryan, PD Come, SE Burstein, HJ Lesnikoski, BA Kamma, M Friedman, PN Gelman, R Iglehart, JD Winer, EP AF Harris, Lyndsay N. You, Fanglei Schnitt, Stuart J. Witkiewicz, Agnes Lu, Xin Sgroi, Dennis Ryan, Paula D. Come, Steven E. Burstein, Harold J. Lesnikoski, Beth-Ann Kamma, Madhavi Friedman, Paula N. Gelman, Rebecca Iglehart, J. Dirk Winer, Eric P. TI Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID EPIDERMAL-GROWTH-FACTOR; SURGICAL ADJUVANT BREAST; PHASE-II TRIAL; GENE-EXPRESSION; MONOCLONAL-ANTIBODY; 1ST-LINE THERAPY; RECEPTOR STATUS; SCATTER FACTOR; BOWEL PROJECT; CHEMOTHERAPY AB Purpose: To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2) - positive breast cancer. Experimental Design: Forty-eight patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response. Results: Eight of 40 (20%) patients achieved pCR (95% confidence interval, 9-36%). Of 9 additional patients recruited for protocol-defined toxicity analysis, 8 were evaluable; 42 of 48 (88%) patients had clinical response (16 patients, clinical complete response; 26 patients, clinical partial response). T, tumors more frequently exhibited clinical complete response (P = 0.05) and showed a trend to exhibit pCR (P = 0.07). Five (13%) patients experienced grade 1 cardiac dysfunction during preoperative treatment. Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine. RNA profiling identified three top-level clusters by unsupervised analysis. Tumors with extremes of response [pCR (n = 3) versus nonresponse (n = 3)] fell into separate groups by hierarchical clustering. No predictive genes were identified in pCR tumors. Nonresponding tumors were more likely to be T-4 stage (P = 0.02) and express basal markers (P < 0.00001), growth factors, and growth factor receptors. Insulinlike growth factor-I receptor membrane expression was associated with a lower response rate (50% versus 97%; P = 0.001). Conclusions: Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive, operable, stage II/III breast cancer. HER2-overexpressing tumors with a basal-like phenotype, or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways, are more likely to be resistant to this regimen. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Abbott Mol, Des Plaines, IL USA. RP Harris, LN (reprint author), Yale Univ, Med Ctr, Dept Med Oncol, 333 Cedar St, New Haven, CT 06510 USA. EM Lyndsay.harris@yale.edu NR 58 TC 155 Z9 160 U1 1 U2 8 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 FEB 15 PY 2007 VL 13 IS 4 BP 1198 EP 1207 DI 10.1158/1078-0432.CCR-06-1304 PG 10 WC Oncology SC Oncology GA 140JO UT WOS:000244501100019 PM 17317830 ER PT J AU Lavery, LA Armstrong, DG Murdoch, DP Peters, EJG Lipsky, BA AF Lavery, Lawrence A. Armstrong, David G. Murdoch, Douglas P. Peters, Edgar J. G. Lipsky, Benjamin A. TI Validation of the Infectious Diseases Society of America's diabetic foot infection classification system SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ULCER CLASSIFICATION; RISK; AMPUTATION; DIAGNOSIS; SCORE AB longitudinal study of 1666 persons with diabetes, there was an observed trend toward an increased risk for amputation (chi(2) test for trend, 108.0; P <.001), higher-level amputation (chi(2) test for trend, 113.3;), and lower P < .001 extremity-related hospitalization (chi(2) test for trend, 118.6;) with increasing infection severity. The Infectious P < .001 Diseases Society of America's foot infection classification system may be a useful tool for grading foot infections. C1 Texas A&M Univ, Hlth Sci Ctr, Scott & White Hosp, Dept Surg,Coll Med, Temple, TX 76508 USA. Rosalind Franklin Univ Med & Sci, Scholls Ctr Lower Extrem Ambulatory Res, CLEAR, N Chicago, IL USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Leiden Univ, Med Ctr, Dept Internal Med, NL-2300 RA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Infect Dis, NL-2300 RA Leiden, Netherlands. RP Lavery, LA (reprint author), 703 Highland Spring Ln, Georgetown, TX 78628 USA. EM llavery@swmail.sw.org RI Lipsky, Benjamin/B-4645-2013; Peters, Edgar /B-7790-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 24 TC 110 Z9 121 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2007 VL 44 IS 4 BP 562 EP 565 DI 10.1086/511036 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 127PB UT WOS:000243597700017 PM 17243061 ER PT J AU Ruvinsky, I Ohler, U Burge, CB Ruvkun, G AF Ruvinsky, Ilya Ohler, Uwe Burge, Christopher B. Ruvkun, Gary TI Detection of broadly expressed neuronal genes in C-elegans SO DEVELOPMENTAL BIOLOGY LA English DT Article DE C elegans; gene expression; pan-neuronal genes; cis-regulatory motifs ID NEMATODE CAENORHABDITIS-ELEGANS; REGULATORY ELEMENTS; DROSOPHILA GENOME; NONCODING DNA; CONSERVATION; SEQUENCES; EVOLUTION; REGIONS; IDENTIFICATION; SPECIFICITY AB The genes that are expressed in most or all types of neurons define generic neuronal features and provide a window into the developmental origin and function of the nervous system. Few such genes (sometimes referred to as pan-neuronal or broadly expressed neuronal genes) have been defined to date and the mechanisms controlling their regulation are not well understood. As a first step in investigating their regulation, we used a computational approach to detect sequences overrepresented in their promoter elements. We identified a ten-nucleotide cis-regulatory motif shared by many broadly expressed neuronal genes and demonstrated that it is involved in control of neuronal expression. Our results further suggest that global and cell-type-specific controls likely act in concert to establish pan-neuronal gene expression. Using the newly discovered motif and genome-level gene expression data, we identified a set of 234 candidate broadly expressed genes. The known involvement of many of these genes in neurogenesis and physiology of the nervous system supports the utility of this set for future targeted analyses. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Mol Biol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Dept Mol Biol, Massachusetts Gen Hosp, 185 Cambridge St,Simches 7, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK070147] NR 48 TC 19 Z9 46 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 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD FEB 15 PY 2007 VL 302 IS 2 BP 617 EP 626 DI 10.1016/j.ydbio.2006.09.014 PG 10 WC Developmental Biology SC Developmental Biology GA 139LK UT WOS:000244433100020 PM 17046742 ER PT J AU Moeller, PDR Beauchesne, KR Huncik, KM Davis, WC Christopher, SJ Riggs-Gelasco, P Gelasco, AK AF Moeller, Peter D. R. Beauchesne, Kevin R. Huncik, Kevin M. Davis, W. Clay Christopher, Steven J. Riggs-Gelasco, Pamela Gelasco, Andrew K. TI Metal complexes and free radical toxins produced by Pfiesteria piscicida SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID PRYMNESIUM PARVUM CARTER; ALGAL TOXINS; MASS-SPECTROMETRY; DOMOIC ACID; SPIN-TRAP; TOXICITY; ASSAY; ICHTHYOTOXIN; SHUMWAYAE; GROWTH AB Metal-containing organic toxins produced by Pfiesteria piscicida were characterized, for the first time, by corroborating data obtained from five distinct instrumental methods: nuclear magnetic resonance spectroscopy (NMR), inductively coupled plasma mass spectrometry (ICP-MS), liquid chromatography particle beam glow discharge mass spectrometry (LC/PB-GDMS), electron paramagnetic resonance spectroscopy (EPR), and X-ray absorption spectroscopy (XAS). The high toxicity of the metal-containing toxins is due to metal-mediated free radical production. This mode of activity explains the toxicity of Pfiesteria, as well as previously reported difficulty in observing the molecular target, due to the ephemeral nature of radical species. The toxins are highly labile in purified form, maintaining activity for only 2-5 days before all activity is lost. The multiple toxin congeners in active extracts are also susceptible to decomposition in the presence of white light, pH variations, and prolonged heat. These findings represent the first formal isolation and characterization of a radical forming toxic organic-ligated metal complex isolated from estuarine/marine dinoflagellates. These findings add to an increased understanding regarding the active role of metals interacting with biological systems in the estuarine environment, as well as their links and implications to human health. C1 Natl Ocean & Atmospher Adm, Natl Ocean Serv, Hollings Marine Lab, Toxin Nat Prod Chem Program,Ctr Coastal Environm, Charleston, SC 29412 USA. Natl Inst Stand & Technol, Hollings Marine Lab, Charleston, SC 29412 USA. Coll Charleston, Dept Chem, Charleston, SC 29424 USA. Med Univ S Carolina, Dept Med, Div Nephrol, Columbia, SC 29425 USA. Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Moeller, PDR (reprint author), Natl Ocean & Atmospher Adm, Natl Ocean Serv, Hollings Marine Lab, Toxin Nat Prod Chem Program,Ctr Coastal Environm, Charleston, SC 29412 USA. EM Peter.Moeller@noaa.gov FU NCRR NIH HHS [P20 RR-016461, RR13656]; NIDDK NIH HHS [DK059950] NR 57 TC 29 Z9 30 U1 4 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD FEB 15 PY 2007 VL 41 IS 4 BP 1166 EP 1172 DI 10.1021/es0617993 PG 7 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 135NZ UT WOS:000244161600020 PM 17598275 ER PT J AU Azouz, A Gunn, TM Duke-Cohan, JS AF Azouz, Abdallah Gunn, Teresa M. Duke-Cohan, Jonatfian S. TI Juvenile-onset loss of lipid-raft domains in attractin-deficient mice SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE attractin; cholesterol; GM(1); plasma membrane; raft domain ID CENTRAL-NERVOUS-SYSTEM; PLASMA-MEMBRANE; MUTANT MICE; CUB-FAMILY; IV CD26; DPPT-L; PROTEINS; MAHOGANY; CELLS; GENE AB Mutations at the attractin (Atrn) locus in mice result in altered pigmentation on an agouti background, higher basal metabolic rate and juvenile-onset hypomyelination leading to neuro degeneration, while studies on human immune cells indicate a chemotaxis regulatory function. The underlying biochemical defect remains elusive. in this report we identify a role for attractin in plasma membrane maintenance. In attractin's absence there is a decline in plasma membrane glycolipid-enriched rafts from normal levels at 8 weeks to a complete absence by 24 weeks. The structural integrity of lipid rafts depends upon cholesterol and sphingomyelin, and can be identified by partitioning within of ganglioside GM1. Despite a significant fall in cellular cholesterol with maturity, and a lesser fall in both membrane and total cellular GM1, these parameters lag behind raft loss, and are normal when hypomyelination/neurodegeneration has already begun thus supporting consequence rather than cause. These findings can be recapitulated in Atrn-deficient cell lines propagated in vitro. Further, signal transduction through complex membrane receptor assemblies is not grossly disturbed despite the complete absence of lipid rafts. We find these results compatible with a role for attractin in plasma membrane maintenance and consistent with the proposal that the juvenile-onset hypomyelination and neurodegeneration represent a defect in attractin-mediated raft-dependent myelin biogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA. RP Duke-Cohan, JS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 77 Ave Louis Pasteur,HIM 423, Boston, MA 02115 USA. EM Jonathan_Duke-Cohan@dfci.harvard.edu OI Gunn, Teresa/0000-0003-2688-6420; Duke-Cohan, Jonathan/0000-0002-9478-9609 NR 43 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 15 PY 2007 VL 313 IS 4 BP 761 EP 771 DI 10.1016/j.yexcr.2006.11.018 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 137HI UT WOS:000244283300012 PM 17196964 ER PT J AU Haigis, KM Wistuba, II Kurie, JM AF Haigis, Kevin M. Wistuba, Ignacio I. Kurie, Jonathan M. TI Lung premalignancy induced by mutant B-Raf, what is thy fate? To senesce or not to senesce, that is the question SO GENES & DEVELOPMENT LA English DT Article ID ONCOGENIC K-RAS; SMALL-CELL LUNG; STEM-CELLS; DEVELOPMENTAL DEFECTS; GENE-EXPRESSION; HUMAN CANCER; MOUSE MODEL; BRAF GENE; MUTATIONS; INHIBITOR C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. RP Kurie, JM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. EM jkurie@mdanderson.org NR 35 TC 7 Z9 7 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 FEB 15 PY 2007 VL 21 IS 4 BP 361 EP 366 DI 10.1101/gad.1532107 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 140ZM UT WOS:000244545500001 PM 17322395 ER PT J AU Chen, W Yang, SY Abe, Y Li, M Wang, YC Shao, JZ Li, E Li, YP AF Chen, Wei Yang, Shuying Abe, Yoke Li, Ming Wang, Yucheng Shao, Jianzhong Li, En Li, Yi-Ping TI Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescence SO HUMAN MOLECULAR GENETICS LA English DT Article ID MOLECULAR-CLONING; TRANSCRIPTION FACTOR; TARGETED DISRUPTION; CYSTEINE PROTEASE; BONE-RESORPTION; DEFICIENT MICE; OSTEOPETROSIS; EXPRESSION; CELLS; GENE AB Pycnodysostosis is a genetic bone disease featuring the unique bone homeostasis disorders of osteolysis and osteopetrosis in the same organism. The pathomechanism for pycnodysostosis has been largely unknown due to the unavailability of a pycnodysostosis mouse model with all the traits of the disease. We generated cathepsin K-/- mouse strains in the 129/Sv and C57BL/6J backgrounds and found that, only in the 129/Sv background, cathepsin K-/- mice exhibit many characteristics of the human pycnodysostosis-like phenotype. Our data indicated that 129/Sv cathepsin K-/- osteoclasts (OCs) lacked normal apoptosis and senescence and exhibited over-growth both in vitro and in vivo. These abnormalities resulted in an unusually high OC number, which is consistent with a recent case study of human pycnodysostosis. Our results show that cathepsin K function has different effects around the skeleton due to site-specific variations in bone homeostasis, such as phenotypes of osteopetrosis in tibiae and osteolysis in calvariae as a result of cathepsin K mutation. Our data demonstrated that the expression levels of p19, p53 and p21 were significantly reduced in 129/Sv cathepsin K-/- OCs and forced expression of cathepsin K in pre-OCs induced premature senescence and increased expression of p19, p53 and p21. This is the first evidence that cathepsin K plays a key role in OC apoptosis and senescence, revealing the importance of OC senescence in bone homeostasis. The finding of this novel cathepsin K function provides insight into the pathomechanism of pycnodysostosis and may provide new drug targets for diseases involved in OC-related abnormal bone homeostasis. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. Zhejiang Univ, Life Sci Coll, Hangzhou 310027, Peoples R China. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM ypli@forsyth.org RI Yang, Shuying/G-4599-2011 FU NIA NIH HHS [R01 AG048388]; NIAMS NIH HHS [AR-44741, AR-48133-01, R01 AR044741, R01 AR048133]; NIDCR NIH HHS [R03 DE016857] NR 45 TC 58 Z9 60 U1 1 U2 8 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 FEB 15 PY 2007 VL 16 IS 4 BP 410 EP 423 DI 10.1093/hmg/ddl474 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 135AO UT WOS:000244126400006 PM 17210673 ER PT J AU Stone, ME AF Stone, Martha E. TI Webster's new explorer medical dictionary. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU 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 FEB 15 PY 2007 VL 132 IS 3 BP 151 EP 151 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 134RZ UT WOS:000244103000217 ER PT J AU Zhou, TQ Xu, L Dey, B Hessell, AJ Van Ryk, D Xiang, SH Yang, XZ Zhang, MY Zwick, MB Arthos, J Burton, DR Dimitrov, DS Sodroski, J Wyatt, R Nabel, GJ Kwong, PD AF Zhou, Tongqing Xu, Ling Dey, Barna Hessell, Ann J. Van Ryk, Donald Xiang, Shi-Hua Yang, Xinzhen Zhang, Mei-Yun Zwick, Michael B. Arthos, James Burton, Dennis R. Dimitrov, Dimiter S. Sodroski, Joseph Wyatt, Richard Nabel, Gary J. Kwong, Peter D. TI Structural definition of a conserved neutralization epitope on HIV-1 gp120 SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; BINDING SITES; RECEPTOR; RECOGNITION; ANTIGEN; PROTEIN; DOMAIN; GP41 AB The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 angstrom resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Ctr Canc Res, Frederick, MD 21702 USA. RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pdkwong@nih.gov RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 FU Intramural NIH HHS; NIAID NIH HHS [U19 AI067854, U19 AI067854-03] NR 50 TC 541 Z9 552 U1 5 U2 70 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 15 PY 2007 VL 445 IS 7129 BP 732 EP 737 DI 10.1038/nature05580 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 136EK UT WOS:000244205200037 PM 17301785 ER PT J AU van der Zijden, JP Wu, O van der Toorn, A Roeling, TP Bleys, RLAW Dijkhuizen, RM AF van der Zijden, Jet P. Wu, Ona van der Toorn, Annette Roeling, Tom P. Bleys, Ronald L. A. W. Dijkhuizen, Rick M. TI Changes in neuronal connectivity after stroke in rats as studied by serial manganese-enhanced MRI SO NEUROIMAGE LA English DT Article ID CEREBRAL-ARTERY OCCLUSION; RESONANCE-IMAGING MEMRI; BRAIN IN-VIVO; FUNCTIONAL RECOVERY; PROJECTIONS; PLASTICITY; MOTOR; ISCHEMIA; MODELS; INJURY AB Loss of function and subsequent spontaneous recovery after stroke have been associated with physiological and anatomical alterations in neuronal networks in the brain. However, the spatiotemporal pattern of such changes has been incompletely characterized. Manganese-enhanced MRI (MEMRI) provides a unique toot for in vivo investigation of neuronal connectivity. In this study, we measured manganese-induced changes in longitudinal relaxation rate, R-1, to assess the spatiotemporal pattern of manganese distribution after focal injection into the intact sensorimotor cortex in control rats (n=10), and in rats at 2 weeks after 90-min unilateral occlusion of the middle cerebral artery (n=10). MEMRI data were compared with results from conventional tract tracing with wheat-germ agglutinin horseradish peroxidase (WGA-HRP). Distinct areas of the sensorimotor pathway were clearly visualized with MEMRI. At 2 weeks after stroke, manganese-induced changes in R, were significantly delayed and diminished in the ipsilateral caudate putamen, thalamus and substantia nigra. Loss of connectivity between areas of the sensorimotor network was also identified from reduced WGA-HRP staining in these areas on post-mortem brain sections. This study demonstrates that MEMRI enables in vivo assessment of spatiotemporal alterations in neuronal connectivity after stroke, which may lead to improved insights in mechanisms underlying functional loss and recovery after stroke. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Utrecht, Med Ctr, Image Sci Inst, NL-3584 CJ Utrecht, Netherlands. Harvard Univ, Sch Med, MIT, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Charlestown, MA USA. Univ Utrecht, Med Ctr, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. RP van der Zijden, JP (reprint author), Univ Utrecht, Med Ctr, Image Sci Inst, Bolognalaan 50, NL-3584 CJ Utrecht, Netherlands. EM jet@invivonmr.uu.nl RI Dijkhuizen, Richard/A-6506-2008; OI Dijkhuizen, Rick/0000-0002-4623-4078 NR 34 TC 41 Z9 41 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 15 PY 2007 VL 34 IS 4 BP 1650 EP 1657 DI 10.1016/j.neuroimage.2006.11.001 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 138GA UT WOS:000244349900032 PM 17175175 ER PT J AU Eddy, MD Schnyer, D Schmid, A Holcomb, PJ AF Eddy, Marianna D. Schnyer, David Schmid, Annette Holcomb, Phillip J. TI Spatial dynamics of masked picture repetition effects SO NEUROIMAGE LA English DT Article DE fMRI; masked priming; repetition priming; picture processing; repetition suppression ID HUMAN EXTRASTRIATE CORTEX; WORD FORM AREA; VISUAL OBJECT RECOGNITION; EVENT-RELATED FMRI; FUNCTIONAL-PROPERTIES; CORTICAL MECHANISMS; FUSIFORM CORTEX; SIGNAL; SPECIFICITY AB The aim of this study was to further elucidate the mechanisms of early and automatic object processing using a masked picture priming paradigm with both identity and exemplar repetition in functional MRI (fMRI). Masked repetition priming has been commonly used with words to isolate automatic, rapidly occurring mechanisms involved in visual word recognition; however, studies using the technique of masked priming with rapid presentation of pictures have been limited. This study demonstrates how the masked priming technique can be used to study early, automatic processing of rapidly presented complex objects. Temporal-occipital regions previously found to be sensitive to repetition priming in both masked word and unmasked picture studies were found to show repetition suppression for the identity primes only. Most notably, when divided into anterior and posterior divisions, the fusiform gyrus showed anatomically specific repetition suppression only in the posterior portion. This finding is comparable to that found in a previous study of masked word priming, and the similarity may suggest an overlap in the early identification processes for visual word form and visual object processing in this region. Finally, masked repetition of different exemplar objects did not result in reliable neural effects, suggesting that the underlying mechanisms of the more semantic-based, different exemplar priming may occur later or require the intervention of conscious processes. (c) 2006 Elsevier Inc. All rights reserved. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02130 USA. RP Eddy, MD (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM Marianna.eddy@tufts.edu OI Schnyer, David/0000-0002-7472-2853 FU NICHD NIH HHS [R01 HD043251-04, HD025889, R01 HD025889, R01 HD025889-16, R01 HD043251, R37 HD025889]; NIMH NIH HHS [K23 MH064004, K23MH64004] NR 38 TC 16 Z9 16 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 15 PY 2007 VL 34 IS 4 BP 1723 EP 1732 DI 10.1016/j.neuroimage.2006.10.031 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 138GA UT WOS:000244349900039 PM 17196398 ER PT J AU Ligon, KL Huillard, E Mehta, S Kesari, S Liu, HY Alberta, JA Bachoo, RM Kane, M Louis, DN DePinho, RA Anderson, DJ Stiles, CD Rowitch, DH AF Ligon, Keith L. Huillard, Emmanuelle Mehta, Shwetal Kesari, Santosh Liu, Hongye Alberta, John A. Bachoo, Robert M. Kane, Michael Louis, David N. DePinho, Ronald A. Anderson, David J. Stiles, Charles D. Rowitch, David H. TI Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma SO NEURON LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR RECEPTOR; FACTOR-BINDING SITES; HUMAN BRAIN-TUMORS; PROGENITOR CELLS; TRANSCRIPTION FACTOR; GENE-EXPRESSION; GLIOBLASTOMA-MULTIFORME; SUBVENTRICULAR ZONE AB Recent studies have identified stem cells in brain cancer. However, their relationship to normal CNS progenitors, including dependence on common lineage-restricted pathways, is unclear. We observe expression of the CNS-restricted transcription factor, OLIG2, in human glioma stem and progenitor cells reminiscent of type C transit-amplifying cells in germinal zones of the adult brain. Olig2 function is required for proliferation of neural progenitors and for glioma formation in a genetically relevant murine model. Moreover, we show p21(WAF1/CIP1), a tumor suppressor and inhibitor of stem cell proliferation, is directly repressed by OLIG2 in neural progenitors and gliomas. Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02129 USA. CALTECH, Howard Hughes Med Inst, Div Biol, Pasadena, CA 91125 USA. Childrens Hosp, Div Neonatol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Regenerat Med, San Francisco, CA 94143 USA. RP Stiles, CD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 4 Binney St, Boston, MA 02115 USA. EM charles_stiles@dfci.harvard.edu; rowitchd@peds.ucsf.edu RI leng, xianwei/F-9073-2011; Kesari, Santosh/E-8461-2013 FU Howard Hughes Medical Institute; NCI NIH HHS [P01 CA095616, P01 CA95616]; NINDS NIH HHS [F32 NS055631, K08 NS047213, K08NS047213, NS05563, P01 NS047572, P01NS047572, R01 NS040511, R01NS40511] NR 83 TC 238 Z9 243 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB 15 PY 2007 VL 53 IS 4 BP 503 EP 517 DI 10.1016/j.neuron.2007.01.009 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 149DJ UT WOS:000245126900010 PM 17296553 ER PT J AU Raoult, D Abbara, S Jassal, DS Kradin, RL Myers, JE Harris, NL Plank, RM Felsenstein, D AF Raoult, Didier Abarra, Suhny Jassal, Davinder S. Kradin, Richard L. Myers, Julie E. Harris, Nancy Lee Plank, Rebeca M. Felsenstein, Donna TI A 53-year-old man with a prosthetic aortic valve and recent onset of fatigue, dyspnea, weight loss, and sweats - C-burnetii (Q fever) endocarditis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INFECTIVE ENDOCARDITIS; DIAGNOSIS; QUINTANA C1 Univ Aix Marseille 2, Fac Med, Dept Clin Microbiol, Unite Rickettsies, Marseille, France. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Raoult, D (reprint author), Univ Aix Marseille 2, Fac Med, Dept Clin Microbiol, Unite Rickettsies, Marseille, France. NR 16 TC 11 Z9 12 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 15 PY 2007 VL 356 IS 7 BP 715 EP 725 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 135ZV UT WOS:000244193300011 PM 17301303 ER PT J AU Ozcan, A Demirci, U AF Ozcan, Aydogan Demirci, Utkan TI Rewritable self-assembled long-period gratings in photonic bandgap fibers using microparticles SO OPTICS COMMUNICATIONS LA English DT Article ID CRYSTAL FIBERS; BRAGG GRATINGS; OPTICAL-FIBER; FILTERS AB We report the demonstration of rewritable self-assembled long-period gratings in air-core photonic bandgap fibers. The long-period gratings are written by filling the air-core region of the fiber with a solution containing polystyrene microspheres. The microspheres are self-assembled into a periodic structure as the liquid inside the fiber evaporates, forming the long-period grating. The formed grating can then be easily erased for rewriting purposes by connecting the end of the fiber to a microlluidic pump through a microlluidic channel and washing out the microparticles with an appropriate liquid. The same microfluidic system can also be used to fine control the writing process of the gratings. This technique creates possibilities for writing various different filtering functions in air-core photonic bandgap fibers by varying the composition and/or the shape of the used microparticles. The presented technique is potentially applicable to solid-core photonic crystal fibers as well. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. Harvard Univ, Sch Med, Harvard MIT Hlth Sci & Technol, Boston, MA USA. RP Ozcan, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. EM aozcan@mgh.harvard.edu; udemirci@partners.org RI Ozcan, Aydogan/I-2608-2013 OI Ozcan, Aydogan/0000-0002-0717-683X NR 22 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0030-4018 J9 OPT COMMUN JI Opt. Commun. PD FEB 15 PY 2007 VL 270 IS 2 BP 225 EP 228 DI 10.1016/j.optcom.2006.09.032 PG 4 WC Optics SC Optics GA 135MM UT WOS:000244157700019 ER PT J AU Deliolanis, N Lasser, T Hyde, D Soubret, A Ripoll, J Ntziachristos, V AF Deliolanis, Nikolaos Lasser, Tobias Hyde, Damon Soubret, Antoine Ripoll, Jorge Ntziachristos, Vasilis TI Free-space fluorescence molecular tomography utilizing 360 degrees geometry projections SO OPTICS LETTERS LA English DT Article AB Fluorescence tomography of diffuse media can yield optimal three-dimensional imaging when multiple projections over 360 degrees geometries are captured, compared with limited projection angle systems such as implementations in the slab geometry. We demonstrate how it is possible to perform noncontact, 360 degrees projection fluorescence tomography of mice using CCD-camera-based detection in free space, i.e., in the absence of matching fluids. This approach achieves high spatial sampling of photons propagating through tissue and yields a superior information content data set compared with fiber-based 360 degrees implementations. Reconstruction feasibility using 36 projections in 10 degrees steps is demonstrated in mice. (c) 2007 Optical Society of America. C1 Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Deliolanis, N (reprint author), Massachusetts Gen Hosp, Lab Bioopt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM ndeliolanis@partners.org RI Ripoll, Jorge/J-8134-2012; OI Ripoll, Jorge/0000-0001-8856-7738; Deliolanis, Nikolaos/0000-0002-6392-3035 FU NIBIB NIH HHS [R01 EB 000750]; NIEHS NIH HHS [R43-ES01236] NR 14 TC 148 Z9 157 U1 1 U2 15 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD FEB 15 PY 2007 VL 32 IS 4 BP 382 EP 384 DI 10.1364/OL.32.000382 PG 3 WC Optics SC Optics GA 134LE UT WOS:000244083700020 PM 17356660 ER PT J AU Peng, LL Motz, JT Redmond, RW Bouma, BE Tearney, GJ AF Peng, Leilei Motz, Jason T. Redmond, Robert W. Bouma, Brett E. Tearney, Guillermo J. TI Fourier transform emission lifetime spectrometer SO OPTICS LETTERS LA English DT Article ID SPECTROSCOPY; DEPENDENCE AB We report a rapid and low cost Fourier transform spectrometer that uses a path length modulated Michelson interferometer to simultaneously measure excitation spectra and excitation wavelength-dependent emission lifetimes. Excitation spectra and lifetimes of excited tris(2,2'-bipyridyl) ruthenium(II) measured using this technique corresponded to values known in the literature. Excitation-dependent lifetimes of porous silicon measured with this technique suggest the influence of quantum confinement effects. This method may be useful for measuring mixtures of emitting species with closely spaced lifetimes as well as studying excitation wavelength-dependent emission phenomena. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Peng, LL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Bar 703, Boston, MA 02114 USA. EM gtearney@partners.org NR 9 TC 4 Z9 4 U1 3 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD FEB 15 PY 2007 VL 32 IS 4 BP 421 EP 423 DI 10.1364/OL.32.000421 PG 3 WC Optics SC Optics GA 134LE UT WOS:000244083700033 PM 17356673 ER PT J AU Hertl, M Cosimi, AB AF Hertl, Martin Cosimi, A. Benedict TI Living donor liver transplantation: How can we better protect the donors? SO TRANSPLANTATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Transplant Unit, Boston, MA 02114 USA. RP Hertl, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplant Unit, 55 Fruit St,Blake 655, Boston, MA 02114 USA. EM mhertl@partners.org NR 5 TC 8 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 2007 VL 83 IS 3 BP 263 EP 264 DI 10.1097/01.tp.0000250676.71656.39 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 138PY UT WOS:000244375900005 PM 17297397 ER PT J AU Blumenthal, RS Michos, ED Nasir, K AF Blumenthal, Roger S. Michos, Erin D. Nasir, Khurram TI Further improvements in CHD risk prediction for women SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; PANEL III GUIDELINES; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; HIGH PREVALENCE; FAMILY-HISTORY; ATHEROSCLEROSIS; CHOLESTEROL; ADULTS C1 Johns Hopkins Univ, Johns Hopkins Hosp, Ciccarone Prevent Cardiol Ctr, Div Cardiol,Sch Med, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Cardiac MRI PET CT Program, Boston, MA 02114 USA. RP Blumenthal, RS (reprint author), Johns Hopkins Univ, Johns Hopkins Hosp, Ciccarone Prevent Cardiol Ctr, Div Cardiol,Sch Med, Blalock 524,600 N Wolfe St, Baltimore, MD 21287 USA. EM rblumenthal@jhmi.edu NR 22 TC 20 Z9 20 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 FEB 14 PY 2007 VL 297 IS 6 BP 641 EP 643 DI 10.1001/jama.297.6.641 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 135TU UT WOS:000244177400029 PM 17299201 ER PT J AU Suntsova, N Guzman-Marin, R Kumar, S Alam, MN Szymusiak, R McGinty, D AF Suntsova, Natalia Guzman-Marin, Ruben Kumar, Sunil Alam, Md. Noor Szymusiak, Ronald McGinty, Dennis TI The median preoptic nucleus reciprocally modulates activity of arousal-related and sleep-related neurons in the perifornical lateral hypothalamus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE perifornical lateral hypothalamus; median preoptic nucleus; electrical stimulation; microdialysis; neuronal activity; sleep-waking cycle ID MELANIN-CONCENTRATING HORMONE; WAKING DISCHARGE PATTERNS; C-FOS EXPRESSION; OREXIN NEURONS; POSTERIOR HYPOTHALAMUS; OREXIN/HYPOCRETIN NEURONS; PARAVENTRICULAR NUCLEUS; PREFRONTAL CORTEX; GABAERGIC CONTROL; CORTICAL-NEURONS AB The perifornical-lateral hypothalamic area (PF/LH) contains neuronal groups playing an important role in control of waking and sleep. Among the brain regions that regulate behavioral states, one of the strongest sources of projections to the PF/LH is the median preoptic nucleus (MnPN) containing a sleep-active neuronal population. To evaluate the role of MnPN afferents in the control of PF/LH neuronal activity, we studied the responses of PF/LH cells to electrical stimulation or local chemical manipulation of the MnPN in freely moving rats. Single-pulse electrical stimulation evoked responses in 79% of recorded PF/LH neurons. No cells were activated antidromically. Direct and indirect transynaptic effects depended on sleep-wake discharge pattern of PF/LH cells. The majority of arousal-related neurons, that is, cells discharging at maximal rates during active waking (AW) or during AW and rapid eye movement (REM) sleep, exhibited exclusively or initially inhibitory responses to stimulation. Sleep-related neurons, the cells with elevated discharge during non-REM and REM sleep or selectively active in REM sleep, exhibited exclusively or initially excitatory responses. Activation of the MnPN via microdialytic application of L-glutamate or bicuculline resulted in reduced discharge of arousal-related and in excitation of sleep-related PF/LH neurons. Deactivation of the MnPN with muscimol caused opposite effects. The results indicate that the MnPN contains subset(s) of neurons, which exert inhibitory control over arousal-related and excitatory control over sleep-related PF/LH neurons. We hypothesize that MnPN sleep-active neuronal group has both inhibitory and excitatory outputs that participate in the inhibitory control of arousal-promoting PF/LH mechanisms. C1 Vet Affairs Greater Los Angeles, Healthcare Syst, Res Serv 151A3, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Rostov State Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu 344091, Russia. RP McGinty, D (reprint author), Vet Affairs Greater Los Angeles, Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM dmcginty@ucla.edu FU NHLBI NIH HHS [P50 HL060296, HL60296]; NIMH NIH HHS [R01 MH063323, R01 MH075076, MH63323, MH47480, R01 MH075076-03, R01 MH047480]; NINDS NIH HHS [NS-50939, R01 NS050939] NR 63 TC 49 Z9 52 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 14 PY 2007 VL 27 IS 7 BP 1616 EP 1630 DI 10.1523/JNEUROSCI.3498-06.2007 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 136QQ UT WOS:000244239600014 PM 17301170 ER PT J AU Manoach, DS Thakkar, KN Cain, MS Polli, FE Edelman, JA Fischl, B Barton, JJS AF Manoach, Dara S. Thakkar, Katherine N. Cain, Matthew S. Polli, Frida E. Edelman, Jay A. Fischl, Bruce Barton, Jason J. S. TI Neural activity is modulated by trial history: A functional magnetic resonance imaging study of the effects of a previous antisaccade SO JOURNAL OF NEUROSCIENCE LA English DT Article DE plasticity; antisaccade; frontal eye field; functional neuroimaging; context; cognition ID EVENT-RELATED FMRI; POSITRON EMISSION TOMOGRAPHY; SACCADIC EYE-MOVEMENTS; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; PREPARATORY SET; ANTI-SACCADES; PRO-SACCADES; COORDINATE SYSTEM; NEURONAL-ACTIVITY AB Saccadic latencies are influenced by what occurred during the previous trial. When the previous trial is an antisaccade, the latencies of both prosaccades and antisaccades are prolonged. The aim of this study was to identify neural correlates of this intertrial effect of antisaccades. Specifically, based on both monkey electrophysiology and human neuroimaging findings, we expected trials preceded by antisaccades to be associated with reduced frontal eye field (FEF) activity relative to those preceded by prosaccades. Twenty-one healthy participants performed pseudorandom sequences of prosaccade and antisaccade trials during functional magnetic resonance imaging (fMRI) with concurrent monitoring of eye position. We compared activity in trials preceded by an antisaccade with activity in trials preceded by a prosaccade. The primary result was that a previous antisaccade prolonged saccadic latency and reduced fMRI activity in the FEF and other regions. No regions showed increased activity. We interpret the reduced FEF activity and slower saccadic responses to reflect inhibitory influences on the response system as a consequence of performing an antisaccade in the previous trial. This demonstrates that neural activity is modulated by trial history, consistent with a rapid, dynamic form of learning. More generally, these results highlight the importance of trial history as a source of variability in both behavioral and neuroimaging studies. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. CUNY, Dept Biol, New York, NY 10031 USA. Univ British Columbia, Dept Ophthalmol, Vancouver, BC V5Z 3N9, Canada. Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 3N9, Canada. Univ British Columbia, Dept Visual Sci, Vancouver, BC V5Z 3N9, Canada. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,Room 2608, Boston, MA 02129 USA. EM dara@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012; OI Thakkar, Katharine/0000-0002-0026-2030; Cain, Matthew/0000-0002-3305-0464 FU NCRR NIH HHS [P41 RR14075, R01 RR16594, U24 RR021382]; NIBIB NIH HHS [R01 EB001550]; NIMH NIH HHS [F21 MH72120, R01 MH67720]; NINDS NIH HHS [R01 NS052858-01] NR 53 TC 48 Z9 48 U1 3 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 FEB 14 PY 2007 VL 27 IS 7 BP 1791 EP 1798 DI 10.1523/JNEUROSCI.3662-06.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 136QQ UT WOS:000244239600030 PM 17301186 ER PT J AU Costanzo, MR Guglin, ME Saltzberg, MT Jessup, ML Bart, BA Teerlink, JR Jaski, BE Fang, JC Feller, ED Haas, GJ Anderson, AS Schollmeyer, MP Sobotka, PA AF Costanzo, Maria Rosa Guglin, Maya E. Saltzberg, Mitchell T. Jessup, Mariell L. Bart, Bradley A. Teerlink, John R. Jaski, Brian E. Fang, James C. Feller, Erika D. Haas, Garrie J. Anderson, Allen S. Schollmeyer, Michael P. Sobotka, Paul A. CA UNLOAD Trial Investigations TI Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; RENAL-FUNCTION; OVERLOADED PATIENTS; BODY-FLUID; FUROSEMIDE; MORTALITY; DIAGNOSIS; REMOVAL; THERAPY; UPDATE AB Objectives This study was designed to compare the safety and efficacy of veno-venous ultrafiltration and standard intravenous diuretic therapy for hypervolemic heart failure (HF) patients. Background Early ultrafiltration may be an alternative to intravenous diuretics in patients with decompensated HF and volume overload. Methods Patients hospitalized for HF with >= 2 signs of hypervolemia were randomized to ultrafiltration or intravenous diuretics. Primary end points were weight loss and dyspnea assessment at 48 h after randomization. Secondary end points included net fluid loss at 48 h, functional capacity, HF rehospitalizations, and unscheduled visits in 90 days. Safety end points included changes in renal function, electrolytes, and blood pressure. Results Two hundred patients (63 +/- 15 years, 69% men, 71% ejection fraction <= 40%) were randomized to ultrafiltration or intravenous diuretics. At 48 h, weight (5.0 +/- 3.1 kg vs. 3.1 +/- 3.5 kg; p = 0.001) and net fluid loss (4.6 vs. 3.3 l; p = 0.001) were greater in the ultrafiltration group. Dyspnea scores were similar. At 90 days, the ultrafiltration group had fewer patients rehospitalized for HF (16 of 89 [18%] vs. 28 of 87 [32%]; p = 0.037), HF rehospitalizations (0.22 +/- 0.54 vs. 0.46 +/- 0.76; p = 0.022), rehospitalization days (1.4 +/- 4.2 vs. 3.8 +/- 8.5; p = 0.022) per patient, and unscheduled visits (14 of 65 [21%] vs. 29 of 66 [44%]; p = 0.009). No serum creatinine differences occurred between groups. Nine deaths occurred in the ultrafiltration group and 11 in the diuretics group. Conclusions In decompensated HF, ultrafiltration safely produces greater weight and fluid loss than intravenous diuretics, reduces 90-day resource utilization for HIP, and is an effective alternative therapy. C1 Midw Heart Fdn, Lombard, IL USA. Wayne State Univ, John D Dingell VA Med Ctr, Dept Med, Div Cardiol, Detroit, MI 48202 USA. Univ Penn, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA. Hennepin Cty Med Ctr, Dept Med, Div Cardiol, Minneapolis, MN 55415 USA. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Sharp Mem Hosp & Rehabil Ctr, San Diego Cardiac Ctr, San Diego, CA 90034 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA 02115 USA. Univ Maryland, Dept Med, Div Cardiol, College Pk, MD 20742 USA. Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA. Univ Chicago, Dept Med, Div Cardiol, Chicago, IL 60637 USA. CHF Solut, Brooklyn Pk, MN USA. RP Costanzo, MR (reprint author), Edward Heart Hosp, Midw Heart Fdn, 4th Floor,801 S Washington St,POB 3226, Naperville, IL 60566 USA. EM mcostanzo@midwestheart.com RI Teerlink, John/D-2986-2012; OI Guglin, Maya/0000-0001-5746-3135 NR 26 TC 407 Z9 449 U1 2 U2 14 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 FEB 13 PY 2007 VL 49 IS 6 BP 675 EP 683 DI 10.1016/j.jacc.2006.07.073 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 137TO UT WOS:000244315300005 PM 17291932 ER PT J AU Persson, H Lonn, E Edner, M Baruch, L Lang, CC Morton, JJ Ostergren, J McKelvie, RS AF Persson, Hans Lonn, Eva Edner, Magnus Baruch, Lawrence Lang, Chim C. Morton, John J. Ostergren, Jan McKelvie, Robert S. CA Investigators CHARM Echocardiograp TI Diastolic dysfunction in heart failure with preserved systolic function: Need for objective evidence - Results from the CHARM echocardiographic Substudy CHARMES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; NATRIURETIC PEPTIDES; DOPPLER-ECHOCARDIOGRAPHY; ATRIAL-FIBRILLATION; NONINVASIVE ASSESSMENT; POPULATION; ABNORMALITIES; HYPERTENSION; CANDESARTAN; PRESSURES AB Objectives We tested the hypothesis that diastolic dysfunction (DD) was an important predictor of cardiovascular (CV) death or heart failure (HF) hospitalization in a subset of patients (ejection fraction [EF] > 40%) in the CHARM-Preserved study. Background More than 40% of hospitalized patients with HF have preserved systolic function (HF-PSF), suggesting that DD may be responsible for the clinical manifestations of HF. Methods Patients underwent Doppler echocardiographic examination that included assessment of pulmonary venous flow or determination of plasma NT-pro-brain natriuretic peptide >= 14 months after randomization to candesartan or placebo. The patients were classified into 1 of 4 diastolic function groups: normal, relaxation abnormality (mild dysfunction), pseudonormal (moderate dysfunction), and restrictive (severe dysfunction). Results There were 312 patients in the study, mean age was 66 +/- 11 years, EF was 50 +/- 10%, and 34% were women. The median follow-up was 18.7 months. Diastolic dysfunction was found in 67% of classified patients (n = 293), and moderate and severe DD were identified in 44%. Moderate and severe DD had a poor outcome compared with normal and mild DD (18% vs. 5%, p < 0.01). Diastolic dysfunction, age, diabetes, previous HF, and atrial fibrillation were univariate predictors of outcome. In multivariate analysis, moderate (hazard ratio [HR] 3.7, 95% confidence interval [CI] 1.2 to 11.1) and severe DD (HR 5.7, 95% CI 1.4 to 24.0) remained the only independent predictors (p = 0.003). Conclusions Objective evidence of DD was found in two-thirds of HF-PSF patients. Moderate and severe DD, which were found in less than one-half of the patients, were important predictors of adverse outcome. The results demonstrate the prognostic significance and need for objective evidence of DD in HF-PSF patients. C1 Danderyd Hosp, Dept Cardiol, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden. Populat Hlth Res Inst, Hamilton, ON, Canada. McMaster Univ, Hamilton, ON L8S 4L8, Canada. Mt Sinai Sch Med, Bronx Vet Affairs Med Ctr, Bronx, NY USA. Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland. Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. Karolinska Univ Hosp, Dept Med, Stockholm, Sweden. RP Persson, H (reprint author), Danderyd Hosp, Dept Cardiol, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden. EM hans.persson@ds.se NR 30 TC 145 Z9 152 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 13 PY 2007 VL 49 IS 6 BP 687 EP 694 DI 10.1016/j.jacc.2006.08.062 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 137TO UT WOS:000244315300007 PM 17291934 ER PT J AU Nigrovic, PA Binstadt, BA Monach, PA Johnsen, A Gurish, M Iwakura, Y Benoist, C Mathis, D Lee, DM AF Nigrovic, Peter A. Binstadt, Bryce A. Monach, Paul A. Johnsen, Alyssa Gurish, Michael Iwakura, Yoichiro Benoist, Christophe Mathis, Diane Lee, David M. TI Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytokine; mouse model; synovitis ID TUMOR-NECROSIS-FACTOR; FC-GAMMA RIII; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; TNF-ALPHA; INFLAMMATORY ARTHRITIS; GENE-EXPRESSION; SYNOVIAL-FLUIDS; DEFICIENT MICE; RESPONSES AB Mast cells are immune sentinels that participate in the defense against bacteria and parasites. Resident within the joint, mast cells become activated in human rheumatoid arthritis and are implicated in the pathogenesis of experimental murine synovitis. However, their arthritogenic role remains undefined. Using a model of autoantibody-induced arthritis, we show that mast cells contribute to the initiation of inflammation within the joint by elaboration of IL-1. Mast cells become activated to produce this cytokine via the IgG immune complex receptor Fc gamma RIII. Interestingly, mast cells become dispensable for the perpetuation of arthritis after delivery of IL-1, highlighting the contribution of this lineage to arthritis induction. These findings illuminate a mechanism by which mast cells can participate in the pathogenesis of autoimmune inflammatory arthritis and provide insights of potential relevance to human rheumatoid arthritis. C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan. RP Lee, DM (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM dlee@rics.bwh.harvard.edu RI Iwakura, Yoichiro/E-5457-2011; Binstadt, Bryce/N-1305-2013 OI Iwakura, Yoichiro/0000-0002-9934-5775; Binstadt, Bryce/0000-0003-3127-3856 FU NIAID NIH HHS [R01-AI059745, R21 AI059745]; NIAMS NIH HHS [K08 AR002214, K08 AR051321, K08-AR02214, K08-AR051321, R01 AR046580, R01-AR046580] NR 56 TC 97 Z9 99 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 FEB 13 PY 2007 VL 104 IS 7 BP 2325 EP 2330 DI 10.1073/pnas.0610852103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139NJ UT WOS:000244438500052 PM 17277081 ER PT J AU Bai, VU Kaseb, A Tejwani, S Divine, GW Barrack, ER Menon, M Pardee, AB Reddy, GPV AF Bai, V. Uma Kaseb, Ahmed Tejwani, Sheela Divine, George W. Barrack, Evelyn R. Menon, Mani Pardee, Arthur B. Reddy, G. Prem-Veer TI Identification of prostate cancer mRNA markers by averaged differential expression and their detection in biopsies, blood, and urine SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE body fluids; differential display ID GENE-EXPRESSION; CELLS; ANTIGEN; METHYLATION; PROGRESSION; SIGNATURE; CARCINOMA; VERSICAN; SYSTEM; ASSAY AB The advent of serum prostate-specific antigen (PSA) as a biomarker has enabled early detection of prostate cancer and, hence, improved clinical outcome. However, a low PSA is not a guarantee of disease-free status, and an elevated PSA is frequently associated with a negative biopsy. Therefore, our goal is to identify molecular markers that can detect prostate cancer with greater specificity in body fluids such as urine or blood. We used the RT-PCR differential display method to first identify mRNA transcripts differentially expressed in tumor vs. patient-matched nontumor prostate tissue. This analysis led to the identification of 44 mRNA transcripts that were expressed differentially in some but not all tumor specimens examined. To identify mRNA transcripts that are differentially expressed in most tumor specimens, we turned to differential display of pooled tissue samples, a technique we name averaged differential expression (ADE). We performed differential display of mRNA from patient-matched nontumor vs. tumor tissue, each pooled from 10 patients with various Gleason scores. Differentially expressed mRNA transcripts identified by AIDE were fewer in number, but were expressed in a greater percentage of tumors (> 75%) than those identified by differential display of mRNA from individual patient samples. Differential expression of these mRNA transcripts was also detected by RT-PCR in mRNA isolated from urine and blood samples of prostate cancer patients. Our findings demonstrate the principle that specific cDNA probes of frequently differentially expressed mRNA transcripts identified by AIDE can be used for the detection of prostate cancer in urine and blood samples. C1 Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI 48202 USA. Henry Ford Hlth Syst, Div Hematol & Oncol, Detroit, MI 48202 USA. Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Reddy, GPV (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, 1 Ford Pl,2D, Detroit, MI 48202 USA. EM preddy1@hfhs.org FU NIDDK NIH HHS [R01 DK057864, R01-DK57864] NR 40 TC 21 Z9 23 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 FEB 13 PY 2007 VL 104 IS 7 BP 2343 EP 2348 DI 10.1073/pnas.0610504104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139NJ UT WOS:000244438500055 PM 17283334 ER PT J AU Almind, K Manieri, M Sivitz, WI Cinti, S Kahn, CR AF Almind, Katrine Manieri, Monia Sivitz, William I. Cinti, Saverio Kahn, C. Ronald TI Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brown fat; UCP1; diabetes; genetics; obesity ID DIET-INDUCED OBESITY; INSULIN-RESISTANCE; UNCOUPLING PROTEINS; SKELETAL-MUSCLE; BODY-WEIGHT; ADAPTIVE THERMOGENESIS; ENERGY-EXPENDITURE; MESSENGER-RNA; WHITE FAT; ADIPOCYTE AB C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is > 700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a beta(3)-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Novo Nordisk AS, DK-2760 Malov, Denmark. Univ Ancona, Inst Normal Human Morphol & Anat, I-6013 Ancona, Italy. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK045935, DK30136, DK45935, DK60837, R01 DK031036, R01 DK060837, R37 DK031036] NR 42 TC 163 Z9 170 U1 1 U2 7 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 FEB 13 PY 2007 VL 104 IS 7 BP 2366 EP 2371 DI 10.1073/pnas.0610415104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139NJ UT WOS:000244438500059 PM 17283342 ER PT J AU Shakhnovich, EA Hung, DT Pierson, E Lee, K Mekalanos, JJ AF Shakhnovich, Elizabeth A. Hung, Deborah T. Pierson, Emily Lee, Kyungae Mekalanos, John J. TI Virstatin inhibits dimerization of the transcriptional activator ToxT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antibiotics; cholera; pharmacology; regulation; virulence ID VIBRIO-CHOLERAE VIRULENCE; SMALL-MOLECULE INHIBITORS; PROTEIN-PROTEIN INTERACTIONS; PSEUDOMONAS-AERUGINOSA; GENE-EXPRESSION; III SECRETION; REGULATOR; FAMILY AB The development of antimicrobials is critical in this time of increasing antibiotic resistance of most clinically relevant bacteria. To date, all current antibiotics focus on inhibiting crucial enzymatic activities of their protein targets (i.e., trimethoprim for dihydrofolate reductase), thus disrupting in vitro essential gene functions. In contrast, we have previously reported the identification of virstatin, a small molecule that inhibits virulence regulation in Vibrio cholerae, thereby preventing intestinal colonization in an infant mouse model for cholera. Virstatin prevents expression of the two major V. cholerae virulence factors, cholera toxin (CT) and the toxin coregulated pilus, by inhibiting the virulence transcriptional activator ToxT. It has previously been described that the N-terminal domain of ToxT has the ability to form homodimers. We now demonstrate that virstatin inhibits ToxT dimerization, thus demonstrating that it further falls into a unique class of inhibitors that works by disrupting protein-protein interactions, particularly homodimerization. Using virstatin, truncation mutants of ToxT, and a virstatin-resistant mutant, we show that dimerization is required for ToxT activation of the ctx promoter. In contrast, ToxT dimerization does not appear to be required at all of the other ToxT-regulated promoters, suggesting multiple mechanisms may exist for its transcriptional activity. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Dept Mol Biol, Boston, MA 02114 USA. MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. New England Reg Ctr Excellence, Boston, MA 02114 USA. RP Mekalanos, JJ (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Armenise Bldg,Room 425,200 Longwood Ave, Boston, MA 02115 USA. EM john_mekalanos@hms.harvard.edu FU NIAID NIH HHS [K08 AI060708, AI26289, K08 AI060708-01, R01 AI026289] NR 25 TC 63 Z9 65 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 13 PY 2007 VL 104 IS 7 BP 2372 EP 2377 DI 10.1073/pnas.0611643104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139NJ UT WOS:000244438500060 PM 17283330 ER PT J AU Nakazawa, T Hisatomi, T Nakazawa, C Noda, K Maruyama, K She, HC Matsubara, A Miyahara, S Nakao, S Yin, YQ Benowitz, L Hafezi-Moghadam, A Miller, JW AF Nakazawa, Toru Hisatomi, Toshio Nakazawa, Chifuyu Noda, Kosuke Maruyama, Kazuichi She, Haicheng Matsubara, Akihisa Miyahara, Shinsuke Nakao, Shintaro Yin, Yuqin Benowitz, Larry Hafezi-Moghadam, Ali Miller, Joan W. TI Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE macrophage recruitment; neuroprotection ID DIABETIC-RETINOPATHY; GENE-EXPRESSION; GANGLION-CELLS; UP-REGULATION; MCP-1 CCL2; IN-VIVO; MICE; ACTIVATION; DEGENERATION; INJURY AB Photoreceptor apoptosis is a major cause of visual loss in retinal detachment (RD) and several other visual disorders, but the underlying mechanisms remain elusive. Recently, increased expression of monocyte chemoattractant protein 1 (MCP-1) was reported in vitreous humor samples of patients with RD and diabetic retinopathy as well as in the brain tissues of patients with neurodegenerative diseases, including Alzheimer's disease and multiple sclerosis. Here we report that MCP-1 plays a critical role in mediating photoreceptor apoptosis in an experimental model of RD. RD led to increased MCP-1 expression in the Muller glia and increased CD11b(+) macrophage/microglia in the detached retina. An MCPA blocking antibody greatly reduced macrophage/microglia infiltration and RD-induced photoreceptor apoptosis. Confirming these results, MCP-1 gene-deficient mice showed significantly reduced macrophage/microglia infiltration after RD and very little photoreceptor apoptosis. In primary retinal mixed cultures, MCP-1 was cytotoxic for recoverin(+) photoreceptors, and this toxicity was eliminated through immunodepleting macrophage/microglia from the culture. In vivo, deletion of the gene encoding CD11b/CD18 nearly eliminated macrophage/microglia infiltration to the retina after RD and the loss of photoreceptors. Thus, MCP-1 expression and subsequent macrophage/microglia infiltration and activation are critical for RD-induced photoreceptor apoptosis. This pathway may be an important therapeutic target for preventing photoreceptor apoptosis in RD and other CNS diseases that share a common etiology. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Childrens Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Neurosurg & Neurobiol, Boston, MA 02114 USA. Tohoku Univ, Sch Med, Dept Ophthalmol, Sendai, Miyagi 9808574, Japan. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Childrens Hosp, 243 Charles St, Boston, MA 02114 USA. EM joan_miller@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697; Hisatomi, Toshio/0000-0003-2552-9595 FU NEI NIH HHS [EY014104, EY05690, P30 EY014104, R01 EY005690]; NIAID NIH HHS [AI50775, K08 AI050775] NR 55 TC 148 Z9 155 U1 1 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 FEB 13 PY 2007 VL 104 IS 7 BP 2425 EP 2430 DI 10.1073/pnas.0608167104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 139NJ UT WOS:000244438500069 PM 17284607 ER PT J AU Kimmel, SE Chen, Z Price, M Parker, CS Metlay, JP Christie, JD Brensinger, CM Newcomb, CW Samaha, FF Gross, R AF Kimmel, Stephen E. Chen, Zhen Price, Maureen Parker, Catherine S. Metlay, Joshua P. Christie, Jason D. Brensinger, Colleen M. Newcomb, Craig W. Samaha, Frederick F. Gross, Robert TI The influence of patient adherence on anticoagulation control with warfarin - Results from the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ATRIAL-FIBRILLATION; ORAL ANTICOAGULANTS; STROKE PREVENTION; ELDERLY PATIENTS; THERAPY; COMPLICATIONS; OUTCOMES; ASPIRIN; RISK AB Background: Warfarin sodium is a highly efficacious drug, but proper levels of anticoagulation are difficult to maintain. Conflicting data exist on the influence of patient adherence on anticoagulation control. Methods: We performed a prospective cohort study at 3 anticoagulation clinics to determine the effect of adherence on anticoagulation control. Patients treated with warfarin with a target international normalized ratio of 2.0 to 3.0 were monitored with electronic Medication Event Monitoring System (MEMS) medication bottle caps. Detailed information was collected on other factors that might alter warfarin response. Results: Among 136 participants observed for a mean of 32 weeks, 92% had at least 1 missed or extra bottle opening; 36% missedmorethan 20% of their bottle openings; and 4% had more than 10% extra bottle openings. In multivariable analyses, there was a significant association between under adherence and underanticoagulation. For each 10% increase in missed pill bottle openings, there was a 14% increase in the odds of underanticoagulation (P <. 001); participants with more than 20% missed bottle openings(1-2 missed days each week) had more than a 2-fold increase in the odds of underanticoagulation (adjusted odds ratio, 2.10; 95% confidence interval, 1.48-2.96). Participants who had extra pill bottle openings on more than 10% of days had a statistically significant increase in over anticoagulation (adjusted odds ratio, 1.73; 95% confidence interval, 1.09-2.74). Conclusion: Patients have substantial difficulties maintaining adequate adherence with warfarin regimens, and this poor adherence has a significant effect on anticoagulation control. C1 Univ Penn, Sch Med, Dept Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Kimmel, SE (reprint author), Univ Penn, Sch Med, Dept Med, Ctr Clin Epidemiol & Biostat, 717 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM skimmel@cceb.med.upenn.edu FU AHRQ HHS [P01 HS 011530]; NHLBI NIH HHS [R01 HL 066176-04] NR 26 TC 128 Z9 136 U1 0 U2 7 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 FEB 12 PY 2007 VL 167 IS 3 BP 229 EP 235 DI 10.1001/archinte.167.3.229 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 135OP UT WOS:000244163200002 PM 17296877 ER PT J AU Glazer, NL Dublin, S Smith, NL French, B Jackson, LA Hrachovec, JB Siscovick, DS Psaty, BM Heckbert, SR AF Glazer, Nicole L. Dublin, Sascha Smith, Nicholas L. French, Benjamin Jackson, Lisa A. Hrachovec, Jennifer B. Siscovick, David S. Psaty, Bruce M. Heckbert, Susan R. TI Newly detected atrial fibrillation and compliance with antithrombotic guidelines SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst ID ADJUSTED-DOSE WARFARIN; STROKE PREVENTION; ASPIRIN THERAPY; CLINICAL-TRIALS; RISK-FACTORS; ANTICOAGULATION; PREDICTORS; PATTERNS; EFFICACY; THROMBOEMBOLISM AB Background: Guidelines recommend the use of antithrombotic therapy for stroke prevention in patients with atrial fibrillation (AF), but compliance with such guidelines has not been widely studied among patients with newly detected AF. Our objective was to assess compliance with antithrombotic guidelines and to identify patient characteristics associated with warfarin use. Methods: A population-based study of newly detected AF (patient age, 30-84 years) was conducted within a large health plan. Cardiovascular disease risk factors, comorbid conditions, medication use, and international normalized ratios were abstracted from the medical record. Patients were stratified by embolic risk according to American College of Chest Physicians (ACCP) criteria. We analyzed the proportion of patients with AF receiving warfarin or aspirin (>= 325 mg/d) during the 6 months following AF. Relative risk regression estimated the association of risk factors and patient characteristics with warfarin use. Results: Overall, 73% of patients (418/572) with newly detected AF had evidence of antithrombotic use after AF onset. Among the 76% (437/572) of patients with AF at high risk for stroke, 59% (257/437) used warfarin, 28% (123/437) used aspirin, and 24% (104/437) used neither. The major predictor of warfarin use was AF classification; intermittent or sustained AF had relative risks for warfarin use of 2.8 (95% confidence interval, 2.23.6) and 2.9 ( 95% confidence interval, 2.2-3.7), respectively, compared with transitory AF. Conclusions: Three quarters of the patients with newly detected AF received antithrombotic therapy, yet many at high risk of stroke did not receive warfarin. Atrial fibrillation classification, rather than stroke risk factors, was strongly associated with warfarin use. C1 Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. Univ Washington, Dept Biostat, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA 98101 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. RP Glazer, NL (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM nlg@u.washington.edu FU NHLBI NIH HHS [T32 HL 07902, HL 43201, HL 68639, HL 68986, HL 73410] NR 33 TC 92 Z9 95 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 12 PY 2007 VL 167 IS 3 BP 246 EP 252 DI 10.1001/archinte.167.3.246 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 135OP UT WOS:000244163200004 PM 17296879 ER PT J AU Singh, H Thomas, EJ Khan, MM Petersen, LA AF Singh, Hardeep Thomas, Eric J. Khan, Myrna M. Petersen, Laura A. TI Identifying diagnostic errors in primary care using an electronic screening algorithm SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 27-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med ID ADVERSE DRUG EVENTS; HOSPITALIZED-PATIENTS; MALPRACTICE CLAIMS; MEDICAL ERROR; RETURN VISITS; HEALTH-CARE; SURVEILLANCE; EMERGENCY; ACCIDENT AB Background: Diagnostic errors are the leading basis for malpractice claims in primary care, yet these errors are underidentified and understudied. Computerized methods used to screen for other types of errors (eg, medication related) have not been applied to diagnostic errors. Our objectives were to assess the feasibility of computerized screening to identify diagnostic errors in primary care and to categorize diagnostic breakdowns using a recently published taxonomy. Methods: We used an algorithm to screen the electronic medical records of patients at a single hospital that is part of a closed health care system. A Structured Query Language-based program detected the presence of 1 of 2 mutually exclusive electronic screening criteria: screen 1, a primary care visit ( index visit) followed by a hospitalization in the next 10 days; or screen 2, an index visit followed by 1 or more primary care, urgent care, or emergency department visits within 10 days. Two independent, blinded reviewers determined the presence or absence of diagnostic error through medical record review of visits with positive and negative screening results. Results: Among screen 1 and 2 positive visits, 16.1% and 9.4%, respectively, were associated with a diagnostic error. The error rate was 4% in control cases that met neither screening criterion. The most common primary errors in the diagnostic process were failure or delay in eliciting information and misinterpretation or suboptimal weighing of critical pieces of data from the history and physical examination. The most common secondary errors were suboptimal weighing or prioritizing of diagnostic probabilities and failure to recognize urgency of illness or its complications. Conclusions: Electronic screening has potential to identify records that may contain diagnostic errors in primary care, and its performance is comparable to screening tools for other types of errors. Future studies that validate these findings in other settings could provide improvement initiatives in this area. C1 Michael E DeBakey VA Med Ctr 152, Div Hlth Policy & Qual, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Med, Div Gen Med, Houston, TX 77030 USA. Univ Texas, Ctr Excellence Patient Safety Res & Practice, Houston, TX 77030 USA. RP Singh, H (reprint author), Michael E DeBakey VA Med Ctr 152, Div Hlth Policy & Qual, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.tmc.edu FU AHRQ HHS [1P01 HS 11544-01]; NCRR NIH HHS [K12 RR 17665] NR 33 TC 52 Z9 52 U1 5 U2 7 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 FEB 12 PY 2007 VL 167 IS 3 BP 302 EP 308 DI 10.1001/archinte.167.3.302 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 135OP UT WOS:000244163200014 PM 17296888 ER PT J AU Kumari, K Augusti, KT AF Kumari, Kumud Augusti, K. T. TI Lipid lowering effect of S-methyl cysteine sulfoxide from Allium cepa Linn in high cholesterol diet fed rats SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE hyperlipidemia; Allium cepa; sulfoxide amino acids; antidiabetic; anti-hyperlipidemic; gugulipid ID METHYLCYSTEINE SULFOXIDE; ACIDS; ONION; ANTAGONIST; BLOOD; LIVER AB The lipid lowering action of S-methyl cysteine sulfoxide (SMCS) isolated from Alliurn cepa Linn (family: Liliaceae) was investigated in Sprague-Dawley rats fed on 1% cholesterol diet, in comparison to the hypolipidernic drug gugulipid. Administration of SMCS at a dose of 200 mg/kg body weight for 45 days ameliorated the hyperlipidemic condition. The lipid profile in serum and tissues showed that concentrations of cholesterol, triglyceride and phospholipids were significantly reduced when compared to their untreated counterparts. The total lipoprotein lipase activity in the adipose tissue was decreased with also a decrease in the free fatty acid levels in serum and tissues. The activities of the lipogenic enzymes glucose 6-phosphate dehydrogenase and malic enzyme as also of HMG CoA reductase in the tissues remained low on treatment indicating that both the drugs did not favor lipogenesis and cholesterogenesis in the hyperlipidemic animals. The fecal excretion of bile acids and sterols was further increased upon treatment with the drugs. The results are directive to that both gugulipid and SMCS cause reduction of enclogenous lipogenesis, increase catabolism of lipids and subsequent excretion of metabolic by-products through the intestinal tract. However, gugulipid is a better drug than SMCS at a low dose of 50 mg/kg body weight. (c) 2006 Elsevier Ireland Ltd. All fights reserved. C1 Univ Kerala, Dept Biochem, Trivandrum 695581, Kerala, India. RP Kumari, K (reprint author), Massachusetts Gen Hosp, Diabet Res Lab, Room 513,65 Landsdowne St, Cambridge, MA 02139 USA. EM kumud_kumari@rediffmail.com; ktaugusti@yahoo.co.uk NR 28 TC 39 Z9 42 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD FEB 12 PY 2007 VL 109 IS 3 BP 367 EP 371 DI 10.1016/j.jep.2006.07.045 PG 5 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 134NI UT WOS:000244089700001 PM 16987625 ER PT J AU McMahon, PM Christiani, DC AF McMahon, Pamela M. Christiani, David C. TI Computed tomography screening for lung cancer SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID CT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP McMahon, PM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM dchristiani@partners.org NR 6 TC 13 Z9 13 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD FEB 10 PY 2007 VL 334 IS 7588 BP 271 EP 271 DI 10.1136/bmj.39090.662963.80 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 142MN UT WOS:000244654100004 PM 17289689 ER PT J AU Zhou, W Heist, RS Liu, G Asomaning, K Neuberg, DS Hollis, BW Wain, JC Lynch, TJ Giovannucci, E Su, L Christiani, DC AF Zhou, Wei Heist, Rebecca S. Liu, Geoffrey Asomaning, Kofi Neuberg, Donna S. Hollis, Bruce W. Wain, John C. Lynch, Thomas J. Giovannucci, Edward Su, Li Christiani, David C. TI Circulating 25-hydroxyvitamin D levels predict survival in early-stage non-small-cell lung cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID VITAMIN-D STATUS; FOOD FREQUENCY QUESTIONNAIRE; MORTALITY; REPRODUCIBILITY; METASTASIS; VALIDITY; HEALTH; SUN; D-3 AB Purpose Our previous analyses suggested that surgery in the summertime with higher vitamin D intake is associated with improved survival in patients with early-stage non-small-cell lung cancer (NSCLC). We further investigated the results of circulating 25-hydroxyvitamin D ( 25[ OH] D) levels on overall survival ( OS) and recurrence-free survival (RFS) in NSCLC patients. Patients and Methods Among 447 patients with early-stage NSCLC, data were analyzed using Cox proportional hazards models, adjusting for age, sex, stage, smoking, and treatment. Results The median follow-up time was 72 months ( range, 0.2 to 141), with 161 recurrences and 234 deaths. For OS, the adjusted hazard ratio (AHR) was 0.74 (95% CI, 0.50 to 1.10; P-trend =.07) for the highest versus lowest quartile of 25( OH) D levels. Stratified by stage, a strong association was observed among stage IB-IIB patients ( AHR, 0.45; 95% CI, 0.24 to 0.82; P-trend =.002), but not among stage IA patients ( AHR, 1.10; 95% CI, 0.62 to 1.96; P-trend =.53). Similar effects of 25(OH) D levels were observed among the 309 patients with dietary information ( AHR, 0.74; 95% CI, 0.46 to 1.17; P-trend =.19). For the joint effects of 25( OH) D level and vitamin D intake, the combined high 25( OH) D levels and high vitamin D intake ( by median) were associated with better survival than the combined low 25( OH) D levels and low vitamin D intake ( AHR, 0.64; 95% CI, 0.42 to 0.98; P-trend =.06). Again, stronger associations were observed among stage IB-IIB than IA patients. Similar effects of 25( OH) D levels and vitamin D intake were observed for RFS. Conclusion Vitamin D may be associated with improved survival of patients with early-stage NSCLC, particularly among stage IB-IIB patients. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Thorac Surg Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. Med Univ S Carolina, Darby Childrens Res Inst, Charleston, SC 29425 USA. RP Zhou, W (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM wzhou@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA074386, CA090578, CA119650-01A1, ES/CA 06409, CA 092824]; NIEHS NIH HHS [ES00002] NR 21 TC 120 Z9 124 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 10 PY 2007 VL 25 IS 5 BP 479 EP 485 DI 10.1200/JCO.2006.07.5358 PG 7 WC Oncology SC Oncology GA 135TI UT WOS:000244176000004 PM 17290055 ER PT J AU Coates, AS Keshaviah, A Thurlimann, B Mouridsen, H Mauriac, L Forbes, JF Paridaens, R Castiglione-Gertsch, M Gelber, RD Colleoni, M Lang, I Del Mastro, L Smith, I Chirgwin, J Nogaret, JM Pienkowski, T Wardley, A Jakobsen, EH Price, KN Goldhirsch, A AF Coates, Alan S. Keshaviah, Aparna Thuerlimann, Beat Mouridsen, Henning Mauriac, Louis Forbes, John F. Paridaens, Robert Castiglione-Gertsch, Monica Gelber, Richard D. Colleoni, Marco Lang, Istvan Del Mastro, Lucia Smith, Ian Chirgwin, Jacquie Nogaret, Jean-Marie Pienkowski, Tadeusz Wardley, Andrew Jakobsen, Erik H. Price, Karen N. Goldhirsch, Aron TI Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: Update of study BIG 1-98 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 31st Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol ID AROMATASE INHIBITORS; RANDOMIZED-TRIAL; ANASTROZOLE AB Purpose Previous analyses of the Breast International Group ( BIG) 1-98 four-arm study compared initial therapy with letrozole or tamoxifen including patients randomly assigned to sequential treatment whose information was censored at the time of therapy change. Because this presentation may unduly reflect early events, the present analysis is limited to patients randomly assigned to the continuous therapy arms and includes protocol-defined updated results. Patients and Methods Four thousand nine hundred twenty-two of the 8,028 postmenopausal women with receptor-positive early breast cancer randomly assigned (double-blind) to the BIG 1-98 trial were assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen; the remainder of women were assigned to receive the agents in sequence. Disease-free survival (DFS) was the primary end point. Results At a median follow-up time of 51 months, we observed 352 DFS events among 2,463 women receiving letrozole and 418 events among 2,459 women receiving tamoxifen. This reflected an 18% reduction in the risk of an event ( hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P =.007). No predefined subsets showed differential benefit. Adverse events were similar to previous reports. Patients on tamoxifen experienced more thromboembolic events, endometrial pathology, hot flashes, night sweats, and vaginal bleeding. Patients on letrozole experienced more bone fractures, arthralgia, low-grade hypercholesterolemia, and cardiovascular events other than ischemia and cardiac failure. Conclusion The present updated analysis, which was limited to patients on monotherapy arms in BIG 1-98, yields results similar to those from the previous primary analysis but more directly comparable with results from other trials of continuous therapy using a single endocrine agent. C1 Int Breast Canc Study Grp Coordinating Ctr, CH-3008 Bern, Switzerland. Kantonsspital, Swiss Grp Clin Canc Res SAKK, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. Oncol Inst So Switzerland, Bellinzona, Switzerland. Univ Sydney, Sydney, NSW 2006, Australia. Univ Newcastle, Newcastle Mater Hosp, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. Box Hill Hosp, Melbourne, Vic, Australia. Maroondah Hosp, Melbourne, Vic, Australia. Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Rigshosp, Danish Breast Canc Grp, DK-2100 Copenhagen, Denmark. Vejle Hosp, Vejle, Denmark. Inst Bergonie, French Breast Canc Grp, Bordeaux, France. Catholic Univ Louvain, Univ Hosp Gasthuisberg, Dept Med Oncol, B-3000 Louvain, Belgium. Inst Jules Bordet, B-1000 Brussels, Belgium. European Inst Oncol, Milan, Italy. Natl Inst Canc Res, Genoa, Italy. Natl Inst Oncol, Budapest, Hungary. Royal Marsden Hosp, London SW3 6JJ, England. S Manchester Univ Hosp Trust, Christie Hosp Natl Hlth Serv Trust, Manchester, Lancs, England. Maria Sklodowska Curie Mem Inst Oncol, Ctr Canc, Warsaw, Poland. RP Coates, AS (reprint author), Int Breast Canc Study Grp Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM alan.coates@ibcsg.org RI Wardley, ANdrew/N-8135-2015; Rimassa, Lorenza/N-4884-2016; OI Wardley, ANdrew/0000-0002-9639-0888; Rimassa, Lorenza/0000-0001-9957-3615; Del Mastro, Lucia/0000-0002-9546-5841 FU NCI NIH HHS [CA-75362] NR 16 TC 583 Z9 604 U1 4 U2 17 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 FEB 10 PY 2007 VL 25 IS 5 BP 486 EP 492 DI 10.1200/JCO.2006.08.8617 PG 7 WC Oncology SC Oncology GA 135TI UT WOS:000244176000005 PM 17200148 ER PT J AU Skapek, SX Ferguson, WS Granowetter, L Devidas, M Perez-Atayde, AR Dehner, LP Hoffer, FA Speights, R Gebhardt, MC Dahl, GV Grier, HE AF Skapek, Stephen X. Ferguson, William S. Granowetter, Linda Devidas, Meenakshi Perez-Atayde, Antonio R. Dehner, Louis P. Hoffer, Fredric A. Speights, Roseanne Gebhardt, Mark C. Dahl, Gary V. Grier, Holcombe E. TI Vinblastine and methotrexate for desmoid fibromatosis in children: Results of a Pediatric Oncology Group phase II trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LOW-DOSE CHEMOTHERAPY; FAMILIAL ADENOMATOUS POLYPOSIS; NONCYTOTOXIC DRUG-THERAPY; AGGRESSIVE FIBROMATOSIS; COMBINATION CHEMOTHERAPY; RADIATION-THERAPY; TUMORS; MANAGEMENT; TAMOXIFEN; RECURRENT AB Purpose To determine the efficacy and safety of using vinblastine (Vbl) and methotrexate (Mtx) in children with desmoid-type fibromatosis that is recurrent or not amenable to treatment with radiation or surgery. Patients and Methods A phase II study was conducted within the Pediatric Oncology Group. Patients were treated using Vbl ( 5 mg/m(2)/dose) and Mtx ( 30 mg/m(2)/dose), both administered by intravenous injection weekly for 26 weeks and every other week for an additional 26 weeks. Response was assessed by bidimensional measurements of tumor on axial imaging ( magnetic resonance imaging or computed tomography). Results Over 35 months, 28 patients were enrolled; 27 were eligible, and 26 were assessable for response. A measurable response was documented in eight patients (31%), and 10 patients had stable disease documented as the best response to treatment. Eighteen patients had disease progression at a median time of 9.1 months. Eight patients remain free of disease progression at a median of 43.4 months from study entry. Nine patients reported no to moderate toxicity. Neutropenia was the most common toxicity ( n = 22) and the most common grade 4 toxicity ( n = 5). Anemia, nausea, vomiting, and elevations in hepatic transaminases were also common and were reversible with interruption of chemotherapy. Conclusion Vbl and Mtx are well tolerated in children with desmoid-type fibromatosis. Furthermore, this combination can promote tumor regression or block tumor growth in most children. C1 St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. Cardinal Glennon Childrens Hosp, Dept Hematol Oncol, St Louis, MO USA. Washington Univ, St Louis Childrens Hosp, Med Ctr, Lauren V Ackerman Lab Surg Pathol, St Louis, MO 63110 USA. Columbia Presbyterian Coll Phys & Surg, Dept Pediat Oncol, New York, NY USA. Univ Florida, Childrens Oncol Grp Data Ctr, Gainesville, FL USA. Univ Florida, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Orthoped Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Dept Pediat Hematol Oncol, Palo Alto, CA 94304 USA. RP Skapek, SX (reprint author), St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM steve.skapek@stjude.org OI Granowetter MD, Linda/0000-0002-2399-9107 FU NCI NIH HHS [CA098543-02, CA29139] NR 37 TC 60 Z9 64 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 FEB 10 PY 2007 VL 25 IS 5 BP 501 EP 506 DI 10.1200/JCO.2006.08.2966 PG 6 WC Oncology SC Oncology GA 135TI UT WOS:000244176000007 PM 17290057 ER PT J AU Balboni, TA Vanderwerker, LC Block, SD Paulk, ME Lathan, CS Peteet, JR Prigerson, HG AF Balboni, Tracy A. Vanderwerker, Lauren C. Block, Susan D. Paulk, M. Elizabeth Lathan, Christopher S. Peteet, John R. Prigerson, Holly G. TI Religiousness and spiritual support among advanced cancer patients and associations with end-of-life treatment preferences and quality of life SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; TERMINALLY-ILL; CARE; ATTITUDES; ACCEPTABILITY; QUESTIONNAIRE; INTERVENTION; ADJUSTMENT; PHYSICIANS; DECISIONS AB Purpose Religion and spirituality play a role in coping with illness for many cancer patients. This study examined religiousness and spiritual support in advanced cancer patients of diverse racial/ ethnic backgrounds and associations with quality of life (QOL), treatment preferences, and advance care planning. Methods The Coping With Cancer study is a federally funded, multi-institutional investigation examining factors associated with advanced cancer patient and caregiver well-being. Patients with an advanced cancer diagnosis and failure of first-line chemotherapy were interviewed at baseline regarding religiousness, spiritual support, QOL, treatment preferences, and advance care planning. Results Most (88%) of the study population ( N = 230) considered religion to be at least somewhat important. Nearly half (47%) reported that their spiritual needs were minimally or not at all supported by a religious community, and 72% reported that their spiritual needs were supported minimally or not at all by the medical system. Spiritual support by religious communities or the medical system was significantly associated with patient QOL ( P =.0003). Religiousness was significantly associated with wanting all measures to extend life ( odds ratio, 1.96; 95% CI, 1.08 to 3.57). Conclusion Many advanced cancer patients' spiritual needs are not supported by religious communities or the medical system, and spiritual support is associated with better QOL. Religious individuals more frequently want aggressive measures to extend life. C1 Harvard Univ, Radiat Oncol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. Univ Texas, SW Med Ctr, Palliat Care Serv, Dallas, TX USA. RP Balboni, TA (reprint author), Harvard Univ, Radiat Oncol Program, 375 Longwood Ave, Boston, MA 02115 USA. EM tbalboni@partners.org FU NCI NIH HHS [CA106370, R01 CA106370, R01 CA106370-04]; NIMH NIH HHS [MH63892, R01 MH063892] NR 45 TC 282 Z9 293 U1 6 U2 36 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 FEB 10 PY 2007 VL 25 IS 5 BP 555 EP 560 DI 10.1200/JCO.2006.07.9046 PG 6 WC Oncology SC Oncology GA 135TI UT WOS:000244176000015 PM 17290065 ER PT J AU Sequist, LV Bell, DW Lynch, TJ Haber, DA AF Sequist, Lecia V. Bell, Daphne W. Lynch, Thomas J. Haber, Daniel A. TI Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TYROSINE KINASE INHIBITOR; PHASE-III TRIAL; PREVIOUSLY TREATED PATIENTS; SOUTHWEST-ONCOLOGY-GROUP; EGFR MUTATIONS; GENE-MUTATIONS; ACTIVATING MUTATIONS; BRONCHIOLOALVEOLAR-CARCINOMA; GEFITINIB SENSITIVITY; ACQUIRED-RESISTANCE AB In the last 5 years the epidermal growth factor receptor ( EGFR) has emerged as one of the most important targets for drug development in oncology. Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefit in colorectal and head and neck cancer when combined with chemotherapy and/or radiation. Small molecules that inhibit the tyrosine kinase (TK) domain of EGFR have become critical new weapons in the treatment of non-small-cell lung cancer (NSCLC). The discovery that mutations in the TK domain are associated with dramatic and sustained responses to EGFR TK inhibitors (TKIs) has allowed the design of trials to test these agents as potential first-line therapies and has provided a fascinating window into the future of genotype-directed targeted therapy. Recent advances in understanding the biologic basis of acquired resistance to these agents have great potential to improve the clinical effectiveness of this class of drugs. This review summarizes the biology of EGFR in NSCLC, the clinical and molecular predictors of benefit from treatment with EGFR TKIs, the use of patient-specific molecular profiling, and future directions of clinical and basic scientific research. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY-7,Bldg 149,13th St, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 83 TC 384 Z9 403 U1 4 U2 35 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 FEB 10 PY 2007 VL 25 IS 5 BP 587 EP 595 DI 10.1200/JCO.2006.07.3585 PG 9 WC Oncology SC Oncology GA 135TI UT WOS:000244176000019 PM 17290067 ER PT J AU Drappatz, J Doherty, LM Wen, PY Kesari, S AF Drappatz, Jan Doherty, Lisa M. Wen, Patrick Y. Kesari, Santosh TI Cerebrospinal fluid spread of anaplastic glioma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTASES; PATTERNS C1 Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. Hacettepe Univ, Sch Med, Ankara, Turkey. Brigham & Womens Hosp, Div Canc Neurol, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Drappatz, J (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. RI Kesari, Santosh/E-8461-2013 NR 7 TC 0 Z9 0 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 FEB 10 PY 2007 VL 25 IS 5 BP 596 EP 597 DI 10.1200/JCO.2006.09.3096 PG 2 WC Oncology SC Oncology GA 135TI UT WOS:000244176000020 ER PT J AU Allen, AM Haddad, RI Tishler, RB AF Allen, Aaron M. Haddad, Robert I. Tishler, Roy B. TI Retropharyngeal nodes in hypopharynx cancer on positron emission tomography SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NECK-CANCER; HEAD; DISSECTION; CARCINOMA C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Allen, AM (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 6 TC 1 Z9 1 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 FEB 10 PY 2007 VL 25 IS 5 BP 599 EP 601 DI 10.1200/JCO.2006.09.1488 PG 4 WC Oncology SC Oncology GA 135TI UT WOS:000244176000022 PM 17290070 ER PT J AU Shuster, E AF Shuster, Evelyne TI Microarray genetic screening: a prenatal roadblock for life? SO LANCET LA English DT Article ID DIAGNOSIS; DNA C1 Philadelphia Vet Affairs Med Ctr, Off Med Eth, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Shuster, E (reprint author), Philadelphia Dept Vet Affairs, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM Evelyn.shuster@med.va.gov NR 31 TC 38 Z9 38 U1 0 U2 1 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 FEB 10 PY 2007 VL 369 IS 9560 BP 526 EP 529 DI 10.1016/S0140-6736(07)60239-6 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 135XX UT WOS:000244188300035 PM 17292772 ER PT J AU Pradel, N Santini, CL Bernadac, A Shih, YL Goldberg, MB Wu, LF AF Pradel, Nathalie Santini, Claire-Lise Bernadac, Alain Shih, Yu-Ling Goldberg, Marcia B. Wu, Long-Fei TI Polar positional information in Escherichia coli spherical cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE periplasm; polar localization information; spherical cells; MreB; GFP; mCherry ID PENICILLIN-BINDING PROTEIN-2; BACTERIAL-CELL; CAULOBACTER-CRESCENTUS; MRE-GENES; SHAPE; MEMBRANE; WALL; LOCALIZATION; SECRETION; ICSA AB Shigella surface protein IcsA and its cytoplasmic derivatives are localized to the old pole of rod-shaped cells when expressed in Escherichia coli. In spherical mreB cells, IcsA is targeted to ectopic sites and close to one extremity of actin-like MamK filament. To gain insight into the properties of the sites containing polar material, we studied the IcsA localization in spherical cells. GFP was exported into the periplasm via the Tat pathway and used as a periplasmic space marker. GFP displayed zonal fluorescence in both mreB and rodA-pbpA spherical K coli cells, indicating an uneven periplasmic space. Deconvolution images revealed that the cytoplasmic IcsA fused to mCherry was localized outside or at the edge of the GFP zones. These observations strongly suggest that polar material is restricted to the positions where the periplasm possesses particular structural or biochemical properties. (c) 2006 Elsevier Inc. All rights reserved. C1 CNRS, Inst Biol Struct & Microbiol, UPR9043, Chim Bacterienne Lab, F-13402 Marseille 20, France. CNRS, Inst Biol Struct & Microbiol, Serv Microscopie Elect, F-13402 Marseille, France. Univ Connecticut, Ctr Hlth, Dept Mol Microbial & Struct Biol, Farmington, CT 06032 USA. Massachusetts Gen Hosp, Div Infect Dis, Bacterial Pathogenesis Labs, Cambridge, MA 02139 USA. RP Wu, LF (reprint author), CNRS, Inst Biol Struct & Microbiol, UPR9043, Chim Bacterienne Lab, 31 Chemin Joseph Aiguier, F-13402 Marseille 20, France. EM wu@ibsm.cnrs-mrs.fr RI Shih, Yu-Ling/F-8396-2011 OI Shih, Yu-Ling/0000-0002-8232-2569 NR 36 TC 8 Z9 8 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 FEB 9 PY 2007 VL 353 IS 2 BP 493 EP 500 DI 10.1016/j.bbrc.2006.12.054 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 126VH UT WOS:000243543100044 PM 17188233 ER PT J AU Haller, AA Lauer, GM King, TH Kemmler, C Fiolkoski, V Lu, YN Bellgrau, D Rodell, TC Apelian, D Franzusoff, A Duke, RC AF Haller, Aurelia A. Lauer, Georg M. King, Thomas H. Kemmler, Charles Fiolkoski, Valerie Lu, Yingnian Bellgrau, Don Rodell, Timothy C. Apelian, David Franzusoff, Alex Duke, Richard C. TI Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCVNS3 and Core proteins SO VACCINE LA English DT Article DE hepatitis C; vaccinc immunotherapy; yeast; HCV; S. cerevisiae ID HEPATITIS-C VIRUS; TOLL-LIKE RECEPTORS; INNATE IMMUNE-SYSTEM; MEDIATED-IMMUNITY; B-VIRUS; INFECTION; VACCINATION; DNA; INDUCTION; PATHOGENS AB Control of primary infection with hepatitis C virus (HCV) is associated with robust and broad T cell immunity. In contrast, chronic infection is characterized by weak T cell responses suggesting that an approach that boosts these responses could be a therapeutic advance. Saccharomyces cerevisiae is an effective inducer of innate and adaptive cellular immunity and we have generated recombinant yeast cells (GI-5005) that produce an HCV NS3-Core fusion protein. Pre-clinical studies in mice showed that GI-5005 induced potent antigen-specific proliferative and cytotoxic T cell responses that were associated with Th1-type cytokine secretion. In studies in which GI-5005 was administered up to 13 times, no detectable vector neutralization or induction of tolerance was observed. Prophylactic as well as therapeutic administration of GI-5005 in mice led to eradication of tumor cells expressing HCV NS3 protein. Immunotherapy with GI-5005 is being evaluated in chronic HCV infected individuals in a Phase 1 clinical trial. (c) 2006 Elsevier Ltd. All rights reserved. C1 GlobelImmune Incwwwtfcoglivenet, Louisville, CO 80027 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. Univ Hartford, Sch Med, Boston, MA 02129 USA. Univ Colorado, Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Dept Med, Denver, CO 80262 USA. Hlth Sci Ctr, Denver, CO 80262 USA. RP Duke, RC (reprint author), GlobelImmune Incwwwtfcoglivenet, 1450 Infinite Dr, Louisville, CO 80027 USA. EM richard.duke@globeimmune.com NR 30 TC 63 Z9 70 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 9 PY 2007 VL 25 IS 8 BP 1452 EP 1463 DI 10.1016/j.vaccine.2006.10.035 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 136PJ UT WOS:000244236300012 PM 17098335 ER PT J AU Sharpless, NE DePinho, RA AF Sharpless, Norman E. DePinho, Ronald A. TI Cancer biology - Gone but not forgotten SO NATURE LA English DT Editorial Material ID IN-VIVO; SENESCENCE C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med & Genet, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Boston, MA 02115 USA. RP Sharpless, NE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Med & Genet, Chapel Hill, NC 27599 USA. EM nes@med.unc.edu; ron_depinho@dfci.harvard.edu NR 12 TC 21 Z9 22 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 8 PY 2007 VL 445 IS 7128 BP 606 EP 607 DI 10.1038/445606a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 133UM UT WOS:000244039400030 PM 17251931 ER PT J AU Ventura, A Kirsch, DG McLaughlin, ME Tuveson, DA Grimm, J Lintault, L Newman, J Reczek, EE Weissleder, R Jacks, T AF Ventura, Andrea Kirsch, David G. McLaughlin, Margaret E. Tuveson, David A. Grimm, Jan Lintault, Laura Newman, Jamie Reczek, Elizabeth E. Weissleder, Ralph Jacks, Tyler TI Restoration of p53 function leads to tumour regression in vivo SO NATURE LA English DT Article ID LUNG-CANCER; MUTANT P53; SUPPRESSION; MICE; ANGIOGENESIS; RECOMBINASES; EXPRESSION; MUTATIONS; GEFITINIB; EFFICACY AB Tumorigenesis is a multi-step process that requires activation of oncogenes and inactivation of tumour suppressor genes(1). Mouse models of human cancers have recently demonstrated that continuous expression of a dominantly acting oncogene ( for example, Hras, Kras and Myc) is often required for tumour maintenance(2-5); this phenotype is referred to as oncogene addiction(6). This concept has received clinical validation by the development of active anticancer drugs that specifically inhibit the function of oncoproteins such as BCR-ABL, c-KIT and EGFR(7-10). Identifying additional gene mutations that are required for tumour maintenance may therefore yield clinically useful targets for new cancer therapies. Although loss of p53 function is a common feature of human cancers(11), it is not known whether sustained inactivation of this or other tumour suppressor pathways is required for tumour maintenance. To explore this issue, we developed a Cre-loxP-based strategy to temporally control tumour suppressor gene expression in vivo. Here we show that restoring endogenous p53 expression leads to regression of autochthonous lymphomas and sarcomas in mice without affecting normal tissues. The mechanism responsible for tumour regression is dependent on the tumour type, with the main consequence of p53 restoration being apoptosis in lymphomas and suppression of cell growth with features of cellular senescence in sarcomas. These results support efforts to treat human cancers by way of pharmacological reactivation of p53. C1 MIT, Ctr Canc Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Jacks, T (reprint author), MIT, Ctr Canc Res, Cambridge, MA 02142 USA. EM tjacks@mit.edu RI Grimm, Jan/B-1937-2008; Ventura, Andrea/F-1789-2011; OI Ventura, Andrea/0000-0003-4320-9907 NR 31 TC 878 Z9 910 U1 19 U2 133 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 8 PY 2007 VL 445 IS 7128 BP 661 EP 665 DI 10.1038/nature05541 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 133UM UT WOS:000244039400047 PM 17251932 ER PT J AU Dalmau, J Gonzalez, RG Lerwill, MF Batchelor Harris Schmahmann Ryan, DP Brown, RH AF Dalmau, Josep Gilberto Gonzalez, R. Lerwill, Melinda F. Batchelor Harris Schmahmann Ryan, David P. Brown, Robert H., Jr. TI A woman with rapidly progressive vertigo and ataxia - Paraneoplastic cerebellar degeneration due to anti-Yo antibodies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EATON MYASTHENIC SYNDROME; FDG-PET; NEUROLOGICAL SYNDROMES; DIAGNOSTIC-CRITERIA; CEREBROSPINAL-FLUID; NERVOUS-SYSTEM; BREAST-CANCER; LUNG-CANCER; DISORDERS; CELLS C1 Univ Penn, Hosp Univ Penn, Dept Neurol, Div Neurooncol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Dalmau, J (reprint author), Univ Penn, Hosp Univ Penn, Dept Neurol, Div Neurooncol, Philadelphia, PA 19104 USA. NR 33 TC 12 Z9 12 U1 3 U2 5 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 FEB 8 PY 2007 VL 356 IS 6 BP 612 EP 620 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 133KV UT WOS:000244012700011 PM 17287482 ER PT J AU MacPherson, D Conkrite, K Tam, M Mukai, S Mu, D Jacks, T AF MacPherson, David Conkrite, Karina Tam, Mandy Mukai, Shizuo Mu, David Jacks, Tyler TI Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression and N-myc gene amplification SO EMBO JOURNAL LA English DT Article DE N-myc; p107; p130; retinoblastoma; ROMA ID COMPARATIVE GENOMIC HYBRIDIZATION; OLIGONUCLEOTIDE MICROARRAY ANALYSIS; RETINAL DEVELOPMENT; CHIMERIC MICE; MOUSE RETINA; STEM-CELLS; RB; MUTATION; P107; EXPRESSION AB Human retinoblastoma is a pediatric cancer initiated by RB gene mutations in the developing retina. We have examined the origins and progression of retinoblastoma in mouse models of the disease. Retina-specific inactivation of Rb on a p130-/- genetic background led to bilateral retinoblastoma with rapid kinetics, whereas on a p107-/- background Rb mutation caused predominantly unilateral tumors that arose with delayed kinetics and incomplete penetrance. In both models, retinoblastomas arose from cells at the extreme periphery of the murine retina. Furthermore, late retinoblastomas progressed to invade the brain and metastasized to the cervical lymph nodes. Metastatic tumors lacking Rb and p130 exhibited chromosomal changes revealed by representational oligonucleotide microarray analysis including high-level amplification of the N-myc oncogene. N-myc was found amplified in three of 16 metastatic retinoblastomas lacking Rb and p130 as well as in retinoblastomas lacking Rb and p107. N-myc amplification ranged from 6- to 400-fold and correlated with high N-myc-expression levels. These murine models closely resemble human retinoblastoma in their progression and secondary genetic changes, making them ideal tools for further dissection of steps to tumorigenesis and for testing novel therapies. C1 Carnegie Inst, Dept Embryol, Baltimore, MD 21218 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Human Canc Genome Ctr, Cold Spring Harbor Lab, Woodbury, NY USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP MacPherson, D (reprint author), Carnegie Inst, Dept Embryol, 3520 San Martin Dr, Baltimore, MD 21218 USA. EM macpherson@ciwemb.edu RI Mu, David/E-8933-2011 OI Mu, David/0000-0002-7762-0182 FU NCI NIH HHS [P01 CA042063, P01-CA42063, P30 CA014051, P30-CA14051] NR 52 TC 41 Z9 45 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 7 PY 2007 VL 26 IS 3 BP 784 EP 794 DI 10.1038/sj.emboj.7601515 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 134KS UT WOS:000244082500015 PM 17235288 ER PT J AU Dupuis, J O'Donnell, CJ AF Dupuis, Josee O'Donnell, Christopher J. TI Interpreting results of large-scale genetic association studies - Separating gold from fool's gold SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; FALSE DISCOVERY; EFFICIENT; VARIANT; POWER; MAP C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. NHLBI, Boston, MA USA. NHLBI Framingham Heart Study, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave 2, Framingham, MA 01702 USA. EM codonnell@nih.gov NR 17 TC 14 Z9 15 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 FEB 7 PY 2007 VL 297 IS 5 BP 529 EP 531 DI 10.1001/jama.297.5.529 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 133FP UT WOS:000243999100032 PM 17284705 ER PT J AU Xie, ZC Dong, YL Maeda, U Moir, RD Xia, WM Culley, DJ Crosby, G Tanzi, RE AF Xie, Zhongcong Dong, Yuanlin Maeda, Uta Moir, Robert D. Xia, Weiming Culley, Deborah J. Crosby, Gregory Tanzi, Rudolph E. TI The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; APP; A beta; apoptosis; anesthesia; isoflurane ID NEURONAL CELL-DEATH; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; CEREBRAL-ISCHEMIA; PRESENILIN; PEPTIDE; CLEAVAGE; GAMMA; CALCIUM; INVOLVEMENT AB The anesthetic isoflurane has been reported to induce apoptosis and increase A beta generation and aggregation. However, the molecular mechanism underlying these effects remains unknown. We therefore set out to assess whether the effects of isoflurane on apoptosis are linked to amyloid beta-protein (A beta) generation and aggregation. For this purpose, we assessed the effects of isoflurane on beta-site amyloid beta precursor protein (APP)-cleaving enzyme (BACE) and gamma-secretase, the proteases responsible for A beta generation. We also tested the effects of inhibitors of A beta aggregation (iA beta 5, a beta-sheet breaker peptide; clioquinol, a copper -zinc chelator) on the ability of isoflurane to induce apoptosis. All of these studies were performed on naive human H4 neuroglioma cells as well as those overexpressing APP (H4-APP cells). Isoflurane increased the levels of BACE and gamma-secretase and secreted A beta in the H4-APP cells. Isoflurane-induced A beta generation could be blocked by the broad-based caspase inhibitor Z-VAD. The A beta aggregation inhibitors, iA beta 5 and clioquinol, selectively attenuated caspase-3 activation induced by isoflurane. However, isoflurane was able to induce caspase-3 activation in the absence of any detectable alterations of A beta generation in naive H4 cells. Finally, A beta potentiated the isoflurane-induced caspase-3 activation in naive H4 cells. Collectively, these findings suggest that isoflurane can induce apoptosis, which, in turn, increases BACE and gamma-secretase levels and A beta secretion. Isoflurane also promotes A beta aggregation. Accumulation of aggregated A beta in the media can then promote apoptosis. The result is a vicious cycle of isoflurane-induced apoptosis, A beta generation and aggregation, and additional rounds of apoptosis, leading to cell death. C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Massgen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, Massgen Inst Neurodegenerat Dis, 114 16th St,C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI xia, weiming/E-5465-2016 OI xia, weiming/0000-0002-7463-3295 FU NIA NIH HHS [K12AG 000294, P60 AG008812, R01AG 014713, R01AG20253]; NIGMS NIH HHS [K08GM077057]; NIMH NIH HHS [R01MH 60009]; NINDS NIH HHS [K08 NS048140] NR 53 TC 145 Z9 166 U1 0 U2 7 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 FEB 7 PY 2007 VL 27 IS 6 BP 1247 EP 1254 DI 10.1523/JNEUROSCI.5320-06.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 134FX UT WOS:000244070000004 PM 17287498 ER PT J AU Kurella, M Covinsky, KE Collins, AJ Chertow, GM AF Kurella, Manjula Covinsky, Kenneth E. Collins, Alan J. Chertow, Glenn M. TI Octogenarians and nonagenarians starting dialysis in the United States SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID STAGE RENAL-DISEASE; REPLACEMENT THERAPY; CLINICAL-OUTCOMES; DECISION-MAKING; SURVIVAL; HEMODIALYSIS; INITIATION; COHORT; PREVALENCE; VALIDATION AB Background: The elderly constitute the fastest-growing segment of the end-stage renal disease (ESRD) population, but the epidemiology and outcomes of dialysis among the very elderly, that is, those 80 years of age and older, have not been previously examined at a national level. Objective: To describe recent trends in the incidence and outcomes of octogenarians and nonagenarians starting dialysis. Design: Observational study. Setting: U.S. Renal Data System, a comprehensive, national registry of patients with ESRD. Participants: Octogenarians and nonagenarians initiating dialysis between 1996 and 2003. Measurements: Rates of dialysis initiation and survival. Results: The number of octogenarians and nonagenarians starting dialysis increased from 7054 persons in 1996 to 13 577 persons in 2003, corresponding to an average annual increase in dialysis initiation of 9.8%. After we accounted for population growth, the rate of dialysis initiation increased by 57% (rate ratio, 1.57 [95% CI, 1.53 to 1.62]) between 1996 and 2003. One-year mortality for octogenarians and nonagenarians after dialysis initiation was 46%. Compared with octogenarians and nonagenarians initiating dialysis in 1996, those starting dialysis in 2003 had a higher glomerular filtration rate and less morbidity related to chronic kidney disease but no difference in 1-year survival. Clinical characteristics strongly associated with death were older age, nonambulatory status, and more comorbid conditions. Limitations: Survival of patients with incident ESRD who did not begin dialysis could not be assessed. Conclusions: The number of octogenarians and nonagenarians initiating dialysis has increased considerably over the past decade, while overall survival for patients on dialysis remains modest. Estimates of prognosis based on patient characteristics, when considered in conjunction with individual values and preferences, may aid in dialysis decision making for the very elderly. C1 Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. US Renal Data Syst, Minneapolis, MN USA. RP Kurella, M (reprint author), Univ Calif San Francisco, Div Nephrol, UCSF Laurel Heights,Suite 430,3333 Calif St, San Francisco, CA 94143 USA. EM manjula.kurella@ucsf.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU NIA NIH HHS [K24 AG029812]; NIDDK NIH HHS [R01 DK01005, R01 DK58411] NR 25 TC 276 Z9 290 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 6 PY 2007 VL 146 IS 3 BP 177 EP 183 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 132QN UT WOS:000243957400003 PM 17283348 ER PT J AU Frangogiannis, NG Dewald, O Xia, Y Ren, GF Haudek, S Leucker, T Kraemer, D Taffet, G Rollins, BJ Entman, ML AF Frangogiannis, Nikolaos G. Dewald, Oliver Xia, Ying Ren, Guofeng Haudek, Sandra Leucker, Thorsten Kraemer, Daniela Taffet, George Rollins, Barrett J. Entman, Mark L. TI Critical role of monocyte chemoattractant protein-1/CC chemokine ligand 2 in the pathogenesis of ischemic cardiomyopathy SO CIRCULATION LA English DT Article DE inflammation; ischemia; reperfusion; immunology; pathology; fibrosis; cardiomyopathy ID HIBERNATING HUMAN MYOCARDIUM; GENE-EXPRESSION; FIBROSIS; CHEMOKINES; FIBROBLASTS; MCP-1; MICE; FIBROCYTES; COLLAGEN; INFARCTS AB Background - Cardiac interstitial fibrosis plays an important role in the pathogenesis of ischemic cardiomyopathy, contributing to systolic and diastolic dysfunction. We have recently developed a mouse model of fibrotic noninfarctive cardiomyopathy due to brief repetitive myocardial ischemia and reperfusion. In this model, fibrotic changes are preceded by marked and selective induction of the CC chemokine monocyte chemoattractant protein-1 (MCP-1). We hypothesized that MCP-1 may mediate fibrotic remodeling through recruitment of mononuclear cells and direct effects on fibroblasts. Methods and Results - Wild-type (WT) and MCP-1-null mice underwent daily 15-minute coronary occlusions followed by reperfusion. Additional WT animals received intraperitoneal injections of a neutralizing anti-MCP-1 antibody after the end of each ischemic episode. Hearts were examined echocardiographically and processed for histological and RNA studies. WT mice undergoing repetitive brief myocardial ischemia and reperfusion protocols exhibited macrophage infiltration after 3 to 5 days and marked interstitial fibrosis in the ischemic area after 7 days, accompanied by ventricular dysfunction. MCP-1-null mice had markedly diminished interstitial fibrosis, lower macrophage infiltration, and attenuated ventricular dysfunction compared with WT animals. MCP-1 neutralization also inhibited interstitial fibrosis, decreasing left ventricular dysfunction and regional hypocontractility. Cardiac myofibroblasts isolated from WT but not from MCP-1-null animals undergoing repetitive myocardial ischemia and reperfusion demonstrated enhanced proliferative capacity. However, MCP-1 stimulation did not induce cardiac myofibroblast proliferation and did not alter expression of fibrosis-associated genes. Conclusions - Defective MCP-1 signaling inhibits the development of ischemic fibrotic cardiomyopathy in mice. The profibrotic actions of MCP-1 are associated with decreased macrophage recruitment and may not involve direct effects on cardiac fibroblasts. C1 Baylor Coll Med, Methodist Hosp, Cardiovasc Sci Sect, Houston, TX 77030 USA. Baylor Coll Med, Methodist Hosp, DeBakey Heart Ctr, Houston, TX 77030 USA. Univ Bonn, Dept Cardiac Surg, D-5300 Bonn, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Frangogiannis, NG (reprint author), Baylor Coll Med, Methodist Hosp, Cardiovasc Sci Sect, 1 Baylor Plaza M-S F-602, Houston, TX 77030 USA. EM ngf@bcm.tmc.edu FU NHLBI NIH HHS [P01 HL-42550, R01 HL-76246] NR 33 TC 121 Z9 124 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 6 PY 2007 VL 115 IS 5 BP 584 EP 592 DI 10.1161/CIRCULATIONAHA.106.646091 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 133GG UT WOS:000244000800010 PM 17283277 ER PT J AU McCarty, KM Ryan, L Houseman, EA Williams, PL Miller, DP Quamruzzaman, Q Rahman, M Mahiuddin, G Smith, T Gonzalez, E Su, L Christiani, DC AF McCarty, Kathleen M. Ryan, Louise Houseman, E. Andres Williams, Paige L. Miller, David P. Quamruzzaman, Quazi Rahman, Mahmuder Mahiuddin, Golam Smith, Thomas Gonzalez, Ernesto Su, Li Christiani, David C. TI A case-control study of GST polymorphisms and arsenic related skin lesions SO ENVIRONMENTAL HEALTH LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; DRINKING-WATER; BILIARY-EXCRETION; METHYLATION CAPACITY; CANCER-RISK; WEST-BENGAL; OMEGA CLASS; BANGLADESH; GROUNDWATER; RESISTANCE AB Background: Polymorphisms in GSTT1, GSTM1 and GSTP1 impact detoxification of carcinogens by GSTs and have been reported to increase susceptibility to environmentally related health outcomes. Individual factors in arsenic biotransformation may influence disease susceptibility. GST activity is involved in the metabolism of endogenous and exogenous compounds, including catalyzing the formation of arsenic-GSH conjugates. Methods: We investigated whether polymorphisms in GSTT1, GSTP1 and GSTM1 were associated with risk of skin lesions and whether these polymorphisms modify the relationship between drinking water arsenic exposure and skin lesions in a case control study of 1200 subjects frequency matched on age and gender in community clinics in Pabna, Bangladesh in 2001-2002. Results and discussion: GSTT1 homozygous wildtype status was associated with increased odds of skin lesions compared to the null status (OR1.56 95% CI 1.10-2.19). The GSTP1 GG polymorphism was associated with greater odds of skin lesions compared to GSTP1 AA, (OR 1.86 ( 95% CI 1.15-3.00). No evidence of effect modification by GSTT1, GSTM1 or GSTP1 polymorphisms on the association between arsenic exposure and skin lesions was detected. Conclusion: GSTT1 wildtype and GSTP1 GG are associated with increased risk of skin lesions. C1 Yale Univ, Sch Med, Div Environm Hlth Sci, New Haven, CT USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dhaka Community Hosp, Dhaka, Bangladesh. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McCarty, KM (reprint author), Yale Univ, Sch Med, Div Environm Hlth Sci, New Haven, CT USA. EM kmccarty@hohp.harvard.edu; lryan@hsph.harvard.edu; ahousema@hsph.harvard.edu; paige@hsph.harvard.edu; dmiller@hohp.harvard.edu; dch@bangla.net; dch@bangla.net; dch@bangla.net; tsmith@hohp.harvard.edu; egonzalez1@partners.org; lisu@hohp.harvard.edu; dchristi@hsph.harvard.edu RI Ryan, Louise/A-4562-2009; OI Ryan, Louise/0000-0001-5957-2490; Houseman, Eugene Andres/0000-0003-0703-1830 FU NIEHS NIH HHS [T32ES 06790, ES 00002, ES 05947, ES011622, P30 ES000002, P42 ES005947, R01 ES011622] NR 43 TC 22 Z9 26 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-UK JI Environ. Health PD FEB 6 PY 2007 VL 6 AR 5 DI 10.1186/1476-069X-6-5 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 180AS UT WOS:000247332800001 PM 17284320 ER PT J AU Ferrantelli, F Buckley, KA Rasmussen, RA Chalmers, A Wang, T Li, PL Williams, AL Hofmann-Lehmann, R Montefiori, DC Cavacini, LA Katinger, H Stiegler, G Anderson, DC McClure, HM Ruprecht, RM AF Ferrantelli, Flavia Buckley, Kathleen A. Rasmussen, Robert A. Chalmers, Alistair Wang, Tao Li, Pei-Lin Williams, Alison L. Hofmann-Lehmann, Regina Montefiori, David C. Cavacini, Lisa A. Katinger, Hermann Stiegler, Gabriela Anderson, Daniel C. McClure, Harold M. Ruprecht, Ruth M. TI Time dependence of protective post-exposure prophylax with human monoclonal antibodies against pathogenic SHIV challenge in newborn macaques SO VIROLOGY LA English DT Article DE post-exposure prophylaxis; passive immunization; neutralizing monoclonal antibodies; pathogenic simian-human immunodeficiency virus (SHIV); rhesus macaques; oral infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; CROSS-CLADE NEUTRALIZATION; NEONATAL MACAQUES; PASSIVE-IMMUNIZATION; PHASE-I; TYPE-1; HIV-1; GLYCOPROTEIN; COMBINATION; EPITOPE AB In a primate model of postnatal virus transmission, we have previously shown that I It post-exposure prophylaxis (PEP) with a triple combination of neutralizing monoclonal antibodies (nmAbs) conferred sterilizing protection to neonatal macaques against oral challenge with pathogenic simian-human immunodeficiency virus (SHIV). Here, we show that nmAbs can also partially protect SHIV-exposed newborn macaques against infection or disease, when given as 12 or 24 h PEP, respectively. This work delineates the potential and the limits of passive immunoprophylaxis with nmAbs. Even though 24 It PEP with nmAbs did not provide sterilizing immunity to neonatal monkeys, it contained viremia and protected infants from acute disease. Taken together with our results from other PEP studies, these data show that the success of passive immunization depends on the nmAb potency/dose and the time window between virus exposure and start of immunotherapy. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Univ Agr Vienna, Inst Appl Microbiol, Vienna, Austria. Polymun Sci Immunobiol Forsch GmbH, Vienna, Austria. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB809, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Hofmann-Lehmann, Regina/C-6528-2009; Ferrantelli, Flavia/J-7794-2016 OI Ferrantelli, Flavia/0000-0002-0768-1078 FU NCRR NIH HHS [RR-00165]; NIAID NIH HHS [AI30034, P01 AI48240, R01 AI34266]; NIDCR NIH HHS [R01 DE12937] NR 44 TC 29 Z9 29 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 5 PY 2007 VL 358 IS 1 BP 69 EP 78 DI 10.1016/j.virol.2006.07.056 PG 10 WC Virology SC Virology GA 131LS UT WOS:000243871100008 PM 16996554 ER PT J AU Agopian, K Wei, BL Garcia, JV Gabuzda, D AF Agopian, Kristin Wei, Bangdong L. Garcia, J. Victor Gabuzda, Dana TI CD4 and MHC-I downregulation are conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable SO VIROLOGY LA English DT Review DE human immunodeficiency virus type 1 (HIV-1); Nef; brain; lymph node; CD4; MHC-1; Pak2 ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; T-CELL-ACTIVATION; RICH PXXP MOTIFS; COMPLEX CLASS-I; TYPE-1 NEF; P21-ACTIVATED KINASE-2; DISEASE PROGRESSION; MUTATIONAL ANALYSIS; SURFACE EXPRESSION AB HIV-1 compartmentalization in the CNS has been demonstrated for gag, pol, and env genes. However, little is known about tissue compartmentalization of nef genes and their functional characteristics in brain. We have cloned 97 nef genes and characterized 10 Nef proteins from autopsy brain and lymphoid tissues from 2 patients with AIDS and HIV-1-associated dementia. Distinct compartmentalization of brain versus lymphoid nef genes was demonstrated within each patient. CD4 and MHC-I downregulation were conserved in all tissue-derived Nefs. However, MHC-I downregulation by brain-derived Nefs was weaker than downregulation by lymphoid-derived Nefs. The motifs KEEE- or EKEE- at the PACs-1 binding site represented brain-specific signature patterns in these 2 patients and contributed to the reduced MHC-1 downregulation activity of brain-derived Nets from these patients. Pak2 association was highly variable in Nets from both patients. Three of 10 tissue-derived Nets coimmunoprecipitated activated Pak2, with strong association demonstrated for only 2 Nefs. The ability of Nef to associate with activated Pak2 did not correlate with brain or lymphoid tissue origin. Nef genes from viruses isolated from brain by coculture with PBMC were not closely related to sequences amplified directly from brain tissue, suggesting that viral selection or adaptation occurred during coculture. This study of tissue-derived HIV-1 Nets demonstrates that CD4 and MHC-1 downregulation are highly conserved Nef functions, while Pak2 association is variable in late stage AIDS patients. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Div Infect Dis, Dept Internal Med, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 816,44 Binney St, Boston, MA 02115 USA. EM dana-gabuzda@dfci.harvard.edu FU NIAID NIH HHS [AI33331, R01 AI033331]; NINDS NIH HHS [NS35734, NS37277, R01 NS035734, R01 NS037277] NR 113 TC 18 Z9 18 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 5 PY 2007 VL 358 IS 1 BP 119 EP 135 DI 10.1016/j.virol.2006.07.053 PG 17 WC Virology SC Virology GA 131LS UT WOS:000243871100013 PM 16979207 ER PT J AU Hochberg, LR Taylor, DM AF Hochberg, Leigh R. Taylor, Down M. TI Intuitive prosthetic limb control SO LANCET LA English DT Editorial Material ID BRAIN-COMPUTER-INTERFACE; DEVICES; ARM; REPRESENTATIONS; RESTORATION; PLASTICITY; MONKEYS; CORTEX C1 Dept Vet Affairs, Rehabil Res & Dev Serv, Ctr Restorat & Regenerat Med, Providence, RI 02912 USA. Brown Univ, Dept Neurosci, Providence, RI 02912 USA. Brown Univ, Brain Sci Program, Providence, RI 02912 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurocrit Care Serv, Boston, MA USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. Cleveland VA Med Ctr, Cleveland Funct Elect Stimulat Ctr, Cleveland, OH USA. RP Hochberg, LR (reprint author), Dept Vet Affairs, Rehabil Res & Dev Serv, Ctr Restorat & Regenerat Med, Providence, RI 02912 USA. EM leigh_hochberg@brown.edu OI Hochberg, Leigh/0000-0003-0261-2273 NR 20 TC 4 Z9 4 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD FEB 3 PY 2007 VL 369 IS 9559 BP 345 EP 346 DI 10.1016/S0140-6736(07)60164-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 132LN UT WOS:000243944400004 PM 17276755 ER PT J AU Garza, R Hudson, RA McMahan, CA Walter, CA Vogel, KS AF Garza, Rene Hudson, Robert A., III McMahan, C. Alex Walter, Christi A. Vogel, Kristine S. TI A mild mutator phenotype arises in a mouse model for malignancies associated with neurofibromatosis type 1 SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE neurofibrornatosis type 1; mutant frequency; peripheral nerve sheath tumor; Big Blue mouse; p53 ID NERVE SHEATH TUMORS; LACI TRANSGENIC MICE; MULTIPLE MUTATIONS; HETEROZYGOUS MICE; FRAUMENI-SYNDROME; MUTANT MICE; DNA-DAMAGE; WILD-TYPE; P53; CANCER AB Defects in genes that control DNA repair, proliferation, and apoptosis can increase genomic instability, and thus promote malignant progression. Although most tumors that arise in humans with neurofibromatosis type 1 (NF1) are benign, these individuals are at increased risk for malignant peripheral nerve sheath tumors (MPNST). To characterize additional mutations required for the development of MPNST from benign plexiform neurofibromas, we generated a mouse model for these tumors by combining targeted null mutations in Nf1 and p53, in cis. CisNf1+/-; p53+/- mice spontaneously develop PNST, and these tumors exhibit loss-of-heterozygosity at both the Nf1 and p53 loci. Because p53 has well-characterized roles in the DNA damage response, DNA repair, and apoptosis, and because DNA repair genes have been proposed to act as modifiers in NF1, we used the cisNf1+/-; p53+/- mice to determine whether a mutator phenotype arises in NF1-associated malignancies. To quantitate spontaneous mutant frequencies (MF), we crossed the Big Blue mouse, which harbors a lacI transgene, to the cisNf1+/-; p53+/- mice, and isolated genomic DNA from both tumor and normal tissues in compound heterozygotes and wild-type siblings. Many of the PNST exhibited increased mutant frequencies (MF = 4.70) when compared to normal peripheral nerve and brain (MF = 2.09); mutations occurred throughout the entire lacI gene, and included base substitutions, insertions, and deletions. Moreover, the brains, spleens, and livers of these cisNf1+/-; p53+/- animals exhibited increased mutant frequencies when compared to tissues from wild-type littermates. We conclude that a mild mutator phenotype arises in the tumors and tissues of cisNf1+/-; p53+/- mice, and propose that genomic instability influences NF1 tumor progression and disease severity. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. RP Vogel, KS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM vogelk@uthscsa.edu NR 54 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD FEB 3 PY 2007 VL 615 IS 1-2 BP 98 EP 110 DI 10.1016/j.mrfmmm.2006.11.031 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 133WP UT WOS:000244044900009 PM 17208258 ER PT J AU Iyer, V Hajjar, RJ Armoundas, AA AF Iyer, Vivek Hajjar, Roger J. Armoundas, Antonis A. TI Mechanisms of abnormal calcium homeostasis in mutations responsible for catecholaminergic polymorphic ventricular tachycardia SO CIRCULATION RESEARCH LA English DT Article DE catecholaminergic polymorphic ventricular tachycardia; delayed afterdepolarization; ryanodine receptor; calsequestrin; calcium handling; simulation ID CARDIAC RYANODINE RECEPTOR; CA2+-INDUCED CA2+ RELEASE; IN MOUSE MODEL; SARCOPLASMIC-RETICULUM; LUMINAL CA2+; SKELETAL-MUSCLE; SUDDEN-DEATH; MATHEMATICAL-MODEL; RYR2 MUTATIONS; CHANNEL AB Catecholaminergic polymorphic ventricular tachycardia is a heritable arrhythmia unmasked by exertion or stress and is characterized by triggered activity and sudden cardiac death. In this study, we simulated mutations in 2 genes linked to catecholaminergic polymorphic ventricular tachycardia, the first located in calsequestrin (CSQN2) and the second in the ryanodine receptor (RyR2). The aim of the study was to investigate the mechanistic basis for spontaneous Ca2+ release events that lead to delayed after depolarizations in affected patients. Sarcoplasmic reticulum (SR) luminal Ca2+ sensing was incorporated into a model of the human ventricular myocyte, and CSQN2 mutations were modeled by simulating disrupted RyR2 luminal Ca2+ sensing. In voltage-clamp mode, the mutant CSQN2 model recapitulated the smaller calcium transients, smaller time to peak calcium transient, and accelerated recovery from inactivation seen in experiments. In current clamp mode, in the presence of beta stimulation, we observed delayed afterdepolarizations, suggesting that accelerated recovery of RyR2 induced by impaired luminal Ca2+ sensing underlies the triggered activity observed in mutant CSQN2-expressing myocytes. In current-clamp mode, in a model of mutant RyR2 that is characterized by reduced FKBP12.6 binding to the RyR2 on beta stimulation, the impaired coupled gating characteristic of these mutations was modeled by reducing cooperativity of RyR2 activation. In current-clamp mode, the mutant RyR2 model exhibited increased diastolic RyR2 open probability that resulted in formation of delayed afterdepolarizations. In conclusion, these minimal order models of mutant CSQN2 and RyR2 provide plausible mechanisms by which defects in RyR2 gating may lead to the cellular triggers for arrhythmia, with implications for the development of targeted therapy. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org FU NHLBI NIH HHS [HL071763, HL080498, HL083156, R01 HL078691] NR 57 TC 19 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD FEB 2 PY 2007 VL 100 IS 2 BP E22 EP E31 DI 10.1161/01.RES.0000258468.31815.42 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 132KT UT WOS:000243942400018 PM 17234962 ER PT J AU Mulky, A Vu, BC Conway, JA Hughes, SH Kappes, JC AF Mulky, Alok Vu, B. Christie Conway, Joan A. Hughes, Stephen H. Kappes, John C. TI Analysis of amino acids in the beta 7-beta 8 loop of human immunodeficiency virus type 1 reverse transcriptase for their role in virus replication SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1; reverse transcriptase; reverse transcription ID TRYPTOPHAN-REPEAT MOTIF; CRYSTAL-STRUCTURE; PRIMER GRIP; NONNUCLEOSIDE INHIBITORS; ANGSTROM RESOLUTION; INFECTIOUS VIRIONS; TSAO DERIVATIVES; DNA-SYNTHESIS; P51 SUBUNIT; RNASE-H AB The HIV-1 p51/p66 reverse transcriptase (RT) heterodimer interface comprises, in part, intermolecular interaction of the loop region between beta-strands 7 and 8 (beta 7-beta 8 loop) in the p51 fingers subdomain with the p66 palm subdomain. In this study, for the first time in the context of infectious HIV-1 particles, we analyzed the contribution of amino acid residues (S134, I135, N136, N137, T139 and P140) in the beta 7-beta 8 loop for RT heterodimerization, enzymatic activity, and virus infectivity. Mutating asparagine 136 to alanine (N136A) reduced viral infectivity and enzyme activity dramatically. The N136A mutation appeared to destabilize the RT heterodimer and render both the p66 and p51 subunits susceptible to aberrant cleavage by the viral protease. Subunit-specific mutagenesis demonstrated that the presence of the N136A mutation in the p51 subunit alone was sufficient to cause degradation of RT within the virus particle. Alanine mutation at other residues of the beta 7-beta 8 loop did not affect either RT stability or virus infectivity significantly. None of the beta 7-beta 8 loop alanine mutations affected the sensitivity of virus to inhibition by NNRTIs. In the context of infectious virions, our results indicate a critical role of the p51 N136 residue within the beta 7-beta 8 loop for RT heterodimer stability and function. These findings suggest the interface comprising N136 in p51 and interacting residues in p66 as a possible target for rational drug design. (c) 2006 Published by Elsevier Ltd. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL 35233 USA. RP Kappes, JC (reprint author), Univ Alabama, Dept Med, Birmingham, AL 35294 USA. EM kappesjc@uab.edu FU Intramural NIH HHS; NIAID NIH HHS [P30 AI 27767, R01 AI 47714]; NIDDK NIH HHS [R24 DK 64400] NR 47 TC 11 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD FEB 2 PY 2007 VL 365 IS 5 BP 1368 EP 1378 DI 10.1016/j.jmb.2006.10.089 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129SE UT WOS:000243749600011 PM 17141805 ER PT J AU Rivera, MN Kim, WJ Wells, J Driscoll, DR Brannigan, BW Han, M Kim, JC Feinberg, AP Gerald, WL Vargas, SO Chin, L Iafrate, AJ Bell, DW Haber, DA AF Rivera, Miguel N. Kim, Woo Jae Wells, Julie Driscoll, David R. Brannigan, Brian W. Han, Moonjoo Kim, James C. Feinberg, Andrew P. Gerald, William L. Vargas, Sara O. Chin, Lynda Iafrate, A. John Bell, Daphne W. Haber, Daniel A. TI An X chromosome gene, WTX, is commonly inactivated in Wilms tumor SO SCIENCE LA English DT Article ID FANCONI-ANEMIA; HUMAN GENOME; CANCER; KIDNEY; MUTATIONS AB Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5 to 10% of cases. Using a high-resolution screen for DNA copy-number alterations in Wilms tumor, we identified somatic deletions targeting a previously uncharacterized gene on the X chromosome. This gene, which we call WTX, is inactivated in approximately one-third of Wilms tumors (15 of 51 tumors). Tumors with mutations in WTX lack WT1 mutations, and both genes share a restricted temporal and spatial expression pattern in normal renal precursors. In contrast to biallelic inactivation of autosomal tumor-suppressor genes, WTX is inactivated by a monoallelic "single-hit" event targeting the single X chromosome in tumors from males and the active X chromosome in tumors from females. C1 Massachusetts Gen Hosp, Ctr Canc, Harvard Med Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Mol Med, Baltimore, MD 21205 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Harvard Med Ctr, Boston, MA 02114 USA. EM haber@helix.mgh.harvard.edu FU NCI NIH HHS [P01-CA101942, R37 CA054358, R37 CA054358-17, R37-CA058596, T32-CA009216] NR 22 TC 195 Z9 212 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 2 PY 2007 VL 315 IS 5812 BP 642 EP 645 DI 10.1126/science.1137509 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 131YR UT WOS:000243909400042 PM 17204608 ER PT J AU Dachman, AH Dawson, DO Lefere, P Yoshida, H Khan, NU Cipriani, N Rubin, DT AF Dachman, Abraham H. Dawson, Damien O. Lefere, Philippe Yoshida, Hiro Khan, Nasreen U. Cipriani, Nicole Rubin, David T. TI Comparison of routine and unprepped CT colonography augmented by low fiber diet and stool tagging: a pilot study SO ABDOMINAL IMAGING LA English DT Article DE CT colonography; colonoscopy; colon cancer; CT technique ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; CATHARTIC PREPARATION; PATIENT ACCEPTANCE; POLYPS AB Background: We performed a pilot study examining the feasibility of a new unprepped CT colonography (CTC) strategy: low fiber diet and tagging (unprepped) vs. low fiber diet, tagging and a magnesium citrate cleansing preparation (prepped). Prior reports of tagging were limited in that the residual stool was neither measured and stratified by size nor did prior reports subjectively evaluate the ease of interpretation by a reader experienced in interpreting CTC examinations. Methods: Prospective randomized to unprepped n = 14 and prepped n = 14. Colonic segments were subjectively evaluated for residual stool that would potentially interfere with interpretation. Scores were given in the following categories: percentage of residual stool that was touching or nearly touching mucosa, the largest piece of retained stool, effectiveness of tagging, height of residual fluid, degree of distention, ease of interpretation, and reading time. Results: Ease of the CT read (scale where 4 = optimal read) averaged 1.3 for the unprepped group and 2.3 for the prepped group. The mean read time averaged 17.5 min for unprepped and 17.9 min for prepped. The degree of distention (scale where 4 = well distended) averaged 3.7 for unprepped and 3.6 for prepped. Supine and prone images combined, the unprepped group had 160 segments with stool; prepped group had 58 segments. The amount of stool covering the mucosa in all segments averaged 1.6 (33%-66% coverage) in the unprepped group and 0.35 (< 33% mucosal coverage) in the prepped group. The mean size of the largest piece of stool was 33.67 mm for unprepped and 4.01 mm for prepped. Percentage of tagged stool was not significantly different between the groups (range of 94-98%). The height of residual fluid averaged 8.37 mm for unprepped and 13.4 mm for prepped. Three polyps in three patients were found during optical colonoscopy (OC) in the unprepped group (5, 6, and 10 mm), none of which were prospectively detected at CTC. Three polyps in three patients were detected during OC in the prepped group (5, 10, and 15 mm), two of which were prospectively detected at CTC. Two false-positive lesions were observed at CTC in one patient in the prepped group. Conclusion: There was more stool in the unprepped group and while this factor did not slow down the reading time, it made the examination subjectively harder to interpret and likely caused the three polyps in this group to be missed. We conclude that a truly unprepped strategy that leaves significant residual stool, even if well tagged, is not desirable. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA USA. Stedelijk Ziekenhuis, Dept Radiol, B-8800 Roeselare, Belgium. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Chicago, Dept Med, Gastroenterol Sect, Chicago, IL 60637 USA. RP Dachman, AH (reprint author), Univ Chicago, Dept Radiol, MC 2026,5841 S Maryland Ave, Chicago, IL 60637 USA. EM ahdachma@uchicago.edu FU NCRR NIH HHS [M01RR00055] NR 13 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD FEB PY 2007 VL 32 IS 1 BP 96 EP 104 DI 10.1007/s00261-006-9044-9 PG 9 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 166UL UT WOS:000246405800015 PM 16969601 ER PT J AU Sherman, SE Fotiades, J Rubenstein, LV Gilman, SC Vivell, S Chaney, E Yano, EM Felker, B AF Sherman, Scott E. Fotiades, John Rubenstein, Lisa V. Gilman, Stuart C. Vivell, Susan Chaney, Edmund Yano, Elizabeth M. Felker, Bradford TI Teaching systems-based practice to primary care physicians to foster routine implementation of evidence-based depression care SO ACADEMIC MEDICINE LA English DT Article ID COLLABORATIVE CARE; OUTCOMES; VETERANS AB Although health care organizations seeking to improve quality often must change the system for delivering care, there is little available evidence on how to educate staff and providers about this change. As part of a 2002-2003 Veterans Health Administration multisite project using collaborative care to improve the management of depression, the authors implemented the Translating Initiatives for Depression into Effective Solutions (TIDES) program. Five steps were followed for teaching systems-based practice: (1) determine providers' educational needs (through administrative data, expert opinion, and provider discussion), (2) develop educational materials (based on needs assessed), (3) help each of seven sites develop an educational intervention, (4) implement the intervention, and (5) monitor the intervention's effectiveness. Sites relied primarily on passive educational strategies. There was variable implementation of the different components (e.g., lecture, educational outreach). No site chose to write up its education plan, as was suggested. The authors thus suggest that the educational model was successful at identifying providers' needs and creating appropriate materials, because the program was not advertised in other ways and because almost all providers referred patients to the program. However, the educational model was only partially successful at getting sites to develop and implement an educational plan, although provider behavior did change. Overall, the program was somewhat effective at teaching systems-based practice. The authors believe the best way to enhance effectiveness is to build education into the system rather than rely on a separate system for education. C1 VA New York Harbor Healthcare Syst, New York, NY 10010 USA. NYU, Sch Med, New York, NY USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Ctr Excellence Study Healthcare Provider Behav, Sepulveda, CA USA. James J Peters VA Med Ctr, Bronx, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RAND Corp, Hlth Program, Santa Monica, CA USA. Vet Hlth Adm, Off Acad Affilitat, Special Fellowships Program, Washington, DC USA. Univ Calif Irvine, Irvine, CA USA. Tulane Univ, New Orleans, LA 70118 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Sherman, SE (reprint author), VA New York Harbor Healthcare Syst, 111,423 E 23rd St, New York, NY 10010 USA. EM scott.sherman@va.gov OI Sherman, Scott/0000-0003-1752-7303 NR 28 TC 9 Z9 9 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2007 VL 82 IS 2 BP 168 EP 175 DI 10.1097/ACM.0b013e31802d9165 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 135HQ UT WOS:000244145100010 PM 17264696 ER PT J AU Prochaska, JJ Fromont, SC Banys, P Eisendrath, SJ Horowitz, MJ Jacobs, MH Hall, SM AF Prochaska, Judith J. Fromont, Sebastien C. Banys, Peter Eisendrath, Stuart J. Horowitz, Mardi J. Jacobs, Marc H. Hall, Sharon M. TI Addressing nicotine dependence in psychodynamic psychotherapy: Perspectives from residency training SO ACADEMIC PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; PRACTICE GUIDELINE; SMOKING; PSYCHIATRY; DEPRESSION; PREVALENCE; DISORDER; CANCER; RISK AB Objective: According to APA treatment recommendations, psychiatrists should assess and intervene in tobacco use with all of their patients who smoke. The ease with which this occurs may vary by treatment model. This study examined perspectives in residency training to identify a framework for addressing nicotine dependence within psychodynamic psychotherapy. Method: The authors collected data from a focus group of psychiatry residents and interviews with psychiatry residency faculty with expertise in psychodynamic psychotherapy. The transcribed interviews were analyzed for key themes and synthesized. Results: Though the residents reported hesitancy to address patients' tobacco use, specifically in psychodynamic psychotherapy, the consensus from the expert faculty consultants was that tobacco interventions can and should be incorporated. The faculty provided suggestions, consistent with a psychodynamic formulation, for assessing patients' tobacco use and their interest in quitting, providing cessation treatment and/or referrals, and following up with patients to address relapse. Conclusions: The findings provide a useful framework, consistent with a psychodynamic model, for assessing and treating tobacco use with patients. Additional training and supervision likely are needed to increase residents' confidence and comfort with implementing these strategies. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Alta Bates Summit Med Ctr, Berkeley, CA USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Prochaska, JJ (reprint author), 401 Parnassus Ave,TRC 0984, San Francisco, CA 94143 USA. EM JProchaska@lppi.ucsf.edu FU NIDA NIH HHS [K23 DA018691, P50 DA009253, K05 DA016752, P50 DA09253] NR 24 TC 2 Z9 2 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FEB PY 2007 VL 31 IS 1 BP 8 EP 14 DI 10.1176/appi.ap.31.1.8 PG 7 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 127PY UT WOS:000243600000003 PM 17242046 ER PT J AU Levine, RE Kelly, PA Karakoc, T Haidet, P AF Levine, Ruth E. Kelly, P. Adam Karakoc, Tayfun Haidet, Paul TI Peer evaluation in a clinical clerkship: Students' attitudes, experiences, and correlations with traditional assessments SO ACADEMIC PSYCHIATRY LA English DT Article ID TUTORIALS; RESIDENCY; RATINGS; SELF AB Objective: The authors performed this study to determine whether clerkship peer evaluations, initiated as part of our "team-based learning" curriculum in 2002, correlated with other student performance measures, and to determine what qualities students rate in their peer evaluations. Method: The authors correlated peer evaluation scores with other student performance measures and performed a qualitative examination of student comments to assess reasons students gave for giving high and low scores. Results: Peer evaluation scores correlated modestly with the National Board of Medical Examiners' (NBME) subject test, in-class quiz, and clinical scores. Qualitative comments demonstrated that students made assessments based on three thematic areas: personal attributes, team contributions, and cognitive abilities. Conclusions: Peers' evaluation scores modestly predict which students will perform well on other measures. However, there may be other qualities that are also important factors in peer evaluation. For example, most students value qualities of preparation and participation. Though students sometimes dislike peer evaluations, their assessments may enhance traditional course assessments and complement a comprehensive evaluation strategy. C1 Univ Texas, Med Branch, Dept Psychiat, Galveston, TX 77550 USA. Houseton Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. RP Levine, RE (reprint author), 301 Univ Blvd,Route 0193, Galveston, TX 77555 USA. EM rlevine@utmb.edu RI Herring, Anna/L-7859-2014; Karakoc, Tahir Hikmet/D-7087-2015 OI Karakoc, Tahir Hikmet/0000-0001-8182-8667 NR 21 TC 20 Z9 20 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FEB PY 2007 VL 31 IS 1 BP 19 EP 24 DI 10.1176/appi.ap.31.1.19 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 127PY UT WOS:000243600000005 PM 17242048 ER PT J AU Otero, HJ Erturk, SM Ondategui-Parra, S Wong, ST Ros, PR AF Otero, Hansel J. Erturk, Sukru Mehmet Ondategui-Parra, Silvia Wong, Stephen T. Ros, Pablo R. TI Molecular imaging programs in the United States: Results of a national survey SO ACADEMIC RADIOLOGY LA English DT Article DE molecular imaging; molecular imaging programs; molecular imaging development ID DISEASE; CANCER AB Rationale and Objectives. We sought to identify and describe the characteristics of molecular imaging (MI) programs in the United States and to determine the factors considered critical for their future. Materials and Methods. In a cross-sectional study, a validated survey was sent to members of the Society of Chairmen in Academic Radiology Departments (SCARD) in the United States, and 26 variables were studied. Results. The response rate was 40.3%; 67.9% of the departments surveyed have an MI program. The main focus of 47.4% of departments is oncology. The number of radiologists working for the department was the only variable found to be significantly positively correlated with (1) number of researchers in the MI program, (2) number of MI modalities available, (3) total number of grants, and (4) having ongoing MI clinical trials. These four variables plus the number of federal grants and the space used by MI programs were independent of the geographical region, hospital size (number of beds), and department size (number of radiological examinations per year). All the MI programs received grants during 2005. Only 16.1% have no alliances with industry. Among all the departments, 82% identified staff training and recruitment as the keys for success; 78.57% considered oncology the most important future application of MI and cancer management the hospital service most affected by MI. Conclusion. MI programs are starting to be more widespread throughout the United States, and the trend is for more academic radiology departments to become engaged in MI activities; their development is independent of department characteristics. Radiology departments strongly agreed about the key components for success of MI initiatives and the areas that will be most affected by MI applications. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Adm, Boston, MA 02115 USA. RP Otero, HJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM hotero@partners.org NR 19 TC 1 Z9 1 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2007 VL 14 IS 2 BP 125 EP 131 DI 10.1016/j.acra.2006.11.002 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 133LY UT WOS:000244015600002 PM 17236985 ER PT J AU Marsell, R Jonsson, KB Cho, TJ Einhorn, TA Ohlsson, C Schipani, E AF Marsell, Richard Jonsson, Kenneth B. Cho, Tae-Joon Einhorn, Thomas A. Ohlsson, Claes Schipani, Ernestina TI Mice expressing a constitutively active PTH/PTHrP receptor in osteoblasts show reduced callus size but normal callus morphology during fracture healing SO ACTA ORTHOPAEDICA LA English DT Article ID HORMONE-RELATED PEPTIDE; BONE-MINERAL DENSITY; PARATHYROID-HORMONE; INDIAN HEDGEHOG; PROTEIN; GROWTH; DIFFERENTIATION; OSTEOPOROSIS; STRENGTH; REPAIR AB Background The parathyroid hormone-/parathyroid hormone-related protein (PTHIPTHrP) receptor plays a crucial role in endochondral bone formation and possibly also in fracture healing. Patients with Jansen's meta-physial chondrodysplasia (JMC) have a gain-of-function mutation in the PTH/PTHrP receptor. Transgenic mice expressing JMC PTH/PTHrP receptor mutants in osteo-blasts are characterized by increased trabecular bone formation and reduced osteoblastic activity at periosteal sites. We have analyzed the bone phenotype and studied the fracture healing process in this model. Methods We performed bone density analysis of tibiae from 17-week-old transgenic mice and controls. Also, tibial fractures were produced in 14-week-old mice. Fracture healing was examined by radiographic and histological analysis. Results Transgenic mice had a lower total bone mineral content (BMC), by a factor of one-third. The changes were bone compartment-specific with an increase in trabecular bone volume and a decrease in cortical thickness. The calluses in the transgenic mice were smaller, with a reduction in BMC and mean crosssectional area by a factor of one-half. Despite the smaller size, however, the morphology and progression through the healing process were similar in both transgenic and wild-type littermates. Interpretation We conclude that the constitutively active PTR/PTHrP receptor has compartment-specific effects on bone formation when expressed in osteoblasts. During fracture healing, however, both the periosteal and the endochondral processes are activated, leading to fracture healing that is temporally and morphologically normal, although the callus tissue is less prominent. C1 Univ Uppsala Hosp, Dept Surg Sci, Uppsala, Sweden. Boston Univ, Med Ctr, Dept Orthopaed Surg, Orthopaed Res Lab, Boston, MA 02215 USA. Sahlgrens Univ Hosp, Dept Internal Med, Div Endocrinol, S-41345 Gothenburg, Sweden. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Seoul Natl Univ, Coll Med, Dept Orthopaed Surg, Seoul, South Korea. RP Jonsson, KB (reprint author), Univ Uppsala Hosp, Dept Surg Sci, Uppsala, Sweden. EM Kenneth.Jonsson@surgsci.uu.se RI Cho, Tae-Joon/I-9355-2012; OI Cho, Tae-Joon/0000-0001-8514-377X; Einhorn, Thomas/0000-0002-5075-4885 NR 21 TC 7 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1745-3674 J9 ACTA ORTHOP JI Acta Orthop. PD FEB PY 2007 VL 78 IS 1 BP 39 EP 45 DI 10.1080/17453670610013402 PG 7 WC Orthopedics SC Orthopedics GA 150TX UT WOS:000245243600007 PM 17453391 ER PT J AU Henderson, DC Fan, X Copeland, PM Borba, CP Daley, TB Nguyen, DD Zhang, H Hayden, D Freudenreich, O Cather, C Evins, AE Goff, DC AF Henderson, D. C. Fan, X. Copeland, P. M. Borba, C. P. Daley, T. B. Nguyen, D. D. Zhang, H. Hayden, D. Freudenreich, O. Cather, C. Evins, A. E. Goff, D. C. TI A double-blind, placebo-controlled trial of sibutramine for clozapine-associated weight gain SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE clozapine; sibutramine; weight; lipids; schizophrenia ID DIABETES-MELLITUS; SCHIZOPHRENIA; OLANZAPINE; OBESITY; EFFICACY; PROFILE AB Objective: This study sought to examine the effectiveness of sibutramine, a weight loss agent, on clozapine-associated weight gain. Method: This was a 12-week double-blind, placebo controlled, randomized trial of sibutramine for weight loss in obese clozapine-treated schizophrenia or schizoaffective disorder subjects. Results: Ten patients were enrolled into the placebo group and 11 patients into the sibutramine group. There were no significant baseline differences between the two groups on age, gender, education, ethnicity, diagnosis, weight, body mass index (BMI), and blood pressure. At week 12, there were no significant differences in changes in weight, BMI, abdominal and waist circumferences, Hba1c, fasting glucose, or cholesterol levels. Conclusion: Sibutramine treatment did not show significant weight loss compared with placebo in clozapine-treated patients with schizophrenia or schizoaffective disorder. Further research with a larger sample size and longer follow-up duration is warranted. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org NR 16 TC 40 Z9 41 U1 1 U2 1 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 FEB PY 2007 VL 115 IS 2 BP 101 EP 105 DI 10.1111/j.1600-0447.2006.00855.x PG 5 WC Psychiatry SC Psychiatry GA 126IM UT WOS:000243506600003 PM 17244173 ER PT J AU Feldner, MT Babson, KA Zvolensky, MJ Vujanovic, AA Lewis, SF Gibson, LE Monson, CM Bernstein, A AF Feldner, Matthew T. Babson, Kimberly A. Zvolensky, Michael J. Vujanovic, Anka A. Lewis, Sarah F. Gibson, Laura E. Monson, Candice M. Bernstein, Amit TI Posttraumatic stress symptoms and smoking to reduce negative affect: An investigation of trauma-exposed daily smokers SO ADDICTIVE BEHAVIORS LA English DT Article DE smoking; posttraumatic stress; comorbidity; affect regulation; smoking motives ID VIETNAM COMBAT VETERANS; ANXIETY SENSITIVITY; CIGARETTE USE; PANIC DISORDER; RISK-FACTORS; SCALE; PTSD; DEPRESSION; MOTIVES; PREVALENCE AB The present investigation examined the relations among posttraumatic stress symptoms and smoking motives. Participants included 100 daily smokers recruited from the community and university settings who reported exposure to at least one traumatic event that met criterion A for posttraumatic stress disorder. Consistent with prediction, higher levels of posttraumatic stress symptoms were associated with smoking to reduce negative affect; this relation was observed after controlling for variance accounted for by number of cigarettes smoked per day and gender. Results are discussed in terms of the implications of smoking to regulate affect among daily smokers who have been exposed to traumatic events. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Arkansas, Dept Psychol, Prevent Sci Div, Intervent Sci Lab, Fayetteville, AR 72701 USA. Univ Vermont, Burlington, VT 05405 USA. Meridian Behav Hlth Serv, Sylva, NC USA. Boston Univ, Sch Med, Vet Affairs Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02215 USA. RP Feldner, MT (reprint author), Univ Arkansas, Dept Psychol, Prevent Sci Div, Intervent Sci Lab, 216 Mem Hall, Fayetteville, AR 72701 USA. EM mfeldne@uark.edu NR 43 TC 37 Z9 38 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2007 VL 32 IS 2 BP 214 EP 227 DI 10.1016/j.addbeh.2006.03.032 PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 128OM UT WOS:000243667200002 PM 16644135 ER PT J AU McChargue, DE Cook, JW AF McChargue, Dennis E. Cook, Jessica Werth TI Depression vulnerability within smoking research: How accurate are one-item screening items? SO ADDICTIVE BEHAVIORS LA English DT Article DE cigarette smoking; assessment; depression ID ANHEDONIA; HISTORY AB Epidemiological and large scale treatment studies within smoking research have utilized many one-item screening items to examine the influence of current depressive symptoms on smoking behavior and quitting. Little is known about that concurrent validity of screening items that may reflect depression vulnerability independent of current symptoms. The present paper evaluated the concurrent validity of two one-item screening items that were essential for diagnosing past episodes of major depression. Screening questions were administered to seventy-seven nicotine dependent participants via a telephone screening interview. Smokers then returned to the laboratory for a comprehensive structured assessment of depressive vulnerability. Vulnerability measures were clinician-diagnosed history of major depressive disorder and other self-reported depressive vulnerability factors. Telephone screening items accurately classified a clinician-diagnosed history of major depression, and predicted the number of recurrent depressive episodes, self-reported rumination, and self-reported depression-proneness (all p < 0.05). Results support the utility of one-item screening questions as a "proxy" of a depressive vulnerability for smoking treatment studies that are not designed for comprehensive assessment procedures. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Nebraska, Lincoln, NE 68588 USA. Univ Illinois, Chicago, IL USA. VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. RP McChargue, DE (reprint author), Univ Nebraska, 238 Burnett Hall,POB 880308, Lincoln, NE 68588 USA. EM dmcchargue2@unl.edu FU NIDA NIH HHS [DA00467, DA14144] NR 12 TC 19 Z9 19 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2007 VL 32 IS 2 BP 404 EP 409 DI 10.1016/j.addbeh.2006.05.006 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 128OM UT WOS:000243667200020 PM 16854531 ER PT J AU Nicholas, PK Kemppainen, JK Canaval, GE Corless, IB Sefcik, EF Nokes, KM Bain, CA Kirksey, KM Eller, LS Dole, PJ Hamilton, MJ Coleman, CL Holzemer, WL Reynolds, NR Portillo, CJ Bunch, EH Wantland, DJ Voss, J Phillips, R Tsai, YF Mendez, MR Lindgren, TG Davis, SM Gallagher, DM AF Nicholas, P. K. Kemppainen, J. K. Canaval, G. E. Corless, I. B. Sefcik, E. F. Nokes, K. M. Bain, C. A. Kirksey, K. M. Eller, L. Sanzero Dole, P. J. Hamilton, M. J. Coleman, C. L. Holzemer, W. L. Reynolds, N. R. Portillo, C. J. Bunch, E. H. Wantland, D. J. Voss, J. Phillips, R. Tsai, Y. -F. Mendez, M. Rivero Lindgren, T. G. Davis, S. M. Gallagher, D. M. TI Symptom management and self-care for peripheral neuropathy in HIV/AIDS SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID DISTAL SENSORY POLYNEUROPATHY; QUALITY-OF-LIFE; HIV-INFECTION; ANTIRETROVIRAL THERAPY; NEUROLOGIC MANIFESTATIONS; RISK-FACTORS; HAT-QOL; COHORT; AIDS; PATHOPHYSIOLOGY AB Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of peripheral neuropathy in HIV disease, sociodemographic and disease-related correlates and self-care strategies. A convenience sample of 1,217 respondents was recruited from data collection sites in several US cities, Puerto Rico, Colombia and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n = 450) identified 20 self-care behaviors including complementary therapies, use of medications, exercise and rest and/or elevation of extremities. Ratings of frequency and effectiveness were also included. An activities checklist summarized into five categories of self-care behaviors including activities/thoughts, exercise, medications, complementary therapies and substance was used to determine self-care behaviors. Taking a hot bath was the most frequent strategy used by those with peripheral neuropathy (n = 292) and received the highest overall rating of effectiveness of any self-management strategies included in this study at 8.1 (scale 1-10). Other self-care strategies to manage this symptom included: staying off the feet (n = 258), rubbing the feet with cream (n = 177), elevating the feet (n = 236), walking (n = 262), prescribed antiepileptic agent (n = 80), prescribed analgesics (n = 84), over-the-counter medications (n = 123), vitamin B (n = 122), calcium supplements (n = 72), magnesium (n = 48), massage (n = 156), acupuncture (n = 43), reflexology (n = 23) and meditation (n = 80). Several behaviors that are often deemed unhealthy were included among the strategies reported to alleviate peripheral neuropathy including use of marijuana (n = 67), cigarette smoking (n = 139), drinking alcohol (n = 81) and street drugs (n = 30). C1 Brigham & Womens Hosp, MGH Inst Hlth Profess, Grad Program Nursing, Boston, MA 02129 USA. Univ N Carolina, Wilmington, NC 28401 USA. Univ Valle, Cali, Colombia. Texas A&M Univ, Corpus Christi, TX USA. CUNY Hunter Coll, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Ben Taub Gen Hosp, Houston, TX 77030 USA. Rutgers State Univ, Newark, NJ 07102 USA. Greenwich House, New York, NY USA. Univ Penn, Philadelphia, PA 19104 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Oslo, N-0316 Oslo, Norway. Natl Inst Hlth, Natl Inst Neuromuscular Dis Sect, Bethesda, MD USA. Chang Gung Univ, Tao Yuan, Taiwan. Univ Puerto Rico, San Juan, PR 00936 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England AIDS Educ & Training Ctr, Boston, MA USA. RP Nicholas, PK (reprint author), Brigham & Womens Hosp, MGH Inst Hlth Profess, Grad Program Nursing, 36 1st Ave, Boston, MA 02129 USA. EM pnicholas@mghihp.edu RI Canaval, Gladys/F-7284-2015; OI Canaval, Gladys/0000-0001-9841-5084; Corless, Inge/0000-0003-0438-2037 NR 47 TC 32 Z9 32 U1 2 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD FEB PY 2007 VL 19 IS 2 BP 179 EP 189 DI 10.1080/09540120600971083 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 130FY UT WOS:000243786400005 PM 17364396 ER PT J AU Morfin, JP Kulig, C Everson, G Beresford, T AF Morfin, John-Paul Kulig, Clark Everson, Gregory Beresford, Thomas TI Controlling for serum albumin level improves the correlation between serum fatty acid ethyl esters and blood ethanol level SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE fatty acid ethyl esters (FAEEs); ethanol; albumin ID HEPG2 CELLS; MARKERS; LIPOPROTEINS; CONSUMPTION; PLASMA AB Background: Fatty acid ethyl esters (FAEEs) are generated by the nonoxidative metabolism of alcohol and correlate positively with blood alcohol levels (BAL). As FAEEs are produced predominantly in the liver and bind to albumin in plasma, blood FAEE concentrations may be affected by serum albumin levels. The aim of this exploratory study was to define the relationship of FAEE levels with BAL after adjustment for serum albumin concentration. Methods: Fatty acid ethyl ester, BAL, and albumin concentrations were measured from de-identified, ethanol-containing serum samples (N=18). The assay focused on 3 FAEE species ethyl palmitate, ethyl stearate, and ethyl oleate. The relationships of individual and total FAEE concentrations with BAL using albumin as a covariate were analyzed. Values for Pearson's r between the BAL and the natural log-transformed FAEE (ln FAEE) levels were calculated, and then compared with partial correlation coefficients when controlling for albumin. The impact of serum albumin levels on the relationship between ln FAEE and BAL was evaluated by simple linear regression analysis. Results: Concentrations of total FAEE ranged from 632 to 20,166 nM, and BAL ranged from 9 to 375 mg/dL. In the 18 samples, the Pearson correlation coefficient between BAL and total FAEE levels was 0.868, and increased to 0.909 when controlling for albumin (p < 0.0001). Similar statistically significant increases in the partial correlation coefficient occurred for each of the individual species of FAEE when controlling for albumin. In simple linear regression, albumin significantly reduced the variability in the model correlating BAL and FAEE for each of the individual species, as well as for total FAEE. Conclusions: The association between FAEE levels and BAL is enhanced by consideration of serum albumin concentrations. Our findings suggest that serum albumin should be included in any model attempting to define the relationship between BAL and FAEE. C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80262 USA. Univ Colorado, Dept Psychiat, Denver, CO 80262 USA. Denver VA Med Ctr, Div Gastroenterol & Hepatol, Denver, CO USA. Univ Colorado, Div Gastroenterol & Hepatol, Hlth Sci Ctr, Denver, CO 80202 USA. RP Morfin, JP (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, 4200 E 9th Ave, Denver, CO 80262 USA. EM john-paul.morfin@uchsc.edu NR 19 TC 2 Z9 2 U1 0 U2 1 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 FEB PY 2007 VL 31 IS 2 BP 265 EP 268 DI 10.1111/j.1530-0277.2006.00302.x PG 4 WC Substance Abuse SC Substance Abuse GA 128QW UT WOS:000243674200011 PM 17250618 ER PT J AU Groeneveld, PW Kruse, GB Chen, Z Asch, DA AF Groeneveld, Peter W. Kruse, Gregory B. Chen, Zhen Asch, David A. TI Variation in cardiac procedure use and racial disparity among Veterans Affairs Hospitals SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE-SYSTEM; DIFFUSION; MORTALITY; CATHETERIZATION; TECHNOLOGY; OUTCOMES; TRENDS; IMPACT; RACE AB Background Lower or less racially equitable cardiac procedure rates at Veterans Affairs medical centers (VAMCs) with larger minority populations may be sources of racial disparities. This study's objectives were to determine if VAMCs with higher proportions of black inpatients performed fewer cardiac procedures or had larger racial differences in procedure rates than predominantly white VAMCs. Methods We identified 87536 potential candidates for bioprosthetic aortic valve replacement, 50517 for implanted card ioverter/defi brillator (ICD), 92 292 for dual-chambered pacemaker (DCP), and 70 269 for percutaneous coronary intervention (PCI) hospitalized between 1998 and 2003. Multivariate regression models were fitted that controlled for patients' demographic and clinical characteristics as well as hospital factors such as academic affiliation and inpatient racial composition. Racial differences in procedure rates both across and within hospital-level classifications were examined. Results Across VA hospital types, there were few significant differences in adjusted procedure rates at VAMCs with larger compared with smaller black inpatient populations. Conversely, within-hospital estimates of black versus white procedure use indicated VAMCs with > 30% black inpatients had greater racial differences compared to predominantly white VAMCs (adjusted black-white odds ratios of 0.45 vs 0.81 for aortic valve replacement [P =.07], 0.54 vs.0.85 for DCPs [ P < .001], 0.54 vs 0.65 for ICDs [ P =.301, and 0.69 vs 0.86 for PCI [P =.01].) Conclusions Although VAMCs with larger black inpatient populations performed cardiac procedures at similar rates as predominantly white VAMCs, racial differences in procedures were greater within VAMCs with larger black populations. Improving equity at VAMCs with larger minority populations is critical to achieving systemwide health care equality. C1 Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Hlth Care Syst Dept, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), 1229 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.groeneveld@va.gov OI Asch, David/0000-0002-7970-286X NR 23 TC 16 Z9 16 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 FEB PY 2007 VL 153 IS 2 BP 320 EP 327 DI 10.1016/j.ahj.2006.10.032 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 133XQ UT WOS:000244047600027 PM 17239696 ER PT J AU Kathiresan, S Larson, MG Keyes, MJ Polak, JF Wolf, PA D'Agostino, RB Jaffer, FA Clouse, ME Levy, D Manning, WJ O'Donnell, CJ AF Kathiresan, Sekar Larson, Martin G. Keyes, Michelle J. Polak, Joseph F. Wolf, Philip A. D'Agostino, Ralph B. Jaffer, Farouc A. Clouse, Melvin E. Levy, Daniel Manning, Warren J. O'Donnell, Christopher J. TI Assessment by cardiovascular magnetic resonance, electron beam computed tomography, and carotid ultrasonography of the distribution of subclinical atherosclerosis across Framingham risk strata SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; ARTERY CALCIUM; AORTIC ATHEROSCLEROSIS; MEDIA THICKNESS; ADULTS; INTIMA AB Screening for subclinical atherosclerosis has been advocated for individuals at intermediate global risk for coronary heart disease (CHD). However, the distribution of subclinical atherosclerosis test values across CHD risk strata is unknown. We studied a stratified random sample of 292 participants (mean age 59.5 years, 50% women) from the offspring cohort of the Framingham Heart Study who were free of clinically apparent cardiovascular disease. We assessed abdominal and thoracic aortic plaque burden by cardiovascular magnetic resonance (CMR), coronary artery calcification (CAC) and thoracic aortic calcification (TAC) by electron beam computed tomography, and common carotid intima-media thickness (C-IMT) by ultrasonography. We categorized the upper 20% of each measurement as a high level of atherosclerosis and evaluated these variables across clinically relevant Framingham CHD risk score strata (low, intermediate, and high risk). In age-adjusted analyses in men and women, correlations across CMR aortic plaque, CAC, TAC, and C-IMT were low (maximum r = 0.30 for CAC:TAC in women, p < 0.005). In men and women, the proportion of subjects with high atherosclerosis test results for any of these measurements increased significantly across Framingham CHD risk score strata (Kruskal-Wallis test, p < 0.0001). In the intermediate Framingham CHD risk score category, 14% of men and 25% of women had a high atherosclerosis result on 2 measurements. However, different participants were identified as having high atherosclerosis by each modality. For example, in a comparison of the overlap across CMR aortic plaque, CAC, and C-IMT, only 4% of men and 16% of women were classified as having high atherosclerosis on all 3 measurements. In conclusion, in a community-based sample, correlations among subclinical atherosclerosis test results are low, and a substantial proportion has high levels of subclinical atherosclerosis detected on >= 2 imaging tests. (c) 2007 Elsevier Inc. All rights reserved. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. Tufts Univ, New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA. EM codonell@nih.gov OI Larson, Martin/0000-0002-9631-1254; Jaffer, Farouc/0000-0001-7980-384X FU NHLBI NIH HHS [N01-HC-25195] NR 14 TC 33 Z9 33 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB PY 2007 VL 99 IS 3 BP 310 EP 314 DI 10.1016/j.amjcard.2006.08.028 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 132MW UT WOS:000243947900004 PM 17261388 ER PT J AU Bonaca, MP Wiviott, SD Sabatine, MS Buros, J Murphy, SA Scirica, BM Rifai, N Antman, EM Morrow, DA AF Bonaca, Marc P. Wiviott, Stephen D. Sabatine, Marc S. Buros, Jacqueline Murphy, Sabina A. Scirica, Benjamin M. Rifai, Nader Antman, Elliott M. Morrow, David A. TI Hemodynamic significance of periprocedural myocardial injury assessed with N-terminal pro-B-Type natriuretic peptide after percutaneous coronary intervention in patients with stable and unstable coronary artery disease (from the JUMBO-TIMI 26 trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID KINASE-MB ELEVATION; TROPONIN-I; RISK; MORTALITY AB The clinical relevance of periprocedural myocardial injury related to percutaneous coronary intervention (PCI) remains controversial. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a sensitive indicator of hemodynamic stress and when increased is associated with higher mortality in patients with acute and chronic ischemic heart disease. We measured the serum level of NT-pro-BNP using the Elecsys 2010 proBNP assay at baseline, 4 to 6 hours, and 12 to 24 hours in 747 patients undergoing elective or urgent PCI and enrolled in the JUMBO-TIMI 26 trial. Periprocedural myocardial infarction (MI) was independently adjudicated and required a new increase in creatine kinase-MB > 3 times the upper limit of normal distinct from MI as the indication for PCI. Patients with procedural MI had significantly higher levels of NT-pro-BNP at 12 to 24 hours (405 vs 146 pg/ml, p < 0.001). Moreover, the greater increase in NT-pro-BNP in patients with periprocedural MI was independent of each clinical and other procedural correlates of NT-pro-BNP after PCI (p < 0.001). In addition, the magnitude of increase in NT-pro-BNP correlated strongly with extent of myocardial injury, including in patients with evidence of injury (creatine kinase-MB I to 3 times upper limit of normal) not meeting criteria for MI (p = 0.001) or low-level increase in troponin T (p = 0.001). In conclusion, periprocedural myocardial injury, even at low levels, during PCI is associated with increased hemodynamic stress as. measured by increasing NT-pro-BNP. This finding supports the physiologic relevance of procedural MI and the continued effort to define therapies that decrease the risk of this complication. (c) 2007 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Childrens Hosp Med Ctr, Boston, MA USA. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org OI Buros, Jacqueline/0000-0001-9588-4889 NR 15 TC 9 Z9 12 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB PY 2007 VL 99 IS 3 BP 344 EP 348 DI 10.1016/j.amjcard.2006.08.035 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 132MW UT WOS:000243947900011 PM 17261395 ER PT J AU Fewtrell, MS Morgan, JB Duggan, C Gunnlaugsson, G Hibberd, PL Lucas, A Kleinman, RE AF Fewtrell, Mary S. Morgan, Jane B. Duggan, Christopher Gunnlaugsson, Geir Hibberd, Patricia L. Lucas, Alan Kleinman, Ronald E. TI Optimal duration of exclusive breastfeeding: what is the evidence to support current recommendations? SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Conference on Maternal Nutrition and Optimal Infant Feeding Practicesqq CY FEB 23-24, 2006 CL Houston, TX SP Natl Inst Child Hlth & Human Dev, Off Dietary Supplements, NIH, US Dept Hlth & Human Serv, Baylor Coll Med, USDA ARS Childrens Nutr Res Ctr DE infants; breastfeeding; complementary feeding; World Health Organization; public health ID COMPLEMENTARY FOODS; FULL-TERM; INFANTS; AGE; CHILDREN; HEALTH; DIET; RISK AB Before 2001, the World Health Organization (WHO) recommended that infants be exclusively breastfed for 4-6 mo with the introduction of complementary foods (any fluid or food other than breast milk) thereafter. In 200 1, after a systematic review and expert consultation, this advice was changed, and exclusive breastfeeding is now recommended for the first 6 mo of life. The systematic review commissioned by the WHO compared infant and maternal outcomes for exclusive breastfeeding for 3-4 mo versus 6 mo. That review concluded that infants exclusively breastfed for 6 mo experienced less morbidity from gastrointestinal infection and showed no deficits in growth but that large randomized trials are required to rule out small adverse effects on growth and the development of iron deficiency in susceptible infants. Others have raised concerns that the evidence is insufficient to confidently recommend exclusive breastfeeding for 6 mo for infants in developed countries, that breast milk may not meet the full energy requirements of the average infant at 6 mo of age, and that estimates of the proportion of exclusively breastfed infants at risk of specific nutritional deficiencies are not available. Additionally, virtually no data are available to form evidence-based recommendations for the introduction of solids in formula-fed infants. Given increasing evidence that early nutrition and growth have effects on both short- and longer-term health, it is vital that this issue be investigated in high-quality randomized studies. Meanwhile, the consequences of the WHO recommendation should be monitored in different settings to assess compliance and record and act on adverse events. The policy should then be reviewed in the context of new data to formulate evidence-based recommendations. C1 Massachusetts Gen Hosp, Pediat Gastrointestinal & Nutr Unit, Dept Pediat, Boston, MA 02114 USA. Inst Child Hlth, MRC Childhood Nutr Res Ctr, London, England. Univ Surrey, Sch Biomed & Mol Sci, Guildford GU2 5XH, Surrey, England. Childrens Hosp, Clin Nutr Serv, Div GI Nutr, Boston, MA 02115 USA. Ctr Child Hlth Serv, Reykjavik, Iceland. Tufts Univ New England Med Ctr, Boston, MA USA. RP Kleinman, RE (reprint author), Massachusetts Gen Hosp, Pediat Gastrointestinal & Nutr Unit, Dept Pediat, Wnag 731,55 Fruit St, Boston, MA 02114 USA. EM rkleinman@partners.org NR 22 TC 62 Z9 68 U1 1 U2 16 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 FEB PY 2007 VL 85 IS 2 BP 635S EP 638S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 137JZ UT WOS:000244290200046 PM 17284769 ER PT J AU Marsh, RD Lima, CMR Levy, DE Mitchell, EP Rowland, KM Benson, AB AF Marsh, Robert de W. Lima, C. M. Rocha Levy, D. E. Mitchell, E. P. Rowland, K. M., Jr. Benson, A. B., III TI A phase II trial of perifosine in locally advanced, unresectable, or metastatic pancreatic adenocarcinoma SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE adenocarcinoma; alkylphosphocholine; pancreas; perifosine; phase II; unresectable ID CURATIVE RESECTION; CANCER; GEMCITABINE; SURVIVAL; RADIATION; D-21266; PATHWAY AB Background: Perifosine, a heterocyclic alkylphosphocholine signal transduction inhibitor, has activity against multiple cell types in vitro. This is a phase II study to determine activity and toxicity of perifosine in pancreatic adenocarcinoma. Patients and Methods: Previously untreated patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma, performance status Eastern Cooperative Oncology Group 0 or 1, were enrolled. An oral loading dose of 900 mg was followed by 100 mg per day until progression or unacceptable toxicity. Response criteria in solid tumors (RECIST) methodology and a 2-stage design were used. Suspension could occur for inadequate response in the first cohort or for more than 25% grade 3 or greater toxicity. Results: Ten patients were enrolled. Six received 1 month and 4 received 2 months of treatment. Four discontinued therapy as a result of progression and 2 because of clinical deterioration. Three died during treatment. One patient had stable disease but discontinued therapy as a result of unacceptable adverse events (95% confidence interval: 0.3-45%). There were no objective responses and all patients died of progressive disease. Median overall and progression-free survival was 1.85 months (95% confidence interval: 0.9-2.7) and 1.5 months (95% confidence interval: 0.9-1.9) respectively. Conclusion: The study was suspended and subsequently terminated as a result of unacceptable adverse events during the first stage. Perifosine does not appear to be worthy of further study in this group of patients. C1 Univ Florida, Dept Med, Div Hematol Oncol, Gainesville, FL 32610 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Carle Clin Assoc, Urbana, IL USA. Northwestern Univ, Chicago, IL 60611 USA. RP Marsh, RD (reprint author), Univ Florida, Dept Med, Div Hematol Oncol, 1600 SW Archer Rd, Gainesville, FL 32610 USA. EM marshrd@medicine.ufl.edu NR 22 TC 32 Z9 32 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2007 VL 30 IS 1 BP 26 EP 31 DI 10.1097/01.coc.000251235.46149.43 PG 6 WC Oncology SC Oncology GA 136AZ UT WOS:000244196300006 ER PT J AU Pashley, DH Tay, FR Carvalho, RM Rueggeberg, FA Agee, KA Carrilho, M Donnelly, A Garcia-Godoy, F AF Pashley, David H. Tay, Franklin R. Carvalho, Ricardo M. Rueggeberg, Frederick A. Agee, Kelli A. Carrilho, Marcela Donnelly, Adam Garcia-Godoy, Franklin TI From dry bonding to water-wet bonding to ethanol-wet bonding. A review of the interactions between dentin matrix and solvated resins using a macromodel of the hybrid layer SO AMERICAN JOURNAL OF DENTISTRY LA English DT Review ID DEMINERALIZED DENTIN; DIMENSIONAL CHANGES; SOLUBILITY PARAMETER; TENSILE PROPERTIES; ADHESIVE RESINS; POLAR-SOLVENTS; STRENGTH; HYDROPHILICITY; PRIMERS; SYSTEMS AB Purpose: To review the use of a new resin-dentin bonding model called the macro-hybrid layer, to quantify resin uptake and matrix shrinkage during resin infiltration and solvent evaporation. A secondary purpose was to introduce the concept of ethanol-wet bonding where water-saturated acid-etched dentin is exchanged with ethanol to create ethanol-saturated dentin. Adhesive monomers seem to penetrate ethanol-saturated dentin more thoroughly than water-saturated dentin. C1 Med Coll Georgia, Sch Dent, Dept Oral Biol & Maxillofacial Pathol, Dent Res Ctr, Augusta, GA 30912 USA. Med Coll Georgia, Dept Oral Rehabil, Div Mat Sci, Augusta, GA 30912 USA. Univ Sao Paulo, Bauru Sch Dent, Dept Prosthodont, Bauru, SP, Brazil. Nova SE Univ, Coll Dent Med, Biosci Res Ctr, Dept Restorat Dent, Ft Lauderdale, FL 33314 USA. Nova SE Univ, Coll Dent Med, Biosci Res Ctr, Dept Pediat Dent, Ft Lauderdale, FL 33314 USA. Forsyth Inst, Boston, MA USA. RP Pashley, DH (reprint author), Med Coll Georgia, Sch Dent, Dept Oral Biol & Maxillofacial Pathol, Dent Res Ctr, 1120 15th St,CL2112, Augusta, GA 30912 USA. EM dpashley@mail.mcg.edu RI Rastelli, Marcio/B-8034-2011; Carrilho, Marcela/D-1154-2013 FU NIDCR NIH HHS [R01 DE014911] NR 51 TC 146 Z9 156 U1 0 U2 16 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 FEB PY 2007 VL 20 IS 1 BP 7 EP 20 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 143DK UT WOS:000244700000003 PM 17380802 ER PT J AU Onodera, H Mihm, MC Sato, T Matsuta, M Akasaka, T Nakamura, SI AF Onodera, Hanae Mihm, Martin C., Jr. Sato, Toshiki Matsuta, Mayumi Akasaka, Toshihide Nakamura, Shin-ichi TI A carcinoma with features of porocarcinoma, dermal ductular carcinoma, and squamous cell carcinoma in situ SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE eccrine carcinoma; porocarcinoma; squamous cell carcinoma in situ; dermal ductular carcinoma; squamoid differentiation; adnexal carcinoma ID MALIGNANT ECCRINE POROMA; DIFFERENTIATION AB We report the case of a 69-year-old Japanese woman with an extraordinary carcinoma on her back. The tumor had three different histologic components including porocarcinoma, dermal ductular carcinoma, and an area resembling squamous cell carcinoma in situ (SCCIS). Sweat gland tumors (SGTs) are known to have a wide spectrum of pathologic appearances and variable grades of differentiation. This report expands the spectrum of reported combinations. C1 Iwate Med Univ, Dept Dermatol, Clin Cent Lab, Morioka, Iwate 0208505, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Sect, Boston, MA USA. Iwate Med Univ, Dept Clin Pathol, Clin Cent Lab, Morioka, Iwate 0208505, Japan. RP Akasaka, T (reprint author), Iwate Med Univ, Dept Dermatol, Clin Cent Lab, 19-1 Uchimaru, Morioka, Iwate 0208505, Japan. EM akatoshi@nnet.ne.jp NR 15 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD FEB PY 2007 VL 29 IS 1 BP 75 EP 78 DI 10.1097/01.dad.0000246389.98258.21 PG 4 WC Dermatology SC Dermatology GA 172GL UT WOS:000246792000014 PM 17284967 ER PT J AU Konstantopoulos, WM Pliakas, J Hong, C Chan, K Kim, G Nentwich, L Thomas, SH AF Konstantopoulos, Wendy Macias Pliakas, John Hong, Christine Chan, Katie Kim, Gina Nentwich, Lauren Thomas, Stephen H. TI Helicopter emergency medical services and stroke care regionalization: measuring performance in a maturing system SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Aeromedical World Congress 2005 CY JUN 20-23, 2005 CL Barcelona, SPAIN ID ACUTE ISCHEMIC-STROKE; TRANSPORT; THROMBOLYSIS; SAFETY AB This study retrospectively analyzed 123 patients undergoing helicopter emergency medical services transport for ischemic stroke (ischemic cerebrovascular accident) to the Massachusetts General Hospital during 2000-2004. To assess for system improvements over time, data were analyzed between the 2 consecutive 30-month periods comprising the 5-year study. Patients transported during the latter 30 months were transported from lesser distances (P = .002), were more likely to be younger than 65 years (P = .005), and were more likely to have documented symptom onset time (P = .03) and National Institutes of Health Stroke Scale (odds ratio, 3.6; 95% confidence interval, 1.7-7.6; P = .001). Time end points analysis found no significant improvements in any intervals compared across the 2 study eras. Age older than 65 years was the only covariate associated with a more rapid arrival at the Massachusetts General Hospital (odds ratio, 2.4; 95% CI, 1.1-5.4; P = .03). This study of our stroke transport system identified both areas of good performance and also areas for focusing further improvement efforts. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. Boston MedFlight, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Thomas, SH (reprint author), MGH Dept Emergency Serv, Boston, MA 02114 USA. EM thomas.stephen@mgb.harvard.edu NR 19 TC 9 Z9 9 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD FEB PY 2007 VL 25 IS 2 BP 158 EP 163 DI 10.1016/j.ajem.2006.06.016 PG 6 WC Emergency Medicine SC Emergency Medicine GA 136YY UT WOS:000244261200005 PM 17276804 ER PT J AU Mannisto, S Yaun, SS Hunter, DJ Spiegelman, D Adami, HO Albanes, D van den Brandt, PA Buring, JE Cerhan, JR Colditz, GA Freudenheim, JL Fuchs, CS Giovannucci, E Goldbohm, RA Harnack, L Leitzmann, M McCullough, ML Miller, AB Rohan, TE Schatzkin, A Virtamo, J Willett, WC Wolk, A Zhang, SM Smith-Warner, SA AF Mannisto, Satu Yaun, Shiaw-Shyuan Hunter, David J. Spiegelman, Donna Adami, Hans-Olov Albanes, Demetrius van den Brandt, Piet A. Buring, Julie E. Cerhan, James R. Colditz, Graham A. Freudenheim, Jo L. Fuchs, Charles S. Giovannucci, Edward Goldbohm, R. Alexandra Harnack, Lisa Leitzmann, Michael McCullough, Marjorie L. Miller, Anthony B. Rohan, Thomas E. Schatzkin, Arthur Virtamo, Jarmo Willett, Walter C. Wolk, Alicja Zhang, Shumin M. Smith-Warner, Stephanie A. TI Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carotenoids; cohort studies; colonic neoplasms; colorectal neoplasms; diet; meta-analysis; rectal neoplasms ID FOOD FREQUENCY QUESTIONNAIRE; BETA-CAROTENE; COLON-CANCER; ALPHA-TOCOPHEROL; WOMENS HEALTH; NEW-YORK; MICRONUTRIENT INTAKE; RECTAL-CANCER; MALE SMOKERS; LUNG-CANCER AB Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in each study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident cases of colorectal cancer were diagnosed among 702,647 participants. The authors calculated study-specific multivariate relative risks and then combined them using a random-effects model. In general, intakes of specific carotenoids were not associated with colorectal cancer risk. The pooled multivariate relative risks of colorectal cancer comparing the highest quintile of intake with the lowest ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein + zeaxanthin intake was the result borderline statistically significant (95% confidence interval: 0.84, 1.00). The associations observed were generally similar across studies, for both sexes, and for colon cancer and rectal cancer. These pooled data did not suggest that carotenoids play an important role in the etiology of colorectal cancer. C1 Natl Inst Publ Hlth, Dept Hlth Promot & Chron Dis Prevent, Helsinki 00300, Finland. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Karolinska Inst, Stockholm, Sweden. NCI, Bethesda, MD 20892 USA. Maastricht Univ, Fac Hlth Sci, Maastricht, Netherlands. Mayo Clin, Coll Med, Rochester, MN USA. SUNY Buffalo, Univ Buffalo, Buffalo, NY 14260 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. TNO Qual Life, Zeist, Netherlands. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Amer Canc Soc, Atlanta, GA 30329 USA. Univ Toronto, Fac Med, Toronto, ON, Canada. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Mannisto, S (reprint author), Natl Inst Publ Hlth, Dept Hlth Promot & Chron Dis Prevent, Mannerheimintie 166, Helsinki 00300, Finland. EM satu.mannisto@ktl.fi RI Albanes, Demetrius/B-9749-2015; Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Cerhan, James/0000-0002-7482-178X; Mannisto, Satu/0000-0002-8668-3046 FU NCI NIH HHS [CA78548, CA55075, N01 CN45035, N01 CN45165] NR 74 TC 28 Z9 29 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2007 VL 165 IS 3 BP 246 EP 255 DI 10.1093/aje/kwk009 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 130PK UT WOS:000243811300002 PM 17158857 ER PT J AU Schillerstrom, JE Rickenbacker, D Joshi, KG Royall, DR AF Schillerstrom, Jason E. Rickenbacker, Denae Joshi, Kaustubh G. Royall, Donald R. TI Executive function and capacity to consent to a noninvasive research protocol SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE decision-making capacity; competency; executive function; cognition ID MACCAT-T; COMPETENCE AB Objective: This study measured the association between executive function and decision-making capacity in subjects consenting to a noninvasive research protocol. Method: Subjects consenting to a noninvasive research protocol (N = 21; mean age: 65.5 [standard deviation: 9.2] years) were administered a modified version of The MacArthur Competency Assessment Tool-Treatment (MacCAT-T), Executive Interview (EXIT25), Executive Clock Drawing Task (CLOX), and Mini-Mental State Examination (MMSE). Results: The EXIT25 was the only instrument to correlate with each decision-making capacity domain: understanding, appreciation, and reasoning. Conclusions: Executive function as measured by the EXIT25 is associated with multiple decision-making capacity domains. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Wilford Hall USAF Med Ctr, Dept Psychiat, Lackland AFB, TX 78236 USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, San Antonio, TX USA. RP Schillerstrom, JE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM schillerstr@uthscsa.edu NR 10 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FEB PY 2007 VL 15 IS 2 BP 159 EP 162 DI 10.1097/01.JGP.0000249392.10426.c6 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 136HF UT WOS:000244212500009 PM 17272736 ER PT J AU Gurrera, RJ Karel, MJ Azar, AR Moye, J AF Gurrera, Ronald J. Karel, Michele J. Azar, Armin R. Moye, Jennifer TI Agreement between instruments for rating treatment decisional capacity SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE treatment decisions; decisional capacity; interrater agreement ID TO-MODERATE DEMENTIA; ALZHEIMERS-DISEASE; KAPPA; COMPETENCE; PREVALENCE; BIAS AB Objective: The objective of this study was to measure agreement between three treatment decisional capacity assessment instruments in mild to moderate dementia. Method: Subjects (N = 79) were recruited from the community. Rating agreement was evaluated with kappa statistics. Results: Three-way agreement was fair for overall capacity (kappa = 0.451), very good for understanding (0.618), very poor for choice (0.158), and no better than chance for reasoning and appreciation. Pairwise agreement showed a similar pattern. Conclusions: With the exception of understanding, current treatment decisional capacity assessment instruments do not consistently agree with one another in assessing treatment decision abilities. C1 VA Boston Healthcare Syst, Mental Hlth Serv, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. RP Gurrera, RJ (reprint author), 940 Belmont St 116A, Brockton, MA 02301 USA. EM ronald.gurrera@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Intramural VA [VA999999]; NIMH NIH HHS [R29 MH57104, R29 MH057104] NR 16 TC 13 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FEB PY 2007 VL 15 IS 2 BP 168 EP 173 DI 10.1097/JGP.0b013e31802e705c PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 136HF UT WOS:000244212500011 PM 17272738 ER PT J AU Cath, D Heutink, P Grados, M Singer, HS Walkup, JT Illmann, C Scharf, JM Santangelo, S Stewart, SE Platko, J Pauls, DL Cox, NJ Robertson, MM Service, S Keen-Kim, D Sabatti, C Freimer, N Rouleau, GA Riviere, JB Chouinard, S Richer, F Lesperance, P Dion, Y King, RA Kidd, JR Pakstis, AJ Leckman, JF Kidd, KK Gericke, G Kurlan, R Como, P Palumbo, D Verkerk, A Oostra, BA McMahon, W Leppert, M Coon, H Mathews, C Sandor, P Barr, CL Betard, C Zelenika, D AF Cath, D. Heutink, P. Grados, M. Singer, H. S. Walkup, J. T. Illmann, C. Scharf, J. M. Santangelo, S. Stewart, S. E. Platko, J. Pauls, D. L. Cox, N. J. Robertson, M. M. Service, S. Keen-Kim, D. Sabatti, C. Freimer, N. Rouleau, G. A. Riviere, J. -B. Chouinard, S. Richer, F. Lesperance, P. Dion, Y. King, R. A. Kidd, J. R. Pakstis, A. J. Leckman, J. F. Kidd, K. K. Gericke, G. Kurlan, R. Como, P. Palumbo, D. Verkerk, A. Oostra, B. A. McMahon, W. Leppert, M. Coon, H. Mathews, C. Sandor, P. Barr, C. L. Betard, C. Zelenika, D. CA Tourette Syndrome Assoc Int Consor TI Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; AUTOSOMAL-DOMINANT TRANSMISSION; BILINEAL TRANSMISSION; SEGREGATION ANALYSIS; TIC DISORDERS; LINKAGE; ASSOCIATION; INHERITANCE; RELIABILITY; PEDIGREE AB Tourette disorder (TD) is a neuropsychiatric disorder with a complex mode of inheritance and is characterized by multiple waxing and waning motor and phonic tics. This article reports the results of the largest genetic linkage study yet undertaken for TD. The sample analyzed includes 238 nuclear families yielding 304 "independent" sibling pairs and 18 separate multigenerational families, for a total of 2,040 individuals. A whole-genome screen with the use of 390 micro-satellite markers was completed. Analyses were completed using two diagnostic classifications: (1) only individuals with TD were included as affected and (2) individuals with either TD or chronic-tic (CT) disorder were included as affected. Strong evidence of linkage was observed for a region on chromosome 2p (-logP = 4.42, P = 3.8 x 10(-5)) in the analyses that included individuals with TD or CT disorder as affected. Results in several other regions also provide moderate evidence (-logP > 2.0) of additional susceptibility loci for TD. C1 Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. RP Pauls, DL (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Richard B Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu OI Barr, Cathy/0000-0003-0361-0106; Stewart, S. Evelyn/0000-0002-0994-6383 NR 49 TC 71 Z9 73 U1 2 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB PY 2007 VL 80 IS 2 BP 265 EP 272 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 129KX UT WOS:000243729500006 ER PT J AU Zardkoohi, O Haupert, GT AF Zardkoohi, Omeed Haupert, Garner T., Jr. TI Scarce among men SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID RENAL-ARTERY STENOSIS; FIBROMUSCULAR DYSPLASIA; INFARCTION; DISEASE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02129 USA. RP Haupert, GT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, CN-8,149 13th St, Charlestown, MA 02129 USA. EM gthaupert@partners.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 2007 VL 120 IS 2 BP 136 EP 139 DI 10.1016/j.amjmed.2006.01.030 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 131ZL UT WOS:000243911400007 PM 17275451 ER PT J AU Hayden, KM Welsh-Bohmer, KA Wengreen, HJ Zandi, PP Lyketsos, CG Breitner, JCS AF Hayden, Kathleen M. Welsh-Bohmer, Kathleen A. Wengreen, Heidi J. Zandi, Peter P. Lyketsos, Constantine G. Breitner, John C. S. CA Cache County Investigators TI Risk of mortality with vitamin E supplements: The Cache County Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE vitamin E; mortality; cardiovascular disease; cohort study; proportional hazards; survival analysis ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; NITRATE TOLERANCE; ALL-CAUSE; ANTIOXIDANT; EVENTS; TOCOPHEROL; HEALTH; CANCER AB PURPOSE: A recent meta-analysis reported increased mortality in clinical trial participants randomized to high-dose vitamin E. We sought to determine whether these mortality risks with vitamin E reflect adverse consequences of its use in the presence of cardiovascular disease. METHODS: In a defined population aged 65 years or older, baseline interviews captured self- or proxy-reported history of cardiovascular illness. A medicine cabinet inventory verified nutritional supplement and medication use. Three sources identified subsequent deaths. Cox proportional hazards methods examined the association between vitamin E use and mortality. RESULTS: After adjustment for age and sex, there was no association in this population between vitamin E use and mortality (adjusted hazard ratio [aHR] 0.93; 95% confidence interval [CI], 0.74-1.15). Predictably, deaths were more frequent with a history of diabetes, stroke, coronary artery bypass graft surgery, or myocardial infarction, and with the use of warfarin, nitrates, or diuretics. None of these conditions or treatments altered the null main effect with vitamin E, but mortality was increased in vitamin E users who had a history of stroke (aHR 3.64; CI, 1.73-7.68), coronary bypass graft surgery (aHR 4.40; CI, 2.83-6.83), or myocardial infarction (aHR 1.95; CI, 1.29-2.95) and, independently, in those taking nitrates (aHR 3.95; CI, 2.04-7.65), warfarin (aHR 3.71; CI, 2.22-6.21), or diuretics (aHR 1.83;CI, 1.35-2.49). Although not definitive, a consistent trend toward reduced mortality was seen in vitamin E users without these conditions or treatments. CONCLUSIONS: In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without. (c) 2007 Elsevier Inc. All rights reserved. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Utah State Univ, Dept Nutr & Food Sci, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD 21205 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Hayden, KM (reprint author), 2200 W Main St,Suite A-200, Durham, NC 27705 USA. EM khayden@duke.edu RI Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [AG-11380, R01 AG011380, T32-AG00029] NR 22 TC 30 Z9 33 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB PY 2007 VL 120 IS 2 BP 180 EP 184 DI 10.1016/j.amjmed.2006.03.039 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 131ZL UT WOS:000243911400016 PM 17275460 ER PT J AU Kojima, T Chang, JH Azar, DT AF Kojima, Takashi Chang, Jin-Hong Azar, Dimitri T. TI Proangiogenic role of ephrinB1/EphB1 in basic fibroblast growth factor-induced corneal angiogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASES; EPH RECEPTORS; VASCULAR MORPHOGENESIS; CARDIOVASCULAR DEVELOPMENT; EXTRACELLULAR-MATRIX; MOUSE CORNEA; TNF-ALPHA; EPHRINS; LIGANDS; NEOVASCULARIZATION AB Corneal neovascularization is a vision-threatening condition caused by various ocular pathological conditions. The aim of this study was to evaluate the function of the ephrin ligands; and Eph receptors in vitro and in vivo in corneal angiogenesis in a mouse model. The Eph tyrosine kinase receptors and their ligands, ephrins, are expressed on the cell surface. The functions of Eph and ephrins have been shown to regulate axonal guidance, segmentation, cell migration, and angiogenesis. Understanding the roles of Eph and ephrin in corneal angiogenesis may provide a therapeutic intervention for the treatment of angiogenesis-related disorders. Immunohistochemical studies demonstrated that ephrinB1 and EphB1 were expressed in basic fibroblast growth factor (bFGF)induced vascularized corneas. EphB1 was specifically colocalized with vascular endothelial marker CD31 surrounded by type IV collagen. EphrinB1 was expressed in corneal-resident keratocytes and neutrophils. Recombinant ephrinB1-Fc, which induces EphB receptor activation, enhanced bFGF-induced tube formation in an in vitro aortic ring assay and promoted bFGF-induced corneal angiogenesis in vivo in a corneal pocket assay. Synergistically enhanced and sustained activation of extracellular signal-regulated kinase was noted in vascular endothelial cell lines after stimulation with ephrin B1 and bFGF combinations. These results suggest that ephrinB1 plays a synergistic role in corneal neovascularization. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu FU NEI NIH HHS [EY10101, EY14048, R01 EY010101, R01 EY014048] NR 44 TC 27 Z9 31 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2007 VL 170 IS 2 BP 764 EP 773 DI 10.2353/ajpath.2007.060487 PG 10 WC Pathology SC Pathology GA 132OB UT WOS:000243951000033 PM 17255342 ER PT J AU Krebs, DE Scarborough, DM McGibbon, CA AF Krebs, David E. Scarborough, Donna Moxley McGibbon, Chris A. TI Functional vs. strength training in disabled elderly outpatients SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE elders; strengthening; functional training; exercises; functional limitations; disability; intervention study ID QUADRICEPS MUSCLE STRENGTH; OLDER-ADULTS; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; MUSCULAR STRENGTH; CONTROLLED-TRIAL; HIGH-INTENSITY; EXERCISE; GAIT; STABILITY AB Objective: To determine whether high-intensity functional training (FT) or strength training (ST) better enables impairment, disability, and functional gains among disabled community-dwelling elders. Design: Randomized, blinded, prospective clinical trial in a large, tertiary care outpatient rehabilitation department. Fifteen elders (62-85 yrs old) referred for physical therapy with one or more impairments, including lower-limb arthritis, participated in 6 wks of FT (weekly outpatient and three to five times per week of home practice in rapid and correct execution of locomotor activities of daily living, including gait, stepping, and sit to stand) or progressive resistive ST using elastic bands with intensity, therapist contact, and home practice similar to those of FT. Results: Both groups significantly improved their combined lower-extremity strength (hip abduction, ankle dorsiflexion, knee flexion, ankle plantarflexion, and knee extension) (P = 0.003), but no statistical difference between the ST and FT group gains (P = 0.203) was found. Subjects in both interventions improved their gait speed, but the FT group improved more than the ST group (P = 0.001). During chair rise, the FT group improved their maximum knee torque more than the ST group (P = 0.033), indicating that they employed a more controlled and efficient movement strategy. Conclusions:. These data suggest that an intensive FT intervention results in strength improvements of comparable magnitude as those attained from ST and that FT also confers greater improvements in dynamic balance control and coordination while performing daily life tasks. C1 MGH Inst Hlth Prof, Biomot Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. RP Krebs, DE (reprint author), MGH Inst Hlth Prof, Biomot Lab, CNY36-36 1st Ave, Boston, MA 02129 USA. FU NIA NIH HHS [P50AG11669, R01AG12561] NR 50 TC 36 Z9 40 U1 4 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD FEB PY 2007 VL 86 IS 2 BP 93 EP 103 DI 10.1097/PHM.0b013e31802ede64 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 131WK UT WOS:000243901700004 PM 17251692 ER PT J AU Contreras-Shannon, V Ochoa, O Reyes-Reyna, SM Sun, DX Michalek, JE Kuziel, WA McManus, LM Shireman, PK AF Contreras-Shannon, Veronica Ochoa, Oscar Reyes-Reyna, Sara M. Sun, Dongxu Michalek, Joel E. Kuziel, William A. McManus, Linda M. Shireman, Paula K. TI Fat accumulation with altered inflammation and regeneration in skeletal muscle of CCR2-/- mice following ischemic injury SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE adipocyte; macrophage; MyoD; myogenic progenitor cell; neutrophil; signal transducers of and activators of transcription-3 ID PERITONEAL-MACROPHAGES; CHEMOKINE RECEPTOR-2; MOLECULAR REGULATION; POSTISCHEMIC TISSUE; CELL-PROLIFERATION; STEM-CELLS; ACTIVATION; STAT3; AGE; MONOCYTE AB Chemokines recruit inflammatory cells to sites of injury, but the role of the CC chemokine receptor 2 ( CCR2) during regenerative processes following ischemia is poorly understood. We studied injury, inflammation, perfusion, capillary formation, monocyte chemotactic protein- 1 ( MCP- 1) levels, muscle regeneration, fat accumulation, and transcription factor activation in hindlimb muscles of CCR2(-/-) and wild- type ( WT) mice following femoral artery excision ( FAE). In both groups, muscle injury and restoration of vascular perfusion were similar. Nevertheless, edema and neutrophil accumulation were significantly elevated in CCR2(-/-) compared with WT mice at day 1 post-FAE and fewer macrophages were present at day 3. MCP- 1 levels in post-ischemic calf muscle of CCR2(-/-) animals were significantly elevated over baseline through 14 days post- FAE and were higher than WT mice at days 1, 7, and 14. In addition, CCR2(-/-) mice exhibited impaired muscle regeneration, decreased muscle fiber size, and increased intermuscular adipocytes with similar capillaries/ mm(2) postinjury. Finally, the transcription factors, MyoD and signal transducers of and activators of transcription3 ( STAT3), were significantly increased above baseline but did not differ significantly between groups at any time point post- FAE. These findings suggest that increases in MCP- 1, and possibly, MyoD and STAT3, may modulate molecular signaling in CCR2(-/-) mice during inflammatory and regenerative events. Furthermore, alterations in neutrophil and macrophage recruitment in CCR2(-/-) mice may critically alter the normal progression of downstream regenerative events in injured skeletal muscle and may direct myogenic precursor cells in the regenerating milieu toward an adipogenic phenotype. C1 Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Periodont, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. Prot Design Labs, Fremont, CA USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shireman, PK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Surg, 7703 Floyd Curl Dr,MC 7741, San Antonio, TX 78229 USA. EM shireman@uthscsa.edu NR 66 TC 73 Z9 76 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 2007 VL 292 IS 2 BP C953 EP C967 DI 10.1152/ajpcell.00154.2006 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 135RQ UT WOS:000244171100034 PM 17020936 ER PT J AU Crawford, RS Hashmi, FF Jones, JE Albadawi, H McCormack, M Eberlin, K Entabi, F Atkins, MD Conrad, MF Austen, WG Watkins, MT AF Crawford, Robert S. Hashmi, Faraz F. Jones, John E. Albadawi, Hassan McCormack, Michael Eberlin, Kyle Entabi, Fateh Atkins, Marvin D. Conrad, Mark F. Austen, W. Gerald, Jr. Watkins, Michael T. TI A novel model of acute murine hindlimb ischemia SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE tourniquets; skeletal muscle ID LOWER-LIMB ISCHEMIA; SYSTEMIC INFLAMMATORY RESPONSE; MUSCLE REPERFUSION INJURY; LOWER-TORSO ISCHEMIA; SKELETAL-MUSCLE; SELECTIN; ISCHEMIA/REPERFUSION; PERMEABILITY; DYSFUNCTION; EXPRESSION AB The McGivney hemorrhoidal ligator ( MHL), a band designed to cause tissue necrosis, is the preferred experimental tool to create hindlimb ischemia-reperfusion ( I/R) injury in rodents. This report defines and compares the ex vivo band tension exerted by MHL and orthodontic rubber bands ( ORBs) along with select in vivo characteristics of I/R. As to method, ex vivo band tension was measured over relevant diameters using a tensiometer. In vivo assessment of murine limb perfusion during ischemia with ORB and MHL was compared using laser Doppler imaging and measurement of wet weight-to-dry weight ratio. Neuromuscular scoring and histological extent of muscle fiber injury after I/R with MHL and ORB were also compared. A dose-response curve, between the duration of ORB-induced I/R with both mitochondrial activity ( methyl-thiazol-tetrazolium) or tail perfusion [ laser Doppler imaging ( LDI)], was generated. As a results, ex vivo measurements showed that ORB exerted significantly less force than the MHL. Despite less tension in ORB, in vivo testing of the ORB confirmed complete ischemia by both LDI and wet weight-to-dry weight ratio. After I/R, caused by ORB, there was significantly less neuromuscular dysfunction. Histological assessment confirmed similar degrees of muscle fiber injury after I/R with either the MHL or ORB. Increasing durations of ischemia created by the ORB followed by reperfusion significantly decreased mitochondrial activity and tail perfusion after 24 h of ischemia. In conclusions, ORB produced similar levels of tissue ischemia in murine models of limb I/R with fewer levels of nonspecific injury. ORB may be the preferred model for selected studies of limb I/R. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02115 USA. RP Watkins, MT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc & Endovasc Surg, 15 Parkman St,Ste 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 32 TC 26 Z9 28 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 2007 VL 292 IS 2 BP H830 EP H837 DI 10.1152/ajpheart.00581.2006 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 134FK UT WOS:000244068700014 PM 17012358 ER PT J AU Deem, S Min, JH Moulding, JD Eveland, R Swenson, ER AF Deem, Steven Min, Jin-Hye Moulding, Jennifer D. Eveland, Randy Swenson, Erik R. TI Red blood cells prevent inhibition of hypoxic pulmonary vasoconstriction by nitrite in isolated, perfused rat lungs SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE erythrocytes; hemoglobin; pulmonary circulation ID S-NITROSOHEMOGLOBIN; CIRCULATING NITRITE; BIOLOGICAL-SYSTEMS; FLOW REGULATION; OXIDE FORMATION; IN-VIVO; HEMOGLOBIN; DEOXYHEMOGLOBIN; ERYTHROCYTES; REDUCTASE AB Nitrite reduction to nitric oxide (NO) may be potentiated by a nitrite reductase activity of deoxyHb and contribute to systemic hypoxic vasodilation. The effect of nitrite on the pulmonary circulation has not been well characterized. We explored the effect of nitrite on hypoxic pulmonary vasoconstriction (HPV) and the role of the red blood cell (RBC) in nitrite reduction and nitrite-mediated vasodilation. As to method, isolated rat lungs were perfused with buffer, or buffer with RBCs, and subjected to repeated hypoxic challenges, with or without nitrite. As a result, in buffer-perfused lungs, HPV was reduced at nitrite concentrations of 7 mu M and above. Nitrite inhibition of HPV was prevented by excess free Hb and RBCs, suggesting that vasodilation was mediated by free NO. Nitrite-inhibition of HPV was not potentiated by mild acidosis (pH = 7.2) or xanthine oxidase activity. RBCs at 15% but not 1% hematocrit prevented inhibition of HPV by nitrite ( maximum nitrite concentration of similar to 35 mu M) independent of perfusate PO2. Degradation of nitrite was accelerated by hypoxia in the presence of RBCs but not during buffer perfusion. In conclusion, low micromolar concentrations of nitrite inhibit HPV in buffer-perfused lungs and when RBC concentration is subphysiological. This effect is lost when RBC concentration approaches physiological levels, despite enhanced nitrite degradation in the presence of RBCs. These data suggest that, although deoxyHb may generate NO from nitrite, insufficient NO escapes the RBC to cause vasodilation in the pulmonary circulation under the dynamic conditions of blood flow through the lungs and that RBCs are net scavengers of NO. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Kwandong, Coll Med, Dept Anesthesiol, Kangnung, South Korea. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. RP Deem, S (reprint author), Harborview Med Ctr, Dept Anesthesiol, Seattle, WA 98104 USA. EM sdeem@u.washington.edu FU NHLBI NIH HHS [1-K02-HL-077614-01A1, HL-66542] NR 42 TC 22 Z9 22 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 2007 VL 292 IS 2 BP H963 EP H970 DI 10.1152/ajpheart.00812.2006 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 134FK UT WOS:000244068700029 PM 17012349 ER PT J AU Sakata, S Lebeche, D Sakata, Y Sakata, N Chemaly, ER Liang, LF Nakajima-Takenaka, C Tsuji, T Konishi, N del Monte, F Hajjar, RJ Takaki, M AF Sakata, Susumu Lebeche, Djamel Sakata, Yuri Sakata, Naoya Chemaly, Elie R. Liang, Lifan Nakajima-Takenaka, Chikako Tsuji, Tsuyoshi Konishi, Noboru del Monte, Federica Hajjar, Roger J. Takaki, Miyako TI Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a Type 2 diabetic rat model SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE gene therapy; heart failure; diabetes mellitus; cardiomyocyte hypertrophy ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; NITRIC-OXIDE; CARDIAC DYSFUNCTION; HEART-FAILURE; INHIBITION; RELAXATION AB The Otsuka Long-Evans Tokushima fatty rat is an animal model of Type 2 diabetes mellitus (DM), which is characterized by diastolic dysfunction associated with decreased sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). The aim of this study was to examine whether gene transfer of SERCA2a can influence coronary blood flow and cardiomyocyte diameter in this model. DM rats were injected with adenovirus carrying SERCA2a (DM + SERCA) or beta-galactosidase gene (DM + beta Gal). Coronary blood flow was measured in cross-circulated excised hearts 3 days after infection. Although in all groups coronary blood flow remained unchanged even if left ventricular (LV) volume or intracoronary Ca2+ infusion was increased, the DM + SERCA group showed a sustained increase in coronary blood flow compared with the other groups. This result suggests that the sustained high coronary blood flow is a specific response in SERCA2a-overexpressed hearts. Although the LV weight-to-body weight ratio (LV/BW) and cardiomyocyte diameter were higher in the DM and DM + beta Gal groups than in the non-DM group, in the DM + SERCA group, these measurements were restored to non-DM size. The percentages of collagen area in the three DM groups was significantly higher than results shown in non-DM rats, and there were no significant differences in collagen area percentage among the three DM groups. These results suggest that a lowered LV/BW by SERCA2a overexpression is due mainly to reduced size of cardiomyocytes without any changes in collagen area percentage. In conclusion, in DM failing hearts, SERCA2a gene transfer can increase coronary blood flow and reduce cardiomyocyte size without reduction in collagen production. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Nara Med Univ, Sch Med, Dept Physiol 2, Kashihara, Nara 634, Japan. Nara Med Univ, Sch Med, Dept Thorac & Cardiovasc Surg, Kashihara, Nara 634, Japan. Nara Med Univ, Sch Med, Dept Pathol, Kashihara, Nara 634, Japan. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY-4, Charlestown, MA 02129 USA. EM rhajjar@partners.org FU NHLBI NIH HHS [HL-071763, K01 HL-076659, HL-080498, HL-057263, K08 HL-069842, R01 HL-078691, HL-083156] NR 17 TC 37 Z9 39 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 2007 VL 292 IS 2 BP H1204 EP H1207 DI 10.1152/ajpheart.00892.2006 PG 4 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 134FK UT WOS:000244068700058 PM 17012346 ER PT J AU Jonker, SS Faber, JJ Anderson, DF Thornburg, KL Louey, S Giraud, GD AF Jonker, Sonnet S. Faber, J. Job Anderson, Debra F. Thornburg, Kent L. Louey, Samantha Giraud, George D. TI Sequential growth of fetal sheep cardiac myocytes in response to simultaneous arterial and venous hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE hypertrophy; hyperplasia; terminal differentiation; cardiomyocyte ID INTRAVASCULAR INFUSIONS; BLOOD-FLOW; STEM-CELLS; HYPERTROPHY; PLASMA; REGENERATION; HYPERPLASIA; MATURATION; CORTISOL; LAMB AB Sequential growth of fetal sheep cardiac myocytes in response to simultaneous arterial and venous hypertension. Am J Physiol Regul Integr Comp Physiol 292: R913-R919, 2007. First published October 5, 2006; doi: 10.1152/ajpregu. 00484.2006.-While the fetal heart grows by myocyte enlargement and proliferation, myocytes lose their capacity for proliferation in the perinatal period after terminal differentiation. The relationship between myocyte enlargement, proliferation, and terminal differentiation has not been studied under conditions of combined arterial and venous hypertension, as occurs in some clinical conditions. We hypothesize that fetal arterial and venous hypertension initially leads to cardiomyocyte proliferation, followed by myocyte enlargement. Two groups of fetal sheep received intravascular plasma infusions for 4 or 8 days (from 130 days gestation) to increase vascular pressures. Fetal hearts were arrested in diastole and dissociated. Myocyte size, terminal differentiation (%binucleation), and cell cycle activity (Ki-67[+] cells as a % of mononucleated myocytes) were measured. We found that chronic plasma infusion greatly increased venous and arterial pressures. Heart (but not body) weights were similar to 30% greater in hypertensive fetuses than controls. The incidence of cell cycle activity doubled in hypertensive fetuses compared with controls. After 4 days of hypertension, myocytes were (similar to 11%) longer, but only after 8 days were they wider (similar to 12%). After 8 days, %binucleation was similar to 50% greater in hypertensive fetuses. We observed two phases of cardiomyocyte growth and maturation in response to fetal arterial and venous hypertension. In the early phase, the incidence of cell cycle activity increased and myocytes elongated. In the later phase, the incidence of cell cycle activity remained elevated, % binucleation increased, and cross sections were greater. This study highlights unique fetal adaptations of the myocardium and the importance of experimental duration when interpreting fetal cardiac growth data. C1 Oregon Hlth Sci Univ, Sch Med Cardiovasc Med, Heart Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Med Cardiovasc Med, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Jonker, SS (reprint author), Univ Iowa, 285 Newton Rd,1270 CBRB, Iowa City, IA 52242 USA. EM sonnet-jonker@uiowa.edu OI Jonker, Sonnet/0000-0002-1097-2562 FU NICHD NIH HHS [HD-034430] NR 24 TC 30 Z9 30 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD FEB PY 2007 VL 292 IS 2 BP R913 EP R919 DI 10.1152/ajpregu.00484.2006 PG 7 WC Physiology SC Physiology GA 132KU UT WOS:000243942500034 PM 17023664 ER PT J AU Janech, MG Raymond, JR Arthur, JM AF Janech, Michael G. Raymond, John R. Arthur, John M. TI Proteomics in renal research SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE two-dimensional gel electrophoresis; DIGE; mass spectrometry; nephron; glomerulus; renal tubule ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; LASER CAPTURE MICRODISSECTION; MEDULLARY COLLECTING DUCT; TANDEM MASS-SPECTROMETRY; KIDNEY PROTEIN EXPRESSION; THICK ASCENDING LIMB; CELL CARCINOMA; CAPILLARY-ELECTROPHORESIS; RAT-KIDNEY; TARGETED PROTEOMICS AB Proteomic technologies are used with increasing frequency in the renal community. In this review, we highlight the use in renal research of a number of available techniques including two-dimensional gel electrophoresis, liquid chromatography/mass spectrometry, surface-enhanced laser desorption/ionization, capillary electrophoresis/mass spectrometry, and antibody and tissue arrays. These techniques have been used to identify proteins or changes in proteins specific to regions of the kidney or associated with renal diseases or toxicity. They have also been used to examine protein expression changes and posttranslational modifications of proteins during signaling. A number of studies have used proteomic methodologies to look for diagnostic biomarkers in body fluids. The rapid rate of development of the technologies along with the combination of classic physiological and biochemical techniques with proteomics will enable new discoveries. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. EM arthurj@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU NHLBI NIH HHS [N01-HV-28181] NR 140 TC 32 Z9 37 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2007 VL 292 IS 2 BP F501 EP F512 DI 10.1152/ajprenal.00298.2006 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 133FC UT WOS:000243997200001 PM 17107941 ER PT J AU Lee, MJ Feliers, D Mariappan, MM Sataranatarajan, K Mahimainathan, L Musi, N Foretz, M Viollet, B Weinberg, JM Choudhury, GG Kasinath, BS AF Lee, Myung-Ja Feliers, Denis Mariappan, Meenalakshmi M. Sataranatarajan, Kavithalakshmi Mahimainathan, Lenin Musi, Nicolas Foretz, Marc Viollet, Benoit Weinberg, Joel M. Choudhury, Goutam Ghosh Kasinath, Balakuntalam S. TI A role for AMP-activated protein kinase in diabetes-induced renal hypertrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE protein synthesis; mRNA translation ID GLOMERULAR EPITHELIAL-CELLS; GROWTH-FACTOR-BETA; ANGIOTENSIN-II; GENE-EXPRESSION; ELONGATION-FACTOR-2 KINASE; SIGNALING PATHWAYS; PROXIMAL TUBULES; SKELETAL-MUSCLE; GAMMA-SUBUNITS; POTENTIAL ROLE AB We tested the hypothesis that AMP-activated protein kinase ( AMPK), an energy sensor, regulates diabetes-induced renal hypertrophy. In kidney glomerular epithelial cells, high glucose ( 30 mM), but not equimolar mannitol, stimulated de novo protein synthesis and induced hypertrophy in association with increased phosphorylation of eukaryotic initiation factor 4E binding protein 1 and decreased phosphorylation of eukaryotic elongation factor 2, regulatory events in mRNA translation. These high-glucose-induced changes in protein synthesis were phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin ( mTOR) dependent and transforming growth factor-beta independent. High glucose reduced AMPK alpha-subunit theronine (Thr) 172 phosphorylation, which required Akt activation. Changes in AMP and ATP content could not fully account for high-glucose-induced reductions in AMPK phosphorylation. Metformin and 5-aminoimidazole-4-carboxamide-1 beta-riboside ( AICAR) increased AMPK phosphorylation, inhibited high-glucose stimulation of protein synthesis, and prevented high-glucose-induced changes in phosphorylation of 4E binding protein 1 and eukaryotic elongation factor 2. Expression of kinase-inactive AMPK further increased high-glucose-induced protein synthesis. Renal hypertrophy in rats with Type 1 diabetes was associated with reduction in AMPK phosphorylation and increased mTOR activity. In diabetic rats, metformin and AICAR increased renal AMPK phosphorylation, reversed mTOR activation, and inhibited renal hypertrophy, without affecting hyperglycemia. AMPK is a newly identified regulator of renal hypertrophy in diabetes. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Obrien Kidney Res Ctr,Div Nephrol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Obrien Kidney Res Ctr,Div Diabet, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. Univ Paris 05, INSERM, Inst Cochin, Dept Endocrinol Metab & Canc,U567, Paris, France. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Obrien Kidney Res Ctr,Div Nephrol, 7703 Floyd Curl Dr,Mail Code 7882, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu OI /0000-0001-5077-3552 FU NIDDK NIH HHS [DK-55815, R01 DK-50190] NR 63 TC 128 Z9 142 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB PY 2007 VL 292 IS 2 BP F617 EP F627 DI 10.1152/ajprenal.00278.2006 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 133FC UT WOS:000243997200014 PM 17018841 ER PT J AU Weiss, AP AF Weiss, Anthony P. TI Measuring the impact of medical research: Moving from outputs to outcomes SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID JOURNAL READING HABITS; HOPKINS-UNIVERSITY SCHOOL; CLINICAL-TRIALS; PUBLIC TRUST; HEALTH-CARE; QUESTIONNAIRE SURVEY; BIOMEDICAL-RESEARCH; ACADEMIC PROMOTION; ANXIETY DISORDERS; MENTAL-ILLNESS AB Billions of dollars are spent every year to support medical research, with a substantial percentage coming from charitable foundations. To justify these expenditures, some measure of the return on investment would be useful, particularly one aligned with the intended ultimate outcome of this scientific effort: the amelioration of disease. The current mode of reporting on the success of medical research is output based, with an emphasis on measurable productivity. This approach falls short in many respects and may be contributing to the well-described efficacy-effectiveness gap in clinical care. The author argues for an outcomes-based approach and describes the steps involved, using an adaptation of the logic model. A shift in focus to the outcomes of our work would provide our funders with clearer mission-central return-on-investment feedback, would make explicit the benefits of science to an increasingly skeptical public, and would serve as a compass to guide the scientific community in playing a more prominent role in reducing the efficacy-effectiveness gap. While acknowledging the enormous complexity involved with the implementation of this approach on a large scale, the author hopes that this essay will encourage some initial steps toward this aim and stimulate further discussion of this concept. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Weiss, AP (reprint author), Dept Psychiat, MGH E,Bldg 149,Rm 2606,13th St, Charlestown, MA 02129 USA. EM aweiss@partners.org NR 100 TC 43 Z9 44 U1 1 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2007 VL 164 IS 2 BP 206 EP 214 DI 10.1176/appi.ajp.164.2.206 PG 9 WC Psychiatry SC Psychiatry GA 131XM UT WOS:000243905700008 PM 17267781 ER PT J AU Viguera, AC Newport, DJ Ritchie, J Stowe, Z Whitfield, T Mogielnicki, J Baldessarini, RJ Zurick, A Cohen, LS AF Viguera, Adele C. Newport, D. Jeffrey Ritchie, James Stowe, Zachary Whitfield, Theodore Mogielnicki, Juliana Baldessarini, Ross J. Zurick, Amanda Cohen, Lee S. TI Lithium in breast milk and nursing infants: Clinical implications SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 158th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 2005 CL Atlanta, GA SP Amer Psychiat Assoc ID MANAGEMENT; PREGNANCY AB Objective: Current practice guidelines discourage use of lithium during breast-feeding, despite limited data. This study aimed to quantify lithium exposure in nursing infants. Method: In 10 mother-infant pairs, the authors obtained assays of lithium in maternal serum, breast milk, and infant serum and indices of infant renal and thyroid function. Results: Maternal serum, breast milk, and infant serum daily trough concentrations of lithium averaged 0.76, 0.35, and 0.16 meq/liter, respectively, each lithium level lower than the preceding level by approximately one-half. No serious adverse events were observed, and elevations of thyroid-stimulating hormone, blood urea nitrogen, and creatinine were few, minor, and transient. Conclusions: Serum lithium levels in nursing infants were low and well tolerated. No significant adverse clinical or behavioral effects in the infants were noted. These findings encourage reassessment of recommendations against lithium during breastfeeding and underscore the importance of close clinical monitoring of nursing infants. C1 Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Emory Univ, Emory Womens Mental Hlth Program, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Psychiat Res Labs, Bipolar & Psychot Disorders Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Res Labs, Psychopharmacol Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Boston, MA 02114 USA. RP Viguera, AC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Simches Res Bldg,2nd Fl,Suite 220,185 Cambridge S, Boston, MA 02114 USA. EM aviguera@partners.org OI Newport, D. Jeffrey/0000-0003-1695-9710 FU NIMH NIH HHS [P50-MH-68036, MH-01609] NR 6 TC 51 Z9 53 U1 2 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2007 VL 164 IS 2 BP 342 EP 345 DI 10.1176/appi.ajp.164.2.342 PG 4 WC Psychiatry SC Psychiatry GA 131XM UT WOS:000243905700028 PM 17267800 ER PT J AU McClintock, DE Ware, LB Eisner, MD Wickersham, N Thompson, BT Matthay, MA AF McClintock, Dana E. Ware, Lorraine B. Eisner, Mark D. Wickersham, Nancy Thompson, B. Taylor Matthay, Michael A. CA Natl Heart Lung Blood Inst ARDS Ne TI Higher urine nitric oxide is associated with improved outcomes in patients with acute lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; nitrogen oxide species; pulmonary endothelium; tidal volume; pulmonary edema ID RESPIRATORY-DISTRESS-SYNDROME; GLOMERULAR-FILTRATION-RATE; TIDAL VOLUME VENTILATION; INTENSIVE-CARE-UNIT; SEPTIC SHOCK; FLUID CLEARANCE; SYNTHASE; DISEASE; NITRATE; NITROTYROSINE AB Rationale: Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI). Objectives: We tested two hypotheses in patients with ALI: (1) higher levels of urine NO would be associated with worse clinical outcomes, and (2) ventilation with lower V-T would reduce urine NO as a result of less stretch injury. Methods: Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg VT ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr). Results: Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 cl), and more organ-failure-free days (mean increase, 2.3 d) on multivariate analysis (p < 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg VT group (p = 0.04). Conclusions: Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg VT strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI. C1 Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Environm & Occupat Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. RP McClintock, DE (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM dana.mcclintock@ucsf.edu OI Wiedemann, Herbert/0000-0002-4587-4401; Shanholtz, Carl/0000-0003-3938-178X FU NHLBI NIH HHS [HL51856, HL74005, HL81332, HL70521] NR 46 TC 42 Z9 43 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 1 PY 2007 VL 175 IS 3 BP 256 EP 262 DI 10.1164/rccm.200607.947OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 132NK UT WOS:000243949300010 PM 17082495 ER PT J AU Abbara, S Pena, AJ Maurovich-Horvat, P Butler, J Sosnovik, DE Lembcke, A Cury, RC Hoffmann, U Ferencik, M Brady, TJ AF Abbara, Suhny Pena, Antonio J. Maurovich-Horvat, Paul Butler, Javed Sosnovik, David E. Lembcke, Alexander Cury, Ricardo C. Hoffmann, Udo Ferencik, Maros Brady, Thomas J. TI Feasibility and optimization of aortic valve planimetry with MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE aorta; aortic valve; cardiac imaging; coronary artery disease; heart disease; MDCT; planimetry ID COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; STENOSIS; ECHOCARDIOGRAPHY; DISEASE; AREA AB OBJECTIVE. The aortic valve can be assessed using MDCT; however, measurements of the aortic opening area vary with the cardiac cycle. In this study, we sought to assess the optimal timing for measuring the area of the aortic opening with MDCT. MATERIALS AND METHODS. Retrospectively gated MDCT was performed in 57 patients with the following parameters: gantry rotation time, 420 milliseconds; tube voltage, 120 kV; tube current, 550 mAs with tube current modulation; and slice collimation, 16 x 0.75 mm. From 72 to 100 mL of contrast agent ( 320 g/mL(3)) was injected IV at 4 - 5 mL/s. High-resolution data sets were obtained for planimetry at phase starts of 0, 50, 100, 150, and 200 milliseconds after the R wave peak and were assessed for aortic opening area and the presence of artifacts. RESULTS. In 41% of patients, the cardiac phase with the largest aortic opening area was at 50 milliseconds after the R wave peak. The area of the aortic opening measured at 0 milliseconds after the R peak was 2.7 +/- 0.8 cm(2) ( mean +/- SD); at 50 milliseconds, 2.9 +/- 0.2 cm(2); at 100 milliseconds, 2.9 +/- 0.7 cm(2); at 150 milliseconds, 2.8 +/- 0.7 cm(2); and at 200 milliseconds, 2.4 +/- 0.8 cm(2). The image quality was best at 50 milliseconds after the R peak in 42% of patients, 100 milliseconds in 29%, 150 milliseconds in 20%, 0 milliseconds in 7%, and 200 milliseconds in 2%. The aortic valve appeared closed in three patients at 0 milliseconds and in four patients at 200 milliseconds. Fewer artifacts were present in the midsystolic phases (i.e., 50 - 150 milliseconds) ("double-leaflet" artifact, 5 - 13%; "incomplete contour" artifact, 20 - 26%) than in the early ( 0 milliseconds) and late ( 200 milliseconds) systolic phases (double-leaflet artifact, 38% and 43% of patients; incomplete contour artifact, 76% and 73%, respectively). CONCLUSION. Aortic valve planimetry is best performed at phase starts of 50 - 100 milliseconds after the R peak because the area of the aortic opening is widest and image quality is best at that phase. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Abbara, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Cambridge St,Ste 400, Boston, MA 02114 USA. EM sabbara@partners.org FU NHLBI NIH HHS [1 T32 HL076136-02] NR 11 TC 25 Z9 29 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2007 VL 188 IS 2 BP 356 EP 360 DI 10.2214/AJR.06.0232 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 156QB UT WOS:000245663000013 PM 17242242 ER PT J AU Uppot, RN Sahani, DV Hahn, PF Gervais, D Mueller, PR AF Uppot, Raul N. Sahani, Dushyant V. Hahn, Peter F. Gervais, Debra Mueller, Peter R. TI Impact of obesity on medical imaging and image-guided intervention SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abdominal imaging; body imaging; interventional radiology; obesity; radiology practice; technologists AB OBJECTIVE. The purpose of this article is to discuss the impact of obesity on medical imaging and provide some solutions that are currently available to tackle the challenges of imaging obese patients. CONCLUSION. Increasingly, radiologists are asked to image morbidly obese patients. The challenges facing radiology departments include difficulties in transporting patients to the department, inability to accommodate large patients on currently designed imaging equipment, and difficulties in acquiring desired image quality. C1 Harvard Univ, Sch Med, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Uppot, RN (reprint author), Harvard Univ, Sch Med, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM ruppot@partners.org NR 6 TC 62 Z9 63 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2007 VL 188 IS 2 BP 433 EP 440 DI 10.2214/AJR.06.0409 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 156QB UT WOS:000245663000024 PM 17242253 ER PT J AU Li, JH Udayasankar, UK Toth, TL Seamans, J Small, WC Kalra, MK AF Li, Jianhai Udayasankar, Unni K. Toth, Thomas L. Seamans, John Small, William C. Kalra, Mannudeep K. TI Automatic patient centering for MDCT: Effect on radiation dose SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; positioning; radiation dose; technology ID COMPUTED-TOMOGRAPHY; CT; OPTIMIZATION; MODULATION; STRATEGIES; REDUCTION AB OBJECTIVE. The purpose of this study was to determine with phantom and patient imaging the effect of an automatic patient-centering technique on the radiation dose associated with MDCT. SUBJECTS AND METHODS. A 32-cm CT dose index (CTDI) phantom was scanned with 64-MDCT in three positions: gantry isocenter and 30 and 60 mm below the isocenter of the scanner gantry. In each position, surface, peripheral, and volume CTDIs were estimated with a standard 10-cm pencil ionization chamber. The institutional review board approved the study with 63 patients (36 men, 27 women; mean age, 51 years; age range, 22-83 years) undergoing chest (n = 18) or abdominal (n = 45) CT using the z-axis automatic exposure control technique. Each patient was positioned according to the region being scanned and then was centered in the gantry. Before scanning of a patient, automatic centering software was used to estimate patient off-centering and percentage of dose reduction with optimum recentering. Data were analyzed with linear correlation and the Student's t test. RESULTS. Peripheral and surface CTDIs increased approximately 12-18% with 30-mm off-center distance and 41-49% with 60-mm off-center distance. Approximately 95% (60/63) of patients were not positioned accurately in the gantry isocenter. The mean radiation dose saving with automatic centering of all patients was 13.0% +/- 0.9% (range, 2.6-29.9%). There was strong correlation between off-center distance and percentage of surface CTDI reduction with recentering of patients in the gantry isocenter (r(2) = 0.85, p < 0.0001). CONCLUSION. Surfaces doses can be reduced if radiologic technologists can better center patients within the CT gantry. Automatic centering technique can help in optimum patient centering and result in as much as 30% reduction in surface dose. C1 Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. GE Healthcare, Waukesha, WI 53188 USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM mkalra@partners.org NR 8 TC 68 Z9 68 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2007 VL 188 IS 2 BP 547 EP 552 DI 10.2214/AJR.06.0370 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 156QB UT WOS:000245663000038 PM 17242267 ER PT J AU Dodd, JD Ferencik, M Liberthson, RR Cury, RC Hoffmann, U Brady, TJ Abbara, S AF Dodd, Jonathan D. Ferencik, Maros Liberthson, Richard R. Cury, Ricardo C. Hoffmann, Udo Brady, Thomas J. Abbara, Suhny TI Congenital anomalies of coronary artery origin in adults: 64-MDCT appearance SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE angiography; cardiac imaging; coronary angiography/methods; CT coronary angiography; tomography; X-ray computed ID PULMONARY TRUNK; HEART-DISEASE; SUDDEN-DEATH; AORTA AB OBJECTIVE. The purpose of this pictorial essay is to review the 64-MDCT appearance of congenital anomalies of the origins of the coronary arteries in adults. CONCLUSION. Increasing use of MDCT for cardiac imaging of adults requires familiarity with the cross-sectional appearance of congenital coronary artery anomalies visualized with noninvasive imaging techniques. Many of these anomalies are benign, but a small number are associated with myocardial ischemia and sudden death. Increasing use of MDCT in cardiac imaging may yield diagnostic information not obtained with coronary angiography. Axial, multiplanar, and 3D volume-rendered reconstructions should aid in detection and improve interpretation of such anomalies. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Dodd, JD (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM jddodd@partners.org NR 17 TC 22 Z9 22 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2007 VL 188 IS 2 BP W138 EP W146 DI 10.2214/AJR.05.2098 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 156QB UT WOS:000245663000051 PM 17242219 ER PT J AU Van de Velde, SK DeFrate, LE Gill, TJ Moses, JM Papannagari, R Li, GA AF Van de Velde, Samuel K. DeFrate, Louis E. Gill, Thomas J. Moses, Jeremy M. Papannagari, Ramprasad Li, Guoan TI The effect of anterior cruciate ligament deficiency on the in vivo elongation of the medial and lateral collateral ligaments SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anterior cruciate ligament (ACL); medial collateral ligament (MCL); lateral collateral ligament (LCL); ACL injury; in vivo; biomechanics; knee stability ID ACUTE TRAUMATIC HEMARTHROSIS; KNEE FLEXION; TIBIOFEMORAL KINEMATICS; GOAT MODEL; CONTACT; ACL; INJURY; MOTION; RECONSTRUCTION; TRANSECTION AB Background: Although anterior cruciate ligament deficiency has been shown to lead to joint degeneration, few quantitative data have been reported on its effect on soft tissue structures surrounding the knee joint. Hypothesis: Anterior cruciate ligament deficiency will alter the deformation of both collateral ligaments during in vivo weight-bearing knee function from 00 to 90 degrees. Study Design: Controlled laboratory study. Methods: Six patients who had acute anterior cruciate ligament injury in 1 knee with the contralateral side intact participated in this study. Using magnetic resonance and dual orthogonal fluoroscopic imaging techniques, we measured the length of the fiber bundles of the superficial medial collateral ligament, deep medial collateral ligament, and lateral collateral ligament of the 6 patients; the healthy contralateral knee of each patient served as a control. Results: Anterior cruciate ligament injury caused a significant elongation of the fiber bundles of the superficial and deep medial collateral ligament at every flexion angle. In contrast, the lateral collateral ligament fiber bundles shortened after anterior cruciate ligament injury. Conclusion: The altered deformations of the collateral ligaments associated with the changes in tibiofemoral joint kinematics after anterior cruciate ligament injury demonstrate that deficiency of 1 of the knee joint structures upsets the in vivo knee homeostasis. Clinical Relevance: Restoring normal knee kinematics after anterior cruciate ligament reconstruction is critical to restore the normal function of the collateral ligaments. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. Katholieke Univ Leuven, Univ Hosp Pellenberg, Dept Orthopaed Surg, Pellenberg, Belgium. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, GRJ 1215,55 Fruit St, Boston, MA 02114 USA. EM gli1@partners.org NR 42 TC 14 Z9 15 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD FEB PY 2007 VL 35 IS 2 BP 294 EP 300 DI 10.1177/0363546506294079 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 132ZD UT WOS:000243980500016 PM 17092925 ER PT J AU Itani, KMF Wilson, SE Awad, SS Jensen, EH Finn, TS Abramson, MA AF Itani, Kamal M. F. Wilson, Samuel E. Awad, Samir S. Jensen, Erin H. Finn, Tyler S. Abramson, Murray A. TI Polyethylene glycol versus sodium phosphate mechanical bowel preparation in elective colorectal surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE mechanical bowel preparation; polyethylene glycol; sodium phosphate; surgical site infection ID RANDOMIZED-TRIAL; COLON AB Background: The type of mechanical bowel preparation (MBP) used before elective colorectal surgery remains controversial. Methods: This post hoc analysis of a prospective randomized controlled antibiotic prophylaxis trial (ertapenem vs. cefotetan) evaluated the effect of polyethylene glycol (PEG) and sodium phosphate (SP) MBPs on the rates of postoperative surgical site infections (SSI). Results: Good to excellent MBPs were observed in 281 of 303 (93%) evaluable patients for the PEG and 336 of 367 (92%) for the SP types. A higher rate of SSI was observed in the PEG (34%) than SP (24%) group (difference, 10%; 95% confidence interval, 3.4-17.2). The MBP type was a significant risk factor for SSI, with SP favored over PEG (odds ratio,.6; 95% confidence interval,.43-85) in univariate analysis; multivariate analysis favored SP, but was not significant (odds ratio,.69; 95% confidence interval,.46-1.02). SSI was lowest with SP and ertapenem (19%) and highest with PEG and cefotetan (44%). Conclusions: SP, coupled with ertapenem antibiotic prophylaxis, may improve outcomes and reduce SSIs in patients undergoing elective colorectal surgery when compared with PEG coupled with cefotetan antibiotic prophylaxis. (c) 2007 Excerpta Medica Inc. All rights reserved. C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Univ Calif Irvine, Sch Med, Orange, CA USA. Michael E DeBakey VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Merck & Co Inc, West Point, PA USA. RP Itani, KMF (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy 112, W Roxbury, MA 02132 USA. EM Kitani@med.va.gov NR 18 TC 20 Z9 20 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD FEB PY 2007 VL 193 IS 2 BP 190 EP 194 DI 10.1016/j.amjsurg.2006.08.024 PG 5 WC Surgery SC Surgery GA 132DV UT WOS:000243923400008 PM 17236845 ER PT J AU Kindelberger, DW Lee, Y Miron, A Hirsch, MS Feltmate, C Medeiros, F Callahan, MJ Garner, EO Gordon, RW Birch, C Berkowitz, RS Muto, MG Crum, CP AF Kindelberger, David W. Lee, Yonghee Miron, Alexander Hirsch, Michelle S. Feltmate, Colleen Medeiros, Fabiola Callahan, Michael J. Garner, Elizabeth O. Gordon, Robert W. Birch, Chandler Berkowitz, Ross S. Muto, Michael G. Crum, Christopher P. TI Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: Evidence for a causal relationship SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE intraepithelial carcinoma; serous carcinoma; BRCA; fallopian tube neoplasms; ovarian neoplasms ID PROPHYLACTIC OOPHORECTOMY SPECIMENS; HIGH-GRADE CARCINOMAS; FALLOPIAN-TUBE; OVARIAN-CANCER; BORDERLINE TUMORS; MUTATION STATUS; BRCA1; PATHOGENESIS; DIAGNOSIS; PATTERNS AB Proposed origins of pelvic serous carcinoma include the ovary, fallopian tube.. and peritoneum. Prophylactic salpingo-oophorectomies in BRCA+ women have recently identified the fimbria as a site of origin for early serous carcinoma (tubal intraepithelial carcinoma or TIC). We explored the relationship of TIC to pelvic serous carcinomas in consecutive cases with complete adnexal exam (SEE-FIM protocol). Cases positive (group A) or negative (group B) for endosalpinx (including fimbria) involvement, were subclassified as tubal, ovarian, or primary peritoneal in origin. Coexisting TIC was recorded in group A when present and p53 mutation status was determined in 5 cases. Of 55 evaluable cases, 41 (75%) were in group A; including tubal (n = 5), peritoneal (n = 6), and ovarian (n = 30) carcinomas. Foci of TIC were identified in 5 of 5, 4 of 6, and 20 of 30, respectively. Ninety-three percent of TICs involved the fimbriae. Five of 5 TICs and concurrent ovarian carcinomas contained identical p53 mutations. Thirteen of 14 cases in group B were classified as primary ovarian carcinomas, 10 with features supporting an origin in the ovary. Overall. 71% and 48% of "ovarian" serous carcinomas had endosalpinx involvement or TIC. TIC coexists with all forms of pelvic serous carcinoma and is a plausible origin for many of these tumors. Further studies are needed to elucidate the etiologic significance of TIC in pelvic serous carcinoma, reevaluate the criteria for tubal, peritoneal, and ovarian serous carcinoma, and define the role of the distal tube in pelvic serous carcinogenesis. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. EM ccrum@partners.org FU NCI NIH HHS [P50 CA10500] NR 33 TC 434 Z9 471 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2007 VL 31 IS 2 BP 161 EP 169 DI 10.1097/01.pas.0000213335.40358.47 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 130XD UT WOS:000243831400001 PM 17255760 ER PT J AU Ferry, JA Fung, CY Zukerberg, L Lucarelli, MJ Hasserjian, RP Preffer, FI Harris, NL AF Ferry, Judith A. Fung, Claire Y. Zukerberg, Lawrence Lucarelli, Mark J. Hasserjian, Robert P. Preffer, Frederic I. Harris, Nancy L. TI Lymphoma of the ocular adnexa: A study of 353 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ocular adnexa; orbit; lacrimal gland; conjuctiva; lymphoma; marginal zone lymphoma ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; BONE-MARROW INVOLVEMENT; MALT LYMPHOMA; MALIGNANT-LYMPHOMA; MARGINAL ZONE; LYMPHOBLASTIC LYMPHOMA; TISSUE LYMPHOMA; BORRELIA-BURGDORFERI; CHLAMYDIA-PSITTACI AB We studied the cases of 353 patients with lymphoma involving the ocular adnexa diagnosed at the Massachusetts General Hospital between 1974 and 2005. The patients included 153 males and 200 females, aged 7 to 95 years, with a mean age of 64 years. In 277 cases, there was no known history of lymphoma. Seventy-six patients had a history of lymphoma, with the ocular adnexa being involved at relapse or with progression of the previously diagnosed lymphoma. The patients had marginal zone lymphoma (182 cases), follicular lymphoma (80 cases), mantle cell lymphoma (18 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (13 cases), lymphoplasmacytic lymphoma (4 cases), splenic marginal zone lymphoma (2 cases), low-grade B cell, not subclassified (19 cases), precursor B lymphoblastic lymphoma (3 cases), diffuse large B-cell lymphoma (26 cases), and I case each of high-grade B-cell lymphoma, not subclassified, peripheral T-cell lymphoma, unspecified type, extranodal NK/T-cell lymphoma, nasal type, and Hodgkin lymphoma, nodular sclerosis type. Almost all marginal zone lymphoma patients (168 of 182, 92%) had primary ocular adnexal lymphoma. Fourteen marginal zone lymphoma patients (8%) had a prior history of lymphoma, usually arising in another extranodal site. Twenty-five of 80 (31%) follicular lymphoma patients had a prior history of lymphoma, usually arising in lymph nodes. Patients with mantle cell lymphoma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and splenic marginal zone lymphoma almost always had a prior history of lymphoma or were known to have widespread disease at the time of diagnosis of ocular adnexal lymphoma. A subset of the diffuse large B-cell lymphomas were associated with large destructive masses involving adjacent structures such as paranasal sinuses, raising the possibility that they may have arisen from one of the adjacent structures and involved the ocular adnexa by direct extension. The relatively high proportion of low-grade lymphoma, not subclassified, highlights the difficulty that may arise in distinguishing different types of low-grade lymphoma, particularly when biopsies are small and artifactually distorted. Ocular adnexal lymphoma is primarily a disease of older adults, with a slight female preponderance. Most lymphomas are low-grade B-cell lymphomas, with marginal zone lymphoma being by far the most common type. Marginal zone lymphoma typically involves the ocular adnexa primarily, whereas other types of low-grade B-cell lymphoma often involve the ocular adnexa secondarily. High-grade B-cell lymphomas only occasionally involve the ocular adnexa, and T-cell lymphoma, NK-cell lymphoma, and Hodgkin lymphoma are only rarely encountered in this site. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Wisconsin, Oculoplast Serv, Madison, WI USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM jferry@partners.org NR 76 TC 146 Z9 163 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2007 VL 31 IS 2 BP 170 EP 184 DI 10.1097/01.pas.0000213350.49767.46 PG 15 WC Pathology; Surgery SC Pathology; Surgery GA 130XD UT WOS:000243831400002 PM 17255761 ER PT J AU Sugiura, M Colby, KA Mihm, MC Zembowicz, A AF Sugiura, Mitsuhiro Colby, Kathiryn A. Mihm, Martin C., Jr. Zembowicz, Artur TI Low-risk and high-risk histologic features in conjunctival primary acquired melanosis with atypia: Clinicopathologic analysis of 29 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE primary acquired melanosis; conjunctival melanocytic proliferation; malignant melanoma ID MALIGNANT-MELANOMA; MELANOCYTIC LESIONS; METASTASIS; RECURRENCE AB The current World Health Organization classification of conjunctival melanocytic proliferations divides them into conjunctival nevi and invasive melanoma but, in contrast to other anatomic sites, does not recognize melanoma in situ. All atypical intraepithelial conjunctival proliferations are included in a heterogeneous category designated as primary acquired melanosis (PAM) with atypia. We performed clinicopathologic analysis of 29 cases of PAM with atypia. On the basis of histologic features and frequency of association with invasive melanoma and metastases. we were able to divide our cases into 2 histologic groups. The low-risk group (13 cases) included lesions composed of small to medium size melanocytes with high nuclear to cytoplasmic ratio and small to medium size hyperchromatic nuclei devoid of nucleoli showing predominantly single cell lentiginous growth pattern. Invasive melanoma occurred in only 2 cases from this group. None of these lesions metastasized. The second, high-risk group (16 cases), showed increased frequency of association with invasive melanoma (15/16 cases, 94%) and metastases (4/16 cases, 25%). These lesions were more heterogeneous architecturally but were all composed of melanocytes showing various degrees of epithelioid features such as abundant cytoplasm, vesicular nuclei, or prominent nucleoli. In 4 cases discrete areas showing high-risk and low-risk features were identified. All 4 lesions were associated with invasion. Our findings offer a practical approach for prognostically useful subclassification of PAM with atypia, which emphasizes cytologic features of intraepithelial conjunctival melanocytic proliferation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Warren 820,55 Fruit St, Boston, MA 02114 USA. EM azembowicz@partners.org NR 21 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2007 VL 31 IS 2 BP 185 EP 192 DI 10.1097/01.pas.0000213339.32734.64 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 130XD UT WOS:000243831400003 PM 17255762 ER PT J AU Colvin, RB AF Colvin, R. B. TI Eye of the needle SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID CHRONIC ALLOGRAFT NEPHROPATHY; SUBCLINICAL REJECTION; PROTOCOL BIOPSIES; RENAL-ALLOGRAFTS; MULTICENTER; C4D C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM colvin@helix.mgh.harvard.edu NR 13 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2007 VL 7 IS 2 BP 267 EP 268 DI 10.1111/j.1600-6143.2006.01609.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 125KF UT WOS:000243440100001 PM 17109722 ER PT J AU Paticoff, J Valovska, A Nedeljkovic, SS Oaklander, AL AF Paticoff, Joshua Valovska, Assia Nedeljkovic, Srdjan S. Oaklander, Anne Louise TI Defining a treatable cause of erythromelalgia: Acute adolescent autoimmune small-fiber axonopathy SO ANESTHESIA AND ANALGESIA LA English DT Article ID GUILLAIN-BARRE-SYNDROME; OF-FUNCTION MUTATION; SENSORY NEUROPATHY; PRIMARY ERYTHERMALGIA; NA(V)1.7; PATIENT; PAIN AB Conditions described as "erythromelalgia" and "erythermalgia" are being formally specified by etiological diagnoses that enable the use of disease-modifying as well symptomatic treatments. We describe an otherwise healthy 20-year-old man as. with acute-onset erythromelalgia. Severe bilateral distal limb pain and vasodilation persisted despite the use of many antihyperalgesics. Pathological examination of cutaneous nerve endings revealed severe small-fiber predominant axonopathy. Treatment of his apparent autoimmune polyneuropathy with high dose corticosteroids, 4 days of lidocaine infusion and a prednisone taper cured him. Similarities to other cases allowed us to tentatively characterize a new treatable cause of erythromelalgia; acute adolescent autoimmune small-fiber axonopathy. In this report we evaluate various options for diagnosis and treatment. C1 Brigham & Womens Hosp, Pain Management Ctr, Chestnut Hill, MA 02467 USA. Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Chestnut Hill, MA 02467 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol Neuropathol, Boston, MA USA. RP Nedeljkovic, SS (reprint author), Brigham & Womens Hosp, Pain Management Ctr, 850 Boylston St, Chestnut Hill, MA 02467 USA. EM srdjan@zeus.bwh.harvard.edu FU NINDS NIH HHS [R01NS42866] NR 28 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 2007 VL 104 IS 2 BP 438 EP 441 DI 10.1213/01.ane.0000252965.83347.25 PG 4 WC Anesthesiology SC Anesthesiology GA 128ME UT WOS:000243661000037 PM 17242106 ER PT J AU Maclayton, DO Hall, RG AF Maclayton, Darego O. Hall, Ronald G., II TI Pharmacologic treatment options for nosocomial pneumonia involving methicillin-resistant Staphylococcus aureus SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE linezolid; methicillin-resistant Staphylococcus aureus; nosocomial pneumonia; vancomycin ID VENTILATOR-ASSOCIATED PNEUMONIA; GRAM-POSITIVE INFECTIONS; RESPIRATORY-TRACT INFECTIONS; CRITICALLY-ILL PATIENTS; SOFT-TISSUE INFECTIONS; INTENSIVE-CARE-UNIT; DOUBLE-BLIND; OBESE-PATIENTS; INTRAPULMONARY PHARMACOKINETICS; ANTIMICROBIAL ACTIVITY AB OBJECTIVE: To discuss current and potential treatment options for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). DATA SOURCES: A MEDLINE search (1966-January 2007) was conducted to identify English-language literature on pharmacotherapy of nosocomial pneumonia and the bibliographies of pertinent articles. Programs and abstracts from infectious disease meetings were also searched. Search terms included MRSA, nosocomial pneumonia, pulmonary infections, vancomycin, quinupristin/dalfopristin, linezolid, daptomycin, tigecycline, dalbavancin, oritavancin, and ceftobiprole. DATA SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all pertinent information was included in this review. DATA SYNTHESIS: Vancomycin has been the drug of choice for MRSA infections for many years. Recent data suggest that linezolid may be superior to vancomycin in the treatment of MRSA nosocomial pneumonia. However, there are limitations to the available data. Therefore, prospective, randomized studies are needed before linezolid is recommended as the preferred first-line therapy. Other approved agents for nosocomial MRSA infections, such as quinupristin/dalfopristin and daptomycin, should not be used in the treatment of MRSA pneumonia, as they were inferior in clinical trials. Tigecycline has excellent activity against MRSA in vitro, but should not be routinely used for the treatment of MRSA pneumonia, as clinical data are lacking. In a Phase III clinical trial, an anti-MRSA cephalosporin, ceftobiprole, is being evaluated for effectiveness against nosocomial pneumonia. Investigational glycopeptides may eventually have a role in the treatment of nosocomial pneumonia, but data are currently lacking. CONCLUSIONS: Vancomycin is still the drug of choice for treatment of MRSA pneumonia, and linezolid should be used as an alternative agent. Linezolid should carry strong consideration for patients with vancomycin-incluced nephrotoxicity or a documented lack of response to vancomycin. Tigecycline and investigational agents with activity against MRSA may be future options for nosocomial pneumonia due to MRSA. C1 Texas So Univ, Coll Pharm & Hlth Sci, Dept Pharm Practice, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77004 USA. Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dallas, TX USA. Univ Texas, SW Med Ctr, Vet Affairs N Texas Hlth Care Syst, Dallas, TX 75230 USA. RP Maclayton, DO (reprint author), Texas So Univ, Coll Pharm & Hlth Sci, Dept Pharm Practice, Michael E DeBakey Vet Affairs Med Ctr, 3100 Cleburne Ave, Houston, TX 77004 USA. EM maclaytondo@tsu.edu NR 85 TC 33 Z9 35 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD FEB PY 2007 VL 41 IS 2 BP 235 EP 244 DI 10.1345/aph.1H414 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 141ZK UT WOS:000244617600008 PM 17299012 ER PT J AU Posner, MC Niedzwiecki, D Venook, AP Hollis, DR Schilsky, RL Goldberg, RM Mayer, RJ AF Posner, M. C. Niedzwiecki, D. Venook, A. P. Hollis, D. R. Schilsky, R. L. Goldberg, R. M. Mayer, R. J. TI A phase II prospective, multi-institutional trial (CALGB 89903) of adjuvant active specific immunotherapy following curative resection of colorectal cancer(CRC) hepatic metastases SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol C1 Univ Chicago, Chicago, IL 60637 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Goldberg , Richard/M-1311-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 SU S BP 3 EP 3 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 134PU UT WOS:000244096200007 ER PT J AU Koch, M Fernando, NT Ryeom, SW D'Amore, PA Yoon, SS AF Koch, M. Fernando, N. T. Ryeom, S. W. D'Amore, P. A. Yoon, S. S. TI Tumor escape from matrix-derived endogenous angiogenesis inhibitors by a common mechanism of vascular endothelial growth facior upregulation SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Surg, Boston, MA 02114 USA. Boston Childrens Hosp, Harvard Med Sch, Vasc Biol Program & Dept Surg, Boston, MA USA. Harvard Med Sch, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 SU S BP 21 EP 21 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 134PU UT WOS:000244096200063 ER PT J AU Pawlik, TM Bauer, TW Reddy, SK Martin, RC Scoggins, CR Tanabe, KK Kooby, DA Vauthey, JN Curley, SA Choti, MA AF Pawlik, T. M. Bauer, T. W. Reddy, S. K. Martin, R. C. Scoggins, C. R. Tanabe, K. K. Kooby, D. A. Vauthey, J. N. Curley, S. A. Choti, M. A. TI Hepatic resection for metastatic squamous cell carcinoma to the liver: a multi-center analysis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Virginia, Med Ctr, Charlottesville, VA USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Louisville, Med Ctr, Louisville, KY 40292 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 SU S BP 22 EP 23 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 134PU UT WOS:000244096200068 ER PT J AU Ito, H Hornick, JL Bertagnolli, MM George, S Morgan, JA Baldini, EH Wagner, AJ Demetri, GD Raut, CP AF Ito, H. Hornick, J. L. Bertagnolli, M. M. George, S. Morgan, J. A. Baldini, E. H. Wagner, A. J. Demetri, G. D. Raut, C. P. TI Leiomyosarcoma of the inferior vena cava: Impact of multidisciplinary management SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 SU S BP 28 EP 28 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 134PU UT WOS:000244096200085 ER PT J AU Javid, SH Carlson, JW Garber, JE Birdwell, RL Lester, S Golshan, M AF Javid, S. H. Carlson, J. W. Garber, J. E. Birdwell, R. L. Lester, S. Golshan, M. TI Comparing resection volume: Breast MRI wire localized excisional biopsy (MRlbx) vs. mammogram wire localized excisional biopsy (Mammobx) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 SU S BP 38 EP 38 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 134PU UT WOS:000244096200114 ER PT J AU Kirstein, LJ Rafferty, E Moore, R Rusby, J Specht, MC Hughes, KS Smith, BL AF Kirstein, L. J. Rafferty, E. Moore, R. Rusby, J. Specht, M. C. Hughes, K. S. Smith, B. L. TI Outcome of multiple wire localization for larger breast cancers: When can mastectomy be avoided? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 SU S BP 41 EP 41 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 134PU UT WOS:000244096200125 ER PT J AU Rusby, JE Brachtel, EF Michaelson, JS Othus, M Koerner, FC Smith, BL AF Rusby, J. E. Brachtel, E. F. Michaelson, J. S. Othus, M. Koerner, F. C. Smith, B. L. TI Predictors of occult nipple involvement to aid selection of patients for nipple-sparing mastectomy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 SU S BP 45 EP 46 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 134PU UT WOS:000244096200141 ER PT J AU Sober, AJ Balch, CM AF Sober, Arthur J. Balch, Charles M. TI Method of biopsy and incidence of positive margins in primary melanoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Johns Hopkins Med, Baltimore, MD 21287 USA. RP Balch, CM (reprint author), Johns Hopkins Med Inst, Baltimore, MD 21205 USA. EM balchch@jhmi.edu NR 4 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 BP 274 EP 275 DI 10.1245/s10434-006-9301-8 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 129YH UT WOS:000243765500003 PM 17219290 ER PT J AU Geiger, AM Nekhlyudov, L Herrinton, LJ Rolnick, SJ Greene, SM West, CN Harris, EL Elmore, JG Altschuler, A Liu, ILA Fletcher, SW Emmons, KM AF Geiger, Ann M. Nekhlyudov, Larissa Herrinton, Lisa J. Rolnick, Sharon J. Greene, Sarah M. West, Carmen N. Harris, Emily L. Elmore, Joann G. Altschuler, Andrea Liu, In- A. Liu Fletcher, Suzanne W. Emmons, Karen M. TI Quality of life after bilateral prophylactic mastectomy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Society-of-Preventive-Oncology CY MAR 13-15, 2005 CL San Francisco, CA SP Amer Soc Prevent Oncol DE breast cancer; prophylaxis; mastectomy; quality of life; satisfaction ID BREAST-CANCER RISK; BRCA2 MUTATION; WOMEN; EFFICACY; HEALTH; SATISFACTION; PREDICTORS; OUTCOMES; IMPACT; SCALE AB Background: Bilateral prophylactic mastectomy in women with increased breast cancer risk dramatically reduces breast cancer occurrence but little is known about psychosocial outcomes. Methods: To examine long-term quality of life after bilateral prophylactic mastectomy, we mailed surveys to 195 women who had the procedure from 1979 to 1999 and to a random sample of 117 women at increased breast cancer risk who did not have the procedure. Measures were modeled on or drawn directly from validated instruments designed to assess quality of life, body image, sexuality, breast cancer concerns, depression, health perception, and demographic characteristics. We used logistic regression to examine associations between quality of life and other domains. Results: The response rate was 58%, with 106 women with and 62 women without prophylactic mastectomy returning complete surveys. Among women who underwent bilateral prophylactic mastectomy, 84% were satisfied with their decision to have the procedure; 61% reported high contentment with quality of life compared with an identical 61% of women who did not have the procedure (P = 1.0). Among all subjects, diminished contentment with quality of life was not associated with bilateral prophylactic mastectomy but with dissatisfaction with sex life (adjusted ratio [OR] = 2.5, 95% confidence interval [CI] = 1.0-6.2), possible depression (CES-D > 16, OR = 4.9, CI = 2.0-11.8), and poor or fair general health perception (OR = 8.3, 95% CI = 2.4-29.0). Conclusions: The majority of women reported satisfaction with bilateral prophylactic mastectomy and experienced psychosocial outcomes similar to women with similarly elevated breast cancer risk who did not undergo prophylactic mastectomy. Bilateral prophylactic mastectomy appears to neither positively nor negatively impact long-term psychosocial outcomes. C1 Kaiser Permanente So Calif, Res & Evaluat Dept, Pasadena, CA 91188 USA. Wake Forest Univ, Sch Med, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. HealthPartners Res Fdn, Minneapolis, MN 55440 USA. Grp Hlth, Ctr Hlth Studies, Seattle, WA 98103 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97227 USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98104 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Geiger, AM (reprint author), Kaiser Permanente So Calif, Res & Evaluat Dept, Pasadena, CA 91188 USA. EM ageiger@wfubmc.edu FU NCI NIH HHS [K05 CA104699, R01 CA090323, U19 CA79689] NR 28 TC 28 Z9 28 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 BP 686 EP 694 DI 10.1245/s10434-006-9206-6 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 129YH UT WOS:000243765500057 PM 17103066 ER PT J AU Leonardi, MJ McGory, ML Ko, CY AF Leonardi, Michael J. McGory, Marcia L. Ko, Clifford Y. TI A systematic review of deep venous thrombosis prophylaxis in cancer patients: Implications for improving quality SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 59th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 23-26, 2006 CL San Diego, CA SP Soc Surg Oncol DE DVT; prophylaxis; cancer; surgery; heparin; review ID MOLECULAR-WEIGHT HEPARIN; LOW-DOSE HEPARIN; GRADUATED COMPRESSION STOCKINGS; GENERAL ABDOMINAL-SURGERY; VEIN THROMBOSIS; UNFRACTIONATED HEPARIN; MULTICENTER TRIAL; STANDARD HEPARIN; PREVENTION; THROMBOEMBOLISM AB Introduction: Deep venous thrombosis (DVT) prophylaxis is particularly important for surgical oncologists given the high rate of DVT in patients with malignancy. Additionally, DVT prophylaxis may soon be implemented by some payers as a "pay for performance" quality measure. This is a systematic review of randomized controlled trial (RCT) evidence for DVT prophylaxis in cancer patients undergoing surgery. We examine overall rates of DVT, the efficacy of high versus low-dose heparin prophylaxis, and the rate of bleeding complications. Methods: The Medline database was searched for English language RCTs using key words DVT, venous thromboembolism, prophylaxis, and general surgery. Inclusion criteria were RCTs evaluating surgical oncology patients. Results: Fifty-five RCTs studied DVT prophylaxis in surgery (nonorthopedic) patients. Twenty-six RCTs evaluated 7,639 cancer patients. The overall DVT rate was 12.7% for pharmacologic prophylaxis and 35.2% for controls. High-dose low-molecular weight heparin (LMWH) was more effective than low dose, lowering the DVT rate from 14.5% to 7.9% (P < 0.01). Heparin decreased the rate of proximal DVTs. Bleeding complications requiring discontinuation of prophylaxis occurred in 3% of the patients. There was no difference between LMWH and unfractionated heparin in efficacy, DVT location, or bleeding complications. Conclusion: Using RCT data, this study demonstrates a greatly reduced DVT rate with pharmacologic prophylaxis in cancer patients, and higher doses appear more effective. Complication rates are low and should not prevent the use of prophylaxis in most patients. Finally, we found no difference between LMWH and unfractionated heparin in these RCTs. These results highlight the importance of routine pharmacologic prophylaxis in surgical patients with malignancy. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Surg Outcomes & Qual, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Leonardi, MJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS,Box 956904, Los Angeles, CA 90095 USA. EM mjleonardi@mednet.ucla.edu NR 33 TC 46 Z9 48 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2007 VL 14 IS 2 BP 929 EP 936 DI 10.1245/s10434-006-9183-9 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 129YH UT WOS:000243765500088 PM 17103259 ER PT J AU Linden, PA Yeap, BY Chang, MY Henderson, WG Jaklitsch, MT Khuri, S Sugarbaker, DJ Bueno, R AF Linden, Philip A. Yeap, Beow Y. Chang, Michael Y. Henderson, William G. Jaklitsch, Michael T. Khuri, Shukri Sugarbaker, David J. Bueno, Raphael TI Morbidity of lung resection after prior lobectomy: Results from the Veterans Affairs National Surgical Quality Improvement Program SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 30-FEB 01, 2006 CL Chicago, IL SP Soc Thorac Surg ID COMPLETION PNEUMONECTOMY; OPERATIVE MORTALITY; CANCER; RISK; SURVIVAL; CARE AB Backround. Lobectomy is the current standard operation for localized lung cancer. Patients who undergo lobectomy have a 1% to 2% chance per year of developing a second lung cancer. The risks of repeat lung resection have not been well quantified or analyzed. We used a national, prospectively recorded database to evaluate the complication rate and risk factors in this population. Methods. The Veterans Affairs National Surgical Quality Improvement Program Database was queried for all patients who underwent lobectomy, followed by an additional lung resection, between 1994 and 2002. Preoperative variables, intraoperative variables, and complications were analyzed. Pulmonary function data were not collected. Results. Excluding 17 patients who underwent repeat resection for complications of lobectomy, 186 patients underwent 191 repeat resections. The 30-day mortality was 11%; the complication rate was 19%. Mortality for pneumonectomy was 34%, lobectomy, 7%; segmentectomy, 0%; and wedge resection, 6%. The most frequent complications were pneumonia (9%), reintubation (8%), ventilator dependence (6%), cardiac arrest (3%), dysrhythmia ( 3%), and sepsis ( 3%). Multivariate analysis revealed that operative time exceeding 2 hours, preoperative dyspnea at rest or with minimal exertion, and white blood cell count of more than 10,000/mm(3) were predictors of complication. Presence of a contaminated/infected case, pneumonectomy, and intraoperative transfusion were predictors of death. Age, complications from prior lobectomy, time interval between lobectomy and repeat resection, smoking history, other comorbidities, and preoperative laboratory values were not independent predictors. Conclusions. Repeat lung resection after lobectomy carries an 11% overall mortality predicted by the presence of a contaminated/infected case, need for intraoperative transfusion, and pneumonectomy versus a lesser resection. (c) 2007 by The Society of Thoracic Surgeons. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Med Ctr, Boston, MA 02115 USA. Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. RP Linden, PA (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM plinden@partners.org NR 21 TC 13 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2007 VL 83 IS 2 BP 425 EP 432 DI 10.1016/j.athoracsur.2006.09.081 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 129GM UT WOS:000243716600012 PM 17257965 ER PT J AU Koster, A Dyke, CM Aldea, G Smedira, NG McCarthy, HL Aronson, S Hetzer, R Avery, E Spiess, B Lincoff, AM AF Koster, Andreas Dyke, Cornelius M. Aldea, Gabriel Smedira, Nicholas G. McCarthy, Harry L., II Aronson, Solomon Hetzer, Roland Avery, Edwin Spiess, Bruce Lincoff, A. Michael TI Bivalirudin during cardiopulmonary bypass in patients with previous or acute heparin-induced thrombocytopenia and heparin antibodies: Results of the CHOOSE-ON trial SO ANNALS OF THORACIC SURGERY LA English DT Article ID EXPERIENCE; SURGERY AB Background. The coronary artery bypass grafting (CABG) heparin-induced thrombocytopenia thrombosis syndrome (HITTS) on- and off-pump safety and efficacy (CHOOSE-ON) trial was designed as a safety and efficacy trial of bivalirudin for use in anticoagulation during cardiopulmonary bypass (CPB) in patients with confirmed or suspected HIT and (or) antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Methods. In an open-label, multicenter trial, 50 patients were enrolled prospectively. The primary study endpoint was in-hospital acute procedural success, defined as the absence of death, Q-wave myocardial infarction (MI), repeat operation for coronary revascularization, and stroke at day seven after surgery or hospital discharge, whichever occurred first. The secondary study endpoints were procedural success, defined as the absence of death, Q-wave MI, repeat operation for coronary revascularization, and stroke, at 30 days and 12 weeks after surgery. Perioperative blood loss, transfusions, and the incidence of major bleeding events were also captured. Results. There were 49 patients treated with bivalirudin of which 43 had acute HIT and thrombosis syndrome HITTS) with antibodies at time of surgery. Procedural success in-hospital or at 7 days was achieved in 46 (94%) patients. At day 30 procedural success was achieved in 42 (86%) patients, and after 12 weeks in 40 (82%) patients. Mean intraoperative blood loss was 575 +/- 524 mL, and mean 24-hour postoperative blood loss was 998 +/- 595 mL. Forty-one (84%) patients received transfusions before day 7 or discharge with a mean of 5.6 +/- 3.8 units of red blood cells, 8.6 +/- 7.2 units of platelets, and 6.0 +/- 4.7 units of fresh frozen plasma. No differences in outcome among bivalirudin-treated patients were observed between those in the overall group and those with moderately impaired renal function (n = 10). Conclusions. The current investigation expands the experience of safe and effective anticoagulation with bivalirudin during CPB to patients with confirmed or suspected HIT and anti-PF4/H antibodies, including in the setting of impaired renal function. C1 Deutsch Herzzentrum, Dept Anesthesia, D-13353 Berlin, Germany. Deutsch Herzzentrum, Dept Cardiothorac & Vasc Surg, D-13353 Berlin, Germany. Gaston Mem Hosp, Dept Cardiovasc & Thorac Surg, Gastonia, NC USA. Washington State Univ, Dept Cardiac Surg, Seattle, WA USA. Cleveland Clin Fdn, Dept Cardiothorac Surg, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Virginia Commonwealth Univ, Dept Cardiac Surg, Richmond, VA USA. Virginia Commonwealth Univ, Dept Cardiothorac Anesthesia, Richmond, VA USA. Duke Univ, Med Ctr, Dept Anesthesia, Durham, NC USA. Massachusetts Gen Hosp, Dept Cardiac Anesthesia, Boston, MA 02114 USA. RP Koster, A (reprint author), Deutsch Herzzentrum, Dept Anesthesia, Augustenburger Pl 1, D-13353 Berlin, Germany. EM koster@dhzb.de NR 15 TC 96 Z9 101 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2007 VL 83 IS 2 BP 572 EP 577 DI 10.1016/j.athoracsur.2006.09.038 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 129GM UT WOS:000243716600033 PM 17257990 ER PT J AU Everett, BM Yeh, R Foo, SY Criss, D Van Cott, EM Laposata, M Avery, EG Hoffman, WD Walker, J Torchiana, D Jang, IK AF Everett, Brendan M. Yeh, Robert Foo, Shi Yin Criss, David Van Cott, Elizabeth M. Laposata, Michael Avery, Edwin G. Hoffman, William D. Walker, Jennifer Torchiana, David Jang, Ik-Kyung TI Prevalence of heparin/platelet factor 4 antibodies before and after cardiac surgery SO ANNALS OF THORACIC SURGERY LA English DT Article ID HEPARIN-INDUCED THROMBOCYTOPENIA; CARDIOPULMONARY BYPASS-SURGERY; UNFRACTIONATED HEPARIN; THROMBOSIS; RISK AB Background. The clinical significance of heparin/platelet factor 4 (PF4) antibodies in subjects undergoing cardiac surgery has not been systematically studied. We prospectively investigated whether the presence of heparin/PF4 antibodies would predict clinical thrombosis in this population. Methods. In 299 patients scheduled for cardiac surgery between October 2003 and March 2005, the heparin/PF4 antibodies and platelet count were measured immediately prior to, and 5 days after, surgery. The patients were followed up at 30 days for thrombotic complications. Results. The prevalence of the heparin/PF4 antibodies was 4.3% (13 of 299) prior to surgery and increased more than fivefold to 22.4% (62 of 277) postoperatively (p < 0.0001). Thromboembolic events occurred in 8.8% of patients with negative antibody and in 6.3% of patients with positive antibody (p = 0.77). Of the 62 patients with positive heparin/PF4 antibodies postoperatively, 22 (35.5%) were treated with a nonheparin anticoagulant. There was a trend toward higher rates of thromboembolic events in subjects who were thrombocytopenic compared with those who were not (17.1% and 6.7%, respectively, p = 0.06), regardless of antibody status. Two out of 8 patients (25%) with both thrombocytopenia and a positive antibody (clinical heparin-induced thrombocytopenia [ HIT]) suffered a thromboembolic event, compared with 17 of 222 (7.7%) without clinical HIT (p = 0.13). Conclusions. The high prevalence of antibodies to the heparin/ PF4 complex after cardiac surgery and the low rate of thromboembolic complications in this population suggest that the antibody alone does not confer an increased risk of thrombotic complications. Monitoring for thrombocytopenia is recommended. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Div,Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Cardiac Anesthesia Di, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Div,Dept Med, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 17 TC 37 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2007 VL 83 IS 2 BP 592 EP 597 DI 10.1016/j.athoracsur.2006.09.040 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 129GM UT WOS:000243716600036 PM 17257993 ER PT J AU Conrad, MF Crawford, RS Davison, JK Cambria, RP AF Conrad, Mark F. Crawford, Robert S. Davison, J. Kenneth Cambria, Richard P. TI Thoracoabdominal aneurysm repair: A 20-year perspective SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT Aortic Surgery Symposium X CY APR 27-29, 2006 CL New York, NY ID AORTIC-ANEURYSMS; EXPERIENCE; OPERATIONS AB Background. A variety of operative approaches and protective adjuncts have been used to minimize organ dysfunction and, in particular, spinal cord injury (SCI) after thoracoabdominal aneurysm (TAA) repair. There is no consensus with respect to the optimal approach. Methods. Reviewed were 445 consecutive TAA repairs done between January 1987 and December 2005. Clinical features included urgent operation in 103 patients (22.6%), of which 52 (11.4%) were ruptures. Operative management consisted of a clamp- and-sew technique with adjuncts in 417 patients (92%). Epidural cooling to prevent SCI was used in 240 (68%) extent I to III repairs. Predictors of mortality and SCI were assessed with multivariate analysis, and long- term survival was determined with Kaplan-Meier life-table analysis. Results. Operative mortality was 8.2% and was associated with preoperative serum creatinine level of 1.8 mg/dL or more (p = 0.005), intraoperative hypotension (p = 0.01), intraoperative transfusion requirement (p = 0.0008), postoperative SCI (p = 0.02), and postoperative renal failure (p < 0.0001). SCI of any severity occurred in 60 patients (13.2%), and 43 (9.5% of the total cohort) sustained major paraplegia. Epidural cooling significantly reduced the risk of SCI in patients with types I to III TAA (13.7% versus 29%, p = 0.01). Independent predictors of SCI included extent I/II aneurysms (p = 0.02), epidural cooling (p = 0.02), urgent/emergent operation (p = 0.02), intraoperative hypotension (p = 0.005), total aortic cross-clamp time (p = 0.01), and postoperative pulmonary complications (p = 0.003). Late survival rates were at 54.4% at 5 years, 28.7% at 10 years, and 20.5% at 15 years. Conclusions. Despite the favorable impact of operative adjuncts on perioperative mortality and SCI, major morbidity after TAA remains a challenge; the implications to further develop stent graft strategies are clear. C1 Massachusetts Gen Hosp, Boston, MA 02180 USA. Harvard Univ, Sch Med, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Thorac Aort Ctr, Boston, MA 02115 USA. RP Conrad, MF (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WAC 4, Boston, MA 02180 USA. EM mconrad@partners.org NR 10 TC 159 Z9 162 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2007 VL 83 IS 2 BP S856 EP S861 DI 10.1016/j.athoracsur.2006.10.096 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 129GM UT WOS:000243716600108 PM 17257941 ER PT J AU Mooney, S Hasssanein, TI Hilsabeck, RC Ziegler, EA Carlson, M Maron, LM Perry, W AF Mooney, Scott Hasssanein, Tarek I. Hilsabeck, Robin C. Ziegler, Elizabeth A. Carlson, Meghan Maron, Leeza M. Perry, William CA UCSD Hepatology Neurobehavioral R TI Utility of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in patients with end-stage liver disease awaiting liver transplant SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Repeatable Battery for the Assessment of Neuropsychological Status; end stage liver disease ID SUBCLINICAL HEPATIC-ENCEPHALOPATHY; QUALITY-OF-LIFE; COGNITIVE IMPAIRMENT; MULTIPLE-SCLEROSIS; CIRRHOTIC-PATIENTS; TEST-PERFORMANCE; SCREENING-TEST; VALIDITY; SCHIZOPHRENIA; SPECTROSCOPY AB Cognitive impairment is common among patients with end-stage liver disease (ESLD). This study examined cognitive dysfunction in patients with ESLD using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). METHOD: 66 patients with ESLD awaiting liver transplant were recruited. Patients were evaluated with the RBANS, Peabody Picture Vocabulary Test-Revised, and Beck Depression Inventory-II. RESULTS: Patients with ESLD uniformly performed below expectations on all RBANS index scores compared to the healthy normative sample (all p's < .0001) and they also displayed a "subcortical" pattern of cognitive performance (p < .0001). Performances on RBANS attention, language, immediate memory, and total index scores were correlated with education and ethnicity (r's range = vertical bar.32-.57 vertical bar; p's < .01). There was no association between performance on any of the RBANS index scores or subtests and ESLD patient characteristics. In summary, the RBANS appears to adequately characterize known patterns of cognitive dysfunction in ESLD patients. (c) 2007 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Perry, W (reprint author), Univ Calif San Diego, Dept Psychiat, 200 W Arbor Dr 8218, San Diego, CA 92103 USA. EM wperry@UCSD.edu NR 58 TC 33 Z9 35 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD FEB PY 2007 VL 22 IS 2 BP 175 EP 186 DI 10.1016/j.acn.2006.12.005 PG 12 WC Psychology, Clinical; Psychology SC Psychology GA 154WT UT WOS:000245539300005 PM 17280813 ER PT J AU Friedl, KE Grate, SJ Proctor, SP Ness, JW Lukey, BJ Kane, RL AF Friedl, Karl E. Grate, Stephen J. Proctor, Susan P. Ness, James W. Lukey, Brian J. Kane, Robert L. TI Army research needs for automated neuropsychological tests: Monitoring soldier health and performance status SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE neuropsychological testing; neurophysiology; military personnel; neuroepidemiology; health surveillance ID GULF-WAR VETERANS; TEST BATTERIES; PERSONNEL; EXPOSURE; UTILITY; STRESS; BRAIN; MOOD AB Information on the mental status of soldiers operating at the limits of human tolerance will be vital to their management in future deployments; it may also allow earlier intervention for conditions such as undiagnosed Gulf War illnesses and Parkinson's Disease. The Army needs a parsimonious set of neuropsychological tests that reliably identify subtle changes for: (1) early detection of individual health and military performance impairments and (2) management of occupational and deployment health risks. Testing must characterize cognitive lapses in healthy individuals faced with relevant operational stressors (i.e., anxiety, information overload, thermal strain, hypoxia, fatigue, head impact, chemical or radiation exposures, metabolic challenges). This effort must also explore the neuropsychological methods in militarily relevant conditions to extend our understanding of relevant functional domains and how well they correspond to modes of testing. The ultimate objective is unobtrusive real-time mental status monitoring. (c) 2006 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 USA, Inst Environm Med, Natick, MA 01760 USA. Mil Operat Med Res Program, Ft Detrick, MD 21702 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. US Mil Acad, Dept Behav Biol, West Point, NY 10996 USA. VA Maryland Hlth Care Syst, Baltimore, MD 21201 USA. RP Friedl, KE (reprint author), USA, Inst Environm Med, Natick, MA 01760 USA. EM karl.friedl@us.army.mil OI Friedl, Karl/0000-0002-3134-8427 NR 41 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD FEB PY 2007 VL 22 IS 1 SU S BP S7 EP S14 DI 10.1016/j.acn.2006.10.002 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA 161DZ UT WOS:000245995900003 PM 17127031 ER PT J AU Kuperberg, GR Deckersbach, T Holt, DJ Goff, D West, C AF Kuperberg, Gina R. Deckersbach, Thilo Holt, Daphne. J. Goff, Donald West, Caroline TI Increased temporal and prefrontal activity in response to semantic associations in schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat ID EVENT-RELATED POTENTIALS; LEXICAL DECISION TASK; HUMAN CEREBRAL-CORTEX; SPREADING ACTIVATION THEORY; FORMAL THOUGHT-DISORDER; SURFACE-BASED ANALYSIS; FUNCTIONAL MRI; CORTICAL SURFACE; WORD PRONUNCIATION; COMMUNICATION DISORDERS AB Context: Loosening of associations has long been considered a core feature of schizophrenia, but its neural correlate remains poorly understood. Objective: To test the hypothesis that, in comparison with healthy control subjects, patients with schizophrenia show increased neural activity within inferior prefrontal and temporal cortices in response to directly and indirectly semantically related (relative to unrelated) words. Design: A functional neuroimaging study using a semantic priming paradigm. Setting: Lindemann Mental Health Center, Boston, Mass. Participants: Seventeen right-handed medicated outpatients with chronic schizophrenia and 15 healthy volunteers, matched for age and parental socioeconomic status. Interventions: Functional magnetic resonance imaging as participants viewed directly related, indirectly related, and unrelated word pairs and performed a lexical decision task. Main Outcome Measures, Event-related functional magnetic resonance imaging measures of blood oxygenation level-dependent activity (1) within a priori temporal and prefrontal anatomic regions of interest and (2) at all voxels across the cortex. Results: Patients and controls showed no behavioral differences in priming but opposite patterns of hemodynamic modulation in response to directly related (relative to unrelated) word pairs primarily within inferior prefrontal cortices, and to indirectly related (relative to unrelated) word pairs primarily within temporal cortices. Whereas controls showed the expected decreases in activity in response to semantic relationships (hemodynamic response suppression), patients showed inappropriate increases in response to semantic relationships (hemodynamic response enhancement) in many of the same regions. Moreover, hemodynamic response enhancement within the temporal fusiform cortices to indirectly related (relative to unrelated) word pairs predicted positive thought disorder. Conclusion: Medicated patients with chronic schizophrenia, particularly those with positive thought disorder, show inappropriate increases in activity within inferior prefrontal and temporal cortices in response to semantic associations. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, CNY2,Bldg 149, Charlestown, MA 02129 USA. EM kuperber@nmr.mgh.harvard.edu FU NIMH NIH HHS [K01 MH65356, K23 MH02034, R01 MH071635] NR 114 TC 67 Z9 68 U1 4 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2007 VL 64 IS 2 BP 138 EP 151 DI 10.1001/archpsyc.64.2.138 PG 14 WC Psychiatry SC Psychiatry GA 133DD UT WOS:000243990900002 PM 17283282 ER PT J AU Stewart, SE Platko, J Fagerness, J Birns, J Jenike, E Smaller, JW Perlis, R Leboyer, M Delorme, R Chabane, N Rauch, SL Jenike, MA Pauls, DL AF Stewart, S. Evelyn Platko, Jill Fagerness, Jesen Birns, Julie Jenike, Eric Smaller, Jordan W. Perlis, Roy Leboyer, Marion Delorme, Richard Chabane, Nadia Rauch, Scott L. Jenike, Michael A. Pauls, David L. TI A genetic family-based association study of OLIG2 in obsessive-compulsive disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 13th World Congress on Psychiatric Genetics CY SEP 04-08, 2005 CL Boston, MA SP Int Soc Psychiat Gen ID WHITE-MATTER ABNORMALITIES; LA-TOURETTE-SYNDROME; SIB PAIRS; LINKAGE; TICS; SCHIZOPHRENIA; EPIDEMIOLOGY; RELIABILITY; FLUVOXAMINE; DEPRESSION AB Context: Obsessive-compulsive disorder (OCD) is a debilitating familial psychiatric illness with associated brain abnormalities in the white matter. The gene for oligodendrocyte lineage transcription factor 2 (OLIG2) is an essential regulator in the development of cells that produce white matter (myelin). The OLIG2 gene is also highly expressed in brain regions implicated in OCD. Objectives: To examine OLIG2 as a candidate gene for OCD susceptibility and to explore whether comorbidity subtypes of OCD have distinct associations with OLIG2 and the functionally related OLIG1 gene. It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone. Design: Family-based association candidate gene study. Setting: Participants and their family members were recruited from tertiary care OCD and TD specialty clinics. Participants: Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD. Main Outcome Measures: Genotypes of single nucleotide polymorphism markers and related haplotypes. Results: The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; P <.001), rs1059004 (minor allele frequency, 44%; P=.005), and rs9653711 (minor allele frequency, 44%; P=.004). A 5-marker haplotype (A/C/T/ T/G) constituting these single nucleotide polymorphisms and exonic single nucleotide polymorphisms rs6517137 and rs13046814 was undertransmitted (frequency, 32%; permuted P=.004), whereas the G/A/T/T/C haplotype (frequency, 22%; permuted P=.02) was overtransmitted to probands with OCD alone, with a significant global P value (permuted P=.008). Conclusions: This is the first study reporting an association between OLIG2 and OCD, specifically when TD comorbidity is absent. The findings support a role for white matter abnormalities in the etiology of the disorder. C1 Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Psychiat Neurosci Res Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Obsess Compuls Disorders Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Paris, Dept Psychiat, Mondor Chenevier Hosp, F-75252 Paris, France. Robert Debre Hosp, Paris, France. RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 FU NINDS NIH HHS [R01 NS16648] NR 38 TC 44 Z9 45 U1 3 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2007 VL 64 IS 2 BP 209 EP 215 DI 10.1001/archpsyc.64.2.209 PG 7 WC Psychiatry SC Psychiatry GA 133DD UT WOS:000243990900008 PM 17283288 ER PT J AU Yamazaki, H Litman, A Margolis, HC AF Yamazaki, Hajime Litman, Amy Margolis, Henry C. TI Effect of fluoride on artificial caries lesion progression and repair in human enamel: Regulation of mineral deposition and dissolution under in vivo-like conditions SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE dental enamel; remineralization; demineralization mineral distribution; fluoride ID DEMINERALIZATION IN-VITRO; DENTAL PLAQUE FLUID; TOOTH DEMINERALIZATION; REMINERALIZATION; SOLUBILITY; RINSE; RATES; NAF AB Objective: This study was carried out to determine in vitro the effect of fluoride on (1) the demineralization of sound human enamel and (2) the progression of artificial caries-like lesions, under relevant oral conditions. Methods: Thin sections of sound human enamel were exposed to solutions undersaturated with respect to tooth enamel to a degree similar to that found in dental plaque fluid following sucrose exposure in vivo, containing fluoride concentrations (0-0.38 ppm) found in plaque fluid. Mineral changes were monitored for 98 days, using quantitative microradiography. The effect of fluoride (1.0-25.0 ppm) on the progression of artificial caries-like lesions was similarly studied. Results: Fluoride concentrations of 0.19 ppm and greater were found to prevent the demineralization of sound enamel in vitro. However, significantly higher concentrations of fluoride (25.0 ppm) were required to prevent further dernineralization of artificial caries-like lesions. Demineralizing solutions with intermediate fluoride concentrations (2.1-10.1 ppm) induced simultaneously remineralization in the outer portion of the lesion and dernineralization in the inner portion. Simultaneous remineralization and demineralization were also observed in hydroxyapatite pellets. Conclusions: Our results show that the observed effect of fluoride on enamel demineralization is not solely a function of bulk solution properties, but also depends on the caries-status of the enamel surface. A mechanistic model presented indicates that, in comparison to sound enamel surfaces, higher concentrations of fluoride are required to prevent the progression of artificial caries-like lesions under in vivo-like conditions since the diffusion of mineral ions that promote remineralization is rate-limiting. (c) 2006 Elsevier Ltd. All rights reserved. C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Kao Corp, Hlth Care Prod Res Labs, Tokyo 1318501, Japan. RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. EM hyamazaki@forsyth.org; hmargolis@forsyth.org FU NIDCR NIH HHS [DE-07493, DE-15163, R01 DE007493, R01 DE007493-14, R01 DE015163, R01 DE015163-04] NR 27 TC 32 Z9 36 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD FEB PY 2007 VL 52 IS 2 BP 110 EP 120 DI 10.1016/j.archoralbio.2006.08.012 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 135HU UT WOS:000244145500002 PM 17049334 ER PT J AU Hartnick, CJ Boseley, ME Franco, RA Cunningham, MJ Pransky, S AF Hartnick, Christopher J. Boseley, Mark E. Franco, Ramon A., Jr. Cunningham, Michael J. Pransky, Seth TI Efficacy of treating children with anterior commissure and true vocal fold respiratory papilloma with the 585-nm pulsed-dye laser SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 20-22, 2006 CL Chicago, IL SP Amer Soc Pediat Otolaryngol ID LARYNGEAL PAPILLOMAS; JUVENILE-ONSET; CIDOFOVIR AB Objective: To report preliminary results regarding the safety and efficacy of the 585-nm pulsed-dye laser (PDL) for the treatment of juvenile-onset recurrent respiratory papillomatosis (JORRP) in the pediatric population. Design: Prospective longitudinal cohort study. Setting: Two pediatric otolaryngology referral centers Patients: Twenty-three pediatric patients ranging in age from 6 months to 17 years. Interventions: The 585-nm PDL was used for at least I treatment on each of these patients to treat JORRP of the true vocal folds or anterior commissure. Main Outcome Measures: Complications from the use of the 585-nm PDL in the treatment of JORRP. Results: There was no evidence of anterior commissure webbing or true vocal fold scarring in this group of 23 patients followed up for 3 months to 1 year. Conclusions: The 585-nm PDL seems to be a safe instrument for treatment of JORRP. There is the potential that improved voice outcomes may be apparent when compared with traditional therapies because the vocal fold epithelium seems to be unharmed when treated with this method. Furthermore, the lack of epithelial damage incurred by the 585-nm PDL should enable more aggressive surgical excision of anterior commissure disease. Further prospective longitudinal studies examining voice outcomes are needed. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Childrens Hosp San Diego, Dept Otolaryngol, San Diego, CA USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 23 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD FEB PY 2007 VL 133 IS 2 BP 127 EP 130 DI 10.1001/archotol.133.2.127 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 135TM UT WOS:000244176400005 PM 17309979 ER PT J AU Kratz, A Salem, RO Van Cott, EM AF Kratz, Alexander Salem, Raneem O. Van Cott, Elizabeth M. TI Effects of a pneumatic tube system on routine and novel hematology and coagulation parameters in healthy volunteers SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID BLOOD-GAS SAMPLES; PLATELET ACTIVATION; SPECIMENS; TRANSPORT; DELIVERY; TIME AB Context.-Technologic advances affecting analyzers used in clinical laboratories have changed the methods used to obtain many laboratory measurements, and many novel parameters are now available. The effects of specimen transport through a pneumatic tube system on laboratory results obtained with such modern instruments are unclear. Objective.-To determine the effects of sample transport through a pneumatic tube system on routine and novel hematology and coagulation parameters obtained on state-of-the-art analyzers. Design.-Paired blood samples from 33 healthy volunteers were either hand delivered to the clinical laboratory or transported through a pneumatic tube system. Results.-No statistically significant differences were observed for routine complete blood cell count and white cell differential parameters or markers of platelet activation, such as the mean platelet component, or of red cell fragmentation. When 2 donors who reported aspirin intake were excluded from the analysis, there was a statistically, but not clinically, significant impact of transport through the pneumatic tube system on the mean platelet component. There were no statistically significant differences for prothrombin time, activated partial thromboplastin time, waveform slopes for prothrombin time or activated partial thromboplastin time, fibrinogen, or fibrin monomers. Conclusions.-Although further study regarding the mean platelet component may be required, transport through a pneumatic tube system has no clinically significant effect on hematology and coagulation results obtained with certain modern instruments in blood samples from healthy volunteers. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kratz, A (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pathol, 622 W 168th St,PH3-303, New York, NY USA. EM ak2651@columbia.edu NR 17 TC 31 Z9 32 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2007 VL 131 IS 2 BP 293 EP 296 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 137UL UT WOS:000244317700018 PM 17284116 ER PT J AU Robbins, J Kays, SA Gangnon, RE Hind, JA Hewitt, AL Gentry, LR Taylor, AJ AF Robbins, JoAnne Kays, Stephanie A. Gangnon, Ronald E. Hind, Jacqueline A. Hewitt, Angela L. Gentry, Lindell R. Taylor, Andrew J. TI The effects of lingual exercise in stroke patients with dysphagia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the Dysphagia-Research-Society CY MAR 24, 2006 CL Scottsdale, AZ SP Dysphagia Res Soc DE deglutition; cerebrovascular disease; exercise; rehabilitation; therapeutics; tongue ID PENETRATION-ASPIRATION SCALE; QOL OUTCOMES TOOL; OROPHARYNGEAL DYSPHAGIA; SWAL-QOL; SWALLOWING PRESSURE; NATURAL-HISTORY; MOTOR FUNCTION; STRENGTH; ADULTS; MUSCLE AB Objective: To examine the effects of lingual exercise on swallowing recovery poststroke. Design: Prospective cohort intervention study, with 4- and 8-week follow-ups. Setting: Dysphagia clinic, tertiary care center. Participants: Ten stroke patients (n=6, acute: <= 3mo poststroke: n=4, chronic: > 3mo poststroke), age 51 to 90 years (mean, 69.7y). Intervention: Subjects performed an 8-week isometric lingual exercise program by compressing an air-filled bulb between the tongue and the hard palate. Main Outcome Measures: Isometric and swallowing lingual pressures, bolus flow parameters, diet, and a dysphagia-specific quality of life questionnaire were collected at baseline, week 4, and week 8. Three of the 10 subjects underwent magnetic resonance imaging at each time interval to measure lingual volume. Results: All subjects significantly increased isometric and swallowing pressures. Airway invasion was reduced for liquids. Two subjects increased lingual volume. Conclusions: The findings indicate that lingual exercise enables acute and chronic dysphagic stroke patients to increase lingual strength with associated improvements in swallowing pressures, airway protection, and lingual volume. C1 William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. Univ Wisconsin, Dept Biomed Engn, Madison, WI USA. Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, 2500 Overlook Ter GRECC 11G, Madison, WI 53705 USA. EM jrobbin2@wisc.edu NR 36 TC 132 Z9 138 U1 3 U2 29 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 2007 VL 88 IS 2 BP 150 EP 158 DI 10.1016/j.apmr.2006.11.002 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 135IX UT WOS:000244148400003 PM 17270511 ER PT J AU Nguyen, LT Jacobs, J Mathis, D Benoist, C AF Nguyen, Linh T. Jacobs, Jonathan Mathis, Diane Benoist, Christophe TI Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; IMMUNE-RESPONSES; SYNOVIAL-FLUID; CUTTING EDGE; VIRAL IL-10; ANTIGEN AB Objective. Regulatory T cells play a suppressive role in many autoimmune diseases and can potentially affect various steps in the progression of disease. The purpose of this study was to analyze the role of Treg cells in the control of arthritis development. Methods. Using crosses and cell transfers, we tested the effect of the scurfy loss-of-function mutation of the Foxp3 gene in the K/BxN mouse model. In this model, arthritis develops as the result of the production of high levels of pathogenic autoantibodies. Results. The absence of Treg cells in K/BxN mice led to faster and more aggressive arthritis. Strikingly, disease also spread to joints not normally affected in this model. The absence of Treg cells resulted in an acceleration of the immunologic phase of disease, with significantly earlier autoantibody production. However, the broadened spectrum of affected joints in Foxp3-mutant mice was not due to the earlier appearance of autoantibodies and could not be reproduced by increasing the anti-glucose-6-phosphate. isomerase antibody load, which demonstrates an impact of Treg cells on effector phase manifestations. In addition, FoxP3+, CD25+ Treg cells accumulated in inflamed joints, even in nontransgenic animals. This preferential localization mimics that in human arthritides and indicates a preferential homing/retention of Treg cells to sites of inflammation. Conclusion. These results indicate that Treg cells play a role in antibody-mediated arthritis at several levels. Treg cells are involved in constraining the immune phase of disease, as well as limiting the articular damage provoked by the pathogenic autoantibodies in terms of severity and of the range of affected joints, which may contribute to the limited distal predominance of many arthritides. C1 Brigham & Womens Hosp, Immunol & Immunogenet Sect, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mathis, D (reprint author), Brigham & Womens Hosp, Immunol & Immunogenet Sect, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu OI Jacobs, Jonathan/0000-0003-4698-0254 FU NIAID NIH HHS [P01-AI-52343]; NIAMS NIH HHS [R01-AR-046580] NR 49 TC 89 Z9 94 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 2007 VL 56 IS 2 BP 509 EP 520 DI 10.1002/art.22272 PG 12 WC Rheumatology SC Rheumatology GA 135HS UT WOS:000244145300015 PM 17265486 ER PT J AU Lopes-Virella, MF McHenry, MB Lipsitz, S Yim, E Wilson, PF Lackland, DT Lyons, T Jenkins, AJ Virella, G AF Lopes-Virella, Maria F. McHenry, Michael Brent Lipsitz, Stuart Yim, Eunsil Wilson, Peter F. Lackland, Daniel T. Lyons, Timothy Jenkins, Alicia J. Virella, Gabriel CA DCCT EDIC Res Grp TI Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes SO ATHEROSCLEROSIS LA English DT Article DE atherosclerosis; type 1 diabetes; autoimmunity; oxidized LDL antibodies; modified lipoprotein IC; intima-media thickness; diabetic complications ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; MODIFIED LDL ANTIBODIES; OXIDIZED LDL; HEART-DISEASE; ATHEROSCLEROTIC LESIONS; COMPLICATIONS TRIAL; METABOLIC-CONTROL; VASCULAR-DISEASE; DEFICIENT MICE AB Modified lipoproteins induce autoimmune responses including the synthesis of autoantibodies with pro-inflammatory characteristics. Circulating modified lipoprotein autoantibodies combine with circulating antigens and form immune complexes (IC). We now report the results of a study investigating the role of circulating IC containing modified lipoproteins in the progression of carotid intima-media thickness (IMT) in patients enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) Trial, a follow-up study of the Diabetes Control and Complications Trial (DCCT). This cohort includes 1229 patients with type 1 diabetes in whom B-mode Ultrasonography of internal and common carotid arteries was performed in 1994-1996 and in 1998-2000. Conventional CHD risk factors, antibodies against modified forms of LDL and modified lipoprotein IC were determined in 1050 of these patients from blood collected in 1996-1998. Cholesterol and apolipoprotein B content of IC (surrogate markers of modified ApoB-rich lipoproteins) were significantly higher in patients who showed progression of the internal carotid IMT than in those showing no progression, regression or mild progression. Multivariate linear and logistic regression modeling using conventional and non-conventional risk factors showed that the cholesterol content of IC was a significant positive predictor of internal carotid IMT progression. In conclusion these data demonstrate that increased levels of modified ApoB-rich IC are associated with increased progression of internal carotid IMT in the DCCT/EDIC cohort of type 1 diabetes. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Met Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Univ Oklahoma, Dept Med, Oklahoma City, OK USA. Univ Melbourne, Dept Med, Melbourne, Vic, Australia. RP Lopes-Virella, MF (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM virellam@musc.edu RI Jenkins, Alicia/N-2482-2015 FU NCRR NIH HHS [M01-RR-1070]; NHLBI NIH HHS [P01 HL55782] NR 54 TC 44 Z9 45 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2007 VL 190 IS 2 BP 359 EP 369 DI 10.1016/j.atherosclerosis.2006.02.007 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 135SJ UT WOS:000244173000016 PM 16530770 ER PT J AU Gow, DW AF Gow, David W., Jr. TI Do the cognitive and behavioral sciences need each other? SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Game theory provides a descriptive or a normative account of an important class of decisions. Given the cognitive sciences' emphasis on explanation, unification with the behavioral sciences under a descriptive model would constitute a step backwards in their development. I argue for the interdependence of the cognitive and behavioral sciences and suggest that meaningful integration is already occurring through problem-based interdisciplinary research programs. C1 Massachusetts Gen Hosp, Cognit Behav Neurol Grp, Boston, MA 02114 USA. RP Gow, DW (reprint author), Massachusetts Gen Hosp, Cognit Behav Neurol Grp, Boston, MA 02114 USA. EM gow@helix.mgh.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD FEB PY 2007 VL 30 IS 1 BP 27 EP + DI 10.1017/S0140525X07000702 PG 11 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 173JS UT WOS:000246869900013 ER PT J AU Bernardi, RE Lattal, KM Berger, SP AF Bernardi, Rick E. Lattal, K. Matthew Berger, S. Paul TI Anisomycin disrupts a contextual memory following reactivation in a cocaine-induced locomotor activity paradigm SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE reconsolidation; cocaine; sensitization; memory ID CONDITIONED PLACE PREFERENCE; LONG-TERM-MEMORY; PROTEIN-SYNTHESIS; RETROGRADE-AMNESIA; BEHAVIORAL SENSITIZATION; RECONSOLIDATION HYPOTHESIS; INCENTIVE-SENSITIZATION; RETRIEVAL; EXTINCTION; FEAR AB In experiments examining the potential reconsolidation of drug-associated contextual memories, rats were given a single pairing of cocaine with a specific context, and the ability of the protein synthesis inhibitor anisomycin administered following a context-only memory retrieval trial to impair conditioned locomotor sensitization was tested. Rats receiving 150 mg/kg anisomycin immediately following a 5-min reexposure to the cocaine-conditioned context showed decreased activity compared with the vehicle control group in response to a low-dose cocaine challenge during a subsequent test for conditioned sensitization. This effect was not seen when anisomycin was administered following a 30-min reexposure to the context or when anisomycin was administered 25 min after a 5-min reexposure. These results are consistent with a growing literature suggesting that following retrieval, associative contextual memories may undergo a transient protein synthesis-dependent reconsolidation phase that normally serves to maintain memory. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland VA Med Ctr, Dept Psychiat, Portland, OR USA. RP Bernardi, RE (reprint author), Oregon Hlth Sci Univ, Dept Behav Neurosci, Mail Code L470,3181 SW Sam Jackson Rd, Portland, OR 97239 USA. EM bernardi@ohsu.edu FU NIAAA NIH HHS [AA01760]; NIMH NIH HHS [MH074547] NR 59 TC 21 Z9 22 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD FEB PY 2007 VL 121 IS 1 BP 156 EP 163 DI 10.1037/0735-7044.121.1.156 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 137IW UT WOS:000244287300015 PM 17324060 ER PT J AU Fogler, JM Tompson, MC Steketee, G Hofmann, SG AF Fogler, Jason M. Tompson, Martha C. Steketee, Gail Hofmann, Stefan G. TI Influence of expressed emotion and perceived criticism on cognitive-behavioral therapy for social phobia SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE social phobia; social anxiety; expressed emotion; perceived criticism; cognitive-behavioral therapy; family factors ID BECK DEPRESSION INVENTORY; STRESS SCALES DASS; ANXIETY DISORDER; PSYCHOMETRIC PROPERTIES; MOOD DISORDERS; RELAPSE; PERCEPTIONS; OUTPATIENTS; VALIDATION; PREDICTORS AB This Study examined significant others' expressed emotion (EE) and a closely related construct, perceived criticism, as predictors of cognitive-behavioral therapy outcome in a sample of 40 patients with social phobia (social anxiety disorder). Patients enrolled in group therapy for social phobia completed pre- and post-treatment questionnaire measures of perceived criticism and anxious and depressive symptoms. Designated significant others were assessed for the components of high EE (criticism, hostility and emotional overinvolvement) using the Camberwell Family Interview. It was hypothesized that these high-EE components and patients' perceived criticism would be associated with poorer treatment outcome, and results ran counter to these expectations. Controlling for initial social phobia severity, lower levels of perceived criticism predicted treatment dropout. There was also a nonsignificant trend for participants with a significant other rated as high in emotional overinvolvement to show less change on a composite symptom measure. Findings from this Study suggest that close relationships impact the Outcome of cognitive-behavioral interventions for social phobia. (c) 2006 Elsevier Ltd. All rights reserved. C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. Boston Univ, Sch Social Work, Boston, MA 02215 USA. RP Fogler, JM (reprint author), Boston VA Healthcare Syst, Natl Ctr PTSD, 116 B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM Jason.Fogler@bmc.org RI Hofmann, Stefan/B-8769-2014; OI Hofmann, Stefan/0000-0002-3548-9681; Tompson, Martha /0000-0003-0557-7856 NR 60 TC 20 Z9 21 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD FEB PY 2007 VL 45 IS 2 BP 235 EP 249 DI 10.1016/j.brat.2006.03.002 PG 15 WC Psychology, Clinical SC Psychology GA 125PL UT WOS:000243454200005 PM 16635478 ER PT J AU Jeffery, IB Madden, SF McGettigan, PA Perriere, G Culhane, AC Higgins, DG AF Jeffery, Ian B. Madden, Stephen F. McGettigan, Paul A. Perriere, Guy Culhane, Aedin C. Higgins, Desmond G. TI Integrating transcription factor binding site information with gene expression datasets SO BIOINFORMATICS LA English DT Article ID PROSTATE-CANCER CELLS; CO-INERTIA ANALYSIS; MALIGNANT PROSTATE; RECEPTOR; ACTIVATION; PROTEIN; DIFFERENTIATION; IDENTIFICATION; PROMOTER; BENIGN AB Motivation: Microarrays are widely used to measure gene expression differences between sets of biological samples. Many of these differences will be due to differences in the activities of transcription factors. In principle, these differences can be detected by associating motifs in promoters with differences in gene expression levels between the groups. In practice, this is hard to do. Results: We combine correspondence analysis, between group analysis and co-inertia analysis to determine which motifs, from a database of promoter motifs, are strongly associated with differences in gene expression levels. Given a database of motifs and gene expression levels from a set of arrays, the method produces a ranked list of motifs associated with any specified split in the arrays. We give an example using the Gene Atlas compendium of gene expression levels for human tissues where we search for motifs that are associated with expression in central nervous system (CNS) or muscle tissues. Most of the motifs that we find are known from previous work to be strongly associated with expression in CNS or muscle. We give a second example using a published prostate cancer dataset where we can simply and clearly find which transcriptional pathways are associated with differences between benign and metastatic samples. C1 Natl Univ Ireland Univ Coll Dublin, Conway Inst, Dublin 4, Ireland. Univ Lyon 1, CNRS, UMR 5558, Lab Biometrie & Biol Evolut, F-69622 Villeurbanne, France. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Jeffery, IB (reprint author), Natl Univ Ireland Univ Coll Dublin, Conway Inst, Dublin 4, Ireland. EM Ian.Jeffery@ucd.ie RI Higgins, des/J-6314-2012; Jeffery, Ian/I-4010-2013; OI McGettigan, Paul/0000-0001-5815-8394; Higgins, Des/0000-0002-3952-3285; Jeffery, Ian/0000-0001-9183-7292 NR 55 TC 24 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD FEB 1 PY 2007 VL 23 IS 3 BP 298 EP 305 DI 10.1093/bioinformatics/btl597 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 134ZX UT WOS:000244124500006 PM 17127681 ER PT J AU Geller, DA AF Geller, Daniel A. TI The promise and challenge of obsessive-compulsive disorder research SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID CHILD-BEHAVIOR CHECKLIST; TOURETTES SYNDROME; SCALE; TWIN C1 Massachusetts Gen Hosp, Pediat OCD Program, Dept Psychiat, Boston, MA 02114 USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat OCD Program, Dept Psychiat, YAW 6A,Fruit St, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 2007 VL 61 IS 3 BP 263 EP 265 DI 10.1016/j.biopsych.2006.12.012 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 131MM UT WOS:000243873100001 PM 17241827 ER PT J AU Hounie, AG Pauls, DL do Rosario-Campos, MC Mercadante, MT Diniz, JB De Mathis, MA De Mathis, ME Chacon, P Shavitt, RG Curi, M Guilherme, L Miguel, EC AF Hounie, Ana Gabriela Pauls, David L. do Rosario-Campos, Maria Conceicao Mercadante, Marcos Tomanik Diniz, Juliana Belo De Mathis, Maria Alice De Mathis, Maria Eugenia Chacon, Priscila Shavitt, Roseli Gedanke Curi, Mariana Guilherme, Luiza Miguel, Euripedes Constantino TI Obsessive-compulsive spectrum disorders and rheumatic fever: A family study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE family study; obsessive-compulsive disorder; rheumatic fever; tics; Tourette ID SCHOOL-AGE-CHILDREN; SYDENHAMS CHOREA; TOURETTES-SYNDROME; SCHIZOPHRENIA; RELIABILITY; DIAGNOSIS; INTERVIEW; PHENOTYPE; SCHEDULE; SYMPTOMS AB Background: Obsessive-compulsive spectrum disorders (OCSDs) are more frequent inpatients with active or prior rheumatic fever (RF), suggesting that OCSD and RF may share underlying etiologic mechanisms. Our objective was to estimate the frequency of OCSD in first-degree relatives (FDRs) of RF patients and controls to determine whether there is a familial relationship between OCSD and RF. Methods: This is a case-control family study. Of the 98 probands included in this study, 31 bad RF without Sydenham's chorea (SO and bad 131 relatives, 28 bad RF with SC and had 120 relatives, and 39 were controls without RF. All probands, 87.9% of the RF FDRs and 93.7% of the control FDRs were assessed directly with structured psychiatric interviews and best-estimate diagnoses were assigned. Odds ratios of morbid risks were estimated using logistic regression by the generalized estimating equations (GEE) method and compared between groups. Results: The rate of OCSDs was significantly higher among FDRs of RF probands than among FDRs of controls (n=37; 14.7% vs. n= 10; 7.3%, i=.0279). A diagnosis of OCSDs in an RF proband was associated with a higher rate of OCSDs among FDRs when compared to control FDRs (p-GEE=.02). There was a trend for a higher rate of OCSDs among FDRs of RF probands presenting no OCSD, although the difference was not significant (p-GEE=.09). Conclusion: The results are consistent with the hypothesis that a familial relationship exists between OCSD and RF, since an OCSD in the RF proband was found to increase the risk qf OCSDs among FDRs. Additional neuroimmunological and genetic studies involving larger samples are needed to./urther elucidate this apparentfamilial relationship between RF and OCSD. C1 Univ Sao Paulo, Inst Psiquiatria, Fac Med, Sch Med, BR-05403010 Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA USA. Univ Fed Bahia, Dept Neuropsychiat, MCdrC, BR-41170290 Salvador, BA, Brazil. Univ Sao Paulo, Sch Med, Heart Inst, BR-05403010 Sao Paulo, Brazil. Millenium Inst, Inst Immunol Invest, Arlington, VA USA. Mackenzie Presbyterian Univ, Pervas Dev Disorder Program, Sao Paulo, Brazil. RP Hounie, AG (reprint author), Univ Sao Paulo, Inst Psiquiatria, Fac Med, Sch Med, Rua Dr Oviedo Pires Campos,785 Cerqueira Cesar, BR-05403010 Sao Paulo, Brazil. EM anah@protoc.com.br RI Miguel, Euripedes/B-2871-2008; de mathis, maria alice/D-7269-2012; Diniz, Juliana/D-2503-2011; Chacon, Priscila/G-9401-2012; Guglielmi, Luiza/E-7676-2013; Curi, Mariana/E-8468-2011; do Rosario, Maria Conceicao/E-5213-2012 OI Diniz, Juliana/0000-0001-9486-3779; do Rosario, Maria Conceicao/0000-0002-9687-0072 NR 27 TC 28 Z9 29 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 2007 VL 61 IS 3 BP 266 EP 272 DI 10.1016/j.biopsych.2006.02.021 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 131MM UT WOS:000243873100002 PM 16616727 ER PT J AU Stewart, SE Rosario, MC Brown, TA Carter, AS Leckman, JF Sukhodolsky, D Katsovitch, L King, R Geller, D Pauls, DL AF Stewart, S. Evelyn Rosario, Maria C. Brown, Timothy A. Carter, Alice S. Leckman, James F. Sukhodolsky, Denis Katsovitch, Liliya King, Robert Geller, Daniel Pauls, David L. TI Principal components analysis of obsessive-compulsive disorder symptoms in children and adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Article DE adolescents; children; dimension; factor; obsessive-compulsive disorder; phenomenology ID SEROTONIN REUPTAKE INHIBITORS; FACTOR-ANALYZED SYMPTOM; LA-TOURETTE-SYNDROME; SEGREGATION ANALYSIS; TIC DISORDERS; FOLLOW-UP; DIMENSIONS; FAMILY; SCALE; PREDICTORS AB ; Background: Obsessive-compulsive disorder (OCD) has a broadly diverse clinical expression that may reflect etiologic heterogeneity. Several adult studies have identified consistent symptom dimensions of OCD. The purpose of this, study was to conduct an exploratory principal components analysis of obsessive-compulsive (OC)symptoms in children and adolescents with OCD to identify improved phenotypes for future studies. Methods: This study examined 1 lifetime occurrence of OC symptoms included in the 13 symptom categories of the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Principal components analysis with promax rotation was performed on 231 children and adolescents with OCD and compared with results of similar adult studies. Results. A four-factor solution emerged explaining 59.8% of symptom variance characterized by 1) symmetry/ordering-repeating/checking ; 2) contamination/cleaning/aggressive; 3) boarding; and 4) sexual/religious symptoms. All factors included core symptoms that have been consistently observed in adult studies of OCD. Conclusions: In children and adolescents, OCD is a multidimensional disorder. Symptom dimensions are predominantly congruent with those described in similar studies of adults with OCD, suggesting fair y consistent covariation of OCD symptoms through the developmental course. Future work is required to understand changes in specific symptom dimensions observed across the life span. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Dept Psychiat, Boston, MA 02114 USA. Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. RP Pauls, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA. EM dpauls@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; do Rosario, Maria Conceicao/E-5213-2012; OI do Rosario, Maria Conceicao/0000-0002-9687-0072; Sukhodolsky, Denis/0000-0002-5401-792X; Stewart, S. Evelyn/0000-0002-0994-6383 FU NIMH NIH HHS [K08 MH01481, MH49351]; NINDS NIH HHS [R01 NS16648] NR 40 TC 59 Z9 60 U1 4 U2 12 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 FEB 1 PY 2007 VL 61 IS 3 BP 285 EP 291 DI 10.1016/j.biopsych.2006.08.040 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 131MM UT WOS:000243873100005 PM 17161383 ER PT J AU Geller, D Petty, C Vivas, F Johnson, J Pauls, D Biederman, J AF Geller, Daniel Petty, Carter Vivas, Fe Johnson, Jessica Pauls, David Biederman, Joseph TI Examining the relationship between obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in children and adolescents: A familial risk analysis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; child and adolescent; familial risk; genetic; obsessive-compulsive disorder ID DEFICIT HYPERACTIVITY DISORDER; LA-TOURETTES SYNDROME; ANXIETY DISORDERS; LEARNING-DISABILITIES; GENETIC-RELATIONSHIP; EPIDEMIOLOGY; PARENTS; DEPRESSION; HISTORY; GIRLS AB Background: To use family study methodology to examine the relationship between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. Methods: We assessed for ADHD and OCD in the 1533,first-degree relatives of three groups of index children: those with ADHD and OCD, those with ADHD but no OCD, and matched controls with neither disorder. Results: The risk for ADHD was similarly elevated in families of ADHD youth with (18.9%) and without OCD (20.1%; p =.91), and both groups bad significantly higher rates of ADHD compared with controls (4.6%; p <= .001), which was consistent with previous research showing a strong familial risk for ADHD. The risk for OCD was significantly elevated only among relatives of youth with ADHD plus comorbid OCD (13.0% compared with controls (.5%; p <= . 001) and was consistent with previous research showing a strong familial risk for OCD. Relatives affected with ADHD had a signficantly elevated risk for OCD compared with relatives unaffected by ADHD (7.4% vs. 13%; P < .001), suggestive of co-segregation between these disorders. There was no evidence of nonrandom mating between ADHD- and OCD-affected spouses. Conclusions: These results extend previously reported findings regarding the heritability of both ADHD and OCD and provide new evidence of a familial relationship between ADHD and pediatric OCD that best fits the hypothesis of a unique familial subtype. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Program, Boston, MA 02113 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02113 USA. Massachusetts Gen Hosp, Psychiat Neurogenet Unit, Ctr Human Genet, Boston, MA 02113 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Geller, D (reprint author), Massachusetts Gen Hosp, Pediat OCD Program, 32 Fruit St,YAW 6900, Boston, MA 02113 USA. EM dageller@partners.org NR 58 TC 26 Z9 27 U1 3 U2 5 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 FEB 1 PY 2007 VL 61 IS 3 BP 316 EP 321 DI 10.1016/j.biopsych.2006.03.083 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 131MM UT WOS:000243873100009 PM 16950231 ER PT J AU Keuthen, NJ Makris, N Schlerf, JE Martis, B Savage, CR McMullin, K Seidman, LJ Schmahmann, JD Kennedy, DN Hodge, SM Rauch, SL AF Keuthen, Nancy J. Makris, Nikos Schlerf, John E. Martis, Brian Savage, Cary R. McMullin, Katherine Seidman, Larry J. Schmahmann, Jeremy D. Kennedy, David N. Hodge, Steven M. Rauch, Scott L. TI Evidence for reduced cerebellar volumes in trichotillomania SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cerebellum; hair pulling; morphometry; MRI; OC spectrum; trichotillomania ID OBSESSIVE-COMPULSIVE DISORDER; BASAL GANGLIA VOLUMES; NEUROPSYCHOLOGICAL TEST-PERFORMANCE; ANATOMICALLY SPECIFIED METHOD; CEREBRAL-BLOOD-FLOW; TOURETTES-SYNDROME; MRI; PARCELLATION; INVENTORY; RELIABILITY AB Background. Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. Methods: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSH-IV diagnoses of TTM and 12 age-, education-, and gender-matcbed normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. Results: As predicted, significant group differences were reported for CBM raw conical volumes (p =.008) that survived correction for total brain volume (TBV; p =.037) and bead circumference (HC;p =.011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV), Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p =.008), with smaller volumes associated with more severe TTM symptoms. Conclusions: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reportedfor the TTM versus NC groups. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Martinos Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Boston, MA 02114 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Psychiat & Behav Sci, Kansas City, KS 66103 USA. Washington Univ, St Louis, MO USA. Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. RP Keuthen, NJ (reprint author), Trichotillomania Clin & Res Unit, Simches Res Bldg,Floor 2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org RI Citations, TLC SAB/C-4006-2011; Kennedy, David/H-3627-2012 NR 59 TC 34 Z9 35 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 2007 VL 61 IS 3 BP 374 EP 381 DI 10.1016/j.biopsych.2006.06.013 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 131MM UT WOS:000243873100017 PM 16945351 ER PT J AU Cutler, C Li, S Ho, V Koreth, J Alyea, E Soiffer, RJ Antin, JH AF Cutler, C. Li, S. Ho, V. Koreth, J. Alyea, E. Soiffer, R. J. Antin, J. H. TI Long-term outcome of methotrexate-free GVHD prophylaxis using sirolimus and tacrolimus in matched related (MRD) and unrelated donor (URD) peripheral blood stem cell transplantation (PBSCT) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 7 BP 5 EP 5 DI 10.1016/j.bbmt.2006.12.010 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300008 ER PT J AU Haspot, F Fehr, T Hogan, T Honjo, T Sykes, M AF Haspot, F. Fehr, T. Hogan, T. Honjo, T. Sykes, M. TI PD-I is required to induce peripheral CD8 T cell tolerance in recipients of allogeneic bone marrow transplantation with anti-CD154 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Massachusetts Gen Hosp, Harvard Med Sch, BMT TBRC, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Med, Dept Immunol & Genom Med, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 24 BP 11 EP 11 DI 10.1016/j.bbmt.2006.12.027 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300025 ER PT J AU Ho, VT Dranoff, G Kim, H Pasek, M Cutler, C Koreth, J Alyea, EP Antin, JH Soiffer, RJ AF Ho, V. T. Dranoff, G. Kim, H. Pasek, M. Cutler, C. Koreth, J. Alyea, E. P. Antin, J. H. Soiffer, R. J. TI GM-CSF secreting leukemia cell vaccinations after allogeneic reduced-intensity peripheral blood stem cell transplantation (SCT) for advanced myelodysplastic syndrome (MDS) or refractory acute myeloid leukemia (AML) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 59 BP 24 EP 24 DI 10.1016/j.bbmt.2006.12.062 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300060 ER PT J AU Avigan, D Rosenblatt, J Vasir, B Wu, Z Bisonette, A Macnamarra, C Uhl, L Lenaban, C Miller, K Joyce, R Levine, J Proper, J Forino, P Donhagoda, D Munshi, N Kufe, D AF Avigan, D. Rosenblatt, J. Vasir, B. Wu, Z. Bisonette, A. Macnamarra, C. Uhl, L. Lenaban, C. Miller, K. Joyce, R. Levine, J. Proper, J. Forino, P. Donhagoda, D. Munshi, N. Kufe, D. TI Vaccination with dendritic cell myeloma fusions alone or in conjunction with stem cell transplantation for patients with multiple myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 63 BP 26 EP 26 DI 10.1016/j.bbmt.2006.12.066 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300064 ER PT J AU Duncan, CN Buonanno, MP Cormier, C Lehmann, LE AF Duncan, C. N. Buonanno, M. P. Cormier, C. Lehmann, L. E. TI Chest radiograph versus computed tomography in the diagnosis of acute pulmonary complications in pediatric stem cell transplant SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 67 BP 27 EP 28 DI 10.1016/j.bbmt.2006.12.070 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300068 ER PT J AU Patel, RC Burzynski, JA Ochoa-Bayona, JL Toro, J Greene, RE Freytes, CO AF Patel, R. C. Burzynski, J. A. Ochoa-Bayona, J. L. Toro, J. Greene, R. E. Freytes, C. O. TI Efficacy and toxicity of a second autologous peripheral blood stem cell transplant for patients with relapsed or recurrent multiple myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 152 BP 57 EP 57 DI 10.1016/j.bbmt.2006.12.156 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300153 ER PT J AU Schiller, GJ Sohn, JP Malone, P Bartoni, K Habtemariam, B Paquette, P deVos, S Territo, M AF Schiller, G. J. Sohn, J. P. Malone, P. Bartoni, K. Habtemariam, B. Paquette, P. deVos, S. Territo, M. TI Phase I/II trial of bortezomib maintenance following autologous peripheral blood progenitor cell transplantation as treatment for intermediate- and advanced-stage multiple myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 153 BP 57 EP 57 DI 10.1016/j.bbmt.2006.12.157 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300154 ER PT J AU Duncan, CN Mayers, KL Lehmann, LE AF Duncan, C. N. Mayers, K. L. Lehmann, L. E. TI Fascutis as a manifestation of chronic graft versus host disease following allogeneic hematopoietic stem cell transplantation in children and adolescents: A single institution experience SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 160 BP 60 EP 60 DI 10.1016/j.bbmt.2006.12.164 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300161 ER PT J AU Lehmann, LE Buonanno, M Duncan, CN AF Lehmann, L. E. Buonanno, M. Duncan, C. N. TI Relapse following busulfan/cyclophosphamide conditioning in children and adolescents undergoing hla-identical sibling transplantation for stable phase chronic myeloid leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 167 BP 62 EP 63 DI 10.1016/j.bbmt.2006.12.171 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300168 ER PT J AU Rosenblatt, J Wu, Z Lenahan, C Vasir, B Bisonette, A Kufie, D Avigan, D AF Rosenblatt, J. Wu, Z. Lenahan, C. Vasir, B. Bisonette, A. Kufie, D. Avigan, D. TI Stimulation of anti-tumor immunity using dendritic cell/tumor fusions and anti CD3/CD28 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 188 BP 69 EP 70 DI 10.1016/j.bbmt.2006.12.192 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300189 ER PT J AU Lin, Y Means, T Alyea, EP Canning, CM Soiffer, RJ Ritz, J Wu, CJ AF Lin, Y. Means, T. Alyea, E. P. Canning, C. M. Soiffer, R. J. Ritz, J. Wu, C. J. TI Effective graft-versus-leukemia responses are associated with the presence of nucleic acid-immunoglobulin complexes that stimulate toll-like receptors (TLR) 8 and 9 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 332 BP 120 EP 121 DI 10.1016/j.bbmt.2006.12.337 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300333 ER PT J AU Ballen, K Nadentanee, A Grahant, M Jaing, TH Tan, P Eames, G Rosenthal, J Karanes, C Gjertson, D Wang, B Petz, L Chow, R AF Ballen, K. Nadentanee, A. Grahant, M. Jaing, T. -H. Tan, P. Eames, G. Rosenthal, J. Karanes, C. Gjertson, D. Wang, B. Petz, L. Chow, R. TI Outcomes of double cord blood transplantation (DCBT) in a diverse population SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Arizona, Arizona Med Ctr, Tucson, AZ 85724 USA. Chang Gung Univ, Chang Gung Childrens Hosp, Linkou, Taiwan. Mt Elizabeth Hosp, Singapore, Singapore. Cook Childrens Hosp, Ft Worth, TX USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. StemCyte Int Cord Blood Ctr, Arcadia, CA USA. StemCyte Taiwan Natl Cord Blood Ctr, Linkou, Taiwan. StemCyte Res Inst, Arcadia, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 336 BP 122 EP 122 DI 10.1016/j.bbmt.2006.12.341 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300337 ER PT J AU Cutler, C Haspel, R Kao, G Ho, V Alyea, W Koreth, J Dey, B Spitzer, T Soiffer, RJ Antin, JH Ballen, K AF Cutler, C. Haspel, R. Kao, G. Ho, V. Alyea, W. Koreth, J. Dey, B. Spitzer, T. Soiffer, R. J. Antin, J. H. Ballen, K. TI Double umbilical cord blood transplantation with reduced intensity conditioning and sirolimus-based GVHD prophylaxis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 337 BP 122 EP 122 DI 10.1016/j.bbmt.2006.12.342 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300338 ER PT J AU Nademance, A Graham, M Ballen, K Tan, AM Rosenthal, J Karanes, C Eames, G Tan, P Jaing, TH Wang, B Wu, T Gjertson, D Petz, L Chow, R Forman, S AF Nademance, A. Graham, M. Ballen, K. Tan, A. M. Rosenthal, J. Karanes, C. Eames, G. Tan, P. Jaing, T. -H. Wang, B. Wu, T. Gjertson, D. Petz, L. Chow, R. Forman, S. TI Adult patients with malignancies transplanted with plasma depleted cord blood (PD CB) - A retrospective audited analysis of 68 patients SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Arizona, Med Ctr, Tucson, AZ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. KK Womens & Childrens Hosp, Singapore, Singapore. Cook Chicago Hosp, Ft Worth, TX USA. Mt Elisabeth Hosp, Singapore, Singapore. Chang Gung Childrens Hosp & Univ, Linkou, Taiwan. Stem Cyte Int Cord Blood Ctr, Arcadia, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 363 BP 131 EP 132 DI 10.1016/j.bbmt.2006.12.368 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300364 ER PT J AU O'Connor, MP Myers, K Melone, M Lehmann, L AF O'Connor, M. P. Myers, K. Melone, M. Lehmann, L. TI Stem cell transplantation for osteopetrosis: One center's experience SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 401 BP 144 EP 145 DI 10.1016/j.bbmt.2007.01.031 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300402 ER PT J AU Tierney, DK Schmit-Pokorny, K Sorensen, S McDermott, K Devine, H AF Tierney, D. K. Schmit-Pokorny, K. Sorensen, S. McDermott, K. Devine, H. TI Do we know the educational needs of nurses working with physicians who refer patients to transplant centers? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT Meeting 2007 CY FEB 08-12, 2007 CL Keystone, CO SP Amer Soc Blood & Marrow Transplantat, Ctr Int Blood & Marrow Transplantat Res, Pfizer Inc C1 Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ Nebraska Med Ctr, Omaha, NE USA. MD Anderson Canc Ctr, Houston, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Arthur G James Canc Hosp, Richard J Solove Res Inst, Columbus, OH USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 SU 2 MA 416 BP 149 EP 149 DI 10.1016/j.bbmt.2007.01.046 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QU UT WOS:000244028300417 ER PT J AU Koreth, J Cutler, CS Djulbegovic, B Behl, R Schlossman, RL Munshi, NC Richardson, PG Anderson, KC Soiffer, RJ Alyea, EP AF Koreth, John Cutler, Corey S. Djulbegovic, Benjamin Behl, Rajesh Schlossman, Robert L. Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. Soiffer, Robert J. Alyea, Edwin P., III TI High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE multiple myeloma; autologous transplantation; meta-analysis ID STEM-CELL TRANSPLANTATION; STANDARD CHEMOTHERAPY; CLINICAL-TRIALS; SURVIVAL; DEXAMETHASONE; MELPHALAN; BIAS; CHEMORADIOTHERAPY; EPIDEMIOLOGY; SUPPORT AB Myeloablative high-dose therapy and single autologous stem cell transplantation (HDT) is frequently performed early in the course of multiple myeloma, supported by some randomized controlled trials (RCTs) indicating overall survival (OS) and progression-free survival (PFS) benefit compared with non-myeloablative standard-dose therapy (SDT). Other RCTs, however, suggest variable benefit. We therefore undertook a systematic review and meta-analysis of all RCTs evaluating upfront HDT versus SDT in myeloma. The primary objective was to quantify OS benefit with HDT, with PFS benefit a secondary objective. Anticipating heterogeneity, sensitivity and subgroup analyses were undertaken to assess robustness of results. Assessment of harms (treatment-related mortality) was also undertaken. We searched the PubMed, Embase, and Cochrane Collection of Controlled Trials databases using the terms myeloma combined with autologous or transplant or myeloablative or stem cell. In total, 3407 articles were accessed, and 10 RCTs prospectively comparing upfront HDT with SDT, with >= 2-year follow-up, and reporting OS benefit on an intent-to-treat basis were identified. Two reviewers independently extracted study characteristics, interventions, and outcomes. Hazard ratios (with 95% confidence interval) were determined. Nine studies comprising 2411 patients were fully analyzed. Significant heterogeneity was present. The combined hazard of death with HDT was 0.92 (95% confidence interval, 0.74-1.13). The combined hazard of progression with HDT was 0.75 (95% confidence interval, 0.59-0.96). The totality of the randomized data indicates PFS benefit but not OS benefit for HDT with single autologous transplantation performed early in multiple myeloma. Sensitivity and subgroup analyses supported the findings and indicated that, contrary to current reimbursement criteria, PFS benefit with upfront HDT is not restricted to chemoresponsive myeloma. However, the overall risk of developing treatment-related mortality with HDT was increased significantly (odds ratio, 3.01; 95% confidence interval, 1.64-5.50). Hence, evaluating alternative therapeutic options upfront may also be reasonable. C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. H Lee Moffitt Canc Ctr & Res Inst, Hematol Malignancies Program, Tampa, FL USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM John_Koreth@dfci.harvard.edu RI Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 NR 38 TC 101 Z9 114 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2007 VL 13 IS 2 BP 183 EP 196 DI 10.1016/j.bbmt.2006.09.010 PG 14 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133QT UT WOS:000244028200006 PM 17241924 ER PT J AU Choi, J Bodugoz-Senturk, H Kung, HJ Malhi, AS Muratoglu, OK AF Choi, Jeeyoung Bodugoz-Senturk, Hatice Kung, Hsiang J. Malhi, Arnaz S. Muratoglu, Orhun K. TI Effects of solvent dehydration on creep resistance of poly(vinyl alcohol) hydrogel SO BIOMATERIALS LA English DT Article DE poly(vinyl alcohol); poly(ethylene glycol); hydrogel; dehydration; osteochondral defects ID ARTICULAR-CARTILAGE REPAIR; DEFECTS; KNEE; TRANSPLANTATION; MOSAICPLASTY AB As a synthetic replacement material for osteochondral defect repair, poly(vinyl alcohol) (PVA) hydrogels offer a great potential due to their high water content and strong mechanical integrity. To survive the high stress environment in the joint space, high creep resistance becomes one of the key requirements for hydrogel implants. We hypothesized that reducing the equilibrium water content (EWC) of hydrogels would improve their creep resistance. We investigated the effect of dehydration of PVA theta-gels in various solvent/solution media followed by rehydration in saline solution. Decreasing EWC increased the creep resistance of PVA theta-gels. The most effective medium was isopropyl alcohol for reducing the EWC and increasing the creep resistance of PVA theta-gels. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM omuratoglu@partners.org NR 17 TC 21 Z9 24 U1 2 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2007 VL 28 IS 5 BP 772 EP 780 DI 10.1016/j.biomaterials.2006.09.049 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 118SE UT WOS:000242961200002 PM 17070904 ER PT J AU Ito, T Yeo, Y Highley, CB Bellas, E Benitez, CA Kohane, DS AF Ito, Taichi Yeo, Yoon Highley, Christopher B. Bellas, Evangelia Benitez, Carlos A. Kohane, Daniel S. TI The prevention of peritoneal adhesions by in situ cross-linking hydrogels of hyaluronic acid and cellulose derivatives SO BIOMATERIALS LA English DT Article DE post-operative adhesion; hydrogel; hyaluronic acid; carboxymethylcellulose; methylcellulose; hydroxylpropylmethylcellulose ID POSTOPERATIVE ABDOMINAL ADHESIONS; REDUCTION; CARBOXYMETHYLCELLULOSE; DEGRADATION; MEMBRANE; OXYGEN; MODEL; GELS AB Post-operative peritoneal adhesions can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We have designed and synthesized injectable hydrogels that are formed by mixing hydrazide-modified hyaluronic acid (HA) with aldehyde-modified versions of cellulose derivatives such as carboxymethylcellulose (CMC), hydroxypropylmethylcellulose (HPMC), and methylcellulose (MC). Gelation of these hydrogels occurred in less than 1 min, and had higher shear moduli than that of HA-HA gel (HAX). Hydrogels degraded in the presence of hyaluronidase in vitro, with HA-MC and HA-HPMC degrading more slowly than HAX and HA-CMC. The aldehyde-modified cellulose derivatives showed dose-dependent mild-to-moderate cytotoxicity to mesothelial cells and macrophages in vitro, but all were biocompatible in the murine peritoneum, causing no adhesions for 3 weeks. All the cellulose-derived gels showed efficacy in reducing the area of adhesion formation in a rabbit sidewall defect-bowel abrasion model. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Pediat Intens Care, Lab Biomat & Drug Delivery, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02142 USA. Univ Massachusetts, Dept Chem Engn, Amherst, MA 01003 USA. RP Kohane, DS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Pediat Intens Care, Lab Biomat & Drug Delivery, Bartlett Extens 413,55 Fruit St, Boston, MA 02114 USA. EM dkohane@partners.org FU NIDDK NIH HHS [DK073626]; NIGMS NIH HHS [R01 GM073626] NR 21 TC 102 Z9 105 U1 10 U2 67 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2007 VL 28 IS 6 BP 975 EP 983 DI 10.1016/j.biomaterials.2006.10.021 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 122II UT WOS:000243219000009 PM 17109954 ER PT J AU Kohane, DS AF Kohane, Daniel S. TI Microparticles and nanoparticles for drug delivery SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE biocompatibility; local delivery; systemic delivery; toxicity ID PROTEIN-SUGAR PARTICLES; LARGE POROUS PARTICLES; IN-VIVO; MICROSPHERES; LIPOSOMES; BUPIVACAINE; RELEASE; SYSTEM; BIOCOMPATIBILITY; DEXAMETHASONE AB Particulate drug delivery systems have become important in experimental pharmaceutics and clinical medicine. The distinction is often made between micro- and nanoparticles, being particles with dimensions best described in micrometers and nanometers respectively. That size difference entails real differences at many levels, from formulation to in vivo usage. Here I will discuss those differences and provide examples of applications, for local and systemic drug delivery. I will outline a number of challenges of interest in particulate drug delivery. C1 Massachusetts Gen Hosp, Lab Biomat & Drug Delivery, Div Crit Pediat Care, Boston, MA 02114 USA. RP Kohane, DS (reprint author), Massachusetts Gen Hosp, Lab Biomat & Drug Delivery, Div Crit Pediat Care, Bartlett Extens 413,55 Fruit St, Boston, MA 02114 USA. EM dkohane@partners.org FU NIGMS NIH HHS [GM073626] NR 30 TC 121 Z9 121 U1 3 U2 46 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD FEB 1 PY 2007 VL 96 IS 2 BP 203 EP 209 DI 10.1002/bit.21301 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 125NP UT WOS:000243449100001 PM 17191251 ER PT J AU Huxley, N Baldessarini, RJ AF Huxley, Nancy Baldessarini, Ross J. TI Disability and its treatment in bipolar disorder patients SO BIPOLAR DISORDERS LA English DT Review DE bipolar disorder; disability; function; psychotherapy; rehabilitation; vocational ID RANDOMIZED CLINICAL-TRIAL; MANIC-DEPRESSIVE PATIENTS; FAMILY-FOCUSED TREATMENT; LONGITUDINAL FOLLOW-UP; QUALITY-OF-LIFE; COGNITIVE THERAPY; I DISORDER; RELAPSE PREVENTION; SOCIAL-ADJUSTMENT; NEUROPSYCHOLOGICAL FUNCTION AB Bipolar disorders (BPD) are major, life-long psychiatric illnesses found in 2-5% of the population. Prognosis for BPD was once considered relatively favorable, but contemporary findings suggest that disability and poor outcomes are prevalent, despite major therapeutic advances. Syndromal recovery from acute episodes of mania or bipolar major depression is achieved in as many as 90% of patients given modern treatments, but full symptomatic recovery is achieved slowly, and residual symptoms of fluctuating severity and functional impact are the rule. Depressive-dysthymic-dysphoric morbidity continues in more than 30% of weeks in follow-up from initial episodes as well as later in the illness-course. As few as 1/3 of BPD patients achieve full social and occupational functional recovery to their own premorbid levels. Pharmacotherapy, though the accepted first-line treatment for BPD patients, is insufficient by itself, encouraging development of adjunctive psychological treatments and rehabilitative efforts to further limit morbidity and disability. Interpersonal, cognitive-behavioral, and psychoeducational therapies all show promise for improving symptomatic and functional outcomes. Much less is known about how these and more specific rehabilitative interventions might improve vocational functioning in BPD patients. C1 Massachusetts Gen Hosp, McLean Div, Harvard Med Sch, Dept Psychiat,Int Consortium Bipolar Disorder Res, Belmont, MA USA. RP Huxley, N (reprint author), McLean Hosp, Schizophrenia & Bipolar Disorders Program, N Belknap 3,115 Mill St, Belmont, MA 02478 USA. EM nancy_huxley@hms.harvard.edu NR 122 TC 126 Z9 128 U1 1 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB-MAR PY 2007 VL 9 IS 1-2 BP 183 EP 196 DI 10.1111/j.1399-5618.2007.00430.x PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 134UF UT WOS:000244108900018 PM 17391360 ER PT J AU Moghrabi, A Levy, DE Asselin, B Barr, R Clavell, L Hurwitz, C Samson, Y Schorin, M Dalton, VK Lipshultz, SE Neuberg, DS Gelber, RD Cohen, HJ Sallan, SE Silverman, LB AF Moghrabi, Albert Levy, Donna E. Asselin, Barbara Barr, Ronald Clavell, Luis Hurwitz, Craig Samson, Yvan Schorin, Marshall Dalton, Virginia K. Lipshultz, Steven E. Neuberg, Donna S. Gelber, Richard D. Cohen, Harvey J. Sallan, Stephen E. Silverman, Lewis B. TI Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia SO BLOOD LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; MINIMAL RESIDUAL DISEASE; ESCHERICHIA-COLI-ASPARAGINASE; CRANIAL RADIATION-THERAPY; ADVANCED BREAST-CANCER; LONG-TERM SURVIVORS; NEUROPSYCHOLOGICAL PERFORMANCE; DOXORUBICIN THERAPY; RISK PATIENTS; CNS RELAPSE AB The Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium Protocol 95-01 was designed to minimize therapy-related morbidity for children with newly diagnosed ALL without compromising efficacy. Patients participated in randomized comparisons of (1) doxorubicin given with or without dexrazoxane, a cardioprotectant (high-risk patients), (2) intensive intrathecal chemotherapy and cranial radiation (standard-risk patients), and (3) Erwinia and Escherichia coli asparaginase (all patients). Between 1996 and 2000, 491 patients (aged 0-18 years) were enrolled (272 standard risk and 219 high risk). With a median of 5.7 years of followup, the estimated 5-year event-free survival (EFS) for all patients was 82% +/- 2%. Dexrazoxane did not have a significant impact on the 5-year EFS of high-risk patients (P =.99), and there was no significant difference in outcome of standard-risk patients based on type of central nervous system (CNS) treatment (P =.26). Compared with E coli asparaginase, Erwinia asparaginase was associated with a lower incidence of toxicity (10% versus 24%), but also an inferior 5-year EFS (78% +/- 4% versus 89% +/- 3%, P =.01). We conclude that (1) dexrazoxane does not interfere with the antileukemic effect of doxorubicin, (2) intensive intrathecal chemotherapy is as effective as cranial radiation in preventing CNS relapse in standard-risk patients, and (3) once-weekly Erwinia is less toxic than E coli asparaginase, but also less efficacious. C1 Univ Montreal, Hop St Justine, Div Hematol & Oncol, Montreal, PQ H3T 1C5, Canada. Dana Farber Canc Inst, Dept Pediat Oncol Biostat & Computat Biol, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Div Pediat Hematol Oncol, Rochester, NY 14642 USA. McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada. San Jorge Childrens Hosp, Div Pediat Oncol, San Juan, PR USA. Maine Childrens Canc Program, Dept Pediat Hematol Oncol, Scarborough, ME USA. CHU Quebec, Quebec City, PQ, Canada. Tulane Hosp Childrens, Sect Pediat Hematol Oncol, New Orleans, LA USA. Univ Miami, Dept Pediat, Leonard M Miller Sch Med, Holtz Childrens Hosp,Jackson Mem Med Ctr, Miami, FL 33152 USA. Batchelor Childrens Res Inst, Mailman Inst Child Dev, Miami, FL USA. Sylvester Comprehens Canc Ctr, Miami, FL USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Moghrabi, A (reprint author), Univ Montreal, Hop St Justine, Div Hematol & Oncol, 3175,Cote St Catherine, Montreal, PQ H3T 1C5, Canada. EM albert.moghrabi@umontreal.ca FU NCI NIH HHS [P01 CA068484, P01 CA 68484] NR 52 TC 207 Z9 221 U1 1 U2 9 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 FEB 1 PY 2007 VL 109 IS 3 BP 896 EP 904 DI 10.1182/blood-2006-06-027714 PG 9 WC Hematology SC Hematology GA 135CX UT WOS:000244132800017 PM 17003366 ER PT J AU Hirakawa, S Brown, LF Kodama, S Paavonen, K Alitalo, K Detmar, M AF Hirakawa, Satoshi Brown, Lawrence F. Kodama, Shohta Paavonen, Karri Alitalo, Kari Detmar, Michael TI VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TRANSGENIC MICE; MELANOMA METASTASIS; CANCER METASTASIS; RECEPTOR; INDUCTION; VESSELS; CARCINOGENESIS; ANGIOGENESIS; VASCULATURE AB The mechanisms by which tumors metastasize to sentinel and distant lymph nodes, and beyond, are poorly understood. We developed transgenic mice that overexpress vascular endothelial growth factor-C (VEGF-C) and green fluorescent protein specifically in the skin and studied the effects of chemically-induced skin carcinogenesis in this model. We found that in contrast to VEF-A, VEGF-C does not increase the growth of primary tumors, but instead induces expansion of lymphatic networks within sentinel lymph nodes, even before the onset of metastasis. Once the metastatic cells arrived at the sentinel lymph nodes, the extent of lymphangiogenesis at these sites increased. Of importance, in mice with metastasis-containing sentinel lymph nodes, tumors that expressed VEGF-C were more likely to metastasize to additional organs, such as distal lymph nodes and lungs. No metastases were observed in distant organs in the absence of lymph node metastases. These findings indicate an important role of VEGF-C-induced lymph node lymphangiogenesis in the promotion of cancer metastasis beyond the sentinel lymph nodes. VEGF-C is therefore a good target to slow or even prevent the onset of metastasis. C1 ETH, Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Immunobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Ehime Univ, Sch Med, Dept Dermatol, Matsuyama, Ehime 790, Japan. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Helsinki, Biomedicum Helsinki, Lab Mol Canc Biol, Helsinki, Finland. RP Detmar, M (reprint author), ETH, Swiss Fed Inst Technol, Inst Pharmaceut Sci, Wolfgang Pauli Str 10,HCI H303, CH-8093 Zurich, Switzerland. EM michael.detmar@pharma.ethz.ch RI Alitalo, Kari/J-5013-2014 OI Alitalo, Kari/0000-0002-7331-0902 FU NCI NIH HHS [CA92644, CA69184, CA86410, P01 CA092644, R01 CA069184, R01 CA086410]; NHLBI NIH HHS [R01 HL075183] NR 33 TC 259 Z9 285 U1 1 U2 9 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 FEB 1 PY 2007 VL 109 IS 3 BP 1010 EP 1017 DI 10.1182/blood-2006-05-021758 PG 8 WC Hematology SC Hematology GA 135CX UT WOS:000244132800032 PM 17032920 ER PT J AU Chauhan, D Neri, P Velankar, M Podar, K Hideshima, T Fulciniti, M Tassone, P Raje, N Mitsiades, C Mitsiades, N Richardson, P Zawel, L Tran, M Munshi, N Anderson, KC AF Chauhan, Dharminder Neri, Paola Velankar, Mugdha Podar, Klaus Hideshima, Teru Fulciniti, Mariateresa Tassone, Pierfrancesco Raje, Noopur Mitsiades, Constantine Mitsiades, Nicholas Richardson, Paul Zawel, Leigh Tran, Mary Munshi, Nikhil Anderson, Kenneth C. TI Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM) SO BLOOD LA English DT Article ID DEXAMETHASONE-INDUCED APOPTOSIS; OVERCOMES DRUG-RESISTANCE; MARROW STROMAL CELLS; NF-KAPPA-B; GROWTH-FACTOR; CYTOCHROME-C; PROTEASOME INHIBITION; STRUCTURAL BASIS; UP-REGULATION; SMAC PEPTIDE AB Second mitochondria-derived activator of caspases (Smac) promotes apoptosis via activation of caspases. Here we show that a low-molecular-weight Smac mimetic LBW242 induces apoptosis in multiple myeloma (MM) cells resistant to conventional and bortezomib therapies. Examination of purified patient MM cells demonstrated similar results, without significant cytotoxicity against normal lymphocytes and bone marrow stromal cells (BMSCs). Importantly, LBW242 abrogates paracrine MM cell growth triggered by their adherence to BMSCs and overcomes MM cell growth and drug-resistance conferred by interleukin-6 or insulin-like growth factor-1. Overexpression of Bcl-2 similarly does not affect LBW242-induced cytotoxicity. Mechanistic studies show that LBW242-induced apoptosis in MM cells is associated with activation of caspase-8, caspase-9, and caspase-3, followed by PARP cleavage. In human MM xenograft mouse models, LBW242 is well tolerated, inhibits tumor growth, and prolongs survival. Importantly, combining LBW242 with novel agents, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the proteasome inhibitors bortezomib and NPI-0052, as well as with the conventional anti-MM agent melphalan, induces additive/synergistic anti-MM activity. Our study therefore provides the rationale for clinical protocols evaluating LBW242, alone and together with other anti-MM agents, to improve patient outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Boston, MA 02115 USA. Novartis Inst Biomed Res, Dept Oncol, Cambridge, England. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA10070, CA 78373, R01 CA050947, CA 50947] NR 65 TC 106 Z9 111 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 FEB 1 PY 2007 VL 109 IS 3 BP 1220 EP 1227 DI 10.1182/blood-2006-04-015149 PG 8 WC Hematology SC Hematology GA 135CX UT WOS:000244132800057 PM 17032924 ER PT J AU Hutchinson, JN Ensminger, AW Clemson, CM Lynch, CR Lawrence, JB Chess, A AF Hutchinson, John N. Ensminger, Alexander W. Clemson, Christine M. Lynch, Christopher R. Lawrence, Jeanne B. Chess, Andrew TI A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION; X-CHROMOSOME; FUNCTIONAL-ORGANIZATION; SC-35 DOMAINS; POLY(A) RNA; MOUSE; METABOLISM; SPECKLES; GENOME; REPLICATION AB Background: Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment. Results: This screen identified no more than three transcripts; XIST, and two unique noncoding nuclear enriched abundant transcripts ( NEAT) RNAs strikingly located less than 70 kb apart on human chromosome II: NEAT1, a noncoding RNA from the locus encoding for TncRNA, and NEAT2 ( also known as MALAT-1). While the two NEAT transcripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding RNAs. NEAT2 is extraordinarily well conserved for a noncoding RNA, more so than even XIST. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA FISH analyses suggest that these noncoding RNAs function in mRNA metabolism as they demonstrate an intimate association of these RNA species with SC35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts, NEAT1 localizes to the periphery of such domains, whereas the neighboring transcript, NEAT2, is part of the long- sought polyadenylated component of nuclear speckles. Conclusion: Our genome- wide screens in two mammalian species reveal no more than three abundant large non- coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2. The function of these noncoding RNAs in mRNA metabolism is suggested by their high levels of conservation and their intimate association with SC35 splicing domains in multiple mammalian species. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA. RP Chess, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM jhutchinson@chgr.mgh.harvard.edu; ensminger@chgr.mgh.harvard.edu; Christine.Clemson@umassmed.edu; Christopher.Lynch@umassmed.edu; Jeanne.Lawrence@umassmed.edu; chess@chgr.mgh.harvard.edu FU NIGMS NIH HHS [GM68138, R01 GM068138] NR 46 TC 291 Z9 316 U1 1 U2 32 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD FEB 1 PY 2007 VL 8 AR 39 DI 10.1186/1471-2164-8-39 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 137XP UT WOS:000244326600002 PM 17270048 ER PT J AU Garcia-Palacios, V Chung, HY Choi, SJ Sarmasik, A Kurihara, N Lee, JW Galson, DL Collins, R Roodman, GD AF Garcia-Palacios, Veronica Chung, Ho Yeon Choi, Sun Jin Sarmasik, Allye Kurihara, Norlyoshi Lee, Jun Won Galson, Deborah L. Collins, Robert Roodman, G. David TI Eosinophil chemotactic factor-L (ECF-L) enhances osteoclast formation by increasing in osteoclast precursors expression of LFA-1 and ICAM-1 SO BONE LA English DT Article DE ECF-L; osteoclast; RANKL; ICAM-1; LFA-1 ID INTERCELLULAR-ADHESION MOLECULE-1; FUNCTION-ASSOCIATED ANTIGEN-1; FACTOR RECEPTOR FAMILY; DIFFERENTIATION; IDENTIFICATION; PROTEIN; LECTIN; LIGAND; CELLS; INFLAMMATION AB ECF-L is a novel autocrine stimulator of osteoclast (OCL) formation that enhances the effects of 1,25-(OH)(2)D-3 and RANK ligand (RANKL) and is increased in inflammatory conditions such as rheumatoid arthritis. ECF-L acts at the later stages of OCL formation and does not increase RANKL expression. Thus, its mechanism of action is unclear. Therefore, RAW 264.7 cells and M-CSF-dependent murine bone marrow macrophage (MDBM) cells were treated with RANKL and/or with recombinant ECF-L expressed as a Fc fusion protein (ECF-L-Fc) to determine their effects on NF-kappa B, AP-1 and JNK activity, and on the expression of the adhesion molecules that have been implicated in OCL formation. These parameters were measured by semiquantitative and PCR and Western blot analysis. In addition, the role of ICAM-I was further assessed by treating normal mouse marrow cultures with ECF-L-Fc and 10(-10) M 1,25-(OH)(2)D-3 in the presence or absence of a blocking ICAM-1 antibody or treating marrow cultures from ICAM-1 knockout mice with ECF-L and 1,25-(OH)2D3. ECF-L-Fc by itself only modestly increased NF-kappa B binding and JNK activity in RAW 264.7 cells, which was further enhanced by RANKL. In contrast, ECF-L-Fc increased LFA-1 alpha and ICAM-1 mRNA levels 1.8-fold in mouse marrow cultures, and anti-ICAM-1 almost completely inhibited OCL formation induced by 10(-10) M 1,25(OH)(2)D-3 and ECF-L. Furthermore, ECF-L did not increase OCL formation in marrow cultures from ICAM-1 knockout mice. Taken together, these results demonstrate that ECF-L enhances RANKL and 1,25-(OH)(2)D-3-induced OCL formation by increasing adhesive interactions between OCL precursors through increased expression of ICAM-1 and LFA-1. (c) 2006 Elsevier Inc. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15260 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, 111-H Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu RI Galson, Deborah/E-9370-2010 OI Galson, Deborah/0000-0002-2045-8807 FU NIAID NIH HHS [AI-32177, R37 AI032177-15, R37 AI032177]; NIAMS NIH HHS [R01 AR041336, R01-AR41336, R01 AR041336-15] NR 19 TC 9 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD FEB PY 2007 VL 40 IS 2 BP 316 EP 322 DI 10.1016/j.bone.2006.08.004 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 129ZD UT WOS:000243767700007 PM 16996813 ER PT J AU Yasui, H Hideshima, T Ikeda, H Jin, J Ocio, EM Kiziltepe, T Okawa, Y Vallet, S Podar, K Ishitsuka, K Richardson, PG Pargellis, C Moss, N Raje, N Anderson, KC AF Yasui, Hiroshi Hideshima, Teru Ikeda, Hiroshi Jin, Janice Ocio, Enrique M. Kiziltepe, Tanyel Okawa, Yutaka Vallet, Sonia Podar, Klaus Ishitsuka, Kenji Richardson, Paul G. Pargellis, Chris Moss, Neil Raje, Noopur Anderson, Kenneth C. TI BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; p38 mitogen-activated protein kinase; BIRB 796; heat shock protein; bone marrow microenvironment ID OVERCOMES DRUG-RESISTANCE; BONE-MARROW MICROENVIRONMENT; MAP KINASE; DROSOPHILA HSP27; APOPTOSIS; STRESS; DEATH; ALPHA; ACTIVATION; EXPRESSION AB We have previously shown that heat shock protein (Hsp) 27 or its upstream activator p38 mitogen-activated protein kinase (MAPK) confers resistance to bortezomib and dexamethasone (Dex) in multiple myeloma (MM) cells. This study examined anti-MM activity of a novel p38 MAPK inhibitor, BIRB 796, alone and in combination with conventional and novel therapeutic agents. BIRB 796 blocked baseline and bortezomib-triggered upregulation of p38 MAPK and Hsp27 phosphorylation, thereby enhancing cytotoxicity and caspase activation. The Hsp90 inhibitor 17-allylamino-17-demethoxy-geldanamycin (17-AAG) upregulated protein expression and phosphorylation of Hsp27; conversely, BIRB 796 inhibited this phosphorylation and enhanced 17-AAG-induced cytotoxicity. Importantly, BIRB 796 inhibited Hsp27 phosphorylation induced by 17-AAG plus bortezomib, thereby enhancing cytotoxicity. In bone marrow stromal cells (BMSC), BIRB 796 inhibited phosphorylation of p38 MAPK and secretion of interleukin-6 (IL-6) and vascular endothelial growth factor triggered by either tumour necrosis factor-alpha or tumour growth factor-beta 1. BIRB 796 also inhibited IL-6 secretion induced in BMSCs by adherence to MM cells, thereby inhibiting tumour cell proliferation. These studies therefore suggest that BIRB 796 overcomes drug-resistance in the BM microenvironment, providing the framework for clinical trials of a p38 MAPK inhibitor, alone and in combination with bortezomib, Hsp90 inhibitor, or Dex, to improve patient outcome in MM. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI 2007, Secribsal/A-1556-2012 FU NCI NIH HHS [IP50 CA10070, R0-1 CA50947]; PHS HHS [P0-1 78378] NR 48 TC 26 Z9 28 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2007 VL 136 IS 3 BP 414 EP 423 DI 10.1111/j.1365-2141.2006.06443.x PG 10 WC Hematology SC Hematology GA 133UG UT WOS:000244038800006 PM 17173546 ER PT J AU Davies, JK Guinan, EC AF Davies, Jeffrey K. Guinan, Eva C. TI An update on the management of severe idiopathic aplastic anaemia in children SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE aplastic anaemia; childhood; haematopoietic stem-cell transplantation; immunotherapy; late effects of therapy ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; CORD-BLOOD TRANSPLANTATION; STEM-CELL TRANSPLANTATION; COLONY-STIMULATING FACTOR; SAA-WORKING-PARTY; ANTI-THYMOCYTE GLOBULIN; HLA-IDENTICAL SIBLINGS; MATCHED UNRELATED DONORS AB The current outlook for a child with severe idiopathic aplastic anaemia (AA) is very much better than in previous decades. In part, this may reflect better differentiation of idiopathic and inherited marrow failure. For children with idiopathic AA and a human leucocyte antigen (HLA)-matched sibling donor (MSD), allogeneic haematopoietic stem-cell transplantation (AHSCT) is the primary therapy of choice, offering long-term disease-free survival of 90%, although graft-versus-host disease remains a cause of long-term morbidity. A greater treatment challenge remains for those children without a MSD. Combination immunosuppressive therapy (IST) is associated with response rates of 70% or more. However, relapse and clonal evolution with transformation to myelodysplasia or acute myeloid leukaemia remain significant problems after IST and long-term event-free survival rates are less impressive. For children who do not have a sustained response to IST, alternate donor AHSCT should be considered. New HLA typing technologies, novel stem cell sources, reduced-intensity conditioning and graft engineering have reduced toxicity and improved the outcome after alternate donor AHSCT. Emerging therapies that capitalise on recent advances in our understanding of the pathophysiology of idiopathic AA and the immunobiology of AHSCT and IST may further improve the long-term outcome of this disease. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM eva_guinan@dfci.harvard.edu NR 114 TC 45 Z9 50 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD FEB PY 2007 VL 136 IS 4 BP 549 EP 564 DI 10.1111/j.1365-2141.2006.06461.x PG 16 WC Hematology SC Hematology GA 128RN UT WOS:000243676100003 PM 17214739 ER PT J AU Adams, BM Banks, HT Davidian, M Rosenberg, ES AF Adams, B. M. Banks, H. T. Davidian, M. Rosenberg, E. S. TI Estimation and prediction with HIV-treatment interruption data SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article DE HIV models; treatment interruptions; censored data; parameter estimation; prediction ID INFECTION; DYNAMICS; CELLS AB We consider longitudinal clinical data for HIV patients undergoing treatment interruptions. We use a nonlinear dynamical mathematical model in attempts to fit individual patient data. A statistically-based censored data method is combined with inverse problem techniques to estimate dynamic parameters. The predictive capabilities of this approach are demonstrated by comparing simulations based on estimation of parameters using only half of the longitudinal observations to the full longitudinal data sets. C1 N Carolina State Univ, Ctr Res Sci Computat, Raleigh, NC 27695 USA. Massachusetts Gen Hosp, ID Unit Gray 5, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Banks, HT (reprint author), N Carolina State Univ, Ctr Res Sci Computat, Box 8205, Raleigh, NC 27695 USA. EM htbanks@ncsu.edu FU NCI NIH HHS [R01CA085848]; NIAID NIH HHS [R37AI031789]; NIGMS NIH HHS [R01GM67299-01] NR 26 TC 33 Z9 35 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD FEB PY 2007 VL 69 IS 2 BP 563 EP 584 DI 10.1007/s11538-006-9140-6 PG 22 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 139RX UT WOS:000244451400006 PM 17211735 ER PT J AU Prelack, K Dylewski, M Sheridan, RL AF Prelack, Kathy Dylewski, Maggie Sheridan, Robert L. TI Practical guidelines for nutritional management of burn injury and recovery SO BURNS LA English DT Review DE nutrition; burns ID TOTAL PARENTERAL-NUTRITION; PLASMA LACTATE CONCENTRATION; ENERGY-EXPENDITURE; ENTERAL NUTRITION; BACTERIAL TRANSLOCATION; INTESTINAL PERMEABILITY; METABOLIC RESPONSE; GLUCOSE KINETICS; TRAUMA PATIENTS; BLUNT TRAUMA AB Nutrition practice in burn injury requires a multifaceted approach aimed at providing metabolic support during a heightened inflammatory state, while accommodating surgical and medical needs of the patient. Nutritional assessment and determination of nutrient requirements is challenging, particularly given the metabolic disarray that frequently accompanies inflammation. Nutritional therapy requires careful decision making, regarding the safe use of enteral or parenteral nutrition and the aggressiveness of nutrient delivery given the severity of the patient's illness and response to treatment. With the discovery that specific nutrients can actually alter the course of disease, the role of nutrition support in critical illness has shifted from one of preventing malnutrition to one of disease modulation. Today the use of glutamine, arginine, essential fatty acids, and other nutritional factors for their effects on immunity and cell regulation is becoming more common, although the evidence is often lagging. An exciting dichotomy exits, forcing nutrition support specialists to make responsible choices while remaining open to new potential helpful therapeutic options. (C) 2006 Elsevier Ltd and ISBI. All rights reserved. C1 Shriners Hosp Children, Boston Burn Hosp, Dept Clin Nutr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Shriners Hosp Children, Boston Burn Hosp, Dept Surg, Boston, MA 02114 USA. RP Prelack, K (reprint author), Shriners Hosp Children, Boston Burn Hosp, Dept Clin Nutr, 51 Blossom St, Boston, MA 02114 USA. EM kprelack@shrinenet.org NR 98 TC 39 Z9 47 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD FEB PY 2007 VL 33 IS 1 BP 14 EP 24 DI 10.1016/j.burns.2006.06.014 PG 11 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 133KZ UT WOS:000244013100004 PM 17116370 ER PT J AU Thakrar, A Shapiro, MD Jassal, DS Neilan, TG King, MEE Abbara, S AF Thakrar, Amar Shapiro, Michael D. Jassal, Davinder S. Neilan, Tomas G. King, Mary Etta E. Abbara, Suhny TI Cor triatriatum: The utility of cardiovascular imaging SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material DE computed tomography coronary angiography; cor triatriatum; echocardiography ID CROSS-SECTIONAL ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY; SURGICAL CORRECTION; DIAGNOSIS; ADULT AB A 44-year-old man with no known cardiac history presented with worsening dyspnea on minimal exertion. During follow-tip, computed tomography angiography and echocardiography confirmed the incidental finding of cor triatriatum. As improvements in spatial and temporal resolution continue, cardiac Computed tomography may become better Suited to the dynamic imaging of anatomical defects in the heart, including, but not limited to, coronary artery disease. C1 Royal Univ Hosp, Dept Internal Med, Saskatoon, SK S7N 0W8, Canada. Massachusetts Gen Hosp, Cardiac CT & MRI Ctr, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Dept Cardiol, Boston, MA 02114 USA. RP Jassal, DS (reprint author), St Boniface Gen Hosp, Inst Cardiovasc Sci, Div Cardiol, 409 Tache Ave, Winnipeg, MB R2H 2A6, Canada. EM djassal@sbgh.mb.ca NR 22 TC 10 Z9 10 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD FEB PY 2007 VL 23 IS 2 BP 143 EP 145 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 140ZO UT WOS:000244545700009 PM 17311121 ER PT J AU Oh, WK Tay, MH Huang, JT AF Oh, William K. Tay, Miah-Hiang Huang, Jiaoti TI Is there a role for platinum chemotherapy in the treatment of patients with hormone-refractory prostate cancer? SO CANCER LA English DT Review DE carboplatin; neuroendocrine; hormone refractory; chemotherapy ID MITOXANTRONE PLUS PREDNISONE; CIRCULATING CHROMOGRANIN-A; ANDROGEN-RECEPTOR GENE; PHASE-II EVALUATION; NEUROENDOCRINE DIFFERENTIATION; CIS-DIAMMINEDICHLOROPLATINUM; ONCOLOGY-GROUP; CELL-LINES; STAGE-D; ESTRAMUSTINE PHOSPHATE AB Docetaxel chemotherapy is the current standard of care for metastatic hormone-refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin and carboplatin, have moderate single-agent activity in HRPC. Next-generation platinum drugs, including satraplatin and oxaliplatin, may have additional activity in the management of HRPC. Furthermore, neuroendocrine differentiation may play a role in disease progression, providing a rationale for platinum-based chemotherapy in the management of HRPC. The authors reviewed the MEDLINE database for reports related to platinum-based chemotherapy in patients with advanced prostate cancer and evaluated studies that reviewed the role of neuroendocrine differentiation in the progression of HRPC. Older studies from the 1970s and 1980s suggested a lack of activity of cisplatin and carboplatin; however, those studies were flawed at least in part by their methods of response assessment. More recent Phase II studies of carboplatin suggested a moderate level of clinical and palliative activity when it was used as a single agent. However, when carboplatin was combined with a taxane and estramustine, high response rates were observed in several recent clinical trials. In addition, a randomized trial suggested that satraplatin plus prednisone improved progression-free survival compared with prednisone alone. For patients who progressed after docetaxel, no standard options existed in the literature that was reviewed. Several preliminary reports suggested that carboplatin and oxaliplatin may have activity as second-line chemotherapy Platinum chemotherapy drugs historically have been considered inactive in HRPC, although a review of the data suggested otherwise. Carboplatin, in particular, induced very-high response rates when it was combined with estramustine and a taxane, but it also appeared to have activity in patients who progressed after docetaxel. Satraplatin plus prednisone is being investigated in a large Phase III trial as second-line chemotherapy for HRPC. Targeting neuroendocrine cells may provide a new therapeutic approach to HRPC. C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Natl Canc Ctr, Dept Med Oncol, Singapore, Singapore. Univ Rochester, Sch Med, Dept Pathol, Rochester, NY 14627 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 108 TC 41 Z9 42 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2007 VL 109 IS 3 BP 477 EP 486 DI 10.1002/cncr.22439 PG 10 WC Oncology SC Oncology GA 131LF UT WOS:000243869700003 PM 17186531 ER PT J AU Sartor, O Reid, RH Bushnell, DL Quick, DP Ell, PJ AF Sartor, Oliver Reid, Robert H. Bushnell, David L. Quick, Donald P. Ell, Peter J. TI Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain SO CANCER LA English DT Article DE samarium Sm 153 lexidronam; bone metastases; prostate cancer; toxicity; repeated dosing; radioisotopes ID SKELETAL METASTASES; CANCER; PALLIATION; TOXICITY; THERAPY; TRIAL AB BACKGROUND. Samarium Sm 153 lexidronam (Sm-153) is an effective and well-tolerated treatment for painful bone metastases. The purpose of the analysis was to assess the safety and efficacy of repeated doses of Sm-153 in patients with metastatic bone pain. METHODS. Data were collected prospectively for 202 patients administered 1.0 mCi/kg of Sm-153. Particular emphasis was placed on analysis of data from 55 patients receiving >= 2 doses. Pain scores, adverse events, and hematologic parameters were assessed after each dose. RESULTS. Mild, transient suppression of platelets and white blood cell counts was the most common adverse event after treatment. Nadirs were approximately half of baseline at 4 weeks after dosing with recovery by Week 8 in 90% of patients. Temporary grade 3 thrombocytopenia occurred in 11%, 12%, and 17% of patients after the first, second, and third drug administration, respectively. Grade 3 leukopenia occurred in less than 7% of patients independent of the number of administrations. Significant decreases in pain scores (P < .001) were observed at Week 4 after each of the first 3 doses and maintained at Week 8 after the first 2 doses (P < .003) but not the third. Decreases in pain scores were observed in 70%, 63%, and 80% of patients, respectively, at Week 4 after the first 3 administrations. CONCLUSIONS. Repeated dosing of 1.0 mCi/kg of Sm-153 was both safe and effective and is a reasonable treatment option in patients whose bone pain responds and then recurs after an initial dose provided that adequate hematologic function is present at the time of drug administration. C1 Harvard Univ, Sch Med, DFCI, Lank Ctr Genintourinary Oncol, Boston, MA 02115 USA. Victoria Hosp, Dept Nucl Med, London, ON N6A 4G5, Canada. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. Joe Arrington Canc Res & Treatment Ctr, Dept Med Oncol, Lubbock, TX USA. UCL Hosp, Dept Nucl Med, London, England. RP Sartor, O (reprint author), Harvard Univ, Sch Med, DFCI, Lank Ctr Genintourinary Oncol, Dana 1230,44 Binney St, Boston, MA 02115 USA. EM oliver_sartor@dfci.harvard.edu NR 15 TC 58 Z9 60 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2007 VL 109 IS 3 BP 637 EP 643 DI 10.1002/cncr.22431 PG 7 WC Oncology SC Oncology GA 131LF UT WOS:000243869700023 PM 17167764 ER PT J AU Sorensen, G Barbeau, EM Stoddard, AM Hunt, MK Goldman, R Smith, A Brennan, AA Wallace, L AF Sorensen, Glorian Barbeau, Elizabeth M. Stoddard, Anne M. Hunt, Mary Kay Goldman, Roberta Smith, Ann Brennan, Angela A. Wallace, Lorraine TI Tools for health: the efficacy of a tailored intervention targeted for construction laborers SO CANCER CAUSES & CONTROL LA English DT Article DE smoking cessation; nutrition; blue-collar workers; labor unions; tailored intervention ID BLUE-COLLAR WORKERS; SMOKING-CESSATION; WORKING-CLASS; CANCER PREVENTION; MULTIETHNIC POPULATIONS; VEGETABLE CONSUMPTION; INCREASING FRUIT; BEHAVIOR-CHANGE; UNITED-STATES; TOBACCO USE AB Objectives Novel approaches to worksite health promotion are needed for high-risk workers who change job sites frequently, and thus may have limited access to worksite health promotion efforts. The objective of this study was to test a behavioral intervention among construction laborers. Methods Using a randomized-controlled design, we tested the efficacy of a tailored telephone-delivered and mailed intervention to promote smoking cessation and increased fruit and vegetable consumption (n = 582). Results At baseline, 40% of control group participants and 45% of intervention group participants reported using any tobacco in the last seven days. At final, 8% of baseline cigarette smokers in the control group had quit, compared to 19% in the intervention group (p = 0.03). In both groups, the mean consumption of fruits and vegetables at baseline was over five servings per day. At final, the intervention group had increased consumption by approximately one and one-half servings, compared to a slight decrease in consumption in the control group (p < 0.001). Conclusions A tailored intervention can be efficacious in promoting tobacco use cessation and increased fruit and vegetable consumption among construction laborers, a high-risk, mobile workforce. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. Brown Univ, Ctr Primary Care & Prevent, Pawtucket, RI 02860 USA. Laborers Hlth & Safety Fund N Amer, Washington, DC USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,SM258, Boston, MA 02115 USA. EM glorian_sorensen@dfci.harvard.edu FU NCI NIH HHS [5 R01 CA84387-04] NR 55 TC 49 Z9 49 U1 2 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2007 VL 18 IS 1 BP 51 EP 59 DI 10.1007/s10552-006-0076-9 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 119RW UT WOS:000243031800005 PM 17186421 ER PT J AU Skates, SJ Horick, NK Moy, JM Minihan, AM Seiden, MV Marks, JR Sluss, P Cramer, DW AF Skates, Steven J. Horick, Nora K. Moy, Joseph M. Minihan, Anna M. Seiden, Michael V. Marks, Jeffrey R. Sluss, Patrick Cramer, Daniel W. TI Pooling of case specimens to create standard serum sets for screening cancer biomarkers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB Background: Multiple identical sets of sera from cancer cases and controls would facilitate standardized testing of biomarkers. We describe the creation and use of standard serum sets developed from healthy donors and pooled sera from ovarian, breast, and endometrial cancer cases. Methods: Two hundred seventy-five 0.3-mL aliquots of sera were created for each of the 95 healthy women, and residual serum was pooled to create 275 identical sets of 20 0.3-mL aliquots. Aliquots (1.0-1.5 mL) from 441 women were combined to create 12 breast and pelvic disease pools with at least 115 0.3-mL aliquots. Sets were assembled to contain aliquots from individual controls, replicates, and disease pools. Cancer antigens (CA), CA 125, CA 19.9, and CA 15.3, and carcinoembryonic antigen were measured in one set and in 217 women comprising six of the pelvic disease pools. Use of a set was illustrated for mesothelin (soluble mesothelin-related protein). Statistical output included concentration differences between pooled cases and controls (z values for single analytes; Mahalanobis distances for pairs), correlation between z values and sensitivities, coefficient of variations, and standardized biases. Results: Marker concentrations in the six pelvic disease pools were generally within 0.25 SD of the actual average, and z values correlated well with sensitivities. CA 125 remains the best single marker for nonmucinous ovarian cancer, complemented by CA 15.3 or soluble mesothelin-related protein. There is no comparable breast cancer biomarker among the current analytes tested. Conclusion: The potential value of standard serum sets for initial assessment of candidate biomarkers is illustrated. Sets are now available through the Early Detection Research Network to evaluate biomarkers for women's cancers. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ovarian Canc Biol Lab, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC USA. RP Cramer, DW (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM dcramer@partners.org FU NCI NIH HHS [U01CA086381] NR 8 TC 11 Z9 12 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2007 VL 16 IS 2 BP 334 EP 341 DI 10.1158/1055-9965.EPI-06-0681 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 137LF UT WOS:000244293400026 PM 17301268 ER PT J AU Tsuda, M Davis, IJ Argani, P Shukla, N McGill, GG Nagai, M Saito, T Lae, M Fisher, DE Ladanyi, M AF Tsuda, Masumi Davis, Ian J. Argani, Pedram Shukla, Neerav McGill, Gael G. Nagai, Makoto Saito, Tsuyoshi Lae, Marick Fisher, David E. Ladanyi, Marc TI TFE3 fusions activate MET signaling by transcriptional up-regulation, defining another class of tumors as candidates for therapeutic MET inhibition SO CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; HUMAN SYNOVIAL SARCOMA; RECEPTOR TYROSINE KINASE; SOFT PART SARCOMA; C-MET; EPITHELIAL MORPHOGENESIS; HUMAN GENOME; FACTOR GENE; TRANSLOCATION; MELANOMA AB Specific chromosomal translocations encoding chimeric transcription factors are considered to play crucial oncogenic roles in a variety of human cancers but the fusion proteins themselves seldom represent suitable therapeutic targets. Oncogenic TFE3 fusion proteins define a subset of pediatric renal adenocarcinomas and one fusion (ASPL-TFE3) is also characteristic of alveolar soft part sarcoma (ASPS). By expression profiling, we identified the MET receptor tyrosine kinase gene as significantly overexpressed in ASPS relative to four other types of primitive sarcomas. We therefore examined MET as a direct transcriptional target of ASPL=TFE3. ASPL TFE3 binds to the MET promoter and strongly activates it. Likewise, PSF-TFE3 and NONO=TFE3 also bind this promoter. Induction of MET by ASPL-TFE3 results in strong MET autophosphorylation and activation of downstream signaling in the presence of hepatocyte growth factor (HGF). In cancer cell lines containing endogenous TFE3 fusion proteins, inhibiting MET by BNA interference or by the inhibitor PHA665752 abolishes HGF-dependent MET activation, causing decreased cell growth and loss of HGF-dependent phenotypes. MET is thus a potential therapeutic target in these cancers. Aberrant transcriptional up-regulation of MET by oncogenic TFE3 fusion proteins represents another mechanism by which certain cancers become dependent on MET signaling. The identification of kinase signaling pathways transcriptionally up-regulated by oncogenic fusion proteins may reveal more accessible therapeutic targets in this class of human cancers. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Dana Farber Canc Inst, Melonoma Program Med Oncol, Boston, MA 02115 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. RP Ladanyi, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, Room S-801,1275 York Ave, New York, NY 10021 USA. EM ladanyim@mskcc.org FU NCI NIH HHS [CA 100400, CA 102309, CA 97585] NR 48 TC 133 Z9 139 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 FEB 1 PY 2007 VL 67 IS 3 BP 919 EP 929 DI 10.1158/0008-5472.CAN-06-2855 PG 11 WC Oncology SC Oncology GA 135EQ UT WOS:000244137300013 PM 17283122 ER PT J AU Lynch, RA Etchin, J Battle, TE Frank, DA AF Lynch, Rebecca A. Etchin, Julia Battle, Traci E. Frank, David A. TI A small-molecule enhancer of signal transducer and activator of transcription 1 transcriptional activity accentuates the antiproliferative effects of IFN-gamma in human cancer cells SO CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; INTERFERON THERAPY; TUMOR-CELLS; STAT1; APOPTOSIS; PATHWAY; GROWTH; ALPHA; PHOSPHORYLATION; IDENTIFICATION AB The transcription factor signal transducer and activator of transcription (STAT) 1 can mediate antiproliferative and proapoptotic effects in cancer cells, and a number of mechanisms have been found whereby STAT1 signaling is attenuated in tumors thereby increasing their malignant behavior. Thus, enhancing gene transcription mediated by STAT1 may be an effective approach to cancer therapy. A high-throughput screen was developed to identify molecules that could enhance STAT1-dependent gene expression. Through this approach, it was found that 2-(1,8-naphthyridin-2-yl)phenol (2-NP) caused a 2-fold increase in STAT1-dependent reporter gene expression compared with that seen with maximally effective concentrations of IFN-gamma alone. This effect was specific to STAT1 because 2-NP had no effect on unrelated transcription factors such as nuclear factor (NF) kappa B or the highly homologous transcription factor STAT3. STAT1-dependent gene activation was enhanced by this compound in a variety of human and murine cell lines and was independent of the stimulus used. Furthermore, 2-NP enhanced the expression of the bona fide endogenous STAT1 target gene interferon regulatory factor 1. 2-NP increased the duration of STAT1 tyrosine phosphorylation in response to IFN-gamma, and this may underlie its enhancement of STAT1-dependent transcription. Reflecting the fact that STAT1 can exert tumor-suppressive effects, 2-NP enhanced the ability of IFN-gamma to inhibit the proliferation of human breast cancer and fibrosarcoma cells. Tumor cells lacking STAT1 were unaffected by either IFN-gamma or 2-NP. These findings indicate that enhancement of STAT1 transcriptional activity may have utility in anticancer therapies, and that cell-based screens for modulators of transcription factor function can be a useful approach for drug discovery. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 522B,44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu NR 41 TC 19 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2007 VL 67 IS 3 BP 1254 EP 1261 DI 10.1158/0008-5472.CAN-06-2439 PG 8 WC Oncology SC Oncology GA 135EQ UT WOS:000244137300053 PM 17283162 ER PT J AU McDonald, DK Kalva, SP Fan, CM Vasilyev, A AF McDonald, Douglas K. Kalva, Sanjeeva P. Fan, Chieh-Min Vasilyev, Aleksandr TI Leiomyosarcoma of the uterus with intravascular tumor extension and pulmonary tumor embolism SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE intravenous leiomyomatosis; intravenous leiomyosarcomatosis; intravascular tumor embolism; leiomyosarcoma ID INTRAVENOUS LEIOMYOMATOSIS; HYPERTENSION; DYSPNEA; CANCER; LUNGS AB We report the case of a 48-year-old woman presenting with recurrent uterine leiomyosarcoma (LMS) associated with right iliac vein and inferior vena cava (IVC) invasion and left lower lobe pulmonary tumor embolus. Because the prognosis and treatment differ from that of thrombotic pulmonary emboli, the differentiating imaging characteristics of intravascular tumor embolism are reviewed. To our knowledge, only two other cases of intravenous uterine leiomyosarcomatosis have been described in the existing literature, and this is the first reported case of the entity with associated intravascular tumor embolism. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB-290,55 Fruit St, Boston, MA 02114 USA. EM sanjeevakalva@gmail.com NR 17 TC 7 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD FEB PY 2007 VL 30 IS 1 BP 140 EP 142 DI 10.1007/s00270-006-0118-4 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 112BS UT WOS:000242500800026 PM 17031731 ER PT J AU Kaul, M Ma, Q Medders, KE Desai, MK Lipton, SA AF Kaul, M. Ma, Q. Medders, K. E. Desai, M. K. Lipton, S. A. TI HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE HIV-1-associated dementia; neuroAIDS; neurodegeneration; apoptosis; immune activation; macrophages/microglia; HIV/gp120; chemokine receptors; CCR5; CXCR4; MIP-1 beta; RANTES; knockout ID IMMUNODEFICIENCY-VIRUS TYPE-1; METHYL-D-ASPARTATE; ACTIVATED PROTEIN-KINASES; CENTRAL-NERVOUS-SYSTEM; CHEMOKINE RECEPTOR; NITRIC-OXIDE; HETEROLOGOUS DESENSITIZATION; TRANSGENIC MICE; GROWTH-FACTOR; INFECTION AB The chemokine receptors CCR5 and CXCR4 serve, in addition to CD4, as coreceptors for human immunodeficiency virus-1 (HIV-1), and infection with HIV-1 can cause dementia. In brain-derived cells, HIV-1 envelope glycoprotein gp120 initiates a signaling cascade that involves p38 mitogen-activated protein kinase and leads to neuronal cell death. Using mixed neuronal/glial cultures from rats and mice genetically deficient in one or both HIV coreceptors, we show here that CCR5, CXCR4 or both can mediate HIV/gp120 neurotoxicity depending on the viral strain. Paradoxically, we also found evidence for a CCR5-mediated neuroprotective pathway. We identify protein kinase Akt/PKB as an essential component of this pathway, which can be triggered by the CCR5 agonists macrophage inflammatory protein-1 beta and regulated-and-normal-T-cell-expressed-and-secreted. Moreover, these CCR5 ligands prevent neuronal cell death induced by stromal cell-derived factor-1, a CXCR4 agonist. Both neurons and glia coexpress CXCR4 and CCR5. Ca2+ imaging experiments demonstrate that engagement of CCR5 prevents CXCR4-triggered increases in intracellular free Ca2+. This finding suggests that CCR5 ligands can protect neurons at least, in part, by modulating CXCR4-mediated toxicity through heterologous desensitization. C1 Burnham Inst, Ctr Neurosci & Aging, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kaul, M (reprint author), Burnham Inst, Ctr Neurosci & Aging, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM mkaul@burnham.org FU NEI NIH HHS [R01 EY09024]; NICHD NIH HHS [P01 HD29587]; NINDS NIH HHS [R01 NS050621, R01 NS41207] NR 53 TC 75 Z9 75 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD FEB PY 2007 VL 14 IS 2 BP 296 EP 305 DI 10.1038/sj.cdd.4402006 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 126DS UT WOS:000243493000010 PM 16841089 ER PT J AU Alvi, F Idkowiak-Baldys, J Baldys, A Raymond, JR Hannun, YA AF Alvi, F. Idkowiak-Baldys, J. Baldys, A. Raymond, J. R. Hannun, Y. A. TI Regulation of membrane trafficking and endocytosis by protein kinase C: emerging role of the pericentrion, a novel protein kinase C-dependent subset of recycling endosomes SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE PKC; endocytosis; trafficking; pericentrion ID BETA-ADRENERGIC-RECEPTOR; GROWTH-FACTOR RECEPTOR; NEUROTRANSMITTER TRANSPORTERS; PHOSPHOLIPASE-D; PHORBOL ESTERS; LIPID RAFTS; PHOSPHORYLATION; INTERNALIZATION; DESENSITIZATION; MECHANISMS AB The protein kinase C (PKC) family of isoenzymes has been shown to regulate a variety of cellular processes, including receptor desensitization and internalization, and this has sparked interest in further delineation of the roles of specific isoforms of PKC in membrane trafficking and endocytosis. Recent studies have identified a novel translocation of PKC to a juxtanuclear compartment, the pericentrion, which is distinct from the Golgi complex but epicentered on the centrosome. Sustained activation of PKC (longer than 30 min) also results in sequestration of plasma membrane lipids and proteins to the same compartment, demonstrating a global effect on endocytic trafficking. This review summarizes these studies, particularly focusing on the characterization of the pericentrion as a distinct PKC-dependent subset of recycling endosomes. We also discuss emerging insights into a role for PKC as a central hub in regulating vesicular transport pathways throughout the cell, with implications for a wide range of pathobiologic processes, e.g. diabetes and abnormal neurotransmission or receptor desensitization. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave,POB 250209, Charleston, SC 29425 USA. EM hannun@musc.edu NR 74 TC 41 Z9 43 U1 1 U2 7 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD FEB PY 2007 VL 64 IS 3 BP 263 EP 270 DI 10.1007/s00018-006-6363-5 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 138UZ UT WOS:000244390100002 PM 17180302 ER PT J AU Ho, IC Pai, SY AF Ho, I-Cheng Pai, Sung-Yun TI GATA-3 - Not just for TH2 cells anymore SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE GATA-3; T cell; transcription factor; thymocyte ID TRANSCRIPTION FACTOR GATA-3; IFN-GAMMA PRODUCTION; REGULATORY T-CELLS; DOMINANT-NEGATIVE MUTANT; CYTOKINE GENE-EXPRESSION; ZINC-FINGER PROTEIN; LINEAGE COMMITMENT; C-MYB; ENFORCED EXPRESSION; CUTTING EDGE AB GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A role for GATA-3 during thymic development has long implied by its continuous and regulated expression through out T lineage development, but the absolute requirement for GATA-3 during early T lymphoid commitment/survival previously precluded definitive answers to this question. Several technical breakthroughs have fueled fruitful investigation in recent years and uncovered unexpected and critical roles for GATA-3 in CD4 thymocyte survival, invariant natural killer T cell generation and function, and also in beta selection. Not only does GATA-3 participate in nearly every stage of T cell development from common lymphoid progenitor to Th2, conditional knockout studies have indicated that the influence of GATA-3 also extends beyond the immune system. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Ho, IC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Smith Bldg,Room 526D,One Jimmy Fund Way, Boston, MA 02115 USA. EM iho@partners.org NR 137 TC 56 Z9 62 U1 0 U2 5 PU CHINESE SOC IMMUNOLOGY PI BEIJING PA 5 SANTIAO DONGDAN, BEIJING, 10005, PEOPLES R CHINA SN 1672-7681 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD FEB PY 2007 VL 4 IS 1 BP 15 EP 29 PG 15 WC Immunology SC Immunology GA 213MK UT WOS:000249671500002 PM 17349208 ER PT J AU Lewis, HD Leveridge, M Strack, PR Haldon, CD O'Neil, J Kim, H Madin, A Hannam, JC Look, AT Kohl, N Draetta, G Harrison, T Kerby, JA Shearman, MS Beherl, D AF Lewis, Huw D. Leveridge, Matthew Strack, Peter R. Haldon, Christine D. O'Neil, Jennifer Kim, Hellen Madin, Andrew Hannam, Joanne C. Look, A. Thomas Kohl, Nancy Draetta, Giulio Harrison, Timothy Kerby, Julie A. Shearman, Mark S. Beherl, Dirk TI Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling SO CHEMISTRY & BIOLOGY LA English DT Article ID GAMMA-SECRETASE INHIBITORS; CHROMOSOMAL TRANSLOCATIONS; THERAPEUTIC TARGET; TRANSGENIC MICE; NERVOUS-SYSTEM; CANCER; ACTIVATION; PATHWAY; TRANSFORMATION; GROWTH AB In this report, inhibitors of the gamma-secretase enzyme have been exploited to characterize the anti proliferative relationship between target inhibition and cellular responses in Notch-dependent human T cell acute lymphoblastic leukemia (T-ALL) cell lines. Inhibition of y-secretase led to decreased Notch signaling, measured by endogenous NOTCH intracellular domain (NICD) formation, and was associated with decreased cell viability. Flow cytometry revealed that decreased cell viability resulted from a G(0)/G(1) cell cycle block, which correlated strongly to the induction of apoptosis. These effects associated with inhibitor treatment were rescued by exogenous expression of NICD and were not mirrored when a markedly less active enantiomer was used, demonstrating the y-secretase dependency and specificity of these responses. Together, these data strengthen the rationale for using y-secretase inhibitors therapeutically and suggest that programmed cell death may contribute to reduction of tumor burden in the clinic. C1 Merck Sharp & Dohme Res Lab, Dept Mol & Cellular Neurosci, Harlow CM20 2QR, Essex, England. Merck Sharp & Dohme Res Lab, Dept Med Chem, Harlow CM20 2QR, Essex, England. Merck Res Labs, Dept Canc Biol & Therapeut, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Lewis, HD (reprint author), Merck Sharp & Dohme Res Lab, Dept Mol & Cellular Neurosci, Terlings Pk, Harlow CM20 2QR, Essex, England. EM huw.lewis.1991@pem.cam.ac.uk; mark_Shearman@merck.com NR 57 TC 99 Z9 103 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD FEB PY 2007 VL 14 IS 2 BP 209 EP 219 DI 10.1016/j.chembiol.2006.12.010 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 148EO UT WOS:000245057500011 PM 17317574 ER PT J AU Labarere, J Stone, RA Obrosky, DS Yealy, DM Meehan, TP Fine, JM Graff, LG Fine, MJ AF Labarere, Jose Stone, Roslyn A. Obrosky, D. Scott Yealy, Donald M. Meehan, Thomas P. Fine, Jonathan M. Graff, Louis G. Fine, Michael J. TI Comparison of outcomes for low-risk outpatients and inpatients with pneumonia - A propensity-adjusted analysis SO CHEST LA English DT Article DE ambulatory care; community-acquired infections; pneumonia; treatment outcomes ID COMMUNITY-ACQUIRED PNEUMONIA; RANDOMIZED-TRIAL; PREDICTION RULE; SEVERITY INDEX; HOSPITALIZATION; GUIDELINES; CARE; MANAGEMENT; DECISIONS; ADULTS AB Background: Low-risk patients with community-acquired pneumonia are often hospitalized despite guideline recommendations for outpatient treatment. Methods: Using data from a randomized trial conducted in 32 emergency departments, we performed a propensity-adjusted analysis to compare 30-day mortality rates, time to the return to work and to usual activities, and patient satisfaction with care between 944 outpatients and 549 inpatients in pneumonia severity index risk classes I to III who did not have evidence of arterial oxygen desaturation, or medical or psychosocial contraindications to outpatient treatment. Results: After adjusting for quintile of propensity score for outpatient treatment, which eliminated all significant differences for baseline characteristics, outpatients were more likely to return to work (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.5 to 2.6) or, for nonworkers, to usual activities (OR, 1.4; 95% Cl, 1.1 to 1.8) than were inpatients. Satisfaction with the site-of-treatment decision (OR, 1.1; 95% CI, 0.7 to 1.8), with emergency department care (OR, 1.4; 95% CI, 0.9 to 1.9), and with overall medical care (OR, 1.1; 95% Cl, 0.8 to 1.6) was not different between outpatients and inpatients. The overall mortality rate was higher for inpatients than outpatients (2.6% vs 0.1%, respectively; p < 0.01); the mortality rate was not different among the 242 outpatients and 242 inpatients matched by their propensity score (0.4% vs 0.8%, respectively; p = 0.99). Conclusions: After adjusting for the propensity of site of treatment, outpatient treatment was associated with a more rapid return to usual activities and to work, and with no increased risk of mortality. The higher observed mortality rate among all low-risk inpatients suggests that physician judgment is an important complement to objective risk stratification in the site-of-treatment decision for patients with pneumonia. C1 VA Pittsburgh Healthcare Syst, Vet Affairs Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15260 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Qualidigm, Middletown, CT USA. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Vet Affairs Ctr Hlth Equ Res & Promot, Univ Dr C,Bldg 28,1A102, Pittsburgh, PA 15240 USA. EM Michael.Fine@med.va.gov RI Labarere, Jose/N-1688-2014; OI Labarere, Jose/0000-0001-7621-6586 FU AHRQ HHS [R01 HS10049]; NIAID NIH HHS [5K24 AI01769] NR 28 TC 31 Z9 32 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2007 VL 131 IS 2 BP 480 EP 488 DI 10.1378/chest.06-1393 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 138AS UT WOS:000244335500026 PM 17296651 ER PT J AU Eckert, DJ Jordan, AS Merchia, P Malhotra, A AF Eckert, Danny J. Jordan, Amy S. Merchia, Pankaj Malhotra, Atul TI Central sleep apnea - Pathophysiology and treatment SO CHEST LA English DT Review DE apnea threshold; arousal; chemoresponsiveness; control of breathing; hypercapnia; hypoxia; sleep-disordered breathing ID CHEYNE-STOKES RESPIRATION; CONGESTIVE-HEART-FAILURE; POSITIVE AIRWAY PRESSURE; OBESITY-HYPOVENTILATION SYNDROME; CONGENITAL CENTRAL HYPOVENTILATION; MAINTENANCE TREATMENT PATIENTS; HYPOXIC VENTILATORY RESPONSE; RANDOMIZED CROSSOVER TRIAL; CARBON-DIOXIDE; NORMAL MEN AB Central sleep apnea (CSA) is characterized by a lack of drive to breathe during sleep, resulting in repetitive periods of insufficient ventilation and compromised gas exchange. These nighttime breathing disturbances can lead to important comorbidity and increased risk of adverse cardiovascular outcomes. There are several manifestations of CSA, including high altitude-induced periodic breathing, idiopathic CSA, narcotic-induced central apnea, obesity hypoventilation syndrome, and Cheyne-Stokes breathing. While unstable ventilatory control during sleep is the hallmark of CSA, the pathophysiology and the prevalence of the various forms of CSA vary greatly. This brief review summarizes the underlying physiology and modulating components influencing ventilatory control in CSA, describes the etiology of each of the various forms of CSA, and examines the key factors that may exacerbate apnea severity. The clinical implications of improved CSA pathophysiology knowledge and the potential for novel therapeutic treatment approaches are also discussed. C1 BIDMC, Sleep Disorders Program, Div Sleep Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Eckert, DJ (reprint author), BIDMC, Sleep Disorders Program, Div Sleep Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM deckert@rics.bwh.harvard.edu RI Eckert, Danny/A-6145-2012; OI Eckert, Danny/0000-0003-3503-2363; Jordan, Amy/0000-0001-8561-9766 FU NHLBI NIH HHS [R01 HL073146-03, R01 HL073146, R01-HL73146-01]; NIA NIH HHS [AG024837-01, K23 AG024837, K23 AG024837-04] NR 128 TC 143 Z9 152 U1 0 U2 11 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2007 VL 131 IS 2 BP 595 EP 607 DI 10.1378/chest.06.2287 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 138AS UT WOS:000244335500043 PM 17296668 ER PT J AU Davidow, LS Breen, M Duke, SE Samollow, PB McCarrey, JR Lee, JT AF Davidow, Lance S. Breen, Matthew Duke, Shannon E. Samollow, Paul B. McCarrey, John R. Lee, Jeannie T. TI The search for a marsupial XIC reveals a break with vertebrate synteny SO CHROMOSOME RESEARCH LA English DT Article DE marsupial; Monodelphis domestica; noncoding RNA; TSIX; X-chromosome; XIC; X inactivation center; XIST ID X-CHROMOSOME INACTIVATION; XIST RNA; EUTHERIAN MAMMALS; SEX-CHROMOSOMES; GENE; MOUSE; TSIX; MICE; EVOLUTION; REGION AB X-chromosome inactivation (XCI) evolved in mammals to deal with X-chromosome dosage imbalance between the XX female and the XY male. In eutherian mammals, random XCI of the soma requires a master regulatory locus known as the 'X-inactivation center' (XIC/Xic), wherein lies the noncoding XIST/Xist silencer RNA and its regulatory antisense Tsix gene. By contrast, marsupial XCI is imprinted to occur on the paternal X chromosome. To determine whether marsupials and eutherians share the XIC-driven mechanism, we search for the sequence equivalents in the genome of the South American opossum, Monodelphis domestica. Positional cloning and bioinformatic analysis reveal several interesting findings. First, protein-coding genes that flank the eutherian XIC are well-conserved in M. domestica, as well as in chicken, frog, and pufferfish. However, in M. domestica we fail to identify any recognizable XIST or TSIX equivalents. Moreover, cytogenetic mapping shows a surprising break in synteny with eutherian mammals and other vertebrates. Therefore, during the evolution of the marsupial X chromosome, one or more rearrangements broke up an otherwise evolutionarily conserved block of vertebrate genes. The failure to find XIST/TSIX in M. domestica may suggest that the ancestral XIC is too divergent to allow for detection by current methods. Alternatively, the XIC may have arisen relatively late in mammalian evolution, possibly in eutherians with the emergence of random XCI. The latter argues that marsupial XCI does not require XIST and opens the search for alternative mechanisms of dosage compensation. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. N Carolina State Univ, Coll Vet Med, Ctr Comparat Med & Translat Res, Raleigh, NC 27606 USA. Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. Univ Texas, Dept Biol, San Antonio, TX USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU NCRR NIH HHS [RR014214]; NICHD NIH HHS [HD46637]; NIGMS NIH HHS [GM58839] NR 49 TC 48 Z9 51 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD FEB PY 2007 VL 15 IS 2 BP 137 EP 146 DI 10.1007/s10577-007-1121-6 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 142XP UT WOS:000244684900002 PM 17333538 ER PT J AU Moy, B Goss, PE AF Moy, Beverly Goss, Paul E. TI TEACH: Tykerb evaluation after chemotherapy SO CLINICAL BREAST CANCER LA English DT Article DE dual tyrosine kinase inhibitors; lapatinib; trastuzumab ID HER2-POSITIVE BREAST-CANCER; ADJUVANT CHEMOTHERAPY; POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; RANDOMIZED-TRIAL; GROWTH; TRASTUZUMAB; INHIBITOR; ONCOGENE; FAMILY C1 Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Canc, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org NR 16 TC 21 Z9 21 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD FEB PY 2007 VL 7 IS 6 BP 489 EP 493 DI 10.3816/CBC.2007.n.007 PG 5 WC Oncology SC Oncology GA 141BG UT WOS:000244550700007 PM 17386127 ER PT J AU Lieberman, D AF Lieberman, David TI Eighty-year-old patient with history of a twelve millimeter adenomatous polyp resected at age of seventy-five years SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID COLORECTAL-CANCER; SCREENING COLONOSCOPY; ELDERLY-PATIENTS; LIFE EXPECTANCY; SURVEILLANCE; POLYPECTOMY; RECURRENCE; IMPACT C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. RP Lieberman, D (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR USA. EM lieberma@ohsu.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2007 VL 5 IS 2 BP 166 EP 169 DI 10.1016/j.cgh.2006.11.018 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 140NH UT WOS:000244511700007 PM 17296526 ER PT J AU Hur, C Chung, DC Schoen, RE Gazelle, GS AF Hur, Chin Chung, Daniel C. Schoen, Robert E. Gazelle, G. Scott TI The management of small polyps found by virtual colonoscopy: Results of a decision analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; HIGH-GRADE DYSPLASIA; COLORECTAL-CANCER; CT COLONOGRAPHY; CONVENTIONAL COLONOSCOPY; EXTRACOLONIC FINDINGS; ASYMPTOMATIC ADULTS; COST-EFFECTIVENESS; LARGE-INTESTINE; LARGE BOWEL AB Background & Aims: There is a firm consensus that larger (>= 10 mm) colonic polyps should be removed; however, the importance of removing smaller polyps (< 10 mm) is more controversial. If computed tomographic colonography (CTC) is used for colorectal cancer screening, the majority of polypoid lesions identified will be less than 10 turn in size. Decision-analytic techniques were used to compare the outcomes of 2 management strategies for smaller (6-9 mm) polyps discovered by CTC. Methods: Hypothetic average-risk patients who had undergone a CTC examination and found to have a small (6-9 mm) polyp were simulated to either: (1) undergo immediate colonoscopy for polypectomy (COLO), or (2) wait 3 years for a repeat CTC examination (WAIT). A Markov model was constructed to analyze outcomes including the number of deaths and cancers after a 3-year follow-up period or time horizon. Values for the model parameters were derived from the published literature and from Surveillance Epidemiology and End Results data, and an extensive sensitivity analysis was performed. Results: The COLO strategy resulted in 14 total deaths per 100,000 patients compared with 79 total deaths in the WAIT strategy, for a difference of 65 deaths. The COLO strategy resulted in 39 cancers per 100,000 patients vs 773 in the WAIT strategy, for a difference of 734 cancers. Sensitivity analysis found that model findings were robust and only sensitive at extreme parameter values. Conclusions: Managing smaller polyps detected on a screening CTC with another CTC examination 3 years later likely will result in more deaths and cancers than immediate colonoscopy and polypectomy. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. Dept Hlth Policy & Management, Boston, MA USA. Univ Pittsburgh, Ctr Med, Pittsburgh, PA USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 FU NCI NIH HHS [K07CA107060] NR 50 TC 43 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2007 VL 5 IS 2 BP 237 EP 244 DI 10.1016/j.cgh.2006.11.003 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 140NH UT WOS:000244511700019 PM 17296532 ER PT J AU Lok, ASF Everhart, JE Chung, RT Padmanabhan, L Greenson, JK Shiffman, ML Everson, GT Lindsay, KL Bonkovsky, HL Di Bisceglie, AM Lee, WM Morgan, TR Ghany, MG Morishima, C AF Lok, Anna S. F. Everhart, James E. Chung, Raymond T. Padmanabhan, Latha Greenson, Joel K. Shiffman, Mitchell L. Everson, Gregory T. Lindsay, Karen L. Bonkovsky, Herbert L. Di Bisceglie, Adrian M. Lee, William M. Morgan, Timothy R. Ghany, Marc G. Morishima, Chihiro CA HALT C Trial Grp TI Hepatic steatosis in hepatitis C: Comparison of diabetic and nondiabetic patients in the hepatitis C antiviral long-term treatment against cirrhosis trial SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; BODY-MASS INDEX; INSULIN-RESISTANCE; FIBROSIS PROGRESSION; VIRUS GENOTYPE-3; NONALCOHOLIC STEATOHEPATITIS; CRYPTOGENIC CIRRHOSIS; HEPATOCYTE STEATOSIS; NATURAL-HISTORY; HCV GENOTYPE AB Background & Aims: Hepatic steatosis often is observed in patients with chronic hepatitis C and has been reported to be associated with hepatic fibrosis and impaired treatment response in some studies. Our aim was to determine the prevalence of and risk factors for hepatic steatosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, and to determine the relationship between steatosis, fibrosis, and sustained virologic response (SVR) to re-treatment with pegylated interferon and ribavirin. Methods: Baseline data from 1143 Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, with a mean body mass index of 30, 5% with genotype 3, 38% with cirrhosis, and 24% with diabetes were analyzed. Results: Steatosis scores of 0, 1, 2, 3, and 4 were observed in 19%, 42%, 30%, 8%, and 1% of patients, respectively. High body mass index, triglyceride and alanine aminotransferase levels, and genotype 3 were associated with higher grades of steatosis. Among nondiabetic patients, steatosis scores of 0-2 but not scores of 3-4 were associated significantly with cirrhosis. For diabetic patients, there was no association between steatosis and cirrhosis. Similarly, steatosis scores of 2-4 were associated with a lack of SVR among nondiabetic but not among diabetic patients. Conclusions: in this cohort with predominantly hepatitis C virus genotype I infection, steatosis was associated strongly with metabolic factors that contribute to nonalcoholic fatty liver disease. Steatosis correlated with increasing stages of fibrosis up to but not including cirrhosis. Steatosis had a negative impact on SVR among nondiabetic but not diabetic patients. The discordant findings between nondiabetic and diabetic patients indicate that these 2 groups should be considered separately when analyzing metabolic factors and liver disease outcomes. C1 Univ Michigan, Ctr Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Med, Dept Pathol, Ann Arbor, MI 48109 USA. NIDDKD, Liver Dis Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. NIDDKD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. Virginia Commonwealth Univ, Hlth Syst, Hepatol Sect, Richmond, VA USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Lok, ASF (reprint author), Univ Michigan, Ctr Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. EM aslok@umich.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00042, M01RR-00043, M01RR-00051, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2319, N01-DK-9-2318, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328, P60 DK020572-28] NR 43 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2007 VL 5 IS 2 BP 245 EP 254 DI 10.1016/j.cgh.2006.11.002 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 140NH UT WOS:000244511700020 PM 17296533 ER PT J AU Greene, RE Schlamm, HT Oestmann, JW Stark, P Durand, C Lortholary, O Wingard, JR Herbrecht, R Ribaud, P Patterson, TF Troke, PF Denning, DW Bennett, JE de Pauw, BE Rubin, RH AF Greene, Reginald E. Schlamm, Haran T. Oestmann, Joerg -W. Stark, Paul Durand, Christine Lortholary, Olivier Wingard, John R. Herbrecht, Raoul Ribaud, Patricia Patterson, Thomas F. Troke, Peter F. Denning, David W. Bennett, John E. de Pauw, Ben E. Rubin, Robert H. TI Imaging findings in acute invasive pulmonary aspergillosis: Clinical significance of the halo sign SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 13th European Congress of Clinical Microbiology and Infectious Diseases CY MAY 10-13, 2003 CL GLASGOW, SCOTLAND SP Belgian Fonds Format Rech Ind Agr, Belgian Fonds Natl Rech Sci, Belgian Fonds Rech Sci Med ID RECEIVING PIPERACILLIN-TAZOBACTAM; NEUTROPENIC PATIENTS; IMMUNOCOMPROMISED PATIENTS; EARLY-DIAGNOSIS; HEMATOLOGICAL MALIGNANCIES; BRONCHOALVEOLAR LAVAGE; TOMOGRAPHIC SCAN; ACUTE-LEUKEMIA; CT; GALACTOMANNAN AB Background. Computed tomography ( CT) of the chest may be used to identify the halo sign, a macronodule surrounded by a perimeter of ground- glass opacity, which is an early sign of invasive pulmonary aspergillosis ( IPA). This study analyzed chest CT findings at presentation from a large series of patients with IPA, to assess the prevalence of these imaging findings and to evaluate the clinical utility of the halo sign for early identification of this potentially life- threatening infection. Methods. Baseline chest CT imaging findings from 235 patients with IPA who participated in a previously published study were systematically analyzed. To evaluate the clinical utility of the halo sign for the early identification and treatment of IPA, we compared response to treatment and survival after 12 weeks of treatment in 143 patients who presented with a halo sign and in 79 patients with other imaging findings. Results. At presentation, most patients ( 94%) had >= 1 macronodules, and many ( 61%) also had halo signs. Other imaging findings at presentation, including consolidations ( 30%), infarct- shaped nodules ( 27%), cavitary lesions ( 20%), and air- crescent signs ( 10%), were less common. Patients presenting with a halo sign had significantly better responses to treatment ( 52% vs. 29%;) and greater survival to 84 days ( 71% vs. 53%;) than P <= .001 P <= .01 did patients who presented with other imaging findings. Conclusions. Most patients presented with a halo sign and/ or a macronodule in this large imaging study of IPA. Initiation of antifungal treatment on the basis of the identification of a halo sign by chest CT is associated with a significantly better response to treatment and improved survival. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Pfizer Global Res & Dev, New York, NY USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Florida, Coll Med, Gainesville, FL 32611 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NIAID, Bethesda, MD 20892 USA. Charite Univ Med Berlin, Berlin, Germany. Hop Bocage, Dijon, France. Inst Pasteur, Paris, France. Hop St Louis, Paris, France. Hop Hautepierre, Strasbourg, France. Pfizer Global Res & Dev, Sandwich, Kent, England. Univ Manchester, Manchester M13 9PL, Lancs, England. Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. RP Greene, RE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders 202, Boston, MA 02114 USA. EM greene.reginald@mgh.harvard.edu RI Herbrecht, Raoul/D-3471-2013; OI Herbrecht, Raoul/0000-0002-9381-4876; Denning, David/0000-0001-5626-2251 NR 54 TC 279 Z9 315 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2007 VL 44 IS 3 BP 373 EP 379 DI 10.1086/509917 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 123SE UT WOS:000243315100016 PM 17205443 ER PT J AU Gandhi, RT AF Gandhi, Rajesh T. TI Cirrhosis is associated with low CD4(+) T cell counts: Implications for HIV-infected patients with liver disease SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE RECOVERY; SPLEEN SIZE; PROGRESSION; COINFECTION; FIBROSIS; IMPACT; HYPERSPLENISM C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM rgandhi@partners.org NR 23 TC 8 Z9 8 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2007 VL 44 IS 3 BP 438 EP 440 DI 10.1086/510682 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 123SE UT WOS:000243315100028 PM 17205455 ER PT J AU Pumbwe, L Wareham, DW Aduse-Opoku, J Brazier, JS Wexler, HM AF Pumbwe, L. Wareham, D. W. Aduse-Opoku, J. Brazier, J. S. Wexler, H. M. TI Genetic analysis of mechanisms of multidrug resistance in a clinical isolate of Bacteroides fragilis SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE Bacteroides fragilis; cross-resistance; efflux pumps; multidrug resistance; plasmid; susceptibility ID ANAEROBIC-BACTERIA; METRONIDAZOLE RESISTANCE; CONJUGATIVE TRANSPOSON; NIM GENES; ANTIMICROBIAL RESISTANCE; ANTIBIOTIC-RESISTANCE; EFFLUX; SUSCEPTIBILITY; CLINDAMYCIN; PREVALENCE AB This study investigated the mechanisms of multidrug resistance (MDR) in an isolate of Bacteroides fragilis (WI1) from a patient with anaerobic sepsis. The MDR of WI1 affected susceptibility to beta-lactams, clindamycin, fluoroquinolones, metronidazole and tetracycline. In addition to its 5.31-Mb chromosome, WI1 possessed two low-copy-number plasmids, pHagl (5.6 kb) and pHag2 (9.9 kb), that were absent from B. fragilis NCTC 9343. Restriction digestion with EcoRV, HindIII and SstI, combined with DNA sequencing, revealed that pHAG2 contained a tet(Q) gene at base position 3689 that resided on the conjugative transposon CTn341. Genes cfiA (encoding a metallo-beta-lactamase) and erm(F) (encoding a macrolide-lincosamide-streptogramin B resistance determinant) were also found in WI1, but were absent from B. fragilis NCTC 9343. Nitrocefin hydrolysis revealed that WI1 had high beta-lactamase activity. Sequencing of the gyrA quinolone resistance-determining region revealed a mutation causing a Ser82 -> Phe substitution, and comparative quantitative real-time RT-PCR revealed that the cfiA, erm(F) and tet(Q) genes were all expressed in WI1. In addition, the resistance-nodulation-division efflux pump genes bmeB9 and bmeB15 were significantly over-expressed (12.30 +/- 0.42-fold and 3541.1 +/- 95.4-fold, respectively), and the efflux pump inhibitors carbonyl cyanide m-chlorophenylhydrazone and reserpine significantly increased the susceptibility of the isolate to several unrelated antibiotics (p < 0.005). These data suggested that WI1 was highly multidrug-resistant because of the additive effects of chromosome- and plasmid-encoded resistance determinants. C1 Univ Calif Los Angeles, Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ London, Dept Microbiol, Queen Marys Sch Med & Dent, Barts London NHS Trust, London, England. Univ London, Ctr Infect Dis, Queen Marys Sch Med & Dent, Inst Cell & Mol Sci, London, England. Univ Wales Hosp, Anaerobe Reference Lab, Natl Publ Hlth Serv Microbiol Cardiff, Cardiff, Wales. RP Wexler, HM (reprint author), Wadsworth Anaerobe Lab, Bldg 304,Room E3-224,GLAVAHCS 691-151J, Los Angeles, CA 90073 USA. EM hwexler@ucla.edu RI Wareham, David/A-3583-2008 OI Wareham, David/0000-0003-4331-5224 NR 36 TC 24 Z9 24 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD FEB PY 2007 VL 13 IS 2 BP 183 EP 189 DI 10.1111/j.1469-0691.2006.01620.x PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 128UE UT WOS:000243683500010 PM 17328731 ER PT J AU Long, AA AF Long, Aidan A. TI Findings from a 1000-patient Internet-based survey assessing the impact of morning symptoms on individuals with allergic rhinitis SO CLINICAL THERAPEUTICS LA English DT Article DE morning; allergic rhinitis; treatment ID QUALITY-OF-LIFE; DIAGNOSIS; ASTHMA; SLEEP; PREVALENCE; CHILDREN AB Background: Although the severity of allergic rhinitis symptoms might depend on the degree of exposure to the triggering allergen, it has also been noted that symptom severity varies over the course of the day. Objectives: The alms of this study were to investigate the reported impact (influence on behavior and/or feelings) of morning symptoms on individuals with allergic rhinitis and determine their perception of the effectiveness of allergy treatment. Methods: In January 2005, online interviews based on a 16-item questionnaire were presented to adults (aged >= 18 years) with physician-diagnosed allergic rhinitis in the United States. Participants were recruited from the Roper Public Affairs and Media US national online panel. The survey sample was balanced to reflect the US population by Census Division, ethnicity, sex, and presence of children living at home. Data were weighted by sex (65% female, 35% male) based on previous research of the adult population suffering from allergies. Results: The first 1000 respondents (sex, female, 550 [55%]; age, >= 55 years, 378 [38%]; race, white, 883 [88%]) that met all inclusion/exclusion criteria were included in the study results. There was no significant difference in the regional distribution of participants: South (34%), Midwest (25%), West (22%), and Northeast (19%). The majority of the sample (83%) reported experiencing morning symptoms of allergic rhinitis; 49% reported that their symptoms were most severe during the morning hours. The most common symptom on awakening was nasal congestion, reported by 85% of those with symptoms when they first woke up. Of those with symptoms on awakening, the majority reported that these affected their feelings (96%) or behavior (87%). Among respondents who experienced symptoms on awakening, the majority reported that their symptoms affected the rest of their day "somewhat" or "a great deal" (51% and 24%, respectively). Of those respondents using allergy medication, 33% reported that its effectiveness wore off before the next dose most or all of the time. A majority of respondents reported feeling that it was very important for an allergy medication to maintain effectiveness until the next dose (68%), provide relief all day and into the next morning (62%), and enable them to wake up with their symptoms under control (63%). Conclusions: Based on the results from this large Internet-based survey, the morning symptoms of allergic rhinitis have a negative impact on individuals, both emotionally and in terms of disruption of daily activities. Medication used for treating allergic rhinitis was reported as not always effective for the whole time interval between doses. This suggests that it might be important, when considering management options in allergic rhinitis, to select medications that offer sustained effectiveness throughout the 24-hour period. C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Long, AA (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Cox 201 MGH,55 Fruit St, Boston, MA 02114 USA. EM aalong@partners.org NR 19 TC 18 Z9 19 U1 0 U2 1 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD FEB PY 2007 VL 29 IS 2 BP 342 EP 351 DI 10.1016/j.clinthera.2007.02.007 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 148SJ UT WOS:000245094600012 PM 17472826 ER PT J AU Ahmed, A AF Ahmed, Ali TI Clinical manifestations, diagnostic assessment, and etiology of heart failure in older adults SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID VENTRICULAR SYSTOLIC FUNCTION; CONVERTING ENZYME-INHIBITORS; EJECTION FRACTION; DIASTOLIC DYSFUNCTION; CARDIOVASCULAR HEALTH; HEPATOJUGULAR REFLUX; NATRIURETIC PEPTIDE; GUIDELINE UPDATE; AMERICAN-COLLEGE; VENOUS-PRESSURE AB Aging is characterized by heterogeneity, both in health and in disease. Older adults who have heart failure (HF) often have atypical and delayed clinical manifestations and many have diastolic HE The assessment and management of HF in older adults may be simplified by a 5-step process called DEFEAT HF: (1) Establish a clinical Diagnosis of HF; (2) Establish an Etiology for HF, preferably in collaboration with a cardiologist; (3) Determine Fluid status and achieve euvolemia; (4) Determine left ventricular Ejection frAction; and (5) Provide evidence-based Therapy C1 Univ Alabama, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Geriatr Heart Failure Clin,Ctr Aging, Birmingham, AL 35294 USA. Univ Alabama, Ctr Heart Failure Res, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Sect Geriatr, Birmingham, AL 35233 USA. Birmingham Vet Affairs Med Ctr, Geriatr Heart Failure Clin, Birmingham, AL 35233 USA. RP Ahmed, A (reprint author), Univ Alabama, Sch Med, Dept Med, Div Gerontol & Geriatr Med, 1530 3rd Ave S,CH19-219, Birmingham, AL 35294 USA. EM aahmed@uab.edu RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 NR 85 TC 8 Z9 9 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 FEB PY 2007 VL 23 IS 1 BP 11 EP + DI 10.1016/j.cger.2006.08.002 PG 21 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 119YG UT WOS:000243049800003 PM 17126753 ER PT J AU Flament, MF Geller, D Irak, M Blier, P AF Flament, Martine F. Geller, Dan Irak, Metehan Blier, Pierre TI Specificities of treatment in pediatric obsessive-compulsive disorder SO CNS SPECTRUMS LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; COGNITIVE-BEHAVIORAL THERAPY; PLACEBO-CONTROLLED TRIAL; 7-YEAR FOLLOW-UP; DOUBLE-BLIND; TOURETTES-SYNDROME; FAMILY TREATMENT; NEUROPSYCHIATRIC DISORDERS; STREPTOCOCCAL INFECTIONS; CLOMIPRAMINE TREATMENT AB Obsessive-compulsive disorder (OCD) experienced in childhood or adolescence is often a chronic disorder with high subjective distress and impairment of family and social functioning. An early comprehensive intervention schedule can have a profound effect on outcome in later years. The clinical manifestations of OCD among children and adolescents do not seem to be inherently different from those of adult patients. In younger subjects, the clinical picture tends to be dominated by compulsions, and insight can be poor, with little recognition of the symptoms as a problem. There is often a shift in symptoms over time, with some symptoms being replaced by others, while in adults, the core obsessions and compulsions tend to be more stable. In addition to depression and anxiety disorders, the spectrum of comorbid psychopathology seen in pediatric OCD patients includes tic, disruptive behavior, and specific developmental disorders. The treatment of childhood and adolescent OCD relies on cognitive-behavioral techniques of psychotherapy and pharmacotherapeutic interventions similar to those recommended in adults. The efficacy of exposure and response prevention in pediatric OCD has been shown in numerous open studies, and four controlled trials. Pharmacotherapy relies on serotonergic medication, and all have been demonstrated to be significantly superior to placebo, as reported in a recently published meta-analysis. Current concerns with the use of SSRIs in children and adolescents were explored as regards OCD and anxiety disorders, and there is no evidence for an increase in suicide or related behaviors. C1 Univ Ottawa, Mental Hlth Res Inst, Ottawa, ON K1Z 7K4, Canada. Massachusetts Gen Hosp, Pediat OCD Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Flament, MF (reprint author), Univ Ottawa, Mental Hlth Res Inst, 1145 Carling Ave, Ottawa, ON K1Z 7K4, Canada. EM mflament@rohcg.on.ca RI Flament, Martine/D-4550-2013 NR 119 TC 7 Z9 7 U1 10 U2 15 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 FEB PY 2007 VL 12 IS 2 SU 3 BP 43 EP 58 PG 16 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 216PB UT WOS:000249889600006 ER PT J AU Enggasser, JL Young, MA AF Enggasser, Justin L. Young, Michael A. TI Cognitive vulnerability to depression in seasonal affective disorder: Predicting mood and cognitive symptoms in individuals with seasonal vegetative changes SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE seasonal affective disorder; symptoms; vulnerability; negative cognition ID DYSFUNCTIONAL ATTITUDES; UNIPOLAR DEPRESSION; ATTRIBUTIONAL STYLE; LIGHT THERAPY; QUESTIONNAIRE; INVENTORY; BEHAVIOR; INDUCTION; DURATION; EPISODES AB Research indicates that seasonal fluctuations in vegetative functions (e.g., sleep, appetite, and energy) occur to varying degrees in the general population and a large fluctuation in vegetative functioning is often considered the core of seasonal affective disorder (SAD). The purpose of the present study was to determine if, among those with seasonal changes in vegetative functioning, a cognitive vulnerability to depression is associated with an increased risk for developing the cognitive and affective symptoms of SAD. Results indicate that participants with more dysfunctional attitudes, a more ruminative response style, and a more internal attributional style for negative events report experiencing more severe mood and cognitive symptoms of depression during the winter, controlling for the severity of vegetative symptoms. This was the case both for retrospective reports of typical symptoms and prospective reports of actual symptoms. These results provide support for Young's dual vulnerability model, in which cognitive factors interact with environmentally mediated biological factors in the pathogenesis of full-symptom SAD, and suggest that cognitively-oriented interventions may be useful as adjunctive or alternative treatments for SAD. C1 VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. IIT, Inst Psychol, Chicago, IL 60616 USA. RP Enggasser, JL (reprint author), VA Boston Healthcare Syst, Psychol Serv, 116B,150 S Huntington Ave, Boston, MA 02130 USA. EM enggasserj@iit.edu NR 49 TC 7 Z9 7 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD FEB PY 2007 VL 31 IS 1 BP 3 EP 21 DI 10.1007/s10608-006-9076-z PG 19 WC Psychology, Clinical SC Psychology GA 142YM UT WOS:000244687200002 ER PT J AU Dobscha, SK Winterbottom, LM Snodgrass, LS AF Dobscha, Steven K. Winterbottom, Lisa M. Snodgrass, LeAnn S. TI Reducing drug costs at a veterans affairs hospital by increasing market-share of generic fluoxetine SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE economics; pharmaceutical; antidepressive agents; decision support systems; clinical; drug utilization ID CONTINUING MEDICAL-EDUCATION; STRATEGIES; TRENDS; CARE AB We previously showed that a multifaceted intervention designed to contain costs of prescribing selective serotonin reuptake inhibitors (SSRIs) at a Veterans Affairs hospital resulted in substantial projected savings. Intervention components included clinician education and pharmacy and computer information process changes. We now report on effects of altering the intervention to promote prescribing of generic fluoxetine. Over 30 months, fluoxetine's market-share increased from 12 to 32% of all SSRIs prescribed. A total of $2,500,000 in cost avoidance resulted from substituting generic for brand fluoxetine, and $600,000 resulted from increases in market-share of fluoxetine. The results highlight the robustness and flexibility of the intervention approach. C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Portland Ctr Evaluat Clin Serv, Portland, OR USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, POB 1034,P3MHDC, Portland, OR 97207 USA. EM steven.dobscha@med.va.gov NR 18 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD FEB PY 2007 VL 43 IS 1 BP 75 EP 84 DI 10.1007/s10597-006-9062-7 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 142GG UT WOS:000244636800006 PM 17029000 ER PT J AU Gregory, SA MacRae, CA Aziz, K Sims, KB Schmahmann, JD Kardan, A Morss, AM Ellinor, PT Tawakol, A Fischman, AJ Gewirtz, H AF Gregory, Shawn A. MacRae, Calum A. Aziz, Kusai Sims, Katherine B. Schmahmann, Jeremy D. Kardan, Arash Morss, Alexander M. Ellinor, Patrick T. Tawakol, Ahmed Fischman, Alan J. Gewirtz, Henry TI Myocardial blood flow and oxygen consumption in patients with Friedreich's ataxia prior to the onset of cardiomyopathy SO CORONARY ARTERY DISEASE LA English DT Article DE cardiomyopathy; Friedreich's ataxia; myocardial blood flow; myocardial oxygen consumption ID NITRIC-OXIDE SYNTHASE; ISCHEMIC-HEART-DISEASE; OXIDATIVE-METABOLISM; IDEBENONE TREATMENT; CARDIAC ENERGETICS; IRON-METABOLISM; FRATAXIN GENE; IN-VITRO; HUMANS; PATHOGENESIS AB Objectives We tested the hypothesis, in patients with Friedreich's ataxia and no overt structural heart disease, that impairment of cardiac oxidative metabolism may be compensated for either by increased rest myocardial blood flow or more efficient oxygen consumption in performance of external work. Background Friedreich's ataxia is characterized by a mutant frataxin gene, which causes mitochondrial iron overload and impaired energy production. Further, it is frequently associated with cardiomyopathy. Studies using magnetic resonance spectroscopy, however, suggest impaired cardiac energetics even in the absence of structural heart disease. Methods Positron emission tomography measured rest myocardial blood flow (N-13-ammonia method) and myocardial oxygen consumption (11-C-acetate, K-mono) in Friedreich's ataxia patients (n = 8; 31 +/- 5 years, mean +/- SD, four women) and healthy controls (n = 8; 30 +/- 7 years, five women) matched for stroke work index and age. Stroke work index and power were determined by electrocardiogram gated positron emission tomography N-13-ammonia using modified Simpson's rule to compute left ventricular volumes. Results Neither stroke work index nor rest myocardial blood flow differed significantly between the groups. Although myocardial oxygen consumption was lower in Friedreich's ataxia (P < 0.001), K-mono/rest myocardial blood flow, an index of myocardial oxygen extraction, did not differ between the groups. Power/K-mono, an index of the efficiency of myocardial oxygen consumption, was greater in Friedreich's ataxia (P < 0.04). Rest myocardial blood flow normalized to rate pressure product was lower in Friedreich's ataxia (P < 0.05). Conclusions Prior to the onset of cardiomyopathy, selected patients with Friedreich's ataxia may compensate for impaired cardiac energetics through more efficient oxygen consumption rather than increased rest myocardial blood flow. The data illustrate a more general mechanism pertaining to metabolic regulation of myocardial blood flow and myocardial oxygen consumption. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Unit,Dept Med,Cardiol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Unit,Dept Med,Cardiol Div, Yawkey 5E, Boston, MA 02114 USA. EM hgewirtz@partners.org FU NHLBI NIH HHS [5K30HL004095-06, R01 HL075431]; NIA NIH HHS [R21 AG037925]; NIBIB NIH HHS [1T32EB001632-01] NR 48 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD FEB PY 2007 VL 18 IS 1 BP 15 EP 22 DI 10.1097/01.mca.0000236289.02178.60 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 126XC UT WOS:000243547800003 PM 17172925 ER PT J AU Mendez, MF Shapira, JS Clark, DG AF Mendez, Mario F. Shapira, Jill S. Clark, David G. TI "apperceptive" alexia in posterior cortical atrophy SO CORTEX LA English DT Article DE posterior cortical atrophy; dementia; Alzheimer's disease; alexia; dyslexia ID ALZHEIMERS-DISEASE; PURE ALEXIA; ATTENTIONAL DYSLEXIA; DEVELOPMENTAL DYSLEXIA; BALINTS-SYNDROME; DEMENTIA; SIMULTANAGNOSIA; PERCEPTION; MECHANISMS; NONWORDS AB The most common presenting complaint in posterior cortical atrophy (PCA) is reading difficulty. Although often described as an alexia without agraphia, alexia in PCA may have multiple causes, including a primary visuoperceptual etiology, attentional alexia, and central reading difficulty. This study evaluated 14 patients with early PCA and disturbances in reading ability in comparison to 14 normal controls. All 14 patients had a progressive disorder of complex visual functions and neuroimaging evidence of occipitoparietal dysfunction. They underwent a task requiring identification of single letters with and without flanking distractors. They also read single words consisting of regular English spelling or irregular grapheme-phoneme correspondence (irregular words) and pronounceable nonsense words (pseudowords). The PCA patients made errors in letter identification when letters were flanked by visually similar letters or numbers. They could read most single regular and irregular words but made visual errors and had particular trouble with pseudowords. They could not use a letter-by-letter reading strategy effectively. The PCA patients had similar difficulties on other visuoperceptual tests. These findings are consistent with an alexia manifested by perceptual and attentional difficulty on attempting serial visual processing of letters in the context of other letters. This "apperceptive alexia" results when the configuration of letters into words is impaired during letter-by-letter reading. Disproportionate difficulty reading pseudowords suggests an additional impairment in phonological processing. PCA patients have variable neuropathology and individual patients may have other contributions to their reading impairment. C1 VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu NR 64 TC 15 Z9 15 U1 0 U2 5 PU MASSON DIVISIONE PERIODICI PI MILANO PA VIA MUZIO ATTENDOLO DETTO SFORZA 7-9, 20141 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD FEB PY 2007 VL 43 IS 2 BP 264 EP 270 DI 10.1016/S0010-9452(08)70481-7 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 155JZ UT WOS:000245575000010 PM 17405672 ER PT J AU Alam, HB AF Alam, Hasan B. TI To cool or not to cool, that is the question SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE induced hypothermia; hypothermia secondary to shock; cardiac arrest ID HYPOTHERMIC CIRCULATORY ARREST; PROFOUND HYPOTHERMIA; SWINE MODEL; LETHAL HEMORRHAGE; CARDIAC-ARREST; SUSPENDED ANIMATION; BRAIN-DAMAGE; DOGS; INDUCTION; INJURIES C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2007 VL 35 IS 2 BP 660 EP 662 DI 10.1097/01.CCM.0000254058.61793.B5 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 129OP UT WOS:000243739100061 PM 17251722 ER PT J AU Mian, P Warchal, S Whitney, S Fitzmaurice, J Tancredi, D AF Mian, Patricia Warchal, Susan Whitney, Susan Fitzmaurice, Joan Tancredi, David TI Impact of a multifaceted intervention on nurses' and physicians' attitudes and behaviors toward family presence during resuscitation SO CRITICAL CARE NURSE LA English DT Article ID INVASIVE PROCEDURES; CARDIOPULMONARY-RESUSCITATION; MEMBER PRESENCE; RELATIVES; EXPERIENCE; EMERGENCY; ROOM; US C1 Massachusetts Gen Hosp, Emergency Dept, Boston, MA 02114 USA. Massachusetts Gen Hosp, Off Qual & Patient Safety, Boston, MA 02114 USA. RP Mian, P (reprint author), Massachusetts Gen Hosp, Emergency Dept, Fruit St, Boston, MA 02114 USA. EM pmian@partners.org NR 25 TC 43 Z9 44 U1 1 U2 2 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 J9 CRIT CARE NURSE JI Crit. Care Nurse PD FEB PY 2007 VL 27 IS 1 BP 52 EP 61 PG 10 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 135QF UT WOS:000244167400007 PM 17244859 ER PT J AU Maudsley, S Martin, B Luttrell, LM AF Maudsley, Stuart Martin, Bronwen Luttrell, Louis M. TI G protein-coupled receptor signaling complexity in neuronal tissue: Implications for novel therapeutics SO CURRENT ALZHEIMER RESEARCH LA English DT Review ID METABOTROPIC GLUTAMATE RECEPTORS; IMMUNODEFICIENCY-VIRUS TYPE-1; BETA(2) ADRENERGIC-RECEPTOR; MU-OPIOID RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTORS; AMYLOID-PRECURSOR PROTEIN; ADENOSINE A(1) RECEPTOR; 3RD INTRACELLULAR LOOP; GENE-RELATED PEPTIDE; ALZHEIMERS-DISEASE AB The manipulation of transmembrane signaling by G protein-coupled receptors (GPCRs) constitutes perhaps the single most important therapeutic target in medicine. Therapeutics acting on GPCRs have traditionally been classified as agonists, partial agonists, or antagonists based on a two state model of receptor function embodied in the ternary complex model. Over the past decade, however, many lines of investigation have shown that GPCR signaling exhibits greater diversity and 'texture' than previously appreciated. Signal diversity arises from numerous factors, among them the ability of receptors to adopt multiple 'active' states with different effector coupling profiles, the formation of receptor dimers that exhibit unique pharmacology, signaling, and trafficking, the dissociation of receptor 'activation' from desensitization and internalization, and the discovery that non-G protein effectors mediate some aspects of GPCR signaling. At the same time, clustering of GPCRs with their downstream effectors in membrane microdomains, and interactions between receptors and a plethora of multidomain scaffolding proteins and accessory/chaperone molecules confers signal preorganization, efficiency, and specificity. More importantly it is likely that alteration in the interactions of these proteins with GPCRs may occur in aging or neurodegenerative disorders, thus defining a distinct 'pharmacology' from that seen in young organisms or normal physiology. In this context, the concept of agonist selective trafficking of receptor signaling, which recognizes that a bound ligand may select between a menu of 'active' receptor conformations and induce only a subset of the possible response profile, presents the opportunity to develop drugs that change the quality as well as the quantity of efficacy and enhance these qualities for specific disorders or other paradigms. As a more comprehensive understanding of the complexity of GPCR signaling is developed, the rational design of ligands possessing increased specific efficacy and attenuated side effects may become the standard mode of drug development. C1 NIA, Lab Neurosci, Intramural Res Program, Gerontol Res Ctr,Johns Hopkins Med Ctr, Baltimore, MD 21224 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Maudsley, S (reprint author), NIA, Lab Neurosci, Intramural Res Program, Gerontol Res Ctr,Johns Hopkins Med Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM maudsleyst@grc.nia.nih.gov RI X, Simon/F-4678-2011 NR 186 TC 29 Z9 29 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD FEB PY 2007 VL 4 IS 1 BP 3 EP 19 DI 10.2174/156720507779939850 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 149AU UT WOS:000245119800002 PM 17316162 ER PT J AU Nierenberg, AA Greist, JH Mallinckrodt, CH Prakash, A Sambunaris, A Tollefson, GD Wohlreich, MM AF Nierenberg, Andrew A. Greist, John H. Mallinckrodt, Craig H. Prakash, Apurva Sambunaris, Angelo Tollefson, Gary D. Wohlreich, Madelaine M. TI Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ, Sch Med, Dept Psychiat DE antidepressants; duloxetine; Escitalopram; major depressive disorder; onset of antidepressant action ID TRUE DRUG RESPONSE; PATTERN-ANALYSIS; VENLAFAXINE-XR; PRIMARY-CARE; RAPID-ONSET; FLUOXETINE TREATMENT; REMISSION RATES; CLINICAL-TRIALS; RATING-SCALE; STRATEGIES AB Objective:The goal of a non-inferiority study is to test whether a new treatment has at least as much efficacy as an established treatment(1). The purpose of this non-inferiority study was to compare the speed of onset of antidepressant efficacy for duloxetine (a dual serotonin and norepinephrine reuptake inhibitor) and escitalopram (a selective serotonin reuptake inhibitor). Research design and methods: This was a randomized, double-blind, placebo- and active comparator-control led study, in which patients (>= 18 years) meeting DSM-IV criteria for Major Depressive Disorder (MOD) received duloxetine 60 mg once daily (QD; N = 273), escitalopram 10 mg OD (N = 274), or placebo (N = 137) for 8 weeks. The primary objective was to compare the onset of antidepressant efficacy, by testing the hypothesis that the percentage of duloxetine-treated patients achieving onset criteria at Week 2 was not inferior to that in the escitalopram group. Main outcome measures: Onset of efficacy was defined as a 20% decrease from baseline on the 17-item Hamilton Rating Scale for Depression (HAMD(17)) Maier subscale that was maintained or exceeded at all subsequent visits. Results: Probabilities of meeting onset criteria at Week 2 for duloxetine- and escitalopram-treated patients were 42.6% versus 35.2%, respectively (treatment difference = 7.4%; 95% confidence interval, -1.3% to 16.2%; p = 0.097). Both drugs showed significant improvement compared with placebo (p <= 0.05) on the primary efficacy measure (Maier subscale) at Week 1 and endpoint (Week 8). No differences were found between duloxetine, escitalopram, and placebo rates of remission or response at 8 weeks. Adverse events that occurred significantly more frequently among duloxetine-treated patients when compared with those receiving escitalopram were nausea, dry mouth, vomiting, yawning, and irritability. The rate of discontinuation due to adverse events did not differ significantly between treatment groups. Limitations: Given the difficulties in constructing appropriate dose comparisons, the results of this study should be interpreted specific to the doses tested and not extrapolated to the drug as a whole. This study employed a fixed-dose design; flexible-dose designs are more likely to find a difference between antidepressants and placebo. Conclusion: In this study, both duloxetine and escitalopram showed significantly greater improvement on the primary efficacy measure than placebo over the 8-week acute treatment period, while no differences were observed between drugs or between drugs and placebo on response and remission rates at 8 weeks. Escitalopram at a starting dose of 10 mg QD was better tolerated than duloxetine at a starting dose of 60 mg OD. This study met its pre-defined primary objective of assessing if duloxetine was non-inferior to escitalopram in antidepressant onset efficacy, and the results show that duloxetine is at least as fast as (non-inferior to) escitalopram. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Healthcare Technol Syst, Madison, WI USA. Atlanta Inst Med & Res, Atlanta, GA USA. RP Wohlreich, MM (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, DC 4103, Indianapolis, IN 46285 USA. EM mwmd@lilly.com NR 59 TC 93 Z9 100 U1 3 U2 13 PU LIBRAPHARM PI NEWBURY PA 29-35 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD FEB PY 2007 VL 23 IS 2 BP 401 EP 416 DI 10.1185/030079906X167453 PG 16 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 140TP UT WOS:000244529900018 PM 17288694 ER PT J AU Berger, JH Bardeesy, N AF Berger, Justin H. Bardeesy, Nabeel TI Modeling INK4/ARF tumor suppression in the mouse SO CURRENT MOLECULAR MEDICINE LA English DT Review ID CELL-CYCLE ARREST; NEURAL STEM-CELL; PANCREATIC DUCTAL ADENOCARCINOMA; HUMAN-DIPLOID FIBROBLASTS; RAS-INDUCED SENESCENCE; AGING HUMAN KIDNEY; INK4A/ARF LOCUS; TGF-BETA; PLASMACYTOMA SUSCEPTIBILITY; P53-DEPENDENT APOPTOSIS AB The INK4/ARF locus encodes the p15(INK4B), p16(INK4A) and p14(ARF) tumor suppressor proteins whose loss of function is associated with the pathogenesis of many human cancers. Dissecting the relative contribution of these genes to growth control in vivo is complicated by their physical contiguity and the frequency of homozygous deletions that inactivate all three components of this locus. While genetically engineered mouse models provide a rigorous system for elucidating cancer gene function, there is some evidence to suggest there are cross-species differences in regulating tumor biology. Given the prevalence of mouse models in cancer research and the potential contribution of such models to preclinical studies, it is important determine to what degree the function of these critical tumor suppressors is conserved between organisms. In this review, we assess the relative biological roles of INK4A, INK4B and ARF in mice and humans with the aim of determining the faithfulness of mouse models and also of obtaining insights into the pattern of specific tumor types that are associated with germline and somatic mutations at components of this locus. We will discuss 1) the contribution of INK4A, INK4B and ARF to growth control in vitro in a series of cell types, 2) the in vivo phenotypes associated with germline loss of function of this locus and 3) the study of Ink4a and Arf in different cancer-specific mouse models. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Bardeesy, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, CPZN 4216,185 Cambridge St, Boston, MA 02114 USA. EM nelbardeesy@partners.org FU NCI NIH HHS [P01 CA117969, K08 CA104647] NR 144 TC 18 Z9 18 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD FEB PY 2007 VL 7 IS 1 BP 63 EP 75 DI 10.2174/156652407779940477 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 128QX UT WOS:000243674300006 PM 17311533 ER PT J AU Sosnovik, DE Weissleder, R AF Sosnovik, David E. Weissleder, Ralph TI Emerging concepts in molecular MRI SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID IMAGING CONTRAST AGENT; MESENCHYMAL STEM-CELLS; MAGNETIC-RESONANCE; PARACEST AGENTS; NANOPARTICLES; ATHEROSCLEROSIS; MYELOPEROXIDASE; ANGIOGENESIS; PARTICLES; PEPTIDES AB Molecular magnetic resonance imaging (MRI) offers the potential to image some events at the cellular and subcellular level and many significant advances have recently been witnessed in this field. The introduction of targeted MR contrast agents has enabled the imaging of sparsely expressed biological targets in vivo. Furthermore, high-throughput screens of nanoparticle libraries have identified nanoparticles that act as novel contrast agents and which can be targeted with enhanced diagnostic specificity and range. Another class of magnetic nanoparticles have also been designed to image dynamic events; these act as 'switches' and could be used in vitro, and potentially in vivo, as biosensors. Other specialized MR probes have been developed to image enzyme activity in vivo. Lastly, the use of chemical exchange and off-resonance techniques have been developed, adding another dimension to the broad capabilities of molecular MRI and offering the potential of multispectral imaging. These and other advances in molecular MRI offer great promise for the future and have significant potential for clinical translation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02115 USA. RP Sosnovik, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02115 USA. EM sosnovik@nmr.mgh.harvard.edu NR 46 TC 148 Z9 154 U1 4 U2 34 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 2007 VL 18 IS 1 BP 4 EP 10 DI 10.1016/j.copbio.2006.11.001 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 141QE UT WOS:000244593000002 PM 17126545 ER PT J AU Leaf, A AF Leaf, Alexander TI Omega-3 fatty acids and prevention of arrhythmias SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE epidemiology; fish oil; n-3 fatty acids; omega-3 fatty acids; ventricular arrhythmias ID N-3 FATTY-ACIDS; FISH-OIL; CARDIOVASCULAR-DISEASE; VENTRICULAR-FIBRILLATION; ATRIAL-FIBRILLATION; CONTROLLED-TRIAL; RISK; DEFIBRILLATORS; DEATH AB Purpose of review There is now a considerable factual basis from labratory and clinical trials that omega-3 fatty acids of fish oil will prevent fatal arrhythmias in animals and humans and this is the focus of the review. Recent findings Several recent trials in humans have strengthened the evidence that omega-3 fatty acids may prevent arrhythmias although this has not been a uniform finding. Summary Since there are at present some 400 000 deaths annually in the US alone and millions more worldwide, what been learned about the antiarrhythmic actions of omega-3 fatty acids has considerable pontential public-health benefit. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Leaf, A (reprint author), 149,Room 4001,13th St, Charlestown, MA 02129 USA. EM aleaf@partners.org NR 17 TC 25 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD FEB PY 2007 VL 18 IS 1 BP 31 EP 34 DI 10.1097/MOL.0b013e328012d61b PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 133DJ UT WOS:000243991500007 PM 17218829 ER PT J AU Crum, CP Drapkin, R Miron, A Ince, TA Muto, M Kindelberger, DW Lee, YH AF Crum, Christopher P. Drapkin, Ronny Miron, Alexander Ince, Tan A. Muto, Michael Kindelberger, David W. Lee, Yonghee TI The distal fallopian tube: a new model for pelvic serous carcinogenesis SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article DE BRCA; fallopian tube; fimbria; intraepithelial carcinoma; ovarian neoplasms; p53; primary peritoneal serous carcinoma; serous carcinoma ID OVARIAN SURFACE EPITHELIUM; MUTATION CARRIERS; INCLUSION CYSTS; BRCA MUTATIONS; GERMLINE BRCA1; UNITED-STATES; CANCER; CARCINOMA; TUMORS; PHENOTYPE AB Purpose of review Research over the past 50 years has yielded little concrete information on the source of pelvic serous cancer in women, creating a knowledge gap that has adversely influenced our ability to identify, remove or prevent the earliest stages of the most lethal form ovarian cancer. Recent findings The distal fallopian tube is emerging as an established source of many early serous carcinomas in women with BRCA mutations (BRCA+). Protocols examining the fimbrial (SEE-FIM) end have revealed a noninvasive but potentially lethal form of tubal carcinoma, designated tubal intraepithelial carcinoma. Tubal intraepithelial carcinoma is present in many women with presumed ovarian or peritoneal serous cancer. A candidate precursor to tubal intraepithelial carcinoma, entitled the 'p53 signature', suggests that molecular events associated with serous cancer (p53 mutations) may be detected in benign mucosa. Summary A fully characterized precursor lesion is a first and necessary step to pelvic serous cancer prevention. The emerging data offer compelling evidence for a model of 'fimbrial-ovarian' serous neoplasia, and call attention to the distal fallopian tube as an important source for this disease, the study of which could clarify pathways to cancer in both organs and generate novel strategies for cancer prevention. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Canc Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal 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 NR 43 TC 218 Z9 227 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD FEB PY 2007 VL 19 IS 1 BP 3 EP 9 DI 10.1097/GCO.0b013e328011a21f PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 130QO UT WOS:000243814300002 PM 17218844 ER PT J AU Murtha, T Cavallerano, J AF Murtha, Timothy Cavallerano, Jerry TI The management of diabetic eye disease in the setting of cataract surgery SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE cataract surgery; combined surgery; diabetic retinopathy ID INTRAOCULAR-LENS IMPLANTATION; POSTERIOR HYALOID MEMBRANE; DIFFUSE MACULAR EDEMA; INTRAVITREAL TRIAMCINOLONE; NEOVASCULAR GLAUCOMA; NATURAL-HISTORY; VISUAL OUTCOMES; RETINOPATHY; PHACOEMULSIFICATION; VITRECTOMY AB Purpose of review The increased incidence of diabetes mellitus worldwide is accompanied by an increased risk of co-morbid conditions, including the intersection of diabetes, diabetic retinopathy and cataracts. In an effort to improve the surgical outcomes for this population, it is necessary to understand the historical perspectives that have evolved into current treatment recommendations. Recent findings While cataract surgery in patients with no or mild retinopathy may result in minimal complications, a substantial minority of patients with diabetes and advanced retinopathy, including macular edema and a history of previous laser treatment, may require additional considerations when planning cataract surgery. Untreated retinopathy, insufficiently treated retinopathy or treatment failures can be challenging. In these instances, a paradigm shift may be indicated, and the occasion of cataract surgery may provide an opportunity to simultaneously treat retinopathy. By utilizing combined vitrectomy/cataract surgical techniques and/or pharmacologic interventions, improved results for a broader diabetic population may be attainable. Summary Newer surgical and pharmacologic therapies may now allow for safe and effective surgery in individuals who were previously not candidates for surgery or who had a limited visual prognosis. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Murtha, T (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM timothy.murtha@joslin.harvard.edu NR 40 TC 13 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD FEB PY 2007 VL 18 IS 1 BP 13 EP 18 DI 10.1097/ICU.0b013e32801129fc PG 6 WC Ophthalmology SC Ophthalmology GA 124NG UT WOS:000243373900004 PM 17159441 ER PT J AU Henderson, BA Ali, R AF Henderson, Bonnie An Ali, Rasha TI Teaching and assessing competence in cataract surgery SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE assessment; cataract surgery; phacoemulsification; teaching; training ID VIRTUAL-REALITY SIMULATOR; RESIDENT EDUCATION; SURGICAL SIMULATOR; TRAINING TOOL; OPHTHALMOLOGY; PHACOEMULSIFICATION; EYE; SKILLS; BLUEPRINT; ADJUNCT AB Purpose of review To review recent literature regarding innovative techniques, methods of teaching and assessing competence and skill in cataract surgery. Recent findings The need for assessment of surgical competency and the requirement of wet lab facilities in ophthalmic training programs are being increasingly emphasized. Authors have proposed the use of standardized forms to collect objective and subjective data regarding the residents' surgical performance. Investigators have reported methods to improve visualization of cadaver and animal eyes for the wet lab, including the use of capsular dyes. The discussion of virtual reality as a teaching tool for surgical programs continues. Studies have proven that residents trained on a laparoscopic simulator outperformed nontrained residents during actual surgery for both surgical times and numbers of errors. Besides virtual reality systems, a program is being developed to separate the cognitive portion from the physical aspects of surgery. Another program couples surgical videos with three-dimensional animation to enhance the trainees' topographical understanding. Summary Proper assessment of surgical competency is becoming an important focus of training programs. The use of surgical data forms may assist in standardizing objective assessments. Virtual reality, cognitive curriculum and animation video programs can be helpful in improving residents' surgical performance. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Univ Illinois, Coll Med, Chicago, IL USA. RP Henderson, BA (reprint author), 50 Staniford St,Suite 600, Boston, MA 02114 USA. EM bahenderson@eyeboston.com NR 39 TC 29 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD FEB PY 2007 VL 18 IS 1 BP 27 EP 31 DI 10.1097/ICU.0b013e328010430e PG 5 WC Ophthalmology SC Ophthalmology GA 124NG UT WOS:000243373900007 PM 17159444 ER PT J AU Lam, F Bhatia, DN Mostofi, SB van Rooyen, K de Beer, JF AF Lam, F. Bhatia, D. N. Mostofi, S. B. van Rooyen, K. de Beer, J. F. TI Biomechanical considerations of the normal and rotator cuff deficient shoulders and the reverse shoulder prosthesis SO CURRENT ORTHOPAEDICS LA English DT Article DE cuff tear arthropathy; reverse shoulder prosthesis; rotator cuff deficient shoulder; biomechanics of shoulder ID GLENOHUMERAL JOINT; STABILITY; ARTHROPLASTY; ARTHRITIS; DESIGN AB The treatment of combined glenohumeral arthritis and massive rotator cuff deficiency remains a unique challenge. Prosthetic reconstruction is aimed at restoring the normal kinematics of the glenohumeral joint. The reverse shoulder prosthesis medialises the centre of rotation of the glenohumeral joint, thereby lengthening the deltoid lever arm. The centre of rotation is also fixed at the glenoid bone prosthesis interface and this has the effect of reducing the torque on the glenoid component and lessens the risk of glenoid loosening. To further enhance the function of deltoid, the humerus is towered relative to the glenoid, thereby increasing the deltoid tension. Although the preliminary results have been encouraging, there are still some unresolved issues such as prosthetic joint instability, scapular notching, wear of the polyethylene cup, fixation of the humeral stem and the lack of external rotation following surgery. (c) 2006 Elsevier Ltd. All rights reserved. C1 Cape Shoulder Inst, Cape Town, South Africa. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lam, F (reprint author), Cape Shoulder Inst, Medgrp Anlin House, Cape Town, South Africa. EM mrflam@hotmail.com NR 33 TC 10 Z9 10 U1 1 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0268-0890 J9 CURR ORTHOPAED JI Curr. Orthop. PD FEB PY 2007 VL 21 IS 1 BP 40 EP 46 DI 10.1016/j.cuor.2006.10.004 PG 7 WC Orthopedics SC Orthopedics GA 156TT UT WOS:000245673500005 ER PT J AU Starks, H Back, AL Pearlman, RA Koenig, BA Hsu, C Gordon, JR Bharucha, AJ AF Starks, Helene Back, Anthony L. Pearlman, Robert A. Koenig, Barbara A. Hsu, Clarissa Gordon, Judith R. Bharucha, Ashok J. TI Family member involvement in hastened death SO DEATH STUDIES LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; TERMINALLY-ILL; EUTHANASIA; CARE; PATIENT; AWARENESS; REQUESTS; ILLNESS; LIFE; END AB Four cases reveal the main themes: "taking care" included mutual protection between patients and family members; "midwifing the death" without professional support left families unprepared for adverse events; "tying up loose ends" included dealing with family members' fear of legal consequences; and "moving ahead" involved a greater risk of complicated grief when families encountered complications during the dying process. These results highlight the positive and negative consequences of family members' participation in a hastened C1 Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Seattle Canc Care Alliance, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Mayo Clin Fdn, Rochester, MN USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. RP Starks, H (reprint author), Univ Washington, Dept Med Hist & Eth, Box 357120, Seattle, WA 98195 USA. EM tigiba@u.washington.edu FU AHRQ HHS [T32 HS-013853] NR 31 TC 8 Z9 8 U1 1 U2 5 PU BRUNNER/MAZEL INC PI BRISTOL PA 1900 FROST RD, STE 101, BRISTOL, PA 19007-1598 USA SN 0748-1187 J9 DEATH STUD JI Death Stud. PD FEB PY 2007 VL 31 IS 2 BP 105 EP 130 DI 10.1080/07481180601100483 PG 26 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 130ZT UT WOS:000243838200001 PM 17410692 ER PT J AU Zraika, S Hull, RL Udayasankar, J Clark, A Utzschneider, KM Tong, J Gerchman, F Kahn, SE AF Zraika, Sakeneh Hull, Rebecca L. Udayasankar, Jayalakshmi Clark, Anne Utzschneider, Kristina M. Tong, Jenny Gerchman, Fernando Kahn, Steven E. TI Identification of the amyloid-degrading enzyme neprilysin in mouse islets and potential role in islet amyloidogenesis SO DIABETES LA English DT Article ID BETA-CELL MASS; ALZHEIMERS-DISEASE; DIABETES-MELLITUS; TRANSGENIC MOUSE; A-BETA; POLYPEPTIDE IAPP; INSULIN; PEPTIDE; MODEL; BRAIN AB Islet amyloid contributes to loss of P-cell mass and function in type 2 diabetes. It is poorly understood how the building block of amyloid, islet amyloid polypeptide (IAPP), misfolds and accumulates within the islet to contribute to cellular dysfunction. We sought to determine whether neprilysin, an amyloid-degrading enzyme, is present in islets and plays a role in the accumulation of amyloid fibrils. Human hIAPP (hIAPP) transgenic mice, a model of islet amyloid in which primarily male mice develop amyloid by 12 months of age, were studied at 10 weeks and 6 months of age, enabling investigation of islet changes before and during early amyloidogenesis. Neprilysin was present in islets, including P-cells, and islet neprilysin mRNA and activity were found to decline with age in nontransgenic mice as well as in hIAPP transgenic female mice. In contrast, neprilysin mRNA and activity did not decrease in amyloid-prone IAPP transgenic male mice at 6 months compared with nontransgenic mice and female hIAPP transgenic mice. Islet amyloid was detected in 43% of the 6-month-old hIAPP transgenic male mice only, suggesting the sustained elevation of islet neprilysin in these mice was a compensatory mechanism aimed at preventing amyloid accumulation. In keeping with amyloid formation, the proportion of insulin-positive area to islet area was significantly reduced in 6-month-old hIAPP transgenic male mice, which also displayed mild fasting hyperglycemia compared with age-matched transgenic female and nontransgenic mice. Together, these findings demonstrate that neprilysin is a factor associated with islet amyloid accumulation and subsequent deterioration of beta-cell function in hIAPP transgenic male mice. C1 VA Puget Sound Hlth Care Syst 151, US Dept Vet Affairs, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. Churchill Hosp, Oxford Ctr Diabet, Diabet Res Labs, Oxford OX3 7LJ, England. RP Zraika, S (reprint author), VA Puget Sound Hlth Care Syst 151, US Dept Vet Affairs, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM zraikas@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 NR 52 TC 22 Z9 22 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2007 VL 56 IS 2 BP 304 EP 310 DI 10.2337/db06-0430 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133CQ UT WOS:000243989600003 PM 17259373 ER PT J AU Pissios, P Ozcan, U Kokkotou, E Okada, T Liew, CW Liu, SM Peters, JN Dahgren, G Karamchandani, J Kudva, YC Kurpad, AJ Kennedy, RT Maratos-Flier, E Kulkarni, RN AF Pissios, Pavlos Ozcan, Umut Kokkotou, Efi Okada, Terumasa Liew, Chong Wee Liu, Siming Peters, Jennifer N. Dahgren, Gabriella Karamchandani, Jason Kudva, Yogish C. Kurpad, Amarnath J. Kennedy, Robert T. Maratos-Flier, Eleftheria Kulkarni, Rohit N. TI Melanin concentrating hormone is a novel regulator of islet function and growth SO DIABETES LA English DT Article ID BETA-CELL REPLICATION; DIET-INDUCED OBESITY; INSULIN-RELEASE; NEUROPEPTIDE-Y; BODY-WEIGHT; GLUCOSE-INTOLERANCE; DEFICIENT MICE; MESSENGER-RNA; RECEPTOR; EXPRESSION AB Melanin concentrating hormone (MCH) is a hypothalamic neuropeptide known to play a critical role in energy balance. We have previously reported that overexpression of MCH is associated with mild obesity. In addition, mice have substantial hyperinsulinemia and islet hyperplasia that is out of proportion with their degree of obesity. In this study, we further explored the role of MCH in the endocrine pancreas. Both MCH and MCHR1 are expressed in mouse and human islets and in clonal P-cell lines as assessed using quantitative real-time PCR and immunohistochemistry. Mice lacking MCH (MCH-KO) on either a C57B1/6 or 129Sv genetic background showed a significant reduction in P-cell mass and complemented our earlier observation of increased P-cell mass in MCH-overexpressing mice. Furthermore, the compensatory islet hyperplasia secondary to a high-fat diet, which was evident in wild-type controls, was attenuated in MCH-KO. Interestingly, MCH enhanced insulin secretion in human and mouse islets and rodent P-cell lines in a dose-dependent manner. Real-time PCR analyses of islet RNA derived from MCH-KO revealed altered expression of islet-enriched genes such as glucagon, forkhead homeobox A2, hepatocyte nuclear factor (HNF)4 alpha, and HNF1 alpha. Together, these data provide novel evidence for an autocrine role for MCH in the regulation of P-cell mass dynamics and in islet secretory function and suggest that MCH is part of a hypothalamic-islet (pancreatic) axis. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA 02215 USA. Univ Michigan, Dept Chem & Pharmacol, Ann Arbor, MI 48109 USA. Mayo Clin, Dept Endocrinol & Metab, Rochester, MN USA. RP Kulkarni, RN (reprint author), Room 602,Joslin Diabet Ctr,1 Joslin Pl, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu RI Kennedy, Robert/G-9095-2016 OI Kennedy, Robert/0000-0003-2447-7471 FU NIDDK NIH HHS [P01 DK 53115, K08 DK 02885, P30 DK 040561, P30 DK040561, P30 DK040561-11, R01 DK 46960, R01 DK 67536, R01 DK 68721, R03 DK 66207]; PHS HHS [5P30 36836] NR 52 TC 37 Z9 41 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2007 VL 56 IS 2 BP 311 EP 319 DI 10.2337/db06-0708 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133CQ UT WOS:000243989600004 PM 17259374 ER PT J AU Russo, LM del Re, E Brown, D Lin, HY AF Russo, Leileata M. del Re, Elisabetta Brown, Dennis Lin, Herbert Y. TI Evidence for a role of transforming growth factor (TGF)-beta 1 in the induction of postglomerular albuminuria in diabetic nephropathy - Amelioration by soluble TGF-beta type II receptor SO DIABETES LA English DT Article ID PROXIMAL TUBULAR CELLS; GLOMERULAR MESANGIAL CELLS; NEGATIVELY CHARGED FICOLL; MATRIX GENE-EXPRESSION; SMAD PROTEINS; HIGH-GLUCOSE; EXTRACELLULAR-MATRIX; FRACTIONAL CLEARANCE; LYSOSOMAL ACTIVITY; RENAL PASSAGE AB Transforming growth factor-beta (TGF-beta) has previously been implicated in the progression of diabetic nephropathy, including the onset of fibrosis and albuminuria. Here we report for the first time the use of a high-affinity TGF-beta 1 binding molecule, the soluble human TGF-beta type II receptor (sT beta RII.Fc), in the treatment of diabetic nephropathy in 12-week streptozotocin-induced diabetic Sprague-Dawley rats. In vitro studies using immortalized rat proximal tubule cells revealed that 50 pmol/l TGF-beta 1 disrupted albumin uptake (P < 0.001 vs. control), an inhibition significantly reversed by the use of the sT beta RII.Fc (1,200 pmol/l). In vivo studies demonstrated that treatment with sT beta RII.Fc reduced urinary albumin excretion by 36% at 4 weeks, 59% at 8 weeks (P < 0.001), and 45% at 12 weeks (P < 0.01 for diabetic vs. treated). This was correlated with an increase in megalin expression (P < 0.05 for diabetic vs. treated) and a reduction in collagen IV expression follow ing sT beta RII.Fc treatment (P < 0.001 for diabetic vs. treated). These changes occurred independently of changes in blood glucose levels. This study demonstrates that the sT beta RII.Fc is a potential new agent for the treatment of fibrosis and albuminuria in diabetic nephropathy and may reduce albuminuria by reducing TGF-beta 1-induced disruptions of renal proximal tubule cell uptake of albumin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Simches Res Ctr,Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Russo, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Simches Res Ctr,Program Membrane Biol, 185 Cambridge St,Rm 8100, Boston, MA 02114 USA. EM leileata.russo@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK 43341, DK 57521] NR 49 TC 73 Z9 82 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2007 VL 56 IS 2 BP 380 EP 388 DI 10.2337/db06-1018 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133CQ UT WOS:000243989600012 PM 17259382 ER PT J AU Mariappan, MM Feliers, D Mummidi, S Choudhury, GG Kasinath, BS AF Mariappan, Meenalakshmi M. Feliers, Denis Mummidi, Srinivas Choudhury, Goutam Ghosh Kasinath, Balakuntalam S. TI High glucose, high insulin, and their combination rapidly induce laminin-beta 1 synthesis by regulation of mRNA translation in renal epithelial cells SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; INITIATION-FACTOR 4E; PROTEIN-SYNTHESIS; GENE-EXPRESSION; MOLECULAR-MECHANISMS; SIGNALING PATHWAYS; DB/DB MICE; PHOSPHORYLATION; NEPHROPATHY; KINASE AB Laminin is a glycoprotein that contributes to renal extracellular matrix expansion in diabetes. We investigated regulation of laminin-beta 1 synthesis in murine renal proximal tubular epithelial cells by 30 mmol/l glucose (high glucose), 1 nmol/l insulin (high insulin), and their combination (high glucose+high insulin), simulating conditions observed during progression of type 2 diabetes. Compared with 5 mmol/l glucose and no insulin (control), high glucose alone, high. insulin alone, or high glucose+high insulin together increased laminin-beta 1 chain protein synthesis within 5 min, lasting for up to 60 min with no change in laminin-beta 1 mRNA levels. Cycloheximide, but not actmiomycin-D, abrogated increased laminin-beta 1 synthesis. High glucose, high insulin, and high glucose+high insulin stimulated phosphorylation of 4E-BP1, a repressor binding protein for eukaryotic initiation factor 4E (eIF4E), that was dependent on activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin. High glucose, high insulin, and high glucose+high insulin also promoted release of eIF4E from 4E-BP1, phosphorylation of eIF4E, and increase in eIF4E association with eIF4G, critical events in the initiation phase of mRNA translation. High glucose, high insulin, and high glucose+high insulin increased Erk phosphorylation, which is an upstream regulator of eIF4E phosphorylation, and PD098059, which is a MEK inhibitor that blocks Erk activation, abolished laminin-beta 1 synthesis. This is the first demonstration of rapid increment in laminin-beta 1 synthesis by regulation of its mRNA translation by cells exposed to high glucose, high insulin, or high glucose+high insulin. C1 Univ Texas, Hlth Sci Ctr, Dept Med,GRECC San Antonio, O Brien Kidney Res Ctr,S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, GRECC San Antonio,Div Infect Dis,Dept Med, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med,GRECC San Antonio, O Brien Kidney Res Ctr,S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr,MC7882, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU NIDDK NIH HHS [DK 50190, DK 55815] NR 53 TC 50 Z9 53 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2007 VL 56 IS 2 BP 476 EP 485 DI 10.2337/db05-1334 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133CQ UT WOS:000243989600024 PM 17259394 ER PT J AU Boonyasrisawat, W Eberle, D Bacci, S Zhang, YY Nolan, D Gervino, EV Johnstone, MT Trischitta, V Shoelson, SE Doria, A AF Boonyasrisawat, Watip Eberle, Delphine Bacci, Simonetta Zhang, Yuan-Yuan Nolan, David Gervino, Ernest V. Johnstone, Michael T. Trischitta, Vincenzo Shoelson, Steven E. Doria, Alessandro TI Tag polymorphisms at the A20 (TNFAIP3) locus are associated with lower gene expression and increased risk of coronary artery disease in type 2 diabetes SO DIABETES LA English DT Article ID NF-KAPPA-B; INSULIN-RESISTANCE; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS; INFLAMMATION; LYMPHOTOXIN; BETA; ATHEROGENESIS; HYPERGLYCEMIA; ACTIVATION AB A20 or tumor necrosis factor (TNF)-induced protein 3 (TNFAIP3) is a negative regulator of nuclear factor-kappa B (NF-kappa B). We have investigated whether polymorphisms in this gene are associated with increased atherosclerosis in diabetic patients. Five tag single nucleotide polymorphisms (SNPs) were typed in 479 type 2 diabetic patients from Boston, including 239 coronary artery disease (CAD)positive case subjects and 240 CAD-negative control subjects. Two tag SNPs (rs5029930 and rs610604) were independently associated with CAD; adjusted odds ratios (ORs) for minor allele carriers were 2.3 (95% CI 1.4-3.8, P = 0.001) and 2.0 (1.3-2.9, P = 0.0008), respectively. The association with rs610604 was dependent on glycemic control, with ORs of 3.9 among subjects with A1C <= 7.0% and 1.2 for those with A1C > 7.0% (P for interaction = 0.015). A similar interaction pattern was found among 231 CAD-positive and 332 CAD-negative type 2 diabetic patients from Italy (OR 2.2, P = 0.05 vs. OR 0.9, P = 0.63 in the low vs. high A1C strata, P for interaction = 0.05). Quantitative RT-PCR in blood mononuclear cells from 83 nondiabetic subjects showed that rs610604 and rs5029930 minor allele homozygotes have 30-45% lower levels of A20 mRNA than major allele homozygotes, and heterozygotes have intermediate levels (P = 0.04 and 0.028, respectively). These findings point to variability in the A20/TNFAIP3 gene as a modulator of CAD risk in type 2 diabetes. This effect is mediated by allelic differences in A20 expression. C1 Harvard Univ, Sect Genet & Epidemiol, Sch Med, Joslin Diabet Ctr,Res Div,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. IRCCS Casa Sollievo Sofferenza, Diabet & Endocrine Unit, San Giovanni Rotondo, Italy. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RP Doria, A (reprint author), Harvard Univ, Sect Genet & Epidemiol, Sch Med, Joslin Diabet Ctr,Res Div,Dept Med, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu RI Trischitta, Vincenzo/K-1487-2016 OI Trischitta, Vincenzo/0000-0003-1174-127X FU NHLBI NIH HHS [R01 HL073168-04, HL 73168, HL 71981, R01 HL073168, HL 38313]; NIDDK NIH HHS [DK 60837, DK 51729, DK 36836, DK 45943] NR 28 TC 44 Z9 48 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2007 VL 56 IS 2 BP 499 EP 505 DI 10.2337/db06-0946 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133CQ UT WOS:000243989600027 PM 17259397 ER PT J AU Florez, JC Jablonski, KA Kahn, SE Franks, PW Dabelea, D Hamman, RF Knowler, WC Nathan, DM Altshuler, D AF Florez, Jose C. Jablonski, Kathleen A. Kahn, Steven E. Franks, Paul W. Dabelea, Dana Hamman, Richard F. Knowler, William C. Nathan, David M. Altshuler, David CA Diabetes Prevention Program Res Gr TI Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the diabetes prevention program SO DIABETES LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; CHANNEL SUBUNIT KIR6.2; SENSITIVE K+ CHANNELS; INSULIN-RESISTANCE; INCREASED RISK; SUR1 ABCC8; GENE; VARIANTS; METFORMIN AB The common polymorphisms KCNJ11 E23K and ABCC A1369S have been consistently associated with type diabetes. We examined whether these variants are also associated with progression from impaired glucose tolerance (IGT) to diabetes and responses to preventive interventions in the Diabetes Prevention Program. We genotyped both variants in 3,534 participants and performed Cox regression analysis using genotype, intervention, and their interactions as predictors of diabetes incidence over similar to 3 years. We also assessed the effect of genotype on insulin secretion and insulin sensitivity at I year. As previously shown in other studies, lysine carriers at KCNJ11 E23K had reduced insulin secretion at baseline; however, they were less likely to develop diabetes than E/E homozygotes. Lysine carriers were less protected by 1-year metformin treatment than E/E homozygotes (P < 0.02). Results for ABCC8 A1369S were essentially identical to those for KCNJ11 E23K. We conclude that the lysine variant in KCNJ11 E23K leads to diminished insulin secretion in individuals with IGT. Given our contrasting results compared with case-control analyses, we hypothesize that its effect on diabetes risk may occur before the IGT-todiabetes transition. We further hypothesize that the diabetes-preventive effect of metformin may interact with the impact of these variants on insulin regulation. C1 George Washington Univ, Ctr Biostat, Diabet Prevent Program, Coordinat Ctr, Rockville, MD 20852 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Umea Hosp, Inst Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. Univ Colorado, Dept Prevent Med & Biostat, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Florez, JC (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program, Coordinat Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU Intramural NIH HHS; NIDDK NIH HHS [U01 DK048489-06, K23 DK065978, 1K23 DK 65978-03, U01 DK048489] NR 30 TC 70 Z9 74 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2007 VL 56 IS 2 BP 531 EP 536 DI 10.2337/db06-0966 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133CQ UT WOS:000243989600033 PM 17259403 ER PT J AU Maney, M Miller, DR Tseng, CL Pogagh, LM Safford, MM AF Maney, Miriam Miller, Donald R. Tseng, Chin-Lin Pogagh, Leonard M. Safford, Monika M. TI Impact of self-reported patient characteristics upon assessment of glycemic control in the Veterans Health Administration SO DIABETES CARE LA English DT Article ID QUALITY-OF-CARE; DIABETES-MELLITUS; SOCIOECONOMIC POSITION; MANAGED CARE; ADULTS; COMPLICATIONS; SYSTEM AB OBJECTIVE-The purpose of this article was to evaluate the impact of self-reported patient factors on quality assessment of Veterans Health Administration medical centers in achieving glycemic control. RESEARCH DESIGN AND METHODS-We linked survey data and administrative records for veterans who self-reported diabetes on a 1999 national weighted survey. Linear regression models were used to adjust A1C levels in fiscal year 2000 for socioeconomic status (education level, employment, and concerns of having enough food), social support (marital status and living alone), health behaviors (smoking, alcohol use, and exercise level), physical and mental health status, BMI, and diabetes duration. Medical centers were ranked by deciles, with and without adjustment for patient characteristics, on proportions of patients achieving A1C < 7 or < 8%. RESULTS-There was substantial medical center level variation in patient characteristics of the 56,740 individuals from 105 centers, e.g., grade school education (mean 15.3% [range 2.3-32.7%]), being retired (38.3% [19.9-59.7%]) or married (65.2% [43.7-77.8%]), food insufficiency (13.9% [7.2-24.6%]), and no reported exercise (43.2% [31.1-53.6%]). The final model had an R-2 of 7.8%. The Spearman rank coefficient comparing the thresholds adjusted only for age and sex to the full model was 0.71 for < 7% and 0.64 for < 8% (P < 0.0001). After risk adjustment, 4 of the 11 best-performing centers changed at least two deciles for the < 7% threshold, and 2 of 11 changed two deciles for the < 8% threshold. CONCLUSIONS-Adjustment for patient self-reported socioeconomic status and health impacts medical center rankings for glycerine control, suggesting the need for risk adjustment to assure valid inferences about quality. C1 VA New Jersey Healthcare Syst, Ctr Healthcare Knowledge Management Res, Dept Vet Affairs, VA HSR&D, E Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Alabama, Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Bedford VA Med Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Pogagh, LM (reprint author), VA New Jersey Healthcare Syst, Ctr Healthcare Knowledge Management Res, Dept Vet Affairs, VA HSR&D, 385 Tremont Ave, E Orange, NJ USA. EM len.pogach@verison.net NR 31 TC 14 Z9 14 U1 0 U2 1 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 FEB PY 2007 VL 30 IS 2 BP 245 EP 251 DI 10.2337/dc06-0771 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133PF UT WOS:000244024100008 PM 17259489 ER PT J AU Lavery, LA Peters, EJG Armstrong, DG Lipsky, BA AF Lavery, Lawrence A. Peters, Edgar J. G. Armstrong, David G. Lipsky, Benjamin A. TI Probe-to-bone test for diagnosing diabetic foot osteomyelitis - Reliable or relic? SO DIABETES CARE LA English DT Article ID LEUKOCYTE SCINTIGRAPHY; UNSUSPECTED OSTEOMYELITIS; ANTIBIOTIC-THERAPY; INFECTIONS; ULCERS; RISK; CLASSIFICATION; PREVALENCE; VALIDATION; MANAGEMENT AB OBJECTIVE-We sought to assess the accuracy of the probe-to-bone (PTB) test in diagnosing foot osteomyelitis in a cohort of diabetic patients with bone culture proven disease. RESEARCH DESIGN AND METHODS-in this 2-year longitudinal cohort study, we enrolled 1,666 consecutive diabetic individuals who under-went an initial standardized detailed foot assessment, followed by examinations at regular intervals. Patients were instructed to immediately come to the foot clinic if they developed a lower-extremity complication. For all patients with a lower-extremity wound, we compared the results of the PTB test with those of a culture of the affected bone. We called PTB positive if the bone or joint was palpable and defined osteomyelitis as a positive bone culture. RESULTS-Over a mean of 27.2 months of follow-up, 247 patients developed a foot wound and 151 developed 199 foot infections. Osteomyelitis was found in 30 patients: 12% of those with a foot wound and 20% in those with a foot infection. When all wounds were considered, the PT13 test was highly sensitive (0.87) and specific (0.91); the positive predictive value was only 0.57, but the negative predictive value was 0.98. CONCLUSIONS-The PTB test, when used in a population of diabetic patients with a foot wound among whom the prevalence of osteomyelitis was 12%, had a relatively low positive predictive value, but a negative test may exclude the diagnosis. C1 Texas A&M Univ, Scott & White Hosp, Hlth Sci Ctr, Coll Med,Dept Surg, Temple, TX 76508 USA. Rosalind Franklin Univ Med & Sci, Scholls Ctr Lower Extrem Ambulatory Res, CLEAR, N Chicago, IL USA. Leiden Univ, Med Ctr, Dept Infect Dis, NL-2300 RA Leiden, Netherlands. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Lavery, LA (reprint author), Scott & White Mem Hosp & Clin, Dept Surg, 703 Highland Spring Lane, Georgetown, TX 78628 USA. EM llavery@swmail.sw.org RI Lipsky, Benjamin/B-4645-2013; Peters, Edgar /B-7790-2014; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 57 TC 106 Z9 107 U1 0 U2 5 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 FEB PY 2007 VL 30 IS 2 BP 270 EP 274 DI 10.2337/dc06-1572 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133PF UT WOS:000244024100012 PM 17259493 ER PT J AU Bonora, E Egger, G Kiechl, S Meigs, JB Willeit, J Bonadonna, RC Oberhollenzer, F Muggeo, M AF Bonora, Enzo Egger, Georg Kiechl, Stefan Meigs, James B. Willeit, Johann Bonadonna, Riccardo C. Oberhollenzer, Friedrich Muggeo, Michele TI Insulin resistance as estimated by homeostasis model assessment predicts incident symptomatic cardiovascular disease in Caucasian subjects from the general population - The Bruneck study SO DIABETES CARE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; CORONARY-HEART-DISEASE; NITRIC-OXIDE SYNTHASE; METABOLIC SYNDROME; ENDOTHELIAL-CELLS; GLUCOSE-TOLERANCE; CAROTID-ARTERY; RISK-FACTORS; SENSITIVITY; EVENTS AB OBJECTIVE - The purpose of this study was to evaluate whether insulin resistance is associated to cardiovascular disease (CVD) and to understand whether this association can be explained by traditional and novel CVD risk factors associated with this metabolic disorder. RESEARCH DESIGN AND METHODS - We examined a sample representative of the population of Bruneck, Italy (n = 919; aged 40-79 years). Insulin-resistant subjects were those with a score in the top quartile of the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR). Risk factors correlated with insulin resistance included BMI, AlC, HDL cholesterol, triglycerides, blood pressure, high-sensitivity C-reactive protein (hsCRP), fibrinogen, oxidized LDL, vascular cell adhesion molecule-1 (VCAM-1), and adiponectin. Subjects without CVD at baseline were followed up for 15 years for incident CVD, a composite end point including fatal and nonfatal myocardial infarction and stroke, transient ischemic attack, and any revascularization procedure. RESULTS - During follow-up, 118 subjects experienced a first symptomatic CVD event. Levels of HOMA-IR were higher at baseline among subjects who developed CVD (2.8) compared with those remaining free of CVD (2.5) (P < 0.05). Levels of HOMA-IR also were significantly correlated (P < 0.05) with most CVD risk factors we evaluated. In Cox proportional hazard models, insulin-resistant subjects had an age-, sex-, and smoking-adjusted 2.1-fold increased risk (95% Cl 1.3-3.1) of incident symptomatic CVD relative to non-insulin-resistant subjects. After sequential adjustment for physical activity and classic risk factors (AIC, LDL cholesterol, and hypertension) as well as BMI, HDL cholesterol, triglycerides, and novel risk factors, including fibrinogen, oxidized LDL, hsCRP, VCAM-1, and adiponectin, the association between HCMA-IR and incident CVD remained significant and virtually unchanged (hazard ratio 2.2 [95% CI 1.4-3.6], P < 0.001). CONCLUSIONS - HOMA-estimated insulin resistance is associated with subsequent symptomatic CVD in the general population independently of all classic and several nontraditional risk factors. These data suggest that insulin resistance may be an important target to reduce CVD risk. C1 Univ Verona, Sch Med, Div Endocrinol & Metab Dis, I-37100 Verona, Italy. Univ Innsbruck, Sch Med, Dept Neurol, A-6020 Innsbruck, Austria. Hosp Bruneck, Div Internal Med, Brunico, Italy. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. RP Bonora, E (reprint author), Osped Maggiore, Piazzale Stefani 1, I-37126 Verona, Italy. EM enzobonora@virgilio.it OI BONORA, Enzo/0000-0003-1074-5164; Bonadonna, Riccardo/0000-0002-9809-1005 NR 54 TC 135 Z9 144 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 FEB PY 2007 VL 30 IS 2 BP 318 EP 324 DI 10.2337/dc06-0919 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133PF UT WOS:000244024100020 PM 17259501 ER PT J AU Wexler, DJ Meigs, JB Cagliero, E Nathan, DM Grant, RW AF Wexler, Deborah J. Meigs, James B. Cagliero, Enrico Nathan, David M. Grant, Richard W. TI Prevalence of hyper- and hypoglycemia among inpatients with diabetes - A national survey of 44 US hospitals SO DIABETES CARE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL PATIENTS; SLIDING-SCALE INSULIN; GLYCEMIC CONTROL; MANAGEMENT; MELLITUS; MORTALITY; ASSOCIATION; INFUSION; TEAM C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Wexler, DJ (reprint author), Massachusetts Gen Hosp, Diabet Unit, Bulfinch 408,55 Fruit St, Boston, MA 02114 USA. EM dwexler@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK080228, K23 DK 067452] NR 24 TC 68 Z9 71 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 FEB PY 2007 VL 30 IS 2 BP 367 EP 369 DI 10.2337/dc06-1715 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133PF UT WOS:000244024100030 PM 17259511 ER PT J AU Cohen, A Lim, KH Lee, Y Rana, S Karumanchi, SA Brown, F AF Cohen, Allison Lim, Kee-Hak Lee, Young Rana, Sarosh Ananth Karumanchi, S. Brown, Florence TI Circulating levels of the antiangiogenic marker soluble FM-like tyrosine kinase 1 are elevated in women with pregestational diabetes and preeclampsia - Angiogenic markers in preeclampsia and preexisting diabetes SO DIABETES CARE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE-1; FACTOR RECEPTOR; RISK; PATHOGENESIS; PREGNANCIES; ENDOGLIN C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. Brown Univ, Providence, RI 02912 USA. RP Brown, F (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM florence.brown@joslin.harvard.edu NR 16 TC 13 Z9 13 U1 0 U2 1 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 FEB PY 2007 VL 30 IS 2 BP 375 EP 377 DI 10.2337/dc06-1514 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133PF UT WOS:000244024100033 PM 17259514 ER PT J AU Nathan, DM AF Nathan, David M. TI Counterpoint: No time to inhale: Arguments against inhaled insulin in 2007 SO DIABETES CARE LA English DT Editorial Material ID AMERICAN-DIABETES-ASSOCIATION; CONSENSUS ALGORITHM; MANAGEMENT; THERAPY; HYPERGLYCEMIA; ADJUSTMENT; INITIATION; STATEMENT; MELLITUS C1 Harvard Univ, Sch Med, Ctr Diabet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Harvard Univ, Sch Med, Ctr Diabet, 50 Staniford St,Suite 340, Boston, MA 02114 USA. EM dnathan@partners.org NR 14 TC 2 Z9 2 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 FEB PY 2007 VL 30 IS 2 BP 442 EP 443 DI 10.2337/dc06-2331 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133PF UT WOS:000244024100047 PM 17259528 ER PT J AU Nathan, DM Chew, E Christophi, CA Davis, MD Fowler, S Goldstein, BJ Hamman, RF Hubbard, LD Knowler, WC Molitch, ME AF Nathan, D. M. Chew, E. Christophi, C. A. Davis, M. D. Fowler, S. Goldstein, B. J. Hamman, R. F. Hubbard, L. D. Knowler, W. C. Molitch, M. E. CA Diabetes Prevention Program R TI The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program SO DIABETIC MEDICINE LA English DT Article DE impaired glucose tolerance; retinopathy; Type 2 diabetes ID RETINAL MICROVASCULAR ABNORMALITIES; DIAGNOSIS; RISK; COMPLICATIONS; MELLITUS; TRIAL; NIDDM AB Aims Retinopathy is considered the complication most closely associated with and characteristic of diabetes mellitus. Hyperglycaemia below levels diagnostic of diabetes, so called pre-diabetes, is associated with a low prevalence of 'diabetic' retinopathy. However, few longitudinal studies of non-diabetic populations have performed repeated measures of glycaemia and screened for retinopathy to determine its occurrence in the non-diabetic population and the onset of retinopathy in new-onset diabetic patients. We determined the prevalence of retinopathy characteristically seen in diabetes in persons with impaired glucose tolerance and in patients with new-onset diabetes of known duration in the Diabetes Prevention Program (DPP) cohort. Methods The DPP recruited persons with elevated fasting glucose (5.3-6.9 mmol/l) and impaired glucose tolerance, and no history of diagnosed diabetes, other than gestational diabetes not persisting after pregnancy. Seven-field, stereoscopic fundus photography was completed a mean of 3.1 years after the development of diabetes in 594 of 878 participants who had developed diabetes during the DPP, and in a random sample of 302 participants who remained non-diabetic. Results Retinopathy consistent with diabetic retinopathy was detected in 12.6 and 7.9% of the diabetic and non-diabetic participants, respectively (P = 0.03, comparing prevalence in the two groups). Systolic blood pressure and HbA(1c) were higher at baseline in the diabetic participants who had retinopathy compared with the diabetic participants without retinopathy. Conclusions Retinopathy characteristic of diabetes is present in persons with elevated fasting glucose and impaired glucose tolerance and no known history of diabetes. The prevalence of retinopathy is significantly higher in persons who develop diabetes, even within 3 years of diagnosis. C1 George Washington Univ, Ctr Biostat, Diabet Prevent Program Res Grp, Rockville, MD 20852 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NEI, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NIDDKD, Phoenix, AZ 85016 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Nathan, DM (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Res Grp, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu NR 24 TC 138 Z9 139 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD FEB PY 2007 VL 24 IS 2 BP 137 EP 144 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 130HO UT WOS:000243790900006 ER PT J AU Ahn, YB Xu, G Marselli, L Toschi, E Sharma, A Bonner-Weir, S Sgroi, DC Weir, GC AF Ahn, Y. B. Xu, G. Marselli, L. Toschi, E. Sharma, A. Bonner-Weir, S. Sgroi, D. C. Weir, G. C. TI Changes in gene expression in beta cells after islet isolation and transplantation using laser-capture microdissection SO DIABETOLOGIA LA English DT Article DE islet; laser-capture microdissection; transplantation ID RAT PANCREATIC-ISLETS; INDUCED INSULIN-SECRETION; LACTATE-DEHYDROGENASE; APOPTOSIS; REVASCULARIZATION; ACTIVATION; LANGERHANS; MASS; PROGRESSION; ANTIOXIDANT AB Aims/hypothesis The process of islet isolation can cause chemical and mechanical injury to beta cells. In addition, hyperglycaemia after islet transplantation can compromise beta cell function. The aim of this experiment was to evaluate changes in gene expression in endogenous islets using laser-capture microdissection (LCM). Materials and methods Islets from B6AF1 mice were studied in situ in the pancreas as well as those freshly isolated or cultured for 24 h. Fresh islets were transplanted under the kidney capsule of syngeneic diabetic (streptozocin-induced) and non-diabetic mice. Frozen sections from all the samples were prepared for LCM to obtain beta cell-enriched tissue; RNA was extracted and amplified using T7 polymerase. RT-PCR was used to assess expression of selected genes critical for beta cell function (Ins, Ipf1 [previously known as Pdx1], Slc2a2 [previously known as GLUT2] and Ldha) and the stress response (Hmox1 [previously known as HO-1], Gpx1, Tnfaip3 [previously known as A20] and Fas). Immunostaining was also performed. Results In freshly isolated and cultured islets, insulin and Ipf1 mRNA levels were decreased by 40% (compared with islets in situ), while stress genes were upregulated. Comparison between in situ pancreatic islets and engrafted beta cells of cured mice showed declines in Ipf1 expression. Conclusions Our experiment, the first report to investigate changes in gene expression in endogenous islets using LCM, indicate that beta cells following islet isolation and residing in a foreign graft environment have decreased expression of genes involved in insulin production and increased expression of stress genes. Our data suggest that an islet graft, even in successful transplantation, may be different from endogenous islets in gene expression. C1 Harvard Univ, Sch Med, Sect Islet Transplantat & Cell Biol, Div Res,Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Mol Pathol Unit, Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Sect Islet Transplantat & Cell Biol, Div Res,Joslin Diabet Ctr, Boston, MA 02215 USA. EM Gordon.Weir@joslin.harvard.edu FU NIDDK NIH HHS [DK 50657, DK36836-16, U19DK6125] NR 37 TC 34 Z9 35 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2007 VL 50 IS 2 BP 334 EP 342 DI 10.1007/s00125-006-0536-5 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123VC UT WOS:000243323200012 PM 17180350 ER PT J AU Wang, H Brun, T Kataoka, K Sharma, AJ Wollheim, CB AF Wang, H. Brun, T. Kataoka, K. Sharma, A. J. Wollheim, C. B. TI MAFA controls genes implicated in insulin biosynthesis and secretion SO DIABETOLOGIA LA English DT Article DE beta cells; human; islet insulin secretion; MAFA; metabolism ID PANCREATIC BETA-CELLS; DIFFERENTIATION FACTOR NKX6.1; TRANSCRIPTION FACTOR; LACTATE-DEHYDROGENASE; KEY REGULATOR; EXPRESSION; GLUCOSE; MICE; GLUCAGON; PDX-1 AB Aims/hypothesis Effects of the transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA) on the regulation of beta cell gene expression and function were investigated. Materials and methods INS-1 stable cell lines permitting inducible up- or downregulation of this transcription factor were established. Results MAFA overproduction enhanced and its dominant-negative mutant (DN-MAFA) diminished binding of the factor to the insulin promoter, correlating with insulin mRNA levels and cellular protein content. Glucose-stimulated insulin secretion was facilitated by MAFA and blunted by DN-MAFA. This is partly due to alterations in glucokinase production, the glucose sensor of beta cells. In addition, the expression of important beta cell genes, e.g. those encoding solute carrier family 2 (facilitated glucose transporter), member 2 (formerly known as GLUT2), pancreatic and duodenal homeobox factor 1 (PDX1), NK6 transcription factor-related, locus 1 (NKX6-1), glucagon-like peptide 1 receptor (GLP1R), prohormone convertase 1/3 (PCSK1) and pyruvate carboxylase (PC), was regulated positively by MAFA and negatively by DN-MAFA. Conclusions/interpretations The data suggest that MAFA is not only a key activator of insulin transcription, but also a master regulator of genes implicated in maintaining beta cell function, in particular metabolism-secretion coupling, proinsulin processing and GLP1R signalling. Our in vitro study provides molecular targets that explain the phenotype of recently reported Mafa-null mice. We also demonstrate that MAFA is produced specifically in beta cells of human islets. Glucose influenced DNA-binding activity of MAFA in rat islets in a bell-shaped manner. MAFA thus qualifies as a master regulator of beta-cell-specific gene expression and function. C1 Nara Inst Sci & Technol, Grad Sch Biol Sci, Mol & Dev Biol Lab, Ikoma, Japan. Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Univ Geneva, Med Ctr, Dept Cell Physiol & Metab, CH-1211 Geneva 4, Switzerland. RP Wang, H (reprint author), Hoffmann La Roche AG, PRBD Metab Dis, Basel, Switzerland. EM haiyan.wang.hw2@Roche.com; claes.wollheim@medecine.unige.ch FU NIDDK NIH HHS [R01 DK060127, R01 DK060127-03, R01 DK060127-05, R01 DK06127, R01 DK060127-02, R01 DK060127-01A2, R01 DK060127-04] NR 50 TC 94 Z9 103 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2007 VL 50 IS 2 BP 348 EP 358 DI 10.1007/s00125-006-0490-2 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123VC UT WOS:000243323200014 PM 17149590 ER PT J AU Tong, J Utzschneider, KM Carr, DB Zraika, S Udayasankar, J Gerchman, F Knopp, RH Kahn, SE AF Tong, J. Utzschneider, K. M. Carr, D. B. Zraika, S. Udayasankar, J. Gerchman, F. Knopp, R. H. Kahn, S. E. TI Plasma pancreatic polypeptide levels are associated with differences in body fat distribution in human subjects SO DIABETOLOGIA LA English DT Article DE insulin resistance; pancreatic polypeptide; parasympathetic nervous system; visceral fat ID PIMA-INDIANS; FOOD-INTAKE; SECRETION; OBESITY AB Pancreatic polypeptide (PP) is produced by the F-cells of the pancreas, and its plasma concentration has been used as a marker of parasympathetic activity. Recent work in rodents suggests that there is both sympathetic and parasympathetic innervation of white adipose tissue and that parasympathetic activity is anabolic resulting in lipid accumulation. We have examined whether in humans increased PP levels are associated with increased intra-abdominal fat (IAF), and thereby insulin resistance. We measured PP levels in 177 non-diabetic subjects (75 male/102 female; age 32-75 years) 3 min after an i.v. glucose bolus during a frequently sampled intravenous glucose tolerance test. IAF and s.c. fat (SCF) areas were measured by CT scan. The insulin sensitivity index (S (I)) was quantified using Bergman's minimal model. PP levels were higher in men than in women (96.2 +/- 72.2 vs 76.1 +/- 55.0 pg/ml, mean +/- SD, p=0.037), as was IAF area (124.7 +/- 67.4 vs 83.0 +/- 57.7 cm(2), p < 0.001). While PP levels were significantly associated with IAF (r=0.16, p=0.031), WHR (r=0.30, p < 0.001) and age (r=0.37, p < 0.01), they were not associated with SCF (r=0.02, p=0.829). The association between PP and IAF was not independent of age and/or sex. S-I was negatively associated with PP levels (r=-0.17, p=0.026) and IAF area (r=-0.65, p < 0.001). The association between S-I and PP disappeared after adjusting for IAF area, indicating that S-I was not a major determinant of PP levels. In humans, age and sex may modulate the association between plasma PP level and IAF area, suggesting that they may be determinants of parasympathetic activity and thus IAF accumulation. C1 Univ Washington, Harborview Med Ctr, VA Puget Sound Hlth Care Syst, Dept Med,Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. RP Tong, J (reprint author), Univ Washington, Harborview Med Ctr, VA Puget Sound Hlth Care Syst, Dept Med,Div Metab Endocrinol & Nutr, 151,1660 S Columbia Way, Seattle, WA 98108 USA. EM tongj@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NHLBI NIH HHS [HL-07028, HL-30086]; NIDDK NIH HHS [DK-17047, DK-02456, DK-02654, DK-35747, DK-35816, DK-59417] NR 10 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2007 VL 50 IS 2 BP 439 EP 442 DI 10.1007/s00125-006-0553-4 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123VC UT WOS:000243323200024 PM 17171555 ER PT J AU Chow, FY Nikolic-Paterson, DJ Ma, FY Ozols, E Rollins, BJ Tesch, GH AF Chow, F. Y. Nikolic-Paterson, D. J. Ma, F. Y. Ozols, E. Rollins, B. J. Tesch, G. H. TI Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice SO DIABETOLOGIA LA English DT Article DE adipose; Ccl2; db; db mice; diabetes; diabetic nephropathy; inflammation; insulin resistance; macrophage; MCP-1 ID INDUCED INSULIN-RESISTANCE; MACROPHAGE ACCUMULATION; ADIPOSE-TISSUE; SIGNAL-TRANSDUCTION; CYTOKINE EXPRESSION; HUMAN ADIPOCYTES; NEPHROPATHY; RECEPTOR; PROTEIN; MCP-1 AB Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy. Monocyte chemoattractant protein-1 (MCP-1) is a potent stimulator of macrophage recruitment. It is increased in adipose tissue during obesity and in diabetic kidneys, suggesting that inflammation of these tissues may be MCP-1-dependent. Based on these findings, the aim of this study was to examine whether a deficiency in MCP-1 would alter the development of type 2 diabetes and its renal complications. The role of MCP-1 in the progression of type 2 diabetes and its associated renal injury was assessed in obese db/db mice that were deficient in the gene encoding MCP-1 (Ccl2). The incidence and development of type 2 diabetes were similar in Ccl2(+/+) and Ccl(-/-) db/db mice between 8 and 32 weeks of age. Body mass, hyperglycaemia, hyperinsulinaemia, glucose and insulin tolerance, plasma triacylglycerol and serum NEFA were not different between these strains. Pathological changes in epididymal adipose tissue, including increases in macrophage accumulation and Tnfa mRNA and reductions in Adipoq mRNA, were unaffected by the absence of MCP-1. In contrast, kidney macrophage accumulation and the progression of diabetic renal injury (albuminuria, histopathology, renal fibrosis) were substantially reduced in Ccl2(-/-) compared with Ccl2(+/+) db/db mice with equivalent diabetes. Our study demonstrates that MCP-1 promotes type 2 diabetic renal injury but does not influence the development of obesity, insulin resistance or type 2 diabetes in db/db mice. MCP-1 plays a critical role in inflammation of the kidney, but not adipose tissue, during the progression of type 2 diabetes. C1 Monash Med Ctr, Dept Nephrol, Clayton, Vic 3168, Australia. Monash Univ, Dept Med, Monash Med Ctr, Clayton, Vic 3168, Australia. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Tesch, GH (reprint author), Monash Med Ctr, Dept Nephrol, Clayton, Vic 3168, Australia. EM gtesch@hotmail.com RI Tesch, Greg/I-1444-2013 OI Tesch, Greg/0000-0002-6137-3092 NR 33 TC 116 Z9 132 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2007 VL 50 IS 2 BP 471 EP 480 DI 10.1007/s00125-006-0497-8 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123VC UT WOS:000243323200028 PM 17160673 ER PT J AU Skaznik-Wikiel, M Tilly, JC Lee, HJ Niikura, Y Kaneko-Tarui, T Johnson, J Tilly, JL AF Skaznik-Wikiel, Malgorzata Tilly, Jacqueline Canning Lee, Ho-Joon Niikura, Yuichi Kaneko-Tarui, Tomoko Johnson, Joshua Tilly, Jonathan L. TI Serious doubts over "Eggs forever?" SO DIFFERENTIATION LA English DT Editorial Material DE ovary; oocyte; stem cell; germ cell; oogenesis ID GERMLINE STEM-CELLS; POSTNATAL OOGENESIS; OOCYTE APOPTOSIS; MAMMALIAN OVARY; TRANSPLANTATION; OVOGENESIS; FERTILITY; BUSULFAN; ATRESIA; TESTIS AB A recent commentary in this journal by Byskov et al. (2005) claims that, despite published results from numerous independent lines of investigation from our laboratory and others, there does not "exist any evidence for neo-folliculogenesis in the adult mammalian ovary." While we agree with Byskov et al. that our work represents a radical departure from the age-old dogma that mammalian females permanently lose the capacity for oocyte and follicle production during the perinatal period, careful examination of all of the available data leaves no doubt that adult female mammals retain the capacity for oogenesis and folliculogenesis. These findings do not change the fact that exhaustion of the oocyte pool occurs with advancing chronological age-a process responsible for driving the menopause in women-but rather question the basic mechanism underlying age-related ovarian failure. In this regard, studies of aging male mice have demonstrated that testicular atrophy is associated with a dramatic decline in the number, activity and quality of germline stem cells that maintain spermatogenesis during adulthood (Zhang et al., 2006). Therefore, to the contrary of the opinion of Byskov et al. that such a process would be "considered exceptional among stem cells," it is certainly reasonable to hypothesize that a similar deterioration of female germline stem cell function underlies the decline in oocyte quality and the onset of ovarian failure in aging females. Further, while we accept that a departure from conventional thinking can take years to gain widespread acceptance, we feel this resistance to change should not be construed as the sole means to voice opinions about the validity of our data or the maturity of our principal conclusion. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06510 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. EM jtilly@partners.org FU NIA NIH HHS [R01-AG024999, R01/R37-AG012279] NR 35 TC 26 Z9 28 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD FEB PY 2007 VL 75 IS 2 BP 93 EP 99 DI 10.1111/j.1432-0436.2006.00117.x PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 136MI UT WOS:000244227500001 PM 17316379 ER PT J AU Leung, FW AF Leung, Felix W. TI Etiologic factors of chronic constipation - Review of the scientific evidence SO DIGESTIVE DISEASES AND SCIENCES LA English DT Review DE chronic constipation; etiology ID FLUID INTAKE; EXERCISE; DIETARY AB Geriatric patient educational material and a general practice review suggest insufficient dietary fiber intake, inadequate fluid intake, decrease physical activity, side effects of drugs, hypothyroidism, sex harmones and colorectal cancer obstructin may play a role in the pathogenesis of constipation. A search of recent literature, however, reveals that there is a paucity of evidence-based publications that address the etiologic factors of chronic constipation. Much of current writings on the subject may be based primarily on myths handed down from one generation to the next. In the absence of well-designed studies, there do not appear to be sufficient evidence-based information to implicate the above as major etilogic factors in the development of chronic constipation. The etiological role of each of these factors in the development of chronic constipation deserves to be assessed by modern techniques and methodologies. Funding agencies including the government and industry sponsors should support the development of evidence-based data sets. The understanding of the etiology of chronic constipation is the foundation on which cost-effective management strategies are to be built. C1 VA Sepulveda Ambulatory Care Ctr, Div Gastroenterol Res & Med Serv, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 91343 USA. RP Leung, FW (reprint author), VA Sepulveda Ambulatory Care Ctr, Div Gastroenterol Res & Med Serv, 111G,16111 Plummer St, Sepulveda, CA 91343 USA. EM felix.leung@va.gov NR 16 TC 27 Z9 27 U1 2 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 2007 VL 52 IS 2 BP 313 EP 316 DI 10.1007/s10620-006-9298-7 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 131XD UT WOS:000243904600002 PM 17219073 ER PT J AU Borsook, D Pendse, G Aiello-Lammens, M Glicksman, M Gostic, J Sherman, S Korn, J Shaw, M Stewart, K Gostic, R Bazes, S Hargreaves, R Becerra, L AF Borsook, David Pendse, Gautam Aiello-Lammens, Mathew Glicksman, Marcie Gostic, Julie Sherman, Seth Korn, Joshua Shaw, Marnie Stewart, Ken Gostic, Richard Bazes, Shelly Hargreaves, Richard Becerra, Lino TI CNS response to a thermal stressor in human volunteers and rats may predict the clinical utility of analgesics SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE pain; drug development; analgesics; fMRI; BOLD response; circuits; translational medicine; drug efficacy ID PRIMATE SPINOTHALAMIC NEURONS; DRUG DEVELOPMENT COSTS; NEUROPATHIC PAIN; HUMAN BRAIN; NOXIOUS HEAT; CYCLOOXYGENASE-2 INHIBITOR; HEALTHY-VOLUNTEERS; CUTANEOUS HYPERALGESIA; CENTRAL SENSITIZATION; GABAPENTIN NEURONTIN AB fMRI was used to test the hypothesis that global brain activation following a stressor (a thermal stimulus) that activates multiple brain circuits in healthy subjects can predict which drugs have higher potential for clinical utility for neuropathic pain. The rationale is that a drug will modulate multiple neural circuits that are activated by the system-specific stressor (e.g., pain). In neuropathic pain, some brain circuits have altered function, but most brain systems are '' normal.'' Thus, the manner in which a drug effect on neural circuits is modulated by the stressor may provide insight into the clinical utility based on the readout of brain activation in response to the stimulus. Six drugs with known clinical efficacy (or lack thereof) in treating neuropathic pain were selected and the CNS response to each drug in the presence or absence of a pain stimulus was examined. The present results suggest that it is possible to identify potentially effective drugs based on patterns of brain activation in healthy human subjects and indicate that CNS activity is a more sensitive measure of drug action than standard psychophysical measures of pain intensity. This approach was repeated in rats and showed that a similar WRI paradigm segregates these drugs in a similar manner suggesting a potential '' translational tool '' in evaluating drug efficacy for neuropathic pain. The sensitivity of this paradigm using fMRI allows clinical screening in small groups of healthy subjects, suggesting it could become a useful tool for drug development as well as for elucidating the mechanisms of neuropathic disease and therapy. C1 Harvard Univ, McLean Hosp, Sch Med, PAIN Grp,Brain Imaging Ctr, Belmont, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula Martinos Ctr Bioengn, Belmont, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Neurodegenerat & Repair, Belmont, MA USA. Merck & Co Inc, Imaging, West Point, PA USA. RP Borsook, D (reprint author), Harvard Univ, McLean Hosp, Sch Med, PAIN Grp,Brain Imaging Ctr, 115 Mill St, Belmont, MA USA. EM dborsook@mclean.harvard.edu OI Aiello-Lammens, Matthew/0000-0002-6180-5959 NR 93 TC 16 Z9 16 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD FEB PY 2007 VL 68 IS 1 BP 23 EP 41 DI 10.1002/ddr.20163 PG 19 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172QR UT WOS:000246819500003 ER PT J AU Matthes, K Sahani, D Holalkere, NS Mino-Kenudson, M Brugge, WR AF Matthes, K. Sahani, D. Holalkere, N. S. Mino-Kenudson, M. Brugge, W. R. TI Feasibility of endoscopic ultrasound-guided embolization of the splenic vein SO ENDOSCOPY LA English DT Editorial Material ID ENCEPHALOPATHY C1 [Matthes, K.; Brugge, W. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Sahani, D.; Holalkere, N. S.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mino-Kenudson, M.] Harvard Univ, Sch Med, Dept Pathol,Gastrointestinal Pathol Serv, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Brugge, WR (reprint author), 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM wbrugge@partners.org OI Holalkere, Nagaraj/0000-0001-6324-7682 NR 5 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD FEB PY 2007 VL 39 SU 1 BP E3 EP E4 DI 10.1055/s-2006-944725 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 366AI UT WOS:000260451400003 PM 17285498 ER PT J AU Neuzil, P Taborsky, M Rezek, Z Vopalka, R Sediva, L Niederle, P Reddy, V AF Neuzil, Petr Taborsky, Milos Rezek, Zdenek Vopalka, Roman Sediva, Lucie Niederle, Petr Reddy, Vivek TI Pacemaker and ICD lead extraction with electrosurgical dissection sheaths and standard transvenous extraction systems: results of a randomized trial SO EUROPACE LA English DT Article DE electrosurgical dissection sheaths; transvenous lead extraction; pacemaker infection ID EXPERIENCE; MANAGEMENT AB Aims The purpose of this prospective randomized study was to evaluate the safety and efficacy of transvenous pacemaker and implantable cardioverter-defibritlator (ICD) lead extraction with an etectrosurgical dissection sheath (EDS) system in a single-centre experience. Methods Over 10 years, 462 patients have undergone transvenous lead extraction in our institution. From these, 120 consecutive patients (with 161 leads) were randomized to either radiofrequency (RF) current supported extraction or standard countertraction lead removal (60 patients in each arm, 96 men and 24 women). The mean age of randomized patients was 62.7 +/- 9.6 years. In 16 patients, we explanted 17 ICD leads. The average time from the date of implantation to the extraction procedure was 73.4 +/- 15.7 months. The most common reason for lead extraction was infection (95.6%). Results The complete extraction of 78 leads (93%) was achieved in the RF group and 56 leads (73%) with the standard transvenous lead extraction system by counter-traction (P < 0.01). Among these leads, we successfully removed nine of 10 ICD leads (90%) in the RF group and only four of seven ICD leads (57%) in the standard group. We also observed a significant reduction in the time taken for the successful removal of pacemaker and ICD leads using the RF system (9.6 +/- 6.2 min versus 21 +/- 9 min, P < 0.01). Partial success was achieved in six patients with the RF system and in I I with standard sheaths. In those cases where we failed to remove the lead from the body we sent all but one patient to cardiac surgery. S erious complications were associated with the standard system in two patients, both of whom developed septic pulmonary embolization. Serious bleeding occurred in three patients, one with standard and two with the EDS lead extraction system. Conclusion The EDS extraction system is significantly more effective and quicker. However, the standard counter-traction method is still an effective alternative when used in a highly experienced centre. C1 Na Homolce Hosp, Dept Cardiol, Prague 515030, Czech Republic. Massachusetts Gen Hosp, Dept Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Neuzil, P (reprint author), Na Homolce Hosp, Dept Cardiol, Roentgenova 2, Prague 515030, Czech Republic. EM petr.neuzil@homolka.cz NR 17 TC 47 Z9 49 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD FEB PY 2007 VL 9 IS 2 BP 98 EP 104 DI 10.1093/europace/eul171 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 143BW UT WOS:000244696000004 PM 17272329 ER PT J AU Awaida, JPS Moreiras, JM Palacios, IF AF Awaida, Jean-Pierre S. Moreiras, Javier M. Palacios, Igor F. TI Three overlapping septal occlusion devices to treat residual shunting across an atrial septal defect SO EUROPEAN HEART JOURNAL LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Awaida, JPS (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 853, Boston, MA 02114 USA. EM awaida.jeanpierre@mgh.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD FEB PY 2007 VL 28 IS 4 BP 385 EP 385 DI 10.1093/eurheartj/ehl145 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 149WG UT WOS:000245177000002 PM 17303590 ER PT J AU Lanuti, M de Delva, PE Wright, CD Gaissert, HA Wain, JC Donahue, DM Allan, JS Mathisen, DJ AF Lanuti, Michael de Delva, Pierre E. Wright, Cameron D. Gaissert, Henning A. Wain, John C. Donahue, Dean M. Allan, James S. Mathisen, Douglas J. TI Post-esophagectomy gastric outlet obstruction: role of pyloromyotomy and management with endoscopic pyloric dilatation SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery/14th Annual Meeting of the European-Society-of-Thoracic-Surgeons CY SEP 10-13, 2006 CL Stockholm, SWEDEN SP European Assoc Cardio Thorac Surg, European Soc Thorac Surg DE esophagectomy; esophageal cancer; gastric outlet obstruction ID RANDOMIZED CONTROLLED TRIAL; INTRATHORACIC STOMACH; NO DRAINAGE; PYLOROPLASTY; REPLACEMENT; ESOPHAGUS AB Objective: Gastric outlet obstruction is common after esophagectomy. Our goal was to determine the incidence of gastric outlet obstruction after esophagectomy with or without pyloromyotomy and analyze its management by endoscopic pyloric dilatation. Methods: Two hundred forty-two patients underwent esophagectomy with gastric conduit from January 2002 to June 2006. Subjects were divided into two groups: Group A had no pyloromyotomy (n = 83) and Group B had a pytoromyotomy (n = 159). Gastric outlet obstruction was strictly defined to include patients with clinical delayed gastric emptying supported by symptoms, barium swallow studies, persistent air-fluid level and dilated conduit on radiography, or endoscopic or surgical intervention to improve gastric drainage. Results: The groups were similar except for a higher percentage of cervical anastomosis and older age (64- vs 61 -year-old) in Group A. The overall incidence of gastric outlet obstruction was 15.3% (37/242). Pyloromyotomy did not reduce the incidence of gastric outlet obstruction (Group A 9.6% vs Group B 18.2%, p = 0.078). One patient required a late pytoroplasty. Successful management of gastric outlet obstruction with pyloric dilatation (96.7%, 28/29) was unaffected by pyloromyotomy. There was no difference in length of stay, pneumonia (Group A 27.7% vs Group B 19.5%, p = 0.15), respiratory failure or anastomotic stricture. There was no difference in anastomotic leaks when controlling for the anatomic location of the anastomosis (p = 0.36). Mortality was equivalent between groups (2.4 vs 2.5%, p = 0.96). Conclusion: Pyloromyotomy does not reduce the incidence of symptomatic delayed gastric emptying after esophagectomy. Post-operative gastric outlet obstruction can be effectively managed with endoscopic pyloric dilatation. Routine pytoromyotomy for the prevention of post-esophagectomy gastric outlet obstruction may be unwarranted. (c) 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lanuti, M (reprint author), 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM Mlanuti@partners.org NR 15 TC 34 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD FEB PY 2007 VL 31 IS 2 BP 149 EP 153 DI 10.1016/j.ejcts.2006.11.010 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 137VO UT WOS:000244320900001 PM 17166733 ER PT J AU Ballantyne, C Cushman, M Psaty, B Furberg, C Khaw, KT Sandhu, M Oldgren, J Rossi, GP Maiolino, G Cesari, M Lenzini, L James, SK Rimm, E Collins, R Anderson, J Koenig, W Brenner, H Rothenbacher, D Berglund, G Persson, M Berger, P Brilakis, E McConnell, JP Koenig, W Sacco, R Elkind, M Talmud, P Rimm, E Cannon, CP Packard, C Cannon, CP Barrett-Connor, E Hofman, A Kardys, I Witteman, JCM Criqui, M Corsetti, JP Rainwater, DL Moss, AJ Robins, S Bloomfield, H Collins, D Packard, C Ridker, P Ballantyne, C Cannon, CP Collins, R Criqui, M Cushman, M Danesh, J Gu, D Hofman, A Nelson, JJ Packard, C Thompson, S Zalewski, A Danesh, J Collins, R Di Angelantonio, E Kaptoge, S Thompson, A Thompson, S Watson, S Wood, A AF Ballantyne, C. Cushman, M. Psaty, B. Furberg, C. Khaw, K. T. Sandhu, M. Oldgren, J. Rossi, G. P. Maiolino, G. Cesari, M. Lenzini, L. James, S. K. Rimm, E. Collins, R. Anderson, J. Koenig, W. Brenner, H. Rothenbacher, D. Berglund, G. Persson, M. Berger, P. Brilakis, E. McConnell, J. P. Koenig, W. Sacco, R. Elkind, M. Talmud, P. Rimm, E. Cannon, C. P. Packard, C. Cannon, C. P. Barrett-Connor, E. Hofman, A. Kardys, I. Witteman, J. C. M. Criqui, M. Corsetti, J. P. Rainwater, D. L. Moss, A. J. Robins, S. Bloomfield, H. Collins, D. Packard, C. Ridker, P. Ballantyne, C. Cannon, C. P. Collins, R. Criqui, M. Cushman, M. Danesh, J. Gu, D. Hofman, A. Nelson, J. J. Packard, C. Thompson, S. Zalewski, A. Danesh, J. Collins, R. Di Angelantonio, E. Kaptoge, S. Thompson, A. Thompson, S. Watson, S. Wood, A. CA Lp-PLA2 Studies Collaboration TI Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA(2) and cardiovascular diseases SO EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION LA English DT Review DE meta-analysis; lipoprotein-associated phospholipase A(2); vascular disease ID ACTIVATING-FACTOR-ACETYLHYDROLASE; LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE-A2; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; MIDDLE-AGED MEN; MYOCARDIAL-INFARCTION; FOLLOW-UP; ATHEROSCLEROSIS RISK; ISCHEMIC-STROKE; ARTERY-DISEASE AB Background A large number of observational epidemiological studies have reported generally positive associations' between circulating mass and activity levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA(2) markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. Objectives By combination of data from individual participants from all relevant observational studies in a systematic,meta-analysis, with correction for regression dilution (using available data on serial measurements of Lp-PLA(2)), the Lp-PLA(2) Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA(2) with coronary heart disease (and, where data are sufficient with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA(2) and cardiovascular outcomes. Methods A central database is being established containing data on circulating Lp-PLA(2) values, sex and other potential confounding factors, age at baseline Lp-PLA(2) Measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA(2) will yield information on a total of about 15 000 cardiovascular disease endpoints. C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Vermont, Burlington, VT 05405 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. EPIC, Norfolk, VA USA. Univ Uppsala Hosp, Uppsala, Sweden. Univ Padua, DMCS Internal Med 4, I-35100 Padua, Italy. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Oxford, Oxford OX1 2JD, England. Univ Utah, Salt Lake City, UT 84112 USA. Univ Ulm, Med Ctr, D-89069 Ulm, Germany. German Canc Res Ctr, D-6900 Heidelberg, Germany. Malmo Diet & Canc Study, Malmo, Sweden. Malmo Univ Hosp, Malmo, Sweden. Mayo Clin Study, Rochester, MN USA. Geisinger Med Ctr, Danville, PA 17822 USA. Univ Texas, SW Med Sch, Dallas, TX 75235 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. GSF, Inst Epidemiol, Neuherberg, Germany. Neurol Inst New York, New York, NY USA. UCL, London WC1E 6BT, England. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland. Univ Calif San Diego, San Diego, CA 92103 USA. Rotterdam Study, Rotterdam, Netherlands. Erasmus MC, Rotterdam, Netherlands. San Diego Vasc Cohort Study, San Diego, CA USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. Fuwai Hosp, Beijing, Peoples R China. MRC, Biostat Unit, London W1N 4AL, England. RP Ballantyne, C (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Site,Worts Causeway, Cambridge CB1 8RN, England. RI Talmud, Philippa/C-4402-2008; Brilakis, Emmanouil/B-5282-2009; Thompson, Alexander/A-6109-2010; Brenner, Hermann/B-4627-2017; OI Brenner, Hermann/0000-0002-6129-1572; bloomfield, hanna/0000-0002-0756-7064; Talmud, Philippa/0000-0002-5560-1933; Meisinger, Christa/0000-0002-9026-6544; Brilakis, Emmanouil/0000-0001-9416-9701 NR 28 TC 34 Z9 36 U1 0 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1741-8267 J9 EUR J CARDIOV PREV R JI Eur. J. Cardiovasc. Prev. Rehabil. PD FEB PY 2007 VL 14 IS 1 BP 3 EP 11 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 144KZ UT WOS:000244796200002 ER PT J AU Mori, S Endo, M AF Mori, Shinichiro Endo, Masahiro TI Candidate image processing for real-time volumetric CT subtraction angiography SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE angiography; CT; image processing; subtraction ID ROW COMPUTED-TOMOGRAPHY; CLINICAL POTENTIALS; PORCINE MODEL; SCANNER; COMPENSATION AB Since a 256-slice CT can perform real time observation of the volumetric cine images at multiple angles, volumetric CT angiography can provide much useful clinical information. Conventional CT subtraction angiography is generated by subtracting the non-enhanced CT image (mask CT image) from each contrast-enhanced CT image. Since even conventional CT subtraction angiography takes a few minutes to compute the image, volumetric CT subtraction angiography images require computation of an enormous amount of volumetric cine data (image base CT subtraction angiography: ICTSA) which means an excessively long calculating time. To reduce calculating time, we developed the raw data base CT subtraction angiography (RCTSA) that subtracts raw data instead of the reconstructed four-dimensional image sets. Image quality of the two image processing methods was evaluated in phantom and animal studies. Evaluation items were image noise, CT number uniformity, and subtracting RCTSA from ICTSA. ICTSA calculates the number of volume data; however, RCTSA uses the number of CT rotations. Moreover, since RCTSA can also be started subtraction early in the process of data acquisition, it reduced the number of calculations considerably. As there is a longer CT acquisition time, RCTSA shortens the ratio of the calculating time compared to that of ICTSA. RCTSA is useful image processing to reduce CT subtraction angiography examination time instead of ICTSA. (c) 2006 Elsevier Ireland Ltd. All rights reserved. RP Mori, S (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM smori1@partners.org OI Mori, Shinichiro/0000-0002-0412-4399 NR 21 TC 4 Z9 5 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD FEB PY 2007 VL 61 IS 2 BP 335 EP 341 DI 10.1016/j.ejrad.2006.09.012 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 137IA UT WOS:000244285100024 PM 17097254 ER PT J AU Cao, ZP Liu, LJ Lickey, M Graves, A Pham, T Gordon, B AF Cao, Zhiping Liu, Lijuan Lickey, Marvin Graves, Aundrea Pham, Tony Gordon, Barbara TI Virally mediated knock-down of NR2 subunits ipsilateral to the deprived eye blocks ocular dominance plasticity SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE knock-down; NMDA; NR2A; NR2B; adenovirus; visual cortex; plasticity; monocular deprivation ID D-ASPARTATE RECEPTOR; RAT VISUAL-CORTEX; AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN-SUPEROXIDE-DISMUTASE; FOCAL CEREBRAL-ISCHEMIA; LONG-TERM POTENTIATION; NMDA RECEPTOR; GENE-TRANSFER; CRITICAL PERIOD; IN-VIVO AB NMDA receptors (NMDARs) are important in developmental plasticity in the visual cortex. The NR2A and NR2B subunits of this receptor develop with different time courses, suggesting that they play different roles in plasticity. To understand the role of the NR2B subunit, we knocked-down NR2B gene expression in visual cortex by injecting a recombinant adenovirus containing an antisense NR2B oligonucleotide. To assess knock-down, we injected the recombinant adenovirus into the right visual cortex of rats (p22) or mice (p30). Eight days later we perfused the animals and processed the visual cortex for NMDAR subunit immunoreactivity (IR). NR2B-IR was depleted dramatically in the neuropil near the injection. Depletion was more modest in the neuronal somata. Surprisingly, NR2A-IR was also reduced, but NR1-IR was not reduced. To assess the functional effects of depletion, we measured ocular dominance plasticity with monocular deprivation (MD). We compared mice receiving the NR2B antisense virus with mice receiving virus containing only the GFP sequence and mice receiving no injection. All injections were between p26 and p29 in the right cortex and bilateral recordings were performed 6-8 days later. Animals receiving the antisense virus lost plasticity if the right eye was deprived. If the left eye was deprived, the cortex was normally plastic bilaterally. Injection of control virus had no effect on plasticity. The data indicate that ocular dominance plasticity requires normal NMDARs in the hemisphere ipsilateral to the deprived eye but not in the hemisphere contralateral to the deprived eye. C1 Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Portland VA Med Ctr, Portland, OR 97239 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Gordon, B (reprint author), Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. EM bgl@uoneuro.uoregon.edu FU NEI NIH HHS [EY04050, R01 EY014238] NR 70 TC 3 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD FEB PY 2007 VL 177 IS 1 BP 64 EP 77 DI 10.1007/s00221-006-0647-8 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 131XJ UT WOS:000243905300006 PM 16944113 ER PT J AU Liu, TX Rhodes, J Deng, M Hsu, K Radomska, HS Kanki, JP Tenen, DG Look, AT AF Liu, Ting Xi Rhodes, Jennifer Deng, Min Hsu, Karl Radomska, Hanna S. Kanki, John P. Tenen, Daniel G. Look, A. Thomas TI Dominant-interfering C/EBP alpha stimulates primitive erythropoiesis in zebrafish SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BINDING PROTEIN-ALPHA; GENE-EXPRESSION; TRANSCRIPTION FACTORS; MYELOID DEVELOPMENT; PU.1 SPI-1; CELLS; DIFFERENTIATION; PROGENITORS; LEUKEMIA; CLOCHE AB Objective. We investigated the role of CCAAT enhancer-binding protein-alpha (C/EBP alpha) during zebrafish embryonic blood development. Methods. Whole-mount mRNA in situ hybridization was performed to determine the spatio-temporal expression pattern of zebrafish cebpa in developing hematopoietic progenitors. A deletion mutation of cebpa (zD420), which mimics the human dominant-negative mutations of C/EBP alpha was transfected into CV1 cell line to evaluate its transcriptional activity in vitro and injected into zebrafish embryos at the one- to two-cell stage to examine its effects on primitive hematopoiesis during early zebrafish development. Results. Zebratish cebpa is expressed in the anterior and posterior lateral plate mesoderm at 12 hours postfertilization, along with scl, pu. 1, and gata 1 in developing hematopoietic progenitors. In vitro, the deletion mutation of cebpa (zD420) prevents expression of the full-length protein, allowing the expression of truncated isoforms from internal translational initiation sites. As in the human, the truncated zebrafish C/EBP alpha proteins did not activate the expression of known target granulocytic genes, and in fact suppressed transactivation that was induced in vitro by the full-length protein. Forced expression of the zD420 mRNA in zebrafish embryos led to an expansion of primitive erythropoiesis, without a discernible effect on granulopoiesis. Conclusion. Expression of the truncated isoforms of cebpa alters the developmental pattern of hematopoietic progenitor cells during embryogenesis. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Lab Dev & Dis, Shanghai, Peoples R China. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mayer 630, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [K08 CA096785, CA93152, CA96785, K08 CA096785-01, R01 CA093152, R01 CA093152-01]; NICHD NIH HHS [F32 HD041330, F32 HD041330-01, HD41330] NR 39 TC 15 Z9 15 U1 1 U2 2 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 FEB PY 2007 VL 35 IS 2 BP 230 EP 239 DI 10.1016/j.exphem.2006.10.008 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 134HC UT WOS:000244073100007 PM 17258072 ER PT J AU Fulci, G Chiocca, EA AF Fulci, Giulia Chiocca, E. Antonio TI The status of gene therapy for brain tumors SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE brain tumors; clinical trials; gene therapy; preclinical research ID HERPES-SIMPLEX-VIRUS; RECURRENT GLIOBLASTOMA-MULTIFORME; THYMIDINE-KINASE GENE; CONVECTION-ENHANCED DELIVERY; HUMAN-MALIGNANT GLIOMA; PHASE-I TRIAL; REPLICATION-DEFICIENT RETROVIRUSES; CENTRAL-NERVOUS-SYSTEM; VECTOR-PRODUCER CELLS; HSV-TK GENE AB The advent of gene therapy in the early 1990's raised expectations for brain tumor therapies; however, whereas clinical trials in patients with malignant gliomas provided evidence of safety, therapeutic benefit was not convincing. These early forays resembled the historical introductions of other therapies that seemed promising, only to fail in human trials. Nevertheless, re-study in the laboratory and retesting in iterative laboratory-clinic processes enabled therapies with strong biological rationales to ultimately show evidence of success in humans and become accepted. Examples, such as organ transplantation, monoclonal antibody therapy and antiangiogenic therapy, provide solace that a strategy's initial lack of success in humans provides an opportunity for its further refinement in the laboratory and development of solutions that will translate into patient success stories. The authors herein summarize results from clinical trials of gene therapy for malignant gliomas, and discuss the influence of these results on present thought in preclinical research. C1 Massachusetts Gen Hosp, Brain Tumor Res Ctr, Neurosurg Serv, Boston, MA 02114 USA. RP Fulci, G (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Neurosurg Serv, Simches Res Bldg CRPZN-3800,185 Cambridge St, Boston, MA 02114 USA. EM gfulci@partners.org FU NCI NIH HHS [P01 CA069246, CA69246-10A1- NIH/NC, P01 CA069246-10A1] NR 117 TC 26 Z9 28 U1 2 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD FEB PY 2007 VL 7 IS 2 BP 197 EP 208 DI 10.1517/14712598.7.2.197 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 130KD UT WOS:000243797600005 PM 17250458 ER PT J AU Kazantsev, AG AF Kazantsev, Aleksey G. TI Developing a neuroprotective therapy for Parkinson's and Huntington's diseases SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE creatine; HDAC; Huntington's disease; neurodegeneration; neuroprotection; PARP-1; Parkinson's disease; sirtuin ID TRANSGENIC MOUSE MODEL; POLY(ADP-RIBOSE) POLYMERASE-1; NEURODEGENERATIVE DISEASES; ALPHA-SYNUCLEIN; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE DAMAGE; RNA INTERFERENCE; COENZYME Q(10); IN-VITRO AB Parkinson's disease (PD) and Huntington's disease (HD) are slow and progressive neurological disorders that affect the lives of many thousands of patients and their families. Both diseases are characterized by selective neurodegeneration in specific brain areas, which causes long-term suffering and, ultimately, death. Although symptomatic treatment is available for Parkinson's patients, therapies that inhibit disease progression are not available. Significant progress has been made in our understanding of the pathological process, although the precise molecular mechanisms causing neuronal dysfunction and death remain elusive. Despite differences in the clinical manifestations of PD and HD, there are striking similarities in the underlying pathological processes. These observations suggest common pathways of neurodegeneration and tempt researchers to focus their efforts on pathological processes shared by both diseases. This article reviews some of the recent literature and discusses the feasibility of discovering neuroprotective agent(s) for treating PD and HD in the near future. C1 Harvard Univ, Dept Neurol, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. RP Kazantsev, AG (reprint author), Harvard Univ, Dept Neurol, Sch Med, Massachusetts Gen Hosp, Bldg 3300-114,16th St, Charlestown, MA USA. EM akazantsev@partners.org NR 106 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD FEB PY 2007 VL 17 IS 2 BP 159 EP 172 DI 10.1517/13543776.17.2.159 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 136OX UT WOS:000244235100003 ER PT J AU MacDonald, SM Taghian, AG AF MacDonald, Shannon M. Taghian, Alphonse G. TI Partial-breast irradiation: towards a replacement for whole-breast irradiation? SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE accelerated; breast cancer; hypofractionated; partial breast; radiation ID DOSE INTRAOPERATIVE RADIOTHERAPY; INITIAL DOSIMETRIC EXPERIENCE; 20-YEAR FOLLOW-UP; CARCINOMA-IN-SITU; CONSERVING SURGERY; RADIATION-THERAPY; CANCER PATIENTS; RANDOMIZED-TRIAL; BRACHYTHERAPY APPLICATOR; CLINICAL-EXPERIENCE AB Largely thanks to all of the investigators and patients who have participated in randomized breast-conservation trials, many women facing a diagnosis of breast cancer today can conserve their breast with the help of adjuvant radiation therapy. A standard course of radiation consists of 5-7 weeks of daily radiation treatments delivered to the whole breast. The success of this treatment has led investigators to attempt to determine whether the same control can be achieved while decreasing the volume of breast tissue irradiated, thus allowing treatment to be delivered in a shorter period of time. This approach could alleviate time and logistical problems faced by patients during their course of treatment as well as improving overall cost-effectiveness. It can also allow complete avoidance of the adjacent heart and lung tissue in the radiation treatment portal. Partial-breast irradiation (the delivery of radiation to the resection cavity, plus a safety margin) delivered in just hours or days, is currently under investigation. Although relatively new, its use is growing rapidly and many institutional and cooperative group trials are quickly enlisting patients, while physicians are gaining experience in a variety of partial-breast irradiation techniques. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM ataghian@partners.org NR 79 TC 7 Z9 7 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD FEB PY 2007 VL 7 IS 2 BP 123 EP 134 DI 10.1586/14737140.7.2.123 PG 12 WC Oncology SC Oncology GA 141VA UT WOS:000244605700010 PM 17288524 ER PT J AU Ye, B Gagnon, A Mok, SC AF Ye, Bin Gagnon, Audrey Mok, Samuel C. TI Recent technical strategies to identify diagnostic biomarkers for ovarian cancer SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE biomarker; diagnosis; dynamic change; metabolomics; ovarian cancer; proteomics; sample collection; strategies; validation ID TISSUE POLYPEPTIDE ANTIGEN; POTENTIAL SERUM BIOMARKER; COLONY-STIMULATING FACTOR; TUMOR-MARKERS; MASS-SPECTROMETRY; CARCINOEMBRYONIC ANTIGEN; MONOCLONAL-ANTIBODY; GENE-PRODUCTS; CARCINOMA; PROTEIN AB Ovarian cancer is the fifth leading cause of cancer deaths among North American women. Regrettably, there is currently no reliable circulating biomarker that can detect ovarian cancer in its early stages. The CA125 biomarker is very useful for treatment response monitoring, but its sensitivity is very low for early detection. Thus, there is an urgent need for the identification of new circulating biomarkers/panel of biomarkers that could be used to diagnose ovarian cancer before it becomes clinically detectable and advanced. Unfortunately, the strategies used in the post years to identity such biomarkers have not led to any outstanding candidate. This review summarizes the different approaches used in the lost decade and suggests which strategies should be adopted in the near future in order to lead to the successful identification of new ovarian cancer diagnostic biomarkers. C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Ctr,Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Ye, B (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Ctr,Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. EM bye@partners.org FU NCI NIH HHS [1P50-CA105009-01, R01-CA054419-13, R21 CA111949-01] NR 79 TC 11 Z9 12 U1 1 U2 4 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD FEB PY 2007 VL 4 IS 1 BP 121 EP 131 DI 10.1586/14789450.4.1.121 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 139ID UT WOS:000244424600016 PM 17288520 ER PT J AU Hafezi-Moghadam, A Noda, K Almulki, L Ilmaki, EF Poulaki, V Thomas, KL Nakazawa, T Hisatomi, T Miller, JW Gragoudas, ES AF Hafezi-Moghadam, A. Noda, K. Almulki, L. Ilmaki, E. F. Poulaki, V. Thomas, K. L. Nakazawa, T. Hisatomi, T. Miller, J. W. Gragoudas, E. S. TI VLA-4 blockade suppresses endotoxin-induced uveitis: in vivo evidence for functional integrin up-regulation SO FASEB JOURNAL LA English DT Article DE EIU; VCAM-1; autoperfused microflow chamber; leukocyle-endothelial interaction ID EXPERIMENTAL AUTOIMMUNE UVEITIS; ADHESION MOLECULES; CELL-ADHESION; MONOCLONAL-ANTIBODIES; P-SELECTIN; LEUKOCYTE; INFLAMMATION; DISEASE; NEUTROPHIL; ICAM-1 AB Leukocyte adhesion to the vascular wall is a critical early step in the pathogenesis of inflammatory diseases and is mediated in part by the leukocyte integrin, VLA-4, which binds to endothelial vascular cell adhesion molecule (VCAM) -1. Here, we investigate VLA-4's role in endotoxin-induced uveitis (EIU). At various time points (6-48 h) after EIU induction, the severity of the inflammation was evaluated by quantifying cell and protein content in the aqueous fluid, firm leukocyte adhesion in the retinal vessels, and the number of extravasated leukocytes into the vitreous. Functional activation of VLA-4 in vivo was investigated in our previously introduced autoperfused micro flow chamber assay. Firm adhesion of EIU leukocytes to immobilized VCAM-1 under physiological blood flow conditions was significantly increased compared with normal controls (P < 0.05), suggesting an important role for VLA-4 in EIU. VLA-4 blockade in vivo significantly suppressed all uveitis-related inflammatory parameters studied, decreasing the clinical score by 45% (P < 0.01), protein content in the aqueous fluid by 21% (P < 0.01), retinal leukostasis by 68% (P < 0.01), and leukocyte accumulation in the vitreous by 75% (P < 0.01). Our data provide novel evidence for functional up-regulation of VLA-4 during EIU and suggest VLA-4 blockade as a promising therapeutic strategy for treatment of acute inflammatory eye diseases. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hafezi-Moghadam, A (reprint author), Angiogenesis Lab, 325 Cambridge St,3rd Floor, Boston, MA 02114 USA. EM ahm@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697; Hisatomi, Toshio/0000-0003-2552-9595 FU NEI NIH HHS [EY14104]; NIAID NIH HHS [AI050775] NR 49 TC 23 Z9 24 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 2007 VL 21 IS 2 BP 464 EP 474 DI 10.1096/fj.06-6390com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 142YD UT WOS:000244686300020 PM 17202250 ER PT J AU Thakkar, K El-Serag, HB Mattek, N Gilger, MA AF Thakkar, Kalpesh El-Serag, Hashem B. Mattek, Nora Gilger, Mark A. TI Complications of pediatric EGD: a 4-year experience in PEDS-CORI SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID UPPER GASTROINTESTINAL ENDOSCOPY; UPPER GI ENDOSCOPY; FIBEROPTIC ENDOSCOPY; CONSCIOUS SEDATION; AMERICAN-SOCIETY; FOLLOW-UP; CHILDREN; INFANTS; ESOPHAGOGASTRODUODENOSCOPY; PERFORATIONS AB Background: Available estimates of the incidence and type of complications during pediatric EGD are inconsistent. Objective: To determine the frequency and the determinants of immediate complications during EGD in children. Design: We conducted a cross-sectional database study. Setting: The study involved 13 pediatric facilities that use the PEDS-CORI (Pediatric Endoscopy Database System Clinical Outcomes Research Initiative). Patients: Children (0-18 years) who underwent EGD at 13 facilities between November 1999 and December 2003. Main Outcome Measurements: We identified complications (recorded shortly after the procedure) and analyzed their occurrence with respect to procedure indication, American Society of Anesthesiologists (ASA) class, sex, age, anesthesia type, and unplanned interventions. Results: We analyzed 10,236 procedures performed in 9234 patients. Immediate complications were reported in 239 procedures (2.3%, 95% confidence interval 2.0%-2.6%). The most common complications were hypoxia (157 [1.5%]) and bleeding (28 [0.3%]). Complication rates were significantly higher in the youngest age group, highest ASA class, female gender, intravenous (IV) sedation group, and in the presence of a fellow. Limitations: The study is limited by a lack of specific details and explicit criteria for reported complications. Conclusions: The overall immediate complication rate of pediatric EGD is 2.3%. All complications were non-fatal, and most were hypoxia related (157/239 [66%]) and reversible. Young age, higher ASA class, female sex, and IV sedation are risk factors for developing complications. C1 Texas Childrens Hosp, Sect Pediat Gastroenterol Hepatol, Houston, TX 77030 USA. Texas Gulf Coast Digest Dis Ctr, Houston, TX USA. Baylor Coll Med, Sect Gastroenterol, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. Oregon Hlth Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Thakkar, K (reprint author), Baylor Coll Med, Dept GI Hepatol & Nutr, 6621 Fannin St CCC 1010, Houston, TX 77030 USA. NR 35 TC 47 Z9 49 U1 0 U2 0 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 FEB PY 2007 VL 65 IS 2 BP 213 EP 221 DI 10.1016/j.gie.2006.03.015 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 133VL UT WOS:000244041900007 PM 17258979 ER PT J AU Matthes, K Mino-Kenudson, M Sahani, DV Holalkere, N Brugge, WR AF Matthes, Kai Mino-Kenudson, Mari Sahani, Dushyant V. Holalkere, Nagaraj Brugge, William R. TI Concentration-dependent ablation of pancreatic tissue by EUS-guided ethanol injection SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ABSOLUTE ETHANOL; HEPATIC CYSTS; CARCINOMA; THERAPY; TRIAL; COMPLICATIONS; ALCOHOL; LESIONS AB Background: Ethanol is a commonly available agent and has been used to successfully and safely ablate cystic lesions of various organs. Objective: The aim of this study was to determine the short-term effects of an EUS-guided injection of ethanol into the pancreas of pigs by using 2 mL ethanol, in increasing concentration of 0% to 100%. Design: Six pigs were sedated by general anesthesia, and ethanol was injected, under EUS-guidance, with a 22-gauge needle into the pancreatic tail. Main Outcome Measurements: End points of this study were gross and microscopic evidence of pancreatitis and clinical tolerance. During the 7-day observational period, the animals were monitored by serum levels of amylase and lipase and by a CT on day 4. Results: At euthanasia, there was no pancreatic lesion in the animals that received normal saline solution or 20% ethanol. The injection of 40% to 100% ethanol led to a visible necrotic area in the pancreatic tail. By histology, the average maximal diameter of the lesions was 20.8 +/- 4.3 mm. The cross-sectional area of necrosis was proportional to the concentration of ethanol (r = 0.961). CT demonstrated a localized site of nonenhancing pancreatic tissue, with an average diameter of 19.4 +/- 10.5 mm; 40% to 100% ethanol. Clinically, the animals appeared to tolerate the procedure without sequelae. Serum levels of amylase and lipase were normal. Conclusions: The EUS-guided injection of ethanol into the pig pancreas resulted in a localized concentration-dependent tissue necrosis without complications. C1 Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Gastrointestinal Pathol Serv, Massachusetts Gen Hosp,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, 55 Fruit St,Blake 4, Boston, MA 02114 USA. OI Holalkere, Nagaraj/0000-0001-6324-7682 NR 23 TC 32 Z9 33 U1 0 U2 2 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 FEB PY 2007 VL 65 IS 2 BP 272 EP 277 DI 10.1016/j.gie.2006.04.043 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 133VL UT WOS:000244041900018 PM 17258986 ER PT J AU Rukstalis, JM Habener, JF AF Rukstalis, J. Michael Habener, Joel F. TI Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas SO GENE EXPRESSION PATTERNS LA English DT Article DE snail2; slug; EMT; neurogenin3; progenitor; pancreas; endocrine; E-cadherin; N-cadherin; PDX-1; delamination; migration; insulin; ISL1; TCF2; development ID TRANSCRIPTION FACTOR SLUG; E-CADHERIN EXPRESSION; N-CADHERIN; EMBRYONIC PANCREAS; BETA-CELLS; CANCER; DIFFERENTIATION; PATHWAY; GENES AB The mammalian pancreas develops by the expansion and morphogenesis of the epithelia] cells of the foregut endoderm via the sequental activation of transcription factors that direct differentiation into the various pancreatic lineages. Implicit in this growth and differentiation are the temporal and spatial processes of cell migration and three-dimensional organization, which cooperate to form a properly functioning organ. In many organ systems, such as the kidney, heart, and neural crest derivatives, migration and tissue morphogenesis is accomplished by the transient conversion of stationary epithelial cells to migratory mesenchymal-like cells in a process known as epithelial-mesenchymal transition (EMT). We report the identification of the expression of the transcription factor Snail2/Slug, a known inducer of EMT and cell movement, in both the endocrine and exocrine cells of the developing mouse pancreas. Snail2 is expressed in Neurogenin3-positive endocrine progenitor cells, and expression is maintained during endocrine cell differentiation where it becomes increasingly restricted to the insulin-producing beta cells and somatostatin-producing delta cells. In the adult pancreas, the expression of Snail2 is maintained at low but detectable levels in all beta cells, indicating a latent role for Snail2 in the mature islet. These findings of Snail2 expression during endocrine pancreas development are relevant to the recent evidence demonstrating the involvement of EMT in the expansion of human islet tissue in vitro. EMT-like events appear to be involved in the development of the mammalian pancreas in vivo. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA 02114 USA. EM JHabener@Partners.org FU NIDDK NIH HHS [DK7028-29, DK55365, DK61251, P30 DK057521, P30 DK057521-06, R01 DK055365, R01 DK055365-05, T32 DK007028, U19 DK061251, U19 DK061251-03, U19 DK061251-03S1] NR 26 TC 39 Z9 40 U1 0 U2 5 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 FEB PY 2007 VL 7 IS 4 BP 471 EP 479 DI 10.1016/j.modgep.2006.11.001 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 141HW UT WOS:000244570400012 PM 17185046 ER PT J AU Mangos, S Liu, Y Drummond, IA AF Mangos, Steve Liu, Yan Drummond, Iain A. TI Dynamic expression of the osmosensory channel trpv4 in multiple developing organs in zebrafish SO GENE EXPRESSION PATTERNS LA English DT Article DE TRPV4; Osm-9; zebrafish; osmosensory; ion channel; pronephros; endocardium; notochord; chondrogenic; pronephric duct ID PAIN PATHWAY; HAIR-CELLS; KIDNEY; IDENTIFICATION; PRONEPHROS; RECEPTOR; XENOPUS; CILIA AB Transient receptor potential channels function in a wide spectrum of tissues and transduce sensory stimuli. The vanilloid (capsaicin) channel TRPV4 is sensitive to osmotic changes and plays a central role in osmoregulatory responses in a variety of organisms. We cloned a zebrafish trpv4 cDNA and assayed its expression during embryogenesis. trpv4 is expressed as maternal mRNA in 4-cell embryos and later zygotic expression is first observed in the forming notochord at the one somite stage. Notochord expression persists to 24 hpf when broad expression in the brain is observed. At 32 hpf trpv4 expression is observed in the endocardium, restricted primarily to the ventricular endothelium. Low level expression of trpv4 is also seen from 32-48 hpf in the pronephric kidney with strongest expression in the most distal nephron segment and in the cloaca. Expression is also observed in lateral line organs starting at 32 hpf, primarily in the hair cells. At 72 hpf, expression of trpv4 in heart, kidney, brain, and lateral line organs persists while expression in the notochord is down-regulated. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. RP Drummond, IA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, 149-800,149 13th St, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK070263-01, R01 DK53093, P01 DK054711, R01 DK070263, R01 DK053093, DK54711] NR 23 TC 25 Z9 27 U1 1 U2 7 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 FEB PY 2007 VL 7 IS 4 BP 480 EP 484 DI 10.1016/j.modgep.2006.10.011 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 141HW UT WOS:000244570400013 PM 17161658 ER PT J AU Fujita, T Timme, TL Tabata, K Naruishi, K Kusaka, N Watanabe, M Abdelfattah, E Zhu, JX Ren, C Ren, C Yang, G Goltsov, A Wang, H Vlachaki, MT Teh, BS Butler, EB Thompson, TC AF Fujita, T. Timme, T. L. Tabata, K. Naruishi, K. Kusaka, N. Watanabe, M. Abdelfattah, E. Zhu, J. X. Ren, C. Ren, C. Yang, G. Goltsov, A. Wang, H. Vlachaki, M. T. Teh, B. S. Butler, E. B. Thompson, T. C. TI Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy with radiotherapy in a preclinical model of metastatic prostate cancer SO GENE THERAPY LA English DT Article DE prostate cancer; radiotherapy; interleukin-12; radio-gene therapy ID VIRUS THYMIDINE KINASE; TK PLUS GCV; INTENSITY-MODULATED RADIOTHERAPY; ORTHOTOPIC MOUSE MODEL; IN-SITU; PHASE-I; GANCICLOVIR THERAPY; IONIZING-RADIATION; INTRATUMORAL INJECTION; HORMONAL-THERAPY AB We investigated the potential benefits of combining adenoviral vector mediated in situ interleukin-12 (AdmIL-12) gene therapy with radiation therapy (XRT) to enhance therapeutic efficacy. In a metastatic mouse prostate cancer cell line, 1782 BMA, AdmIL-12+XRT demonstrated enhanced therapeutic activities in vitro as determined by clonogenic survival, apoptosis, and mIL-12 levels. At the molecular level, increased expression of tumor necrosis factor-alpha mRNA was specific for the combined therapy. In a subcutaneous 178-2 BMA in vivo model, the combination of AdmIL-12+XRT produced statistically significant tumor growth suppression compared to control vector Ad beta gal, Ad beta gal XRT, or AdmIL-12 as monotherapy. In addition, significant prolongation of survival was demonstrated for the combination of AdmIL-12+XRT. The combination of AdmIL-12+XRT significantly suppressed both spontaneous and pre-established lung metastases, and led to a prolonged elevation of serum IL-12 and significantly increased natural killer (NK) activities. Importantly, in vivo depletion of NK cells resulted in significant attenuation of the antimetastatic activities of AdmIL-12 alone or AdmIL-12+XRT. These combined effects suggest that AdIL-12 gene therapy together with radiotherapy may achieve maximal tumor control (both local and systemic) in selected prostate cancer patients via radio-gene therapy induced local cytotoxicity and local and systemic antitumor immunity. C1 Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Thompson, TC (reprint author), Baylor Coll Med, Scott Dept Urol, 6560 Fannin,Suite 2100, Houston, TX 77030 USA. EM timothyt@bcm.tmc.edu FU NCI NIH HHS [P50-CA58204] NR 55 TC 10 Z9 11 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD FEB PY 2007 VL 14 IS 3 BP 227 EP 236 DI 10.1038/sj.gt.3302788 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 127OZ UT WOS:000243597500005 PM 17024109 ER PT J AU Giel-Moloney, M Krause, DS Chen, G Van Etten, RA Leiter, AB AF Giel-Moloney, Maryann Krause, Daniela S. Chen, Gang Van Etten, Richard A. Leiter, Andrew B. TI Ubiquitous and uniform in vivo fluorescence in ROSA26-EGFP BAC transgenic mice SO GENESIS LA English DT Article DE transgenic; ROSA26; EGFP; hematolymphoid; cells; transplantation; bone marrow transplantation ID STEM-CELLS; HEMATOPOIETIC STEM; ESCHERICHIA-COLI; EXPRESSION; GENE; PROMOTER; TRANSPLANTATION; RECOMBINATION; EMBRYOS; SYSTEM AB Transplantation studies and cell lineage analyses require the ability to explicitly distinguish morphologically identical cells that have an identifiable marker indicating their origin in vivo. Several reporter mouse strains have been generated for such studies, but pancellular detection of the marker in all tissues has not been achieved. In this report, we describe the generation of transgenic mice that express enhanced green fluorescent protein (EGFP) under control of a 187 kb bacterial artificial chromosome (BAC) containing the murine ROSA26 locus, and show several advantages over existing EGFP reporter lines. It is demonstrated that EGFP is ubiquitously and reproducibly expressed from the murine BAC transgene in all organs and tissues analyzed, including the hematolymphoid compartment. Using this new reporter strain in hematopoietic cell transplantation studies, it is demonstrated that leukocytes in recipients maintain uniform transgene expression and are easily distinguished by flow cytometric analysis of live cells. The results suggest that the ROSA26 BAC is an efficient strategy for expressing complex transgene cassettes in vivo. C1 Tufts Univ New England Med Ctr, Div Gastroenterol, GRASP Digest Dis Ctr, Boston, MA USA. Tufts Univ, Sch Med, Dept Cellular & Mol Physiol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Immunol, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Leiter, AB (reprint author), Tufts Univ New England Med Ctr, Div Gastroenterol, GRASP Digest Dis Ctr, Boston, MA USA. EM aleiter@tufts-nemc.org FU NCI NIH HHS [CA105043, CA90576, R01 CA090576, R01 CA090576-07, R01 CA105043, R01 CA105043-03]; NIDDK NIH HHS [P30 DK034928-239002, DK43673, DK52870, DK67166, P30 DK034928, P30-DK34928, R01 DK043673, R01 DK067166, R01 DK067166-02, T32 DK007542, T32 DK007542-20, T32 DK007542-21, T32-DK007542] NR 22 TC 16 Z9 20 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD FEB PY 2007 VL 45 IS 2 BP 83 EP 89 DI 10.1002/dvg.20269 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 141UE UT WOS:000244603500005 PM 17269129 ER PT J AU Crest, J Oxnard, N Ji, JY Schubiger, G AF Crest, Justin Oxnard, Nathan Ji, Jun-Yuan Schubiger, Gerold TI Onset of the DNA replication checkpoint in the early Drosophila embryo SO GENETICS LA English DT Article ID MAJOR DEVELOPMENTAL TRANSITION; EARLY XENOPUS-EMBRYOS; CYCLIN-B; CELL-CYCLE; PROTEIN-A; DAMAGE CHECKPOINT; MIDBLASTULA TRANSITION; EXCISION REPAIR; MITOTIC-CYCLES; MITOSIS AB The Drosophila embryo is a promising model for isolating gene products that coordinate S phase and mitosis. We have reported before that increasing maternal Cyclin B dosage to up to six copies (six cycB) increases Cdk1-Cyclin B (CycB) levels and activity in the embryo, delays nuclear migration at cycle 10, and produces abnormal nuclei at cycle 14. Here we show that the level of CycB in the embryo inversely correlates with the ability to lengthen interphase as the embryo transits from preblastoderm to blastoderm stages and defines the on set of a checkpoint that regulates mitosis when DNA replication is blocked with aphidicolin. A screen for modifiers of the six cycB phenotypes identified 10 new suppressor deficiencies. In addition, hecterozygote dRPA2 (a DNA replication gene) Mutants suppressed only the abnormal nuclear phenotype at cycle 14. Reduction of dRPA2 also restored interphase duration and checkpoint efficacy to control levels. We propose that lowered dRPA2 levels activate Grp/Chk1 to counteract excess Cdk1-CycB activity and restore interphase duration and the ability to block mitosis in response to aphidicolin. Our results suggest an antagonistic interaction between DNA replication checkpoint activation and Cdk1-CycB activity during the transition from preblastoderm to blastoderm cycles. C1 Univ Washington, Dept Biol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Crest, J (reprint author), Univ Calif Santa Cruz, MCD Biol Dept, Santa Cruz, CA 95064 USA. EM jcrest@ucsc.edu NR 59 TC 20 Z9 20 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2007 VL 175 IS 2 BP 567 EP 584 DI 10.1534/genetics.106.065219 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 142ZK UT WOS:000244689600013 PM 17151243 ER PT J AU Tyler, DM Li, W Zhuo, N Pellock, B Baker, NE AF Tyler, David M. Li, Wei Zhuo, Ning Pellock, Brett Baker, Nicholas E. TI Genes affecting CeR competition in Drosophila SO GENETICS LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; DEPENDENT KINASE INHIBITOR; TUMOR-SUPPRESSOR GENE; PLANAR CELL POLARITY; PROMOTES APOPTOSIS; MORPHOGEN GRADIENT; WING DEVELOPMENT; IMAGINAL DISKS; PROTEIN-KINASE; CYCLE EXIT AB Cell competition is a homeostatic mechanism that regulates the size attained by growing tissues. We performed an unbiased genetic screen for mutations that permit the survival of cells being competed due to haplo-insufficiency for RpL36 Mutations that protect RpL36 heterozygous clones include the tumor suppressors expanded, hippo, salvador, mats, and warts, which are members of the Warts pathway, the tumor suppressor fat, and a novel tumor-suppressor mutation. Other hyperplastic or neoplastic Initiations did not rescue RpL36 heterozygous clones. Most mutations that rescue cell competition elevated Dpp-signaling activity, and the Dsmurf mutation that elevates Dpp signaling was also hyperplastic and rescued. Two nonlethal, nonhyperplastic mutations prevent the apoptosis of Minute heterozygous cells and suggest an apoptosis pathway for cell competition. In addition to rescuing RpL36 heterozygous cells, mutations in Warts pathway genes were supercompetitors that could eliminate wild-type cells nearby. The findings show that differences in Warts pathway activity can lead to competition and implicate the Warts pathway, certain other tumor suppressors, and novel cell death components in cell competition, in addition to the Dpp pathway implicated by previous studies. We suggest that cell competition might occur during tumor development in mammals. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Baker, NE (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM nbaker@aecom.yu.edu FU NIGMS NIH HHS [GM61230, R01 GM061230] NR 82 TC 79 Z9 80 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2007 VL 175 IS 2 BP 643 EP 657 DI 10.1534/genetics.106.061929 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 142ZK UT WOS:000244689600019 PM 17110495 ER PT J AU Arar, N Nath, S Thameem, F Bauer, R Voruganti, S Comuzzie, A Cole, S Blangero, J MacCluer, J Abboud, H AF Arar, Nedal Nath, Subrata Thameem, Farook Bauer, Richard Voruganti, Saroja Comuzzie, Anthony Cole, Shelley Blangero, John MacCluer, Jean Abboud, Hanna TI Genome-wide scans for microalbuminuria in Mexican Americans: The San Antonio Family Heart Study SO GENETICS IN MEDICINE LA English DT Article DE microalbuminuria; albumin to creatinine ratio; cardiovascular diseases; Mexican Americans; family genetic study ID CARDIOVASCULAR RISK-FACTORS; QUANTITATIVE TRAIT LOCUS; URINARY ALBUMIN EXCRETION; DIABETIC-NEPHROPATHY; LINKAGE ANALYSIS; BLOOD-PRESSURE; INSULIN-RESISTANCE; GENES; DISEASE; CHROMOSOME-20 AB Purpose: Microalbuminuria, defined as urine albumin-to-creatinine ratio of 0.03 to 0.299 mg/mg, is a major risk factor for cardiovascular disease. Several genetic epidemiological studies have established that microalbuminuria clusters in families, suggesting a genetic predisposition. Method: We estimated heritability of microalbuminuria and performed a genome-wide linkage analysis to identify chromosomal regions influencing urine albumin-to-creatinine ratio in 486 Mexican Americans from 26 multiplex families. Results: Significant heritability was demonstrated for urine albumin-to-creatinine ratio (h(2) = 24%, P < 0.003) after accounting for age, sex, body mass index, triglycerides, and hypertension. Genome scan revealed significant evidence of linkage of urine albumin-to-creatinine ratio to a region on chromosome 20q12 (LOD score of 3.5, P < 0.001) near marker D20S481. This region also exhibited a LOD score of 2.8 with diabetes status as a covariate and 3.0 with hypertension status as a covariate suggesting that the effect of this locus on urine albumin-to-creatinine ratio is largely independent of diabetes and hypertension. Conclusion: Findings indicate that there is a gene or genes located on human chromosome 20q12 that may have functional relevance to albumin excretion in Mexican Americans. Identifying and understanding the role of the genes that determine albumin excretion would lead to the development of novel therapeutic strategies targeted at high-risk individuals in whom intensive preventive measures may be most beneficial. C1 Univ Texas, Hlth Sci Ctr, Dept Med Nephrol, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Arar, N (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Nephrol, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM ararn@uthscsa.edu FU NCRR NIH HHS [M01-RR01346]; NHLBI NIH HHS [HL45522]; NIDDK NIH HHS [P50-DK-061597] NR 52 TC 10 Z9 12 U1 0 U2 0 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 FEB PY 2007 VL 9 IS 2 BP 80 EP 87 DI 10.1097/GIM.0b013e31803068ec PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 140FX UT WOS:000244491100005 PM 17304049 ER PT J AU Kociok, N Krohne, TU Poulaki, V Joussen, AM AF Kociok, Norbert Krohne, Tim U. Poulaki, Vassiliki Joussen, Antonia M. TI Geldanamycin treatment reduces neovascularization in a mouse model of retinopathy of prematurity SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article DE retina; geldanamycin; neovascularization; retinopathy of prematurity; kinase inhibitor ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; HEAT-SHOCK-PROTEIN; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; IN-VIVO ANGIOGENESIS; CANCER CELLS; SIGNALING PATHWAY; RETINAL-VESSELS; EXPRESSION; ANGIOPOIETIN-2 AB The benzoquinoid antibiotic 17-allylaminogeldanamycin (17-AAG) inhibits the Ras/Raf/MEK and PI3-Kinase signaling pathways and down-regulates vascular endothelial factor expression. Here we use a mouse model of oxygen-induced retinopathy to investigate the effect of 17-AAG on retinal neovascularization and vascular recovery. C57BL/6 mice were exposed to 75% oxygen from postnatal day 7 (P7) to P12 and recovered in room air thereafter. Beginning with P12 mice were treated for 5 days by daily IP injection of 17-AAG (12.5 mg/kg body weight) micro dispersed in an emulsion of 4% Lipoid EPC, 5% sucrose, and 0.9% NaCl or Wortmannin (100 mu g/kg body weight). On P17, the retinal vascular and avascular area, neovascular blood vessel tufts, and main vessel tortuosity were quantified after perfusion of the mice with FITC-Concanavalin A. The mRNA levels of VEGF, angiopoietin 1 and 2 were quantified by real-time RT-PCR. After 17-AAG treatment, a reduction of the vascular area was measured from 37.8 +/- 5.2% to 30.8 +/- 5.7% (P=0.005), and an increase of the avascular area from 10.8 +/- 5.6% to 20.3 +/- 6.6% (P=0.001). No alteration of the vascular pattern, the number of blood vessel tufts and the main vessel tortuosity was achieved by treatment with the PI-3 kinase inhibitor Wortmannin. After treatment with 17-AAG, the numbers of tufts (127.9 +/- 33.2) were different from the controls (173.7 +/- 55.2, P=0.035), but not the main vessel tortuosity. No significant change in VEGF and angiopoietin 1 mRNA expression could be achieved with either of the treatments. Wortmannin treatment also did not change the angiopoietin 2 mRNA level, whereas the level was reduced in 17-AAG treated mice retina from 436-fold (+/- 64) to 200-fold (+/- 55) (P=0.035). An IP injection of 17-AAG is able to reduce angioproliferative retinopathy in a mouse model for oxygen-induced retinopathy. Our data indicate that the mechanism does not involve a direct or indirect reduction of the VEGF mRNA level, but acts downstream of the VEGF pathway. Thus, 17-AAG probably does not work by PI-3 kinase inhibition but via the Ras/Raf/MEK pathway. These data underline the potential utility of tyrosine kinase inhibitors in hypoxia induced neovascularization. C1 Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-50937 Cologne, Germany. Univ Cologne, CMMC, D-50937 Cologne, Germany. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Kociok, N (reprint author), Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Kerpener Str 62, D-50937 Cologne, Germany. EM Norbert.Kociok@uni-koeln.de; JoussenA@aol.com RI Krohne, Tim/D-1497-2013 OI Krohne, Tim/0000-0003-2280-925X NR 41 TC 12 Z9 14 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD FEB PY 2007 VL 245 IS 2 BP 258 EP 266 DI 10.1007/s00417-006-0355-x PG 9 WC Ophthalmology SC Ophthalmology GA 137LX UT WOS:000244295200010 PM 16741710 ER PT J AU Rikli, DA Babst, R Jupiter, JB AF Rikli, D. A. Babst, R. Jupiter, J. B. TI Distal radius fractures: New concepts as basis for surgical treatment SO HANDCHIRURGIE MIKROCHIRURGIE PLASTISCHE CHIRURGIE LA German DT Review DE distal radius fracture; biomechanics; locking implants; internal fixation ID INTERNAL-FIXATION; COLLES FRACTURE; JOINT C1 Kantonsspital, CH-6000 Luzern, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rikli, DA (reprint author), Kantonsspital, Spitalstr, CH-6000 Luzern, Switzerland. EM daniel.rikli@ksl.ch NR 21 TC 6 Z9 6 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0722-1819 J9 HANDCHIR MIKROCHIR P JI Handchir. Mikrochir. Plast. Chir. PD FEB PY 2007 VL 39 IS 1 BP 2 EP 8 DI 10.1055/s-2007-964921 PG 7 WC Surgery SC Surgery GA 163GX UT WOS:000246148700002 PM 17402134 ER PT J AU Hunt, MK Barbeau, EM Lederman, R Stoddard, AM Chetkovich, C Goldman, R Wallace, L Sorensen, G AF Hunt, Mary K. Barbeau, Elizabeth M. Lederman, Ruth Stoddard, Anne M. Chetkovich, Carol Goldman, Roberta Wallace, Lorraine Sorensen, Glorian TI Process evaluation results from the Healthy Directions-Small Business study SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE process evaluation; worksite health promotion; occupational health; prevention research ID BLUE-COLLAR WORKERS; PROMOTION PROGRAMS; WORKING-CLASS; CANCER PREVENTION; MULTIETHNIC POPULATIONS; BEHAVIOR-CHANGE; HEART HEALTH; WORKSITE; INTERVENTION; MODEL AB The Healthy Directions-Small Business randomized, controlled study aimed to reduce cancer risk among multiethnic workers in small manufacturing businesses by increasing fruit and vegetable consumption, physical activity, and daily multivitamin intake and decreasing consumption of red meat. The intervention incorporated participatory strategies and was built on a social-contextual framework that addressed people with varying cultural backgrounds and literacy levels. In addition, the intervention aimed to reduce worker exposure to occupational hazards. Process evaluation was conducted using quantitative and qualitative research methods. Quantitative results showed high levels of worker awareness of and participation in programs. Qualitative findings suggested that management support, worker input, and a history of social interaction between workers and management may have contributed to high participation rates. Future studies need to examine characteristics associated with participation and nonparticipation of both managers and nonmanagers to increase the likelihood of participation and ultimately improve health behavior. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Hunt, MK (reprint author), 221 Stn Circle N, Hudson, WI 54016 USA. EM huntmk@comcast.com FU NCI NIH HHS [P01 CA 75308] NR 64 TC 19 Z9 19 U1 0 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD FEB PY 2007 VL 34 IS 1 BP 90 EP 107 DI 10.1177/1090198105277971 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 128HN UT WOS:000243648900007 PM 16740502 ER PT J AU Ross, JS Siu, AL AF Ross, Joseph S. Siu, Albert L. TI The importance of population-based performance measures SO HEALTH SERVICES RESEARCH LA English DT Editorial Material ID QUALITY-OF-CARE; CLINICAL-TRIALS; HEART-FAILURE; DISEASE; GUIDELINES; MEDICARE; PITFALLS; SYSTEM; PAY C1 Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Ross, JS (reprint author), Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2007 VL 42 IS 1 BP 1 EP 6 DI 10.1111/j.1475-6773.2006.00693.x PN 1 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 128CN UT WOS:000243634800002 PM 17355578 ER PT J AU Hysong, SJ Best, RG Pugh, JA AF Hysong, Sylvia J. Best, Richard G. Pugh, Jacqueline A. TI Clinical practice guideline implementation strategy patterns in veterans affairs primary care clinics SO HEALTH SERVICES RESEARCH LA English DT Article DE guidelines; qualitative research; implementation research; evidence based medicine; health services research ID QUALITY-OF-CARE; GENERAL-PRACTICE; CONTROLLED-TRIAL; DISEASES; TIME AB Background. The Department of Veterans Affairs (VA) mandated the system-wide implementation of clinical practice guidelines (CPGs) in the mid-1990s, arming all facilities with basic resources to facilitate implementation; despite this resource allocation, significant variability still exists across VA facilities in implementation success. Objective. This study compares CPG implementation strategy patterns used by high and low performing primary care clinics in the VA. Research Design. Descriptive, cross-sectional study of a purposeful sample of six Veterans Affairs Medical Centers (VAMCs) with high and low performance on six CPGs. Subjects. One hundred and two employees ( management, quality improvement, clinic personnel) involved with guideline implementation at each VAMC primary care clinic. Measures. Participants reported specific strategies used by their facility to implement guidelines in 1-hour semi-structured interviews. Facilities were classified as high or low performers based on their guideline adherence scores calculated through independently conducted chart reviews. Findings. High performing facilities (HPFs) ( a) invested significantly in the implementation of the electronic medical record and locally adapting it to provider needs, (b) invested dedicated resources to guideline-related initiatives, and ( c) exhibited a clear direction in their strategy choices. Low performing facilities exhibited ( a) earlier stages of development for their electronic medical record, ( b) reliance on preexisting resources for guideline implementation, with little local adaptation, and ( c) no clear direction in their strategy choices. Conclusion. A multifaceted, yet targeted, strategic approach to guideline implementation emphasizing dedicated resources and local adaptation may result in more successful implementation and higher guideline adherence than relying on standardized resources and taxing preexisting channels. C1 Baylor Coll Med, Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Lcokheed Martin Informat Technol, Healthcare Solut, Alexandria, VA USA. S Texas Vet Helth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Hysong, SJ (reprint author), Baylor Coll Med, Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Hysong, Sylvia/B-8420-2008; OI Hysong, Sylvia/0000-0002-9063-5207; Pugh, Jacqueline/0000-0003-4933-141X NR 29 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2007 VL 42 IS 1 BP 84 EP 103 DI 10.1111/j.1475-6773.2006.00610.x PN 1 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 128CN UT WOS:000243634800007 PM 17355583 ER PT J AU Richardson, SS Sullivan, G Hill, A Yu, W AF Richardson, Samuel S. Sullivan, Greer Hill, Ariel Yu, Wei TI Use of aggressive medical treatments near the end of life: Differences between patients with and without dementia SO HEALTH SERVICES RESEARCH LA English DT Article DE acute inpatient care; end-of-life decisions; VA health care system; administrative data uses ID INTENSIVE-CARE-UNIT; ADVANCE DIRECTIVES; ALZHEIMERS-DISEASE; MYOCARDIAL-INFARCTION; HOSPITALIZED-PATIENTS; REVERSIBLE DEMENTIAS; QUALITY INDICATORS; CRITICALLY-ILL; SERIOUSLY ILL; NURSING-HOME AB Objectives. To analyze whether acute care patients with dementia are more or less likely to receive each of five aggressive medical services near the end of life, compared with patients without dementia. Data Source. Two years of Veterans Affairs (VA) and Medicare utilization data for all 169,036 VA users nationwide age 67 and older who died between October 1, 1999 and September 30, 2001. Study Design. We performed a retrospective analysis of acute care stays discharged in the final 30 days of life. The main outcome measure was the patient's likelihood of receiving each of five aggressive services (intensive care unit [ICU] admission, ventilator, cardiac catheterization, pulmonary artery monitor, and dialysis), controlling for demographic and clinical factors in probit regressions. Principal Findings. There were 122,740 acute-stay discharges during the final 30 days of life, representing 94,100 unique patients (31,654 with dementia). In probit models comparing acute care patients with and without dementia, patients with dementia were 7.5 percentage points less likely to be admitted to the ICU (95 percent confidence interval [CI], 6.9-8.1; percent of stays with ICU admission=36.8 percent), 5.4 percentage points less likely to be placed on a ventilator (95 percent CI, 5.0-5.9; percent of stays with ventilator use=17.1 percent), 0.7 percentage points less likely to receive cardiac catheterization (95 percent CI, 0.6-0.8; percent of stays with cardiac catheterization=2.7 percent), 1.4 percentage points less likely to receive pulmonary artery monitoring (95 percent CI, 1.2-1.5; percent of stays with pulmonary artery monitoring=2.6 percent), and 0.6 percentage points less likely to receive dialysis (95 percent CI, 0.4-0.8; percent of stays with dialysis=4.6 percent). Conclusions. During the final 30 days of life, acute care patients with dementia are treated substantially less aggressively than patients without dementia. Further research is warranted to determine the causes and appropriateness of these patterns of care. C1 VA Palo Alto Hlth Care Syst, Menlo Pk, CA 94025 USA. US Dept Vet Affairs, Hlth Econ Resource Ctr, Hlth Serv Res & Dev Serv, Menlo Pk, CA USA. US Dept Vet Affairs, S Cent Mental Illness Res Educ & Clin Ctr, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. RP Richardson, SS (reprint author), VA Palo Alto Hlth Care Syst, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. NR 50 TC 12 Z9 12 U1 3 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2007 VL 42 IS 1 BP 183 EP 200 DI 10.1111/j.1475-6773.2006.00608.x PN 1 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 128CN UT WOS:000243634800012 PM 17355588 ER PT J AU Schmidt, EJ Reddy, VK Ruskin, JN AF Schmidt, Ehud J. Reddy, Vivek K. Ruskin, Jeremy N. TI Nonenhanced magnetic resonance imaging for characterization of acute and subacute radiofrequency ablation lesions - Editorial Commentary SO HEART RHYTHM LA English DT Editorial Material ID MYOCARDIAL-INFARCTION; TUMOR ABLATION; MRI; GUIDANCE; MODEL; TISSUE; LIVER; DENSE C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. GE Healthcare Appl Sci Lab, Boston, MA USA. RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Arrhythmia Serv, GRB-122,55 Fruit St, Boston, MA 02114 USA. EM jruskin@partners.org NR 24 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD FEB PY 2007 VL 4 IS 2 BP 215 EP 217 DI 10.1016/j.hrthm.2006.11.013 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 134RW UT WOS:000244102600017 PM 17275760 ER PT J AU Sundar, PD Yu, CE Sieh, W Steinbart, E Garruto, RM Oyanagi, K Craig, UK Bird, TD Wijsman, EM Galasko, DR Schellenberg, GD AF Sundar, Purnima Desai Yu, Chang-En Sieh, Weiva Steinbart, Ellen Garruto, Ralph M. Oyanagi, Kiyomitsu Craig, Ulla-Katrina Bird, Thomas D. Wijsman, Ellen M. Galasko, Douglas R. Schellenberg, Gerard D. TI Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia SO HUMAN MOLECULAR GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROGRESSIVE SUPRANUCLEAR PALSY; SPORADIC ALZHEIMERS-DISEASE; SAITOHIN Q7R POLYMORPHISM; PARKINSONISM-DEMENTIA; TAU-GENE; NEUROFIBRILLARY TANGLES; NEURODEGENERATIVE DISEASES; CORTICOBASAL DEGENERATION; LINKAGE DISEQUILIBRIUM AB Unusual forms of amyotrophic lateral sclerosis (ALS-G), Parkinsonism dementia complex (PDC-G) and Guam dementia (GD) are found in Chamorros, the indigenous people of Guam. Neurofibrillary tangles composed of hyperphosphorylated tau are a neuropathologic feature of these closely related disorders. To determine if variation in the gene that encodes microtubule-associated protein tau gene (MAPT) contributes to risk for these disorders, we genotyped nine single nucleotide polymorphism (SNP) sites and one insertion/deletion in the 5' end of MAPT in 54 ALS-G, 135 PDC-G, 153 GD and 258 control subjects, all of whom are Chamorros. Variation at three SNPs (sites 2, 6 and 9) influenced risk for ALS-G, PDC-G and GD. SNP2 acts through a dominant mechanism and is independent of the risk conferred by SNPs 6 and 9, the latter two acting by a recessive mechanism. Persons with the high-risk SNP6 and SNP9 AC/AC diplotype had an increased risk of 3-fold [95% confidence interval (CI)=1.10-8.25] for GD, 4-fold (95% CI=1.40-11.64) for PDC-G and 6-fold (95% CI=1.44-32.14) for ALS-G, compared to persons with other diplotypes after adjusting for SNP2. Carriers of the SNP2 G allele had an increased risk of 1.6-fold (95% CI=1.00-2.62) for GD, 2-fold (95% CI=1.28-3.66) for PDC-G, and 1.5-fold (95% CI=0.74-3.00) for ALS-G, compared to non-carriers after adjusting for SNPs 6 and 9. Others have shown that SNP6 is also associated with risk for progressive supranuclear palsy. These two independent cis-acting sites presumably influence risk for Guam neuro-degenerative disorders by regulating MAPT expression. C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC S 182B, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Neurol & Pharmacol, Seattle, WA 98195 USA. SUNY Binghamton, Dept Anthropol, Lab Biomed Anthropol & Neurosci, Binghamton, NY 13902 USA. Tokyo Metropolitan Inst Neurosci, Dept Neuropathol, Tokyo, Japan. Univ Guam, Mangilao, GU 96923 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC S 182B, 1660 S Columbia Way, Seattle, WA 98108 USA. EM zachdad@u.washington.edu OI Wijsman, Ellen/0000-0002-2725-6669 FU NIA NIH HHS [P50 AG 05136, P01 AG14382] NR 73 TC 39 Z9 40 U1 0 U2 2 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 FEB 1 PY 2007 VL 16 IS 3 BP 295 EP 306 DI 10.1093/hmg/ddl463 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 135AK UT WOS:000244126000006 PM 17185385 ER PT J AU Hull, MJ Nazarian, RM Wheeler, AE Black-Schaffer, WS Mark, EJ AF Hull, Mindy J. Nazarian, Rosalynn M. Wheeler, Amy E. Black-Schaffer, W. Stephen Mark, Eugene J. TI Resident physician opinions on autopsy importance and procurement SO HUMAN PATHOLOGY LA English DT Article DE autopsy; resident physician; survey; procurement; quality control; medical education ID CONSECUTIVE AUTOPSIES; QUALITY IMPROVEMENT; INFORMATION; CHALLENGE; RATES; DEATH AB The national decline in hospital autopsy cases negatively impacts physician education and medical quality control to an unknown degree. The current non-medicolegal autopsy rate is less than 5% of hospital deaths. This study compares internal medicine and pathology resident physician perceptions of the autopsy, including the importance, procurement, technique, and the pathologist-internist interaction. An 84-item survey based on autopsy literature was designed, piloted, and distributed to 214 residents at a single 800+ bed tertiary care academic teaching hospital (Massachusetts General Hospital, Boston) to accomplish this goal. Completed surveys were obtained from 72% of medicine (n = 118) and 84% of pathology (n = 42) residents. Residents strongly agree on the importance of autopsies for education, answering clinical questions, public health, and research. Autopsy rates are deemed inadequate. Internists are comfortable requesting autopsies, but report insufficient guidance and difficulty with answering technical questions. Although not requested on all hospital deaths, internists are more likely to initiate an autopsy request than a decedent's family, and worry significantly less about institutional costs and malpractice litigation than pathologists believe. Internists expressed interest in having an instructional brochure to give families, observing an autopsy, and having increased communication and support with autopsies from pathology residents. The main reasons why autopsy consent is not requested (it is unpleasant, cause of death is known, family is upset or seems unwilling) and why families refuse (patient has suffered enough, body may be handled disrespectfully, religious/moral objections, lack information) were similar for both resident groups. Despite their decline, autopsies still remain important to medicine as indicated by internal medicine and pathology residents at a large academic center. Improving autopsy education, enhancing availability of resources, and strengthening the pathologist-internist collaboration may serve to heighten awareness and ultimately procurement. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Hull, MJ (reprint author), Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA. EM mjhull@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 23 TC 36 Z9 39 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2007 VL 38 IS 2 BP 342 EP 350 DI 10.1016/j.humpath.2006.08.011 PG 9 WC Pathology SC Pathology GA 131QB UT WOS:000243883700018 PM 17134740 ER PT J AU Meeker, JD Missmer, SA Cramer, DW Hauser, R AF Meeker, J. D. Missmer, S. A. Cramer, D. W. Hauser, R. TI Maternal exposure to second-hand tobacco smoke and pregnancy outcome among couples undergoing assisted reproduction SO HUMAN REPRODUCTION LA English DT Article DE ETS; IVF; pregnancy; second-hand smoke; spontaneous abortion ID CIGARETTE-SMOKING; URINARY COTININE; US POPULATION; DNA-DAMAGE; BIOMARKERS; IVF; SUSCEPTIBILITY; MAINSTREAM; FERTILITY; CHILDREN AB BACKGROUND: Exposure to second-hand tobacco smoke is preventable, yet common. This study assessed relationships between maternal exposure to second-hand tobacco smoke and adverse pregnancy outcomes. METHODS: We measured cotinine (a biomarker of tobacco smoke) in urine from 921 women undergoing assisted reproductive technologies (ARTs) between 1994 and 1998. We also collected information on self-reported exposure to second-hand smoke at home or at work, in addition to parental smoking during the women's childhood. RESULTS: In crude analysis, creatinine-adjusted cotinine levels were associated with a slight decrease in implantation rate among non-smoking women (11.1% in the lowest cotinine quintile versus 8.2% in the highest cotinine quintile; P = 0.13). However, in multivariate logistic regression, cotinine levels above the median were not associated with failed fertilization, failed implantation or spontaneous abortion, nor was there evidence of a dose-response relationship among cotinine quintiles. After excluding women in couples diagnosed with male factor infertility, there were increased odds of having a spontaneous abortion among non-smoking women who reported that both parents smoked while they were children growing up compared with women reporting that neither parent smoked [adjusted odds ratio (OR) = 4.35; 95% confidence interval (CI) = 1.04-18.1]. CONCLUSIONS: Female exposure to second-hand smoke as a child or in utero may be associated with an increased risk of spontaneous abortion in adulthood. However, this may be a chance finding due to multiple comparisons. Similar associations should be explored in additional studies with more refined estimates of childhood and in utero exposure to tobacco smoke. C1 Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, N6226 SPH 2,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu OI Meeker, John/0000-0001-8357-5085 FU NICHD NIH HHS [R01-HD32153] NR 46 TC 28 Z9 29 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 2007 VL 22 IS 2 BP 337 EP 345 DI 10.1093/humrep/de1406 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 127MU UT WOS:000243591200004 PM 17053002 ER PT J AU Tyrrell, JA di Tomaso, E Fuja, D Tong, R Kozak, K Jain, RK Roysam, B AF Tyrrell, James Alexander di Tomaso, Emmanuelle Fuja, Daniel Tong, Ricky Kozak, Kevin Jain, Rakesh K. Roysam, Badrinath TI Robust 3-D modeling of vasculature imagery using superellipsoids SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE robust detection/estimation; superellipsoid; vessel detection/segmentation ID GLOBAL DEFORMATIONS; ACTIVE CONTOURS; RETINAL IMAGES; BLOOD-VESSELS; FUNDUS IMAGES; TUMORS; NORMALIZATION; SUPERQUADRICS; EXTRACTION; MICROSCOPY AB This paper presents methods to model complex vasculature in three-dimensional (3-D) images using cylindroidal superellipsoids, along with robust estimation and detection algorithms for automated image analysis. This model offers an explicit, low-order parameterization, enabling joint estimation of boundary, centerlines, and local pose. It provides a geometric framework for directed vessel traversal, and extraction of topological information like branch point locations and connectivity. M-estimators provide robust region-based statistics that are used to drive the superellipsoid toward a vessel boundary. A robust likelihood ratio test is used to differentiate between noise, artifacts, and other complex unmodeled structures, thereby verifying the model estimate. The proposed methodology behaves well across scale-space, shows a high degree of insensitivity to adjacent structures and implicitly handles branching. When evaluated on synthetic imagery mimicking specific structural complexities in tumor microvasculature, it consistently produces ubvoxel accuracy estimates of centerlines and widths in the presence of closely-adjacent vessels, branch points, and noise. An edit-based validation demonstrated a precision level of 96.6% at a recall level of 95.4%. Overall, it is robust enough for large-scale application. C1 Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Charlestown, MA 02129 USA. RP Roysam, B (reprint author), Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA. RI Tyrrell, James/A-6359-2010 FU NCI NIH HHS [BRP-R24-CA85140]; NCPDCID CDC HHS [NCI-P01-CA80124] NR 45 TC 74 Z9 78 U1 2 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD FEB PY 2007 VL 26 IS 2 BP 223 EP 237 DI 10.1109/TMI.2006.889722 PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 132AM UT WOS:000243914200008 PM 17304736 ER PT J AU Culshaw, S LaRosa, K Tolani, H Han, X Eastcott, JW Smith, DJ Taubman, AA AF Culshaw, S. LaRosa, K. Tolani, H. Han, X. Eastcott, J. W. Smith, D. J. Taubman, A. A. TI Immunogenic and protective potential of mutans streptococcal glucosyltransferase peptide constructs selected by major histocompatibility complex class II allele binding SO INFECTION AND IMMUNITY LA English DT Article ID DENTAL-CARIES; GLUCAN-BINDING; IMMUNOLOGICAL CHARACTERISTICS; LOCAL IMMUNIZATION; RATS; ANTIBODY; IMMUNITY; PROTEIN; DOMAIN; PREDICTION AB Mutans streptococcal glucosyl transferases (GTF) have been demonstrated to be effective components of dental caries vaccines. We had previously selected peptide subunits of GTF for vaccine development based on putative functional significance and conservation of GTF primary structure among enzyme isoforms. In this study, 20 20-mer linear GTF peptides were synthesized, 17 identified on the basis of the highest potential major histocompatibility complex (MHC) class II-binding activity using computer-generated algorithms (Epitnatrix and ProPred) and 3 with previously demonstrated functional significance. The immunoreactivities of these peptides were explored with rodent systems. Sera from GTF-immunized rats, assessed for binding to linear peptides by enzyme-linked immunosorbent assay, demonstrated immunoglobulin G antibody reactivity with peptides 6 and 11 and a T-cell proliferation response to peptides 6, 9, 11, and 16. Multiple antigenic peptide (MAP) constructs were synthesized from promising linear sequences. Rats that were immunized with MAP 7, 11, or 16, respectively, responded well to the immunizing MAP. Most importantly, a robust immune response (antibody and T-cell proliferation) was observed to native GTF following MAP 11 (amino acids 847 to 866; VVINNDKFVSWGITDFEM) immunization. This response inhibited GTF enzyme function. Two dental caries pathogenesis experiments were performed wherein rats were immunized with MAP constructs 11, 16, and/or 11 plus 16, followed by infection with cariogenic Streptococcus sobrinus. In both experiments cariogenic bacterial recoveries were reduced relative to total streptococci in the MAP 11- and MAP 11 plus 16-immunized groups, and the extent of dental caries was also significantly reduced in these groups. Thus, we have identified a peptide with projected avid MHC-binding activity that elicited immunoreactivity with native GTF and demonstrated protection against dental caries infection after immunization, implying that this peptide may be important in a subunit dental caries vaccine. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Taubman, AA (reprint author), Forsyth Inst, Dept Immunol, 140 The Fenway, Boston, MA 02115 USA. EM mtauban@forsyth.org FU NIDCR NIH HHS [L30 DE020037, DE-04733, R01 DE003420, R01 DE004733, R56 DE004733] NR 33 TC 14 Z9 15 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2007 VL 75 IS 2 BP 915 EP 923 DI 10.1128/IAI.01582-06 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 131JQ UT WOS:000243865500041 PM 17088351 ER PT J AU Christ, M Noack, F Schroeder, T Hagmueller, A Koch, R May, SA Morgenstern, U Ragaller, M Steinmeier, R AF Christ, Melanie Noack, Frank Schroeder, Tobias Hagmueller, Andreas Koch, Rainer May, Sven-Axel Morgenstern, Ute Ragaller, Maximilian Steinmeier, Ralf TI Continuous cerebral autoregulation monitoring by improved cross-correlation analysis: comparison with the cuff deflation test SO INTENSIVE CARE MEDICINE LA English DT Article DE cerebral autoregulation; continuous neuromonitoring; cross-correlation; transcranial Doppler; head injury; subarachnoid hemorrhage ID ARTERIAL-BLOOD-PRESSURE; ANEURYSMAL SUBARACHNOID HEMORRHAGE; TRAUMATIC BRAIN-INJURY; SEVERE HEAD-INJURY; FLOW VELOCITY; TRANSCRANIAL DOPPLER; PERFUSION-PRESSURE; CEREBROVASCULAR AUTOREGULATION; HUMANS; OSCILLATIONS AB Objectives: To improve the cross-correlation method for noninvasive, continuous monitoring of cerebral autoregulation, to evaluate this method in humans with intact and impaired autoregulatory capacity, and to compare it to the cuff deflation test. Design and setting: Prospective study in the intensive care unit of a university hospital. Patients and participants: Fourteen patients with severe head injury, six patients with subarachnoid hemorrhage, and nine healthy volunteers. Interventions and measurements: Middle cerebral artery flow velocities and arterial blood pressure were monitored continuously. Aaslid's thigh cuff tests were performed and results were scored using Tiecks' model for autoregulation index. Data were then collected without any patient manipulation. The mean time delay between slow spontaneous oscillations of blood pressure and middle cerebral artery flow velocity was calculated by cross-correlation analysis. Data are expressed as median (lower/upper quartile). Results: Healthy subjects had a higher autoregulation index than patients, 5.0 (5.0/5.5) vs. 3.3 (2.0/4.5). Slow oscillations of blood pressure and middle cerebral artery flow velocity showed a time delay of -2.0 s (-2.7/-1.7) in healthy subjects but were almost synchronal in patients, -0.07 s (-0.5/0.45). Inter-method agreement in diagnosing an intact or impaired cerebral autoregulation was obtained in 108 of 147 examinations of autoregulation (73.5%) and was considered moderate. Conclusions: Cross-correlation analysis may serve as a simple, noninvasive, and continuous measure of cerebral autoregulation. The time delay of -2.0 s in healthy subjects is in good agreement with other studies. Short-term autoregulation tests and monitoring techniques based on slow spontaneous oscillations should not be used interchangeably. C1 Tech Univ Dresden, Dept Anesthesiol & Intens Care Med, Carl Gustav Carus Univ Hosp, D-01307 Dresden, Germany. Tech Univ Dresden, Inst Biomed Engn, Dept Elect Engn & Informat Technol, D-01062 Dresden, Germany. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christ, M (reprint author), Tech Univ Dresden, Dept Anesthesiol & Intens Care Med, Carl Gustav Carus Univ Hosp, Fetscherstasse 74, D-01307 Dresden, Germany. EM Melanie.Christ@uniklinikum-dresden.de OI Schroeder, Tobias/0000-0002-4439-8060 NR 40 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD FEB PY 2007 VL 33 IS 2 BP 246 EP 254 DI 10.1007/s00134-006-0451-8 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 133QA UT WOS:000244026200007 PM 17143638 ER PT J AU Shea, JA Guerra, CE Ravenell, KL Mcdonald, VJ Henry, CAN Asch, DA AF Shea, Judy A. Guerra, Carmen E. Ravenell, Karima L. Mcdonald, Vanessa J. Henry, Camille A. N. Asch, David A. TI Health literacy weakly but consistently predicts primary care patient dissatisfaction SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE health literacy; patient satisfaction; Veterans Health Administration ID AFRICAN-AMERICAN; MEDICAL-CARE; SATISFACTION; SERVICES; QUALITY; QUESTIONNAIRE; COMORBIDITY; PERCEPTIONS; INSTRUMENT; VETERANS AB Objectives. To study relationships between health literacy and multiple satisfaction domains. Health literacy is related to some domains of patient satisfaction such as communication and understanding, but little is known about relationships of health literacy with other satisfaction domains. Moreover, the importance of health literacy in predicting satisfaction compared with other patient sociodemographics is underexplored. Design. Cross-sectional survey. Setting. Primary care waiting areas with a Veterans Administration Medical Center and a university health system. Participants. One thousand five hundred and twenty-eight primary care patients. Main outcome measures. A brief demographics questionnaire, the Rapid Estimate of Adult Literacy in Medicine, the Veterans Affairs ambulatory care patient satisfaction survey, and an adaptation of the Charlson Comorbidity Index. Results. In unadjusted regression analyses, lower health literacy level was a significant predictor of worse satisfaction in 7 of 10 domains (P < 0.01). When adjusting for patient sociodemographics, predicted relationships remained significant in six of the seven domains (P < 0.05), with each unit change in the 4-stage literacy classification associated with a 3-6 point decrease in dissatisfaction scores (0-100 scale). Health literacy did not predict overall dissatisfaction (P = 0.55). Conclusions. These results suggest that health literacy, as assessed through a pronunciation exercise that is closely related to more comprehensive measures of literacy, has a consistent, albeit weak relationship with patient satisfaction. Future work is needed to clarify if patients with lower literacy are really receiving different care than those with higher literacy and to pinpoint the sources of their more negative responses. C1 Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Shea, JA (reprint author), Univ Penn, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sheaja@mail.med.upenn.edu OI Asch, David/0000-0002-7970-286X NR 27 TC 14 Z9 15 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD FEB PY 2007 VL 19 IS 1 BP 45 EP 49 DI 10.1093/intqhc/mzl068 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 133DU UT WOS:000243993000008 PM 17178765 ER PT J AU Garrison, MW Nuemiller, JJ AF Garrison, Mark W. Nuemiller, Joshua J. TI In vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article; Proceedings Paper CT 45th Interscience Conference on Antimicrobial Agents and Chemotherapy CY DEC 16-19, 2005 CL Washington, DC DE tigecycline; quinolone-resistant S. pneumoniae; MRSA; VRE; pharmacodynamics ID TRIAL TEST PROGRAM; UNITED-STATES; GLYCYLCYCLINE; GAR-936; UPDATE; US AB Tigecycline is a glycylcycline with promising broad-spectrum activity, including resistant Gram-positive organisms. This study characterizes in vitro activity of tigecycline against quinolone-resistant Streptococcus pneumoniae (QRSP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcusfaecalis (VRE). An in vitro pharmacodynamic model generated specific bacterial kill profiles for tigecycline against clinical isolates of QRSP, MRSA and VRE. Tigecycline produced a 6.6 log total reduction and cleared QRSP from the pharmacodynamic model by 18 h. Tigecycline and vancomycin were unable to achieve 3-log reductions in the MRSA and VRE isolates; log reductions in MRSA and VRE were 1.5 and 1.2 logs for figecycline and 2.8 and zero for vancomycin, respectively. Area under the concentration time curve to minimum inhibitory concentration (AUC/MIC) values for figecycline ranged from 79 to 158 mu g h/mL and tigecycline concentrations remained above the MIC (T > MIC) throughout the simulated dosing interval. Tigecycline showed in vitro activity against the QRSP, MRSA and VRE isolates studied. Low MIC values, prolonged elimination half-life and the associated post-antibiotic effect (PAE) observed with figecycline are desirable attributes that make it a potentially attractive option for treating resistant Gram-positive organisms. (c) 2006 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 Washington State Univ, Coll Pharm, Spokane, WA 99210 USA. Deaconess Med Ctr, Spokane, WA 99210 USA. RP Garrison, MW (reprint author), Washington State Univ, Coll Pharm, Spokane, WA 99210 USA. EM garrism@wsu.edu NR 20 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD FEB PY 2007 VL 29 IS 2 BP 191 EP 196 DI 10.1016/j.ijantimicag.2006.08.048 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 134KQ UT WOS:000244082300011 PM 17174074 ER PT J AU Kang, H O'Connell, JB Leonardi, MJ Maggard, MA McGory, ML Ko, CY AF Kang, Hakjung O'Connell, Jessica B. Leonardi, Michael J. Maggard, Melinda A. McGory, Marcia L. Ko, Clifford Y. TI Rare tumors of the colon and rectum: a national review SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Review DE colorectal; SEER; carcinoid; lymphoma; rare tumor ID NON-HODGKINS-LYMPHOMA; SQUAMOUS-CELL CARCINOMA; GASTROINTESTINAL-TRACT; TIME TRENDS; EXPERIENCE; PROGNOSIS; SURVIVAL; JAPAN AB Background Most literature available on rare colorectal cancer (CRC) is from case series reports. This population-based evaluation is the first comprehensive look at four rare histologic types of CRC, allowing comparisons with the more common adenocarcinoma for clinical and pathological features and survival rates. Materials and ethods All patients diagnosed with carcinoid (n=2,565), malignant lymphoma (n=955), non-carcinoid neuroendocrine (n=455), squamous cell (n=437), and adenocarcinoma (n=164,638) in SEER cancer database (1991-2000) were analyzed. Evaluation of age-adjusted incidence rate, stage at presentation, and 5-year relative survival were determined for each histologic subtype. Results All rare histologic subtypes had younger mean age than adenocarcinomas (70 years; p < 0.05). Lymphoma was more common in males (65.1%; P < 0.01). Incidence rates in 2000 per million were: carcinoid 10.6, lymphoma 3.5, neuroendocrine 2.0, squamous 1.9, and adenocarcinoma 496.3. The annual percent change in incidence for each rare tumor increased significantly during the 10 years (range: 3.1-9.4%, p < 0.05), except squamous cell carcinoma (5.9%, p > 0.05). Squamous (93.4%) and carcinoid (73.7%) tumors occurred more often in the rectum; lymphoma (79.0%), neuroendocrine (70.8%), and adenocarcinoma (70.1%) occurred more often in the colon (P < 0.01). Carcinoids presented at earlier stage (localized/regional, 90.5%) more often than adenocarcinoma (80.6%; p < 0.01), but squamous cell (82.1%; p=0.50), lymphoma (70.6%; p < 0.01), and neuroendocrine (37.8%; p < 0.01) presented at earlier stage similarly or less often than adenocarcinoma. Relative 5-year survival rate was highest for carcinoid (91.3%), and lowest for neuroendocrine tumors (21.4%). Conclusion This study provides the first population-based analysis of the epidemiology, tumor characteristics, and survival rates for rare CRC. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. Daehang Hosp, Dept Surg, Seoul, South Korea. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Surg Outcomes & Qual, Los Angeles, CA 90095 USA. RP Ko, CY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS,POB 956904, Los Angeles, CA 90095 USA. NR 24 TC 48 Z9 51 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-1958 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD FEB PY 2007 VL 22 IS 2 BP 183 EP 189 DI 10.1007/s00384-006-0145-2 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 117PE UT WOS:000242884400011 PM 16845516 ER PT J AU Akilov, OE Khachemoune, A Hasan, T AF Akilov, Oleg E. Khachemoune, Amor Hasan, Tayyaba TI Clinical manifestations and classification of Old World cutaneous leishmaniasis SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Review ID AZAR DERMAL LEISHMANIASIS; CHRONIC LUPOID LEISHMANIASIS; LYMPH-NODE INVOLVEMENT; KALA-AZAR; GENUS LEISHMANIA; SAUDI-ARABIA; SPOROTRICHOID LEISHMANIASIS; DIFFUSE; EVOLUTION; DISSEMINATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Khachemoune, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, 40 Blossom St,BAR 314, Boston, MA 02114 USA. EM amorkh@pol.net NR 82 TC 31 Z9 34 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD FEB PY 2007 VL 46 IS 2 BP 132 EP 142 PG 11 WC Dermatology SC Dermatology GA 132KF UT WOS:000243941000003 PM 17269962 ER PT J AU Yang, MQ Yang, JY Ersoy, OK AF Yang, Mary Q. Yang, Jack Y. Ersoy, Okan K. TI Classification of proteins multiple-labelled and single-labelled with protein functional classes SO INTERNATIONAL JOURNAL OF GENERAL SYSTEMS LA English DT Article DE computational intelligence; machine learning; classification; multifunctional proteins; bioinformatics ID DATABASE AB Advances in high-throughput genome sequencing technology have led to an explosion in the amount of sequence data that are available. The determination of protein function using experimental techniques is time-consuming and expensive; the use of machine-learning techniques rapidly to assess protein function may be useful in streamlining this process. The problem of assigning functional classes to proteins is complicated by the fact that a single protein can participate in several different pathways and thus can have multiple functions. We have developed a tree-based classifier that is capable of handling multiple-labelled data and gaining an insight into the multi-functional nature of proteins. We call the resulting tree a recursive maximum contrast tree (RMCT) and the resulting classifier a multiple-labelled instance classifier (MLIC). We investigate the synergy of machine-learning-based ensemble methods and physiochemical-based feature augments. We test our algorithm on protein phylogenetic profiles generated from 60 completely sequenced genomes and we compare our results with those achieved by algorithms such as support vector machines and decision trees. C1 Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. US Dept HHS, NHGRI, NIH, Rockville, MD 20852 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yang, JY (reprint author), Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. EM jyang@hadron.mgh.harvard.edu NR 29 TC 4 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0308-1079 EI 1563-5104 J9 INT J GEN SYST JI Int. J. Gen. Syst. PD FEB PY 2007 VL 36 IS 1 BP 91 EP 109 DI 10.1080/03081070600950868 PG 19 WC Computer Science, Theory & Methods; Ergonomics SC Computer Science; Engineering GA 115XN UT WOS:000242767200005 ER PT J AU Sillanpaa, H Lahdenne, P Sarvas, H Arnez, M Steere, A Peltomaa, M Seppala, L AF Sillanpaa, Heidi Lahdenne, Pekka Sarvas, Heikki Arnez, Maja Steere, Allen Peltomaa, Miikka Seppala, Llkka TI Immune responses to borrelial VIsE IR6 peptide variants SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article DE borrelia; Lyme disease; ELISA; IR6 peptide; C6 ID IMMUNODOMINANT CONSERVED REGION; LINKED-IMMUNOSORBENT-ASSAY; LYME-DISEASE; ANTIGENIC VARIATION; ERYTHEMA MIGRANS; BURGDORFERI; VLSE; SERODIAGNOSIS; SEROLOGY; AFZELII AB Laboratory confirmation of Lyme borreliosis (LB) relies mainly on the demonstration of anti-borrelial antibodies. In recent studies, a novel VIsE protein IR6 peptide-based assay has been introduced. Our aim was to evaluate the IR6 peptides from three Borrelia burgdorferi sensu lato genospecies in the serodiagnosis of European and North American patients. Five VIsE protein IR6 peptide variants representing sequences from B. burgdorferi sensu stricto, B. garinii, and B. afzelii were used as antigens in both IgG and IgM enzyme-linked immunosorbent assays (ELISA). Serum antibodies of 187 patients at different stages of LB from Europe and the United States were evaluated for serodiagnosis. For comparison samples were tested with one of the commercial IR6 ELISAs. Three B. afzelii IR6 variant peptides revealed antibodies that were concordant with each other. R burgdorferi sensu stricto peptide antibodies mostly paralleled B. afzelii peptide antibodies, and positive values were also obtained in the majority of European sera. For several sera, B. garinii IR6 peptide antibodies were discordant to B. afzelii peptide antibodies. The commercial IR6 peptide antibody assay (C6 ELISA) results correlated better with B. burgdorferi sensu stricto IR6 than with B. garinii IR6 peptide IgG results, especially in sera from patients with facial palsy. Thus, antibody specificity to IR6 peptides may vary according to the infecting Borrelia species. In some manifestations of the disease, C6 ELISA may not cover all LB cases. Evidently, the methodological aspects in ELISA design for peptide antibody measurements are important as well as the amino acids sequence of the antigen. (c) 2007 Published by Elsevier GmbH. C1 Haartman Inst, Dept Bacteriol & Immunol, FI-00014 Helsinki, Finland. Univ Helsinki, Hosp Children & Adoelscents, Helsinki, Finland. Univ Helsinki, HUSLAB, Cent Hosp Lab, Helsinki, Finland. Univ Ljubljana, Dept Infect Dis, Med Ctr, Ljubljana, Slovenia. Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Sch Med, Boston, MA 02114 USA. RP Seppala, L (reprint author), Haartman Inst, Dept Bacteriol & Immunol, POB 21, FI-00014 Helsinki, Finland. EM ilkka.j.seppala@helsinki.fi NR 28 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4221 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD FEB PY 2007 VL 297 IS 1 BP 45 EP 52 DI 10.1016/j.ijmm.2006.09.001 PG 8 WC Microbiology; Virology SC Microbiology; Virology GA 139EV UT WOS:000244416000006 PM 17234451 ER PT J AU Purnell, JQ Cummings, D Weigle, DS AF Purnell, J. Q. Cummings, D. Weigle, D. S. TI Changes in 24-h area-under-the-curve ghrelin values following diet-induced weight loss are associated with loss of fat-free mass, but not with changes in fat mass, insulin levels or insulin sensitivity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE ghrelin; insulin; insulin sensitivity; fat mass; fat-free mass; weight loss ID PRADER-WILLI-SYNDROME; PLASMA GHRELIN; CIRCULATING GHRELIN; HUMAN OBESITY; HUMANS; RESISTANCE; SECRETION; GLUCOSE; INDEX; MEN AB Objective: To determine which parameters of body composition or metabolism best correlate with changes in 24 h ghrelin levels following weight loss. Design: A 3-month low-calorie diet followed by 3 months of weight stabilization. Subjects: Twelve overweight and obese adult men and women. Measurements: Body composition by underwater weighing, abdominal fat depots, leptin, ghrelin and parameters of insulin and lipid metabolism. Results: Increased 24 h ghrelin levels after weight loss correlated with decreases in body mass index, subcutaneous fat and fat-free mass (FFM), but not with changes in fat mass, fat cell size, leptin, insulin, insulin sensitivity, lipids or free fatty acid levels. The change in FFM correlated with the rise in ghrelin levels independently of body adiposity. Discussion: Alterations in FFM with diet-induced weight loss may play a role in ghrelin regulation. Changes in ghrelin levels could, then, serve as an integrative signal reflecting changes in FFM to hypothalamic centers controlling energy homeostasis. C1 Oregon Hlth Sci Univ, Ctr Study Weight Regulat & Associated Disorders, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Harborview Med Ctr, Seattle, WA USA. RP Purnell, JQ (reprint author), Oregon Hlth Sci Univ, Ctr Study Weight Regulat & Associated Disorders, Dept Med, Div Endocrinol Diabet & Clin Nutr, Mail Stop L607,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM purnellj@ohsu.edu RI Biguzzi, Felipe/E-4724-2015 FU NCRR NIH HHS [M01RR00037, M01RR00334]; NIDDK NIH HHS [K23 DK02689, K24 DK02860, P30DK17047, R01 DK 61516, R01 DK55460] NR 28 TC 20 Z9 21 U1 1 U2 3 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 FEB PY 2007 VL 31 IS 2 BP 385 EP 389 DI 10.1038/sj.ijo.0803401 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 134KI UT WOS:000244081500029 PM 16819531 ER PT J AU Shih, YH Scarcelli, G Berardi, V AF Shih, Yanhua Scarcelli, Giuliano Berardi, Vincenzo TI Two-photon correlation of chaotic light: A quantum interference phenomenon SO INTERNATIONAL JOURNAL OF QUANTUM INFORMATION LA English DT Article; Proceedings Paper CT Workshop on Advances in Foundations of Quantum Mechanics and Quantium Information with Atoms and Photons CY MAY 03-05, 2006 CL Ints Nazl Ric Metrol, Turin, ITALY SP Univ Bari, Univ Torino HO Ints Nazl Ric Metrol DE two-photon correlation; two-photon interference; chaotic light ID ELECTRON-PARAMAGNETIC-RES; PHOTONS; COHERENCE; BEAMS AB Two-photon correlation phenomena of chaotic light, including the historical Hanbury Brown and Twiss effect, are essentially the quantum effect of two-photon interference, instead of the classical statistical correlation between intensity fluctuations. To support our view, we analyze a "ghost" imaging experiment with chaotic light for which the classical understanding does not give a satisfactory interpretation. We also provide a two-photon optical picture of ghost imaging with chaotic light in terms of a two-photon phase-conjugate mirror, which suggests lensless imaging applications for radiations for which no effective lens is available. C1 Univ Maryland Baltimore Cty, Dept Phys, Baltimore, MD 21250 USA. Univ Polyclin Bari, Dipartimento Interateneo Fis, I-70126 Bari, Italy. RP Shih, YH (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Wellaman Ctr Photomed, Boston, MA 02114 USA. EM shih@umbc.edu RI Berardi, Vincenzo/H-4550-2011; OI scarcelli, giuliano/0000-0002-1736-077X NR 35 TC 0 Z9 0 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0219-7499 EI 1793-6918 J9 INT J QUANTUM INF JI Int. J. Quantum Inf. PD FEB-APR PY 2007 VL 5 IS 1-2 BP 131 EP 141 DI 10.1142/S0219749907002591 PG 11 WC Computer Science, Theory & Methods; Physics, Particles & Fields; Physics, Mathematical SC Computer Science; Physics GA 230FV UT WOS:000250862500018 ER PT J AU Zelefsky, MJ Kuban, DA Levy, LB Potters, L Beyer, DC Blasko, JC Moran, BJ Ciezki, JP Zietman, AL Pisansky, TM Elshaikh, M Horwitz, EM AF Zelefsky, Michael J. Kuban, Deborah A. Levy, Larry B. Potters, Louis Beyer, David C. Blasko, John C. Moran, Brian J. Ciezki, Jay P. Zietman, Anthony L. Pisansky, Thomas M. Elshaikh, Mohamed Horwitz, Eric M. TI Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE brachytherapy; prostate cancer; prostate-specific antigen; isotope; dose ID PATIENT SELECTION; BRACHYTHERAPY; I-125; IRRADIATION AB Purpose: To assess long-term prostate-specific antigen (PSA) outcome after permanent prostate brachytherapy (BT) and identify predictors of improved disease-free survival. Methods and Materials: Eleven institutions combined data on 2,693 patients treated with permanent interstitial BT monotherapy for T1-T2 prostate cancer. Of these patients, 1,831 (68%) were treated with I-125 (median dose, 144 Gy) and 862 (32%) were treated with Pd-103 (median dose, 130 Gy). Criteria for inclusion were: available pre-BT PSA, BT >= 5 years before data submission, BT between 1988-1998, and no androgen deprivation before failure. The median follow-up was 63 months. Results: Among patients where the I-125 dose to 90% of the prostate (D90) was >= 130 Gy, the 8-year PSA relapse-free survival (PRFS) was 93% compared with 76% for those with lower D90 dose levels (p < 0.001). A multivariable analysis identified tumor stage (p = 0.002), Gleason score (p < 0.001), pretreatment PSA level (p < 0.001), treatment year (p = 0.001), and the isotope used (p = 0.004) as pretreatment and treatment variables associated with PRFS. When restricted to patients with available postimplantation dosimetric information, D90 emerged as a significant predictor of biochemical outcome (p = 0.01), and isotope was not significant. The 8-year PRFS was 92%, 86%, 79%, and 67%, respectively, for patients with PSA nadir values of 0-0.49, 0.5-0.99, 1.0-1.99, and > 2.0 ng/mL (p < 0.001). Among patients free of biochemical relapse at 8 years, the median nadir level was 0.1 ng/mL, and 90% of these patients achieved a nadir PSA level < 0.6 ng/mL. Conclusions: Outcome after permanent BT for prostatic cancer relates to tumor stage, Gleason score, pretreatment PSA, BT year, and post-BT dosimetric quality. PSA nadir <= 0.5 ng/mL was particularly associated with durable long-term PSA disease-free survival. The only controllable factor to impact on long-term outcome was the D90 which is a reflection of implant quality. (c) 2007 Elsevier Inc. C1 Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Arizona Oncol Serv, Scottsdale, AZ USA. New York Prostate Inst, Oceanside, NY USA. Seattle Prostate Inst, Seattle, WA USA. Chicago Prostate Canc Ctr, Chicago, IL USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Dept Radiat Oncol, Rochester, MN 55905 USA. Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. RP Zelefsky, MJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA. EM zelefskm@mskcc.org OI Potters, Louis/0000-0003-4922-2061 NR 13 TC 277 Z9 288 U1 0 U2 6 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 FEB 1 PY 2007 VL 67 IS 2 BP 327 EP 333 DI 10.1016/j.ijrobp.2006.08.056 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 128PE UT WOS:000243669300002 PM 17084558 ER PT J AU Koroshetz, WJ AF Koroshetz, Walter J. TI What's hot in neuroimaging acute stroke? SO INTERNATIONAL JOURNAL OF STROKE LA English DT Editorial Material ID PENUMBRA; THERAPY; CORE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neuro Intens Care Serv, Boston, MA 02115 USA. RP Koroshetz, WJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neuro Intens Care Serv, Boston, MA 02115 USA. EM wkoroshetz@partners.org NR 10 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2007 VL 2 IS 1 BP 43 EP 44 DI 10.1111/j.1747-4949.2007.00083.x PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 178DP UT WOS:000247201700009 PM 18705986 ER PT J AU Andreas, JB O'Farrell, TJ AF Andreas, Jasmina Burdzovic O'Farrell, Timothy J. TI Longitudinal associations between fathers' heavy drinking patterns and children's psychosocial adjustment SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article; Proceedings Paper CT Biennial Meeting of the Society-for-Research-in-Child-Development CY APR 07-10, 2005 CL Atlanta, GA SP Soc Res Child Dev DE children of alcoholics; psychosocial adjustment; fathers' drinking patterns; longitudinal associations ID PEDIATRIC SYMPTOM CHECKLIST; ALCOHOLIC FATHERS; BEHAVIOR PROBLEMS; MIDDLE CHILDHOOD; FAMILY CONFLICT; SUBSTANCE USE; PSYCHOPATHOLOGY; ABUSE; RISK; TRAJECTORIES AB Psychosocial adjustment in children of alcoholics (N = 114) was examined in the year before and at three follow-ups in the 15 months after their alcoholic fathers entered alcoholism treatment, testing the hypothesis that children's adjustment problems will vary over time as a function of their fathers' heavy drinking patterns. Three unique patterns of heavy drinking in alcoholic fathers were identified through cluster analysis. The results demonstrated significant and meaningful associations between these drinking patterns in fathers and adjustment problems in children over time. Overall, children whose fathers remained mostly abstinent following their treatment showed lowest and decreasing adjustment problems, while children whose fathers continued and increased heavy drinking following their treatment showed greatest and increasing adjustment problems over time. C1 Harvard Univ, Sch Med, Dept Psychiat, VAMC, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Brockton, MA USA. RP Andreas, JB (reprint author), Harvard Univ, Sch Med, Dept Psychiat, VAMC, 116B1,940 Belmont St, Brockton, MA 02301 USA. EM jba@hms.harvard.edu; timothy_ofarrell@hms.harvard.edu FU NIAAA NIH HHS [R01AA12834, K02AA00234]; NIMH NIH HHS [T32MH16259] NR 37 TC 14 Z9 14 U1 1 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 2007 VL 35 IS 1 BP 1 EP 16 DI 10.1007/s10802-006-9067-2 PG 16 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 144ZQ UT WOS:000244835500001 PM 17089075 ER PT J AU Burbridge, JA Barch, DM AF Burbridge, Jennifer A. Barch, Deanna M. TI Anhedonia and the experience of emotion in individuals with schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE anhedonia; schizophrenia; emotion ID SOCIAL ANHEDONIA; STARTLE REFLEX; MODULATION; DEFICITS; DEPRESSION; MEMORY; SYMPTOMATOLOGY; VULNERABILITY; MEDICATION; EXPRESSION AB Research shows that individuals with schizophrenia report symptoms of anhedonia when assessed by interview or questionnaire. However, when presented with emotional stimuli, they report emotional experiences that are similar to those of control participants. The authors hypothesized that deficits in working memory and episodic memory contribute to such discrepancies. They administered measures of working and episodic memory, self-report anhedonia questionnaires, and several types of emotional stimuli to 49 individuals with schizophrenia and 47 control participants. All participants reported experiencing similar amounts of pleasant-unpleasant emotion (valence) in response to stimuli, but individuals with schizophrenia reported experiencing less arousal for negative stimuli. Individuals with schizophrenia also reported greater social and physical anhedonia on a traditional anhedonia questionnaire. Disturbances in working memory moderated the relationship between physical anhedonia and participants' emotional experience of positive stimuli. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Washington Univ, Dept Psychiat, St Louis, MO 63130 USA. RP Burbridge, JA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. EM jburbridge@partners.org RI Barch, Deanna/G-8638-2013 FU PHS HHS [R01-06603101] NR 68 TC 63 Z9 66 U1 9 U2 19 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2007 VL 116 IS 1 BP 30 EP 42 DI 10.1037/0021-843X.116.1.30 PG 13 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 135OF UT WOS:000244162200003 PM 17324014 ER PT J AU He, XM Fowler, A Toner, M AF He, Xiaoming Fowler, Alex Toner, Mehmet TI Water activity and mobility in solutions of glycerol and small molecular weight sugars: Implication for cryo- and lypopreservation (vol 100, art no 074702, 2006) SO JOURNAL OF APPLIED PHYSICS LA English DT Correction C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Massachusetts Dartmouth, Dept Mech Engn, N Dartmouth, MA 02747 USA. RP He, XM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu NR 1 TC 1 Z9 1 U1 1 U2 3 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD FEB 1 PY 2007 VL 101 IS 3 AR 039901 DI 10.1063/1.2434975 PG 1 WC Physics, Applied SC Physics GA 136UR UT WOS:000244250100180 ER PT J AU Lewis, MA Butterfield, RM AF Lewis, Megan A. Butterfield, Rita M. TI Social control in marital relationships: Effect of one's partner on health behaviors SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID PSYCHOLOGICAL DISTRESS; CLOSE RELATIONSHIPS; POWER STRATEGIES; MARRIAGE; PERSPECTIVE; COUPLES; GENDER AB The present study examined the role that health-related social control plays in promoting health-enhancing behavioral reactions among married couples. Health-related social control refers to interactions entailing influence and regulation of health practices. A sample of 109 couples answered questions about their social control interactions during structured phone interviews. Analyses maintaining the couple as the unit of analysis indicated that spouses' reports of more frequent social control overall and the use of positive, bilateral, and direct social control tactics predicted their partners' reports of health-enhancing behavioral reactions. C1 RTI Int, Hlth Commun Program, Res Triangle Pk, NC 27709 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Lewis, MA (reprint author), RTI Int, Hlth Commun Program, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM melewis@rti.org NR 37 TC 45 Z9 45 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9029 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD FEB PY 2007 VL 37 IS 2 BP 298 EP 319 DI 10.1111/j.0021-9029.2007.00161.x PG 22 WC Psychology, Social SC Psychology GA 129UE UT WOS:000243754800006 ER PT J AU Aslan, FM Yu, Y Vajda, S Mohr, SC Cantor, CR AF Aslan, Filiz M. Yu, Yong Vajda, Sandor Mohr, Scott C. Cantor, Charles R. TI Engineering a novel, stable dimeric streptavidin with lower isoelectric point SO JOURNAL OF BIOTECHNOLOGY LA English DT Article DE biotin binding; dimeric streptavidin; molecular modeling; protein engineering; protein-protein interaction; radioimmunotherapy ID BIOTIN-BINDING; PRETARGETED RADIOIMMUNOTHERAPY; MONOMERIC STREPTAVIDIN; SUBUNIT ASSOCIATION; AFFINITY; PROTEINS; AVIDIN; TRYPTOPHAN; ACCUMULATION; PURIFICATION AB We have engineered a soluble, stable two-chain dimeric streptavidin (TCD) in Escherchia coli. Examination of the three-dimensional structure of streptavidin aided by empirical binding free-energy calculations helped us to select mutations at subunit interfaces that dissociate the native tetramer and stabilize the desired dimer. We chose positions W120, L124, V125 and H127 and mutated them to 120D/124D/125D/127D (TCD-1); 120D/124N/125S/127D (TCD-2); and 120D/124D/125S/127D(TCD-3). The H127D mutation creates electrostatic repulsion that disrupts the dimer-dimer interface, but leaves it very hydrophobic. Therefore, W120, L124 and V125 were mutated to hydrophilic residues to increase dimer solubility. Among the three candidates, TCD-2 gave the best result: a stable, active dimer with K-d for biotin of similar to 1 x 10(-7) M after purification by gel-filtration chromatography. The experimental results confirm the possibility of rational engineering of low-pI dimeric streptavidins. Reduced-size streptavidin mutants with a net negative charge may be more suitable than antibodies or wild-type streptavidin for the targeting step in radioimmunotherapy because they should clear faster from the bloodstream and the kidney. (c) 2006 Elsevier B.V. All rights reserved. C1 Boston Univ, Ctr Adv Biotechnol, Boston, MA 02215 USA. Boston Univ, Dept Chem, Boston, MA 02215 USA. Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. Boston Univ, Biomol Engn Res Ctr, Boston, MA 02215 USA. Sequenom Inc, San Diego, CA 92121 USA. RP Aslan, FM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,M615, Boston, MA 02115 USA. EM Filiz_Aslan@dfci.harvard.edu NR 32 TC 8 Z9 8 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD FEB 1 PY 2007 VL 128 IS 2 BP 213 EP 225 DI 10.1016/j.jbiotec.2006.08.014 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 133QG UT WOS:000244026900001 PM 17000019 ER PT J AU Bhattacharyya, T Hooper, DC AF Bhattacharyya, Timothy Hooper, David C. TI Antibiotic dosing before primary hip and knee replacement as a pay-for-performance measure SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SURGEON PROCEDURE VOLUME; SURGICAL VOLUME; INFECTION; CARE; ASSOCIATION; OUTCOMES; QUALITY; COMPLICATIONS; ARTHROPLASTY; PROPHYLAXIS AB Background: There is a trend toward linking the reimbursement for health care services to clinical outcome. One such pay-for-performance proposal that affects orthopaedic surgeons is linking reimbursement for hip and knee replacements to measures such as the percentage of patients receiving antibiotics before surgery. We analyzed the risk factors associated with failing to optimally administer preoperative antibiotics before primary hip and knee arthroplasty. Methods: Data on 988 elective primary total hip and knee replacements done at one institution were collected. Multivariate analysis was performed to determine clinical factors associated with administration of antibiotics outside the recommended window (within one hour before the incision). Results: Thirteen percent of the patients did not receive optimal antibiotic therapy (within the one-hour window prior to the elective arthroplasty). Five patients (0.5%) received no documented preoperative antibiotics. Patients undergoing total hip arthroplasty were more likely to receive antibiotics outside the one-hour window than were patients undergoing total knee arthroplasty. Longer induction times were associated with administration of antibiotics outside the one-hour window. Certain individual surgeons and anesthesiologists were more likely to administer antibiotics on time. The anesthesiologist effect was more significant than the surgeon effect. Conclusions: Approximately 13% of the patients did not receive optimal antibiotic therapy before total hip and knee replacement. Surgeons can improve their performance score for this measure by focusing antibiotic strategies on patients receiving a hip replacement and on complex cases, by developing systems for antibiotic dosing with the anesthesia team, and by improving documentation. C1 Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02118 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, 55 Fruit St,Yawkey 3600, Boston, MA 02118 USA. NR 25 TC 12 Z9 13 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2007 VL 89A IS 2 BP 287 EP 291 DI 10.2106/JBJS.F.00136 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 134YX UT WOS:000244121800009 PM 17272442 ER PT J AU Jupiter, JB Goldfarb, CA Nagy, L Boyer, MI AF Jupiter, Jesse B. Goldfarb, Charles A. Nagy, Ladislav Boyer, Martin I. TI Posttraumatic reconstruction in the hand SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PROXIMAL INTERPHALANGEAL JOINT; METACARPAL ROTATIONAL OSTEOTOMY; BONE LOSS; INTRAARTICULAR OSTEOTOMY; FRACTURE-DISLOCATION; BENNETTS-FRACTURE; 5TH METACARPAL; MALUNION; MANAGEMENT; PHALANGEAL C1 Amer Acad Orthopaed Surg, Rosemont, IL USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Yawkey Bldg,Suite 2100,55 Parkman St, Boston, MA 02114 USA. EM jjupiter1@partners.org OI Goldfarb, Charles/0000-0001-9672-8853 NR 64 TC 6 Z9 7 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2007 VL 89A IS 2 BP 428 EP 435 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 134YX UT WOS:000244121800031 PM 17326313 ER PT J AU Ho, I Holmvang, G D'Avila, A Heist, EK Mansour, M AF Ho, Ivan Holmvang, Godtfred D'Avila, Andre Heist, E. Kevin Mansour, Moussa TI Compression of the posterior left atrium by a nonaneurysmal descending thoracic aorta in a patient undergoing pulmonary vein isolation procedure for atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD FEB PY 2007 VL 18 IS 2 BP 229 EP 229 DI 10.1111/j.1540-8167.2006.00695.x PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 127CL UT WOS:000243562800020 PM 17338772 ER PT J AU Albadawi, H Patton, GA Bratton, CF Peterson, BG Watkins, MT AF Albadawi, Hassan Patton, George A. Bratton, Charles F. Peterson, Brian G. Watkins, Michael T. TI Human microvascular endothelial synthesis of interleukin-8 during in vitro ischemia and reperfusion SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE vascular endothelium; ischemia; cytokines; reperfusion injury ID WEIBEL-PALADE BODIES; SKELETAL-MUSCLE; CXC CHEMOKINES; UP-REGULATION; SHEAR-STRESS; CELLS; INJURY; EXPRESSION; PATHOPHYSIOLOGY; ANGIOGENESIS AB These studies were undertaken to evaluate human microvascular endothelial cell (MEC) synthesis of interleukin-8 (IL-8), a potent neutrophil chemoattractant, under in vitro conditions of ischemia and reperfusion. IL-8 and other related CXC chemokines are believed to mediate tissue injury in a variety of pathologic conditions in humans. MEC grown on microcarrier beads were exposed to 3 or 6 h of in vitro ischemia followed by 2 h of reperfusion. Conditioned medium, MEC protein, and total RNA extracts were assayed for IL-8 using an ELISA. During ischemia alone, MEC increased intracellular, but not extracellular levels of IL-8 secretion. In contrast, reperfusion markedly stimulated both intracellular and extracellular IL-8 secretion. Neither 3h of ischemia alone or followed by reperfusion altered steady-state levels of IL-8 mRNA when compared to pre-ischemic levels. In contrast, after 6 h of ischemia alone and ischemia followed by reperfusion, IL-8 mRNA was increased eight- and sixfold, respectively, when compared to pre-ischemic levels. These studies demonstrate an inverse relationship between the rate of IL-8 protein secretion and the steady-state levels of IL-8 mRNA during ischemia and reperfusion. During ischemia and reperfusion both the increase in cell-associated IL-8 protein and the release of IL-8 into the medium is dependent on de novo protein synthesis rather than the intracellular accumulation of IL-8. These experiments indicate that post-ischemic modulation of IL-8 release and synthesis following ischemia reperfusion will require strategies directed towards inhibition of IL-8 transcription and in depth knowledge of the mechanisms regulating IL-8 secretion. C1 Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Div Vasc Surg,Med Sch, Boston, MA 02114 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, 15 Parkman St,Suite 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 40 TC 1 Z9 1 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 1 PY 2007 VL 100 IS 2 BP 412 EP 420 DI 10.1002/jcb.21002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 126MR UT WOS:000243517500013 PM 16927373 ER PT J AU Clark, RSB Nathaniel, PD Zhang, XP Dixon, CE Alber, SM Watkins, SC Melick, JA Kochanek, PM Graham, SH AF Clark, Robert S. B. Nathaniel, Paula D. Zhang, Xiaopeng Dixon, C. Edward Alber, Sean M. Watkins, Simon C. Melick, John A. Kochanek, Patrick M. Graham, Steven H. TI boc-Aspartyl(OMe)-fluoromethylketone attenuates mitochondrial release of cytochrome c and delays brain tissue loss after traumatic brain injury in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; caspase; cysteine protease; head injury; nerve growth factor; programmed cell death ID CONTROLLED CORTICAL IMPACT; NEURONAL APOPTOSIS; CELL-DEATH; COGNITIVE DEFICITS; CASPASE ACTIVATION; DNA FRAGMENTATION; SPATIAL PROFILE; IN-VITRO; INHIBITION; RECEPTOR AB The pathobiology of traumatic brain injury (TBI) includes activation of multiple caspases followed by cell death with a spectrum of apoptotic phenotypes. There are initiator (e. g. caspase-2, -8, and -9) and effector (e. g. caspase-3 and -7) caspases. Recently, caspase-2 and -8 have been shown to regulate cell death via provoking cytochrome c release from the mitochondria upstream of caspase-9. Here, we show that an intracerebral injection of the pan-caspase inhibitor boc-Aspartyl(OMe)fluoromethylketone (BAF; 1 mu mol) 1 min after TBI in rats reduces caspase-3-like activity, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and tissue damage, and cytochrome c release in ipsilateral cortex at 24 h versus vehicle. To investigate whether either caspase-2 and/or caspase-8 activation may contribute to cytochrome release, the effect of BAF treatment on caspase-2 and caspase-8 proteolysis was also examined. boc-aspartyl(OMe) fluoromethylketone treatment inhibited proteolysis of caspase-2 but not caspase-8 24 h after TBI in rats versus vehicle. However, BAF with or without nerve growth factor (12.5 ng/h x 14 days intracerebrally via osmotic pump) did not result in differences in motor function, Morris water maze performance, hippocampal neuron survival, nor contusion volume at 14 days. These data suggest that BAF treatment reduces acute cell death after TBI by inhibiting mitochondrial release of cytochrome c, possibly via a mechanism involving initiator caspases; however, BAF appears to delay cell death, rather than result in permanent protection. C1 Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Crit Care Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Clark, RSB (reprint author), Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Crit Care Med, 3434 5th Ave, Pittsburgh, PA 15260 USA. EM clarkrs@ccm.upmc.edu RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NINDS NIH HHS [P50 NS30318, R01 NS38620] NR 46 TC 19 Z9 19 U1 0 U2 2 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 FEB PY 2007 VL 27 IS 2 BP 316 EP 326 DI 10.1038/sj.jcbfm.9600338 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 128UY UT WOS:000243685700008 PM 16736044 ER PT J AU Raymond, SB Skoch, J Hynynen, K Bacskai, BJ AF Raymond, Scott B. Skoch, Jesse Hynynen, Kullervo Bacskai, Brian J. TI Multiphoton imaging of ultrasound/Optison mediated cerebrovascular effects in vivo SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood-brain barrier; drug delivery; induced vasospasm; optical imaging; ultrasound ID BLOOD-BRAIN-BARRIER; BRIEF CEREBRAL-ISCHEMIA; FOCUSED ULTRASOUND; RADIATION-FORCE; CONTRAST AGENT; CORONARY-ARTERY; CAROTID-ARTERY; DISRUPTION; MICROBUBBLES; DYNAMICS AB Ultrasound (US) enhanced with microbubble contrast agents may transiently disrupt the blood-brain barrier (BBB) with minimal damage, providing a technique for noninvasive, localized drug-delivery deep within the brain. The mechanism and temporal profile of disruption are not understood, owing to the limitations of imaging modalities used previously. In this study, we monitored US- induced BBB disruption with multiphoton microscopy, providing high- resolution temporal and spatial information about the permeabilization mechanism and immediate effects of US exposure. Anesthetized C57 mice were prepared with a craniotomy and injected intravenously with fluorescent dyes to permit visualization of the vasculature and BBB integrity. The animals were imaged through a cranial window while exposed to low- intensity US (f = 1.029MHz, power = 0.2 W) with a coincident intravenous injection of Optison (a microbubble contrast agent). We observed arteriolar vasoconstriction on US exposure that disrupted blood flow and lasted up to 5 mins; BBB disruption occurred via two characteristically distinct processes-perivascular fluorescence gradually increased (over minutes) along the length of the affected vessel without apparent rupture of the vessel wall or rapidly (seconds) increased in select, focal regions. These data corroborated previous studies suggesting increased endothelial transcytosis and breached tight junctions and demonstrated vasoconstriction, which might alter BBB permeability by modifying cerebral blood flow. C1 Harvard Univ, Harvard Biophys Program, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Lab, Charlestown, MA USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Bacskai, BJ (reprint author), Alzheimers Res Unit, Bldg 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org OI Raymond, Scott/0000-0001-7008-8974 FU NIBIB NIH HHS [EB000705, EB00768] NR 40 TC 75 Z9 75 U1 1 U2 6 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 FEB PY 2007 VL 27 IS 2 BP 393 EP 403 DI 10.1038/sj.jcbfm.9600336 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 128UY UT WOS:000243685700015 PM 16685254 ER PT J AU Mazumdar, M Pandharipande, P Poduri, A AF Mazumdar, Maitreyi Pandharipande, Pari Poduri, Annapurna TI Does albendazole affect seizure remission and computed tomography response in children with neurocysticercosis? A systematic review and meta-analysis SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE neurocysticercosis; drug therapy; epilepsy ID DOUBLE-BLIND TRIAL; CEREBRAL CYSTICERCOSIS; THERAPY; LESIONS AB A recent trial suggested that albendazole reduces seizures in adults with neurocysticercosis. There is still no consensus regarding optimal management of neurocysticercosis in children. The authors conducted a systematic review and meta-analysis to assess the efficacy of albendazole in children with neurocysticercosis, by searching the Cochrane Databases, MEDLINE, EMBASE, and LILACS. Three reviewers extracted data using an intent-to-treat analysis. Random effects models were used to estimate relative risks. Four randomized trials were selected for meta-analysis, and 10 observational studies were selected for qualitative review. The relative risk of seizure remission in treatment versus control was 1.26 (1.09, 1.46). The relative risk of improvement in computed tomography in these trials was 1.15 (0.97, 1.36). Review of observational studies showed conflicting results, likely owing to preferential administration of albendazole to sicker children. C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA USA. RP Mazumdar, M (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM maitreyi.mazumdar@childrens.harvard.edu FU PHS HHS [T32 HP-100063] NR 28 TC 7 Z9 7 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD FEB PY 2007 VL 22 IS 2 BP 135 EP 142 DI 10.1177/0883073807300295 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 161ZE UT WOS:000246054900001 PM 17621473 ER PT J AU Lafosse, JM Corboy, JR Leehey, MA Seeberger, LC Filley, CM AF Lafosse, Jose M. Corboy, John R. Leehey, Maureen A. Seeberger, Lauren C. Filley, Christopher M. TI MS vs. HD: Can white matter and subcortical gray matter pathology be distinguished neuropsychologically? SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; MULTIPLE-SCLEROSIS; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; RECOGNITION MEMORY; VERBAL RECOGNITION; CORTICAL DEMENTIA; IMPLICIT MEMORY AB This study was conducted to examine the neuropsychological effects of white matter and subcortical gray matter pathology. Nineteen patients with multiple sclerosis (MS), 16 with Huntington's disease (HD), and 17 normal controls (NC) participated. Participants completed the California Verbal Learning Test (CVLT), Rotary Pursuit (RP) and Mirror Tracing (MT) tasks, and the Symbol Digit Modalities Test (SDMT). The principal findings pertain to a dissociation in procedural memory: on RP, the HD group demonstrated impaired sequence learning compared to the MS group, which performed similarly to the NC group, yet on MT, the MS and HD groups demonstrated normal perceptual-motor integration learning. On the CVLT, both patient groups performed better on recognition than on recall. On the SDMT, both patient groups performed worse than the NC group, with the HD group performing more poorly than the MS and NC groups. These results suggest that involvement of white and subcortical gray matter may produce different neuropsychological effects. C1 Regis Univ, Dept Psychol, Denver, CO 80221 USA. Regis Univ, Neurosci Program D12, Denver, CO 80221 USA. Univ Colorado, Sch Med, Boulder, CO 80309 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Colorado Neurol Inst, Denver, CO USA. RP Lafosse, JM (reprint author), Regis Univ, Dept Psychol, 3333 Regis Blvd, Denver, CO 80221 USA. EM jlafosse@regis.edu NR 79 TC 15 Z9 16 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD FEB PY 2007 VL 29 IS 2 BP 142 EP 154 DI 10.1080/13803390600582438 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 146HX UT WOS:000244926200003 PM 17365249 ER PT J AU Benedetto, WJ Hess, DR Gettings, E Bigatello, LM Toon, H Hurford, WE Schmidt, U AF Benedetto, William J. Hess, Dean R. Gettings, Elise Bigatello, Luca M. Toon, Hannah Hurford, William E. Schmidt, Ulrich TI Urgent tracheal intubation in general hospital units: an observational study SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE airway complications; cardiopulmonary resuscitation; intubation; outcomes ID ENDOTRACHEAL INTUBATION; AIRWAY MANAGEMENT; COMPLICATIONS; SURVIVAL AB Study Objective: To determine the frequency of complications and outcomes of urgent intubations in general hospital units. Design: Prospective, observational, cohort study. Setting: University-affiliated hospital. Patients: 150 patients who underwent tracheal intubation in the general care units. Interventions: A standardized data collection form was used prospectively to record events at the time of intubation. Patient outcomes were extracted from the medical record. Measurements and Main Results: The complication rate was 27%. The most common complications were multiple attempts (9% required >2 intubations) and esophageal intubation (9%). The complication rate for elective intubation (22%) was similar to the complication rate for emergent intubations (27%). Of patients intubated in the general care units, 52% survived and 33% of these were discharged. There was no significant difference (P = 0.46) in survival between the patients intubated electively (59%) and emergently (50%). There was no significant difference (P = 0.63) in survival between patients with (48%) and without complications (54%). Conclusions: Endotracheal intubation in general hospital units carries a high rate of complications, and patients who are intubated in general hospital units have a high mortality. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. Univ Cincinnati, Med Ctr, Dept Anesthesia, Cincinnati, OH 45267 USA. RP Schmidt, U (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA. EM uschmidt@partners.org RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 13 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2007 VL 19 IS 1 BP 20 EP 24 DI 10.1016/j.jclinane.2006.05.018 PG 5 WC Anesthesiology SC Anesthesiology GA 145PN UT WOS:000244877100005 PM 17321922 ER PT J AU Rosner, W Auchus, RJ Azziz, R Sluss, PM Raff, H AF Rosner, William Auchus, Richard J. Azziz, Ricardo Sluss, Patrick M. Raff, Hershel TI Position statement: Utility, limitations, and pitfalls in measuring testosterone: An endocrine society position statement SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TANDEM MASS-SPECTROMETRY; POLYCYSTIC-OVARY-SYNDROME; HORMONE-BINDING GLOBULIN; TOTAL SERUM TESTOSTERONE; FREE ANDROGEN INDEX; CLINICAL-PRACTICE; WOMEN; MEN; RADIOIMMUNOASSAY; HEALTHY AB Objective: The objective of the study was to evaluate the current state of clinical assays for total and free testosterone. Participants: The five participants were appointed by the Council of The Endocrine Society and charged with attaining the objective using published data and expert opinion. Evidence: Data were gleaned from published sources via online databases (principally PubMed, Ovid MEDLINE, Google Scholar), the College of American Pathologists, and the clinical and laboratory experiences of the participants. Consensus Process: The statement was an effort of the committee and was reviewed in detail by each member. The Council of The Endocrine Society reviewed a late draft and made specific recommendations. Conclusions: Laboratory proficiency testing should be based on the ability to measure accurately and precisely samples containing known concentrations of testosterone, not only on agreement with others using the same method. When such standardization is in place, normative values for total and free testosterone should be established for both genders and children, taking into account the many variables that influence serum testosterone concentration. C1 St Lukes Roosevelt Hosp, Dept Med, New York, NY 10019 USA. Columbia Univ Coll Phys & Surg, New York, NY 10019 USA. Univ Texas, SW Med Ctr, Div Endocrinol & Metab, Dallas, TX 75390 USA. Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Ctr Androgen Related Disorders, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Dept Obstet Gynecol, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90048 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Med Coll Wisconsin, Aurora St Lukes Med Ctr, Div Endocrinol Metab & Clin Nutr, Endocrine Res Lab, Milwaukee, WI 53215 USA. RP Rosner, W (reprint author), St Lukes Roosevelt Hosp, Dept Med, 1000 10th Ave,AJA 403, New York, NY 10019 USA. EM wr7@columbia.edu RI Azziz, Ricardo/N-7229-2014 OI Azziz, Ricardo/0000-0002-3917-0483 NR 47 TC 541 Z9 561 U1 6 U2 37 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 FEB PY 2007 VL 92 IS 2 BP 405 EP 413 DI 10.1210/jc.2006-1864 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 134ED UT WOS:000244064900005 PM 17090633 ER PT J AU Seal, KH Currie, SL Shen, H Anand, BS Bini, EJ Brau, N Jeffers, L Wright, TL AF Seal, Karen H. Currie, Sue L. Shen, Hui Anand, Bhupinderjit S. Bini, Edmund J. Brau, Norbert Jeffers, Lennox Wright, Teresa L. CA VA HCV-001 Study Grp TI Hepatitis C treatment candidacy and outcomes among 4318 US veterans with chronic hepatitis C virus infection - Does a history of injection drug use matter? SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE injection drug use; hepatitis C; hepatitis C treatment; alcohol ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; ANTIVIRAL THERAPY; INITIAL TREATMENT; RANDOMIZED-TRIAL; UNITED-STATES; RISK; CARE; ELIGIBILITY; DRINKERS; BARRIERS AB Background/Goals: Many patients with a history of injection drug use (IDU) are excluded from hepatitis C virus (HCV) treatment. This prospective multicenter study aimed to determine the impact of IDU history on HCV treatment candidacy and outcomes. Study: Between 1999 and 2001, 4318 HCV-infected patients seen at 24 VA Medical Centers were evaluated for HCV treatment candidacy and followed prospectively. Univariate and multivariate logistic regression analyses were used to determine whether an IDU history was associated with HCV treatment candidacy, HCV treatment acceptance, early treatment discontinuation, and virologic response. Results: Of 4318 participants, 2611 (61%) reported an IDU history. IDU history was not significantly associated with HCV treatment candidacy, acceptance, early discontinuation of therapy, or virologic response (all P values nonsignificant). Instead, reduced HCV treatment candidacy was independently associated with low-income [odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.22-1.74), education <= 12 years (OR = 1.23, 95% CI = 1.03-1.46), and alcohol consumption >= 3 drinks/d (OR = 2.08, 95% CI = 1.68-2.57), whereas early discontinuation of HCV therapy was independently associated with low-income and consuming >= 3 alcoholic drinks/d. Conclusions: A history of IDU was not associated with HCV treatment candidacy or outcomes, supporting national guidelines to evaluate former IDUs on a case-by-case basis for HCV treatment. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Med Ctr, Houston, TX USA. VA New York Harbor Healthcare Syst, New York, NY USA. NYU, Sch Med, New York, NY USA. VA Med Ctr, Bronx, NY USA. VA Med Ctr, Miami, FL USA. RP Seal, KH (reprint author), San Francisco VA Med Ctr, Box 111A-1,4150 Clement St, San Francisco, CA 94121 USA. EM Karen.Seal@va.gov NR 34 TC 22 Z9 22 U1 2 U2 4 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 FEB PY 2007 VL 41 IS 2 BP 199 EP 205 DI 10.1097/01.mcg.0000212644.82853.51 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 135DD UT WOS:000244133400014 PM 17245220 ER PT J AU Li, DN Ji, HB Zaghlul, S McNamara, K Liang, MC Shimamura, T Kubo, S Takahashi, M Chirieac, LR Padera, RF Scott, AM Jungbluth, AA Cavenee, WK Old, LJ Demetri, GD Wong, KK AF Li, Danan Ji, Hongbin Zaghlul, Sara McNamara, Kate Liang, Mei-Chih Shimamura, Takeshi Kubo, Shigeto Takahashi, Masaya Chirieac, Lucian R. Padera, Robert F. Scott, Andrew M. Jungbluth, Achim A. Cavenee, Webster K. Old, Lloyd J. Demetri, George D. Wong, Kwok-Kin TI Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; TARGETED THERAPY; CANCER; MUTATIONS; RESISTANCE; TUMORS; DE2-7; TUMORIGENESIS; SENSITIVITY AB Activating EGFR mutations occur in human non-small cell lung cancer (NSCLC), with 5% of human lung squamous cell carcinomas having EGFRvIII mutations and approximately 10%-30% of lung adenocarcinomas having EGFR kinase domain mutations. An EGFR-targeting monoclonal antibody, mAb806, recognizes a conformational epitope of WT EGFR as well as the truncated GFRvIII mutant. To explore the anticancer spectrum of this antibody for EGFR targeted cancer therapy, mAb806 was used to treat genetically engineered mice with lung tumors that were driven by either EGFRvIII or EGFR kinase domain mutations. Our results demonstrate that mAb806 is remarkably effective in blocking EGFRvIII signaling and inducing tumor cell apoptosis, resulting in dramatic tumor regression in the EGFRvIII-driven murine lung cancers. Another EGFR-targeting antibody, cetuximab, failed to show activity in these lung tumors. Furthermore, treatment of murine lung tumors driven by the EGFR kinase domain mutation with mAb806 also induced significant tumor regression, albeit to a less degree than that observed in EGFRvIII-driven tumors. Taken together, these data support the hypothesis that mAb806 may lead to significant advancements in the treatment of the population of NSCLC patients with these 2 classes of EGFR mutations. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Ludwig Ctr Dana Farber, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Ludwig Inst Canc Res, Melbourne Tumour Biol Branch, Melbourne, Vic, Australia. Ludwig Inst Canc Res, New York, NY USA. Univ Calif San Diego, Ludwig Inst Canc Res, San Diego Branch, Ctr Mol Genet,Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, Ctr Canc, San Diego, CA 92103 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, 44 Binney St,D810, Boston, MA 02115 USA. EM Kwongl@partners.org OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [CA95616, P01 CA095616, R01 CA122794]; NIA NIH HHS [K08AG 2400401] NR 30 TC 36 Z9 38 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2007 VL 117 IS 2 BP 346 EP 352 DI 10.1172/JCI30446 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 133ZD UT WOS:000244051500014 PM 17256054 ER PT J AU Pitteloud, N Quinton, R Pearce, S Raivio, T Acierno, J Dwyer, A Plummer, L Hughes, V Seminara, S Cheng, YZ Li, WP Maccoll, G Eliseenkova, AV Olsen, SK Ibrahimi, OA Hayes, FJ Boepple, P Hall, JE Bouloux, P Mohammadi, M Crowley, W AF Pitteloud, Nelly Quinton, Richard Pearce, Simon Raivio, Taneli Acierno, James Dwyer, Andrew Plummer, Lacey Hughes, Virginia Seminara, Stephanie Cheng, Yu-Zhu Li, Wei-Ping Maccoll, Gavin Eliseenkova, Anna V. Olsen, Shaun K. Ibrahimi, Omar A. Hayes, Frances J. Boepple, Paul Hall, Janet E. Bouloux, Pierre Mohammadi, Moosa Crowley, William, Jr. TI Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; FACTOR RECEPTOR 1; LINKED KALLMANN-SYNDROME; HORMONE RECEPTOR; GNRH RECEPTOR; FGF RECEPTOR; GENE; NEURONS; INHERITANCE; EXPRESSION AB (GnRH) secretion and/or action is a developmental disorder of sexual maturation. To date, several single-gene defects have been implicated in the pathogenesis of IHH. However, significant inter- and intrafamilial variability and apparent incomplete penetrance in familial cases of IHH are difficult to reconcile with the model of a single-gene defect. We therefore hypothesized that mutations at different IHH loci interact in some families to modify their phenotypes. To address this issue, we studied 2 families, one with Kallmann syndrome (IHH and anosmia) and another with normosmic IHH, in which a single-gene defect had been identified: a heterozygous FGF receptor 1 (FGFR1) mutation in pedigree 1 and a compound heterozygous gonadotropin-releasing hormone receptor (GNRHR) mutation in pedigree 2, both of which varied markedly in expressivity within and across families. Further candidate gene screening revealed a second heterozygous deletion in the nasal embryonic LHRH factor (NELF) gene in pedigree 1 and an additional heterozygous FGFR1 mutation in pedigree 2 that accounted for the considerable phenotypic variability. Therefore, 2 different gene defects can synergize to produce a more severe phenotype in IHH families than either alone. This genetic model could account for some phenotypic heterogeneity seen in GnRH deficiency. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Reprod Endorcine Sci Ctr, Boston, MA 02114 USA. Univ Newcastle Upon Tyne, Dept Endocrinol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Newcastle Upon Tyne, Royal Victoria Infirm, Sch Clin Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Newcastle Upon Tyne, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Royal Free Hosp, Dept Endocrinol, London NW3 2QG, England. NYU, Sch Med, Dept Pharmacol, New York, NY USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHE 5, Boston, MA 02114 USA. EM npitteloud@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Pearce, Simon/0000-0001-8384-8063; Mohammadi, Moosa/0000-0003-2434-9437 FU NICHD NIH HHS [HD15788, HD028138, P30 HD028138, P50 HD028138, R01 HD015788, U54 HD028138]; NIDCR NIH HHS [DE13686, R01 DE013686] NR 49 TC 182 Z9 186 U1 0 U2 1 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 FEB PY 2007 VL 117 IS 2 BP 457 EP 463 DI 10.1172/JCI29884 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 133ZD UT WOS:000244051500025 PM 17235395 ER PT J AU Zhang, JL Scadden, DT Crumpacker, CS AF Zhang, Jielin Scadden, David T. Crumpacker, Clyde S. TI Primitive hematopoietic ceHs resist HIV-1 infection via p21(Waf1/Cip1/Sdi1) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR-LOCALIZATION SIGNAL; CYCLIN-DEPENDENT KINASES; STEM-CELLS; IN-VIVO; MONOCLONAL-ANTIBODIES; QUANTITATIVE ASSAY; TYPE-1 INTEGRASE; DNA-REPLICATION; MATRIX PROTEIN AB Hematopoietic stem cells are resistant to HIV-1 infection. Here, we report a novel mechanism by which the cyclin-dependent kinase inhibitor (CKI) p21(Waf1)/(Cip1)/(Sdi1) (p21), a known regulator of stem cell pool size, restricts HIV-1 infection of primitive hematopoietic cells. Modifying p21 expression altered HIV-1 infection prior to changes in cell cycling and was selective for p21 since silencing the related CKIs, p27(Kip1) and p18(INK4C), had no effect on HIV-1. We show that p21 blocked viral infection by complexing with HIV-1 integrase and aborting chromosomal integration. A closely related lentivirus with a distinct integrase, SlVmac-251, and the other cell-intrinsic inhibitors of HIV-1, Trim5 alpha, PML, Murr1, and IFN-alpha, were unaffected by p21. Therefore, p21 is an endogenous cellular component in stem cells that provides a unique molecular barrier to HIV-1 infection and may explain how these cells remain an uninfected "sanctuary" in HIV disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02115 USA. Harvard Stem Cell Inst, Cambridge, MA USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, 185 Cambridge,CPZN-4265A, Boston, MA 02114 USA. EM ccrumpac@caregroup.harvard.edu FU NHLBI NIH HHS [R01 HL044851, R01 HL071859, R01 HL71859]; NIAID NIH HHS [K18 AI055313, K18 AI55313] NR 53 TC 82 Z9 83 U1 0 U2 1 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 FEB PY 2007 VL 117 IS 2 BP 473 EP 481 DI 10.1172/JCI28971 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 133ZD UT WOS:000244051500027 PM 17273559 ER PT J AU Langer, C Li, SG Schiller, J Tester, W Rapoport, BL Johnson, DH AF Langer, Corey Li, Sigui Schiller, Joan Tester, William Rapoport, Bernardo L. Johnson, David H. TI Randomized phase II trial of paclitaxel plus carboplatin or gemcitabine plus cisplatin in eastern cooperative oncology group performance status 2 non-small-cell lung cancer patients: ECOG 1599 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGNOSTIC-FACTORS; ELDERLY-PATIENTS; SURVIVAL; CHEMOTHERAPY; VINORELBINE; REGIMENS; VINDESINE AB Purpose Appropriate therapy for Eastern Cooperative Oncology Group (ECOG) performance status (PS)-2 patients with advanced non-small-cell lung cancer (NSCLC) remains challenging. PS-2 patients on ECOG 1594 had a median survival (MS) of only 4.1 months and 1-year overall survival (OS) of 19%. Three percent had grade 5 toxicity. Patients and Methods ECOG 1599, the first PS 2-specific, US cooperative group trial for treatment-naive advanced NSCLC, randomly assigned patients to dose-attenuated carboplatin/paclitaxel (the least toxic regimen in ECOG 1594) or gemcitabine/cisplatin (which yielded an MS of 7.9 months in PS-2 patients). Patients received either carboplatin (area under the concentration-time curve, 6) and paclitaxel 200 mg/m(2) every 3 weeks (CbP) or gemcitabine 1 g/m(2) days 1 and 8 and cisplatin 60 mg/m(2) day 1 every 3 weeks (CG). Results One hundred three patients were enrolled; 100 proved eligible. Median age was 66 years; 46% had at least 5% weight loss; 88% had stage IV or recurrent disease. Median number of cycles administered was three per arm. CbP featured more grade 3 neutropathy (10% v 0%) and more grade >= 3 neutropenia (59% v 33%), whereas CG yielded more grade >= 3 thrombocytopenia (33% v 14%), more grade >= 3 fatigue (22% v 14%), and more grade >= 1 creatinine elevations (43% v 6%). One grade 5 toxicity, confined to the CbP arm, occurred. Response rate, time to progression, MS, and 1-year OS rates for CG and CbP, were 23%, 4.8 months, 6.9 months, and 25%, and 14%, 4.2 months, 6.2 months, and 19%, respectively. Conclusion Platinum-based combination chemotherapy for PS-2 patients with NSCLC is feasible with acceptable toxicity, but survival in these patients remains inferior to that of PS-0 to -1 patients. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Albert Einstein Canc Ctr, Philadelphia, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Ctr Canc, Madison, WI USA. Mayo Clin, Rochester, MN USA. Vanderbilt Univ, Nashville, TN USA. RP Langer, C (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM cj_langer@fccc.edu RI Johnson, David/A-7437-2009; OI Rapoport, Bernardo/0000-0001-7610-3653 FU NCI NIH HHS [CA49957, CA13650, CA21076, CA21115, CA23318, CA66636] NR 22 TC 42 Z9 43 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2007 VL 25 IS 4 BP 418 EP 423 DI 10.1200/JCO.2005.04.9452 PG 6 WC Oncology SC Oncology GA 134GB UT WOS:000244070400012 PM 17264337 ER PT J AU Moynihan, TJ Schapira, L AF Moynihan, Timothy J. Schapira, Lidia TI Preparing ourselves, our trainees, and our patients: A commentary on truthtelling SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Moynihan, TJ (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. EM moynihan.timothy@mayo.edu NR 2 TC 4 Z9 4 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 FEB 1 PY 2007 VL 25 IS 4 BP 456 EP 457 DI 10.1200/JCO.2006.09.6941 PG 2 WC Oncology SC Oncology GA 134GB UT WOS:000244070400021 PM 17264346 ER PT J AU Kobak, KA Kane, JM Thase, ME Nierenberg, AA AF Kobak, Kenneth A. Kane, John M. Thase, Michael E. Nierenberg, Andrew A. TI Why do clinical trials fail? The problem of measurement error in clinical trials: Time to test new paradigms? SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID DEPRESSION RATING-SCALE; SEQUENCED TREATMENT ALTERNATIVES; OBSESSIVE-COMPULSIVE DISORDER; SAMPLE-SIZE REQUIREMENTS; FACE-TO-FACE; TELEPSYCHIATRY; RELIABILITY; TELEPHONE; PLACEBO; INTERVIEWS C1 MedAvante Inc, Madison, WI 53719 USA. Zucker Hillside Hosp, Glen Oaks, NY USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kobak, KA (reprint author), MedAvante Inc, 7601 Ganser Way, Madison, WI 53719 USA. EM kkobak@medavante.net NR 61 TC 66 Z9 67 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2007 VL 27 IS 1 BP 1 EP 5 DI 10.1097/JCP.0b013e31802eb4b7 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 128HF UT WOS:000243648100001 PM 17224705 ER PT J AU Dalessandro, M Conti, CM Gambi, F Falasca, K Doyle, R Conti, P Caciagli, F Fulcheri, M Vecchiet, J AF Dalessandro, Margherita Conti, Chiara M. Gambi, Francesco Falasca, Katia Doyle, Robert Conti, Pio Caciagli, Francesco Fulcheri, Mario Vecchiet, Jacopo TI Antidepressant therapy can improve adherence to antiretroviral regimens among HIV-infected and depressed patients SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SELF-REPORTED SYMPTOMS; MEDICATION; INHIBITORS; DISORDERS; OUTCOMES; HAART AB Several strategies have been introduced to manage nonadherence to highly active antiretroviral therapy (HAART). Treatment with antidepressants may improve self-reported adherence. In this brief report, a small sample of HIV-depressed patients (n = 9) were treated for a 6-month period with antidepressants improving self-reported adherence based on the HAART scale (poor, good, satisfactory, and optimal). Before the antidepressant treatment, adherence was reported as "good" by 3 patients and "satisfactory" by 6 patients. After antidepressant therapy, adherence to antiretroviral regimes was statistically higher in HIVdepressed on treatment than in HIV-depressed patients not treated with antidepressants (P < 0.0001). We used chi(2) test with a significance level at P < 0.05. Treating depression in HIV-infected patients may serve to improve adherence to HAART. C1 Univ G Annunzio, Clin Infect Dis, Chieti, Italy. Univ G Annunzio, Div Immunol, Chieti, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Univ G Annunzio, Div Pharmacol, Chieti, Italy. Univ G Annunzio, Clin Psychol, Chieti, Italy. Univ Chieti, Div Psychiat, Chieti, Italy. RP Vecchiet, J (reprint author), Univ Chieti, Sch Med, Div Infect Dis, Via Vestini, I-66100 Chieti, Italy. EM pconti@unich.it OI Fulcheri, Mario/0000-0002-2389-9800 NR 27 TC 32 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2007 VL 27 IS 1 BP 58 EP 61 DI 10.1097/jcp.0b013e31802f0dd1 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 128HF UT WOS:000243648100011 PM 17224714 ER PT J AU Davidson, JRT Brady, K Mellman, TA Stein, MB Pollack, MH AF Davidson, Jonathan R. T. Brady, Kathleen Mellman, Thomas A. Stein, Murray B. Pollack, Mark H. TI The efficacy and tolerability of tiagabine in adult patients with post-traumatic stress disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ANXIETY DISORDER; RATING-SCALE; PLACEBO; SERTRALINE; TRAUMA; BENZODIAZEPINES; MULTICENTER; RESILIENCE; FLUOXETINE AB The aim of this study was to evaluate the efficacy and tolerability of tiagabine in adult patients with post-traumatic stress disorder (PTSD). This 12-week, multicenter, double-blind study randomized patients to receive either tiagabine or placebo. Tiagabine (administered in divided doses) was initiated at 4 mg/d (2 mg BID) and individually titrated of up to 4 mg/d weekly to a maximum dose of 16 mg/d. Assessments included the Clinician-Administered PTSD Scale, Clinical Global Impressions of Change, Treatment Outcome PTSD Scale, Davidson Trauma Scale, Connor-Davidson Resilience Scale, Sheehan Disability Scale, Massachusetts General Hospital Sexual Functioning Questionnaire, and Montgomery-angstrom sberg Depression Rating Scale. A total of 232 patients (tiagabine, n = 116,- placebo, n = 116) were randomized. There were no significant differences in change from baseline in the Clinician-Administered PTSD Scale total score at final visit for tiagabine compared with placebo (P = 0.85). Similarly, no significant differences were observed with tiagabine on the other efficacy outcome measures (described above) compared with placebo. Tiagabine was generally well tolerated and not associated with weight gain, changes in sexual function, or worsening of depressive symptoms. Tiagabine was not significantly different from placebo in the treatment of symptoms of PTSD. Additional studies are needed to assess the role of drugs that target the gamma-aminobutyric acid system in the treatment of PTSD. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Howard Univ, Sch Med, Dept Psychiat, Washington, DC 20059 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. San Diego Healthcare Syst, Vet Affairs, La Jolla, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Davidson, JRT (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Trent Dr,4th Floor,Yellow Zone,Room 4082B, Durham, NC 27710 USA. EM david011@mc.duke.edu NR 35 TC 47 Z9 48 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2007 VL 27 IS 1 BP 85 EP 88 DI 10.1097/JCP.0b013e31802e5115 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 128HF UT WOS:000243648100017 PM 17224720 ER PT J AU Petersen, TJ Feldman, G Harley, R Fresco, DM Graves, L Holmes, A Bogdan, R Papakostas, GI Bohn, L Lury, RA Fava, M Segal, ZV AF Petersen, Timothy J. Feldman, Greg Harley, Rebecca Fresco, David M. Graves, Lesley Holmes, Avram Bogdan, Ryan Papakostas, George I. Bohn, Laurie Lury, R. Alana Fava, Maurizio Segal, Zindel V. TI Extreme response style in recurrent and chronically depressed patients: Change with antidepressant administration and stability during continuation treatment SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE fluoxetine; major depressive disorder; cognitive behavioral therapy; extreme response style ID COGNITIVE-BEHAVIORAL THERAPY; SEQUENTIAL TREATMENT; RESIDUAL DEPRESSION; RISK-FACTORS; DISORDER; RELAPSE; FLUOXETINE; PREVENTION; PHARMACOTHERAPY; REMISSION AB The authors examined extreme response style in recurrently and chronically depressed patients, assessing its role in therapeutic outcome. During the acute phase, outpatients with major depressive disorder (N = 384) were treated with fluoxetine for 8 weeks. Remitted patients (n = 132) entered a continuation phase during which their fluoxetine dose increased and they were randomly assigned to treatment with or without cognitive-behavioral therapy (CBT). Results showed a predictive relationship between extreme response style and clinical outcome. Patients in the medication-only group showed a significant increase in the frequency of extreme responses, whereas patients receiving CBT showed no significant change. These results are consistent with recent findings suggesting that metacognitive factors may be as important as changes in thought content when treating depression. C1 Rhode Isl Hosp, Dept Psychiat, Mood Disorders Program, Providence, RI 02903 USA. Simmons Coll, Dept Psychol, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Dept Clin & Res Program, Boston, MA 02114 USA. Kent State Univ, Dept Psychol, Kent, OH 44242 USA. Univ Toronto, Ctr Addict & Mental Hlth Clarke, Toronto, ON, Canada. RP Petersen, TJ (reprint author), Rhode Isl Hosp, Dept Psychiat, Mood Disorders Program, 593 Eddy St,Potter 300, Providence, RI 02903 USA. EM tpetersen1@lifespan.org RI Fresco, David/F-6522-2013; Papakostas, George/I-6905-2013; Segal, Zindel/F-8008-2014; OI Papakostas, George/0000-0002-2465-5103; Bogdan, Ryan/0000-0002-1430-1045; Fresco, David/0000-0001-6736-3912 NR 44 TC 17 Z9 18 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 2007 VL 75 IS 1 BP 145 EP 153 DI 10.1037/0022-006X.75.1.145 PG 9 WC Psychology, Clinical SC Psychology GA 131VI UT WOS:000243898500016 PM 17295573 ER PT J AU Iwata, T Yamakoshi, Y Hu, JCC Ishikawa, I Bartlett, JD Krebsbach, PH Simmer, JP AF Iwata, T. Yamakoshi, Y. Hu, J. C. -C. Ishikawa, I. Bartlett, J. D. Krebsbach, P. H. Simmer, J. P. TI Processing of ameloblastin by MMP-20 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamelysin; ameloblastin; AMBN; MMP-20; enamel; amelogenesis ID HYPOMATURATION AMELOGENESIS-IMPERFECTA; DEVELOPING DENTAL ENAMEL; SHEATH PROTEINS; PORCINE ENAMEL; CALCIUM-BINDING; IMMATURE ENAMEL; EXPRESSION; MATRIX; MUTATION; RAT AB Ameloblastin ( AMBN) cleavage products are the most abundant non-amelogenin proteins in the enamel matrix of developing teeth. AMBN N-terminal cleavage products accumulate in the sheath space between enamel rods, while AMBN C-terminal products localize within rods. We tested the hypothesis that MMP-20 is the protease that cleaves AMBN. Glycosylated recombinant porcine AMBN (rpAMBN) was expressed in human kidney 293F cells, and recombinant porcine enamelysin (rpMMP-20) was expressed in bacteria. The purified proteins were incubated together at an enzyme: substrate ratio of 1:100. N-terminal sequencing of AMBN digestion products determined that rpMMP-20 cleaved rpAMBN after Pro(2), Gln(130), Gln(139), Arg(170), and Ala(222). This shows that MMP-20 generates the 23-kDa AMBN starting at Tyr(223), as well as the 17-kDa (Val(1)Arg(170)) and 15-kDa (Val(1)-Gln(130)) AMBN cleavage products that concentrate in the sheath space during the secretory stage. We conclude that MMP-20 processes ameloblastin in vitro and in vivo. C1 Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48108 USA. Univ Michigan, Sch Dent, Dept Orthodont & Pediat Dent, Dent Res Lab, Ann Arbor, MI 48108 USA. Tokyo Med & Dent Univ, Dept Hard Tissue Engn, Tokyo, Japan. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. RP Simmer, JP (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA. EM jsimmer@umich.edu FU NIDCR NIH HHS [R01 DE016276, DE12769, DE15846] NR 38 TC 45 Z9 47 U1 2 U2 5 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 FEB PY 2007 VL 86 IS 2 BP 153 EP 157 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 138TO UT WOS:000244385700009 PM 17251515 ER PT J AU Tiamfook-Morgan, TO Brown, DFM Nadel, ES Takayesu, K Nagurney, JT Levine, M Shah, S Listwa, T Walta, M Marsh, R AF Tiamfook-Morgan, Tami O. Brown, David F. M. Nadel, Eric S. Takayesu, Kimo Nagurney, J. Tobias Levine, Michael Shah, Sachita Listwa, Todd Walta, Michael Marsh, Regan TI Change in mental status SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. NR 9 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 FEB PY 2007 VL 32 IS 2 BP 201 EP 203 DI 10.1016/j.jemermed.2006.12.001 PG 3 WC Emergency Medicine SC Emergency Medicine GA 142AB UT WOS:000244619500014 PM 17307634 ER PT J AU Sun, BC Binstadt, ES Pelletier, A Camargo, CA AF Sun, Benjamin C. Binstadt, Emily Spilseth Pelletier, Andrea Camargo, Carlos A., Jr. TI Characteristics and temporal trends of "left before being seen" visits in US emergency departments, 1995-2002 SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE left before being seen; NHAMCS; ED crowding ID PUBLIC HOSPITAL EMERGENCY; PHYSICIAN; LEAVE; CONSEQUENCES; CARE C1 W Los Angeles Vet Affairs Med Ctr, Off 3214A, Dept Med, Los Angeles, CA USA. Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Sun, BC (reprint author), W Los Angeles Vet Affairs Med Ctr, Off 3214A, Dept Med, Bldg 500,11301 Wilshire Blvd, Los Angeles, CA USA. NR 9 TC 20 Z9 20 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 FEB PY 2007 VL 32 IS 2 BP 211 EP 215 DI 10.1016/j.jemermed.2006.05.045 PG 5 WC Emergency Medicine SC Emergency Medicine GA 142AB UT WOS:000244619500021 PM 17307641 ER PT J AU Chattergoon, NN Giraud, GD Thornburg, KL AF Chattergoon, N. N. Giraud, G. D. Thornburg, K. L. TI Thyroid hormone inhibits proliferation of fetal cardiac myocytes in vitro SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CARDIOMYOCYTE DNA-SYNTHESIS; CYCLIN D1; POSTNATAL-DEVELOPMENT; RAT CARDIOMYOCYTES; ANDROGEN RECEPTOR; ESTROGEN-RECEPTOR; LATE-GESTATION; NEONATAL-RAT; SHEEP FETUS; GROWTH AB Thyroid hormone (T-3) is a key regulator of fetal organ maturation. Premature elevations of thyroid hormone may lead to a 'mature' cardio-phenotype. Thyroid hormone will stimulate maturation of ovine fetal cardiomyocytes in culture by decreasing their proliferative capacity. Group 1 fetal cardiomyocytes (similar to 135 days gestation) were incubated with T-3 (1.5, 3, 10, and 100 nM) and bromodeoxyuridine (BrdU; 10 mu M) for 24 and 48 h. Group 2 cardiomyocytes were cultured with T-3 alone for later protein analysis of cell cycle regulators. At all concentrations, T-3 decreased BrdU uptake fourfold in serum media (P < 0.001 versus serum, n=5). Following serum-free (SF) T3 treatment, BrdU uptake was inhibited when compared with serum (P < 0-001 versus serum, n=5). p21 expression increased threefold (P < 0.05 versus serum free, n=4) and cyclin D1 expression decreased twofold (P < 0.05 versus serum, n=4) in T-3-treated cardiomyocytes. (1) T-3 inhibits fetal cardiomyocyte proliferation, while (2) p21 protein levels increase, and (3) cyclin D1 levels decrease. Thus, T-3 may be a potent regulator of cardiomyocyte proliferation and maturation in the late gestation fetus. C1 Oregon Hlth Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med Cardiovasc Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. RP Chattergoon, NN (reprint author), Oregon Hlth Sci Univ, Heart Res Ctr, L464,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM chatterg@ohsu.edu FU NICHD NIH HHS [3 P01 HD034430-09S1, P01HD34430] NR 44 TC 18 Z9 18 U1 0 U2 2 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD FEB PY 2007 VL 192 IS 2 BP R1 EP R8 DI 10.1677/JOE-06-0114 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 146TS UT WOS:000244958200021 PM 17283226 ER PT J AU Vargas, RB Mangione, CM Asch, S Keesey, J Rosen, M Schonlau, M Keeler, EB AF Vargas, Roberto B. Mangione, Carol M. Asch, Steven Keesey, Joan Rosen, Mayde Schonlau, Matthias Keeler, Emmett B. TI Can a chronic care model collaborative reduce heart disease risk in patients with diabetes? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE chronic care; diabetes; cardiovascular disease; collaborative; intervention ID QUALITY IMPROVEMENT; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; CLINICAL-RESEARCH; CONTROLLED-TRIAL; CHRONIC ILLNESS; MELLITUS; COMPLICATIONS; COMMUNITY; HYPERTENSION AB BACKGROUND: There is a need to identify effective practical interventions to decrease cardiovascular disease risk in patients with diabetes. OBJECTIVE: We examine the impact of participation in a collaborative implementing the chronic care model (CCM) on the reduction of cardiovascular disease risk in patients with diabetes. DESIGN: Controlled pre- and postintervention study. PATIENTS/PARTICIPANTS: Persons with diabetes receiving care at 13 health care organizations exposed to the CCM collaborative and controls receiving care in nonexposed sites. MEASUREMENTS AND MAIN RESULTS: Ten-year risk of cardiovascular disease; determined using a modified United Kingdom Prospective Diabetes Study risk engine score. A total number of 613 patients from CCM intervention sites and 557 patients from usual care control sites met the inclusion criteria. The baseline mean 10-year risk of cardiovascular disease was 31% for both the intervention group and the control group. Participants in both groups had improved blood pressure, lipid levels, and HbA1c levels during the observation period. Random intercept hierarchical regression models showed that the intervention group had a 2.1% (95% CI -3.7%, -0.5%) greater reduction in predicted risk for future cardiovascular events when compared to the control group. This would result in a reduced risk of one cardiovascular disease event for every 48 patients exposed to the intervention. CONCLUSIONS: Over a 1-year interval, this collaborative intervention using the CCM lowered the cardiovascular disease risk factors of patients with diabetes who were cared for in the participating organization's settings. Further work could enhance the impact of this promising multifactorial intervention on cardiovascular disease risk reduction. C1 Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. Univ Calif Los Angeles, Div Gen Internal Med, David Geffen Sch Med, W Los Angeles Vet Adm Hosp, Los Angeles, CA 90024 USA. RP Vargas, RB (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, 911 Broxton Ave, Los Angeles, CA 90024 USA. EM RBVargas@mednet.ucla.edu FU NIMHD NIH HHS [P20 MD000148] NR 47 TC 47 Z9 47 U1 1 U2 7 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 FEB PY 2007 VL 22 IS 2 BP 215 EP 222 DI 10.1007/s11606-006-0072-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 140QX UT WOS:000244521900009 PM 17356989 ER PT J AU Goodroe, R Bonnema, DD Lunsford, S Anderson, P Ryan-Baille, B Uber, W Ikonomidis, J Crumbley, AJ VanBakel, A Zile, MR Pereira, N AF Goodroe, Randy Bonnema, D. Dirk Lunsford, Shayna Anderson, Phillip Ryan-Baille, Barbara Uber, Walt Ikonomidis, John Crumbley, Arthur J. VanBakel, Adrian Zile, Michael R. Pereira, Naveen TI Severe left ventricular hypertrophy 1 year after transplant predicts mortality in cardiac transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID CYCLOSPORINE-INDUCED HYPERTENSION; SYSTEMIC HYPERTENSION; ECHOCARDIOGRAPHIC MEASUREMENTS; BLOOD-PRESSURE; HEART; MASS; TACROLIMUS; THERAPY; INDEXATION; MECHANISMS AB Background: Left ventricular hypertrophy (LVH) is a known predictor of morbidity and mortality in patients with essential hypertension. The prevalence and significance of LVH in heart transplant recipients is unknown. Methods: Transthoracic echocardiograms were performed as part of a routine protocol I year after heart transplantation in 141 consecutive patients. Demographic and echocardiographic data were collected using patients' records and center-specific data from the Cardiac Transplant Research Database and analyzed to determine the prevalence and predictors of LVH at 1 year posttransplantation. Patients were divided into three groups based on left ventricular mass (LVM): normal (LVM < 150 g); mild-moderate LVH (LVM 150 to 250 g); and severe LVH (LVM > 250 g). Results: LVH was common at 1 year after heart transplantation, present in 83% of heart transplant recipients. Univariate predictors of severe LVH were increased body mass index (p < 0.01), pre-transplant diabetes mellitus (p = 0.02) and pre-transplant hypertension (p = 0.01). By multivariate analysis, pre-transplant hypertension was the only independent predictor of severe LVH (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1 to 5.4,p = 0.05). Heart transplant recipients with severe LVH had significantly decreased survival, as compared to patients with normal LVM and mild-moderate LVH (P = 0.03). After multivaniate analysis adjusting for age, race, gender, pre-transplant hypertension and diabetes, severe LVH remained a strong, independent predictor of mortality (HR 3.6, 95% CI 1.0 to 12.1, P = 0.04). Conclusions: LVH is common at 1 year after heart transplantation and is a strong, independent predictor of increased mortality. Hypertension before transplantation is an independent predictor of the presence of severe LVH at 1 year after heart transplantation. C1 Med Univ S Carolina, Div Cardiol, Dept Med, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. Med Univ S Carolina, Div Transplant Surg, Dept Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Transplant Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharm Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Div Cardiothorac Surg, Dept Surg, Charleston, SC 29425 USA. RP Pereira, N (reprint author), Med Univ S Carolina, Div Cardiol, Dept Med, 135 Rutledge Ave,Suite 1201,POB 250592, Charleston, SC 29425 USA. EM pereiran@musc.edu FU NCRR NIH HHS [M01-RR-01070-251]; NHLBI NIH HHS [P01-HL-48788] NR 32 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 BP 145 EP 151 DI 10.1016/j.healun.2006.11.003 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 137KG UT WOS:000244290900008 PM 17258148 ER PT J AU Houser, S Muniappan, A Allan, J Sachs, D Madsen, J AF Houser, Stuart Muniappan, Ashok Allan, James Sachs, David Madsen, Joren TI Cardiac allograft vasculopathy: Real or a normal morphologic variant? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; SMOOTH-MUSCLE-CELLS; MINIATURE SWINE; HEART-TRANSPLANTATION; CORONARY-ARTERIES; DONOR ORIGIN; ATHEROSCLEROSIS; REJECTION; CORRELATE; CHILDREN AB Background: Naive coronary vessels may appear to have intimal thickening histologically characteristic of cardiac allograft vasculopathy (CAV). This study appraises the experimental and clinical impact of this observation. Methods: Tissue sections from 12 naive hearts of miniature swine, 13 native porcine hearts of recipients of heterotopic cardiac allografts, 3 native human hearts and 3 human hearts with CAV were compared with light microscopy and morphometric analysis. Results were also compared with morphometric data previously gathered from 3 grafts in a standard experimental model of CAV (rejectors) and 3 grafts harvested from swine rendered tolerant to their donor hearts (chimeras). Results: In the naive and native porcine hearts, the prevalence of CAV "mimics" was 0% to 6.94% (mean +/- SD: 1.99 +/- 1.97%) and 0% to 7.57% (2.97 +/- 2.20%), respectively (p = 0.12). The prevalence of CAV in the grafts of porcine rejectors and chimeras was 9.9% to 14.8% (12.4 +/- 2.5%) and 0.6% to 4.5% (2.6 +/- 2.09%), respectively (p < 0.05). CAV in the chimeras was similar in prevalence to that of the naive and native hearts. In native human hearts and human grafts, the prevalence was 1.86% to 2.00% (1.95 +/- 0.08%) and 9.09% to 17.50% (12.80 +/- 4.29%), respectively (P = 0.01). Conclusions: Smooth muscle bundles inside the internal elastic laminae are similarly prevalent in human and porcine coronary vasculature. Their histologic similarity to intimal thickening of CAV could lead to an inaccurate distinction between graft tolerance and CAV in both clinical and experimental studies of heart transplantation. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Houser, S (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM houser.stuart@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL054211] NR 27 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 BP 167 EP 173 DI 10.1016/j.healun.2006.11.012 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 137KG UT WOS:000244290900011 PM 17258151 ER PT J AU Bastani, S Schnickel, GT Hsieh, GR Garcia, C Fishbein, MC Ardebali, A AF Bastani, S. Schnickel, G. T. Hsieh, G. R. Garcia, C. Fishbein, M. C. Ardebali, A. TI CXCR3 and CCR5 blockade prevents acute rejection via induction of regulatory CD4 lymphocytes SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiac Surg, Dept Surg, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Div Cardiac Surg, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 422 BP S212 EP S212 DI 10.1016/j.healun.2006.11.444 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200421 ER PT J AU Ennis, S Moukarbel, GV Moore, SA Ennis, C MacGillivray, TE AF Ennis, S. Moukarbel, G. V. Moore, S. A. Ennis, C. MacGillivray, T. E. TI The impact of new mechanical circulatory support technology on post-operative recovery and length of hospital stay SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Med Sch, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 97 BP S94 EP S95 DI 10.1016/j.healun.2006.11.112 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200098 ER PT J AU Franco, V Tallaj, JA Rayburn, BK Pamboukian, SV Benza, RL Kirklin, JK McGiffin, DC Smallfield, M Bourge, RC AF Franco, V. Tallaj, J. A. Rayburn, B. K. Pamboukian, S. V. Benza, R. L. Kirklin, J. K. McGiffin, D. C. Smallfield, M. Bourge, R. C. TI Ibutilide is safe and efficatious in heart transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Alabama, Div Cardiovasc Med, Birmingham, AL USA. Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 259 BP S153 EP S153 DI 10.1016/j.healun.2006.11.278 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200260 ER PT J AU Houser, S Muniappan, A Allan, J Madsen, J AF Houser, S. Muniappan, A. Allan, J. Madsen, J. TI Cardiac allograft vasculopathy: Real or a normal morphologic variant? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 265 BP S155 EP S155 DI 10.1016/j.healun.2006.11.284 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200266 ER PT J AU Lewis, GD Frankel, DS Brown, RN Rodeheffer, RJ Heroux, AL Cabuay, BM Keck, SA Kirklin, JK Semigran, MJ AF Lewis, G. D. Frankel, D. S. Brown, R. N. Rodeheffer, R. J. Heroux, A. L. Cabuay, B. M. Keck, S. A. Kirklin, J. K. Semigran, M. J. TI Predictors of early development of chronic kidney disease following heart transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Alabama, Dept Surg, Cardiac Transplant Res Database, Birmingham, AL 35294 USA. Mayo Clin, Div Cardiol, Rochester, MN USA. Loyola Univ, Ctr Med, Div Cardiol, Maywood, IL 60153 USA. Univ Iowa, Div Cardiol, Iowa City, IA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 217 BP S137 EP S138 DI 10.1016/j.healun.2006.11.235 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200218 ER PT J AU Moukarbel, GV Jneid, H Hoyer, HK Kuhn, EW Gonczarek, KM Keck, SA Haggan, CD Semigran, MJ AF Moukarbel, G. V. Jneid, H. Hoyer, H. K. Kuhn, E. W. Gonczarek, K. M. Keck, S. A. Haggan, C. D. Semigran, M. J. TI Impact of donor-recipient race-mismatch on outcomes of cardiac transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Sch, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 360 BP S189 EP S189 DI 10.1016/j.healun.2006.11.381 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200360 ER PT J AU Moukarbel, GV Ennis, S Moore, SA MacGillivray, TE AF Moukarbel, G. V. Ennis, S. Moore, S. A. MacGillivray, T. E. TI New generation axial-flow left-ventricular assist device supports patients with various degrees of right ventricular dysfunction SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Med Sch, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Div Cardiac Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 86 BP S90 EP S91 DI 10.1016/j.healun.2006.11.101 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200087 ER PT J AU Sahara, H Weiss, MJ Ng, CY Houser, SI Pujara, AC Sayer, JK Wain, JC Sachs, DH Madsen, JC Allan, JS AF Sahara, H. Weiss, M. J. Ng, C. Y. Houser, S. I. Pujara, A. C. Sayer, J. K. Wain, J. C. Sachs, D. H. Madsen, J. C. Allan, J. S. TI Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung allografts SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Med Sch, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 374 BP S194 EP S194 DI 10.1016/j.healun.2006.11.395 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200373 ER PT J AU Sahara, H Shoji, T Ng, CY Weiss, MJ Muniappan, A Guenther, DA Houser, SL Pujara, AC Sayer, JK Wain, JC Sachs, DH Madsen, JC Allan, JS AF Sahara, H. Shoji, T. Ng, C. Y. Weiss, M. J. Muniappan, A. Guenther, D. A. Houser, S. L. Pujara, A. C. Sayer, J. K. Wain, J. C. Sachs, D. H. Madsen, J. C. Allan, J. S. TI The role of indirect recognition of MHC class I and II allopeptides in lung transplantation in miniature swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Med Sch, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 349 BP S185 EP S185 DI 10.1016/j.healun.2006.11.369 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200349 ER PT J AU Sahara, H Weiss, MJ Wikiel, KJ Sayre, JK Pujara, AC Ng, CY Cho, PL Horner, BM Houser, SL Wain, JC Sachs, DH Madsen, JC Huang, CA Allan, JS AF Sahara, H. Weiss, M. J. Wikiel, K. J. Sayre, J. K. Pujara, A. C. Ng, C. Y. Cho, P. L. Horner, B. M. Houser, S. L. Wain, J. C. Sachs, D. H. Madsen, J. C. Huang, C. A. Allan, J. S. TI Mixed hematopoietic chimerism prevents lung allograft rejection in miniature swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Harvard Med sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 31 BP S71 EP S72 DI 10.1016/j.healun.2006.11.045 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200032 ER PT J AU Shoji, T Sahara, H Muniappan, A Guenther, DA Houser, SL Pujara, AC Bravard, MA Wain, JC Sachs, DH Madsen, JC Allan, JS AF Shoji, T. Sahara, H. Muniappan, A. Guenther, D. A. Houser, S. L. Pujara, A. C. Bravard, M. A. Wain, J. C. Sachs, D. H. Madsen, J. C. Allan, J. S. TI An MHC class H disparity raises the threshold for tolerance induction in pulmonary allografts in miniature swine SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 551 BP S258 EP S258 DI 10.1016/j.healun.2006.11.576 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200550 ER PT J AU Weiss, MJ Guenther, DA Mezrich, JD Sahara, H Ng, CY Meltzer, AJ Oriyanhan, W Sayre, JK Pujara, AC Cochrane, ME Houser, SL Sachs, DH Allan, JS Madsen, JC AF Weiss, M. J. Guenther, D. A. Mezrich, J. D. Sahara, H. Ng, C. Y. Meltzer, A. J. Oriyanhan, W. Sayre, J. K. Pujara, A. C. Cochrane, M. E. Houser, S. L. Sachs, D. H. Allan, J. S. Madsen, J. C. TI Donor class I peptide immunization affects the induction but not maintenance phase of tolerance SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 379 BP S196 EP S196 DI 10.1016/j.healun.2006.11.400 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200378 ER PT J AU Zieroth, S Thangaroopan, M Carasso, S Rao, V Delgado, D Rakowski, H Ross, H AF Zieroth, S. Thangaroopan, M. Carasso, S. Rao, V. Delgado, D. Rakowski, H. Ross, H. TI Biplanar 2D-echo strain imaging documents improvement in LV function in patients with VAD SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract C1 St Boniface Gen Hosp, Dept Cardiol, Winnipeg, MB R2H 2A6, Canada. Univ Hlth Network, Dept Cardiac Transplant, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2007 VL 26 IS 2 SU S MA 3 BP S61 EP S62 DI 10.1016/j.healun.2006.11.017 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 138DB UT WOS:000244342200004 ER PT J AU Hubeau, C Apostolou, I Kobzik, L AF Hubeau, Cedric Apostolou, Irina Kobzik, Lester TI Targeting of CD25 and glucocorticoid-induced TNF receptor family-related gene-expressing T cells differentially modulates asthma risk in offspring of asthmatic and normal mother mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; IN-VIVO; MATERNAL TRANSMISSION; IMMUNE-RESPONSES; ALLERGIC DISEASE; MURINE MODEL; MEDIATED SUPPRESSION; AIRWAY INFLAMMATION; CUTTING EDGE; MOUSE MODEL AB Immunological mechanisms leading to increased asthma susceptibility in early life remain obscure. In this study, we examined the effects of neonatal Ab treatments targeting T cell populations on the development of an asthma syndrome. We used a model of increased asthma susceptibility where offspring of asthmatic BALB/c mother mice are more prone (than normal pups) to develop the disease. Neonatal pretreatment of naive pups with mAb directed against the IL-2R alpha chain (CD25), the costimulatory molecule glucocorticoid-induced TNFR family related gene, and the inhibitory molecule CTLA-4 elicited contrasting effects in offspring depending on the mother's asthma status. Specifically, neonatal CD25(high) T cell depiction stimulated asthma susceptibility in normal offspring whereas it ameliorated the condition of pups born of asthmatic mothers. Conversely, glucocorticoid-induced TNFR family related gene ligation as a primary signal reduced the spleen cellularity and largely abrogated asthma susceptibility in asthma-prone offspring, without inducing disease in normal pups. Striking changes in Th1/Th2 cytokine levels, especially IL-4, followed mAb pretreatment and were consistent with the impact on asthma susceptibility. These results point to major differences in neonatal T cell population and responsiveness related to maternal asthma history. Interventions that temporarily remove and/or inactivate specific T cell subsets may therefore prove useful to attenuate early life asthma susceptibility and prevent the development of Th2-driven allergic airway disease. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Kobzik, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM lkobzik@hsph.harvard.edu FU NHLBI NIH HHS [HL69760] NR 66 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2007 VL 178 IS 3 BP 1477 EP 1487 PG 11 WC Immunology SC Immunology GA 130TC UT WOS:000243820900031 PM 17237396 ER PT J AU Aiello, FB Keller, JR Klarmann, KD Dranoff, G Mazzucchelli, R Durum, SK AF Aiello, Francesca B. Keller, Jonathan R. Klarmann, Kimberly D. Dranoff, Glenn Mazzucchelli, Renata Durum, Scott K. TI IL-7 induces myelopoiesis and erythropoiesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; RECOMBINANT HUMAN INTERLEUKIN-7; HEMATOPOIETIC STEM-CELLS; MURINE FLT3 LIGAND; CD4(+) T-CELLS; KAPPA-B LIGAND; DEFICIENT MICE; BONE-MARROW; GM-CSF; PROGENITOR CELLS AB IL-7 administration to mice was previously reported to increase the mobilization of progenitor cells from marrow to peripheral sites. We now report that IL-7 increases the number of mature myeloid and monocytic cells in spleen and peripheral blood. This effect required T cells, and we show that IL-7 treatment in vivo induced GNI-CSF and IL-3 production by T cells with memory phenotype. However, additional myelopoietic cytokines were shown to be involved because mice deficient in both GNI-CSF and IL-3 also responded to IL-7 with increased myelopoiesis. Candidate cytokines included IFN-gamma and Flt3 ligand, which were also produced in response to IL-7. Because IFN-gamma-deficient mice also increased myelopoiesis, it was suggested that IL-7 induced production of redundant myelopoietic cytokines. In support of this hypothesis, we found that the supernatant from IL-7-treated, purified T cells contained myelopoietic activity that required a combination of Abs against GNI-CSF, IL-3, and anti-Flt3 ligand to achieve maximum neutralization. IL-7 administration increased the number of splenic erythroid cells in either normal, Ragl or GM-CSF-IL-3-deficient mice, suggesting that IL-7 might directly act on erythroid progenitors. In support of this theory, we detected a percentage of TER-119(+) erythroid cells that expressed the IL-7R alpha-chain and common gamma-chain. Bone marrow cells expressing IL-7R and B220 generated erythroid colonies in vitro in response to IL-7, erythropoietin, and stem cell factor. This study demonstrates that IL-7 can promote nonlymphoid hemopoiesis and production of cytokines active in the host defense system in vivo, supporting its possible clinical utility. C1 NCI, Sect Cytokines & Immun, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Univ Chieti, Dept Oncol & Neurosci, Chieti, Italy. NCI, SAIC Frederick, Canc & Dev Biol Lab, Frederick, MD 21701 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Durum, SK (reprint author), NCI, Sect Cytokines & Immun, Mol Immunoregulat Lab, Bldg 560,Room 31-56, Frederick, MD 21702 USA. EM durum@nciferf.gov FU Intramural NIH HHS NR 88 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2007 VL 178 IS 3 BP 1553 EP 1563 PG 11 WC Immunology SC Immunology GA 130TC UT WOS:000243820900039 PM 17237404 ER PT J AU Mehendiratta, V McCarty, BC Gomez, L Graviss, EA Musher, DM AF Mehendiratta, Vaibhav McCarty, Brandon Chase Gomez, Luis Graviss, Edward A. Musher, Daniel M. TI Computerized tomography (CT)-guided aspiration of abscesses: Outcome of therapy at a tertiary care hospital SO JOURNAL OF INFECTION LA English DT Article DE CT-guided; aspiration; abscesses; outcome of therapy ID PERCUTANEOUS CATHETER DRAINAGE; INTRAABDOMINAL ABSCESSES; ABDOMINAL ABSCESSES; OPERATIVE DRAINAGE; SCORE AB Objective: To review the experience with percutaneous aspiration of abscesses at a general, tertiary care hospital from 2000 to 2005. Methods: Computerized medical records of 90 patients who underwent radiologically guided drainage of 92 fluid collections were reviewed for demographic data, co-morbid conditions, location, radiographic imaging characteristics and culture results and to determine the tong-term outcome of the procedure. Results: Sixty-seven of 92 (73%) abscesses were cured without the need for open surgical drainage; 44 were cured within 14 days, and 23 had delayed resolution requiring prolonged antibiotics and/or a second drainage. Of the abscesses 85% were drained using a catheter in situ, the remaining aspirated using a needle. Twenty-five (27%) of the 92 abscesses failed percutaneous drainage, requiring open surgical drainage or lead to sepsis and death. Neither co-morbid conditions nor the location of abscesses affected the outcome of drainage. Patients who had sterile cultures of aspirated material after receiving antibiotics prior to the procedure had a significantly higher cure rate than otherwise (P < 0.05). Catheter drainage was associated with a significantly higher cure rate than was needle aspiration (P < 0.05). Conclusion: Percutaneous drainage, along with appropriate antibiotics, is an effective approach to treat deep abscesses. Drainage, itself, is the major determinant of outcome, rather than the Location, characteristics of the abscess or condition of the patient prior to the procedure. Published by Elsevier Ltd on behalf of The British Infection Society. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Phys Assistant Program, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. EM daniel.musher@med.va.gov NR 24 TC 6 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD FEB PY 2007 VL 54 IS 2 BP 122 EP 128 DI 10.1016/j.jinf.2006.03.004 PG 7 WC Infectious Diseases SC Infectious Diseases GA 129SB UT WOS:000243749300003 PM 16678902 ER PT J AU Raspollini, MR Oliva, E Roberts, DJ AF Raspollini, Maria Rosaria Oliva, Esther Roberts, Drucilla J. TI Placental histopathologic features in patients with thrombophilic mutations SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE placenta; thrombophilia; decidual vasculopathy; fetal thrombotic vasculopathy; fetal outcome ID FETAL THROMBOTIC VASCULOPATHY; FACTOR-V-LEIDEN; ANTIPHOSPHOLIPID-ANTIBODY SYNDROME; INTRAUTERINE GROWTH RESTRICTION; MATERNAL FLOOR INFARCTION; ACTIVATED PROTEIN-C; SEVERE PREGNANCY COMPLICATIONS; RENAL-VEIN THROMBOSIS; OXIDATIVE STRESS; HEMORRHAGIC ENDOVASCULITIS AB The purpose of this article is to review the histopathologic findings in the placenta of women with a known thrombophilic mutation. The findings range from normal to severe pathologic features including decidual vasculopathy, placental infarctions, syncytial knotting, maternal floor infarction, fetal thrombotic vasculopathy, vasculitis, and chronic villitis. They are, however, not pathognomonic of thrombophilic states, nor are necessarily markers of perinatal damage. The prospective evaluation of cases with known thrombophilic mutations and the application of tissue microarray examination of the placenta may allow identification of major histopathologic features and molecular parameters associated with maternal and/or fetal thrombophilic states. This may assist clinicians in their consultation with patients and optimize management in future pregnancies. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Florence, Sch Med, Dept Human Pathol & Oncol, Florence, Italy. RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM djroberts@partners.org NR 79 TC 13 Z9 14 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD FEB PY 2007 VL 20 IS 2 BP 113 EP 123 DI 10.1080/14767050601178345 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 145LK UT WOS:000244866400003 PM 17437209 ER PT J AU Angelow, S Schneeberger, EE Yu, ASL AF Angelow, Susanne Schneeberger, Eveline E. Yu, Alan S. L. TI Claudin-8 expression in renal epithelial cells augments the paracellular barrier by replacing endogenous claudin-2 SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE tight junction; claudin; paracellular transport; renal epithelia ID RECESSIVE DEAFNESS DFNB29; CANINE KIDNEY-CELLS; TIGHT JUNCTIONS; DIFFERENTIAL EXPRESSION; SELECTIVE CHANNELS; CONDUCTANCE; PROTEINS; MICE; TRANSPORT; PERMEABILITY AB Claudins are transmembrane proteins of the tight junction that determine and regulate paracellular ion permeability. We previously reported that claudin-8 reduces paracellular cation permeability when expressed in low-resistance Madin-Darby canine kidney (MDCK) II cells. Here, we address how the interaction of heterologously expressed claudin-8 with endogenous claudin isoforms impacts epithelial barrier properties. In MDCK II cells, barrier improvement by claudin-8 is accompanied by a reduction of endogenous claudin-2 protein at the tight junction. Here, we show that this is not because of relocalization of claudin-2 into the cytosolic pool but primarily due to a decrease in gene expression. Claudin-8 also affects the trafficking of claudin-2, which was displaced specifically from the junctions at which claudin-8 was inserted. To test whether replacement of cation-permeable claudin-2 mediates the effect of claudin-8 on the electrophysiological phenotype of the host cell line, we expressed claudin-8 in high-resistance MDCK I cells, which lack endogenous claudin-2. Unlike in MDCK II cells, induction of claudin-8 in MDCK I cells (which did not affect levels of endogenous claudins) did not alter paracellular ion permeability. Furthermore, when endogenous claudin-2 in MDCK II cells was downregulated by epidermal growth factor to create a cell model with low transepithelial resistance and low levels of claudin-2, the permeability effects of claudin-8 were also abolished. Our findings demonstrate that claudin overexpression studies measure the combined effect of alterations in both endogenous and exogenous claudins, thus explaining the dependence of the phenotype on the host cell line. C1 Univ So Calif, Keck Sch Med, Dept Med, Div Nephrol, Los Angeles, CA 90033 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Yu, ASL (reprint author), Univ So Calif, Keck Sch Med, Dept Med, Div Nephrol, 2025 Zonal Ave,RMR 406, Los Angeles, CA 90033 USA. EM alanyu@usc.edu OI Yu, Alan/0000-0002-1776-2533 FU NHLBI NIH HHS [HL 25822]; NIDDK NIH HHS [R01 DK062283, DK 062283, DK 48522] NR 37 TC 42 Z9 42 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD FEB PY 2007 VL 215 IS 2-3 BP 147 EP 159 DI 10.1007/s00232-007-9014-3 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 201XE UT WOS:000248865100009 PM 17516019 ER PT J AU Byers, RJ Di Vizio, D O'Connell, F Tholouli, E Levenson, RM Gossard, K Twomey, D Yang, Y Benedettini, E Rose, J Ligon, KL Finn, SP Golub, TR Loda, M AF Byers, Richard J. Di Vizio, Dolores O'Connell, Fionnuala Tholouli, Eleni Levenson, Richard M. Gossard, Kirk Twomey, David Yang, Yu Benedettini, Elisa Rose, Joshua Ligon, Keith L. Finn, Stephen P. Golub, Todd R. Loda, Massimo TI Semiautomated multiplexed quantum dot-based in situ hybridization and spectral deconvolution SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID PARAFFIN-EMBEDDED TISSUE; SEMICONDUCTOR NANOCRYSTALS; MESSENGER-RNAS; FLUORESCENCE; PREDICTION; MOUSE; GENE; PROTEIN; CANCER; PROBES AB Gene expression profiling has identified several potentially useful gene signatures for predicting outcome or for selecting targeted therapy. However, these signatures have been developed in fresh or frozen tissue, and there is a need to apply them to routinely processed samples. Here, we demonstrate the feasibility of a potentially high-throughput methodology combining automated in situ hybridization with quantum dot-labeled oligonucleotide probes followed by spectral imaging for the detection and subsequent deconvolution of multiple signals. This method is semiautomated and quantitative and can be applied to formalin-fixed, paraffin-embedded tissues. We have combined dual in situ hybridization with immunohistochemistry, enabling simultaneous measurement of gene expression and cell lineage determination. The technique achieves levels of sensitivity and specificity sufficient for the potential application of known expression signatures to biopsy specimens in a semiquantitative way, and the semiautomated nature of the method enables application to high-throughput studies. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Manchester, Div Lab & Regenerat Med, Manchester M13 9PL, Lancs, England. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Univ Manchester, Manchester Royal Infirm, Dept Hematol, Manchester M13 9PL, Lancs, England. Cambridge Res & Instrumentat, Woburn, MA USA. MIT, Harvard Mit Div Hlth Sci & Technol, Broad Inst, Cambridge, MA 02139 USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D1536,44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu OI Byers, Richard/0000-0003-0796-0365; Ligon, Keith/0000-0002-7733-600X; Finn, Stephen/0000-0002-8628-5814 FU NCI NIH HHS [2P01 CA089021, 5P50CA90381, P01 CA089021, P50 CA090381] NR 35 TC 35 Z9 37 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD FEB PY 2007 VL 9 IS 1 BP 20 EP 29 DI 10.2353/jmoldx.2007.060119 PG 10 WC Pathology SC Pathology GA 131VF UT WOS:000243898200004 PM 17251332 ER PT J AU Hims, MM Ibrahim, EC Leyne, M Mull, J Liu, L Lazaro, C Shetty, RS Gill, S Gusella, JF Reed, R Slaugenhaupt, SA AF Hims, Matthew M. Ibrahim, El Cherif Leyne, Marie Mull, James Liu, Lijuan Lazaro, Conxi Shetty, Ranjit S. Gill, Sandra Gusella, James F. Reed, Robin Slaugenhaupt, Susan A. TI Therapeutic potential and mechanism of kinetin as a treatment for the human splicing disease familial dysautonomia SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE mRNA splicing; dysautonomia; kinetin ID NEUROFIBROMATOSIS TYPE-1; HUMAN GENES; NF1 GENE; MUTATIONS; MESSENGER; IDENTIFICATION; PROTEIN; DEFECTS; COMPLEX; GENOME AB Mutations that affect the splicing of pre-mRNA are a major cause of human disease. Familial dysautonomia (FD) is a recessive neurodegenerative disease caused by a T to C transition at base pair 6 of IKBKAP intron 20. This mutation results in variable tissue-specific skipping of exon 20. Previously, we reported that the plant cytokinin kinetin dramatically increases exon 20 inclusion in RNA isolated from cultured FD cells. The goal of the current study was to investigate the nature of the FD splicing defect and the mechanism by which kinetin improves exon inclusion, as such knowledge will facilitate the development of future therapeutics aimed at regulating mRNA splicing. In this study, we demonstrate that treatment of FD lymphoblast cell lines with kinetin increases IKBKAP mRNA and IKAP protein to normal levels. Using a series of minigene constructs, we show that deletion of a region at the end of IKBKAP exon 20 disrupts the ability of kinetin to improve exon inclusion, pinpointing a kinetin responsive sequence element. We next performed a screen of endogenously expressed genes with multiple isoforms resulting from exon skipping events and show that kinetin's ability to improve exon inclusion is not limited to IKBKAP. Lastly, we highlight the potential of kinetin for the treatment of other human splicing disorders by showing correction of a splicing defect in neurofibromatosis. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Inst Catala Oncol, Translat Res Lab, Barcelona, Spain. RP Slaugenhaupt, SA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN-5254, Boston, MA 02114 USA. EM slaugenhaupt@chgr.mgh.harvard.edu RI Ibrahim, El Cherif/K-3899-2016 OI Ibrahim, El Cherif/0000-0003-3973-7862 NR 50 TC 29 Z9 29 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD FEB PY 2007 VL 85 IS 2 BP 149 EP 161 DI 10.1007/s00109-006-0137-2 PG 13 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 137NS UT WOS:000244299900007 PM 17206408 ER PT J AU Banta, S Megeed, Z Casali, M Rege, K Yarmush, ML AF Banta, Scott Megeed, Zaki Casali, Monica Rege, Kaushal Yarmush, Martin L. TI Engineering protein and peptide building blocks for nanotechnology SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY LA English DT Review DE nanotechnology; protein engineering; proteins; peptides; molecular motors; transducers; biosensors ID ELASTIN-LIKE POLYPEPTIDE; TEMPERATURE-TRIGGERED PRECIPITATION; THERMALLY-RESPONSIVE POLYPEPTIDES; SELF-COMPLEMENTARY OLIGOPEPTIDE; INFLUENZA-VIRUS HEMAGGLUTININ; RESONANCE ENERGY-TRANSFER; CARBON NANOTUBES; DRUG-DELIVERY; QUANTUM DOTS; FLUORESCENT NANOSENSORS AB The tremendous diversity in the structure and function of proteins has stimulated intense interest in using them for nanotechnology applications. In this review, we discuss recent developments in the engineering of proteins and peptides for the design and construction of functional and structural elements of nanodevices. We begin with a short discussion highlighting the differences between chemical and biological synthesis of proteins and peptides. Subsequently, we review recent applications of proteins and peptides as molecular motors, transducers, biosensors, and structural elements of nanodevices. We supplement this review with highlights of our own work in the areas of peptide-based transducers for stand-alone and intra-molecular applications. This is followed by a short discussion of nanotechnology safety issues, and how proteins and peptides may enable the development of biocompatible nanomaterials. The future outlook for protein and peptide-based nanomaterials is then discussed, with an eye toward the significant impact of improved computational techniques on the field. C1 Massachusetts Gen Hosp, Ctr Engn Med, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Columbia Univ, Dept Chem Engn, New York, NY 10027 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Surg Serv, Boston, MA 02114 USA. NR 213 TC 32 Z9 32 U1 1 U2 26 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1533-4880 EI 1533-4899 J9 J NANOSCI NANOTECHNO JI J. Nanosci. Nanotechnol. PD FEB PY 2007 VL 7 IS 2 BP 387 EP 401 DI 10.1166/jnn.2007.153 PG 15 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 126LR UT WOS:000243514900001 PM 17450770 ER PT J AU Marci, CD Ham, J Moran, E Orr, SP AF Marci, Carl D. Ham, Jacob Moran, Erin Orr, Scott P. TI Physiologic correlates of perceived therapist empathy and social-emotional process during psychotherapy SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE psychotherapy; perceived empathy; skin conductivity; psychophysiology; neurobiology ID ELECTRODERMAL ACTIVITY; THERAPEUTIC ALLIANCE; FMRI; MECHANISMS; BRAIN; METAANALYSIS; NEUROSCIENCE; ACTIVATION; RESPONSES; HUMANS AB The present study was designed to investigate the relationship among physiologic concordance, patient-perceived therapist empathy, and social-emotional process during psychotherapy. Simultaneous measures of skin conductance (SC) were obtained from 20 unique and established patient-therapist dyads during a live therapy session followed by patient ratings of therapist empathy. Paired SC data of hypothetical dyads were used to test the reliability of the proposed measure of SC concordance. Observer microanalyses of social-emotional process were used to compare short segments of high versus low physiologic concordance. Results show a significant positive correlation (r = 0.47, p = 0.03) between SC concordance and patient ratings of perceived therapist empathy. Microanalyses suggest that during moments of high versus low SC concordance, there were significantly more positive social-emotional interactions for both patients and therapists (p = 0.01). The results support a biological model of perceived patient empathy and patient-therapist social-emotional process during psychotherapy. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mt Sinai Hosp, Dept Psychiat, New York, NY 10029 USA. Vet Affairs Med Ctr, Manchester, Lancs, England. RP Marci, CD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. FU NIMH NIH HHS [F32MH072073] NR 59 TC 67 Z9 68 U1 5 U2 26 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 FEB PY 2007 VL 195 IS 2 BP 103 EP 111 DI 10.1097/01.nmd.0000253731.71025.fc PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 138YD UT WOS:000244398300001 PM 17299296 ER PT J AU Manguno-Mire, G Sautter, F Lyons, J Myers, L Perry, D Sherman, M Glynn, S Sullivan, G AF Manguno-Mire, Gina Sautter, Frederic Lyons, Judith Myers, Leann Perry, Dana Sherman, Michelle Glynn, Shirley Sullivan, Greer TI Psychological distress and burden among female partners of combat veterans with PTSD SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE PTSD; psychological distress; marital relationships; partner burden; spouses; family factors ID POSTTRAUMATIC-STRESS-DISORDER; MALE VIETNAM VETERANS; EXPRESSED EMOTION; CAREGIVER BURDEN; SOCIAL SUPPORT; PSYCHOMETRIC PROPERTIES; MENTAL-ILLNESS; FAMILY BURDEN; FOLLOW-UP; PREDICTORS AB Psychological distress among cohabitating female partners of combat veterans with posttraumatic stress disorder (PTSD) was examined in a cross-sectional study using a modified version of the Health Belief Model. A convenience sample of 89 cohabitating female partners of male veterans in outpatient PTSD treatment was interviewed by telephone using a structured interview. Partners endorsed high levels of psychological distress with elevations on clinical scales at or exceeding the 90th percentile. Severe levels of overall psychological distress, depression, and suicidal ideation were prevalent among partners. Multivariate analyses revealed that perceived threat, recent mental health treatment, and level of involvement with veterans predicted global partner psychological distress. Partner burden was predicted by partner self-efficacy, perceived threat, barriers to mental health treatment, and partner treatment engagement. These findings are compelling since they demonstrate that partners of veterans with combat-related PTSD experience significant levels of emotional distress that warrant clinical attention. Psychological distress and partner burden were each associated with a unique combination of predictors, suggesting that although these constructs are related, they have distinct correlates and potentially different implications within the family environment. Future research should examine these constructs separately using causal modeling analyses to identify modifiable targets for interventions to reduce psychological distress among partners of individuals with PTSD. C1 Tulane Hlth Sci Ctr, Sch Med, Dept Psychiat & Neurol, New Orleans, LA 70112 USA. VA S Cent VISN 16, Mental Illness Res Educ & Clin Ctr, Little Rock, AR USA. GV Sonny Montgomery Vet Affairs Med Ctr, Jackson, MS USA. Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. Oklahoma City Vet Affairs Med Ctr, Oklahoma City, OK USA. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlth Care Syst W, Los Angeles, CA USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. RP Manguno-Mire, G (reprint author), Tulane Hlth Sci Ctr, Sch Med, Dept Psychiat & Neurol, 1440 Canal St TB-53, New Orleans, LA 70112 USA. NR 63 TC 53 Z9 53 U1 1 U2 12 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 FEB PY 2007 VL 195 IS 2 BP 144 EP 151 DI 10.1097/01.nmd.0000254755.53549.69 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 138YD UT WOS:000244398300008 PM 17299302 ER PT J AU Silove, D Manicavasagar, V Mollica, R Thai, M Khiek, D Lavelle, J Tor, S AF Silove, Derrick Manicavasagar, Vijaya Mollica, Richard Thai, Meng Khiek, Dorani Lavelle, James Tor, Svang TI Screening for depression and PTSD in a Cambodian population unaffected by war - Comparing the Hopkins Symptom Checklist and Harvard Trauma Questionnaire with the structured clinical interview SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Cambodians; PTSD; depression; trauma; screening ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; GENERAL-POPULATION; REFUGEES; TORTURE; IMPACT; DIAGNOSES; VALIDITY; ANXIETY; VERSION AB The Hopkins Symptom Checklist depression scale (HSCL-D) and the Harvard Trauma Questionnaire (HTQ) have been used extensively in international studies, particularly among refugees and conflict-affected populations. Like many other screening measures, however, the HSCL-D and HTQ have not been subjected to extensive epidemiologic testing, particularly among communities not affected by war. The present study examined the psychometric properties of the HSCL-D and HTQ by comparing the measures with the Structured Clinical Interview for DSM-IV (SCID) among ethnic Cambodians living in Surin, Thailand, a community that was spared the long period of mass violence that affected Cambodia proper. The PTSD data of the HTQ were then contrasted with those obtained from a refugee clinic. The main finding was that in the Surin study, the screening measures showed greater agreement with the SCID in identifying noncases (negative prediction) than cases (positive prediction). In contrast, in the earlier clinic study, the HTQ showed high positive and moderately low negative prediction. The results support previous observations that clinical interviews such as the SCID may be more conservative in identifying cases. We raise the possibility, however, that structured interviews may perform differently across clinic and community populations. In particular, clinicians may be more accurate in identifying cases than noncases in highly symptomatic clinic populations, with the converse applying in low prevalence community populations. These issues warrant further investigation to specify more clearly the value of using the two approaches to case identification. C1 Univ New S Wales, Sch Psychiat, Psychiat Res & Teaching Unit, Sydney, NSW 2107, Australia. Ctr Populat Mental Hlth Res, Sydney SW Area Hlth Serv, Sydney, NSW, Australia. Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. Massachusetts Gen Hosp, Harvard Program Refuge Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Serv Treatment & Rehabil Torture & Trauma Survivo, Sydney, NSW, Australia. Liverpool Fairfield Sexual Assault Serv, Sydney, NSW, Australia. RP Silove, D (reprint author), Univ New S Wales, Sch Psychiat, Psychiat Res & Teaching Unit, Sydney, NSW 2107, Australia. NR 30 TC 37 Z9 37 U1 2 U2 18 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 FEB PY 2007 VL 195 IS 2 BP 152 EP 157 DI 10.1097/01.nmd.0000254747.03333.70 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 138YD UT WOS:000244398300009 PM 17299303 ER PT J AU Iosifescu, DV Renshaw, PF Dougherty, DD Lyoo, IK Lee, HK Fraguas, R Cassano, P Nierenberg, AA Fava, M AF Iosifescu, Dan V. Renshaw, Perry F. Dougherty, Darin D. Lyoo, In Kyoon Lee, Ho Kyu Fraguas, Renerio Cassano, Paolo Nierenberg, Andrew A. Fava, Maurizio TI Major depressive disorder with anger attacks and subcortical MRI white matter hyperintensities SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article; Proceedings Paper CT 157th Annual Meeting of the American-Psychiatric-Association CY MAY 01-06, 2004 CL New York, NY SP Amer Psychiat Assoc DE major depressive disorder; anger attacks; white matter lesions ID RISK-FACTORS; CAROTID ATHEROSCLEROSIS; POSTMENOPAUSAL WOMEN; ATYPICAL DEPRESSION; YOUNG-ADULTS; HOSTILITY; OUTPATIENTS; FLUOXETINE; LESIONS; BRAIN AB Previous reports of increased rates of cardiovascular risk factors in major depressive disorder (MDD) with anger attacks led the authors to hypothesize that MDD with anger attacks may be associated with brain vascular changes (magnetic resonance imaging white matter hyperintensities [WMHs]). Sixty-five subjects meeting DSM-III-R criteria for major depressive disorder were administered brain magnetic resonance imaging scans at 1.5T to detect T2 WMH. The severity of brain WMH was classified with the Fazekas scale. We used standardized scales to assess melancholic MDD, atypical MDD, and MDD with anger attacks. In logistic regression analyses, MDD with anger attacks, was associated with higher severity of subcortical WMH and of total WMH, but not with periventricular WMH. Atypical and melancholic MDD subtypes were not significantly associated with brain WMH. In conclusion, subcortical brain vascular lesions may be more prevalent or severe in MDD with anger attacks. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, Boston, MA USA. Sungkyunkwan Univ, Dept Radiol, Seoul, South Korea. RP Iosifescu, DV (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Suite 401, Boston, MA 02114 USA. RI Cassano, Paolo/I-6959-2012 FU NIMH NIH HHS [R01-MH48483, K23 MH 067111, R01- MH58681] NR 33 TC 17 Z9 17 U1 2 U2 5 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 FEB PY 2007 VL 195 IS 2 BP 175 EP 178 DI 10.1097/01.nmd.0000253820.69362.87 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 138YD UT WOS:000244398300013 PM 17299307 ER PT J AU Groves, MD Puduvalli, VK Chang, SM Conrad, CA Gilbert, MR Tremont-Lukats, IW Liu, TJ Peterson, P Schiff, D Cloughesy, TF Wen, PY Greenberg, H Abrey, LE DeAngelis, LM Hess, KR Lamborn, KR Prados, MD Yung, WKA AF Groves, Morris D. Puduvalli, Vinay K. Chang, Susan M. Conrad, Charles A. Gilbert, Mark R. Tremont-Lukats, Ivo W. Liu, Ta-Jen Peterson, Pamela Schiff, David Cloughesy, Timothy F. Wen, Patrick Y. Greenberg, Harry Abrey, Lauren E. DeAngelis, Lisa M. Hess, Kenneth R. Lamborn, Kathleen R. Prados, Michael D. Yung, W. K. Alfred TI A North American brain tumor consortium (NABTC 99-04) phase II trial of temozolomide plus thalidomide for recurrent glioblastoma multiforme SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE glioblastoma multiforme; clinical trial; controlled; temozolomide; thalidomide; angiogenesis inhibitors; vascular endothelial growth factor; basic fibroblast growth factor; interleukin 8 ID FIBROBLAST-GROWTH-FACTOR; RADIATION-THERAPY; ANGIOGENESIS; GLIOMAS; CHEMOTHERAPY; METAANALYSIS; PROCARBAZINE; EXPRESSION; AGENT AB Background Laboratory and clinical data suggest that the anti-angiogenic agent, thalidomide, if combined with cytotoxic agents, may be effective against recurrent glioblastoma multiforme (GBM). Objectives: To determine 6-month progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in adults with recurrent GBM. Patients and methods Eligible patients had recurrent GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was given at 150 200 mg/m(2)/day on days 1 - 5 of each 28-day cycle. Thalidomide was given orally at 400 mg at bedtime ( days 1 - 28) and increased to 1,200 mg as tolerated. Patients were evaluated with magnetic resonance imaging scans every 56 days. The study was designed to detect an increase of the historical 6PFS for GBM from 10 to 30%. Results Forty-four patients were enrolled, 43 were evaluable for efficacy and safety. The study population included 15 women, 29 men; median age was 53 years ( range 32 - 84); median Karnofsky performance status was 80% ( range 60 - 100%). Thirty-six (82%) patients were chemotherapy-naive. There were 57 reports of toxicity of grade 3 or greater. Non-fatal grade 3 - 4 granulocytopenia occurred in 15 patients (34%). The objective response rate was 7%. The estimated probability of being progression-free at 6 months with this therapy is 24% [95% confidence interval ( C. I.) 12 - 38%]. The median time to progression is 15 weeks ( 95% C. I. 10 - 20 weeks). There was no observed correlation between serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and the 6PFS outcome. Conclusion This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone. C1 Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Groves, MD (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, 1400 Holcombe,431, Houston, TX 77030 USA. EM mgroves@mdanderson.org RI Puduvalli, Vinay/A-2411-2016; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU NCI NIH HHS [CA62422, CA16672, CA62399, CA62412, U01CA62405, U01CA62407]; NCRR NIH HHS [M01-RR00042, M01-RR00056, M01-RR00079, M01-RR0865] NR 34 TC 46 Z9 49 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 FEB PY 2007 VL 81 IS 3 BP 271 EP 277 DI 10.1007/s11060-006-9225-y PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 127WJ UT WOS:000243616700008 PM 17031561 ER PT J AU Spires, TL Hannan, AJ AF Spires, Tara L. Hannan, Anthony J. TI Molecular mechanisms mediating pathological plasticity in Huntington's disease and Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE adult neurogenesis; Alzheimer's; Huntington's; protein aggregation; synaptic plasticity ID TRANSGENIC MOUSE MODEL; AMYLOID-BETA-PROTEIN; HIPPOCAMPAL CELL-PROLIFERATION; DEPENDENT CORTICAL PLASTICITY; GENE-ENVIRONMENT INTERACTIONS; AGE-OF-ONSET; NEUROFIBRILLARY TANGLES; IN-VIVO; NEURONAL LOSS; SYNAPTIC PLASTICITY AB Neurodegenerative diseases such as Huntington's disease and Alzheimer's disease, although very different in etiology, share common degenerative processes. These include neuronal dysfunction, decreased neural connectivity, and disruption of cellular plasticity. Understanding the molecular mechanisms underlying the neural plasticity deficits in these devastating conditions may lead the way toward new therapeutic targets, both disease-specific and more generalized, which can ameliorate degenerative cognitive deficits. Furthermore, investigations of 'pathological plasticity' in these diseases lend insight into normal brain function. This review will present evidence for altered plasticity in Huntington's and Alzheimer's diseases, relate these findings to symptomatology, and review possible causes and commonalities. C1 Univ Melbourne, Howard Florey Inst, Parkville, Vic 3010, Australia. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Hannan, AJ (reprint author), Univ Melbourne, Howard Florey Inst, Parkville, Vic 3010, Australia. EM ajh@hfi.unimelb.edu.au OI Spires-Jones, Tara/0000-0003-2530-0598 FU NIA NIH HHS [AG00277] NR 126 TC 18 Z9 19 U1 3 U2 6 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 FEB PY 2007 VL 100 IS 4 BP 874 EP 882 DI 10.1111/j.1471-4159.2006.04275.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 132KH UT WOS:000243941200003 PM 17217424 ER PT J AU Nakazawa, T Takahashi, H Nishijima, K Shimura, M Fuse, N Tamai, M Hafezi-Moghadam, A Nishida, K AF Nakazawa, Toru Takahashi, Hidetoshi Nishijima, Kazuaki Shimura, Masahiko Fuse, Nobuo Tamai, Makoto Hafezi-Moghadam, Ali Nishida, Kohji TI Pitavastatin prevents NMDA-induced retinal ganglion cell death by suppressing leukocyte recruitment SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cluster of differentiation 18; excitotoxicity; leukocyte recruitment; retina; statin ID ISCHEMIA-REPERFUSION INJURY; TRANSIENT CEREBRAL-ISCHEMIA; COA REDUCTASE INHIBITOR; NITRIC-OXIDE SYNTHASE; METHYL-D-ASPARTATE; RAT RETINA; DIABETIC-RETINOPATHY; AXON REGENERATION; CORTICAL-NEURONS; GENE-EXPRESSION AB Excitotoxicity is a major cause of retinal ganglion cell (RGC) death during ischemic diseases such as vessel occlusion and diabetic retinopathy. However, the underlying mechanisms are not well understood. Statins, inhibitors of the HMG-CoA reductase, have neuroprotective effects in addition to their original role in lowering cholesterol. We hypothesize that pitavastatin, a recently introduced potent statin, is protective against N-methyl-D-aspartic acid (NMDA)-induced RGC death. Pitavastatin, administered by gavage, abolished NMDA-induced loss of RGCs. To elucidate the mechanisms underlying the neuroprotective effect of pitavastatin, we investigated its impact on inflammation. NMDA increased the expression of interleukin-1 beta and TNF-alpha, and endothelial adhesion molecules, including ICAM-1, and induced leukocyte accumulation in the retinal vessels. Pitavastatin significantly reduced NMDA-induced leukocyte accumulation and upregulation of endothelial adhesion molecules, whereas cytokine expression was unaffected. Systemic blockade of ICAM-1 in wild-type mice or absence of CD18 in gene-deficient (CD18(-/-)) mice significantly suppressed NMDA-induced leukocyte accumulation and RGC death. These findings suggest a novel and causative role for inflammatory leukocyte recruit-ment in NMDA-induced excitotoxicity. Furthermore, we show the novel neuroprotective effect of statins against excitotoxicity-induced RGC death. Statins or other anti-inflammatory agents may thus have therapeutic benefits in excitotoxicity- associated neuronal diseases through blockade of leukocyte recruitment. C1 Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Aoba Ku, Sendai, Miyagi 9808574, Japan. NTT E Japan Tohoku Hosp, Wakabayashi, Miyagi, Japan. Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Shogoin, Kyoto, Japan. Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Nakazawa, T (reprint author), Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Aoba Ku, 1-1 Seiryo, Sendai, Miyagi 9808574, Japan. EM ntoru@fa2.so-net.ne.jp OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 NR 61 TC 52 Z9 56 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2007 VL 100 IS 4 BP 1018 EP 1031 DI 10.1111/j.1471-4159.2006.04274.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 132KH UT WOS:000243941200015 PM 17266736 ER PT J AU Merabet, LB Swisher, JD McMains, SA Halko, MA Amedi, A Pascual-Leone, A Somers, DC AF Merabet, Lotfi B. Swisher, Jascha D. McMains, Stephanie A. Halko, Mark A. Amedi, Amir Pascual-Leone, Alvaro Somers, David C. TI Combined activation and deactivation of visual cortex during tactile sensory processing SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VENTRAL OCCIPITAL CORTEX; TERM LIGHT DEPRIVATION; SURFACE-BASED ANALYSIS; HUMAN BRAIN; FUNCTIONAL MRI; CORTICAL SURFACE; BLIND HUMANS; MULTISENSORY CONVERGENCE; SIGHTED INDIVIDUALS; COORDINATE SYSTEM AB The involvement of occipital cortex in sensory processing is not restricted solely to the visual modality. Tactile processing has been shown to modulate higher-order visual and multisensory integration areas in sighted as well as visually deprived subjects; however, the extent of involvement of early visual cortical areas remains unclear. To investigate this issue, we employed functional magnetic resonance imaging in normally sighted, briefly blindfolded subjects with well-defined visuotopic borders as they tactually explored and rated raised-dot patterns. Tactile task performance resulted in significant activation in primary visual cortex (V1) and deactivation of extrastriate cortical regions V2, V3, V3A, and hV4 with greater deactivation in dorsal subregions and higher visual areas. These results suggest that tactile processing affects occipital cortex via two distinct pathways: a suppressive top-down pathway descending through the visual cortical hierarchy and an excitatory pathway arising from outside the visual cortical hierarchy that drives area V1 directly. C1 Boston Univ, Perceptual Neuroimaging Lab, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Program Neurosci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med,Ctr Noninvas Brain Stimulat, Boston, MA 02115 USA. RP Merabet, LB (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 330 Brookline Ave,KS 430, Boston, MA 02215 USA. EM lmerabet@bidmc.harvard.edu RI Somers, David/G-5802-2010; Halko, Mark/G-8633-2016; OI Halko, Mark/0000-0002-7427-0789; Somers, David/0000-0002-4169-5895 FU NCRR NIH HHS [K24 RR 018875]; NEI NIH HHS [K23 EY 016131-01, R01 EY 12091] NR 69 TC 60 Z9 61 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2007 VL 97 IS 2 BP 1633 EP 1641 DI 10.1152/jn.00806.2006 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 134NQ UT WOS:000244090500061 PM 17135476 ER PT J AU Wooltorton, JRA Gaboyard, S Hurley, KM Price, SD Garcia, JL Zhong, M Lysakowski, A Eatock, RA AF Wooltorton, Julian R. A. Gaboyard, Sophie Hurley, Karen M. Price, Steven D. Garcia, Jasmine L. Zhong, Meng Lysakowski, Anna Eatock, Ruth Anne TI Developmental changes in two voltage-dependent sodium currents in utricular hair cells SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ROOT GANGLION NEURONS; RODENT VESTIBULAR PERIPHERY; CHANNEL ALPHA-SUBUNITS; DEVELOPING RAT UTRICLE; CARDIAC NA CHANNELS; FUNCTIONAL-ANALYSIS; SENSORY NEURONS; IONIC CURRENTS; MOUSE UTRICLE; INNER-EAR AB Two kinds of sodium current (I-Na) have been separately reported in hair cells of the immature rodent utricle, a vestibular organ. We show that rat utricular hair cells express one or the other current depending on age (between postnatal days 0 and 22, P0-P22), hair cell type (I, II, or immature), and epithelial zone (striola vs. extrastriola). The properties of these two currents, or a mix, can account for descriptions of INa in hair cells from other reports. The patterns of Na channel expression during development suggest a role in establishing the distinct synapses of vestibular hair cells of different type and epithelial zone. All type I hair cells expressed I-Na,I- 1, a TTX-insensitive current with a very negative voltage range of inactivation (midpoint: -94 mV). I-Na,I- 2 was TTX sensitive and had less negative voltage ranges of activation and inactivation (inactivation midpoint: similar to 72 mV). I-Na,I- 1 dominated in the striola at all ages, but current density fell by two- thirds after the first postnatal week. I (Na, 2) was expressed by 60% of hair cells in the extrastriola in the first week, then disappeared. In the third week, all type I cells and about half of type II cells had I-Na,I- 1; the remaining cells lacked sodium current. I (Na, 1) is probably carried by Na(V)1.5 subunits based on biophysical and pharmacological properties, mRNA expression, and immunoreactivity. Na(V)1.5 was also localized to calyx endings on type I hair cells. Several TTX- sensitive subunits are candidates for I (Na, 2). C1 Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Baylor Coll Med, Bobby R Alford Dept Otorhinolaryngol Head & Neck, Houston, TX 77030 USA. Univ Illinois, Coll Med, Dept Anat & Cell Biol, Chicago, IL USA. RP Eatock, RA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM eatock@meei.harvard.edu RI Lysakowski, Anna/F-9534-2010; yu, yan/C-2322-2012; Eatock, Ruth/F-6404-2013; OI Lysakowski, Anna/0000-0001-6259-0294; Eatock, Ruth Anne/0000-0001-7547-2051; Wooltorton, Julian/0000-0003-0778-0196; Gaboyard-Niay, Sophie/0000-0001-8256-8692 FU NIDCD NIH HHS [R01 DC002290, DC 02290] NR 108 TC 32 Z9 32 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2007 VL 97 IS 2 BP 1684 EP 1704 DI 10.1152/jn.00649.2006 PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 134NQ UT WOS:000244090500066 PM 17065252 ER PT J AU Darrow, KN Maison, SF Liberman, MC AF Darrow, Keith N. Maison, Stephane F. Liberman, M. Charles TI Selective removal of lateral olivocochlear efferents increases vulnerability to acute acoustic injury SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GUINEA-PIG COCHLEA; INDUCED HEARING-LOSS; NICOTINIC ACETYLCHOLINE-RECEPTORS; AUDITORY-NERVE ACTIVITY; HAIR CELL AFFERENTS; MIDDLE-EAR MUSCLES; BRAIN-STEM; SUPERIOR OLIVE; ELECTRICAL-STIMULATION; INFERIOR COLLICULUS AB Cochlear sensory cells and neurons receive efferent feedback from the olivocochlear (OC) system. The myelinated medial component of the OC system and its effects on outer hair cells (OHCs) have been implicated in protection from acoustic injury. The unmyelinated lateral (L) OC fibers target ipsilateral cochlear nerve dendrites and pharmacological studies suggest the LOC's dopaminergic component may protect these dendrites from excitotoxic effects of acoustic overexposure. Here, we explore LOC function in vivo by selective stereotaxic destruction of LOC cell bodies in mouse. Lesion success in removing the LOC, and sparing the medial (M) OC, was assessed by histological analysis of brain stem sections and cochlear whole mounts. Auditory brain stem responses (ABRs), a neural-based metric, and distortion product otoacoustic emissions (DPOAEs), an OHC-based metric, were measured in control and surgical mice. In cases where the LOC was at least partially destroyed, there were increases in suprathreshold neural responses that were frequency- and level-independent and not attributable to OHC-based effects. These interaural response asymmetries were not found in controls or in cases where the lesion missed the LOC. In LOC-lesion cases, after exposure to a traumatic stimulus, temporary threshold shifts were greater in the ipsilateral ear, but only when measured in the neural response; OHC-based measurements were always bilaterally symmetric, suggesting OHC vulnerability was unaffected. Interaural asymmetries in threshold shift were not found in either unlesioned controls or in cases that missed the LOC. These findings suggest that the LOC modulates cochlear nerve excitability and protects the cochlea from neural damage in acute acoustic injury. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Harvard Univ, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA USA. MIT, Cambridge, MA USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Charles_Liberman@meei.harvard.edu FU NIDCD NIH HHS [R01 DC 00188, P30 DC 05209, P30 DC005209, R01 DC000188, T32 DC 0038, T32 DC000038] NR 55 TC 53 Z9 54 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 2007 VL 97 IS 2 BP 1775 EP 1785 DI 10.1152/jn.00955.2006 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 134NQ UT WOS:000244090500071 PM 17093118 ER PT J AU Halpern, LR Dodson, TB AF Halpern, Leslie R. Dodson, Thomas B. TI Does prophylactic administration of systemic antibiotics prevent postoperative inflammatory complications after third molar surgery? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MAXILLOFACIAL SURGEONS; ALVEOLAR OSTEITIS; HEALTH-POLICY; DRY SOCKET; NECESSITY; 3RD-MOLAR; OUTCOMES; OPINION; TRIALS; RISK AB Purpose: To estimate and compare the frequencies of inflammatory complications after third molar (M3) surgery in subjects receiving intravenous prophylactic antibiotics or saline placebo. Materials and Methods: Using a placebo-controlled, double-blind, randomized clinical trial, the investigators enrolled a sample composed of subjects who required extraction of at least 1 impacted M3 and requested intravenous sedation or general anesthesia. The predictor variable was treatment group classified as active treatment (penicillin or clindamycin for penicillin-allergic subjects) or placebo (0.9% saline). Study medications were randomly assigned. Both surgeon and subject were blinded to treatment assignment. The medication was administered intravenously prior to any incision. The outcome variable was postoperative inflammatory complication classified as present or absent and included alveolar osteitis (AO) or surgical site infection (SSI). Other variables were demographic, anatomic, or operative. Descriptive and bivariate statistics were computed. Statistical significance was set at P <=.05, single-tailed test of hypothesis. Results: The sample was composed of 118 subjects (n = 59 per study group). In the active treatment group, there were no postoperative inflammatory complications. In the, placebo group, 5 subjects (8.5%) were diagnosed with SSI, (P =.03). No subject met the case definition for AO. All SSIs were associated with the removal of partial bony or full bony impacted mandibular M3s. Conclusion: In the setting of third molar removal, these results suggest that the use of intravenous antibiotics administered prophylactically decrease the frequency of SSIs. The authors cannot comment on the efficacy of intravenous antibiotics in comparison to other antibacterial treatment regimens, eg chlorhexidine mouthrinse or intrasocket antibiotics. (C) 2007 American. Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Halpern, LR (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM lhalpern1@partners.org NR 27 TC 37 Z9 40 U1 1 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD FEB PY 2007 VL 65 IS 2 BP 177 EP 185 DI 10.1016/j.joms.2006.10.016 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 133LH UT WOS:000244013900004 PM 17236918 ER PT J AU Soong, M Ring, D AF Soong, Maximillian Ring, David TI Ulnar nerve palsy associated with fracture of the distal radius SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE distal radius fracture; ulnar nerve injury ID COLLES FRACTURES; INJURY; CLASSIFICATION; COMPLICATIONS; SECONDARY AB Objective: To describe the clinical features and outcome of a series of patients with complete motor and sensory ulnar nerve palsy associated with a fracture of the distal radius. Design: Retrospective case series. Setting: Level I trauma center. Patients/Participants: Five adults with acute complete motor and sensory ulnar nerve palsy associated with fracture of the distal radius were treated during a 2 year period. There were 3 men and 2 women, with an average age of 42 years (range, 33 to 56 years). All 5 distal radius fractures were high energy and widely displaced. Three patients had an associated ulna fracture (2 styloid, I styloid and distal diaphysis), and I had a complete triangular fibrocartilage complex (TFCC) avulsion from the distal ulna (associated with an open wound). Two patients had open fractures. Intervention: Open reduction and internal fixation of the distal radius fracture in 4 patients and external fixation in I patient. Three patients had exploration and release of the ulnar nerve because it was associated with an acute carpal tunnel syndrome. Main Outcome Measurements: Recovery of ulnar nerve function. Results: At an average follow-up of 17 months, 4 patients had complete or near-complete recovery of ulnar nerve function. One patient had moderate motor and mild sensory dysfunction. Conclusions: Acute ulnar nerve palsy may occur in association with high-energy, widely displaced fractures of the distal radius. These are usually neurapraxic injuries that recover to normal or near-normal strength and sensation. We recommend exploration and release of a complete ulnar nerve palsy associated with a fracture of the distal radius fracture when there is an open wound or an acute carpal tunnel syndrome, and observation without exploration otherwise. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 32 Fruit St,Yawkey 2, Boston, MA 02114 USA. EM dring@partners.org NR 25 TC 5 Z9 10 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 FEB PY 2007 VL 21 IS 2 BP 113 EP 116 DI 10.1097/BOT.0b013e31802f7335 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 135OO UT WOS:000244163100007 PM 17304066 ER PT J AU Rodriguez, KL Barnato, AE Arnold, RM AF Rodriguez, Keri L. Barnato, Amber E. Arnold, Robert M. TI Perceptions and utilization of palliative care services in acute care hospitals SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE; MECHANICAL VENTILATION; DECISION-MAKING; TEAMS IMPROVE; END; DISEASE; DEATH; DOCTORS; CANCER; NEEDS AB Objective: To understand perceptions of palliative care in acute care hospitals and identify barriers to earlier use of palliative care in the illness trajectory. Methods: In Pennsylvania hospitals, we completed semistructured interviews with 131 providers involved in decision making or discharge planning. We used qualitative methods to analyze transcripts. Results: Most interviewees characterized palliative care as end-of-life or hospice care that is initiated after the decision to limit curative treatment is made. Few recognized the role of palliative care in managing symptoms and addressing psychosocial needs of patients with chronic illnesses other than cancer. Interviewees viewed earlier and broader palliative care consultations less in terms of clinical benefits than in terms of cost savings accrued from shorter terminal hospitalizations. In general, they thought nurses were most likely to facilitate these consultations, surgeons were most likely to resist them, and intensive care specialists were most likely to view palliative care as within their own scope of practice. Suggestions for broadening palliative care utilization included providing education and training, improving financial reimbursement and sustainability for palliative care, and fostering a hospital culture that turns to high-intensity care only if it meets individual needs and goals of chronically ill patients. Conclusions: In acute care hospitals, palliative care is primarily perceived as a means to limit life-sustaining treatment or allow death. Moving consultation earlier in the hospitalization of "dying" patients is a greater preoccupation than increasing palliative service use earlier in the illness trajectory. Any move short of far upstream will require palliative care specialists to market benefits to patients and referring providers in ways that emphasize compatibility with parallel treatment plans and do not threaten provider autonomy. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Family Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA. Univ Pittsburgh, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. Univ Pittsburgh, Inst Entrance Palliat Care, Pittsburgh, PA USA. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Family Equity Res & Promot, Univ Dr C 151C-U,Bldg 28,Room 1A129, Pittsburgh, PA 15240 USA. EM keri.rodriguez@med.va.gov FU NCATS NIH HHS [UL1 TR000005]; NIA NIH HHS [AG 21921, P01 AG019783, P01 AG019783-07, AG 19783, K08 AG021921] NR 53 TC 52 Z9 52 U1 3 U2 10 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 FEB PY 2007 VL 10 IS 1 BP 99 EP 110 DI 10.1089/jpm.2006.0155 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 135DU UT WOS:000244135100018 PM 17298258 ER PT J AU Cherlin, EJ Barry, CL Prigerson, HG Schulman-Green, D Johnson-Hurzeler, R Kasl, SV Bradley, EH AF Cherlin, Emily J. Barry, Colleen L. Prigerson, Holly G. Schulman-Green, Dena Johnson-Hurzeler, Rosemary Kasl, Stanislav V. Bradley, Elizabeth H. TI Bereavement services for family caregivers: How often used, why, and why not SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Gerontological-Society-of-America CY NOV, 2005 CL Orlando, FL SP Gerontol Soc Amer ID PSYCHIATRIC-DISORDERS; COMPLICATED GRIEF; ADVANCED CANCER; SUPPORT GROUPS; OLDER-ADULTS; HEALTH; SCALE; INTERVENTION; DEPRESSION; WIDOWHOOD AB Background: Bereavement services are central to high-quality end-of-life care, however, little is known about how frequently and why such bereavement services are used and not used. We examined family caregiver reports about how often they used bereavement services, predictors of their use, and reported reasons for not using bereavement services. Methods: Prospective cohort study of family caregivers (n = 161) of patients with cancer enrolled with hospice between October 1999 and September 2001. We conducted bivariate and multivariable analyses to determine predictors of bereavement service use, adjusted for a broad range of factors including caregiving experiences, major depressive disorder (MDD), relationship with the deceased, and demographic factors. We used content analysis to summarize responses to open-ended questions concerning why individuals did not use bereavement services. Results: We found that approximately 30% of family caregivers used bereavement services in the year postloss, and the majority of these caregivers used services in the first 6 months postloss. Even among bereaved caregivers with MDD, less than half (47.6%) used bereavement services. Factors associated with using bereavement services included being a spouse caregiver, younger age, having MDD at study enrollment, witnessing highly distressing events pertaining to the patient's death, having assisted the patient with more Instrumental Activities of Daily Living (IADLs) prior to the patient's death, having greater availability of instrumental support for oneself, and physician communication with the caregiver about the patient's prognosis before the patient's death. The most common given reason for nonuse was the perception that bereavement services were not needed or would not help. Conclusion: Addressing caregiver receptivity to bereavement services will be an important aspect of increasing appropriate use of such services. Future studies might examine specific interventions for reducing barriers and increasing receptivity to bereavement service use. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Yale Univ, Sch Nursing, New Haven, CT 06536 USA. Connecticut Hospice, Branford, CT USA. John D Thompson Hospice Inst Educ Training & Res, Branford, CT USA. Yale Univ, Sch Med, Dept Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. RP Bradley, EH (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. EM Elizabeth.Bradley@yale.edu FU NCI NIH HHS [CA 106370, R01 CA106370]; NIA NIH HHS [P30 AG 21342]; NIMH NIH HHS [MH 63892] NR 39 TC 43 Z9 43 U1 3 U2 10 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 FEB PY 2007 VL 10 IS 1 BP 148 EP 158 DI 10.1089/jpm.2006.0108 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 135DU UT WOS:000244135100023 PM 17298263 ER PT J AU Marr, L Billings, JA Weissman, DE AF Marr, Lisa Billings, J. Andrew Weissman, David E. TI Spirituality training for palliative care fellows SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID MEDICAL-STUDENTS ATTITUDES; INTEGRATING SPIRITUALITY; SCHOOL; HUMANITIES; CURRICULUM; EDUCATION; EXPOSURE; PROGRAM; EMPATHY AB Introduction: Spirituality is a major domain of palliative medicine training. No data exist on how it is taught, nor is there a consensus about the content or methods of such education. We surveyed palliative medicine fellowship directors in the United States to learn how they teach spirituality, who does the teaching, and what they teach. Methods: A, PubMed (www.pubmed.gov)) search using the terms "spirituality" and "medical education" was completed. Thirty-two articles outlined spirituality education content and methods in in medical schools and residency programs. From these articles, a survey on spirituality education in palliative medicine fellowship training was prepared, pilot-tested, revised, and then distributed by e-mail in June 2004 to the 48 U.S. palliative medicine fellowship directors listed on the American Board of Hospice and Palliative Medicine (AAHPM) website, but excluding the three fellowship programs represented by the authors. Follow up requests were sent by email twice during the 6-week collection period. The Institutional Review Board at the Medical College of Wisconsin approved the study. Results: Fourteen fellowship directors completed the survey (29% of all programs; 42% of those currently teaching fellows as indicated on the AAHPM website). All programs indicated they taught "spirituality"; 12 of 14 had separate programs for teaching spirituality and 2 of 14 reported they taught spirituality to their fellows but not as a distinct, separate program. All respondents taught the definitions of spirituality and religion, common spiritual issues faced by patients at end of life (which was not defined further), and the role of chaplains and clergy. Chaplains provided spirituality education in all of the responding programs, but other team members were frequently involved. The most common formats for education in the domains of knowledge and attitudes were small group discussion, lecture, and self-study. Small group discussion, supervision, and shadowing a chaplain or other professional were the most common methods used for skills. Faculty written or oral evaluations of fellows were the most common forms of evaluation, with little evidence of more robust assessment methods, such as structured role-play (none of the programs surveyed). Conclusions: Palliative medicine fellowship programs generally agree on the content of training on spirituality, but have not incorporated robust educational and evaluation methods to ensure that fellows have obtained the desired attitudes, knowledge, and skills to meet the Initial Voluntary Program Standards for Residency Education in Palliative Medicine of the American Board of Hospice and Palliative Medicine. Based on the survey data and results from the literature review, broad recommendations are made to enhance spirituality education. C1 Med Coll Wisconsin, Dept Palliat Med, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Dept Palliat Med, Boston, MA 02114 USA. Med Coll Wisconsin, Palliat Care Ctr, Div Neoplast Dis & Related Disorders, Milwaukee, WI 53226 USA. RP Marr, L (reprint author), Med Coll Wisconsin, Dept Palliat Med, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM lmarr@mcw.edu NR 43 TC 15 Z9 16 U1 0 U2 3 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 FEB PY 2007 VL 10 IS 1 BP 169 EP 177 DI 10.1089/jpm.2006.0076.R1 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 135DU UT WOS:000244135100025 PM 17298265 ER PT J AU Fanjiang, G Guelrud, M Gupta, M Dayal, Y Katz, AJ AF Fanjiang, Gary Guelrud, Moises Gupta, Mamta Dayal, Yogeshwar Katz, Aubrey J. TI Intraductal papillary-mucinous neoplasm of the pancreas in a 14-year-old SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID DUCTAL ECTASIA; CLINICOPATHOLOGICAL FEATURES; ENDOSCOPIC ULTRASONOGRAPHY; TUMOR; MALIGNANCY; ENTITY C1 Massachusetts Gen Hosp Children, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Dept Gastroenterol, Boston, MA 02111 USA. Tufts Univ, Dept Pathol, Dept Gastroenterol, Boston, MA 02111 USA. RP Fanjiang, G (reprint author), Massachusetts Gen Hosp, 55 Fruit St,VBK 107, Boston, MA 02114 USA. EM gfanjiang@partners.org NR 30 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 2007 VL 44 IS 2 BP 287 EP 290 DI 10.1097/01.mpg.0000239991.35517.f6 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 131EU UT WOS:000243851900025 PM 17255848 ER PT J AU Nareika, A Maldonado, A He, L Game, BA Slate, EH Sanders, JJ London, SD Lopes-Virella, MF Huang, Y AF Nareika, A. Maldonado, A. He, L. Game, B. A. Slate, E. H. Sanders, J. J. London, S. D. Lopes-Virella, M. F. Huang, Y. TI High glucose-boosted inflammatory responses to lipopolysaccharide are suppressed by statin SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE diabetes mellitus; glucose; lipopolysaccharide; periodontal diseases ID TUMOR-NECROSIS-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; C-REACTIVE PROTEIN; DIABETIC-PATIENTS; GENE-EXPRESSION; FACTOR-ALPHA; ATORVASTATIN; DISEASE; INTERLEUKIN-1; MACROPHAGES AB Background and Objective: It has been established that periodontal diseases are more prevalent and of greater severity in diabetic patients than in nondiabetic patients. Recent studies have underscored the role of monocytes and macrophages in periodontal tissue inflammation and destruction in diabetic patients. Although it has been shown that monocytes isolated from diabetic patients produce more inflammatory cytokines and that gingival crevicular fluid collected from diabetic patients contains higher levels of inflammatory cytokines than that obtained from nondiabetic patients, the underlying mechanisms are not well understood. Material and Methods: U937 histiocytes cultured in medium containing either normal (5 mM) or high (25 mM) glucose were treated with 100 ng/ml of lipopolysaccharide for 24h. After the treatment, cytokines in the medium and cytokine mRNA in the cells were quantified using enzyme-linked immunosorbet assay and real-time polymerase chain reaction, respectively. Results: In this study, we demonstrated that the pre-exposure of U937 histiocytes to high glucose concentrations markedly increased the lipopolysaccharide-induced secretion of pro-inflammatory cytokines and chemokines and the cellular inducible nitric oxide level compared with pre-exposure to normal glucose. Our data also showed that the increased secretion of cytokines was a result of increased mRNA expression. Furthermore, the effects of statin and peroxisome proliferators-activated receptor agonists on high glucose-enhanced secretion of cytokines were determined. The results showed that simvastatin, but not fenofibrate or pioglitazone, inhibited high glucose-enhanced cytokine release. Conclusion: This study has shown that high glucose concentrations and lipopolysaccharide act synergistically to stimulate the secretion of inflammatory mediators, and that statin is capable of suppressing the high glucose-boosted proinflammatory response. This study therefore delineates a novel mechanism by which hyperglycemia enhances the inflammatory responses of macrophages and suggests that statin may be useful in the treatment of periodontal disease in diabetic patients. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29403 USA. Med Univ S Carolina, Coll Dent Med, Charleston, SC 29403 USA. Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU NIDCR NIH HHS [DE16353] NR 32 TC 17 Z9 19 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD FEB PY 2007 VL 42 IS 1 BP 31 EP 38 DI 10.1111/j.1600-0765.2006.00911.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 122PY UT WOS:000243240100005 PM 17214637 ER PT J AU Moore, PA Doll, B Delie, RA Hersh, EV Korostoff, J Johnson, S Goodson, JM Halem, S Palys, M Leonel, JS Kozlowski, VA Peterson, C Hutcheson, M AF Moore, Paul A. Doll, Bruce Delie, Robert A. Hersh, Elliot V. Korostoff, Jonathan Johnson, Sharon Goodson, J. Max Halem, Stephen Palys, Michael Leonel, Juliana S. Kozlowski, Vitoldo A. Peterson, Carrie Hutcheson, Matthew TI Hemostatic and anesthetic efficacy of 4% articaine HCl with 1 : 200,000 epinephrine and 4% articaine HCl with 1 : 100,000 epinephrine when administered intraorally for periodontal surgery SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE articaine; blood loss; epinephrine; hemostasis; surgery ID VASOCONSTRICTORS; BLOOD AB Background: The objective of this double-masked, randomized, multicenter crossover study was to compare the efficacy of 4% articaine HCl with 1: 100,000 epinephrine (A100) to 4% articaine HCl with 1:200,000 epinephrine (A200) for providing effective local anesthesia and hemostasis for periodontal surgery. Methods: Anesthetic efficacy was based on patient self-report and lack of need for reinjection during the surgical procedures. Hemostatic properties of the formulations were compared using ratings of the surgeons' ability to visualize the surgical field and expectation for bleeding. The volume of blood collected during each surgical session also was measured and compared. Results: Forty-two adult subjects (26 males and 16 females, mean age 46.3 +/- 9.7 years) diagnosed with moderate to severe periodontal disease requiring local anesthesia for matched bilateral periodontal surgery were enrolled and completed the study. Subjects reported satisfactory surgical anesthesia following the A 100 and A200 formulations; no supplemental local anesthesia was administered. Significant differences between the A 100 and A200 treatments were found for the surgeons' ability to visualize the surgical field (rated as clear 83.3% of the time with A100 and 59.5% of the time with A200; P = 0.008), bleeding expectation (rated as equal to or better than expected 85.7% of the time with A100 and 71.4% of the time with A200; P = 0.034), and volume of blood loss (54.9 +/- 36.0 ml for A100 and 70.2 +/- 53.0 ml for A200; P = 0.018). Sixteen patients experienced 27 mild or moderate adverse events; the most common were postoperative pain (nine patients) and swelling (eight patients). Six adverse events may have been related to treatment. The frequency of adverse events did not vary between formulations. Conclusions: For patients undergoing periodontal surgery, 4% articaine anesthetic formulations containing epinephrine (1:100,000 or 1:200,000) provided excellent surgical pain control. For patients who can tolerate higher amounts of epinephrine, the 4% articaine 1:100,000 epinephrine formulation had the additional therapeutic advantage of providing better visualization of the surgical field and less bleeding. C1 Univ Pittsburgh, Sch Dent Med, Dept Pharmacol & Dent Publ Hlth, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Dent Med, Dept Periodont, Pittsburgh, PA 15261 USA. Univ Penn, Sch Dent Med, Dept Oral Surg Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA 19104 USA. Forsyth Inst, Boston, MA USA. Novocol Pharmaceut Canada, Toronto, ON, Canada. Tegra Analyt, Doylestown, PA USA. RP Moore, PA (reprint author), Univ Pittsburgh, Sch Dent Med, Dept Anesthesiol, Oral Hlth Sci Inst, 552 Salk Hall, Pittsburgh, PA 15261 USA. EM pam7@pitt.edu NR 19 TC 17 Z9 18 U1 0 U2 1 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 FEB PY 2007 VL 78 IS 2 BP 247 EP 253 DI 10.1902/jop.2007.060314 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 137BO UT WOS:000244268000009 PM 17274713 ER PT J AU Kurtz, JE Blais, MA AF Kurtz, John E. Blais, Mark A. TI Introduction to the special issue on the Personality Assessment Inventory SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID VALIDITY RATES; PAI; DISORDERS; SCALES; STYLE AB This special issue of the Journal of Personality Assessment brings together 13 new research studies on the Personality Assessment Inventory (PAI; Morey, 1991) that should inform users and stimulate future empirical activity with this measure. In 4 articles, authors evaluate the validity scales and indexes of the PAI using both analog and criterion designs and samples from a variety of clinical and forensic settings. In a 5th article, the authors describe a novel approach to profile interpretation using two PAI negative distortion measures. The authors present applications of the PAI to new populations and problems including a German translation of the PAI and profile information for male batterers and victims of head injury. The authors of 2 studies extend research on the validity of the PAI for the assessment of borderline personality disorder. In the final 3 studies, the authors evaluate the validity of PAI measures of violence and aggression to predict subsequent aggressive behavior and institutional misconduct. Finally, the authors offer several suggestions for future research with the PAI. C1 Villanova Univ, Dept Psychol, Villanova, PA 19085 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kurtz, JE (reprint author), Villanova Univ, Dept Psychol, 800 Lancaster Ave, Villanova, PA 19085 USA. EM John.Kurtz@Villanova.edu NR 25 TC 10 Z9 10 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 2007 VL 88 IS 1 BP 1 EP 4 PG 4 WC Psychology, Clinical; Psychology, Social SC Psychology GA 136QD UT WOS:000244238300001 PM 17266408 ER PT J AU Baity, MR Siefert, CJ Chambers, A Blais, MA AF Baity, Matthew R. Siefert, Caleb J. Chambers, Anthony Blais, Mark A. TI Deceptiveness on the PAI: A study of naive faking with psychiatric inpatients SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article; Proceedings Paper CT Midwinter Meeting of the Society-for-Personality-Assessment CY MAR, 2004 CL Miami, FL SP Soc Personal Assessment ID PERSONALITY-ASSESSMENT INVENTORY; DISORDERS; MMPI-2 AB In this study, we sought to explore the diagnostic accuracy of the Personality Assessment Inventory (PAI; Morey, 1991) Validity scales (Negative Impression Management [NIM] and Positive Impression Management [PIM]) and indexes (Malingering index, Defensiveness index [DEF]; Morey, 1993, 1996; Cashel Discriminant Function; Cashel, Rogers, Sewell, & Martin-Cannici, 1995; and Rogers Discriminant Function [RDF]; Rogers, Sewell, Morey, & Ustad, 1996) to identify differences in profiles completed by psychiatric inpatients under standardized instructions (Time 1) and after random assignment (Time 2) to a fake good (n = 21), fake bad (n = 20), or retest (n = 21) scenario. Repeated measures analysis of variance revealed a significant interaction effect. Whereas the retest group did not show any significant changes on the PAI variables from Time I to Time 2, both faking groups showed changes in expected directions. Discriminant function analyses revealed that NIM, RDF, and lower scores on DEF best differentiated between the faking bad and retest groups. PIM was the only nonredundant significant score discriminating the faking good and retest groups. Cutoffs for these scales and indexes established in prior research were supported using diagnostic efficiency statistics. Results suggest that NIM and RDF in faking bad scenarios and PIM in faking good scenarios are most sensitive to unsophisticated attempts to dissimulate by inpatient psychiatric patients. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Ctr Appl Psychol & Family Studies, Evanston, IL 60208 USA. RP Baity, MR (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM mbaity@partners.org NR 21 TC 20 Z9 20 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 2007 VL 88 IS 1 BP 16 EP 24 DI 10.1207/s15327752jpa8801_03 PG 9 WC Psychology, Clinical; Psychology, Social SC Psychology GA 136QD UT WOS:000244238300003 PM 17266410 ER PT J AU Jacobo, MC Blais, MA Baity, MR Harley, R AF Jacobo, Michelle C. Blais, Mark A. Baity, Matthew R. Harley, Rebecca TI Concurrent validity of the Personality Assessment Inventory borderline scales in patients seeking dialectical behavior therapy SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID DSM-IV BORDERLINE; DISORDER FEATURES; CRITERIA AB The purpose of this study was to explore the usefulness of the Personality Assessment Inventory (PAI; Morey, 1991) Borderline full scale (BOR) and subscales in the assessment of patients being evaluated for dialectical behavior therapy (DBT; Linehan, 1993). We administered 67 patients both the PAI and the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) Structured Clinical Interview for Axis II disorders (SCID-II; First, Spitzer, Gibbon, Williams, & Benjamin, 1997). Point biserial correlations showed a significant relationship between the presence of borderline personality disorder (BPD) and scores on the BOR and Schizophrenia (SCZ) scales. A regression analysis showed that among the BOR subscales, those measuring identity disturbance, self-harming behavior, and negative relationships were significantly related to the total number of SCID-II BPD criteria. Diagnostic efficiency statistics between the BOR scale and the number of SCID-II BPD criteria indicated that a T score cutoff of 65 optimally differentiates patients who do and do not meet criteria for BPD. The relationship between BOR and SCID-II BPD demonstrates the concurrent validity of the PAI and shows its usefulness in this setting. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jacobo, MC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Warren 1220,55 Fruit St, Boston, MA 02114 USA. EM mjacobo@Partners.org NR 20 TC 39 Z9 39 U1 1 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 2007 VL 88 IS 1 BP 74 EP 80 DI 10.1207/s15327752jpa8801_10 PG 7 WC Psychology, Clinical; Psychology, Social SC Psychology GA 136QD UT WOS:000244238300010 PM 17266417 ER PT J AU Khwaja, FW Reed, MS Olson, JJ Schmotzer, BJ Gillespie, GY Guha, A Groves, MD Kesari, S Pohl, J Van Meir, EG AF Khwaja, Fatima W. Reed, Matthew S. Olson, Jeffrey J. Schmotzer, Brian J. Gillespie, G. Yancey Guha, Abhijit Groves, Morris D. Kesari, Santosh Pohl, Jan Van Meir, Erwin G. TI Proteomic identification of biomarkers in the cerebrospinal fluid (CSF) of astrocytoma patients SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE cerebrospinal fluid; central nervous system; brain tumor; glioma; proteomics; two-dimensional gel electrophoresis; cleavable isotope-coded affinity tag (clCAT); mass spectrometry; biomarker discovery ID CENTRAL-NERVOUS-SYSTEM; CODED AFFINITY TAGS; GLIOMA-CELLS; DOWN-REGULATION; T-LYMPHOCYTES; GROWTH-FACTOR; BRAIN-TUMORS; CUB-FAMILY; IN-VIVO; GLIOBLASTOMA AB The monitoring of changes in the protein composition of the cerebrospinal fluid (CSF) can be used as a sensitive indicator of central nervous system (CNS) pathology, yet its systematic application to analysis of CNS neoplasia has been limited. There is a pressing need for both a better understanding of gliomagenesis and the development of reliable biomarkers of the disease. In this report, we used two proteomic techniques, two-dimensional gel electrophoresis (2-DE), and cleavable Isotope-Coded Affinity Tag (cICAT) to compare CSF proteomes to identify tumor- and grade-specific biomarkers in patients bearing brain tumors of differing histologies and grades. Retrospective analyses were performed on 60 samples derived from astrocytomas WHO grade II, III, and IV, schwannomas, metastastic brain tumors, inflammatory samples, and non-neoplastic controls. We identified 103 potential tumor-specific markers of which 20 were high-grade astrocytoma-specific. These investigations allowed us to identify a spectrum of signature proteins that could be used to distinguish CSF derived from control patients versus those with low- (AII) or high-grade (AIV) astrocytoma. These proteins may represent new diagnostic, prognostic, and disease follow-up markers when used alone or in combination. These candidate biomarkers may also have functional properties that play a critical role in the development and malignant progression of human astrocytomas, thus possibly representing novel therapeutic targets for this highly lethal disease. C1 Emory Univ, Winship Canc Inst, Sch Med, Atlanta, GA 30322 USA. Emory Univ, Lab Mol Neurooncol, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA. Emory Univ, Lab Mol Neurooncol, Sch Med, Dept Hematol Oncol, Atlanta, GA 30322 USA. Emory Univ, Microchem & Proteom Facil, Sch Med, Atlanta, GA 30322 USA. Emory Univ, Gen Clin Res Ctr, Sch Med, Sch Publ Hlth, Atlanta, GA 30322 USA. Univ Alabama, Birmingham, AL USA. Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatts Brain Tumor Ctr, Toronto, ON M5G 1X8, Canada. Univ Toronto, Wellesley Hosp, Div Neurosurg, Toronto, ON M4Y 1J3, Canada. MD Anderson Canc Ctr, Houston, TX USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Van Meir, EG (reprint author), Emory Univ, Winship Canc Inst, Sch Med, 1365C Clifton Rd NE,C5078, Atlanta, GA 30322 USA. EM evanmei@emory.edu RI Kesari, Santosh/E-8461-2013; OI Van Meir, Erwin G./0000-0003-2444-7707 FU NCI NIH HHS [CA 86335, R01 CA086335, R01 CA086335-05]; NCRR NIH HHS [M01 RR 00039, M01 RR000039, RR 02878, RR 12878, RR 13948] NR 48 TC 35 Z9 38 U1 0 U2 6 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. PY 2007 VL 6 IS 2 BP 559 EP 570 DI 10.1021/pr060240z PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 132FK UT WOS:000243927900012 PM 17269713 ER PT J AU Starkebaum, G AF Starkebaum, Gordon TI Rheumatoid arthritis and lymphoma: Risky business for B cells SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID EPSTEIN-BARR-VIRUS; NON-HODGKIN-LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS; T-CELLS; METHOTREXATE; THERAPY; EPIDEMIOLOGY; AUTOIMMUNITY; INDUCTION; ANTIGEN C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Starkebaum, G (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, S-01 COS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Gordon.Starkebaum@va.gov NR 33 TC 10 Z9 10 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 2007 VL 34 IS 2 BP 243 EP 246 PG 4 WC Rheumatology SC Rheumatology GA 134VQ UT WOS:000244112900001 PM 17304645 ER PT J AU Shera, CA Guinan, JJ AF Shera, Christopher A. Guinan, John J., Jr. TI Cochlear traveling-wave amplification, suppression, and beamforming probed using noninvasive calibration of intracochlear distortion sources SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AUDITORY-NERVE FIBERS; OTOACOUSTIC EMISSION; FREQUENCY MAP; PRODUCT; GENERATION; MODEL; CAT; EAR; MECHANISMS; SOUND AB Originally developed to estimate the power gain of the cochlear amplifier, so-called "Allen-Fahey" and related experiments have proved invaluable for probing the mechanisms of wave generation and propagation within the cochlea. The experimental protocol requires simultaneous measurement of intracochlear distortion products (DPs) and ear-canal otoacoustic emissions (DPOAEs) under tightly controlled conditions. To calibrate the intracochlear response to the DP, Allen-Fahey experiments traditionally employ invasive procedures such as recording from auditory-nerve fibers or measuring basilar-membrane velocity. This paper describes an alternative method that allows the intracochlear distortion source to be calibrated noninvasively. In addition to ' the standard pair of primary tones used to generate the principal DP, the noninvasive method employs a third, fixed tone to create a secondary DPOAE whose amplitude and phase provide a sensitive assay of the intracochlear value of the principal DP near its characteristic place. The method is used to perform noninvasive Allen-Fahey experiments in cat and shown to yield results in quantitative agreement with the original, auditory-nerve-based paradigm performed in the same animal. Data obtained using a suppression-compensated variation of the noninvasive method demonstrate that neither traveling-wave amplification nor two-tone suppression constitutes the controlling influence in DPOAE generation at close frequency ratios. Rather, the dominant factor governing the emission magnitude appears to be the variable directionality of the waves radiated by the distortion-source region, which acts as a distortion beamformer tuned by the primary frequency ratio. (c) 2007 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [F32 DC000108, F32 DC00108, R01 DC00235, R01 DC03687] NR 42 TC 27 Z9 29 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD FEB PY 2007 VL 121 IS 2 BP 1003 EP 1016 DI 10.1121/1.2404620 PG 14 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 134VW UT WOS:000244113500030 PM 17348523 ER PT J AU Tramell, M Geller, D AF Tramell, Michael Geller, Daniel TI Evidence-based psychopharmacology. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Univ Calif San Diego, Rady Childrens Hosp & Hlth Ctr, Div Child & Adolescent Psychiat, San Diego, CA 92103 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Pediat Psychopharmacol, Boston, MA 02115 USA. RP Tramell, M (reprint author), Univ Calif San Diego, Rady Childrens Hosp & Hlth Ctr, Div Child & Adolescent Psychiat, San Diego, CA 92103 USA. NR 2 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 FEB PY 2007 VL 46 IS 2 BP 263 EP 264 DI 10.1097/01.chi.0000251260.74043.9f PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 129OD UT WOS:000243737900015 ER PT J AU Perkins, AC Choi, JM Kimball, AB AF Perkins, Alexis C. Choi, Joanna Mimi Kimball, Alexa B. TI Reporting of ethical review of clinical research submitted to the Journal of the American Academy of Dermatology SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Background: In recent years there has been an increasing focus on human subject protection and on documentation of ethical review in published clinical research. The JAAD clearly states in its instructions to authors, which adhere to the guidelines set forth by the International Committee of Medical Journal Editors, 1 studies involving live human subjects must have been approved by the author's Institutional Review Board or its equivalent." Objective: To determine what proportion of prospective studies on human subjects submitted to the clinical trials and therapeutics section lacked mention of review by an ethics board and to determine the outcome of these manuscripts. Methods: We reviewed 150 prospective studies submitted from July 1, 2004 to January 16, 2006 to a single associate editor, who receives the majority of reports requiring ethics board review. Results: Of 150 prospective studies, 36% (n=54) had no mention of ethics review or consent, whereas 15% (n=22) mentioned consent but not ethics review. Forty-two papers were returned asking for ethics information, and of these, 48% were resubmitted with confirmation of ethics review, 22% were withdrawn, 12% were never resubmitted, 12% responded that ethical review was not obtained, and 7% were clarified is exempt from review. Of the 150 papers 45% were from US authors and 55% were from international authors. Sixty-seven percent of US papers and 35% of international papers included ethics board information (P <=.001). Of the remaining authors who did not initially provide information on ethics review, 25% of US and 53% of international authors were able to provide documentation of ethics board review when asked. Of international authors asked for ethics information, 67% of European authors provided confirmation of ethical review, as compared with 48% of non-European authors. Limitations: It is not possible to know with certainty whether each study not citing ethics review actually did not undergo review by an ethics board. Additionally, other editors may have handled some studies requiring ethics review. Conclusions: One half of authors submitting papers on prospective clinical studies to the JAAD did not provide evidence of ethical review on initial submission. The reason for omission was likely oversight in half of the cases, but in others ethics review and approval were likely not obtained. International authors were more likely to omit mention of ethics review, but, although sample size was too small for statistical analysis, international authors were more often able to provide it when asked, suggesting oversight or misunderstanding as a reason for omission. Furthermore, ethics review may be more standard in the European Union, as European authors were more likely to he able to provide the information when asked, although small sample size precluded statistical analysis. C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 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 9 TC 5 Z9 5 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 FEB PY 2007 VL 56 IS 2 BP 279 EP 284 DI 10.1016/j.jaad.2006.08.072 PG 6 WC Dermatology SC Dermatology GA 131TD UT WOS:000243891900014 PM 17224370 ER PT J AU Choi, JM Salter, SA Kimball, AB AF Choi, Joanna Mimi Salter, Sharon A. Kimball, Alexa B. TI Innovative care, medical research, and the ethics of informed consent SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Dept Dermatol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Dept Dermatol, 50 Staniford St,246 Dermatol, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2007 VL 56 IS 2 BP 330 EP 332 DI 10.1016/j.jaad.2006.08.070 PG 3 WC Dermatology SC Dermatology GA 131TD UT WOS:000243891900021 PM 17224375 ER PT J AU Blyumin, M Kazanis, M Brown, K Kimball, A AF Blyumin, Marianna Kazanis, Maryanne Brown, Katherine Kimball, Alexandra TI Lack of awareness of the medical professionals about nonphysician clinicians SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Dermatology CY FEB 02-06, 2007 CL Washington, DC SP Amer Acad Dermatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 FEB PY 2007 VL 56 IS 2 SU S BP AB104 EP AB104 PG 1 WC Dermatology SC Dermatology GA 132WE UT WOS:000243972800410 ER PT J AU Gordon, K Kimball, A Langley, R Okun, M AF Gordon, Kenneth Kimball, Alexa Langley, Richard Okun, Martin TI PASI-100 is associated with better dermatology-specific patient reported outcomes compared with PASI-75-99: Subanalysis of a phase II psoriasis trial of adalimumab SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Dermatology CY FEB 02-06, 2007 CL Washington, DC SP Amer Acad Dermatol C1 Evanston Northwestern Hlthcare, Skokie, IL USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA USA. Dalhousie Univ, Halifax, NS, Canada. Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2007 VL 56 IS 2 SU S BP AB186 EP AB186 PG 1 WC Dermatology SC Dermatology GA 132WE UT WOS:000243972801281 ER PT J AU Hu, S Decristafaro, S Werchniak, A AF Hu, Stephanie Decristafaro, Susan Werchniak, Andrew TI Success of Boston skin cancer screening initiative for the underserved serves as model for a nationwide program SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Dermatology CY FEB 02-06, 2007 CL Washington, DC SP Amer Acad Dermatol C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2007 VL 56 IS 2 SU S BP AB100 EP AB100 PG 1 WC Dermatology SC Dermatology GA 132WE UT WOS:000243972800393 ER PT J AU White, WM Makin, IRS Slayton, MH Gliklich, R AF White, W. Matthew Makin, Inder Raj S. Slayton, Michael H. Gliklich, Richard TI Creation of micro-ablative thermal regions within the deep dermis by intense ultrasound (IUS): A new tool for nonablative facial rejuvenation SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Dermatology CY FEB 02-06, 2007 CL Washington, DC SP Amer Acad Dermatol C1 Wellman Labs Photomed, Boston, MA USA. Ulthera Inc, Mesa, AZ USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 FEB PY 2007 VL 56 IS 2 SU S BP AB1 EP AB1 PG 1 WC Dermatology SC Dermatology GA 132WE UT WOS:000243972800005 ER PT J AU Williams, CM Qureshi, A Geller, A Kvedar, J AF Williams, Christy M. Qureshi, Abrar Geller, Alan Kvedar, Joseph TI Skin cancer education program via teledermatology: Is it effective? SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Dermatology CY FEB 02-06, 2007 CL Washington, DC SP Amer Acad Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Lebanon, NH USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. NR 0 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD FEB PY 2007 VL 56 IS 2 SU S BP AB100 EP AB100 PG 1 WC Dermatology SC Dermatology GA 132WE UT WOS:000243972800395 ER PT J AU Gawande, AA Kwaan, MR Regenbogen, SE Lipsitz, SA Zinner, MJ AF Gawande, Atul A. Kwaan, Mary R. Regenbogen, Scott E. Lipsitz, Stuart A. Zinner, Michael J. TI An Apgar score for surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID NONCARDIAC SURGERY; INTRAOPERATIVE TACHYCARDIA; BLOOD-PRESSURE; CLASSIFICATION; HANDWRITTEN; RECORDS; EVENTS; SYSTEM AB BACKGROUND: Surgical teams have not had a routine, reliable measure of patient condition at the end of an operation. We aimed to develop an Apgar score for the field of surgery, an outcomes score that teams could calculate at the end of any general or vascular surgical procedure to accurately grade a patient's condition and chances of major complications or death. STUDY DESIGN: We derived our surgical score in a retrospective analysis of data from medical records and the National Surgical Quality Improvement Program for 303 randomly selected patients undergoing colectomy at Brigham and Women's Hospital, Boston. The primary outcomes measure was incidence of major complication or death within 30 days of operation. We validated the score in two prospective, randomly selected cohorts: 102 colectomy patients and 767 patients undergoing general or vascular operations at the same institution. RESULTS: A 10-point score based on a patient's estimated amount of blood loss, lowest heart rate, and lowest mean arterial pressure during general or vascular operations was significantly associated with major complications or death within 30 days (p < 0.0001; c-index = 0.72). Of 767 general and vascular surgery patients, 29 (3.8%) had a surgical score <= 4. Major complications or death occurred in 17 of these 29 patients (58.6%) within 30 days. By comparison, among 220 patients with scores of 9 or 10, only 8 (3.6%) experienced major complications or died (relative risk 16.1; 95% Cl, 7.6-34.0; p < 0.0001). CONCLUSIONS: A simple score based on blood loss, heart rate, and blood pressure can be useful in rating the condition of patients after general or vascular operations. C1 Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Gawande, AA (reprint author), Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. EM agawande@partners.org OI Gawande, Atul/0000-0002-1824-9176 NR 24 TC 146 Z9 149 U1 3 U2 8 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 FEB PY 2007 VL 204 IS 2 BP 201 EP 208 DI 10.1016/j.jamcollsurg.2006.11.011 PG 8 WC Surgery SC Surgery GA 135DF UT WOS:000244133600002 PM 17254923 ER PT J AU Friedlander, AH Weinreb, J Friedlander, I Yagiela, JA AF Friedlander, Arthur H. Weinreb, Jane Friedlander, Ida Yagiela, John A. TI Metabolic syndrome - Pathogenesis, medical care and dental implications SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE hypertension; obesity; atherosclerosis; metabolic syndrome ID CARDIOVASCULAR RISK-FACTORS; LOW-DOSE ASPIRIN; NUTRITION EXAMINATION SURVEY; CORONARY-HEART-DISEASE; 3RD NATIONAL-HEALTH; TREATMENT PANEL-III; NUTRIENT INTAKE; DIABETES-MELLITUS; ORAL-HEALTH; US ADULTS AB Background. The dental literature contains little information about metabolic syndrome (MetS) and its dental implications. Types of Studies Reviewed. The authors conducted a MEDLINE search for the period 2000 through 2005, using the term "metabolic syndrome" to define its pathophysiology, medical treatment and dental implications. Results. MetS is the co-occurrence of abdominal obesity, hypertriglyceridemia, reduced high-density lipoprotein cholesterol levels, hypertension and impaired fasting glucose, which results from consumption of a high-calorie diet and decreased levels of physical activity superimposed on the appropriate genetic setting. Components of MetS synergistically promote the development of atherosclerosis, resulting in myocardial infarction and stroke. Clinical Implications. Deteriorating oral health status is associated with worsening of the atherogenic profile. Tooth loss often results in chewing difficulties because of inadequate occlusive surfaces and may lead to alterations in food selection and dietary quality. This, in turn, adversely affects body composition and nutritional status, both of which are related to vascular health. Dentists should develop treatment plans that preserve and restore the dentition, thus ensuring maximum masticatory efficiency and affording patients the optimum opportunity to consume food that will not foster atherogenesis. C1 VA Greater Los Angeles Healthcare Syst, Diabet Program, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. N Hollywood Hlth Ctr, N Hollywood, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Diabet Program, 11301 Wilshire Blvd, Los Angeles, CA USA. EM arthur.friedlander@med.va.gov RI Biguzzi, Felipe/E-4724-2015 NR 80 TC 13 Z9 15 U1 0 U2 6 PU AMER DENTAL ASSN 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 FEB PY 2007 VL 138 IS 2 BP 179 EP 187 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 136QG UT WOS:000244238600017 PM 17272372 ER PT J AU Rubenstein, LZ Alessi, CA Josephson, KR Hoyl, MT Harker, JO Pietruszka, FM AF Rubenstein, Laurence Z. Alessi, Cathy A. Josephson, Karen R. Hoyl, M. Trinidad Harker, Judith O. Pietruszka, Fern M. TI A randomized trial of a screening, case finding, and referral system for older veterans in primary care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatric assessment; elderly; health screening ID OUTPATIENT GERIATRIC EVALUATION; ELDERLY-PEOPLE; GENERAL-PRACTICE; CLINICAL-TRIAL; QUESTIONNAIRE; RELIABILITY; VALIDITY; HOME; MANAGEMENT; SF-36 AB OBJECTIVES: To test whether a system of screening, assessment, referral, and follow-up provided within primary care for high-risk older outpatients improves recognition of geriatric conditions and healthcare outcomes. DESIGN: Controlled clinical trial with 3-year follow-up; intervention versus control group allocation based on practice group assignment. SETTING: Department of Veterans Affairs (VA) ambulatory care center. PARTICIPANTS: Seven hundred ninety-two community-dwelling patients aged 65 and older identified by postal screening survey. INTERVENTION: The intervention combined a structured telephone geriatric assessment by a physician assistant, individualized referrals and recommendations, selected referral to outpatient geriatric assessment, and ongoing telephone case management. MEASUREMENTS: Main outcomes were VA medical record evidence of recognition and evaluation of target geriatric conditions (depression, cognitive impairment, urinary incontinence, falls, functional impairment), functional status (Functional Status Questionnaire, FSQ), and hospitalization (VA databases and self-reported non-VA usage). RESULTS: Intervention participants were more likely to have target conditions recognized, evaluated, and referred to specialized services within 12 months of enrollment, although there were no significant differences in FSQ scores or acute hospitalization between intervention and control groups at 1, 2, or 3 years follow-up. Subgroup analyses suggested improvements in depression symptoms and functional impairment at 1-year follow-up in intervention participants with these problems at baseline, but these findings were not evident at later follow-up. CONCLUSION: The intervention increased recognition and evaluation of target geriatric conditions but did not improve functional status or decrease hospitalization. Innovative screening methods can identify older people in need of geriatric services, but achieving measurable improvement in functional status or hospitalization rates will likely require a more-intensive intervention than a program involving primarily unsolicited referrals and short-term consultations. C1 VA Greater Los Angeles Healthcare Syst, GRECC, North Hills, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90024 USA. Catholic Univ Chile, Sch Med, Dept Internal Med, Geriatr Program, Santiago, Chile. RP Alessi, CA (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC, 11E,16111 Plummer St, North Hills, CA 91343 USA. EM cathy.alessi@va.gov NR 24 TC 37 Z9 39 U1 2 U2 7 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 FEB PY 2007 VL 55 IS 2 BP 166 EP 174 DI 10.1111/j.1532-5415.2007.01044.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 131LH UT WOS:000243869900003 PM 17302651 ER PT J AU Mavandadi, S Ten Have, TR Katz, IR Durai, UNB Krahn, DD Llorente, MD Kirchner, JE Olsen, EJ Van Stone, WW Cooley, SL Oslin, DW AF Mavandadi, Shahrzad Ten Have, Thomas R. Katz, Ira R. Durai, U. Nalla B. Krahn, Dean D. Llorente, Maria D. Kirchner, Joann E. Olsen, Edwin J. Van Stone, William W. Cooley, Susan L. Oslin, David W. TI Effect of depression treatment on depressive symptoms in older adulthood: The moderating role of pain SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depressive symptoms; pain; primary care; depression treatment ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; LATE-LIFE DEPRESSION; LOW-BACK-PAIN; PHYSICAL-DISABILITY; TREATMENT RESPONSE; ELDERLY COMMUNITY; PRISM-E; OUTCOMES; POPULATIONS AB OBJECTIVES: To investigate whether pain severity and interference with normal work activities moderate the effects of depression treatment on changes in depressive symptoms over time in older adults in primary care. DESIGN: Patient-randomized, clinical trial. SETTING: Multisite: three clinics located in Veterans Affairs Medical Centers. PARTICIPANTS: Adults aged 60 and older (n=524) who screened positive for depression and participated in the Primary Care Research in Substance Abuse and Mental Health for the Elderly Study. INTERVENTION: Integrated care versus enhanced specialty referral care. MEASUREMENTS: Pain severity, the degree to which pain interferes with work inside and outside of the home, and depressive symptoms were examined at baseline and 3, 6, and 12 months. RESULTS: Intention-to-treat analyses revealed that both treatment groups showed reduced depressive symptoms over time, although self-reported pain moderated reductions in depressive symptoms. At higher levels of pain severity and interference with work activities, improvements in depressive symptoms were blunted. Furthermore, pain interference appeared to have a greater effect on depressive symptoms than did pain severity; in individuals with major depression, pain interference fully accounted for the moderating effects of pain severity on changes in depressive symptoms over time. CONCLUSION: Pain and its interference with functioning interfere with recovery from depression. Findings highlight the importance of addressing multiple domains of functioning (e.g., physical and social disability) and the degree to which pain and other forms of physical comorbidity may hinder or minimize treatment-related improvements in depressive symptoms. C1 Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epiodemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Study Addict, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res, Educ & Clin Ctr, Philadelphia, PA USA. Univ Illinois, VA W Side Med Ctr, Dept Psychiat, Chicago, IL 60607 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Univ Miami, Miami Va Med Ctr, Dept Psychiat, Miami, FL 33152 USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. US Dept Vet Affairs, Off Mental Hlth Serv, Washington, DC USA. US Dept Vet Affairs, Off Geriatr & Extended Care, Washington, DC USA. RP Mavandadi, S (reprint author), 3535 Market St,3005, Philadelphia, PA 19104 USA. EM smavanda@mail.med.upenn.edu NR 35 TC 30 Z9 30 U1 0 U2 4 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 FEB PY 2007 VL 55 IS 2 BP 202 EP 211 DI 10.1111/j.1532-5415.2007.01042.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 131LH UT WOS:000243869900008 PM 17302656 ER PT J AU Holroyd-Leduc, JM Sen, S Bertenthal, D Sands, LP Palmer, RM Kresevic, DM Covinsky, KE Landefeld, CS AF Holroyd-Leduc, Jayna M. Sen, Saunak Bertenthal, Dan Sands, Laura P. Palmer, Robert M. Kresevic, Denise M. Covinsky, Kenneth E. Landefeld, C. Seth TI The relationship of indwelling urinary catheters to death, length of hospital stay, functional decline, and nursing home admission in hospitalized older medical patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE urinary catheters; hospitalized older patients; mortality; morbidity ID REGIONAL-VARIATIONS; ELDERLY-PATIENTS; OUTCOMES; CARE; MORTALITY; DISEASE AB OBJECTIVES: To determine the association between indwelling urinary catheterization without a specific medical indication and adverse outcomes. DESIGN: Prospective cohort. SETTING: General medical inpatient services at a teaching hospital. PARTICIPANTS: Five hundred thirty-five patients aged 70 and older admitted without a specific medical indication for urinary catheterization. INTERVENTION: Indwelling urinary catheterization within 48 hours of admission. MEASUREMENTS: Death, length of hospital stay, decline in ability to perform activities of daily living (ADLs), and new admission to a nursing home. RESULTS: Indwelling urinary catheters were placed in 76 of the 535 (14%) patients without a specific medical indication. Catheterized patients were more likely to die in the hospital (6.6% vs 1.5% of those not catheterized, P=.006) and within 90 days of hospital discharge (25% vs 10.5%, P <.001); the greater risk of death with catheterization persisted in a propensity-matched analysis (hazard ratio (HR)=2.42, 95% confidence interval (CI)=1.04-5.65). Catheterized patients also had longer lengths of hospital stay (median, 6 days vs 4 days; P=.001); this association persisted in a propensity-matched analysis (HR=1.46, 95% CI=1.03-2.08). Catheterization was not associated (P >.05) with decline in ADL function or with admission to a nursing home. CONCLUSION: In this cohort of older patients, urinary catheterization without a specific medical indication was associated with greater risk of death and longer hospital stay. C1 Univ Calgary, Dept Med, Calgary, AB T2N 1N4, Canada. San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. Purdue Univ, Ctr Aging & Life Course, W Lafayette, IN 47907 USA. Cleveland Clin, Geriatr Med Sect, Cleveland, OH 44106 USA. Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH USA. Univ Hosp Cleveland, Dept Med Surg Nursing, Cleveland, OH 44106 USA. RP Holroyd-Leduc, JM (reprint author), Foothills Med Ctr, Room 707,7th Floor N Tower,1403-29th St NW, Calgary, AB T2N 2T9, Canada. EM jayna.holroyd-leduc@calgaryhealthregion.ca RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU NIA NIH HHS [AG 00912, AG 10418] NR 33 TC 39 Z9 40 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 FEB PY 2007 VL 55 IS 2 BP 227 EP 233 DI 10.1111/j.1532-5415.2007.01064.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 131LH UT WOS:000243869900011 PM 17302659 ER PT J AU Radcliff, TA Dobalian, A Levy, C AF Radcliff, Tiffany A. Dobalian, Aram Levy, Cari TI Do orders limiting aggressive treatment impact care for acute myocardial infarction? SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article ID COOPERATIVE CARDIOVASCULAR PROJECT; NOT-RESUSCITATE ORDERS; QUALITY-OF-CARE; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; ADVANCE DIRECTIVES; MEDICARE BENEFICIARIES; NURSING-HOME; RACIAL-DIFFERENCES; AMERICAN-COLLEGE AB Objectives: Little is known about whether advance directives impact inpatient care for a condition with clear treatment guidelines. The goal of this research was to determine the association between limitation of aggressive treatment (LAT) orders and guideline adherence for acute myocardial infarction (AMI). Design: Secondary examination of data from the national Cooperative Cardiovascular Project (CCP) baseline data. We used seemingly unrelated regression to correct for potential selection bias between patients with and without LAT orders and to determine whether such orders predict guideline adherence for several treatments related to acute myocardial infarction. Setting: The setting included 4111 short-term non-federal acute care hospitals in the United States. Participants: Participants were 147,475 AMI cases with complete data abstracted from inpatient hospital charts, representing most fee-for-service Medicare patients who were hospitalized with AMI between February 1994 and July 1995. Measurements: Adherence to guidelines for treating acute myocardial infarction, including aspirin, Beta blockers, and reperfusion via thrombolytics or PTCA. Results: Patients with LAT orders are less likely to receive care in accordance with guidelines when controlling for other factors that may explain a lower likelihood of guideline adherence. After adjustment for selection effects, we found a lower predicted probability that patients received more invasive treatments. Conclusion: Patients with LAT orders appear to receive care that is less aggressive and less congruent with acute myocardial infarction care guidelines compared with patients without such orders. Quality improvement measures will need to take this difference into account and ensure that physicians are not penalized for complying with patient care preferences. C1 VA Eastern Colorado Healthcare Syst, HSR&D TREP Long Term Care Res, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Hlth Care Policy & Res, Aurora, CO USA. VA Greater Los Angeles Healthcare Syst HSR&D, Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. Univ Calif Los Angeles, Dept Hlth Sci, Los Angeles, CA USA. RP Radcliff, TA (reprint author), 1055 Clemont St,MS 151, Denver, CO 80220 USA. EM Tiffany.Radcliff@uchsc.edu NR 49 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD FEB PY 2007 VL 8 IS 2 BP 91 EP 97 DI 10.1016/j.jamda.2006.06.004 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 138RX UT WOS:000244381100006 PM 17289538 ER PT J AU French, DD Werner, DC Campbell, RR Powell-Cope, GM Nelson, AL Rubenstein, LZ Bulat, T Spehar, AM AF French, Dustin D. Werner, Dennis C. Campbell, Robert R. Powell-Cope, Gail M. Nelson, Audrey L. Rubenstein, Laurence Z. Bulat, Tatjana Spehar, Andrea M. TI A multivariate fall risk assessment model for VHA nursing homes using the Minimum Data Set SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE accidental falls; falls; patient safety; nursing homes; long-term care; minimum data set; risk factors; risk assessment; multivariate analysis; veterans ID LONG-TERM-CARE; OLDER-ADULTS; RESIDENTIAL CARE; ELDERLY FALLERS; PREVENTION; COMMUNITY; PEOPLE; GAIT; INJURIES; BALANCE AB Objectives: The purpose of this study was to develop a multivariate fall risk assessment model beyond the current fall Resident Assessment Protocol (RAP) triggers for nursing home residents using the Minimum Data Set (MDS). Design: Retrospective, clustered secondary data analysis. Setting: National Veterans Health Administration (VHA) long-term care nursing homes (N = 136). Participants: The study population consisted of 6577 national VHA nursing home residents who had an annual assessment during FY 2005, identified from the MDS, as well as an earlier annual or admission assessment within a 1-year look-back period. Measurement. A dichotomous multivariate model of nursing home residents coded with a fall on selected fall risk characteristics from the MDS, estimated with general estimation equations (GEE). Results: There were 17 170 assessments corresponding to 6577 long-term care nursing home residents. The increased odds ratio (OR) of being classified as a faller relative to the omitted "dependent" category of activities of daily living (ADL) ranged from OR = 1.35 for "limited" ADL category up to OR = 1.57 for "extensive-2" ADL (P < .0001). Unsteady gait more than doubles the odds of being a faller (OR = 2.63, P < .0001). The use of assistive devices such as canes, walkers, or crutches, or the use of wheelchairs increases the odds of being a faller (OR = 1.17, P < .0005) or (OR = 1.19, P < .0002), respectively. Foot problems may also increase the odds of being a faller (OR = 1.26, P < .0016). Alzheimer's or other dementias also increase the odds of being classified as a faller (OR = 1.18, P < .0219) or (OR = 1.22, P < .0001), respectively. In addition, anger (OR = 1.19, P < .0065); wandering (OR = 1.53, P < .0001); or use of antipsychotic medications (OR = 1.15, P < .0039), antianxiety medications (OR = 1.13, P < .0323), or antidepressant medications (OR = 1.39, P < .0001) was also associated with the odds of being a faller. Conclusions: This national study in one of the largest managed healthcare systems in the United States has empirically confirmed the relative importance of certain risk factors for falls in long-term care settings. The model incorporated an ADL index and adjusted for case mix by including only long-term care nursing home residents. The study offers clinicians practical estimates by combining multiple univariate MDS elements in an empirically based, multivariate fall risk assessment model. C1 James A Haley VAMC, Patient Safety Ctr Inquiry VISN8, Tampa, FL 33612 USA. Univ Calif Los Angeles, David Geffen Sch Med, North Hills, CA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda Div, North Hills, CA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, W Los Angeles Div, North Hills, CA USA. Univ S Florida, Coll Publ Hlth, Tampa, FL USA. RP French, DD (reprint author), James A Haley VAMC, Patient Safety Ctr Inquiry VISN8, 13000 Bruce B Downs Blvd 118M, Tampa, FL 33612 USA. EM Dustin.French@va.gov OI French, Dustin/0000-0003-4064-3206; Powell-Cope, Gail/0000-0002-4608-0128 NR 67 TC 35 Z9 35 U1 6 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD FEB PY 2007 VL 8 IS 2 BP 115 EP 122 DI 10.1016/j.jamda.2006.08.005 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 138RX UT WOS:000244381100010 PM 17289542 ER PT J AU Nace, DA Hoffman, EL Resnick, NM Handler, SM AF Nace, David A. Hoffman, Erika L. Resnick, Neil M. Handler, Steven M. TI Achieving and sustaining high rates of influenza immunization among long-term care staff SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE nursing homes; immunization programs; influenza; health care workers ID NURSING-HOME; WORKERS; VACCINATION; MORTALITY; OUTBREAK AB Background: Influenza causes significant morbidity and mortality in long-term care facilities. Immunization of health care workers has been shown to reduce the impact of influenza in this setting, yet few studies address improvement efforts aimed at long-term care staff immunization. Objective: To determine the feasibility of achieving and sustaining high rates of staff influenza immunization for a community-based long-term care facility. Methods: A needs analysis was conducted to determine the organizational and individual level barriers to influenza vaccination of staff. Systems changes, educational interventions, and reminders were implemented based on the barriers assessment. Staff immunization rates were calculated over a 10-year period from 1996 to 2006. Results: Organizational and individual barriers were identified and targeted. Using data from 1996 and 1997 as a baseline, staff immunization rates improved from 54% to 55% to between 74% and 95% over the past 4 years. Conclusions: Achieving and sustaining high staff influenza immunization rates is possible in a community-based long-term care facility with an involved quality improvement team and medical director. C1 Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA USA. Univ Pittsburgh, Inst Aging, Pittsburgh, PA USA. RP Nace, DA (reprint author), Univ Pittsburgh, Div Geriatr Med, 3471 5th Ave,Suite 500, Pittsburgh, PA 15213 USA. EM naceda@upmc.edu RI Nace, David/D-2638-2014; OI Handler, Steven/0000-0002-3940-3224 FU NCRR NIH HHS [8K12RR023267] NR 38 TC 21 Z9 21 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD FEB PY 2007 VL 8 IS 2 BP 128 EP 133 DI 10.1016/j.jamda.2006.09.014 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 138RX UT WOS:000244381100012 PM 17289544 ER PT J AU Farjah, F Symons, RG Krishnadasan, B Wood, DE Flum, DR AF Farjah, Farhood Symons, Rebecca Gaston Krishnadasan, Bahirathan Wood, Douglas E. Flum, David R. TI Management of pleural space infections: A population-based analysis SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Western-Thoracic-Surgical-Association CY JUN 21-24, 2006 CL Sun Valley, ID SP Western Thorac Surg Assoc ID PARAPNEUMONIC EFFUSIONS; THORACIC EMPYEMA; EXPERIENCE; TRIAL AB Objective: Management options for pleural space infections have changed over the last 2 decades. This study evaluated trends over time in the incidence of disease and use of different management strategies and their associated outcomes. Methods: A retrospective study was performed by using a statewide administrative database of all hospitalizations for pleural space infections between 1987 and 2004. Results: Four thousand four hundred twenty-four patients (age, 57.1 +/- 18.6 years; 67% male; comorbidity index, 1.1 +/- 1.9) were hospitalized with pleural space infections. The incidence rate increased 2.8% per year (95% confidence interval, 2.2%-3.4%; P < .001). Overall, 51.6% of patients underwent an operation, and the proportion increased from 42.4% in 1987 to 58.4% in 2004 (P < .001). The risk of death within 30 days was less for patients undergoing operations compared with that for patients not undergoing operations (5.4% vs 16.6%, P < .001); however, patients undergoing operations were younger (52.9 +/- 17.6 years vs 61.5 +/- 18.6 years, P < .001) and had a lower comorbidity index (0.8 +/- 1.6 vs 1.4 +/- 2.1, P < .001). After adjusting for age, sex, comorbidity index, and insurance status, patients undergoing operative therapy had a 58% lower risk of death (odds ratio, 0.42; 95% confidence interval, 0.32-0.56; P < .001) than those undergoing nonoperative management. Conclusions: The incidence of pleural space infections and the proportion of patients undergoing operative management have increased over time. Patients undergoing operations were younger and had less comorbid illness than those not undergoing operations but had a much lower risk of early death, even after adjusting for these factors. C1 Univ Washington, Div Gen Surg, Dept Surg, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Surg, Div Cardiothorac Surg, Seattle, WA USA. Univ Washington, Div Cardiovasc Surg, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Div Gen Surg, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Div Gen Surg, Dept Hlth Serv, Seattle, WA 98195 USA. RP Flum, DR (reprint author), Univ Washington, Div Gen Surg, Dept Surg, 1959 NE Pacific,Box 356410, Seattle, WA 98195 USA. EM daveflum@u.washington.edu NR 15 TC 54 Z9 55 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 FEB PY 2007 VL 133 IS 2 BP 346 EP U10 DI 10.1016/j.jctvs.2006.09.038 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 130FB UT WOS:000243783900013 PM 17258562 ER PT J AU Vogt, DS Tanner, LR AF Vogt, Dawne S. Tanner, Lynlee R. TI Risk and resilience factors for posttraumatic stress symptomatology in Gulf War I veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID MALE VIETNAM VETERANS; PSYCHOMETRIC PROPERTIES; NATIONAL SAMPLE; ZONE STRESSORS; PTSD CHECKLIST; PHYSICAL ABUSE; DISORDER; FEMALE; SYMPTOMS; METAANALYSIS AB What factors distinguish war-exposed veterans who experience posttraumatic stress symptomatology (PTSS) from those who do not? This study used structural equation modeling procedures to examine the complex interplay among predeployment, war-zone, and postdeployment factors as they relate to PTSS in a sample of Gulf War I veterans. A primary goal was to determine to what extent previously documented associations among Vietnam veterans would replicate in this more contemporary veteran cohort. Results supported a multivariate etiological perspective on PTSS, with war-zone factors accounting for the largest proportion of variance in PTSS. The majority of hypothesized associations held, suggesting that the mechanisms underlying PTSS may be similar across veteran cohorts. C1 Boston Univ, Sch Med, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div,VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02130 USA. RP Vogt, DS (reprint author), Boston Univ, Sch Med, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div,VA Boston Healthcare Syst, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM Dawne.Vogt@va.gov NR 46 TC 45 Z9 45 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2007 VL 20 IS 1 BP 27 EP 38 DI 10.1002/jts.20187 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 147CP UT WOS:000244981300004 PM 17345645 ER PT J AU Clarke, SB Koenen, KC Taft, CT Street, AE King, LA King, DW AF Clarke, Stephanie B. Koenen, Karestan C. Taft, Casey T. Street, Amy E. King, Lynda A. King, Daniel W. TI Intimate partner psychological aggression and child behavior problems SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID VIOLENCE AB The present study examined the relationship between intimate partner psychological aggression and children behavior problems in a community sample of families (N = 470 children). The results showed that psychological aggression experienced by the mother has adverse effects on children externalizing and internalizing behavior problems over and above the effects of physical aggression. The association between psychological aggression and child behavior problems was partially mediated by maternal distress. Exposure to psychological aggression appears to have unique direct and indirect adverse effects on children. C1 Harvard Univ, Sch Publ Hlth, Dept Social Human Dev & Hlth, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Koenen, KC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social Human Dev & Hlth, 677 Huntington Ave,Kresge 613, Boston, MA 02115 USA. EM kkoenen@hsph.harvard.edu NR 20 TC 4 Z9 4 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2007 VL 20 IS 1 BP 97 EP 101 DI 10.1002/jts.20193 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 147CP UT WOS:000244981300010 ER PT J AU Bush, RL Johnson, ML Hedayati, N Henderson, WG Lin, PH Lumsden, AB AF Bush, Ruth L. Johnson, Michael L. Hedayati, Nasim Henderson, William G. Lin, Peter H. Lumsden, Alan B. TI Performance of endovascular aortic aneurysm repair in high-risk patients: Results from the Veterans Affairs National Surgical Quality Improvement Program SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 01-04, 2006 CL Philadelphia, PA SP Soc Vasc Surg ID RANDOMIZED CONTROLLED-TRIAL; LOGISTIC-REGRESSION MODELS; OPERATIVE MORTALITY; SERUM-ALBUMIN; AAA REPAIR; OF-LIFE; OUTCOMES; OCTOGENARIANS; COST; CARE AB Objective: Recent results after endovascular abdominal aortic aneurysm repair (EVAR) have brought into question its value in patients deemed at high-risk for surgical intervention. The Department of Veteran Affairs (VA) National Surgical Quality Improvement Program (NSQIP) is the largest prospectively collected and validated United States surgical database representing current clinical practice. The purpose of our study was to evaluate outcomes after elective EVAR performed in high-risk veterans. Methods: Using NSQIP data from 123 participating VA hospitals, we retrospectively evaluated patients who underwent elective aneurysm repair from May 2001 to December 2004. High-risk criteria were used to identify a cohort for analysis (EVAR, n = 788; open, n = 1580). High-risk criteria analyzed included age >= 60 years, American Society of Anesthesiology (ASA) classification 3 or 4, and the comorbidity variables of history of cardiac, respiratory, or hepatic disease, cardiac revascularization, renal insufficiency, and low serum albumin level. Our primary end points were 30-day and 1-year all-cause mortality, and we evaluated a secondary end point of perioperative complications. Statistical analysis included univariate analysis and multivariate modeling. Results: Veterans who were classified as high-risk underwent elective EVAR with significantly lower 30-day (3.4% vs 5.2%, P = .047) and 1-year all-cause mortality (9.5% vs 12.4%, P = .038) than patients having open repair. EVAR was associated with a decrease in 30-day postoperative mortality (adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.42 to 1.03; P = .067) as well as 1-year mortality (adjusted OR, 0.68; 95% CI, 0.51 to 0.91; P = .0094) despite the presence of severe comorbid conditions. The risk of perioperative complications was significantly lower after EVAR (16.2% vs 31.0%; P < .0001; adjusted OR, 0.41; 95% CI, 0.33 to 0.52; P < .0001). A subset analysis of higher-risk patients (ASA 4 and the above comorbidity variables) still demonstrated an acceptable 30-day mortality rate. Conclusion: In veterans deemed high-risk for surgical therapy, outcomes after elective EVAR are excellent, and the procedure is relatively safe in this special patient population. Our retrospective data demonstrate that patients with considerable medical comorbidities and infrarenal abdominal aortic aneurysms benefit from and should be considered for primary EVAR. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Univ Houston, Michael E DeBakey Dept Surg, Coll Pharm, Baylor Coll Med, Houston, TX 77030 USA. Univ Colorado, Hlth Outcomes Program, Boulder, CO 80309 USA. RP Bush, RL (reprint author), Univ Houston, Michael E DeBakey Dept Surg, Coll Pharm, Baylor Coll Med, 1709 Dryden,Suite 1568, Houston, TX 77030 USA. EM rbush@bcm.tmc.cdu NR 42 TC 60 Z9 63 U1 0 U2 0 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 FEB PY 2007 VL 45 IS 2 BP 227 EP 233 DI 10.1016/j.jvs.2006.10.005 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 133BS UT WOS:000243987200001 PM 17263992 ER PT J AU Gangireddy, C Rectenwald, JR Upchurch, GR Wakefield, TW Khuri, S Henderson, WG Henke, PK AF Gangireddy, Chethan Rectenwald, John R. Upchurch, Gilbert R. Wakefield, Thomas W. Khuri, Shukri Henderson, William G. Henke, Peter K. TI Risk factors and clinical impact of postoperative symptomatic venous thromboembolism SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 01-04, 2006 CL Philadelphia, PA SP Soc Vasc Surg ID DEEP-VEIN THROMBOSIS; ILL MEDICAL PATIENTS; PULMONARY-EMBOLISM; SURGICAL RISK; HOSPITALIZED-PATIENTS; CANCER-SURGERY; PREVENTION; ENOXAPARIN; MORBIDITY; PROPHYLAXIS AB Background: Although common risk factors for venous thromboembolism (VTE) are well known, little data exist concerning the clinical impact of VTE in postoperative patients outside of controlled studies. This study evaluated prospective perioperative demographic and clinical variables associated with occurrence of postoperative symptomatic VTE. Methods Demographic and clinical data were collected on surgical patients undergoing nine common general, vascular, and orthopedic operations presenting to the Veterans Health Administration Hospitals between 1996 and 2001 as part of the National Surgical Quality Improvement Program (NSQIP). The association between covariates and the incidence of postoperative symptomatic VTE (includes deep venous thrombosis and pulmonary embolism) was assessed using bivariable and multivariable regression. Results: Complete demographic and clinical information for analysis were available for 75,771 patients. The mean patient age was 65 years, and 96.6% were men. Major comorbidities included diabetes mellitus (DM), 25%; chronic obstructive pulmonary disease (COPD), 18.3%; and congestive heart failure (CHF), 3.9%. Symptomatic VTE was diagnosed in 805 patients (0.68%), varied significantly with procedure (0.14% for carotid endarterectomy vs 1.34% for total hip arthroplasty), and was associated with increased 30-day mortality (16.9% vs 4.4%, P < .0001). The incidence of VTE did not decline substantially between 1996 and 2001 (0.72% vs 0.68%). Preoperative factors associated with symptomatic VTE were older age, male gender, corticosteroid use, COPD, recent weight loss, disseminated cancer, low albumin, and low hematocrit (all P < .01) but not DM. Postoperative factors associated with VTE were myocardial infarction (MI), blood transfusion (> 4 units), coma, pneumonia, and urinary tract infection (UTI), whereas those with hemodialysis-dependent renal failure were less likely to experience VTE (all P < .01). In multivariable analysis, adjusting for age and the variables significant by bivariable analysis, the strongest positive predictors of symptomatic VTE included UTI (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3 to 2.5), acute renal insufficiency (OR, 1.9; 95% CI, 1.1 to 3.2), postoperative transfusion (OR, 2.3; 95% CI, 1.4 to 3.7), perioperative MI (OR, 2.4; 95% CI, 1.5 to 3.9), and pneumonia (OR, 2.7; 95% CI, 2.1 to 3.5). In contrast, hemodialysis (OR, 0.3; 95% CI, 0.07 to 0.71), DM (OR, 0.75; 95% CI, 0.61 to 0.93), and higher preoperative albumin levels (OR, 0.8; 95% CI, 0.74 to 0.96, per mg/dL change) were protective from symptomatic VTE. Conclusions: Although the overall incidence of symptomatic VTE is low in surgical patients, it is associated with significantly increased 30-day mortality. In addition to previously recognized risk factors, patients who have postoperative complications of an infectious nature, bleeding, or MI are at particular risk. C1 Univ Michigan, Sch Med, Vasc Surg Sect, Ann Arbor, MI 48109 USA. VA Boston Hlth Care Syst, Boston, MA USA. Univ Colorado, Denver, CO 80202 USA. RP Henke, PK (reprint author), Univ Michigan Hlth Syst, 1500 E Med Ctr Dr,2210 Taubman Hlth Care Ctr, Ann Arbor, MI 48109 USA. EM henke@umich.edu NR 31 TC 110 Z9 117 U1 0 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 FEB PY 2007 VL 45 IS 2 BP 335 EP 341 DI 10.1016/j.jvs.2006.10.034 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 133BS UT WOS:000243987200022 PM 17264013 ER PT J AU Raffetto, JD Ross, RL Khalil, RA AF Raffetto, Joseph D. Ross, Reagan L. Khalil, Raouf A. TI Matrix metalloproteinase 2-induced venous dilation via hyperpolarization and activation of K+ channels: Relevance to varicose vein formation SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 01-04, 2006 CL Philadelphia, PA SP Soc Vasc Surg ID ABDOMINAL AORTIC-ANEURYSMS; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE; ARTERIOLAR VASODILATION; GENERAL-POPULATION; ENDOTHELIAL-CELLS; SAPHENOUS-VEIN; EDINBURGH VEIN; MATRIX-METALLOPROTEINASE-9; INSUFFICIENCY AB Background: Varicose veins are a common disorder of extensive venous dilation and remodeling with an as-yet unclear mechanism. Studies have shown increased plasma and tissue levels of matrix metalloproteinases (MMPs) in human varicose veins and animal models of venous hypertension. Although the effects of MMPs are generally attributed to extracellular matrix degradation, their effects on the mechanisms of venous contraction/relaxation are unclear. Our preliminary experiments have demonstrated that MMP-2 causes inhibition of phenylephrine-induced venous contraction. The purpose of this study was to determine whether MMP-induced inhibition of venous contraction involves an endothelium-dependent and/or -independent pathway. Methods: Circular segments of the inferior vena cava (IVC) were isolated from male Sprague-Dawley rats and suspended between two wire hooks in a tissue bath, and the effects of MMP-2 on phenylephrine- and KCl-induced contraction were measured. To study the role of endothelium-derived vasodilators, experiments were performed in the presence and absence of endothelium; N-L-nitro-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis; indomethacin, an inhibitor of prostacyclin synthesis; cromakalim, an activator of adenosine triphosphate-sensitive K+ channels (K-ATP); and iberiotoxin, a blocker of large-conductance Ca2+-dependent K+ channels (BKCa) and smooth muscle hyperpolarization. Results: In endothelium-intact IVC segments, phenylephrine (10(-5) mol/L) caused significant contraction that slowly declined to 82.0% in 30 minutes. The addition of MMP-2 (1 mu g/mL) caused a gradual decrease of phenylephrine contraction to 39.5% at 30 minutes. In endothelium-denuded IVC, MMP-2 induced a greater reduction of phenylephrine contraction, to 7.6%. In the presence of L-NAME (10(-4) mol/L), MMP-2 caused a marked decrease in phenylephrine contraction, to 4.4%. Large MMP-2-induced inhibition of phenylephrine contraction was also observed in IVC treated with L-NAME plus indomethacin. MMP-2 caused relaxation of phenylephrine contraction in IVC pretreated with cromakalim (10(-7) mol/L), an activator of K-ATP channels. MMP-2-induced inhibition of phenylephrine contraction was abrogated in the presence of iberiotoxin (10(-8) mol/L), a blocker of BKCa. MMP-2 did not inhibit venous contraction during membrane depolarization by 96 mmol/L KCl, a condition that prevents outward K+ conductance and cell hyperpolarization. Conclusions: MMP-2 causes significant IVC relaxation that is potentiated in the absence of endothelium or during blockade of endothelium-mediated nitric oxide and prostacyclin synthesis. The lack of effects of MMP-2 on KCl contraction and in iberiotoxin-treated veins suggests MMP-2-induced smooth muscle hyperpolarization and activation of BKCa channels-a novel effect of MMP that may play a role in the early stages of venous dilation and varicose vein formation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Vasc Surg, Boston, MA 02115 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. RP Khalil, RA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Vasc Surg, Thorn 10,75 Francis St, Boston, MA 02115 USA. EM raouf_khalil@hms.harvard.edu FU NHLBI NIH HHS [R01 HL070659, R01 HL065998, HL-70659, HL-65998] NR 41 TC 52 Z9 56 U1 0 U2 1 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 FEB PY 2007 VL 45 IS 2 BP 373 EP 380 DI 10.1016/j.jvs.2006.10.041 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 133BS UT WOS:000243987200028 PM 17264019 ER PT J AU Yu, XG Lichterfeld, M Chetty, S Williams, KL Mui, SK Miura, T Frahm, N Feeney, ME Tang, Y Pereyra, F LaBute, MX Pfafferott, K Leslie, A Crawford, H Allgaier, R Hildebrand, W Kaslow, R Brander, C Allen, TM Rosenberg, ES Kiepiela, P Vajpayee, M Goepfert, PA Altfeld, M Goulder, PJR Walker, BD AF Yu, Xu G. Lichterfeld, Mathias Chetty, Senica Williams, Katie L. Mui, Stanley K. Miura, Toshiyuki Frahm, Nicole Feeney, Margaret E. Tang, Yanhua Pereyra, Florencia LaBute, Montiago X. Pfafferott, Katja Leslie, Alisdair Crawford, Hayley Allgaier, Rachel Hildebrand, William Kaslow, Richard Brander, Christian Allen, Todd M. Rosenberg, Eric S. Kiepiela, Photini Vajpayee, Madhu Goepfert, Paul A. Altfeld, Marcus Goulder, Philip J. R. Walker, Bruce D. TI Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; LYMPHOCYTE ESCAPE; HIV-1 INFECTION; ANTIGEN RECEPTOR; SLOW PROGRESSORS; CTL ESCAPE; SELECTION; RECOGNITION; RESPONSES; EPITOPES AB The relative contributions of HLA alleles and T-cell receptors (TCRs) to the prevention of mutational viral escape are unclear. Here, we examined human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T-cell responses restricted by two closely related HLA class I alleles, B*5701 and B*5703, that differ by two amino acids but are both associated with a dominant response to the same HIV-1 Gag epitope KF11 (KAFSPEVIP MF). When this epitope is presented by HLA-13*5701, it induces a TCR repertoire that is highly conserved among individuals, cross-recognizes viral epitope variants, and is rarely associated with mutational escape. In contrast, KF11 presented by HIA-B*5703 induces an entirely different, more heterogeneous TCR beta-chain repertoire that fails to recognize specific KF11 escape variants which frequently arise in clade C-infected HLA-B*5703(+) individuals. These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. Univ KwaZulu Natal, HIV Pathogenesis Program, Doris Duke Med Res Inst, Durban, South Africa. Los Alamos Natl Lab, Div Theoret, Theoret Biol & Biophys Grp, Los Alamos, NM USA. Univ Oxford, Dept Paediat, Nuffield Dept Clin Med, Oxford, England. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Alabama, Birmingham, AL USA. All India Inst Med Sci, New Delhi, India. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Room 5212, Charlestown, MA 02129 USA. EM bwalker@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [P30 AI060354]; NICHD NIH HHS [U01 HD040533, U01 HD040474, U01 HD40533] NR 39 TC 58 Z9 60 U1 1 U2 2 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 FEB PY 2007 VL 81 IS 4 BP 1619 EP 1631 DI 10.1128/JVI.01580-06 PG 13 WC Virology SC Virology GA 136RI UT WOS:000244241400009 PM 17121793 ER PT J AU Appelt, CJ Burant, CJ Siminoff, LA Kwoh, CK Ibrahim, SA AF Appelt, Cathleen J. Burant, Christopher J. Siminoff, Laura A. Kwoh, C. Kent Ibrahim, Said A. TI Arthritis-specific health beliefs related to aging among older male patients with knee and/or hip osteoarthritis SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT National Annual Meeting of the US Department of Veterans Affairs Health Services Research and Development Service CY FEB, 2005 CL Baltimore, MD ID AFRICAN-AMERICAN; RHEUMATOID-ARTHRITIS; ETHNIC-DIFFERENCES; JOINT REPLACEMENT; UNITED-STATES; ARTHROPLASTY; PERCEPTIONS; CARE; EXPECTATIONS; PREFERENCES AB Background. Disease-specific beliefs may impact patients' perceptions of the efficacy of various treatment options, thus, it is important to understand these beliefs. We examined the relationship between patients' demographic characteristics and arthritis-specific beliefs related to aging. Methods. We performed a cross-sectional survey of 591 elderly primary care patients, who had symptomatic osteoarthritis (OA) of the knee and/or hip, at the Louis Stokes VA Medical Center in Cleveland, Ohio. Data were collected on age, race, educational level, income, and whether patients agreed or disagreed with four statements regarding aging and arthritis. We also assessed OA symptom severity using the Western Ontario McMaster Universities Index (WOMAC) and depressive symptoms using the Geriatric Depression Scale. We used logistic regression analyses to examine relationships between patients' age, race, and educational level and arthritis-specific health beliefs, while adjusting for OA symptom severity, radiographic confirmation of OA, OA joint burden, depressive symptoms, and income. Results. Patients 70 years old or older, as compared to patients 50-59 years old, were more likely to believe that: arthritis is a natural part of growing old; people should expect that when they get older, they won't be able to walk as well, and people should expect to live with pain as they grow older. Conclusion. Among older, male veterans, health beliefs regarding the relationship between aging and arthritis vary by age. Clinicians should consider these differences when discussing treatment strategies with their patients with knee and/or hip OA. C1 VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. Virginia Commonwealth Univ, Sch Med, Dept Social & Behav Hlth, Richmond, VA 23284 USA. Vet Adm Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. RP Appelt, CJ (reprint author), VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, 7180 Highland Dr Div,151R-HD, Pittsburgh, PA 15206 USA. EM cathleen.appelt@va.gov RI Siminoff, Laura /H-6277-2012 NR 38 TC 16 Z9 16 U1 2 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD FEB PY 2007 VL 62 IS 2 BP 184 EP 190 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 178KU UT WOS:000247220400009 PM 17339644 ER PT J AU Keller, CR Odden, MC Fried, LF Newman, AB Angleman, S Green, CA Cummings, SR Harris, TB Shlipak, MG AF Keller, C. R. Odden, M. C. Fried, L. F. Newman, A. B. Angleman, S. Green, C. A. Cummings, S. R. Harris, T. B. Shlipak, M. G. TI Kidney function and markers of inflammation in elderly persons without chronic kidney disease: The health, aging, and body composition study SO KIDNEY INTERNATIONAL LA English DT Article DE inflammation; biomarkers; cystatin; kidney; epidemiology ID SERUM CYSTATIN-C; GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; CHRONIC-RENAL-FAILURE; REACTIVE PROTEIN; HEMODIALYSIS-PATIENTS; CARDIOVASCULAR EVENTS; PLASMA; RISK; INTERLEUKIN-6 AB Inflammatory markers are elevated in persons with estimated glomerular filtration rates less than 60ml/min/1.73m(2). As cystatin C may detect small changes in kidney function not detected by estimated glomerular filtration rate, we evaluated the association between cystatin C and serum markers of inflammation in older adults with estimated glomerular filtration rate >= 60. This is an analysis using measures from the Health, Aging, and Body Composition Study, a cohort of well-functioning adults aged 70-79 years. Cystatin C correlated with all five inflammatory biomarkers: C-reactive protein ( r = 0.08), interleukin-6 ( r = 0.19), tumor necrosis factor alpha ( TNF-alpha) ( r = 0.41), soluble TNF receptor 1 ( STNF-R1) ( r = 0.61), and soluble TNF receptor 2 ( STNF-R2) ( r = 0.54); P < 0.0005 for all. In adjusted analyses, cystatin C concentrations appeared to have stronger associations with each biomarker compared with estimated glomerular filtration rate or serum creatinine. Participants with a cystatin C >= 1.0mg/l had significantly higher levels of all five biomarkers compared to those with a cystatin C < 1.0 ( mean differences ranging 16-29%, all P < 0.05). Cystatin C has a linear association with inflammatory biomarkers in an ambulatory elderly cohort with estimated glomerular filtration rates >= 60; associations are particularly strong with TNF-alpha and the STNF-R. C1 Vet Adm Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Sch Med, Renal Sect, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Renal Sect, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15260 USA. NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. Univ Tennessee, Dept Med, Div Nephrol, Knoxville, TN 37996 USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Shlipak, MG (reprint author), Vet Adm Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Angleman, Sara/0000-0002-9520-5716 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL073208-01]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIDDK NIH HHS [R01 DK066488-01] NR 42 TC 77 Z9 79 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2007 VL 71 IS 3 BP 239 EP 244 DI 10.1038/sj.ki.5002042 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 129LK UT WOS:000243730800011 PM 17183246 ER PT J AU Lum, G Szuflad, P AF Lum, Gifford Szuflad, Paula TI Profound thrombocytopenia associated with administration of eptifibatide SO LABMEDICINE LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; GLYCOPROTEIN IIB-IIIA; PLATELET TRANSFUSIONS; THERAPY AB Acute profound thrombocytopenia may be associated with the administration of eptifibatide, a glycoprotein antagonist, A case report of a 61-year-old male is presented. The reported incidence of acute profound thrombocytopenia associated with eptifibatide is 0.1% to 1.0% and usually occurs within 24 hours following therapy. However, cases of profound thrombocytopenia have been reported to occur within 1 to 4 hours following infusion. Platelet counts should be monitored in patients receiving eptifibatide at least within 24 hours and preferably within 2 to 4 hours after administration. C1 VA Boston Healthcare Syst, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD FEB PY 2007 VL 38 IS 2 BP 97 EP 99 DI 10.1309/2AFBQJOH4REBGX8A PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 130BG UT WOS:000243773500012 ER PT J AU Roman, GC Navarro-Roman, LI AF Roman, Gustavo C. Navarro-Roman, Lydia I. TI The discovery of HTLV-1 myelitis: 21 years later SO LANCET NEUROLOGY LA English DT Editorial Material ID TROPICAL SPASTIC PARAPARESIS; MYELOPATHY C1 Univ Texas, Hlth Sci Ctr, Dept Med Neurol, San Antonio, TX 78229 USA. Vet Adm Hosp, San Antonio, TX USA. Alliance Wellness Grp, San Antonio, TX USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Neurol, San Antonio, TX 78229 USA. NR 7 TC 1 Z9 1 U1 1 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD FEB PY 2007 VL 6 IS 2 BP 104 EP 105 DI 10.1016/S1474-4422(07)70012-1 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 130JG UT WOS:000243795300007 PM 17239794 ER PT J AU Broadhurst, MS Akst, LM Burns, JA Kobler, JB Heaton, JT Anderson, RR Zeitels, SM AF Broadhurst, Matthew S. Akst, Lee M. Burns, James A. Kobler, James B. Heaton, James T. Anderson, R. Rox Zeitels, Steven M. TI Effects of 532 nm pulsed-KTP laser parameters on vessel ablation in the avian chorioallantoic membrane: Implications for vocal fold mucosa SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 109th Annual Meeting of the Triological-Society CY MAY, 2006 CL Chicago, IL SP Triol Soc DE vocal fold; vocal cord; glottic; laryngoscopy; photoangiolysis; larynx; KTP laser ID DYE-LASER; LARYNGEAL PAPILLOMAS; GLOTTAL DYSPLASIA; PHONOSURGERY; LARYNGOLOGY; SINGERS; FUTURE AB Objectives. Selective vascular ablation (photoangiolysis) using pulsed lasers that target hemoglobin is an effective treatment strategy for many vocal fold lesions. However, vessel rupture with extravasation of blood reduces selectivity for vessels, which is frequently observed with the 0.45-ms, 585-nm pulsed dye laser. Previous studies have shown that vessel rupture is the result of vaporization of blood, an event that varies with laser pulse width and pulse fluence (energy per unit area). Clinical observations using a 532-nm wavelength pulsed potassium-titanylphosphate (KTP) laser revealed less laser-induced hemorrhage than the pulsed dye laser. This study investigated settings for the pulsed KTP laser to achieve selective vessel destruction without rupture using the avian chorioallantoic membrane under conditions similar to flexible laryngoscopic delivery of the laser in clinical practice. Study Design. The chick chorioallantoic membrane offers convenient access to many small blood vessels similar in size to those targeted in human vocal fold. Using a 532-nm pulsed KTP laser, pulse width, pulse energy, and working distance from the optical delivery fiber were varied to assess influence on the ability to achieve vessel coagulation without vessel wall rupture. Methods. Third-order vessels (n=135) were irradiated: Energy (471-550 mJ), pulse width (10, 15,30 ms), and fiber-to-tissue distance (1 mm, 3 mm) were varied systematically. Results: Selective vessel destruction without vessel wall rupture was more often achieved by increasing pulse width, increasing the fiber-to-tissue distance, and decreasing energy. Vessel destruction without rupture was consistently achieved using 15- or 30-ms pulses with a fiber-to-tissue distance of 3 mm (pulse fluence of 13-16 J/cm(2)). Conclusions: This study substantiates our clinical observation that a 532-mn pulsed KTP laser was effective for ablating microcirculation while minimizing vessel wall rupture and hemorrhage. C1 Harvard Univ, Massachusetts Gen Hosp, Casey Chair Laryngeal Surg, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Casey Chair Laryngeal Surg, Sch Med, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM zeitels.steven@mgh.harvard.edu NR 19 TC 24 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2007 VL 117 IS 2 BP 220 EP 225 DI 10.1097/mlg.0b013e31802b5c1c PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 131SK UT WOS:000243890000005 PM 17204988 ER PT J AU Pletcher, SD Metson, R AF Pletcher, Steven D. Metson, Ralph TI Endoscopic ligation of the anterior ethmoid artery SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Combined Sections Meeting of the Triological-Society CY FEB 18, 2007 CL Marco Isl, FL SP Triol Soc DE epistaxis; anterior ethmoid artery; endocopic ligation ID REFRACTORY POSTERIOR EPISTAXIS; SPHENOPALATINE ARTERY; EMBOLIZATION; MANAGEMENT C1 Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Pletcher, SD (reprint author), 400 Parnassus Ave,ACC 7th Floor, San Francisco, CA 94143 USA. EM spletcher@ohns.ucsf.edu NR 13 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 2007 VL 117 IS 2 BP 378 EP 381 DI 10.1097/01.mlg.0000250778.29957.a1 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 131SK UT WOS:000243890000036 PM 17204990 ER PT J AU Sherwood, ME Flotte, TJ AF Sherwood, Margaret E. Flotte, Thomas J. TI Improved staining method for determining the extent of thermal damage to cells SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE lactate dehydrogenase; pathology; thermal damage ID LASER TREATMENT; SKIN; VIABILITY; DEPTH AB Background and Objective: Enzyme histochernical stains of frozen sections have been used by investigators to assess thermal damage. The assessment of thermal damage to cells in lipid-rich tissues such as subcutaneous tissue and sebaceous glands can be difficult due to the quality of frozen sections of such tissues. The purpose of this study is to develop an improved method for this type of evaluation. Study Design/Materials and Methods: Thick frozen sections of thermally damaged pig and human skin were stained for lactate dehydrogenase. The sections were fixed in formalin and processed for paraffin-embedded sections. Results: The sections showed well-defined localization of the enzymatic deposits as well as preservation of the tissue architecture. Conclusion: The paraffin-embedded lactate dehydrogenase stained sections provide improved evaluation of thermally damaged tissues, particularly the lipid rich tissues. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Flotte, TJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, WRN 829,55 Fruit St, Boston, MA 02114 USA. EM tflotte@partners.org NR 9 TC 9 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2007 VL 39 IS 2 BP 128 EP 131 DI 10.1002/lsm.20450 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 141WK UT WOS:000244609500006 PM 17163480 ER PT J AU Obasaju, CK Ye, Z Wozniak, AJ Belani, CP Keohan, ML Ross, HJ Polikoff, JA Mintzer, DM Monberg, MJ Janne, PA AF Obasaju, Coleman K. Ye, Zhishen Wozniak, Antoinette J. Belani, Chandra P. Keohan, Mary-Louise Ross, Helen J. Polikoff, Jonathan A. Mintzer, David M. Monberg, Matthew J. Janne, Pasi A. TI Single-arm, open label study of pemetrexed plus cisplatin in chemotherapy naive patients with malignant pleural mesothelioma: Outcomes of an expanded access program SO LUNG CANCER LA English DT Article DE chemotherapy naive; first-line; malignant pleural mesothelioma ID RANDOMIZED PHASE-III; MULTITARGETED ANTIFOLATE; EUROPEAN-ORGANIZATION; PROGNOSTIC-FACTORS; CANCER; COMBINATION; LY231514; TRIAL; MTA AB Background: An expanded access program (EAP) provided patient access to pemetrexed prior to its commercial availability. The current report consists of US patients in the EAP who had chemotherapy naive pleural mesothelioma. Methods: Eligible patients had a histologic or cytologic diagnosis-of malignant mesothetioma that was not amenable to curative treatment with surgery. Study treatment consisted of pemetrexed 500mg/m(2) in combination with cisplatin 75 mg/m(2) once every 21 days. Vitamin B12, folic acid, and dexamethasone were administered as prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmacovigilance database for all patients enrolled in the EAR Results: Of 1056 patients receiving at least one dose of pemetrexed in the EAR 728 had chemotherapy naive pleural mesothelioma. Median age of this group was 70 years (range 23-89 years) and 84% were mate. Among 615 patients, overall response rate was 20.5%, including 12 complete responses (2.0%) and 114 partial responses (18.5%). An additional 290 patients (47.2%) had stable disease. Median survival for all 728 patients was 10.8 months (95% Cl = 9.8, 12.3; 60.3% censorship) and 1 year survival was 45.4%. The most commonly reported SAEs in the overall EAP irrespective of causality were dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%). Conclusions: In this large cohort, 67.7% of patients treated with first-tine chemotherapy experienced a response or stable disease. Survival time and toxicity from this EAP were promising for this difficult-to-treat disease. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Wayne State Univ, Karmanos Inst, Detroit, MI USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Earle A Chiles Res Inst, Portland, OR USA. Kaiser Hosp, San Diego, CA USA. Penn Hosp, Philadelphia, PA 19107 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Obasaju, CK (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop Code 6831, Indianapolis, IN 46285 USA. EM cobasaju@lilly.com OI Belani, Chandra/0000-0001-5049-5329 NR 24 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD FEB PY 2007 VL 55 IS 2 BP 187 EP 194 DI 10.1016/j.lungcan.2006.09.023 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 134SC UT WOS:000244103300008 PM 17092602 ER PT J AU Ardekani, S Kumar, A Bartzokis, G Sinha, U AF Ardekani, Siamak Kumar, Anand Bartzokis, George Sinha, Usha TI Exploratory voxel-based analysis of diffusion indices and hemispheric asymmetry in normal aging SO MAGNETIC RESONANCE IMAGING LA English DT Article DE diffusion tensor imaging; voxel-based analysis; aging; hemispheric asymmetry ID WHITE-MATTER; HUMAN BRAIN; RHESUS-MONKEY; NERVE-FIBERS; AGE; MRI; SCHIZOPHRENIA; ANISOTROPY; INTEGRITY; BREAKDOWN AB Age-related microstructural changes in brain white matter can be studied by utilizing indices derived from diffusion tensor imaging (DTI): apparent difftision coefficient (ADC) and fractional anisotropy (FA). The objective of this study is to examine alterations in FA and ADC by employing exploratory voxel-based analysis (VBA) and region(s) of interest (ROI)-based analysis. A highly nonlinear registration algorithm was used to align the ADC and FA image volumes of different subjects to perform accurate voxel-level statistics for two age groups, as well as for hemispheric asymmetry for both age groups. VBA shows significant age-related decline in FA with frontal predominance (frontal white matter, and genu and anterior body of the corpus callosum), superior portions of a splenium and highly oriented fibers of the posterior limb of the internal capsule and the anterior and posterior limbs of the external capsule. Hemispheric asymmetry of FA, as assessed by VBA, showed that for the young-age group, significant right-greater-than-left asymmetry exists in the genu, splenium and body of the corpus callosum and that left-greater-than-right asymmetry exists in the anterior limb of the external capsule and in the posterior limb of the internal capsule, thalamus, cerebral peduncle and temporal-parietal regions. VBA of the hemispheric asymmetry of the middle-age group revealed much less asymmetry. Regions showing age-related changes and hemispheric asymmetry from VBA were, for a majority of the findings, in conformance with ROI analysis and with the known pattern of development and age-related degradation of fiber tracks. The study shows the feasibility of the VBA of DTI indices for exploratory investigations of subtle differences in population cohorts, especially when findings are not localized and/or known a priori. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Biomed Engn IDP, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Radiol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Div Brain Mapping,Lab Neuroimaging, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Dept Psychiat, West Los Angeles, CA 90073 USA. RP Sinha, U (reprint author), Univ Calif Los Angeles, Biomed Engn IDP, Los Angeles, CA 90095 USA. EM usinha@mii.ucla.edu RI Ardekani, Siamak/A-3487-2010; Bartzokis, George/K-2409-2013 FU NIBIB NIH HHS [P01-EB00216] NR 42 TC 76 Z9 77 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD FEB PY 2007 VL 25 IS 2 BP 154 EP 167 DI 10.1016/j.mri.2006.09.045 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 136YZ UT WOS:000244261300002 PM 17275609 ER PT J AU Lin, FH Tsai, SY Otazo, R Caprihan, A Wald, LL Belliveau, JW Posse, S AF Lin, Fa-Hsuan Tsai, Shang-Yueh Otazo, Ricardo Caprihan, Arvind Wald, Lawrence L. Belliveau, John W. Posse, Stefan TI Sensitivity-encoded (SENSE) proton echo-planar spectroscopic imaging (PEPSI) in the human brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine CY MAY 07-13, 2005 CL Miami Beach, FL SP Int Soc Magnet Resonance Med DE SENSE; PEPSI; parallel MRI; spectroscopic imaging; MRS ID MAGNETIC-RESONANCE; METABOLIC-RESPONSE; MRI; COIL; RESOLUTION; ANGIOGRAPHY; ACQUISITION; TESLA; SPEED; ARRAY AB Magnetic resonance spectroscopic imaging (MRSI) provides spatially resolved metabolite information that is invaluable for both neuroscience studies and clinical applications. However, lengthy data acquisition times, which are a result of time-consuming phase encoding, represent a major challenge for MRSI. Fast MRSI pulse sequences that use echo-planar readout gradients, such as proton echo-planar spectroscopic imaging (PEPSI), are capable of fast spectra I-spatia I encoding and thus enable acceleration of image acquisition times. Combining PEPSI with recent advances in parallel MRI utilizing RF coil arrays can further accelerate MRSI data acquisition. Here we investigate the feasibility of ultrafast spectroscopic imaging at high field (3T and 4T) by combining PEPSI with sensitivity-encoded (SENSE) MRI using eight-channel head coil arrays. We show that the acquisition of single-average SENSE-PEPSI data at a short TE (15 ms) can be accelerated to 32 s or less, depending on the field strength, to obtain metabolic images of choline (Cho), creatine (Cre), N-acetyl-aspartate (NAA), and J-coupled metabolites (e.g., glutamate (Glu) and inositol (Ino)) with acceptable spectral quality and localization. The experimentally measured reductions in signal-to-noise ratio (SNR) and Cramer-Rao lower bounds (CRLBs) of metabolite resonances were well explained by both the g-factor and reduced measurement times. Thus, this technology is a promising means of reducing the scan times of 3D acquisitions and time-resolved 2D measurements. C1 MGH HMS MIT, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. MIND Inst, Albuquerque, NM USA. Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. New Mexico Resonance, Albuquerque, NM USA. Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. RP Lin, FH (reprint author), MGH HMS MIT, Athinoula A Martinos Ctr Biomed Imaging, 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 FU NCRR NIH HHS [P41 RR14075]; NIBIB NIH HHS [R01 EB000790-04]; NICHD NIH HHS [R01 HD040712]; NIDA NIH HHS [R01 DA14178-01]; NINDS NIH HHS [R01 NS037462] NR 35 TC 48 Z9 48 U1 1 U2 5 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 FEB PY 2007 VL 57 IS 2 BP 249 EP 257 DI 10.1002/mrm.21119 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132MG UT WOS:000243946300003 PM 17260356 ER PT J AU Khachaturian, MH Wisco, JJ Tuch, DS AF Khachaturian, Mark H. Wisco, Jonathan J. Tuch, David S. TI Boosting the sampling efficiency of q-ball imaging using multiple wavevector fusion SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion MRI; diffusion tensor imaging; high-angular-resolution diffusion imaging; q-ball imaging; image fusion ID DIFFUSION-WEIGHTED MRI; HUMAN BRAIN; TENSOR; ARCHITECTURE; VALIDATION AB q-Ball imaging (QBI) is a high-angular-resolution diffusion imaging (HARDI) method that is capable of resolving complex, subvoxel white matter (WM) architecture. QBI requires time-intensive sampling of the diffusion signal and large diffusion wavevectors. Here we describe a reconstruction scheme for QBI, termed multiple wavevector fusion (MWF), that substantially boosts the sampling efficiency and signal-to-noise ratio (SNR) of QBI. The MWF reconstruction operates by nonlinearly fusing the diffusion signal from separate low and high wavevector acquisitions. The combination of wavevectors provides the benefits of the high SNR of the low wavevector signal and the high angular contrast-to-noise ratio (CNR) and peak separation of the high wavevector signal. The MWF procedure provides a framework for combining diffusion tensor imaging (DTI) and QBI. Numerical simulations show that MWF of DTI and QBI provides a more accurate estimate of the diffusion orientation distribution function (ODF) than QBI alone. The accuracy improvement can be translated into an efficiency gain of 274-377%. An intravoxel peak connectivity metric (IPCM) is presented that calculates the peak connectivity between an ODF and its neighboring voxels. In human WM, MWF reveals more detailed WM architecture than QBI as measured by the IPCM for all sampling schemes presented. Magn Reson Med 57: 289-296, 2007. (c) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. RP Khachaturian, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM markk@nmr.mgh.harvard.edu FU NCI NIH HHS [5T32CA09502, CA09502]; NCRR NIH HHS [RR14075]; NIBIB NIH HHS [EB05149]; NINDS NIH HHS [NS46532] NR 25 TC 32 Z9 32 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 FEB PY 2007 VL 57 IS 2 BP 289 EP 296 DI 10.1002/mrm.21090 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132MG UT WOS:000243946300008 PM 17260358 ER PT J AU Federman, AD Halm, EA Siu, AL AF Federman, Alex D. Halm, Ethan A. Siu, Albert L. TI Use of generic cardiovascular medications by elderly medicare beneficiaries receiving generalist or cardiologist care SO MEDICAL CARE LA English DT Article DE medicare; generic drugs; elderly; cardiovascular disease; generalist; cardiologist ID PHARMACEUTICAL SALES REPRESENTATIVES; DRUG BENEFIT PLANS; PRESCRIPTION DRUGS; POTENTIAL SAVINGS; PHYSICIANS; COST; SUBSTITUTION; UNDERUSE; COMMUNICATION; FORMULARY AB Background: Elderly Medicare beneficiaries can reduce out-of-pocket spending and increase their options for low-cost Medicare Part D plans by using generic drugs. Physicians play a key role in determining use of generics and specialty may be a particularly influential factor. Objectives: We sought to compare generic cardiovascular drug use by older adults receiving cardiologist and generalist care. Research Design: We undertook a cross-sectional analysis of data from the nationally representative Medicare Current Beneficiary Survey. Included were community-dwelling adults 66 years of age or older with hypertension, coronary disease, or congestive heart failure, one or more Medicare Part B claims for outpatient visits with generalists (internist or family practitioner) or cardiologists, using one or more cardiovascular drug available in both brand-name and generic formulations (n = 1828). Measures: The primary outcome was use of one or more generic medication aggregated across 5 drug classes: beta-blockers, thiazides, calcium channel blockers (CCB), angiotensin-converting enzyme (ACE) inhibitors, and alpha(1)-adrenergic receptor antagonists. Within-class generic use also was examined. The main independent variable was cardiologist (20.7%) versus generalist-only care (79.3%). Results: In the aggregate, fewer individuals under cardiologist care used generics compared with generalist-only care (75% vs. 81%, P = 0.03; adjusted relative risk 0.89, 95% confidence interval = 0.79-0.99). Overall use of generic beta-blockers was 86.6%; thiazides, 92.0%; ACE inhibitors, 59.0%; CCB, 55.5%; alpha-blockers 47.7%. In adjusted analysis, generic CCB use occurred 34% less often among cardiologist versus generalist-only patients. Conclusions: Older patients of generalists and, to a greater extent, cardiologists, often use brand-name drugs when generic equivalents are available. Promoting generic prescribing among specialists and generalists may increase opportunities for patients and third-party payers to reduce spending on prescription drugs. C1 CUNY Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Federman, AD (reprint author), CUNY Mt Sinai Sch Med, Div Gen Internal Med, 1470 Madison Ave,Box 1087, New York, NY 10029 USA. EM alex.federman@mssm.edu NR 32 TC 15 Z9 17 U1 1 U2 3 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 FEB PY 2007 VL 45 IS 2 BP 109 EP 115 DI 10.1097/01.mlr.0000250293.24939.2e PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 138GR UT WOS:000244351600002 PM 17224772 ER PT J AU Parodi, K Paganetti, H Cascio, E Flanz, JB Bonab, AA Alpert, NM Lohmann, K Bortfeld, T AF Parodi, Katia Paganetti, Harald Cascio, Ethan Flanz, Jacob B. Bonab, Ali A. Alpert, Nathaniel M. Lohmann, Kevin Bortfeld, Thomas TI PET/CT imaging for treatment verification after proton therapy: A study with plastic phantoms and metallic implants SO MEDICAL PHYSICS LA English DT Article DE proton therapy; positron emission tomography; Monte Carlo ID POSITRON-EMISSION-TOMOGRAPHY; MONTE-CARLO SIMULATIONS; IN-BEAM PET; DOSE CALCULATIONS; CT NUMBERS; RADIOACTIVITY; RADIOTHERAPY; CARBON; DISTRIBUTIONS; FEASIBILITY AB The feasibility of off-line positron emission tomography/computed tomography (PET/CT) for routine three dimensional in-vivo treatment verification of proton radiation therapy is currently under investigation at Massachusetts General Hospital in Boston. In preparation for clinical trials, phantom experiments were carried out to investigate the sensitivity and accuracy of the method depending on irradiation and imaging parameters. Furthermore, they addressed the feasibility of PET/CT as a robust verification tool in the presence of metallic implants. These produce x-ray CT artifacts and fluence perturbations which may compromise the accuracy of treatment planning algorithms. Spread-out Bragg peak proton fields were delivered to different phantoms consisting of polymethylmethacrylate (PMMA), PMMA stacked with lung and bone equivalent materials, and PMMA with titanium rods to mimic implants in patients. PET data were acquired in list mode starting within 20 min after irradiation at a commercial luthetium-oxyorthosilicate (LSO)-based PET/CT scanner. The amount and spatial distribution of the measured activity could be well reproduced by calculations based on the GEANT4 and FLUKA Monte Carlo codes. This phantom study supports the potential of millimeter accuracy for range monitoring and lateral field position verification even after low therapeutic dose exposures of 2 Gy, despite the delay between irradiation and imaging. It also indicates the value of PET for treatment verification in the presence of metallic implants, demonstrating a higher sensitivity to fluence perturbations in comparison to a commercial analytical treatment planning system. Finally, it addresses the suitability of LSO-based PET detectors for hadron therapy monitoring. This unconventional application of PET involves countrates which are orders of maonitude lower than in diagnostic tracer imaging, i.e., the signal of interest is comparable to the noise originating from the intrinsic radioactivity of the detector itself. In addition to PET alone, PET/CT imaging provides accurate information on the position of the imaged object and may assess possible anatomical changes during fractionated radiotherapy in clinical applications. (c) 2007 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Siemens Med Solut USA, Mol Imaging, Knoxville, TN 37932 USA. RP Parodi, K (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM k.parodi@gsi.de FU NCI NIH HHS [P01 CA021239-28, P01 CA021239, P01 CA21239-25] NR 44 TC 86 Z9 87 U1 0 U2 12 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 FEB PY 2007 VL 34 IS 2 BP 419 EP 435 DI 10.1118/1.2401042 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 139HZ UT WOS:000244424200006 PM 17388158 ER PT J AU Holmes, WC Gariti, KO Sadeghi, L Joisa, SD AF Holmes, William C. Gariti, Katherine O. Sadeghi, Leila Joisa, Sowmya D. TI Abuse of war zone detainees: Veterans' perceptions of acceptability SO MILITARY MEDICINE LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the International-Society-for-Traumatic-Stress-Studies (ISTSS) CY NOV 02-05, 2005 CL Toronto, CANADA SP Int Soc Traumat Stress Studies, Natl Inst Ment Hlth ID POSTTRAUMATIC-STRESS-DISORDER AB We assessed detainee abuse acceptance and variables associated with it. Outpatients from a veterans' hospital were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Three questionnaire versions differed in the final line of each version's scenarios, describing abuse either as: soldier initiated, superior ordered, or wrong by a "whistleblower" soldier. Three hundred fifty-one veterans participated, 80% with service during the Vietnam War. Zero tolerance for abuse-"completely unacceptable" regardless of who the detainee was-increased with abuse severity (16% for exposure, 31% for humiliation, and 48% for rape of detainee) and with soldier initiation. The strongest, most consistently significant odds were of depressed veterans, veterans with comorbid depression/post-traumatic stress disorder, and men being approximately 2, 3, and 4 to 20 times more tolerant of abuse than those without depression/post-traumatic stress disorder and women, respectively. There may be potential value to using similar scenario-based questionnaires to study active duty military perceptions of detainee abuse. Results may inform prevention policies. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Mental Hlth Clin, Philadelphia, PA 19104 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Holmes, WC (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 16 TC 1 Z9 1 U1 1 U2 2 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD FEB PY 2007 VL 172 IS 2 BP 175 EP 181 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 136NY UT WOS:000244232600015 PM 17357773 ER PT J AU Meuter, S Schaerli, P Roos, RS Brandau, O Bosl, MR von Andrian, UH Moser, B AF Meuter, Simone Schaerli, Patrick Roos, Regula Stuber Brandau, Oliver Boesl, Michael R. von Andrian, Ulrich H. Moser, Bernhard TI Murine CXCL14 is dispensable for dendritic cell function and localization within peripheral tissues SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INFLAMMATORY PROTEIN 3-ALPHA; MOUSE LYMPH-NODES; LANGERHANS CELLS; IN-VIVO; CHEMOKINE RECEPTORS; B-CELL; SKIN; EXPRESSION; MIGRATION; BRAK AB Dendritic cells (DCs) have long been recognized as key regulators of immune responses. However, the process of their recruitment to peripheral tissues and turnover during homeostasis remains largely unknown. The chemokine CXCL14 (BRAK) is constitutively expressed in skin and other epithelial tissues. Recently, the human chemokine was proposed to play a role in the homeostatic recruitment of macrophage and/or DC precursors toward the periphery, such as skin. Although so far no physiological function could be demonstrated for the murine CXCL14, it shows a remarkable homology to the human chemokine. In order to elucidate the in vivo role of CXCL14, we generated a mouse defective for this chemokine. We studied various components of the immune system with emphasis on monocytes/macrophages and DC/Langerhans cell (LC) populations in different tissues during steady state but did not find a significant difference between knockout (CXCL14(-/-)) and control mice. Functionally, LCs were able to become activated, to migrate out of skin, and to elicit a delayed type of hypersensitivity reaction. Overall, our data indicate that murine CXCL14 is dispensable for the homeostatic recruitment of antigen-presenting cells toward the periphery and for LC functionality. C1 Univ Bern, Inst Cell Biol, CH-3012 Bern, Switzerland. Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany. RP Moser, B (reprint author), Univ Cardiff Wales, Sch Med, Dept Med Biochem & Immunol, Henry Wellcome Bldg, Cardiff CF14 4XN, S Glam, Wales. EM moserb@cf.ac.uk RI von Andrian, Ulrich/A-5775-2008 NR 54 TC 39 Z9 41 U1 1 U2 3 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 FEB PY 2007 VL 27 IS 3 BP 983 EP 992 DI 10.1128/MCB.01648-06 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 132MD UT WOS:000243946000017 PM 17130243 ER PT J AU Zheng, Q Davis, EC Richardson, JA Starcher, BC Li, TS Gerard, RD Yanagisawa, H AF Zheng, Qian Davis, Elaine C. Richardson, James A. Starcher, Barry C. Li, Tiansen Gerard, Robert D. Yanagisawa, Hiromi TI Molecular analysis of fibulin-5 function during de novo synthesis of elastic fibers SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; CUTIS LAXA; IN-VIVO; HUMAN TROPOELASTIN; MISSENSE MUTATION; LYSYL-OXIDASE; BINDING; MICROFIBRILS; FIBRILLIN-1; IDENTIFICATION AB Elastic fibers contribute to the structural support of tissues and to the regulation of cellular behavior. Mice deficient for the fibulin-5 gene (fbln5(-/-)) were used to further elucidate the molecular mechanism of elastic fiber assembly. Major elastic fiber components were present in the skin of fbln5(-/-) mice despite a dramatic reduction of mature elastic fibers. We found that fibulin-5 preferentially bound the monomeric form of elastin through N-terminal and C-terminal elastin-binding regions and to a preexisting matrix scaffold through calcium-binding epidermal growth factor (EGF)-like (CB-EGF) domains. We further showed that adenovirus-mediated gene transfer of fbln5 was sufficient to regenerate elastic fibers and increase elastic fiber-cell connections in vivo. A mutant fibulin-5 lacking the first 28 amino acids of the first CB-EGF domain, however, was unable to rescue elastic fiber defects. Fibulin-5 thus serves as an adaptor molecule between monomeric elastin and the matrix scaffold to aid in elastic fiber assembly. These results also support the potential use of fibulin-5 as a therapeutic agent for the treatment of elastinopathies. C1 Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 2T5, Canada. Univ Texas, Ctr Hlth, Dept Biochem, Tyler, TX 75710 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Yanagisawa, H (reprint author), Univ Texas, SW Med Ctr, Dept Mol Biol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM hiromi.yanagisawa@utsouthwestern.edu RI Davis, Elaine/F-3449-2012 FU NHLBI NIH HHS [R01 HL071157, HL 071157] NR 36 TC 40 Z9 41 U1 1 U2 3 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 FEB PY 2007 VL 27 IS 3 BP 1083 EP 1095 DI 10.1128/MCB.01330-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 132MD UT WOS:000243946000025 PM 17130242 ER PT J AU Brunelle, JK Shroff, EH Perlman, H Strasser, A Moraes, CT Flavell, RA Danial, NN Keith, B Thompson, CB Chandel, NS AF Brunelle, Joslyn K. Shroff, Emelyn H. Perlman, Harris Strasser, Andreas Moraes, Carlos T. Flavell, Richard A. Danial, Nika N. Keith, Brian Thompson, Craig B. Chandel, Navdeep S. TI Loss of Mcl-1 protein and inhibition of electron transport chain together induce anoxic cell death SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BCL-2 FAMILY-MEMBERS; FACTOR-INDEPENDENT SURVIVAL; STRESS-INDUCED APOPTOSIS; BH3-ONLY PROTEINS; CYTOCHROME-C; OXYGEN DEPRIVATION; ANTIAPOPTOTIC PROPERTIES; MITOCHONDRIAL APOPTOSIS; MICE LACKING; BH3 DOMAINS AB How cells die in the absence of oxygen (anoxia) is not understood. Here we report that cells deficient in Bax and Bak or caspase-9 do not undergo anoxia-induced cell death. However, the caspase-9 null cells do not survive reoxygenation due to the generation of mitochondrial reactive oxygen species. The individual loss of Bim, Bid, Puma, Noxa, Bad, caspase-2, or hypoxia-inducible factor 1 beta, which are potential upstream regulators of Bax or Bak, did not prevent anoxia-induced cell death. Anoxia triggered the loss of the Mcl-1 protein upstream of Bax/Bak activation. Cells containing a mitochondrial DNA cytochrome b 4-base-pair deletion ([rho(-)] cells) and cells depleted of their entire mitochondrial DNA ([rho(0)] cells) are oxidative phosphorylation incompetent and displayed loss of the Mcl-1 protein under anoxia. [rho(0)] cells, in contrast to [rho-] cells, did not die under anoxia. However, [rho(0)] cells did undergo cell death in the presence of the Bad BH3 peptide, an inhibitor of Bcl-X-L/Bcl-2 proteins. These results indicate that [rho(0)] cells survive under anoxia despite the loss of Mcl-1 protein due to residual prosurvival activity of the Bcl-X-L/Bcl-2 proteins. Collectively, these results demonstrate that anoxia-induced cell death requires the loss of Mcl-1 protein and inhibition of the electron transport chain to negate Bcl-X-L/Bcl-2 proteins. C1 Univ Penn, Sch Med, Abramson Family Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Yale Univ, Sch Med, Immunobiol Sect, Howard Hughes Med Inst, New Haven, CT 06520 USA. Univ Miami, Sch Med, Dept Cell Biol & Anat, Miami, FL 33136 USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63104 USA. Northwestern Univ, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA. St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63104 USA. RP Chandel, NS (reprint author), Northwestern Univ, Sch Med, McGaw Pavill,240 E huron Ave,M-334, Chicago, IL 60611 USA. EM nav@northwestern.edu RI Strasser, Andreas/C-7581-2013; OI Strasser, Andreas/0000-0002-5020-4891 FU NCI NIH HHS [CA 009560, T32 CA009560]; NHLBI NIH HHS [HL 076139, P01 HL 071643-03-04, T32 HL076139]; NIGMS NIH HHS [GM 60472-07, R01 GM060472] NR 60 TC 34 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 2007 VL 27 IS 4 BP 1222 EP 1235 DI 10.1128/MCB.01535-06 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 136OE UT WOS:000244233200003 PM 17145774 ER PT J AU Lerma, EI Nguyen, VA Wang, T Tipping, A Melo, JV Kufe, D Austin, DJ Deisseroth, A AF Lerma, Enrica I. Nguyen, Viet-Anh Wang, Tao Tipping, Alex Melo, Junia V. Kufe, Donald Austin, David J. Deisseroth, Albert TI Novel compounds with antiproliferative activity against imatinib-resistant cell lines SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; BCR-ABL; SELECTIVE INHIBITOR; MECHANISMS; DASATINIB; PROTEIN; CYCLOADDITION; MUTATIONS AB Chronic myelogenous leukemia is caused by the Bcr-Abl hybrid gene that encodes the p210Bcr-Abl chimeric oncoprotein. Although it reduces the total body burden of leukemia cells, the use of imatinib mesylate as a single agent may be accompanied by the evolution of resistance due mainly to the acquisition of point mutations. Imatinilb has been combined with drugs that inhibit both the active and the inactive states of the p21013cr-Abl kinase. These combinations have reduced but not completely eliminated the rate at which point mutations are acquired in the p210Bcr-Abl kinase. Thus, it is important to identify additional new inhibitors of the p210Bcr-Abl kinase. One possible method to prevent evolution of resistance is to simultaneously use multiple kinase inhibitors each with a different mechanism of action. To identify such a new class of inhibitors that could suppress the growth of chronic myelogenous leukemia cells and prevent the evolution of cells that are resistant to imatinib, we screened two low-complexity libraries of compounds based on planar and linear scaffolds. These libraries were screened using a cell-based assay for molecules that suppress p21OBcr-Abl-dependent cell growth. The application of this method resulted in the isolation of two new classes of drugs, both of which inhibited imatinib-resistant cells in the low micromolar range. Some of these drugs were potent inhibitors not only of Abl tyrosine kinase but also of the Src, Lyn, and Fyn tyrosine kinases. C1 Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. Yale Univ, New Haven, CT 06520 USA. Imperial Coll Sch Med, London, England. Hammersmith Hosp, London, England. Dana Farber Canc Ctr, Boston, MA USA. RP Deisseroth, A (reprint author), Sidney Kimmel Canc Ctr, 10835 Altman Row, San Diego, CA 92121 USA. EM adeisseroth@skcc.org FU NCI NIH HHS [P01 CA 49639-09] NR 30 TC 3 Z9 3 U1 0 U2 3 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 FEB PY 2007 VL 6 IS 2 BP 655 EP 666 DI 10.1158/1535-7163.MCT-04-0307 PG 12 WC Oncology SC Oncology GA 136ZN UT WOS:000244262700026 PM 17267662 ER PT J AU Matsuo, K Glahn, DC Peluso, MAM Hatch, JP Monkul, ES Najt, P Sanches, M Zamarripa, F Li, J Lancaster, JL Fox, PT Gao, JH Soares, JC AF Matsuo, K. Glahn, D. C. Peluso, M. A. M. Hatch, J. P. Monkul, E. S. Najt, P. Sanches, M. Zamarripa, F. Li, J. Lancaster, J. L. Fox, P. T. Gao, J-H Soares, J. C. TI Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder SO MOLECULAR PSYCHIATRY LA English DT Article; Proceedings Paper CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat DE gyrus cinguli; attention; cognition; prefrontal cortex; mood disorders; functional magnetic resonance imaging; memory ID FUNCTIONAL MAGNETIC-RESONANCE; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; UNIPOLAR DEPRESSION; BIPOLAR DISORDER; MOOD DISORDERS; PANIC DISORDER; FRONTAL LOBES AB The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, there are few functional neuroimaging studies of MDD patients during working memory processing, and most of the available ones included medicated patients or patients with both MDD and bipolar disorder. We used functional magnetic resonance imaging (fMRI) to measure prefrontal cortex function during working memory processing in untreated depressed patients with MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition recurrent MDD (mean age +/- s.d. = 34.3 +/- 11.5 years) and 15 healthy comparison subjects (37.7 +/- 12.1 years) matched for age, sex and race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back) was used to elicit frontal cortex activation. Data were analyzed with a multiple regression analysis using the FSL-FEAT software. MDD patients showed significantly greater left dorsolateral cortex activation during the n-back task compared to the healthy controls (P < 0.01), although task performance was similar in the two groups. Furthermore, the patients showed significant anterior cingulate cortex activation during the task, but the comparison subjects did not (P < 0.01). This study provides in vivo imaging evidence of abnormal frontolimbic circuit function during working memory processing in individuals with MDD. C1 Univ Texas, Hlth Sci Ctr, MOOD CNS Program, Dept Psychiat,Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX USA. Univ Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, MOOD CNS Program, Dept Psychiat,Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI Lancaster, Jack/F-2994-2010; Li, Jinqi/F-7778-2010; Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU NCRR NIH HHS [RR020571, M01-RR-01346]; NIMH NIH HHS [MH 068662, MH 01736] NR 75 TC 103 Z9 106 U1 7 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2007 VL 12 IS 2 BP 158 EP 166 DI 10.1038/sj.mp.4001894 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 130EZ UT WOS:000243783700005 PM 16983390 ER PT J AU Shefner, JM Cudkowicz, ME Zhang, H Schoenfeld, D Jillapalli, D AF Shefner, J. M. Cudkowicz, M. E. Zhang, H. Schoenfeld, D. Jillapalli, D. CA NE ALS Consortium TI Revised statistical motor unit number estimation in the Celecoxib/ALS trial SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; clinical trial; motor unit; motor unit number estimation; statistical MUNE ID AMYOTROPHIC-LATERAL-SCLEROSIS; CLINICAL-TRIAL; ALS; MUNE; MICE; VARIABILITY; STIMULATION AB Techniques to estimate motor unit number (MUNE) measure the number of functioning motor units in a muscle. As amyotrophic lateral sclerosis (ALS) is characterized by progressive motor unit loss, this disease offers an ideal setting for the use of MUNE. Statistical MUNE was employed in a recent multicenter trial of creatine in ALS, and was shown to be reliable, reproducible, and to decline with disease progression. However, motor unit amplitude stayed constant over 7 months, a finding believed to reflect an artifact of the method. The statistical method was revised to reflect more accurately the presence of larger motor units and employed in a 12-month study of Celecoxib in ALS. MUNE declined by 49% in 12 months; however, motor unit amplitude again stayed constant over the same period. Statistical MUNE estimates motor unit number based on the variability of response to a repeated stimulus of constant strength, with an underlying assumption that this variability is due solely to the number of motor units responding in an intermittent manner. Based on studies showing that single motor units in ALS display excessive amplitude variability when stimulated repeatedly, we show that response variability in ALS patients is in large part due to single unit changes. Thus, we conclude that the statistical method is not an appropriate measure of motor unit number in any disease associated with motor unit instability. C1 SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. RP Shefner, JM (reprint author), SUNY Upstate Med Univ, Dept Neurol, 750 E Adams St, Syracuse, NY 13210 USA. EM shefnerj@upstate.edu NR 20 TC 32 Z9 33 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD FEB PY 2007 VL 35 IS 2 BP 228 EP 234 DI 10.1002/mus.20671 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 132LM UT WOS:000243944300013 PM 17058270 ER PT J AU Adams, GB Martin, RP Alley, IR Chabner, KT Cohen, KS Calvi, LM Kronenberg, HM Scadden, DT AF Adams, Gregor B. Martin, Roderick P. Alley, Ian R. Chabner, Karissa T. Cohen, Kenneth S. Calvi, Laura M. Kronenberg, Henry M. Scadden, David T. TI Therapeutic targeting of a stem cell niche SO NATURE BIOTECHNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; UMBILICAL-CORD BLOOD; HEMATOPOIETIC STEM; BONE-MARROW; COMPETITIVE REPOPULATION; PARATHYROID-HORMONE; CYTOTOXIC AGENTS; PROGENITOR CELLS; G-CSF; CYCLOPHOSPHAMIDE AB The specialized microenvironment or niche where stem cells reside provides regulatory input governing stem cell function. We tested the hypothesis that targeting the niche might improve stem cell-based therapies using three mouse models that are relevant to clinical uses of hematopoietic stem ( HS) cells. We and others previously identified the osteoblast as a component of the adult HS cell niche and established that activation of the parathyroid hormone ( PTH) receptor on osteoblasts increases stem cell number(1-3). Here we show that pharmacologic use of PTH increases the number of HS cells mobilized into the peripheral blood for stem cell harvests, protects stem cells from repeated exposure to cytotoxic chemotherapy and expands stem cells in transplant recipients. These data provide evidence that the niche may be an attractive target for drug-based stem cell therapeutics. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Rochester, Sch Med, Rochester, NY 14642 USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu OI Calvi, Laura Maria/0000-0001-6969-239X FU NIDDK NIH HHS [R21 DK069563, R21 DK069563-02] NR 29 TC 184 Z9 188 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD FEB PY 2007 VL 25 IS 2 BP 238 EP 243 DI 10.1038/nbt1281 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 134DV UT WOS:000244064000030 PM 17237769 ER PT J AU Ozsolak, F Song, JS Liu, XS Fisher, DE AF Ozsolak, Fatih Song, Jun S. Liu, X. Shirley Fisher, David E. TI High-throughput mapping of the chromatin structure of human promoters SO NATURE BIOTECHNOLOGY LA English DT Article ID TRANSCRIPTIONAL REGULATION; NUCLEOSOME POSITIONS; LINEAGE SURVIVAL; GENE-REGULATION; GENOME-WIDE; DNA; MELANOMA; YEAST; MITF; CHROMOSOME AB Our understanding of how chromatin structure influences cellular processes such as transcription and replication has been limited by a lack of nucleosome-positioning data in human cells. We describe a high-resolution microarray approach combined with an analysis algorithm to examine nucleosome positioning in 3,692 promoters within seven human cell lines. Unlike unexpressed genes without transcription-preinitiation complexes at their promoters, expressed genes or genes containing preinitiation complexes exhibit characteristic nucleosome-free regions at their transcription start sites. The combination of these nucleosome data with chromatin immunoprecipitation-chip analyses reveals that the melanocyte master regulator microphthalmia-associated transcription factor ( MITF) predominantly binds nucleosome-free regions, supporting the model that nucleosomes limit sequence accessibility. This study presents a global view of human nucleosome positioning and provides a high-throughput tool for analyzing chromatin structure in development and disease. C1 Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Melanoma Program Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Melanoma Program Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM xsliu@jimmy.harvard.edu; david_fisher@dfci.harvard.edu FU NHGRI NIH HHS [R01 HG004069-01, R01 HG004069, R01 HG004069-02] NR 30 TC 231 Z9 238 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD FEB PY 2007 VL 25 IS 2 BP 244 EP 248 DI 10.1038/nbt1279 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 134DV UT WOS:000244064000031 PM 17220878 ER PT J AU Fulga, TA Elson-Schwab, I Khurana, V Steinhilb, ML Spires, TL Hyman, BT Feany, MB AF Fulga, Tudor A. Elson-Schwab, Ilan Khurana, Vikram Steinhilb, Michelle L. Spires, Tara L. Hyman, Bradley T. Feany, Mel B. TI Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo SO NATURE CELL BIOLOGY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEINS; HIRANO BODIES; MOUSE MODEL; NEURODEGENERATIVE DISEASES; NEUROFIBRILLARY PATHOLOGY; ALZHEIMERS-DISEASE; CELL-DEATH; DROSOPHILA; TAUOPATHY; FILAMENTS AB Hyperphosphorylated forms of the microtubule-associated protein (MAP) tau accumulate in Alzheimer's disease and related tauopathies and are thought to have an important role in neurodegeneration. However, the mechanisms through which phosphorylated tau induces neurodegeneration have remained elusive. Here, we show that tau-induced neurodegeneration is associated with accumulation of filamentous actin (F-actin) and the formation of actin-rich rods in Drosophila and mouse models of tauopathy. Importantly, modulating F-actin levels genetically leads to dramatic modification of tau-induced neurodegeneration. The ability of tau to interact with F-actin in vivo and in vitro provides a molecular mechanism for the observed phenotypes. Finally, we show that the Alzheimer's disease-linked human beta-amyloid protein (A beta) synergistically enhances the ability of wild-type tau to promote alterations in the actin cytoskeleton and neurodegeneration. These findings raise the possibility that a direct interaction between tau and actin may be a critical mediator of tau-induced neurotoxicity in Alzheimer's disease and related disorders. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Fulga, TA (reprint author), Brigham & Womens Hosp, Dept Pathol, Harvard New Res Bldg Room 652,77 Loius Pasteur Av, Boston, MA 02115 USA. EM Tudor_Fulga@hms.harvard.edu OI Spires-Jones, Tara/0000-0003-2530-0598 FU NIA NIH HHS [AG5134, AG19790] NR 49 TC 197 Z9 206 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2007 VL 9 IS 2 BP 139 EP U17 DI 10.1038/ncb1528 PG 14 WC Cell Biology SC Cell Biology GA 131WR UT WOS:000243903000006 PM 17187063 ER PT J AU Binne, UK Classon, MK Dick, FA Wei, W Rape, M Kaelin, WG Naar, AM Dyson, NJ AF Binne, Ulrich K. Classon, Marie K. Dick, Frederick A. Wei, Wenyi Rape, Michael Kaelin, William G., Jr. Naar, Anders M. Dyson, Nicholas J. TI Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit SO NATURE CELL BIOLOGY LA English DT Article ID UBIQUITIN LIGASE; DEGRADATION; BINDING; SKP2; PRB; DIFFERENTIATION; DOMAIN; TRANSCRIPTION; DESTRUCTION; INHIBITOR AB The retinoblastoma protein (pRB) negatively regulates the progression from G1 to S phase of the cell cycle, in part, by repressing E2F-dependent transcription(1). pRB also possesses E2F-independent functions that contribute to cell-cycle control - for example, during pRB-mediated cell-cycle arrest pRB associates with Skp2, the F-box protein of the Skp1-Cullin-F-box protein (SCF) E3 ubiquitin ligase complex, and promotes the stability of the cyclin-dependent kinase-inhibitor p27(Kip1) through an unknown mechanism(2,3). Degradation of p27(Kip1) is mediated by ubiquitin-dependent targeting of p27(Kip1) by SCF-Skp2 (ref. 4). Here, we report a novel interaction between pRB and the anaphase-promoting complex/cyclosome (APC/C) that controls p27(Kip1) stability by targeting Skp2 for ubiquitin-mediated degradation. Cdh1, an activator of APC/C, not only interacts with pRB but is also required for a pRB-induced cell-cycle arrest. The results reveal an unexpected physical convergence between the pRB tumour-suppressor protein and E3 ligase complexes, and raise the possibility that pRB may direct APC/C to additional targets during pRB-mediated cell-cycle exit. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Schulich Sch Med, Dept Biochem, London, ON N6A 4L6, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM Naar@helix.mgh.harvard.edu; Dyson@helix.mgh.harvard.edu FU NCI NIH HHS [CA64402] NR 34 TC 86 Z9 87 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2007 VL 9 IS 2 BP 225 EP U140 DI 10.1038/ncb PG 15 WC Cell Biology SC Cell Biology GA 131WR UT WOS:000243903000016 PM 17187060 ER PT J AU Varma, H Voisine, C DeMarco, CT Cattaneo, E Lo, DC Hart, AC Stockwell, BR AF Varma, Hemant Voisine, Cindy DeMarco, C. Todd Cattaneo, Elena Lo, Donald C. Hart, Anne C. Stockwell, Brent R. TI Selective inhibitors of death in mutant huntingtin cells SO NATURE CHEMICAL BIOLOGY LA English DT Article ID MOUSE MODEL; DISEASE; CASPASE-1 AB Huntington disease (HD) is an inherited neurodegenerative disorder with unclear pathophysiology. We developed a high-throughput assay in a neuronal cell culture model of HD, screened 43,685 compounds and identified 29 novel selective inhibitors of cell death in mutant huntingtin - expressing cells. Four compounds were active in diverse HD models, which suggests a role for cell death in HD; these compounds are mechanistic probes and potential drug leads for HD. C1 Columbia Univ, Dept Biol Sci, Fairchild Ctr, New York, NY 10027 USA. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. Duke Univ, Med Ctr, Ctr Drug Discovery, Durham, NC 27704 USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27704 USA. Univ Milan, Dept Pharmacol Sci, I-20133 Milan, Italy. Columbia Univ, Dept Chem, New York, NY 10027 USA. RP Stockwell, BR (reprint author), Columbia Univ, Dept Biol Sci, Fairchild Ctr, MC 2406,1212 Amsterdam Ave, New York, NY 10027 USA. EM stockwell@biology.columbia.edu OI CATTANEO, ELENA/0000-0002-0755-4917 FU Telethon [GGP06250] NR 11 TC 31 Z9 33 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD FEB PY 2007 VL 3 IS 2 BP 99 EP 100 DI 10.1038/nchembio852 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 128UZ UT WOS:000243685800012 PM 17195849 ER PT J AU Xia, B Dorsman, JC Ameziane, N de Vries, Y Rooimans, MA Sheng, Q Pals, G Errami, A Gluckman, E Llera, J Wang, W Livingston, DM Joenje, H de Winter, JP AF Xia, Bing Dorsman, Josephine C. Ameziane, Najim de Vries, Yne Rooimans, Martin A. Sheng, Qing Pals, Gerard Errami, Abdellatif Gluckman, Eliane Llera, Julian Wang, Weidong Livingston, David M. Joenje, Hans de Winter, Johan P. TI Fanconi anemia is associated with a defect in the BRCA2 partner PALB2 SO NATURE GENETICS LA English DT Article AB The Fanconi anemia and BRCA networks are considered interconnected, as BRCA2 gene defects have been discovered in individuals with Fanconi anemia subtype D1. Here we show that a defect in the BRCA2- interacting protein PALB2 is associated with Fanconi anemia in an individual with a new subtype. PALB2- deficient cells showed hypersensitivity to cross- linking agents and lacked chromatin- bound BRCA2; these defects were corrected upon ectopic expression of PALB2 or by spontaneous reversion. C1 Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MRC Holland BV, NL-1057 SN Amsterdam, Netherlands. Hop St Louis, Bone Marrow Transplant Unit, F-75475 Paris 10, France. Hosp Italiano Buenos Aires, Dept Pediat, Buenos Aires, DF, Argentina. NIA, Genet Lab, US Natl Inst Hlth, Baltimore, MD 21224 USA. RP de Winter, JP (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Van Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM David_Livingston@dfci.harvard.edu; j.dewinter@vumc.nl RI Pals, Gerard/A-5198-2011 FU Intramural NIH HHS NR 13 TC 256 Z9 260 U1 1 U2 7 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 FEB PY 2007 VL 39 IS 2 BP 159 EP 161 DI 10.1038/ng1942 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 134DU UT WOS:000244063900011 PM 17200672 ER PT J AU St Onge, RP Mani, R Oh, J Proctor, M Fung, E Davis, RW Nislow, C Roth, FP Giaever, G AF St Onge, Robert P. Mani, Ramamurthy Oh, Julia Proctor, Michael Fung, Eula Davis, Ronald W. Nislow, Corey Roth, Frederick P. Giaever, Guri TI Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions SO NATURE GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE GENOME; DELETERIOUS MUTATIONS; DNA-REPAIR; HOMOLOGOUS RECOMBINATION; INTERACTION NETWORKS; YEAST; REPLICATION; PROTEINS; HELICASE; MUTANTS AB Systematic genetic interaction studies have illuminated many cellular processes. Here we quantitatively examine genetic interactions among 26 Saccharomyces cerevisiae genes conferring resistance to the DNA- damaging agent methyl methanesulfonate ( MMS), as determined by chemogenomic fitness profiling of pooled deletion strains. We constructed 650 double- deletion strains, corresponding to all pairings of these 26 deletions. The fitness of single- and double- deletion strains were measured in the presence and absence of MMS. Genetic interactions were defined by combining principles from both statistical and classical genetics. The resulting network predicts that the Mph1 helicase has a role in resolving homologous recombination - derived DNA intermediates that is similar to ( but distinct from) that of the Sgs1 helicase. Our results emphasize the utility of small molecules and multifactorial deletion mutants in uncovering functional relationships and pathway order. C1 Harvard Univ, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. Univ Toronto, Dept Pharmaceut Chem, Leslie Dan Fac Pharm, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada. Ctr Canc Syst Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Roth, FP (reprint author), Harvard Univ, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM froth@hms.harvard.edu; guri.giaever@utoronto.ca RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X; Nislow, Corey/0000-0002-4016-8874 FU NHGRI NIH HHS [R01 HG003224-03, R01 HG003224, R01 HG003224-01A2, R01 HG003224-02] NR 48 TC 159 Z9 162 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 2007 VL 39 IS 2 BP 199 EP 206 DI 10.1038/ng1948 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 134DU UT WOS:000244063900017 PM 17206143 ER PT J AU Hill, JA Benoist, C Mathis, D AF Hill, Jonathan A. Benoist, Christophe Mathis, Diane TI T-reg cells: guardians for life SO NATURE IMMUNOLOGY LA English DT Editorial Material ID TRANSCRIPTION FACTOR FOXP3; CUTTING EDGE; DEPLETION; IMPINGE AB Regulatory T cells expressing the transcription factor Foxp3 are known to control autoreactivity during and subsequent to the development of the peripheral immune system. New evidence emphasizes the fact that those cells are constant and powerful guardians against the state of 'horror autotoxicus'. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Hill, JA (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu NR 11 TC 21 Z9 27 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2007 VL 8 IS 2 BP 124 EP 125 DI 10.1038/ni0207-124 PG 3 WC Immunology SC Immunology GA 127PA UT WOS:000243597600007 PM 17242683 ER PT J AU Djuretic, IM Levanon, D Negreanu, V Groner, Y Rao, A Ansel, KM AF Djuretic, Ivana M. Levanon, Ditsa Negreanu, Varda Groner, Yoram Rao, Anjana Ansel, K. Mark TI Transcription factors T-bet and Runx3 cooperate to activate lfng and silence ll4 in T helper type 1 cells SO NATURE IMMUNOLOGY LA English DT Article ID LOCUS-CONTROL REGION; IFN-GAMMA EXPRESSION; TH2 CYTOKINE LOCUS; IL-4 GENE; ENHANCER ACTIVITY; CUTTING EDGE; DIFFERENTIATION; CHROMATIN; CD4; PROTEINS AB Cell differentiation involves activation and silencing of lineage-specific genes. Here we show that the transcription factor Runx3 is induced in T helper type 1 (T(H)1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of interferon-gamma (IFN-gamma) and silencing of the gene encoding interleukin 4 (Il4) in T(H)1 cells. T-bet does not repress Il4 in Runx3- deficient T(H)2 cells, but coexpression of Runx3 and T-bet induces potent repression in those cells. Both T-bet and Runx3 bind to the Ifng promoter and the Il4 silencer, and deletion of the silencer decreases the sensitivity of Il4 to repression by either factor. Our data indicate that cytokine gene expression in TH1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. CBR, Biomed Res Inst, Boston, MA 02115 USA. Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. RP Ansel, KM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu; ansel@cbr.med.harvard.edu FU NHLBI NIH HHS [HL67664]; NIAID NIH HHS [AI144432] NR 57 TC 238 Z9 243 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2007 VL 8 IS 2 BP 145 EP 153 DI 10.1038/ni1424 PG 9 WC Immunology SC Immunology GA 127PA UT WOS:000243597600011 PM 17195845 ER PT J AU Lee, JW Epardaud, M Sun, J Becker, JE Cheng, AC Yonekura, AR Heath, JK Turley, SJ AF Lee, Je-Wook Epardaud, Mathieu Sun, Jing Becker, Jessica E. Cheng, Alexander C. Yonekura, Ai-ris Heath, Joan K. Turley, Shannon J. TI Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self SO NATURE IMMUNOLOGY LA English DT Article ID DENDRITIC CELLS; EPITHELIAL-CELLS; IN-VIVO; PRESENTING CELLS; STEADY-STATE; A33 ANTIGEN; INDUCTION; THYMUS; IMMUNITY; DIFFERENTIATION AB The intestinal epithelium functions to absorb nutrients and to protect the organism against microbes. To prevent autoimmune attack on this vital tissue, T cell tolerance to intestinal self-antigens must be established. Central tolerance mechanisms involve medullary thymic epithelial cells (mTECs), which use endogenously expressed peripheral-tissue antigens (PTAs) to delete self-reactive thymocytes. The prevailing model for the induction of peripheral tolerance involves cross-presentation of tissue antigens by quiescent dendritic cells. Here we show that lymph node stromal cells present endogenously expressed PTAs to T cells. Moreover, antigen presentation by lymph node stroma is sufficient to induce primary activation and subsequent tolerance among CD8(+) T cells. Thus, lymph node stromal cells are functionally akin to mTECs and provide a direct strategy for purging the peripheral repertoire of self-reactive T cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. INRA, UR892, F-78352 Jouy En Josas, France. Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. Post Off Royal Melbourne Hosp, Melbourne Branch, Ludwig Inst Canc Res, Parkville, Vic 3050, Australia. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu RI Heath, Joan/D-3054-2012 OI Heath, Joan/0000-0001-6955-232X FU NIDDK NIH HHS [P30 DK36836-19] NR 46 TC 213 Z9 222 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2007 VL 8 IS 2 BP 181 EP 190 DI 10.1038/ni1427 PG 10 WC Immunology SC Immunology GA 127PA UT WOS:000243597600016 PM 17195844 ER PT J AU Hsu, YMS Zhang, YL You, Y Wang, DH Li, HX Duramad, O Qin, XF Dong, C Lin, X AF Hsu, Yen-Michael S. Zhang, Yongliang You, Yun Wang, Donghai Li, Hongxiu Duramad, Omar Qin, Xiao-Feng Dong, Chen Lin, Xin TI The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens SO NATURE IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; TOLL-LIKE RECEPTORS; DOUBLE-STRANDED-RNA; RIG-I; SIGNALING PATHWAY; RECOGNITION; ACTIVATION; CARMA1; VIRUS; TRAF3 AB The caspase-recruitment domain-containing adaptor protein CARD9 regulates the innate signaling responses to fungal infection. Here we show that CARD9 is required for innate immune responses against intracellular pathogens. We generated Card9(-/-) mice and found that CARD9-deficient macrophages had defects in activation of the kinases p38 and Jnk but not of transcription factor NF-kappa B after bacterial and viral infection. CARD9-deficient mice failed to clear infection and showed altered cytokine production after challenge with Listeria monocytogenes. In wild-type cells, we found CARD9 inducibly associated with both the intracellular 'biosensor' Nod2 and the serine-threonine kinase RICK. Our data demonstrate that CARD9 has a critical function in Nod2-mediated activation of p38 and Jnk in innate immune responses to intracellular pathogens. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Lin, X (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. EM xllin@mdanderson.org RI dong, chen /B-3181-2009 OI dong, chen /0000-0002-0084-9130 NR 33 TC 208 Z9 218 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD FEB PY 2007 VL 8 IS 2 BP 198 EP 205 DI 10.1038/ni1426 PG 8 WC Immunology SC Immunology GA 127PA UT WOS:000243597600018 PM 17187069 ER PT J AU Rodgers, JT Puigserver, P AF Rodgers, Joseph T. Puigserver, Pere TI Receptor feasts on sugar and cholesterol SO NATURE MEDICINE LA English DT Editorial Material ID GLUCOSE-HOMEOSTASIS AB The nuclear hormone receptor LXR - best known for sensing cholesterol metabolites - also responds to glucose. The findings give LXR a central role in modulating the body's response to metabolic inputs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Rodgers, JT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM pere_puigserver@dfci.harvard.edu NR 6 TC 3 Z9 3 U1 1 U2 2 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 FEB PY 2007 VL 13 IS 2 BP 128 EP 129 DI 10.1038/nm0207-128 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 133RW UT WOS:000244031700017 PM 17290267 ER PT J AU Gao, BB Clermont, A Rook, S Fonda, SJ Srinivasan, VJ Wojtkowski, M Fujimoto, JG Avery, RL Arrigg, PG Bursell, SE Aiello, LP Feener, EP AF Gao, Ben-Bo Clermont, Allen Rook, Susan Fonda, Stephanie J. Srinivasan, Vivek J. Wojtkowski, Maciej Fujimoto, James G. Avery, Robert L. Arrigg, Paul G. Bursell, Sven-Erik Aiello, Lloyd Paul Feener, Edward P. TI Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation SO NATURE MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; OPTICAL COHERENCE TOMOGRAPHY; DIABETIC MACULAR EDEMA; PIGMENT EPITHELIUM; MICROVASCULAR COMPLICATIONS; INTRACEREBRAL HEMORRHAGE; PLASMA PREKALLIKREIN; DEFICIENT MICE; BLOOD-PRESSURE; RETINOPATHY AB Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy-based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I-induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I-induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Santa Barbara Cottage Hosp Eye Ctr, Santa Barbara, CA 93103 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM edward.feener@joslin.harvard.edu RI Wojtkowski, Maciej/D-6822-2014 FU NEI NIH HHS [EY011289, EY014106]; NIDDK NIH HHS [P30 DK036836, DK 36836, DK 60165] NR 47 TC 161 Z9 167 U1 1 U2 15 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 FEB PY 2007 VL 13 IS 2 BP 181 EP 188 DI 10.1038/nm1534 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 133RW UT WOS:000244031700027 PM 17259996 ER PT J AU Leopold, JA Dam, A Maron, BA Scribner, AW Liao, R Handy, DE Stanton, RC Pitt, B Loscalzo, J AF Leopold, Jane A. Dam, Aamir Maron, Bradley A. Scribner, Anne W. Liao, Ronglih Handy, Diane E. Stanton, Robert C. Pitt, Bertram Loscalzo, Joseph TI Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity SO NATURE MEDICINE LA English DT Article ID NITRIC-OXIDE SYNTHASE; CONGESTIVE-HEART-FAILURE; EARLY REPRESSOR ICER; ENDOTHELIAL DYSFUNCTION; OXIDATIVE STRESS; ANGIOTENSIN-II; NO SYNTHASE; CELLS; CAMP; SPIRONOLACTONE AB Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanisms by which aldosterone promotes endothelial dysfunction remain unknown. Glucose-6-phosphate dehydrogenase (G6PD) modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO center dot). Here we show that aldosterone (10(-9) - 10(-7) mol/l) decreased endothelial G6PD expression and activity in vitro, resulting in increased oxidant stress and decreased NO center dot levels - similar to what is observed in G6PD-deficient endothelial cells. Aldosterone decreased G6PD expression by increasing expression of the cyclic AMP-response element modulator (CREM) to inhibit cyclic AMP-response element binding protein (CREB)-mediated G6PD transcription. In vivo, infusion of aldosterone decreased vascular G6PD expression and impaired vascular reactivity. These effects were abrogated by spironolactone or vascular gene transfer of G6pd. These findings demonstrate that aldosterone induces a G6PD-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6PD activity. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Renal Sect, Boston, MA 02215 USA. Univ Michigan, Sch Med, Taubman Med Ctr, Div Cardiol, Ann Arbor, MI 48109 USA. RP Leopold, JA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Med Div, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM jleopold@partners.org FU NHLBI NIH HHS [N01HV28178, HL04399, HL067297, HL071775, HL073756, HL081110, HL58976, HL61828, HV28178, K02 HL081110, K08 HL004399, N01 HV028178, P01 HL81587, P50 HL055993, R01 HL058976, R01 HL067297, R01 HL071775, R01 HL073756, R37 HL061795, U01 HL108630]; NIDDK NIH HHS [DK053480-05, R01 DK054380] NR 48 TC 196 Z9 197 U1 2 U2 8 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 FEB PY 2007 VL 13 IS 2 BP 189 EP 197 DI 10.1038/nm1545 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 133RW UT WOS:000244031700028 PM 17273168 ER PT J AU O'Connor, KC McLaughlin, KA De Jager, PL Chitnis, T Bettelli, E Xu, CQ Robinson, WH Cherry, SV Bar-Or, A Banwell, B Fukaura, H Fukazawa, T Tenembaum, S Wong, SJ Tavakoli, NP Idrissova, Z Viglietta, V Rostasy, K Pohl, D Dale, RC Freedman, M Steinman, L Kuchroo, VK Hafler, DA Wucherpfennig, KW AF O'Connor, Kevin C. McLaughlin, Katherine A. De Jager, Philip L. Chitnis, Tanuja Bettelli, Estelle Xu, Chenqi Robinson, William H. Cherry, Sunil V. Bar-Or, Amit Banwell, Brenda Fukaura, Hikoaki Fukazawa, Toshiyuki Tenembaum, Silvia Wong, Susan J. Tavakoli, Norma P. Idrissova, Zhannat Viglietta, Vissia Rostasy, Kevin Pohl, Daniela Dale, Russell C. Freedman, Mark Steinman, Lawrence Kuchroo, Vijay K. Hafler, David A. Wucherpfennig, Kai W. TI Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein SO NATURE MEDICINE LA English DT Article ID ACUTE DISSEMINATED ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; OLIGODENDROCYTE GLYCOPROTEIN; MULTIPLE-SCLEROSIS; BASIC-PROTEIN; ANTIMYELIN ANTIBODIES; FOLLOW-UP; DEMYELINATION; PLASMAPHERESIS; PREDICTION AB The role of autoantibodies in the pathogenesis of multiple sclerosis (MS) and other demyelinating diseases is controversial, in part because widely used western blotting and ELISA methods either do not permit the detection of conformation-sensitive antibodies or do not distinguish them from conformation-independent antibodies. We developed a sensitive assay based on self-assembling radiolabeled tetramers that allows discrimination of antibodies against folded or denatured myelin oligodendrocyte glycoprotein (MOG) by selective unfolding of the antigen domain. The tetramer radioimmunoassay (RIA) was more sensitive for MOG autoantibody detection than other methodologies, including monomer-based RIA, ELISA or fluorescent-activated cell sorting (FACS). Autoantibodies from individuals with acute disseminated encephalomyelitis (ADEM) selectively bound the folded MOG tetramer, whereas sera from mice with experimental autoimmune encephalomyelitis induced with MOG peptide immunoprecipitated only the unfolded tetramer. MOG-specific autoantibodies were identified in a subset of ADEM but only rarely in adult-onset MS cases, indicating that MOG is a more prominent target antigen in ADEM than MS. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. Stanford Univ, Sch Med, Div Immunol & Rheumatol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. Hosp Sick Children, Dept Paediat Neurol, Toronto, ON M5G 1X8, Canada. Iwate Med Univ, Dept Neurol, Morioka, Iwate 0208505, Japan. Hokkaido Univ, Hokuyukai Neurol Hosp, Kita Ku, Sapporo, Hokkaido 0608638, Japan. Dr JP Garrahan Natl Pediat Hosp, Dept Pediat Neurol, RA-1249 Buenos Aires, DF, Argentina. New York State Dept Hlth, Wadsworth Ctr, Diagnost Immunol Lab, Albany, NY 12201 USA. Kazakh Natl Med Univ, Dept Neurol, Alma Ata 050012, Kazakhstan. Univ Gottingen, Dept Pediat & Pediat Neurol, D-37075 Gottingen, Germany. Great Ormond St Hosp Sick Children, Dept Neurol, London WC1N 3JH, England. Ottawa Gen Hosp, Dept Neurol, Ottawa, ON K1H 8L6, Canada. RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM Kai_Wucherpfennig@dfci.harvard.edu RI Bar-Or, Amit/C-4213-2011 FU NIAID NIH HHS [P01 AI039671, P01 AI045757, P01AI39671]; NIDDK NIH HHS [U01DK6192601]; NINDS NIH HHS [P01 NS038037, P01NS38037, R01 NS024247, R01NS2424710] NR 30 TC 138 Z9 140 U1 0 U2 8 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 FEB PY 2007 VL 13 IS 2 BP 211 EP 217 DI 10.1038/nm1488 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 133RW UT WOS:000244031700031 PM 17237795 ER PT J AU Ley, CD Horsman, MR Kristjansen, PEG AF Ley, Carsten D. Horsman, Michael R. Kristjansen, Paul E. G. TI Early effects of combretastatin-A4 disodium phosphate on tumor perfusion and interstitial fluid pressure SO NEOPLASIA LA English DT Article DE combretastatin-A4 disodium phosphate; interstitial fluid pressure; perfusion; wick-in-needle; vascular-damaging agent ID VASCULAR-TARGETING AGENT; NEAR-INFRARED SPECTROSCOPY; LASER-DOPPLER FLOWMETRY; HUMAN ENDOTHELIAL-CELLS; A4 PHOSPHATE; A-4 PHOSPHATE; SOLID TUMORS; IN-VITRO; COMBRETUM-CAFFRUM; NORMAL-TISSUES AB Combretastatin-A4 disodium phosphate (CA4DP) is a vascular-disruptive agent that causes an abrupt decrease in tumor blood flow. The direct actions of CA4DP include increases in vascular permeability and destabilization of the endothelial cytoskeleton, which are thought to contribute to occlusion of the tumor vasculature. It has been proposed that increased permeability causes a transient increase in interstitial fluid pressure (IFP), which in turn could collapse intratumoral blood vessels. We examined the immediate effects of CA4DP on tumor IFP in C3H mammary carcinoma. Mice were treated with 100 mg/kg CA4DP by intraperitoneal injection. Tumor perfusion was recorded by laser Doppler flowmetry at separate time points, and IFP was recorded continuously by the wick-in-needle method. In this study, we found that CA4DP treatment resulted in a rapid reduction in tumor perfusion, followed by a decrease in IFP; no increases in IFP were observed. This suggests that CA4DP-induced reductions in tumor perfusion are not dependent on increases in IFP. C1 Univ Copenhagen, Inst Mol Pathol, Expt Oncol Lab, DK-2100 Copenhagen, Denmark. Aarhus Univ Hosp, Dept Expt Oncol, DK-8000 Aarhus C, Denmark. RP Kristjansen, PEG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Edwin L Steele Lab, 100 Blossom St, Boston, MA 02114 USA. EM science@ley.dk NR 34 TC 26 Z9 26 U1 0 U2 7 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD FEB PY 2007 VL 9 IS 2 BP 108 EP 112 DI 10.1593/neo.06733 PG 5 WC Oncology SC Oncology GA 139XN UT WOS:000244466200003 PM 17356706 ER PT J AU Yaffe, K Barnes, D Lindquist, K Cauley, J Simonsick, EM Penninx, B Satterfield, S Harris, T Cummings, SR AF Yaffe, K. Barnes, D. Lindquist, K. Cauley, J. Simonsick, E. M. Penninx, B. Satterfield, S. Harris, T. Cummings, S. R. CA Hlth ABC Investigators TI Endogenous sex hormone levels and risk of cognitive decline in an older biracial cohort SO NEUROBIOLOGY OF AGING LA English DT Article DE cognition; dementia; sex hormones; estrogen ID CENTRAL-NERVOUS-SYSTEM; HEALTH INITIATIVE MEMORY; ESTROGEN-RECEPTOR-ALPHA; BETA-AMYLOID PEPTIDES; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; MESSENGER-RNA; ELDERLY-WOMEN; FREE TESTOSTERONE; MEN AB Background: Older women treated with conjugated estrogens may have an increased risk of dementia. but the effect of naturally occurring sex hormones on cognition is not certain. Methods: Bioavailable estradio and free testosterone level were obtained from 792 (55% men, 51% black) participants. We assessed cognition with the Modified Mini-Mental State Examination (3MS). Selective Reminding Test (SRT) and CLOX 1 at baseline and 2 years later. Results: Women in the lowest estradiol tertile were more likely than those in the highest fertile to decline (>= 1.0 S.D. of change) on 3MS (25% versus 9%, adjusted odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.6-9.6) and on SRT (28% versus 12%, adjusted OR [95% CI] = 3.3 [1.4-7.9]) but not CLOX 1. There was a borderline association between low estradiol tertile and decline on SRT in men (22% versus 14%, adjusted OR [95% CI] = 1.9 [0.0-3.9]). Testosterone level was not associated with decline in cognition in either men or women. Findings did not differ by race. Conclusions: Older women with low estradiol levels were more likely to experience decline in global cognitive function and verbal memory and a similar trend was observec for verbal memory in men. This supports, the hypothesis that endogenous sex hormones may play an important role in the maintenance of cognitive function in older adults. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Geriatr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, EMGO Inst, NL-1007 MB Amsterdam, Netherlands. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. Calif Pacific Med Ctr, San Francisco, CA 94107 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM Kristine.Yaffe@ucsf.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-2103, N01-AG-2106, N01-AG-6-2101, R01 AG021918-03] NR 47 TC 66 Z9 71 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2007 VL 28 IS 2 BP 171 EP 178 DI 10.1016/j.neurobiolaging.2006.10.004 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 128ZK UT WOS:000243698000001 PM 17097195 ER PT J AU Quinn, JF Bussiere, JR Hammond, RS Montine, TJ Henson, E Jones, RE Stackman, RW AF Quinn, Joseph F. Bussiere, Joseph R. Hammond, Rebecca S. Montine, Thomas J. Henson, Edward Jones, Richard E. Stackman, Robert W., Jr. TI Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Neuroscience CY NOV 08-12, 2003 CL NEW ORLEANS, LA SP Soc Neurosci DE spatial memory; cortex memory; hippocampus; antioxidant; Alzheimer's disease; amyloid; nitrotyrosine ID TRANSGENIC MOUSE MODEL; AMYLOID-BETA PROTEIN; LONG-TERM POTENTIATION; RADICAL-CATALYZED MECHANISM; ACETYL-L-CARNITINE; ALZHEIMERS-DISEASE; A-BETA; IN-VIVO; OXIDATIVE STRESS; COGNITIVE IMPAIRMENT AB Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology. Here, the effects of the antioxidant, a-lipoic acid (ALA) were tested on the Tg2576 mouse, a transgenic model of cerebral amyloidosis associated with AD. Ten-month old T-2576 and wild type mice were fed an ALA-contain ng diet (0.1%) or control diet for 6 months and then assessed for the influence of diet on memory and neuropathology. ALA-treated Tg2576 mice exhibited significantly improved learning, and memory retention in the Morris water maze task compared to untreated T-2576 mice. Twenty-four hours after contextual fear conditioning, untreated Tg2576 mice exhibited significantly impaired context-dependent freezing. ALA-treated T,,2576 mice exhibited significantly more context freezing than the untreated Tg2576 mice. Assessment of brain soluble and insoluble beta-amyloid levels revealed no differences between ALA-treated and untreated Tg2576 mice. Brain levels of nitrotyrosine, a marker of nitrative stress, were elevated in T-2576 mice, while F2 isoprostanes and neuroprostanes, oxidative stress markers, were not elevated in the Tg2576 mice relative to wild type. These data indicate that chronic dietary ALA can reduce hippocampal-dependent memory deficits of Tg2576 mice without affecting beta-amyloid levels or plaque deposition. (c) 2006 Elsevier Inc. All rights reserved. C1 Portland Vet Affairs Med Ctr, R&D P3, Portland, OR USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Stackman, RW (reprint author), Florida Atlantic Univ, Dept Psychol, BS 101,777 Glades Rd, Boca Raton, FL 33431 USA. EM rstackma@fau.edu FU NCCIH NIH HHS [AT00066] NR 91 TC 88 Z9 92 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2007 VL 28 IS 2 BP 213 EP 225 DI 10.1016/j.neurobiolaging.2005.12.014 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 128ZK UT WOS:000243698000006 PM 16448723 ER EF