FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bray, GA Bouchard, C Church, TS Cefalu, WT Greenway, FL Gupta, AK Kaplan, LM Ravussin, E Smith, SR Ryan, DH AF Bray, George A. Bouchard, Claude Church, Timothy S. Cefalu, William T. Greenway, Frank L. Gupta, Alok K. Kaplan, Lee M. Ravussin, Eric Smith, Steven R. Ryan, Donna H. TI Is it Time to Change the Way We Report and Discuss Weight Loss? SO OBESITY LA English DT Article ID BODY-FAT; OBESITY C1 [Bray, George A.; Bouchard, Claude; Church, Timothy S.; Cefalu, William T.; Greenway, Frank L.; Gupta, Alok K.; Ravussin, Eric; Smith, Steven R.; Ryan, Donna H.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kaplan, Lee M.] Harvard Univ, Sch Med, Baton Rouge, LA USA. RP Bray, GA (reprint author), Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. EM brayga@pbrc.edu RI Bouchard, Claude/A-7637-2009; OI Gupta, Alok/0000-0002-0102-7155 FU NIDDK NIH HHS [P30 DK072476] NR 14 TC 27 Z9 27 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD APR PY 2009 VL 17 IS 4 BP 619 EP 621 DI 10.1038/oby.2008.597 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 425TA UT WOS:000264658800001 PM 19322140 ER PT J AU Wadden, TA West, DS Neiberg, RH Wing, RR Ryan, DH Johnson, KC Foreyt, JP Hill, JO Trence, DL Vitolins, MZ AF Wadden, Thomas A. West, Delia S. Neiberg, Rebecca H. Wing, Rena R. Ryan, Donna H. Johnson, Karen C. Foreyt, John P. Hill, James O. Trence, Dace L. Vitolins, Mara Z. CA Look AHEAD Res Grp TI One-year Weight Losses in the Look AHEAD Study: Factors Associated With Success SO OBESITY LA English DT Article ID RESTING ENERGY-EXPENDITURE; TERM DIETARY INTERVENTION; PLACEBO-CONTROLLED TRIAL; AFRICAN-AMERICAN; OBESE-PATIENTS; WHITE WOMEN; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; BODY-COMPOSITION; CONTROL PROGRAM AB This report provides a further analysis of the first year weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with success. Participants were a total of 5,145 men and women with type 2 diabetes who were recruited at 16 sites and randomly assigned to an intensive lifestyle intervention (ILI) or a control condition, Diabetes Support and Education (DSE). During year 1, participants in ILI received comprehensive diet and physical activity counseling in a total of 42 group and individual sessions, compared with three educational sessions for DSE participants. As reported previously, at the end of the year, ILI participants lost 8.6% of initial weight, compared to 0.7% for DSE (P < 0.001). Within the ILI group, all racial/ethnic groups achieved clinically significant weight losses (>5.5%), although there were significant differences among groups. For the year, ILI participants attended an average of 35.4 treatment sessions and reported exercising a mean of 136.6 min/week and consuming a total of 360.9 meal replacement products. Greater self-reported physical activity was the strongest correlate of weight loss, followed by treatment attendance and consumption of meal replacements. The use of orlistat, during the second half of the year, increased weight loss only marginally in those ILI participants who had lost <5% of initial weight during the first 6 months and chose to take the medication thereafter as a toolbox option. The lifestyle intervention was clinically effective in all subsets of an ethnically and demographically diverse population. C1 [Wadden, Thomas A.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [West, Delia S.] Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Dept Hlth Behav & Hlth Educ, Little Rock, AR 72205 USA. [Neiberg, Rebecca H.] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Wing, Rena R.] Miriam Hosp, Providence, RI 02906 USA. [Wing, Rena R.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Ryan, Donna H.] Pennington Biomed Res Ctr, Dept Clin Res, Baton Rouge, LA USA. [Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Foreyt, John P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Hill, James O.] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. [Trence, Dace L.] Univ Washington, Dept Endocrinol, Washington, DC USA. [Trence, Dace L.] VA Puget Sound Hlth Care Syst, Washington, DC USA. [Look AHEAD Res Grp] Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. RP Wadden, TA (reprint author), Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. EM Wadden@mail.med.upenn.edu FU National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992, DK 046204]; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; Johns Hopkins Medical Institutions [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee [M01RR0021140]; University of Pittsburgh [M01RR00005644]; University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs [M01RR01346] FX This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056 44) and NIH grant (DK 046204); and the University of Washington/VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter General Clinical Research Center (M01RR01346). The following organizations have committed to make major contributions to Look AHEAD: Federal Express; Health Management Resources; Johnson & Johnson, LifeScan Inc.; OptifastNovartis Nutrition; Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories; Slim-Fast Foods Company; and Unilever. NR 39 TC 204 Z9 209 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD APR PY 2009 VL 17 IS 4 BP 713 EP 722 DI 10.1038/oby.2008.637 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 425TA UT WOS:000264658800023 PM 19180071 ER PT J AU Lieb, W Manning, AK Florez, JC Dupuis, J Cupples, LA McAteer, JB Vasan, RS Hoffmann, U O'Donnell, CJ Meigs, JB Fox, CS AF Lieb, Wolfgang Manning, Alisa K. Florez, Jose C. Dupuis, Josee Cupples, L. Adrienne McAteer, Jarred B. Vasan, Ramachandran S. Hoffmann, Udo O'Donnell, Christopher J. Meigs, James B. Fox, Caroline S. TI Variants in the CNR1 and the FAAH Genes and Adiposity Traits in the Community SO OBESITY LA English DT Article ID BODY-MASS INDEX; CANNABINOID-1 RECEPTOR BLOCKER; GENOMEWIDE LINKAGE ANALYSIS; METABOLIC RISK-FACTORS; FOOD-INTAKE; OVERWEIGHT PATIENTS; ENERGY-BALANCE; HEART-DISEASE; OBESITY; RIMONABANT AB Pharmacologic blockade of the endocannabinoid receptor 1 leads to weight loss and an improved metabolic risk profile in overweight and obese individuals. We hypothesize that common genetic variants in the CNR1 (encoding endocannabinoid receptor 1) and FAAH genes (encoding fatty acid amide hydrolase, a key enzyme hydrolyzing endocannabinoids) are associated with adiposity traits. We genotyped 18 single-nucleotide polymorphisms (SNPs) in the CNR1 gene and 9 SNPs in the FAAH gene in 2,415 Framingham Offspring Study participants (mean age 61 +/- 10 years; 52.6% women; mean BMI 28.2 +/- 5.4 kg/m(2); 30.3% obese) and studied them for association with cross-sectional and longitudinal measures of adiposity (BMI, waist circumference, change over time in BMI and waist circumference, visceral and subcutaneous adipose tissue) using linear mixed-effect models. The selected SNPs captured 85% (r(2) = 0.8) of the common variation (minor allele frequency >5%) at the CNR1 locus and 96% (r(2) = 0.8) of the common variation at the FAAH locus (defined as the genomic segment containing the gene + 20 kb upstream and + 10 kb downstream). After correction for multiple testing, none of the SNPs in the CNR1 gene or in the FAAH gene displayed statistical evidence for association with BMI, waist circumference, and visceral adipose tissue or subcutaneous adipose tissue (all P > 0.18). Despite comprehensive SNP mapping across the genes and their regulatory regions in a large unselected sample, we failed to find evidence for an association of common variants in the CNR1 and FAAH genes with measures of adiposity in our community-based sample. C1 [Lieb, Wolfgang; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Manning, Alisa K.; Dupuis, Josee; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Florez, Jose C.; McAteer, Jarred B.] Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. [Florez, Jose C.; McAteer, Jarred B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.; McAteer, Jarred B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.; McAteer, Jarred B.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Div Endocrinol, Sch Med, Boston, MA 02115 USA. RP Fox, CS (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. EM foxca@nhlbi.nih.gov RI Lieb, Wolfgang/C-1990-2012; OI Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Dupuis, Josee/0000-0003-2871-3603 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; American Diabetes Association Career Development Award; sanofi-aventis; NIH NCRR [1S10RR163736-01A1]; NIDDK [K24 DK080140]; NIH [K23 DK65978-04]; [2K24HL04334] FX This study was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), an American Diabetes Association Career Development Award (J.B.M.), a research grant from sanofi-aventis (J.B.M.), and the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the NIH NCRR Shared Instrumentation grant (1S10RR163736-01A1). J.B.M. is also supported by NIDDK K24 DK080140. R. S. V. is supported by 2K24HL04334. J.C.F. is supported by NIH Research Career Award K23 DK65978-04 NR 37 TC 19 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD APR PY 2009 VL 17 IS 4 BP 755 EP 760 DI 10.1038/oby.2008.608 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 425TA UT WOS:000264658800028 PM 19165169 ER PT J AU Paramsothy, P Lin, YS Kernic, MA Foster-Schubert, KE AF Paramsothy, Pathmaja Lin, Yvonne S. Kernic, Mary A. Foster-Schubert, Karen E. TI Interpregnancy Weight Gain and Cesarean Delivery Risk in Women With a History of Gestational Diabetes SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ADVERSE PREGNANCY OUTCOMES; VENOUS THROMBOEMBOLISM; MATERNAL MORTALITY; PLACENTA PREVIA; OBESITY; SECTION; COMPLICATIONS AB OBJECTIVE: Along with the rising prevalence of obesity, rates of gestational diabetes mellitus (GDM) and associated adverse outcomes also have increased. We conducted a population-based, retrospective cohort study to assess the association of weight gain between pregnancies with cesarean delivery for the subsequent pregnancy among women with a history of GDM. METHODS: Using linked birth-certificate data for women with at least two singleton births in Washington State during the period from 1992-2005, we identified 2,753 women with GDM who delivered vaginally at the baseline pregnancy (first pregnancy on record). The interpregnancy weight change (subsequent-baseline prepregnancy weight) for each woman was calculated and assigned to one of three categories: weight loss (more than 10 lb), weight stable (10 lb), or weight gain (more than 10 lb). Multiple logistic regression was used to calculate the risk (odds ratio [OR]) of cesarean delivery at the subsequent pregnancy among the weight-gain and weight-loss groups relative to the weight-stable category. RESULTS: Among 2,581 eligible women, 10.9% lost more than 10 lb between pregnancies, 54.0% were weight-stable, and 35.1% gained more than 10 lb. Women who gained more than 10 lb had an adjusted OR for subsequent cesarean delivery of 1.70 (95% confidence interval [CI] 1.16-2.49, 9.7% of women who gained weight), whereas the adjusted OR for women who lost weight was 0.55 (95% CI 0.28-1.10, 4.7% of women who lost weight). CONCLUSION: Women with a history of GDM who gained more than 10 lb between pregnancies are at increased risk of future cesarean delivery. Appropriate weight management among women with a history of GDM may result in decreased cesarean delivery rates along with decreases in associated excess risks and costs. (Obstet Gynecol 2009;113:817-23) C1 Univ Washington, Dept Internal Med, Div Cardiol, Dept Pharmaceut, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Div Cardiol, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Div Endocrinol, Seattle, WA 98195 USA. RP Foster-Schubert, KE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Endocrinol 111, 1660 S Columbian Way, Seattle, WA 98108 USA. EM kfoster@u.washington.edu FU National Center for Research Resources [1KL2RR025015-01]; National Institutes of Health (NIH); NIH Roadmap for Medical Research FX Supported by grant number 1KL2RR025015-01 from the National Center for Research Resources, a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research (P.P., YS.L., K.E.F-S.). NR 21 TC 8 Z9 8 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2009 VL 113 IS 4 BP 817 EP 823 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 424PG UT WOS:000264578000009 PM 19305325 ER PT J AU Laubach, J Mitsiades, C Anderson, K Richardson, P AF Laubach, Jacob Mitsiades, Constantine Anderson, Kenneth Richardson, Paul TI Maximizing the Clinical Benefit of Novel Therapies in Multiple Myeloma The Laubach article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 [Laubach, Jacob; Mitsiades, Constantine; Anderson, Kenneth; Richardson, Paul] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Laubach, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 34 TC 1 Z9 1 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2009 VL 23 IS 5 BP 415 EP 419 PG 3 WC Oncology SC Oncology GA V18PO UT WOS:000208016900002 PM 19476274 ER PT J AU Cheng, EM Giaconi, JA Coleman, AL Lee, BL Weinreb, RN Newberry, SJ Suttorp, MJ Schonlau, M Fingeret, M Gupta, N Hitchings, RA Jampel, HD Lewis, TL Miglior, S Mills, RP Pfeiffer, N Topouzis, F Samuelson, TW AF Cheng, Eric M. Giaconi, JoAnn A. Coleman, Anne L. Lee, Brian L. Weinreb, Robert N. Newberry, Sydne J. Suttorp, Marika J. Schonlau, Matthias Fingeret, Murray Gupta, Neeru Hitchings, Roger A. Jampel, Henry D. Lewis, Thomas L. Miglior, Stefano Mills, Richard P. Pfeiffer, Norbert Topouzis, Fotis Samuelson, Thomas W. TI For Which Glaucoma Suspects Is It Appropriate to Initiate Treatment? SO OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; OCULAR HYPERTENSION; CORONARY REVASCULARIZATION; PHYSICIAN RATINGS; LIFE-EXPECTANCY; PANEL; SPECIALTY; UNDERUSE; CANCER AB Objective: Because uncertainty exists about which glaucoma suspects should be treated, this study sought to identify the glaucoma suspects who an expert panel could agree would be appropriate or inappropriate to treat. Design: The RAND/UCLA appropriateness method, a well-established procedure to synthesize the scientific literature with expert opinion to resolve uncertainty on a health topic. Participants: Eleven-member panel composed of recognized international leaders in the field of glaucoma. Methods: Based on a systematic review of the literature on potentially important factors to consider when deciding to initiate treatment, more than 1000 scenarios of glaucoma suspects initially were created. The panel formally rated the appropriateness of initiating treatment for glaucoma suspects through a 2-round modified Delphi method, a technique that preserves the confidentiality of individual panelists' ratings but allows panelists to compare their own ratings with those of the entire panel. Main Outcome Measures: Final ratings for scenarios were categorized as appropriate, uncertain, or inappropriate to treat according to typical prespecified statistical criteria previously used in projects using the RAND/UCLA appropriateness method. Tools were developed to help clinicians to approximate the panel ratings of glaucoma suspects. Results: The panel chose age, life expectancy, intraocular pressure (IOP), central corneal thickness, cup-to-disc ratio, disc size, and family history as the variables to consider when deciding whether to treat glaucoma suspects. Permutations of these variables created 1800 unique scenarios. The panel rated 587 (33%) scenarios as appropriate, 585 (33%) as uncertain, and 628 (35%) as inappropriate for treatment initiation. Analysis of variance determined that IOP had greater impact than any other variable on panel ratings. A point system was created with 96% sensitivity and 93% specificity for predicting panel ratings of appropriateness for a glaucoma suspect. Conclusions: An expert panel can reach agreement on the appropriateness and inappropriateness of treatment for glaucoma suspects. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009; 116:710-716 (C) 2009 by the American Academy of Ophthalmology. C1 [Cheng, Eric M.; Giaconi, JoAnn A.; Coleman, Anne L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Weinreb, Robert N.] Univ Calif San Diego, Hamilton Glaucoma Ctr, San Diego, CA 92103 USA. [Weinreb, Robert N.] Shiley Eye Ctr, La Jolla, CA USA. [Fingeret, Murray] St Albans VA Hosp, St Albans, NY USA. [Gupta, Neeru] Univ Toronto, St Michaels Hosp, Carter Wing, Toronto, ON M5B 1W8, Canada. [Hitchings, Roger A.] Moorfields Eye Hosp, London, England. [Jampel, Henry D.] Johns Hopkins Univ, Baltimore, MD USA. [Lewis, Thomas L.] Penn Coll Optometry, Elkins Pk, PA USA. [Miglior, Stefano] Policlin Monza, Clin Oculist, Monza, MI, Italy. [Mills, Richard P.] Swedish Med Ctr, Seattle, WA USA. [Pfeiffer, Norbert] Johannes Gutenberg Univ Mainz, Univ Augenklin, Mainz, Germany. [Topouzis, Fotis] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Samuelson, Thomas W.] Minnesota Eye Consultants PA, Minneapolis, MN USA. RP Cheng, EM (reprint author), VA Greater Los Angeles Healthcare Syst, B 500,ML127, Los Angeles, CA 90073 USA. EM eric.cheng@va.gov FU Pfizer, Inc., New York, New York; National Institute of Neurological Disorders and Stroke (NINDS, Washington, DC) [K23NS058571] FX Supported by Pfizer, Inc., New York, New York. Dr. Cheng is also supported by a Career Development Award, K23NS058571, from National Institute of Neurological Disorders and Stroke (NINDS, Washington, DC). NR 19 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2009 VL 116 IS 4 BP 710 EP 716 DI 10.1016/j.ophtha.2008.12.065 PG 7 WC Ophthalmology SC Ophthalmology GA 427YI UT WOS:000264814600016 ER PT J AU Rah, MJ Deng, L Johns, L Lang, J AF Rah, Marjorie J. Deng, Li Johns, Lynette Lang, Jacob TI A comparison of multipurpose and conventional 2-step rigid gas-permeable solutions with Paragon corneal refractive therapy lenses SO OPTOMETRY-JOURNAL OF THE AMERICAN OPTOMETRIC ASSOCIATION LA English DT Article DE Orthokeratology; Contact lens care system; Visual acuity; Contact lens comfort AB PURPOSE: This investigation compared 2 commonly used care systems, Boston Advance (R) care system and Boston Simplus (TM) (Bausch & Lomb, Rochester, New York) multipurpose solution, and the effects of these solutions on unaided daytime vision, care, and handling and comfort with Paragon corneal refractive therapy (CRT)(R) (Paragon Vision Sciences, Mesa, Arizona) lenses. METHODS: Eighteen subjects wearing CRT lenses were recruited. Three evaluations were conducted over 2 months. Subjects were randomly assigned a solution and returned for a follow-up visit after month. At the conclusion of the 1-month visit, each patient was reassigned the other solution for the second month. The final visit included an additional questionnaire regarding which solution was deemed the best and worst for unaided daytime vision, comfort, care, and handling. RESULTS: From the responses of the 18 patients, a trend is evident that patients favor Boston Simplus over Boston Advance for comfort, unaided daytime vision, and care and handling. However, the sample size is small in this study; therefore, most of the differences are not significant at the 0.05 level except the preference for care and handling (P = 0.03). CONCLUSIONS: Patients preferred Boston Simplus to Boston Advance with corneal reshaping lens wear when evaluated for comfort, unaided daytime vision, and care and handling. The preference of Boston Simplus to Boston Advance for care and handling is very strong and statistically significant, whereas other such advantages of Boston Simplus were not found to be statistically significant in this study. Further confirmation of these results as well as a better understanding of other visual and ocular interactions of Boston Simplus versus conventional solutions, will require using a larger sample in further studies. Optometry 2009;80:193-196 C1 [Rah, Marjorie J.; Deng, Li] New England Coll Optometry, Boston, MA USA. [Johns, Lynette] Boston Fdn Sight, Boston, MA USA. [Lang, Jacob] Associated Eye Care, Stillwater, MN USA. RP Rah, MJ (reprint author), Massachusetts Eye & Ear Infirm, Contact Lens Serv, 243 Charles St, Boston, MA 02114 USA. EM marjorie_rah@meei.harvard.edu FU National Institutes of Health [R24 EY014817] FX This study was supported by National Institutes of Health Grant R24 EY014817. NR 14 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-1839 J9 OPTOMETRY JI Optometry PD APR PY 2009 VL 80 IS 4 BP 193 EP 196 DI 10.1016/j.optm.2008.07.020 PG 4 WC Ophthalmology SC Ophthalmology GA V18QE UT WOS:000208018500007 PM 19329063 ER PT J AU Lorch, JH Posner, MR Wirth, LJ Haddad, RI AF Lorch, Jochen H. Posner, Marshall R. Wirth, Lori J. Haddad, Robert I. TI Seeking alternative biological therapies: The future of targeted molecular treatment SO ORAL ONCOLOGY LA English DT Review ID SQUAMOUS-CELL CARCINOMA; PHASE-II TRIAL; GROWTH-FACTOR; NECK-CANCER; GENE AMPLIFICATION; EARLY MARKERS; HEAD; RECURRENT; CETUXIMAB; RECEPTOR AB In recent years targeted therapies have expanded treatment options for patients with squamous cell cancer of the head and neck (SCCHN) considerably and have led to clinically significant benefit. However, the multitude of new targeted drugs that have emerged and are in development also represent a challenge and many years of carefully conducted clinical studies will be needed to explore their full potential. This article summarizes the most important recent developments in the targeted treatment of SCCHN and provides an overview of pathways and promising potential targets that could impact the treatment of patients with SCCHN in the future. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Lorch, Jochen H.; Posner, Marshall R.; Wirth, Lori J.; Haddad, Robert I.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lorch, JH (reprint author), Dana Farber Canc Inst, 44 Binney St,SW430, Boston, MA 02115 USA. EM Jochen_Lorch@dfci.harvard.edu NR 48 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD APR-MAY PY 2009 VL 45 IS 4-5 BP 447 EP 453 DI 10.1016/j.oraloncology.2008.08.009 PG 7 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 440EJ UT WOS:000265682700020 PM 19027348 ER PT J AU Grady, D Cauley, JA Stock, JL Cox, DA Mitlak, BH Song, JL Cummings, SR AF Grady, Deborah Cauley, Jane A. Stock, John L. Cox, David A. Mitlak, Bruce H. Song, Jingli Cummings, Steven R. TI EFFECT OF RALOXIFENE ON ALL-CAUSE MORTALITY ACROSS CLINICAL TRIALS SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 8th International Symposium on Osteoporosis - Translating Research into Clinical Practice CY APR 01-09, 2009 CL Washington, DC C1 [Grady, Deborah; Cummings, Steven R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. [Cummings, Steven R.] CPMC Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA USA. [Stock, John L.; Cox, David A.; Mitlak, Bruce H.; Song, Jingli] Eli Lilly & Co, Indianapolis, IN 46285 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2009 VL 20 BP S206 EP S207 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 536AF UT WOS:000273012900032 ER PT J AU Mehra, S Eavey, RD Keamy, DG AF Mehra, Saral Eavey, Roland D. Keamy, Donald G., Jr. TI The epidemiology of hearing impairment in the United States: Newborns, children, and adolescents SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review ID NUTRITION EXAMINATION SURVEY; METROPOLITAN ATLANTA; NATIONAL-HEALTH; PREVALENCE; DEAFNESS; ETIOLOGY; MUTATION AB OBJECTIVE: Hearing loss ranks high among disabilities in the United States. The epidemiologic parameters of hearing impairment in the United States have not been systematically Studied and important historic data have not diffused to relevant stakeholders; even otolaryngologists are unfamiliar with epidemiologic data. We wished to compile known studies to establish an epidemiologic baseline beginning with pediatric data. DATA SOURCES: Relevant literature was retrieved from medical databases and Centers for Disease Control and Prevention reports. METHODS: Candidate articles and national data sets encompassing pediatric hearing loss were analyzed and compared. Whenever possible. group analyses were performed. RESULTS: The average incidence of neonatal hearing loss in the United States is 1.1 per 1000 infants, with variation among states (0.22 to 3.61 per 1000). Childhood and adolescent prevalence rates demonstrate variability. The prevalence of mild hearing impairment or worse (>20 dB) is 3.1 percent based on the average of comparable audiometric screening studies; self-reporting prevalence is 1.9 percent. Hispanic Americans demonstrate a higher prevalence of hearing impairment than other children, Low-income households demonstrate a higher prevalence of hearing loss compared to households with higher income levels. Genetic causes were attributed to 23 percent across studies. CONCLUSIONS: Analysis of the data reveals gaps in our knowledge of the epidemiology of hearing loss and stresses the importance of consistent definitions of hearing impairment for systematic assessment of changes over time. Hearing loss in childhood deserves further epidemiologic investigation and elevated awareness among health care professionals and the public. Genetic etiologies are likely underestimated in this review. C1 [Mehra, Saral; Eavey, Roland D.; Keamy, Donald G., Jr.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Pediat Otolaryngol, Dept Otolaryngol,Dept Otol & Laryngol, Boston, MA 02114 USA. [Mehra, Saral] Columbia Univ, Dept Otolaryngol, New York, NY USA. RP Keamy, DG (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm,Pediat Otolaryngol, Dept Otolaryngol,Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM Donald.keamyjr@meei.harvard.edu NR 33 TC 71 Z9 76 U1 0 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2009 VL 140 IS 4 BP 461 EP 472 DI 10.1016/j.otohns.2008.12.022 PG 12 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 425FP UT WOS:000264622700004 PM 19328331 ER PT J AU Halpin, C Rauch, SD AF Halpin, Chris Rauch, Steven D. TI Clinical implications of a damaged cochlea: Pure tone thresholds vs information-carrying capacity SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material ID SPEECH AB The pure tone audiogram is an accurate measure of auditory threshold as a function of stimulus frequency. However, it does not provide the complete picture in patients with sensorineural hearing loss (SNHL) because it is not a direct measure of damage to the cochlear epithelium or of the associated limits on information-carrying capacity that restrict word recognition. Diagnostic use of the audiogram leads to the error of viewing SNHL as "dB of hearing loss." which may seem reversible by gain. Cochlear disorders. on the other hand, often give rise to abnormal thresholds because regions are damaged and may best be thought of more in terms of intractable sensory limitations, comparable to vision loss in retinal disease. We argue that word recognition testing at low vs high presentation levels provides a quantification of the cochlea's information-carrying capacity and is a useful predictor of word recognition limits with hearing aids. (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 [Halpin, Chris] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Halpin, Chris; Rauch, Steven D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Halpin, C (reprint author), Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St, Boston, MA 02114 USA. EM cfhalpin@meei.harvard.edu FU NIDCD NIH HHS [DC 0085598] NR 8 TC 11 Z9 12 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2009 VL 140 IS 4 BP 473 EP 476 DI 10.1016/j.otohns.2008.12.021 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 425FP UT WOS:000264622700005 PM 19328332 ER PT J AU Wieland, A Belden, L Cunningham, M AF Wieland, Aaron Belden, Laura Cunningham, Michael TI Preoperative coagulation screening for adenotonsillectomy: A review and comparison of current physician practices SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID POST-TONSILLECTOMY; HEMOSTATIC ASSESSMENT; THROMBOPLASTIN TIME; PEDIATRIC-PATIENTS; ADENOIDECTOMY; HEMORRHAGE; PREDICTOR; CHILDREN AB OBJECTIVE: To determine the current practice of pediatric otolaryngologists oil a national level and general otolaryngologists on a regional level regarding preoperative coagulation screening prior to adenotonsillectomy. STUDY DESIGN: A five-question survey of members of the American Society of Pediatric Otolaryngology (ASPO) and the Massachusetts Society of Otolarynggology-Head and Neck Surgery (MSO-HNS). SUBJECTS AND METHODS: Surveys results, were analyzed to determine current preoperative screening practices relative to awareness of screeninu recommendations published in the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) 1999 Clinical Indicators Compendium. RESULTS: The survey response rate was 27 percent (54/190) and 29 percent (76/260) for MSO-HNS and ASPO members. respectively. In patients with no known bleeding, risk, 21 percent of respondents continue to obtain coagulation screening including, at a minimum, a partial thromboplastin time and a prothrombin time. MSO-HNS respondents reported ordering more preoperative coagulation Studies than did ASPO respondents (135% vs 10%). Interestingly awareness of the AAO-HNS consensus statement was similar between the two groups and did not impact screening practices. CONCLUSIONS: The survey results indicate it discrepancy between current practice relative to pre-adenotonsillectomy coagulation screening and the recommendations of the AAO-HNS 1999 consensus statement. C1 [Wieland, Aaron; Belden, Laura; Cunningham, Michael] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02116 USA. [Wieland, Aaron; Cunningham, Michael] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Wieland, A (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02116 USA. EM aaron_wieland@meei.harvard.edu NR 19 TC 14 Z9 15 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2009 VL 140 IS 4 BP 542 EP 547 DI 10.1016/j.otohns.2008.12.016 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 425FP UT WOS:000264622700017 PM 19328344 ER PT J AU Donaldson, DM Singh, JP Heist, EK Mela, T Ruskin, JN Das, S AF Donaldson, David M. Singh, Jagmeet P. Heist, E. Kevin Mela, Theofanie Ruskin, Jeremy N. Das, Saumya TI Multiple ICD Discharges Associated with Lead Fracture Without Triggering of High Impedance Alert SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter defibrillator; Sprint Fidelis lead; impedance; inappropriate shock; fracture ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR AB The Sprint Fidelis(R) lead has an increased incidence of lead fracture. The manufacturer has recommended programming alerts to preempt lead malfunction due to fracture. The current trigger for an alert is an increase in the right ventricular pacing impedance to greater than 1,000 Omega. Our patient suffered multiple inappropriate implantable cardioverter defibrillator therapies with stable impedance less than 1,000 Omega. This case of lead fracture would not have been detected with these programming alerts. Additional programming measures may detect lead fractures, including changing the lower detection for impedances, arranging for a percentage change in the impedance trend to trigger an alarm, or programming the device to warn if there is an increase in nonphysiologic short R-R interval counts. (PACE 2009; 32: 543-546) C1 [Donaldson, David M.; Singh, Jagmeet P.; Heist, E. Kevin; Mela, Theofanie; Ruskin, Jeremy N.; Das, Saumya] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Das, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM sdas@partners.org NR 4 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD APR PY 2009 VL 32 IS 4 BP 543 EP 546 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 424GF UT WOS:000264552800018 PM 19335867 ER PT J AU Jaffe, E AF Jaffe, Emily TI Regulating Complexity SO PAIN MEDICINE LA English DT Editorial Material C1 Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15260 USA. RP Jaffe, E (reprint author), Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15260 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD APR PY 2009 VL 10 IS 3 BP 429 EP 431 DI 10.1111/j.1526-4637.2009.00585.x PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 431QI UT WOS:000265077500001 PM 19425206 ER PT J AU Becker, WC Fiellin, DA Gallagher, RM Barth, KS Ross, JT Oslin, DW AF Becker, William C. Fiellin, David A. Gallagher, Rollin M. Barth, Kelly S. Ross, Jennifer T. Oslin, David W. TI The Association Between Chronic Pain and Prescription Drug Abuse in Veterans SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Prescription Drug Abuse; Multivariable Analysis ID NONMEDICAL USE; UNITED-STATES; SUBSTANCE USE; OPIOID ANALGESICS; USE DISORDERS; RISK-FACTORS; MEDICAL USE; US ADULTS; DEPENDENCE; ADDICTION AB We sought to investigate the association between chronic pain and self-reported prescription drug abuse in a large cohort of patients referred from primary care for a behavioral health assessment. We performed a cross-sectional analysis of responses to a telephone assessment administered to patients referred for a behavioral health evaluation between April 25, 2005 and October 31, 2007. We conducted descriptive statistics and investigated multivariable associations. Multivariable analyses included age, gender, race, financial status, employment, current smoking, drinking problem, past-year illicit drug use, depression, and chronic pain. Veterans referred from primary care (N = 6,377). Mean age of the sample was 56.5 years with a range of 19-97. The majority of respondents was white, unmarried, and was unemployed. Nearly 5% of the sample reported past 6-month prescription drug abuse. On multivariable analysis, younger age, possible depression (odds ratio [OR] 1.9; 1.3-2.8), probable depression (OR 2.4; 1.6-3.4), smoking (OR 1.4; 1.1-1.8), illicit drug use (OR 2.8; 2.2-3.7), and chronic pain (OR 1.9; 1.4-2.5) were associated with prescription drug abuse. We have identified specific variables associated with self-reported prescription drug abuse in primary care patients. Chronic pain is associated both with an indication for prescribing opioids and with abuse of prescription medications. Clinicians are encouraged to follow treatment algorithms when managing patients with chronic pain as a method for reducing misuse. C1 [Becker, William C.; Gallagher, Rollin M.; Ross, Jennifer T.; Oslin, David W.] Philadelphia Vet Affairs Med Ctr, MIRECC, VISN4, Philadelphia, PA USA. [Barth, Kelly S.] Univ Penn, Sch Med, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19104 USA. [Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Becker, WC (reprint author), Philadelphia VAMC, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM William.Becker4@va.gov OI Becker, William/0000-0002-0788-1467; Fiellin, David/0000-0002-4006-010X NR 27 TC 29 Z9 29 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD APR PY 2009 VL 10 IS 3 BP 531 EP 536 DI 10.1111/j.1526-4637.2009.00584.x PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 431QI UT WOS:000265077500015 PM 19425211 ER PT J AU Srinivasan, R Asselin, J Gildengorin, G Wiener-Kronish, J Flori, HR AF Srinivasan, Ramya Asselin, Jeanette Gildengorin, Ginny Wiener-Kronish, J. Flori, H. R. TI A Prospective Study of Ventilator-Associated Pneumonia in Children SO PEDIATRICS LA English DT Article DE intensive care; outcome; pneumonia; prospective study; ventilator-associated ID INTENSIVE-CARE-UNIT; DYSFUNCTION PELOD SCORE; ACUTE LUNG INJURY; NOSOCOMIAL INFECTIONS; OUTCOMES; SURVEILLANCE; TRANSFUSION; MULTICENTER; STRATEGIES; RISK AB OBJECTIVE. We conducted a prospective, observational study in a tertiary care pediatric center to determine risk factors for the development of and outcomes from ventilator-associated pneumonia. METHODS. From November 2004 to June 2005, all NICU and PICU patients mechanically ventilated for >24 hours were eligible for enrollment after parental consent. The primary outcome measure was the development of ventilator-associated pneumonia, which was defined by both Centers for Disease Control and Prevention/National Nosocomial Infections Surveillance criteria and clinician diagnosis. Secondary outcome measures were length of mechanical ventilation, hospital and ICU length of stay, hospital cost, and death. RESULTS. Fifty-eight patients were enrolled. The median age was 6 months, and 57% were boys. The most common ventilator-associated pneumonia organisms identified were Gram-negative bacteria (42%), Staphylococcus aureus (22%), and Haemophilus influenzae (11%). On multivariate analysis, female gender, postsurgical admission diagnosis, presence of enteral feeds, and use of narcotic medications were associated with ventilator-associated pneumonia. Patients with ventilator-associated pneumonia had greater need for mechanical ventilation (12 vs 22 median ventilator-free days), longer ICU length of stay (6 vs 13 median ICU-free days), higher total median hospital costs ($308 534 vs $252 652), and increased absolute hospital mortality (10.5% vs 2.4%) than those without ventilator-associated pneumonia. CONCLUSIONS. In mechanically ventilated, critically ill children, those with ventilator-associated pneumonia had a prolonged need for mechanical ventilation, a longer ICU stay, and a higher mortality rate. Female gender, postsurgical diagnosis, the use of narcotics, and the use of enteral feeds were associated with an increased risk of developing ventilator-associated pneumonia in these patients. Pediatrics 2009; 123: 1108-1115 C1 [Srinivasan, Ramya] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Asselin, Jeanette] Childrens Hosp & Res Ctr Oakland, Neonatal Pediat Res Grp, Oakland, CA 94609 USA. [Srinivasan, Ramya; Flori, H. R.] Childrens Hosp & Res Ctr Oakland, Pediat Crit Care Dept, Oakland, CA 94609 USA. [Gildengorin, Ginny] Childrens Hosp Oakland, Res Inst, Pediat Clin Res Ctr, Oakland, CA 94609 USA. [Wiener-Kronish, J.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Srinivasan, R (reprint author), Childrens Hosp & Res Ctr Oakland, Pediat Crit Care Dept, 747 52nd St, Oakland, CA 94609 USA. EM rsrinivasan2004@yahoo.com FU SCCOR [PH50HL 074005, RR01271]; CHRCO Neonatal Pediatric Research Group FX This study was supported by SCCOR grants PH50HL 074005 and RR01271 and the CHRCO Neonatal Pediatric Research Group. NR 21 TC 79 Z9 85 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2009 VL 123 IS 4 BP 1108 EP 1115 DI 10.1542/peds.2008-1211 PG 8 WC Pediatrics SC Pediatrics GA 425UO UT WOS:000264663100005 PM 19336369 ER PT J AU Mansbach, JM Espinola, JA Macias, CG Ruhlen, ME Sullivan, AF Camargo, CA AF Mansbach, Jonathan M. Espinola, Janice A. Macias, Charles G. Ruhlen, Michael E. Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Variability in the Diagnostic Labeling of Nonbacterial Lower Respiratory Tract Infections: A Multicenter Study of Children Who Presented to the Emergency Department SO PEDIATRICS LA English DT Article DE bronchiolitis; lower respiratory tract infection; asthma ID SYNCYTIAL-VIRUS BRONCHIOLITIS; INHALED CORTICOSTEROIDS; YOUNG-CHILDREN; CONTROLLED-TRIAL; UNITED-STATES; CLINICAL PATHWAY; RISK-FACTORS; ACUTE ASTHMA; INFANTS; HOSPITALIZATIONS AB OBJECTIVE. The diagnostic labeling of presumed nonbacterial lower respiratory tract infection is unclear. Our objective was to identify patterns of specific diagnoses and treatments that were given to children who presented with lower respiratory tract infection to US academic emergency departments. METHODS. Data were collected on all children who were aged <2 years and had lower respiratory tract infection symptoms during a similar 2- to 3-week winter period at 4 pairs of emergency departments from the same state or region. The children were identified by using relevant International Classification of Diseases, Ninth Revision, Clinical Modification codes in the primary diagnosis field. Data were collected by using standardized chart review forms for the index emergency department visit and also for 1 month before through 1 year after the index visit. RESULTS. Among the 928 children who presented with lower respiratory tract infection symptoms, 676 (73%) were younger than 12 months and 624 (67%) had a primary diagnosis of bronchiolitis. When comparing the assigned diagnoses between emergency department pairs, bronchiolitis was the more common diagnosis at certain hospitals, whereas asthma, cough, and wheeze were more frequent at others. Independent predictors of corticosteroid treatment were visiting specific emergency departments, older age, an asthma diagnosis (compared with bronchiolitis), documented history of wheezing, observed wheezing during the index visit, eosinophil values >4%, previous use of corticosteroids, and parental history of asthma. CONCLUSIONS. For children who are age <2 years and present to an emergency department with lower respiratory tract infection symptoms, there is large variability in the assigned diagnosis. Children who present to emergency departments that more commonly diagnose lower respiratory tract infection as " asthma" are more likely to receive corticosteroids. As clinicians, we need to develop evidence-and outcome-based definitions for lower respiratory tract infections to guide diagnosis and treatment better. Pediatrics 2009; 123: e573-e581 C1 [Mansbach, Jonathan M.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Espinola, Janice A.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Macias, Charles G.] Baylor Coll Med, Dept Pediat, Sect Emergency Med, Houston, TX 77030 USA. [Ruhlen, Michael E.] Toledo Childrens Hosp, Dept Pediat, Toledo, OH USA. RP Mansbach, JM (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Main Clin Bldg 9 S,9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu NR 47 TC 16 Z9 16 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2009 VL 123 IS 4 BP E573 EP E581 DI 10.1542/peds.2008-1675 PG 9 WC Pediatrics SC Pediatrics GA 425UO UT WOS:000264663100032 PM 19273503 ER PT J AU van Noord, C Aarnoudse, AJLHJ Eijgelsheim, M Sturkenboom, MCJM Sabine, MJM Hofman, A Kors, JA Newton-Cheh, C Witteman, JCM Stricker, BHC AF van Noord, Charlotte Aarnoudse, Albert-Jan L. H. J. Eijgelsheim, Mark Sturkenboom, Miriam C. J. M. Straus, Sabine M. J. M. Hofman, Albert Kors, Jan A. Newton-Cheh, Christopher Witteman, Jacqueline C. M. Stricker, Bruno H. Ch. TI Calcium channel blockers, NOS1AP, and heart-rate-corrected QT prolongation SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE calcium channel blockers; NOS1AP variant; QTc prolongation ID NITRIC-OXIDE SYNTHASE; TORSADE-DE-POINTES; LEFT-VENTRICULAR HYPERTROPHY; MYOCARDIAL-INFARCTION; CARDIAC REPOLARIZATION; GENETIC-VARIANTS; DRUG DEVELOPMENT; INTERVAL; ROTTERDAM; DURATION AB Objectives To study whether NOS1AP single nucleotide polymorphisms (SNPS), rs10494.366 T>G and rs10918594 C>G, modify the heart-rate-corrected QT (QTc) prolonging effect of calcium channel blockers. Background Common variation in the NOS1AP gene has been associated with QT interval variation in several large population samples. NOS1 is presumed to influence intracellular calcium. Methods The prospective population-based Rotterdam Study includes 16 603 ECGs from 7565 participants (>= 55 years), after exclusion of patients with left ventricular hypertrophy, left and right bundle branch block, as well as carriers of pacemakers. The endpoint was the length of the QTc interval in calcium channel blocker users and non-users with the minor alleles compared with the major alleles (wild type). We used a repeated-measurement analysis, adjusted for all known confounders. Results Use of verapamil was associated with a significant QTc interval prolongation [6.0 ms 95% confidence interval (CI) 1.7; 10-2] compared with non-users. Furthermore, users of verapamil with the rs 10494366 GG genotype showed significantly more QTc prolongation than users with the TT genotype [25.4 ms (95% Cl: 5.9-44.9)] (P value for multiplicative interaction 0.0038). Users of isradipine with the GG genotype showed more QTc prolongation than users with the TT genotype [19.8 ms (95% CI: 1.9-37.7)]; however, SNP rs10494366 did not modify the effect on QTc interval on a multiplicative scale (P=0.3563). SNP rs10918594 showed similar results. Conclusion In conclusion, we showed that the minor alleles of both NOS1AP SNPs significantly potentiate the QTc prolonging effect of verapamil. Pharmacogenetics and Genomics 19:260-266 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [van Noord, Charlotte; Aarnoudse, Albert-Jan L. H. J.; Eijgelsheim, Mark; Sturkenboom, Miriam C. J. M.; Straus, Sabine M. J. M.; Hofman, Albert; Witteman, Jacqueline C. M.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Stricker, Bruno H. Ch.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands. [Sturkenboom, Miriam C. J. M.; Kors, Jan A.] Erasmus MC, Dept Med Informat, NL-3015 GE Rotterdam, Netherlands. [van Noord, Charlotte; Straus, Sabine M. J. M.] Dutch Med Evaluat Board, The Hague, Netherlands. [Aarnoudse, Albert-Jan L. H. J.; Stricker, Bruno H. Ch.] Inspectorate Hlth Care, The Hague, Netherlands. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. EM b.stricker@erasmusmc.nl FU Pfizer; MerckJohnsonJohnson; Amgen; Roche; GSK; Boehringer; Yamanouchi and Altana FX Conflicts of interest: As employee of Erasmus Medical Center, M.C.J.M.S. has been involved as project leader and in analyses contracted by various pharmaceutical companies and received unconditional research grants from Pfizer, Merck, Johnson&Johnson, Amgen, Roche, GSK, Boehringer, Yamanouchi and Altana, none of which are related to the subject of this-study. M.C.J.M.S. has been consultant to Pfizer, Servier, Celgene, Novartis and Lundbeck on issues not related to this paper. All other authors have no conflicts of interest. NR 49 TC 16 Z9 16 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD APR PY 2009 VL 19 IS 4 BP 260 EP 266 DI 10.1097/FPC.0b013e328324e556 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 429TV UT WOS:000264943900002 PM 19247217 ER PT J AU Fedorov, VB Goropashnaya, AV Toien, O Stewart, NC Gracey, AY Chang, CL Qin, SZ Pertea, G Quackenbush, J Showe, LC Showe, MK Boyer, BB Barnes, BM AF Fedorov, Vadim B. Goropashnaya, Anna V. Toien, Oivind Stewart, Nathan C. Gracey, Andrew Y. Chang, Celia Qin, Shizhen Pertea, Geo Quackenbush, John Showe, Louise C. Showe, Michael K. Boyer, Bert B. Barnes, Brian M. TI Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus) SO PHYSIOLOGICAL GENOMICS LA English DT Article DE gene expression; hibernation; translation; RNA binding protein motif 3 ID ARCTIC GROUND-SQUIRRELS; MAMMALIAN HIBERNATION; METABOLIC-RATE; WINTER SLEEP; TEMPERATURE; PHYSIOLOGY; TORPOR; STRENGTH; GOMINER; PLASMA AB Fedorov VB, Goropashnaya AV, Toien O, Stewart NC, Gracey AY, Chang C, Qin S, Pertea G, Quackenbush J, Showe LC, Showe MK, Boyer BB, Barnes BM. Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus). Physiol Genomics 37: 108-118, 2009. First published February 24, 2009; doi:10.1152/physiolgenomics.90398.2008.-We conducted a large-scale gene expression screen using the 3,200 cDNA probe microarray developed specifically for Ursus americanus to detect expression differences in liver and skeletal muscle that occur during winter hibernation compared with animals sampled during summer. The expression of 12 genes, including RNA binding protein motif 3 (Rbm3), that are mostly involved in protein biosynthesis, was induced during hibernation in both liver and muscle. The Gene Ontology and Gene Set Enrichment analysis consistently showed a highly significant enrichment of the protein biosynthesis category by overexpressed genes in both liver and skeletal muscle during hibernation. Coordinated induction in transcriptional level of genes involved in protein biosynthesis is a distinctive feature of the transcriptome in hibernating black bears. This finding implies induction of translation and suggests an adaptive mechanism that contributes to a unique ability to reduce muscle atrophy over prolonged periods of immobility during hibernation. Comparing expression profiles in bears to small mammalian hibernators shows a general trend during hibernation of transcriptional changes that include induction of genes involved in lipid metabolism and carbohydrate synthesis as well as depression of genes involved in the urea cycle and detoxification function in liver. C1 [Fedorov, Vadim B.; Goropashnaya, Anna V.; Toien, Oivind; Stewart, Nathan C.; Boyer, Bert B.; Barnes, Brian M.] Univ Alaska Fairbanks, Inst Arctic Biol, Fairbanks, AK 99775 USA. [Gracey, Andrew Y.] Univ So Calif, Los Angeles, CA USA. [Chang, Celia; Showe, Louise C.; Showe, Michael K.] Wistar Inst Anat & Biol, Syst Biol Div, Philadelphia, PA 19104 USA. [Qin, Shizhen] Inst Syst Biol, Seattle, WA USA. [Pertea, Geo; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Pertea, Geo; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Fedorov, VB (reprint author), Univ Alaska Fairbanks, Inst Arctic Biol, Fairbanks, AK 99775 USA. EM fnvf@uaf.edu FU National Science Foundation (NSF); USAMRMC [05178001]; NSF [0076039, DBI-0649614] FX This work was supported by the National Science Foundation (NSF) EPSCOR program and USAMRMC proposal number 05178001. B. M. Barnes was also supported by NSF grant 0076039. J. Quackenbush and G. Pertea were supported by NSF Grant DBI-0649614. NR 47 TC 40 Z9 43 U1 3 U2 25 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR PY 2009 VL 37 IS 2 BP 108 EP 118 DI 10.1152/physiolgenomics.90398.2008 PG 11 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 433QI UT WOS:000265220500005 PM 19240299 ER PT J AU Howrylak, JA Dolinay, T Lucht, L Wang, ZX Christiani, DC Sethi, JM Xing, EP Donahoe, MP Choi, AMK AF Howrylak, Judie A. Dolinay, Tamas Lucht, Lorrie Wang, Zhaoxi Christiani, David C. Sethi, Jigme M. Xing, Eric P. Donahoe, Michael P. Choi, Augustine M. K. TI Discovery of the gene signature for acute lung injury in patients with sepsis SO PHYSIOLOGICAL GENOMICS LA English DT Article DE classification; microarray; acute respiratory distress syndrome ID RESPIRATORY-DISTRESS-SYNDROME; PULMONARY-EDEMA FLUID; FIBROBLAST PROLIFERATION; CONSENSUS CONFERENCE; EXPRESSION; ARDS; DEFINITIONS; MORTALITY; BIOMARKER; OUTCOMES AB Howrylak JA, Dolinay T, Lucht L, Wang Z, Christiani DC, Sethi JM, Xing EP, Donahoe MP, Choi AM. Discovery of the gene signature for acute lung injury in patients with sepsis. Physiol Genomics 37: 133-139, 2009. First published January 27, 2009; doi:10.1152/physiolgenomics.90275.2008.-The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) was described 30 yr ago, yet making a definitive diagnosis remains difficult. The identification of biomarkers obtained from peripheral blood could provide additional noninvasive means for diagnosis. To identify gene expression profiles that may be used to classify patients with ALI, 13 patients with ALI + sepsis and 20 patients with sepsis alone were recruited from the Medical Intensive Care Unit of the University of Pittsburgh Medical Center, and microarrays were performed on peripheral blood samples. Several classification algorithms were used to develop a gene signature for ALI from gene expression profiles. This signature was validated in an independently obtained set of patients with ALI + sepsis (n = 8) and sepsis alone (n = 1). An eight-gene expression profile was found to be associated with ALI. Internal validation found that the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 100% accuracy, corresponding to a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100%. In the independently obtained external validation set, the gene signature was able to distinguish patients with ALI + sepsis from patients with sepsis alone with 88.9% accuracy. The use of classification models to develop a gene signature from gene expression profiles provides a novel and accurate approach for classifying patients with ALI. C1 [Howrylak, Judie A.; Lucht, Lorrie; Sethi, Jigme M.; Donahoe, Michael P.] Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Dolinay, Tamas; Choi, Augustine M. K.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Wang, Zhaoxi; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Xing, Eric P.] Carnegie Mellon Univ, Dept Machine Learning, Pittsburgh, PA 15213 USA. RP Howrylak, JA (reprint author), UPMC, Montefiore NW 628,3459 5th Ave, Pittsburgh, PA 15213 USA. EM howrylakj@upmc.edu FU National Heart, Lung, and Blood Institute Grants [R01-HL-060-234, P01-HL-70807, R01-HL-55330, R01-HL-079904] FX Support for this study: National Heart, Lung, and Blood Institute Grants R01-HL-060-234, P01-HL-70807, R01-HL-55330, R01-HL-079904. NR 28 TC 28 Z9 28 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR PY 2009 VL 37 IS 2 BP 133 EP 139 DI 10.1152/physiolgenomics.90275.2008 PG 7 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 433QI UT WOS:000265220500007 PM 19174476 ER PT J AU Wang, XF Elling, AA Li, XY Li, N Peng, ZY He, GM Sun, H Qi, YJ Liu, XS Deng, XW AF Wang, Xiangfeng Elling, Axel A. Li, Xueyong Li, Ning Peng, Zhiyu He, Guangming Sun, Hui Qi, Yijun Liu, X. Shirley Deng, Xing Wang TI Genome-Wide and Organ-Specific Landscapes of Epigenetic Modifications and Their Relationships to mRNA and Small RNA Transcriptomes in Maize SO PLANT CELL LA English DT Article ID DNA METHYLATION; ARABIDOPSIS-THALIANA; TRANSPOSABLE ELEMENTS; CHROMATIN-STRUCTURE; ENDOGENOUS SIRNAS; GENE-EXPRESSION; DRAFT SEQUENCE; MOUSE OOCYTES; RICE; EPIGENOME AB Maize (Zea mays) has an exceptionally complex genome with a rich history in both epigenetics and evolution. We report genomic landscapes of representative epigenetic modifications and their relationships to mRNA and small RNA (smRNA) transcriptomes in maize shoots and roots. The epigenetic patterns differed dramatically between genes and transposable elements, and two repressive marks (H3K27me3 and DNA methylation) were usually mutually exclusive. We found an organ-specific distribution of canonical microRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs), indicative of their tissue-specific biogenesis. Furthermore, we observed that a decreasing level of mop1 led to a concomitant decrease of 24-nucleotide siRNAs relative to 21-nucleotide miRNAs in a tissue-specific manner. A group of 22-nucleotide siRNAs may originate from long-hairpin double-stranded RNAs and preferentially target gene-coding regions. Additionally, a class of miRNA-like smRNAs, whose putative precursors can form short hairpins, potentially targets genes in trans. In summary, our data provide a critical analysis of the maize epigenome and its relationships to mRNA and smRNA transcriptomes. C1 [Wang, Xiangfeng; Peng, Zhiyu; Deng, Xing Wang] Peking Univ, Coll Life Sci, Peking Yale Joint Ctr Plant Mol Genet & Agrobiote, Beijing 100871, Peoples R China. [Wang, Xiangfeng; Li, Xueyong; He, Guangming; Qi, Yijun; Deng, Xing Wang] Natl Inst Biol Sci, Beijing 102206, Peoples R China. [Wang, Xiangfeng; Elling, Axel A.; Li, Xueyong; Sun, Hui; Deng, Xing Wang] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Wang, Xiangfeng; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wang, Xiangfeng; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Li, Ning; Peng, Zhiyu] Beijing Genom Inst Shenzhen, Shenzhen 518083, Peoples R China. RP Deng, XW (reprint author), Peking Univ, Coll Life Sci, Peking Yale Joint Ctr Plant Mol Genet & Agrobiote, Beijing 100871, Peoples R China. EM xingwang.deng@yale.edu FU National Institutes of Health [GM047850]; National Science Foundation Plant Genome Program [DBI0421675]; National Science Foundation program; Ministry of Science and Technology of China; Beijing Commission of Science and Technology; Yale University Brown-Coxe Postdoctoral Fellowship FX The Deng laboratory at Yale University was supported by grants from the National Institutes of Health (GM047850), the National Science Foundation Plant Genome Program (DBI0421675), and the National Science Foundation 2010 program. Studies conducted at the National Institute of Biological Sciences were supported by special funds from the Ministry of Science and Technology of China and Beijing Commission of Science and Technology. We thank the Maize Genome Sequencing Consortium (http://www.maizesequence.org) for communicating maize sequence information before publication and Will Terzaghi and Tim Nelson for critical reading of the manuscript. A. A. E. was supported by a Yale University Brown-Coxe Postdoctoral Fellowship. NR 66 TC 160 Z9 170 U1 2 U2 51 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD APR PY 2009 VL 21 IS 4 BP 1053 EP 1069 DI 10.1105/tpc.109.065714 PG 17 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 448XR UT WOS:000266295800008 PM 19376930 ER PT J AU Pitman's, RK AF Pitman's, Roger K. TI Preventing Postsurgical Dissatisfaction Syndrome after Rhinoplasty with Propranolol: A Pilot Study (vol 123, pg 1072, 2009) SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Correction C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pitman's, RK (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 2009 VL 123 IS 4 BP 1402 EP 1402 DI 10.1097/PRS.0b013e3181a61846 PG 1 WC Surgery SC Surgery GA 440AG UT WOS:000265669400039 ER PT J AU Hurwitz, ME Vanderzalm, PJ Bloom, L Goldman, J Garriga, G Horvitz, HR AF Hurwitz, Michael E. Vanderzalm, Pamela J. Bloom, Laird Goldman, Julia Garriga, Gian Horvitz, H. Robert TI Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans SO PLOS BIOLOGY LA English DT Article ID DISTAL TIP CELLS; C-ELEGANS; APOPTOTIC CELLS; TYROSINE KINASE; GROWTH-FACTOR; CORPSE ENGULFMENT; BCR-ABL; CRKII/DOCK180/RAC PATHWAY; TRANSFORMING ACTIVITY; SELECTIVE INHIBITOR AB The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway includes the adaptor protein CED-2 CrkII and the small GTPase CED-10 Rac, and acts to rearrange the cytoskeleton of the engulfing cell. The other pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Although many components required for engulfment have been identified, little is known about inhibition of engulfment. The tyrosine kinase Abl regulates the actin cytoskeleton in mammals and Drosophila in multiple ways. For example, Abl inhibits cell migration via phosphorylation of CrkII. We tested whether ABL-1, the C. elegans ortholog of Abl, inhibits the CED-2 CrkII-dependent engulfment of apoptotic cells. Our genetic studies indicate that ABL-1 inhibits apoptotic cell engulfment, but not through CED-2 CrkII, and instead acts in parallel to the two known engulfment pathways. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The loss of ABL-1 function partially restores normal DTC migration in the CED-10 Rac pathway mutants. We found that ABI-1 the C. elegans homolog of mammalian Abi (Abl interactor) proteins, is required for engulfment of apoptotic cells and proper DTC migration. Like Abl, Abi proteins are cytoskeletal regulators. ABI-1 acts in parallel to the two known engulfment pathways, likely downstream of ABL-1. ABL-1 and ABI-1 interact physically in vitro. We propose that ABL-1 opposes the engulfment of apoptotic cells by inhibiting ABI-1 via a pathway that is distinct from the two known engulfment pathways. C1 [Hurwitz, Michael E.; Bloom, Laird; Goldman, Julia; Horvitz, H. Robert] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Hurwitz, Michael E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Vanderzalm, Pamela J.; Garriga, Gian] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Garriga, Gian] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. RP Horvitz, HR (reprint author), MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. EM horvitz@mit.edu FU National Cancer Institute [K08CA104890, NS32057]; National Science Foundation FX MEH was supported by Award Number K08CA104890 from the National Cancer Institute. HRH is the David H. Koch Professor of Biology and an Investigator of the Howard Hughes Medical Institute. GG was supported by National Institutes of Health Grant NS32057. PJV was supported by a National Science Foundation predoctoral fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 87 TC 36 Z9 51 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD APR PY 2009 VL 7 IS 4 BP 876 EP 891 AR e1000099 DI 10.1371/journal.pbio.1000099 PG 16 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 451VW UT WOS:000266500000014 PM 19402756 ER PT J AU Missiuro, PV Liu, KS Zou, LH Ross, BC Zhao, GY Liu, JS Ge, H AF Missiuro, Patrycja Vasilyev Liu, Kesheng Zou, Lihua Ross, Brian C. Zhao, Guoyan Liu, Jun S. Ge, Hui TI Information Flow Analysis of Interactome Networks SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID PROTEIN-INTERACTION NETWORK; CAENORHABDITIS-ELEGANS; C-ELEGANS; YEAST; CENTRALITY; MAP; BETWEENNESS; BIOLOGY; ESSENTIALITY; GENOMICS AB Recent studies of cellular networks have revealed modular organizations of genes and proteins. For example, in interactome networks, a module refers to a group of interacting proteins that form molecular complexes and/or biochemical pathways and together mediate a biological process. However, it is still poorly understood how biological information is transmitted between different modules. We have developed information flow analysis, a new computational approach that identifies proteins central to the transmission of biological information throughout the network. In the information flow analysis, we represent an interactome network as an electrical circuit, where interactions are modeled as resistors and proteins as interconnecting junctions. Construing the propagation of biological signals as flow of electrical current, our method calculates an information flow score for every protein. Unlike previous metrics of network centrality such as degree or betweenness that only consider topological features, our approach incorporates confidence scores of protein-protein interactions and automatically considers all possible paths in a network when evaluating the importance of each protein. We apply our method to the interactome networks of Saccharomyces cerevisiae and Caenorhabditis elegans. We find that the likelihood of observing lethality and pleiotropy when a protein is eliminated is positively correlated with the protein's information flow score. Even among proteins of low degree or low betweenness, high information scores serve as a strong predictor of loss-of-function lethality or pleiotropy. The correlation between information flow scores and phenotypes supports our hypothesis that the proteins of high information flow reside in central positions in interactome networks. We also show that the ranks of information flow scores are more consistent than that of betweenness when a large amount of noisy data is added to an interactome. Finally, we combine gene expression data with interaction data in C. elegans and construct an interactome network for muscle-specific genes. We find that genes that rank high in terms of information flow in the muscle interactome network but not in the entire network tend to play important roles in muscle function. This framework for studying tissue-specific networks by the information flow model can be applied to other tissues and other organisms as well. C1 [Missiuro, Patrycja Vasilyev; Liu, Kesheng; Ross, Brian C.; Ge, Hui] Whitehead Inst Biomed Res, Cambridge, MA USA. [Missiuro, Patrycja Vasilyev] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Zou, Lihua] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhao, Guoyan] Washington Univ, Dept Genet, St Louis, MO 63110 USA. [Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Missiuro, PV (reprint author), Whitehead Inst Biomed Res, Cambridge, MA USA. EM hge@wi.mit.edu OI Ross, Brian/0000-0003-2432-4678 FU Whitehead Institute for Biomedical Research; National Institutes of Health [R01 HG00249, F32 GM73444] FX PVM, KL, BC, and HG are supported by the Whitehead Institute for Biomedical Research. GZ is supported by National Institutes of Health grants R01 HG00249 and F32 GM73444. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 57 Z9 59 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2009 VL 5 IS 4 AR e1000350 DI 10.1371/journal.pcbi.1000350 PG 15 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 447TH UT WOS:000266214200015 PM 19503817 ER PT J AU Harsha, HC Kandasamy, K Ranganathan, P Rani, S Ramabadran, S Gollapudi, S Balakrishnan, L Dwivedi, SB Telikicherla, D Selvan, LDN Goel, R Mathivanan, S Marimuthu, A Kashyap, M Vizza, RF Mayer, RJ DeCaprio, JA Srivastava, S Hanash, SM Hruban, RH Pandey, A AF Harsha, H. C. Kandasamy, Kumaran Ranganathan, Prathibha Rani, Sandhya Ramabadran, Subhashri Gollapudi, Sashikanth Balakrishnan, Lavanya Dwivedi, Sutopa B. Telikicherla, Deepthi Selvan, Lakshmi Dhevi N. Goel, Renu Mathivanan, Suresh Marimuthu, Arivusudar Kashyap, Manoj Vizza, Robert F. Mayer, Robert J. DeCaprio, James A. Srivastava, Sudhir Hanash, Samir M. Hruban, Ralph H. Pandey, Akhilesh TI A Compendium of Potential Biomarkers of Pancreatic Cancer SO PLOS MEDICINE LA English DT Editorial Material ID STEM-CELL ANTIGEN; GENE-EXPRESSION; INTRAEPITHELIAL NEOPLASIA; ADENOCARCINOMA; DATABASE; PROFILES; PROTEINS; MARKERS C1 [Harsha, H. C.; Kandasamy, Kumaran; Ranganathan, Prathibha; Rani, Sandhya; Ramabadran, Subhashri; Gollapudi, Sashikanth; Balakrishnan, Lavanya; Dwivedi, Sutopa B.; Telikicherla, Deepthi; Selvan, Lakshmi Dhevi N.; Goel, Renu; Mathivanan, Suresh; Marimuthu, Arivusudar; Kashyap, Manoj; Pandey, Akhilesh] Int Technol Pk, Inst Bioinformat, Bangalore, Karnataka, India. [Harsha, H. C.; Marimuthu, Arivusudar] Manipal Univ, Manipal, Karnataka, India. [Harsha, H. C.; Kandasamy, Kumaran; Mathivanan, Suresh; Marimuthu, Arivusudar; Kashyap, Manoj; Pandey, Akhilesh] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Harsha, H. C.; Kandasamy, Kumaran; Mathivanan, Suresh; Marimuthu, Arivusudar; Kashyap, Manoj; Pandey, Akhilesh] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD USA. [Vizza, Robert F.] Lustgarten Fdn Pancreat Canc Res, Bethpage, NY USA. [Mayer, Robert J.; DeCaprio, James A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Hanash, Samir M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hruban, Ralph H.; Pandey, Akhilesh] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Hruban, Ralph H.; Pandey, Akhilesh] Johns Hopkins Med Inst, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. RP Harsha, HC (reprint author), Int Technol Pk, Inst Bioinformat, Bangalore, Karnataka, India. EM pandey@jhmi.edu RI Kandasamy, Kumaran/C-8981-2009; Pandey, Akhilesh/B-4127-2009; Mathivanan, Suresh/D-2045-2009; OI Pandey, Akhilesh/0000-0001-9943-6127; Mathivanan, Suresh/0000-0002-7290-5795; Kashyap, Manoj K./0000-0003-3314-3318 NR 20 TC 129 Z9 131 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2009 VL 6 IS 4 AR e1000046 DI 10.1371/journal.pmed.1000046 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 447TN UT WOS:000266214800002 PM 19360088 ER PT J AU Scholz, J Mannion, RJ Hord, DE Griffin, RS Rawal, B Zheng, H Scoffings, D Phillips, A Guo, JL Laing, RJC Abdi, S Decosterd, I Woolf, CJ AF Scholz, Joachim Mannion, Richard J. Hord, Daniela E. Griffin, Robert S. Rawal, Bhupendra Zheng, Hui Scoffings, Daniel Phillips, Amanda Guo, Jianli Laing, Rodney J. C. Abdi, Salahadin Decosterd, Isabelle Woolf, Clifford J. TI A Novel Tool for the Assessment of Pain: Validation in Low Back Pain SO PLOS MEDICINE LA English DT Article ID MECHANISM-BASED CLASSIFICATION; CLINICAL-PRACTICE GUIDELINE; NEUROPATHIC PAIN; SCREENING QUESTIONNAIRE; POSTHERPETIC NEURALGIA; SYMPTOMS; MANAGEMENT; SCALE; SIGNS; RECOMMENDATIONS AB Background: Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology. Methods and Findings: Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%-97%) and specificity (97%; 95% CI 89%-100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs. Conclusions: We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment. C1 [Scholz, Joachim; Hord, Daniela E.; Griffin, Robert S.; Guo, Jianli; Woolf, Clifford J.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Mannion, Richard J.; Laing, Rodney J. C.] Addenbrookes Hosp, Acad Neurosurg Unit, Cambridge, England. [Rawal, Bhupendra; Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Scoffings, Daniel] Addenbrookes Hosp, Dept Radiol, Cambridge CB2 2QQ, England. [Phillips, Amanda] Addenbrookes Hosp, Dept Physiotherapy Serv, Cambridge, England. [Abdi, Salahadin] Univ Miami, Sch Med, Dept Anesthesiol Perioperat Med & Pain Management, Miami, FL USA. [Decosterd, Isabelle] Univ Hosp Ctr, Dept Anesthesiol, Lausanne, Switzerland. [Decosterd, Isabelle] Univ Lausanne, Dept Cell Biol & Morphol, Lausanne, Switzerland. RP Scholz, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM scholz.joachim@mgh.harvard.edu FU Pfizer FX This work was supported by an unrestricted grant initially awarded by Pharmacia through The Academic Medicine and Managed Care Forum, with supplementary support from Pfizer. The sponsors had no role in study design, data collection and analysis, interpretation of results, decision to publish or preparation of the manuscript. NR 56 TC 118 Z9 120 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2009 VL 6 IS 4 AR e1000047 DI 10.1371/journal.pmed.1000047 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 447TN UT WOS:000266214800003 PM 19360087 ER PT J AU Dahlem, MA Hadjikhani, N AF Dahlem, Markus A. Hadjikhani, Nouchine TI Migraine Aura: Retracting Particle-Like Waves in Weakly Susceptible Cortex SO PLOS ONE LA English DT Article ID HUMAN VISUAL-CORTEX; CORTICAL SPREADING DEPRESSION; HUMAN STRIATE CORTEX; EXCITABLE MEDIA; CEREBRAL-CORTEX; CHICKEN RETINA; EXCITATION WAVES; AUDITORY-CORTEX; FUNCTIONAL MRI; MODEL AB Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD observed in animal cortex and aura symptoms mapped to the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value sigma = 1 at the instability point. We predict that human cortex is only weakly susceptible to SD (sigma < 1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. Moreover, we use retinal SD to give a proof of concept of the existence of this instability point and describe how cortical susceptibility to SD must be adjusted for migraine drug testing. Close to the instability point at sigma = 1 the dynamical repertoire of cortical tissue is increased. As a consequence, the picture of an engulfing SD that became paradigmatic for migraine with aura needs to be modified in most cases towards a more spatially confined pattern that remains within the originating major gyrus or sulcus. Furthermore, we discuss the resulting implications on migraine pharmacology that is hitherto tested in the regime (sigma > 1), and potentially silent aura occurring below a second bifurcation point at sigma = 0 on the susceptible scale. C1 [Dahlem, Markus A.] Tech Univ Berlin, Inst Theoret Phys, Berlin, Germany. [Dahlem, Markus A.] Otto Von Guericke Univ, Klin Neurol II, Magdeburg, Germany. [Dahlem, Markus A.] Leibniz Inst Neurobiol, Magdeburg, Germany. [Hadjikhani, Nouchine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imag, Charlestown, MA USA. [Hadjikhani, Nouchine] Brain Mind Inst, EPFL, Lausanne, Switzerland. RP Dahlem, MA (reprint author), Tech Univ Berlin, Inst Theoret Phys, Berlin, Germany. EM dahlem@physik.tu-berlin.de RI Hadjikhani, Nouchine/C-2018-2008; Dahlem, Markus/A-8805-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106; Dahlem, Markus/0000-0002-7532-0127 FU Deutsche Forschungsgemeinschaft [DA 602/1-1, SFB 555]; NIH [5PO1NS 35611] FX Deutsche Forschungsgemeinschaft DA 602/1-1 and SFB 555, and by an NIH grant 5PO1NS 35611. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 26 Z9 26 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 1 PY 2009 VL 4 IS 4 AR e5007 DI 10.1371/journal.pone.0005007 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437PY UT WOS:000265500600008 PM 19337363 ER PT J AU Cureton, DK Massol, RH Saffarian, S Kirchhausen, TL Whelan, SPJ AF Cureton, David K. Massol, Ramiro H. Saffarian, Saveez Kirchhausen, Tomas L. Whelan, Sean P. J. TI Vesicular Stomatitis Virus Enters Cells through Vesicles Incompletely Coated with Clathrin That Depend upon Actin for Internalization SO PLOS PATHOGENS LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; MAMMALIAN-CELLS; ARP2/3 COMPLEX; DYNAMIC ACTIN; HOST-CELLS; RNA INTERFERENCE; PLASMA-MEMBRANE; N-WASP; ENTRY; RECRUITMENT AB Many viruses that enter cells by clathrin-dependent endocytosis are significantly larger than the dimensions of a typical clathrin-coated vesicle. The mechanisms by which viruses co-opt the clathrin machinery for efficient internalization remain uncertain. Here we examined how clathrin-coated vesicles accommodate vesicular stomatitis virus (VSV) during its entry into cells. Using high-resolution imaging of the internalization of single viral particles into cells expressing fluorescent clathrin and adaptor molecules, we show that VSV enters cells through partially clathrin-coated vesicles. We found that on average, virus-containing vesicles contain more clathrin and clathrin adaptor molecules than conventional vesicles, but this increase is insufficient to permit full coating of the vesicle. We further show that virus-containing vesicles depend upon the actin machinery for their internalization. Specifically, we found that components of the actin machinery are recruited to virus-containing vesicles, and chemical inhibition of actin polymerization trapped viral particles in vesicles at the plasma membrane. By analysis of multiple independent virus internalization events, we show that VSV induces the nucleation of clathrin for its uptake, rather than depending upon random capture by formation of a clathrin-coated pit. This work provides new mechanistic insights into the process of virus internalization as well as uptake of unconventional cargo by the clathrin-dependent endocytic machinery. C1 [Cureton, David K.; Whelan, Sean P. J.] Harvard Univ, Sch Med, Dept Microbiol, Boston, MA 02115 USA. [Cureton, David K.; Whelan, Sean P. J.] Harvard Univ, Sch Med, Dept Mol Genet, Boston, MA USA. [Cureton, David K.; Whelan, Sean P. J.] Harvard Univ, Sch Med, Program Virol, Boston, MA USA. [Massol, Ramiro H.] Childrens Hosp, Boston, MA 02115 USA. [Massol, Ramiro H.; Saffarian, Saveez; Kirchhausen, Tomas L.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Massol, Ramiro H.; Saffarian, Saveez; Kirchhausen, Tomas L.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. RP Cureton, DK (reprint author), Harvard Univ, Sch Med, Dept Microbiol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu; swhelan@hms.harvard.edu FU NIH [U54 AI057159, GM075252]; Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease FX This work was supported by NIH grants U54 AI057159 (NERCE Project 1C and Imaging Resource) and GM075252 to TLK (http://www.nih.gov). SPJW is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease (http://www.bwfund.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 130 Z9 133 U1 4 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2009 VL 5 IS 4 AR e1000394 DI 10.1371/journal.ppat.1000394 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 447UC UT WOS:000266216300037 PM 19390604 ER PT J AU Grotzke, JE Harriff, MJ Siler, AC Nolt, D Delepine, J Lewinsohn, DA Lewinsohn, DM AF Grotzke, Jeff E. Harriff, Melanie J. Siler, Anne C. Nolt, Dawn Delepine, Jacob Lewinsohn, Deborah A. Lewinsohn, David M. TI The Mycobacterium tuberculosis Phagosome Is a HLA-I Processing Competent Organelle SO PLOS PATHOGENS LA English DT Article ID CD8(+) T-LYMPHOCYTES; ANTIGEN PRESENTATION; EXOGENOUS ANTIGENS; CROSS-PRESENTATION; DENDRITIC CELLS; INFECTED-CELLS; PEPTIDE; PATHWAY; TAP; MACROPHAGES AB Mycobacterium tuberculosis (Mtb) resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-gamma release by CD8(+) T cell clones, we examined the processing and presentation pathway for two Mtb-derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib). Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER-golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER-golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I: peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E: peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER-localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb-derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens. C1 [Grotzke, Jeff E.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Harriff, Melanie J.; Siler, Anne C.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Dept Med, Portland VA Med Ctr, Portland, OR 97201 USA. [Nolt, Dawn; Delepine, Jacob; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Div Infect Dis, Dept Pediat, Portland, OR 97201 USA. RP Grotzke, JE (reprint author), Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. EM lewinsod@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NIH [R01AI048090]; VA Merit Review Grant; Portland VA Medical Center FX This research was supported by NIH grant R01AI048090, VA Merit Review Grant, and the Portland VA Medical Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 33 Z9 33 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2009 VL 5 IS 4 AR e1000374 DI 10.1371/journal.ppat.1000374 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 447UC UT WOS:000266216300018 PM 19360129 ER PT J AU Haim, H Si, ZH Madani, N Wang, LP Courter, JR Princiotto, A Kassa, A DeGrace, M McGee-Estrada, K Mefford, M Gabuzda, D Smith, AB Sodroski, J AF Haim, Hillel Si, Zhihai Madani, Navid Wang, Liping Courter, Joel R. Princiotto, Amy Kassa, Aemro DeGrace, Marciella McGee-Estrada, Kathleen Mefford, Megan Gabuzda, Dana Smith, Amos B., III Sodroski, Joseph TI Soluble CD4 and CD4-Mimetic Compounds Inhibit HIV-1 Infection by Induction of a Short-Lived Activated State SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TO-CELL TRANSMISSION; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; NEUTRALIZATION EPITOPES; CONFORMATIONAL-CHANGES; MONOCLONAL-ANTIBODIES; CHEMOKINE RECEPTORS; GP120-CD4 BINDING; ATOMIC-STRUCTURE AB Binding to the CD4 receptor induces conformational changes in the human immunodeficiency virus (HIV-1) gp120 exterior envelope glycoprotein. These changes allow gp120 to bind the coreceptor, either CCR5 or CXCR4, and prime the gp41 transmembrane envelope glycoprotein to mediate virus-cell membrane fusion and virus entry. Soluble forms of CD4 (sCD4) and small-molecule CD4 mimics (here exemplified by JRC-II-191) also induce these conformational changes in the HIV-1 envelope glycoproteins, but typically inhibit HIV-1 entry into CD4-expressing cells. To investigate the mechanism of inhibition, we monitored at high temporal resolution inhibitor-induced changes in the conformation and functional competence of the HIV-1 envelope glycoproteins that immediately follow engagement of the soluble CD4 mimics. Both sCD4 and JRC-II-191 efficiently activated the envelope glycoproteins to mediate infection of cells lacking CD4, in a manner dependent on coreceptor affinity and density. This activated state, however, was transient and was followed by spontaneous and apparently irreversible changes of conformation and by loss of functional competence. The longevity of the activated intermediate depended on temperature and the particular HIV-1 strain, but was indistinguishable for sCD4 and JRC-II-191; by contrast, the activated intermediate induced by cell-surface CD4 was relatively long-lived. The inactivating effects of these activation-based inhibitors predominantly affected cell-free virus, whereas virus that was prebound to the target cell surface was mainly activated, infecting the cells even at high concentrations of the CD4 analogue. These results demonstrate the ability of soluble CD4 mimics to inactivate HIV-1 by prematurely triggering active but transient intermediate states of the envelope glycoproteins. This novel strategy for inhibition may be generally applicable to high-potential-energy viral entry machines that are normally activated by receptor binding. C1 [Haim, Hillel; Si, Zhihai; Madani, Navid; Wang, Liping; Princiotto, Amy; Kassa, Aemro; DeGrace, Marciella; McGee-Estrada, Kathleen; Mefford, Megan; Gabuzda, Dana; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, Boston, MA 02115 USA. [Courter, Joel R.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Haim, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU National Institutes of Health [AI24755, GM56550, AI67854]; International AIDS Vaccine Initiative FX This work was supported by grants from the National Institutes of Health (AI24755, GM56550, and AI67854)(http://www.nih.gov), by the International AIDS Vaccine Initiative (http://www.iavi.org), and by the late William F. McCarty-Cooper. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 90 Z9 90 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2009 VL 5 IS 4 AR e1000360 DI 10.1371/journal.ppat.1000360 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 447UC UT WOS:000266216300005 PM 19343205 ER PT J AU Troyer, RM McNevin, J Liu, Y Zhang, SC Krizan, RW Abraha, A Tebit, DM Zhao, H Avila, S Lobritz, MA McElrath, MJ Le Gall, S Mullins, JI Arts, EJ AF Troyer, Ryan M. McNevin, John Liu, Yi Zhang, Shao Chong Krizan, Randall W. Abraha, Awet Tebit, Denis M. Zhao, Hong Avila, Santiago Lobritz, Michael A. McElrath, M. Juliana Le Gall, Sylvie Mullins, James I. Arts, Eric J. TI Variable Fitness Impact of HIV-1 Escape Mutations to Cytotoxic T Lymphocyte (CTL) Response SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL ESCAPE; DISEASE PROGRESSION; PRIMARY INFECTION; IMMUNE SELECTION; CAPSID PROTEIN; IN-VIVO; EPITOPE; GAG; HLA AB Human lymphocyte antigen (HLA)-restricted CD8(+) cytotoxic T lymphocytes (CTL) target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs. C1 [Troyer, Ryan M.; Krizan, Randall W.; Abraha, Awet; Tebit, Denis M.; Avila, Santiago; Arts, Eric J.] Case Western Reserve Univ, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. [McNevin, John; McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, Div Clin Res, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA. [Liu, Yi; Zhao, Hong; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Zhang, Shao Chong; Le Gall, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. [Avila, Santiago] Ctr Res Infect Dis, Natl Inst Resp Dis, Mexico City, DF, Mexico. [Lobritz, Michael A.] Case Western Reserve Univ, Dept Mol & Microbiol, Cleveland, OH 44106 USA. RP Troyer, RM (reprint author), Case Western Reserve Univ, Dept Med, Div Infect Dis, Cleveland, OH 44106 USA. EM eja3@case.edu FU NIAID; NIH [AI49170, AI57005, AI058894]; University of Washington by NIAID; American Foundation for AIDS Research (amfAR) FX Research at Case Western Reserve University was supported by NIAID; NIH grants AI49170, AI57005, and AI058894; and at University of Washington by NIAID, NIH grants AI57005 and AI058894. RMT was supported by an American Foundation for AIDS Research (amfAR) fellowship 106532-35-RFGN. The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript. NR 54 TC 102 Z9 107 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2009 VL 5 IS 4 AR e1000365 DI 10.1371/journal.ppat.1000365 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 447UC UT WOS:000266216300009 PM 19343217 ER PT J AU Ackerson, LK Viswanath, K AF Ackerson, Leland K. Viswanath, Kasisomayajula TI Communication Inequalities, Social Determinants, and Intermittent Smoking in the 2003 Health Information National Trends Survey SO PREVENTING CHRONIC DISEASE LA English DT Article AB Introduction Intermittent smokers account for a large proportion of all smokers, and this trend is increasing. Social and communication inequalities may account for disparities in intermittent smoking status. Methods Data for this study came from 2,641 ever-smokers from a 2003 nationally representative cross-sectional survey. Independent variables of interest included race/ethnicity, sex, household income, education, health media attention, and cancer-related beliefs. The outcome of interest was smoking status categorized as daily smoker, intermittent smoker, or former smoker. Analyses used 2 sets of multivariable logistic regressions to investigate the associations of covariates with intermittent smokers compared with former smokers and with daily smokers. Results People with high education and high income, Spanish-speaking Hispanics, and women were the most likely to be intermittent rather than daily smokers. Women and Spanish-speaking Hispanics were the most likely to be intermittent rather than former smokers. Attention to health media sources increased the likelihood that a person would be an intermittent smoker instead of a former or daily smoker. Believing that damage from smoking is avoidable and irreversible was associated with lower odds of being an intermittent smoker rather than a former smoker but did not differentiate intermittent smoking from daily smoking. Conclusion The results indicate that tailoring smoking-cessation campaigns toward intermittent smokers from specific demographic groups by using health media may improve the effect of these campaigns and reduce social health disparities. C1 [Ackerson, Leland K.; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Ackerson, LK (reprint author), Univ Massachusetts, Dept Community Hlth & Sustainabil, 3 Solomont Way,Ste 3, Lowell, MA 01854 USA. EM leland_ackerson@uml.edu FU Dana-Farber Harvard Cancer Center; Tobacco Research Network on Disparities FX We thank the National Cancer Institute for making the Health Information National Trends Survey data available to us. The authors acknowledge the support of the Dana-Farber Harvard Cancer Center and the Tobacco Research Network on Disparities. NR 33 TC 15 Z9 16 U1 3 U2 9 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD APR PY 2009 VL 6 IS 2 AR A40 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20RV UT WOS:000208158000002 PM 19288983 ER PT J AU Crilly, JF Caine, ED Lamberti, JS Brown, T Friedman, B AF Crilly, John F. Caine, Eric D. Lamberti, J. Steven Brown, Theodore Friedman, Bruce TI Mental Health Services Use and Symptom Prevalence in a Cohort of Adults on Probation SO PSYCHIATRIC SERVICES LA English DT Article ID ILLNESS AB Objective: This study examined the prevalence of mental disorder symptoms among adult probationers and the probability of mental health service use. Methods: Data from the 2001 National Household Survey on Drug Abuse were used to obtain information on adults reporting mental disorder symptoms who had been on probation within the past year and those who had not. Results: Twenty-seven percent of probationers (N=311 of 1,168) and 17% of nonprobationers (N=5,830 of 34,230) had mental disorder symptoms. Mental health service use was reported by 23% of both groups. Compared with persons who had not been on probation, probationers were more likely to report psychosis, mania, and post-traumatic stress disorder; both groups were as likely to report depression. Conclusions: The prevalence of mental disorder symptoms did not differ by probation status. However, the type and distribution of symptoms were significantly different in the two groups. These are important considerations when planning for service connection with mental health providers. (Psychiatric Services 60: 542-544, 2009) C1 [Crilly, John F.; Caine, Eric D.; Lamberti, J. Steven; Friedman, Bruce] Univ Rochester, Dept Psychiat, Rochester, NY 14642 USA. [Friedman, Bruce] Univ Rochester, Dept Community Prevent Med, Rochester, NY 14642 USA. [Crilly, John F.; Brown, Theodore] US Dept Vet Affairs, VA Healthcare Network Upstate New York VISN2, Ctr Excellence Canandaigua, Canandaigua, NY USA. RP Crilly, JF (reprint author), Univ Rochester, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM john_crilly@urmc.rochester.edu FU National Institute of Mental Health [P20-MH071897] FX The writing of this brief report was supported in part by grant P20-MH071897 ( principal investigator, Dr. Caine) from the National Institute of Mental Health. This brief report draws on a portion of Dr. Crilly's dissertation, completed under the supervision of Dr. Friedman and coauthors. NR 9 TC 8 Z9 8 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2009 VL 60 IS 4 BP 542 EP 544 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 427QJ UT WOS:000264793500021 PM 19339332 ER PT J AU Horan, WP Nuechterlein, KH Wynn, JK Lee, J Castelli, F Green, MF AF Horan, W. P. Nuechterlein, K. H. Wynn, J. K. Lee, J. Castelli, F. Green, M. F. TI Disturbances in the spontaneous attribution of social meaning in schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anthropomorphizing; mentalizing; schizophrenia; social cognition; theory of mind ID HIGHER-FUNCTIONING AUTISM; PSYCHIATRIC RATING-SCALE; INTENTIONAL MOVEMENT; ASPERGER-SYNDROME; BRAIN MECHANISMS; MIND; PERCEPTION; CAUSALITY; PEOPLE; MOTION AB Background. Schizophrenia patients show disturbances on a range of tasks that assess mentalizing or 'Theory of Mind' (ToM). However, these tasks are often developmentally inappropriate, make large demands on verbal abilities and explicit problem-solving skills, and involve after-the-fact reflection as opposed to spontaneous mentalizing. Method. To address these limitations, 55 clinically stable schizophrenia out-patients and 44 healthy controls completed a validated Animations Task designed to assess spontaneous attributions of social meaning to ambiguous abstract visual stimuli. In this paradigm, 12 animations depict two geometric shapes 'interacting' with each other in three conditions: (1) ToM interactions that elicit attributions of mental states to the agents, (2) Goal-Directed (GD) interactions that elicit attributions of simple actions, and (3) Random scenes in which no interaction occurs. Verbal descriptions of each animation are rated for the degree of Intentionality attributed to the agents and for accuracy. Results. Patients had lower Intentionality ratings than controls for ToM and GD scenes but the groups did not significantly differ for Random scenes. The descriptions of the patients less closely matched the situations intended by the developers of the task. Within the schizophrenia group, performance on the Animations Task showed minimal associations with clinical symptoms. Conclusions. Patients demonstrated disturbances in the spontaneous attribution of mental states to abstract visual stimuli that normally evoke such attributions. Hence, in addition to previously established impairment on mentalizing tasks that require logical inferences about others' mental states, individuals with schizophrenia show disturbances in implicit aspects of mentalizing. C1 [Green, M. F.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Castelli, F.] CALTECH, Pasadena, CA 91125 USA. RP Horan, WP (reprint author), 300 UCLA Med Plaza,Suite 2240, Los Angeles, CA 90095 USA. EM horan@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU NARSAD [MH43292, MH65707]; National Institute of Mental Health [MH14584]; Department of Veterans Affairs FX This research was supported by a NARSAD Young Investigator Award (W. P. Horan), by research grants MH43292 and MH65707 (PI: M. F. Green) and Institutional NRSA MH14584 (PI: K. H. Nuechterlein) from the National Institute of Mental Health, and by the Department of Veterans Affairs VISN 22 MIRECC. We thank Tamara A. Russell for helpful consultation during the planning of this study, and Shelly M. Crosby, Kelly Tillery, Karina Shokat-Fadai, Joseph Ventura, and Sarah Wilson for their contributions to this project. NR 54 TC 23 Z9 23 U1 2 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2009 VL 39 IS 4 BP 635 EP 643 DI 10.1017/S0033291708003838 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 426EO UT WOS:000264691000010 PM 18606048 ER PT J AU Kern, RS Green, MF Fiske, AP Kee, KS Lee, J Sergi, MJ Horan, WP Subotnik, KL Sugar, CA Nuechterlein, KH AF Kern, R. S. Green, M. F. Fiske, A. P. Kee, K. S. Lee, J. Sergi, M. J. Horan, W. P. Subotnik, K. L. Sugar, C. A. Nuechterlein, K. H. TI Theory of mind deficits for processing counterfactual information in persons with chronic schizophrenia SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Counterfactual information; deception; sarcasm; schizophrenia; theory of mind ID TRAUMATIC BRAIN-INJURY; SOCIAL-PERCEPTION; MENTALIZING ABILITY; PEOPLE; COMPREHENSION; REMISSION; COMMUNICATION; PRAGMATICS; INFERENCE; VALIDITY AB Background. Interpersonal communication problems are common among persons with schizophrenia and may be linked, in part, to deficits in theory of mind (ToM), the ability to accurately perceive the attitudes, beliefs and intentions of others. Particular difficulties might be expected in the processing of counterfactual information such as sarcasm or lies. Method. The present study included 50 schizophrenia or schizo-affective out-patients and 44 demographically comparable healthy adults who were administered Part III of The Awareness of Social Inference Test (TASIT; a measure assessing comprehension of sarcasm Versus lies) as well as measures of positive and negative symptoms and community functioning. Results. TASIT data were analyzed using a 2 (group: patients versus healthy adults) x 2 (condition: sarcasm versus lie) repeated-measures ANOVA. The results show significant effects for group, condition, and the group x condition interaction. Compared to controls, patients performed significantly worse on sarcasm but not lie scenes. Within-group contrasts showed that patients performed significantly worse on sarcasm versus lie scenes; controls performed comparably on both. In patients, performance on TASIT showed a significant correlation with positive, but not negative, symptoms. The group and interaction effects remained significant when rerun with a subset of patients with low-level positive symptoms. The findings for a relationship between TASIT performance and community functioning were essentially negative. Conclusions. The findings replicate a prior demonstration of difficulty in the comprehension of sarcasm using a different test, but are not consistent with previous studies showing global ToM deficits in schizophrenia. C1 [Kern, R. S.; Green, M. F.; Kee, K. S.; Lee, J.; Sergi, M. J.; Horan, W. P.; Subotnik, K. L.; Nuechterlein, K. H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA. [Kern, R. S.; Green, M. F.; Kee, K. S.; Lee, J.; Sergi, M. J.; Horan, W. P.] Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, VISN 22, Los Angeles, CA USA. [Fiske, A. P.] Univ Calif Los Angeles, Dept Anthropol, Ctr Culture Brain & Dev, Los Angeles, CA 90024 USA. [Fiske, A. P.] Univ Calif Los Angeles, Ctr Behav Evolut & Culture, Los Angeles, CA 90024 USA. [Kee, K. S.] Calif State Univ, Channel Isl, CA USA. [Sergi, M. J.] Calif State Univ Northridge, Northridge, CA 91330 USA. [Nuechterlein, K. H.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Psychol, Los Angeles, CA 90024 USA. RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare Syst MIRECC 210, Bldg 210,Room 116,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rkern@ucla.edu RI Lee, Junghee/C-5226-2014 OI Lee, Junghee/0000-0001-9567-8700 FU NIMH [P50 MH 66586] FX We thank the patients for their participation in the project, and Mike DeGroot, Robin Kite, Jeff Nishii, and Samantha Swain for their help in the data collection. The project was supported by an NIMH Center grant to K.H.N. (P50 MH 66586). NR 56 TC 42 Z9 42 U1 3 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2009 VL 39 IS 4 BP 645 EP 654 DI 10.1017/S0033291708003966 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 426EO UT WOS:000264691000011 PM 18694537 ER PT J AU Faraone, SV Kunwar, A Adamson, J Biederman, J AF Faraone, S. V. Kunwar, A. Adamson, J. Biederman, J. TI Personality traits among ADHD adults: implications of late-onset and subthreshold diagnoses SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Attention deficit hyperactivity disorder (ADHD); diagnosis; personality ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CHILD-BEHAVIOR CHECKLIST; EXECUTIVE FUNCTION DEFICITS; AGE-DEPENDENT DECLINE; GENERAL-POPULATION; UNITED-STATES; TWIN; INATTENTION; COMORBIDITY AB Background. Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish onset prior to the DSM-IV criterion of age 7 or if the number of symptoms does not achieve the DSM threshold for diagnosis. Previous work has assessed the validity of such diagnoses based on psychiatric co-morbidity, family history and neuropsychological functions but none of these studies have used personality as a validation criterion. Method. We compared four groups of adults: (1) full ADHD subjects who met all DSM-IV criteria for childhood-onset ADHD; (2) late-onset subjects who met all criteria except the age at onset criterion, (3) subthreshold subjects who did not meet full symptom criteria and (4) non-ADHD subjects who did not meet any of the above criteria. Diagnoses were made by using the Structured Clinical Interview for DSM-IV (SCID) and the Temperament and Character Inventory (TCI) was used to assess personality traits. Results. We found that full ADHD and late-onset ADHD showed similar personality profiles with significant deviations on all TO scales except reward dependence and self-transcendence. By contrast, subthreshold cases only showed deviations on novelty seeking and self-directiveness. Conclusions. These data call into question the stringent age of onset of ADHD symptom criteria for adults when making retrospective diagnoses of ADHD. Subthreshold ADHD seems to be a milder form of the disorder that is consistent with dimensional views of the disorder. C1 [Faraone, S. V.; Kunwar, A.] SLTNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Adamson, J.; Biederman, J.] Harvard Univ, Sch Med, Dept Psychiat,Yawkey Ctr Outpatient Care, Massachusetts Gen Hosp,Pediat Psychopharmacol Uni, Boston, MA 02115 USA. RP Faraone, SV (reprint author), SLTNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Health [R01MH57934] FX This work was supported in part by grants to S.V.F. from the National Institute of Health (R01MH57934). NR 56 TC 61 Z9 61 U1 2 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2009 VL 39 IS 4 BP 685 EP 693 DI 10.1017/S0033291708003917 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 426EO UT WOS:000264691000015 PM 18588742 ER PT J AU Caska, CM Hendrickson, BE Wong, MH Ali, S Neylan, T Whooley, MA AF Caska, Catherine M. Hendrickson, Bethany E. Wong, Michelle H. Ali, Sadia Neylan, Thomas Whooley, Mary A. TI Anger Expression and Sleep Quality in Patients With Coronary Heart Disease: Findings From the Heart and Soul Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE anger expression; sleep quality; coronary heart disease ID CORTICOTROPIN-RELEASING HORMONE; POSTTRAUMATIC-STRESS-DISORDER; C-REACTIVE PROTEIN; BLOOD-PRESSURE; ATHEROSCLEROSIS RISK; CARDIOVASCULAR CONSEQUENCES; PERSEVERATIVE COGNITION; MYOCARDIAL-INFARCTION; CHRONIC ILLNESS; WHITE MALES AB Objective: To evaluate if anger expression affects sleep quality in patients with coronary heart disease (CHD). Research has indicated that poor sleep quality independently predicts adverse outcomes in patients with CHID. Risk factors for poor sleep quality include older age, socioeconomic factors, medical comorbidities, lack of exercise, and depression. Methods: We sought to examine the association of anger expression with sleep quality in 1020 outpatients with CHD from the Heart and Soul Study. We assessed anger-in, anger-out, and anger temperament, using the Spielberger State-Trait Anger Expression Inventory 2, and measured sleep quality, using items from the Cardiovascular Health Study and Pittsburgh Sleep Quality Index. We used multivariate analysis of variance to examine the association between anger expression and sleep quality, adjusting for potential confounding variables. Results: Each standard deviation (SD) increase in anger-in was associated with an 80% greater odds of poor sleep quality (odds ratio (OR)=1.8, 95% Confidence Interval (CI)=1.6-2.1; p<.0001). This association remained strong after adjusting for demographics, comorbidities, lifestyle factors, medications, cardiac function, depressive symptoms, anger-out, and anger temperament (adjusted OR=1.4, 95% CI=1.5-1.7; p=.001). In the same model, each SD increase in anger-out was associated with a 21% decreased odds of poor sleep quality (OR=0.79,95% CI=0.64-0.98; p=.03). Anger temperament was not independently associated with sleep quality. Conclusions: Anger suppression is associated with poor sleep quality in patients with CHD. Whether modifying anger expression can improve sleep quality or reduce cardiovascular morbidity and mortality deserves further study. C1 [Caska, Catherine M.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. [Hendrickson, Bethany E.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Wong, Michelle H.; Ali, Sadia; Neylan, Thomas; Whooley, Mary A.] San Francisco VA Med Ctr, Dept Vet Affairs, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA USA. [Neylan, Thomas] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Caska, CM (reprint author), Univ Utah, Dept Psychol, 380 S 1530 E,Room 502, Salt Lake City, UT 84112 USA. EM cmcaska@gmail.com FU Department of Veterans Affairs (Epidemiology Merit Review Program); National Heart, Lung and Blood Institute [R01 HI-079235]; Robert Wood Johnson Foundation; American Federation for Aging Research; Ischemia Research and Education Foundation; Nancy Kirwan Heart Research Fund FX Supported by grants from the Department of Veterans Affairs (Epidemiology Merit Review Program), the National Heart, Lung and Blood Institute (Grant R01 HI-079235), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), the American Federation for Aging Research (Paul Beeson Faculty Scholars in Aging Research Program), the Ischemia Research and Education Foundation, and the Nancy Kirwan Heart Research Fund. None of these funding sources had any role in the collection of data, interpretation of results, or preparation of this manuscript. All funding was received by M.A.W. NR 63 TC 17 Z9 18 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2009 VL 71 IS 3 BP 280 EP 285 DI 10.1097/PSY.0b013e31819b6a08 PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 434NQ UT WOS:000265281800005 PM 19251866 ER PT J AU Yared, K Wood, MJ AF Yared, Kibar Wood, Malissa J. TI Is Marathon Running Hazardous to Your Cardiovascular Health? The Jury Is Still Out SO RADIOLOGY LA English DT Editorial Material ID CARDIAC TROPONIN-T; MYOCARDIAL-PERFUSION; ENDURANCE EXERCISE; BOSTON-MARATHON; RUNNERS; DYSFUNCTION; INJURY; HEART C1 [Yared, Kibar; Wood, Malissa J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Wood, MJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Blake 25, Boston, MA 02114 USA. EM mjwood@partners.org NR 15 TC 11 Z9 12 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2009 VL 251 IS 1 BP 3 EP 5 DI 10.1148/radiol.2511090041 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 439QV UT WOS:000265643000002 PM 19332839 ER PT J AU Sistrom, CL Dang, PA Weilburg, JB Dreyer, KJ Rosenthal, DI Thrall, JH AF Sistrom, Christopher L. Dang, Pragya A. Weilburg, Jeffrey B. Dreyer, Keith J. Rosenthal, Daniel I. Thrall, James H. TI Effect of Computerized Order Entry with Integrated Decision Support on the Growth of Outpatient Procedure Volumes: Seven-year Time Series Analysis SO RADIOLOGY LA English DT Article ID HEALTH-CARE COSTS AB Purpose: To determine the effect of a computerized radiology order entry (ROE) and decision support (DS) system on growth rate of outpatient computed tomography (CT), magnetic resonance (MR) imaging, and ultrasonography (US) procedure volumes over time at a large metropolitan academic medical center. Materials and Methods: Institutional review board approval was obtained for this study of deidentified aggregate administrative data. The research was compliant with HIPAA; informed consent was waived. This was a retrospective study of outpatient advanced imaging utilization before, during, and after implementation of a Web-based ROE and DS system. Dependent variables were the quarterly volumes of outpatient CT, MR imaging, and US examinations from quarter 4 of 2000 through quarter 4 of 2007. Outpatient visits during each quarter were included as control variables. These data were analyzed as three separate time series with piecewise linear regression for simultaneous estimation of quarterly examination volume trends before and after ROE and DS system implementation. This procedure was repeated with log-transformed quarterly volumes to estimate percentage growth rates. Results: There was a significant decrease in CT volume growth (274 per quarter) and growth rate (2.75% per quarter) after ROE and DS system implementation (P < .001). For MR imaging, growth rate decreased significantly (1.2%, P = .016) after ROE and DS system implementation; however, there was no significant change in quarterly volume growth. With US, quarterly volume growth (n = 98, P = .014) and growth rate (1.3%, P = .001) decreased significantly after ROE implementation. These changes occurred during a steady growth in clinic visit volumes in the associated referral practices. Conclusion: Substantial decreases in the growth of outpatient CT and US procedure volume coincident with ROE implementation (supplemented by DS for CT) were observed. The utilization of outpatient MR imaging decreased less impressively, with only the rate of growth being significantly lower after interventions were in effect. (c) RSNA, 2009 C1 [Sistrom, Christopher L.] Univ Florida, Ctr Hlth, Dept Radiol, Gainesville, FL 32610 USA. [Dang, Pragya A.; Dreyer, Keith J.; Rosenthal, Daniel I.; Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Weilburg, Jeffrey B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Sistrom, CL (reprint author), Univ Florida, Ctr Hlth, Dept Radiol, POB 100374, Gainesville, FL 32610 USA. EM sistrc@radiology.ufl.edu NR 17 TC 153 Z9 155 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2009 VL 251 IS 1 BP 147 EP 155 DI 10.1148/radiol.2511081174 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 439QV UT WOS:000265643000018 PM 19221058 ER PT J AU Floyd, SR Taghian, AG AF Floyd, Scott R. Taghian, Alphonse G. TI Post-mastectomy radiation in large node-negative breast tumors: Does size really matter? SO RADIOTHERAPY AND ONCOLOGY LA English DT Review DE Breast cancer; T3N0; Post-mastectomy radiation therapy ID SURGICAL ADJUVANT BREAST; CLINICAL-PRACTICE GUIDELINES; COOPERATIVE-ONCOLOGY-GROUP; LOCO-REGIONAL RECURRENCE; END RESULTS DATABASE; CANCER PATIENTS; LOCOREGIONAL RECURRENCE; POSTOPERATIVE RADIOTHERAPY; RANDOMIZED-TRIAL; CONSERVATIVE SURGERY AB Treatment decisions regarding local control can be particularly challenging for T3N0 breast tumors because of difficulty in estimating rates of local failure after mastectomy. Reports in the literature detailing the rates of local failure vary widely, likely owing to the Uncommon incidence of this clinical situation. The literature regarding this clinical scenario is reviewed, including recent reports that specifically address the issue of local failure rates after mastectomy in the absence of radiation for large node-negative breast tumors. (C) 2009 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology 91 (2009) 33-37 C1 [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Breast Serv, Boston, MA 02114 USA. [Floyd, Scott R.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Breast Serv, 55 Fruit St, Boston, MA 02114 USA. EM atagahian@partners.org NR 52 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2009 VL 91 IS 1 BP 33 EP 37 DI 10.1016/j.radonc.2008.09.015 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 435QG UT WOS:000265357800005 PM 19201501 ER PT J AU Pru, JK Kaneko-Tarui, T Jurisicova, A Kashiwagi, A Selesniemi, K Tilly, JL AF Pru, James K. Kaneko-Tarui, Tomoko Jurisicova, Andrea Kashiwagi, Aki Selesniemi, Kaisa Tilly, Jonathan L. TI Induction of Proapoptotic Gene Expression and Recruitment of p53 Herald Ovarian Follicle Loss Caused by Polycyclic Aromatic Hydrocarbons SO REPRODUCTIVE SCIENCES LA English DT Article DE Apoptosis; AHR; BAX; cell death; oocyte; ovary; p53; DNA damage; PAH ID TRANSCRIPTION FACTOR; HYDROXYLASE-ACTIVITY; CYTOCHROME-C; AH RECEPTOR; DNA-DAMAGE; CELL-DEATH; BAX GENE; ACTIVATION; APOPTOSIS; MICE AB Activation of the aryl hydrocarbon receptor (AHR) by polycyclic aromatic hydrocarbons (PAH), a ubiquitous class of environmental and occupational biohazards, accelerates germ cell depletion in female mice during prenatal and postnatal life. Like AHR, BAX is also functionally required for PAH to kill oocytes. Here, we show that PAH upregulates ovarian expression of not just Bax but a large cassette of proapoptotic genes that function at multiple steps of the cell death signaling pathway. We further show that ovarian expression of p52 and several proapoptotic genes that are known transcriptional targets of p53 are increased by PAH treatment, and that mice lacking functional p53 are resistant to the ovotoxic effects of in vivo PAH exposure. This study provides further mechanistic insights into how PAH accelerate oocyte depletion in females and adds p53 to the list of genes whose functional importance to PAH-induced ovotoxicity has been demonstrated by gene knockout technology. C1 [Pru, James K.; Kaneko-Tarui, Tomoko; Kashiwagi, Aki; Selesniemi, Kaisa; Tilly, Jonathan L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, Boston, MA 02114 USA. [Pru, James K.; Kaneko-Tarui, Tomoko; Kashiwagi, Aki; Selesniemi, Kaisa; Tilly, Jonathan L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [Jurisicova, Andrea] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON, Canada. [Jurisicova, Andrea] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Tilly, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Vincent Obstet & Gynecol, THR 901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org RI Jurisicova, Andrea/E-4580-2013 FU NIEHS NIH HHS [R01-ES08430] NR 46 TC 18 Z9 19 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 EI 1933-7205 J9 REPROD SCI JI Reprod. Sci. PD APR PY 2009 VL 16 IS 4 BP 347 EP 356 DI 10.1177/1933719108327596 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 444FP UT WOS:000265966400004 PM 19087973 ER PT J AU Meeker, JD Barr, DB Hauser, R AF Meeker, John D. Barr, Dana B. Hauser, Russ TI Pyrethroid insecticide metabolites are associated with serum hormone levels in adult men SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Biomarkers; Endocrine disruption; Environment; Epidemiology; Exposure; Permethrin; Pesticide ID REPORTER GENE ASSAY; SEMEN QUALITY; INHIBIN-B; URINARY METABOLITES; TESTOSTERONE LEVELS; SPERM CONCENTRATION; GRANULOSA-CELLS; MALE-MOUSE; MALE RATS; FENVALERATE AB Experimental studies have reported that pyrethroid insecticides affect male endocrine and reproductive function, but human data are limited. We recruited 161 men from an infertility clinic between years 2000-2003 and measured serum reproductive and thyroid hormone levels, as well as the pyrethroid metabolites 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA and trans-DCCA) in spot urine samples. When adjusting for potential confounders, categories for all three metabolites, as well as their summed values, were positively associated with FSH (all p-values for trend <0.05). Statistically significant or suggestive positive relationships with LH were also found. In addition, cis-DCCA and trans-DCCA were inversely associated with inhibin B (p for trend = 0.03 and 0.02, respectively). Finally, there was evidence that trans-DCCA was inversely associated with testosterone and free androgen index (the ratio of testosterone to sex hormone binding globulin; p for trend = 0.09 and 0.05, respectively). The observed relationships were consistent with previous findings, but further research is needed for a better understanding of the potential association between pyrethroid insecticides and male reproduction. (C) 2009 Elsevier Inc. All rights reserved. C1 [Meeker, John D.] Univ Michigan, Dept Environm Hlth Sci, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Barr, Dana B.] Ctr Dis & Control & Prevent, Atlanta, GA USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. [Hauser, Russ] Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Meeker, JD (reprint author), Univ Michigan, Dept Environm Hlth Sci, Sch Publ Hlth, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA. EM meekerj@umich.edu RI Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013; OI Meeker, John/0000-0001-8357-5085 FU National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) [ES009718, ES00002] FX This work was supported by grant ES009718 and ES00002 from the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). The opinions expressed in this manuscript are those of the authors and do not necessarily reflect the official opinion of the Centers for Disease Control and Prevention. NR 48 TC 70 Z9 76 U1 2 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD APR PY 2009 VL 27 IS 2 BP 155 EP 160 DI 10.1016/j.reprotox.2008.12.012 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 429BA UT WOS:000264894600008 PM 19429394 ER PT J AU Walker, RN Heuberger, RA AF Walker, Renee N. Heuberger, Roschelle A. TI Predictive Equations for Energy Needs for the Critically Ill SO RESPIRATORY CARE LA English DT Review DE indirect calorimetry; energy needs; prediction equations; mechanical ventilation; critical illness; nutrition support; review ID INTENSIVE-CARE-UNIT; RESTING METABOLIC-RATE; NUTRITIONAL SUPPORT; CRITICAL ILLNESS; ICU PATIENTS; INFLAMMATORY RESPONSE; HOSPITALIZED-PATIENTS; PARENTERAL-NUTRITION; INDIRECT CALORIMETRY; REFEEDING SYNDROME AB Nutrition may affect clinical outcomes in critically ill patients, and providing either more or fewer calories than the patient needs can adversely affect outcomes. Calorie need fluctuates substantially over the course of critical illness, and nutrition delivery is often influenced by: the risk of refeeding syndrome; a hypocaloric feeding regimen; lack of feeding access; intolerance of feeding; and feeding-delay for procedures. Lean body mass is the strongest determinant of resting energy expenditure, but age, sex, medications, and metabolic stress also influence the calorie requirement. Indirect calorimetry is the accepted standard for determining calorie requirement, but is unavailable or unaffordable in many centers. Moreover, indirect calorimetry is not infallible and care must be taken when interpreting the results. In the absence of calorimetry, clinicians use equations and clinical judgment to estimate calorie need. We reviewed 7 equations (American College of Chest Physicians, Harris-Benedict, Ireton-Jones 1992 and 1997, Penn State 1998 and 2003, Swinamer 1990) and their prediction accuracy. Understanding an equation's reference population and using the equation with similar patients are essential for the equation to perform similarly. Prediction accuracy among equations is rarely within 10% of the measured energy expenditure; however, in the absence of indirect calorimetry, a prediction equation is the best alternative. C1 [Walker, Renee N.] Michael E DeBakey Vet Affairs Med Ctr, Nutr Serv, Houston, TX 77030 USA. [Walker, Renee N.] Michael E DeBakey Vet Affairs Med Ctr, Food Serv, Houston, TX 77030 USA. [Heuberger, Roschelle A.] Cent Michigan Univ, Dept Human Environm Studies, Mt Pleasant, MI 48859 USA. RP Walker, RN (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Nutr Serv, 2002 Holcombe Blvd,Room 4A-340, Houston, TX 77030 USA. EM renee.walker2@va.gov NR 99 TC 37 Z9 41 U1 0 U2 5 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD APR PY 2009 VL 54 IS 4 BP 509 EP 521 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 431PL UT WOS:000265075000014 PM 19327188 ER PT J AU Rouvas, AA Papakostas, TD Vavvas, D Vergados, I Moschos, MM Kotsolis, A Ladas, ID AF Rouvas, Alexandros A. Papakostas, Thanos D. Vavvas, Demetrios Vergados, Ioannis Moschos, Marilita M. Kotsolis, Athanasios Ladas, Ioannis D. TI INTRAVITREAL RANIBIZUMAB, INTRAVITREAL RANIBIZUMAB WITH PDT, AND INTRAVITREAL TRIAMCINOLONE WITH PDT FOR THE TREATMENT OF RETINAL ANGIOMATOUS PROLIFERATION A Prospective Study SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE ranibizumab; PDT; triamcinolone; retinal angiomatous proliferation ID INDOCYANINE GREEN ANGIOGRAPHY; BEVACIZUMAB AVASTIN TREATMENT; PHOTODYNAMIC THERAPY; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; SURGICAL ABLATION; LASER PHOTOCOAGULATION; ACETONIDE; VERTEPORFIN; INJECTION AB Purpose: To compare 1) intravitreal ranibizumab, 2) intravitreal ranibizumab plus photodynamic therapy (PDT), and 3) intravitreal triamcinolone plus PDT in retinal angiomatous proliferation. Methods: In this prospective study, 37 eyes of 37 patients with retinal angiomatous proliferation were randomly assigned in 1 of the 3 groups. The patients in Group 1 (n = 13) received 3 monthly injections of 0.5 mg of ranibizumab. The patients in Group 2 (n = 13) received one session of PDT and 3 monthly intravitreal injections of 0.5 mg ranibizumab and the patients in Group 3 (n = 11) received one session of PDT and 1 injection of 4 mg triamcinolone. Retreatment, with the same therapeutic scheme in each group, was considered in case of persistence or recurrence of subretinal fluid or intraretinal fluid. Results: All the patients completed at least 6 months of follow-up. A total of 61.53% patients in Group 1, 76.92% in Group 2, and all in Group 3 had the same or better visual acuity at the end of the follow-up (P = 0.0232). The mean central retinal thickness reduction in Group 1 was 32.23 mu m (P = 0.548), in Group 2 20.31 mu m (P = 0.042), and in Group 3 73.92 mu m (P < 0.0001). Also, the patients in Group 3 received on average the lowest number of injections (P < 0.0001). Conclusion: All groups resulted in stabilization of the disease, while a significant trend towards better visual acuity and anatomic restoration of the affected area was observed in the intravitreal triamcinolone & PDT group. C1 [Papakostas, Thanos D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Rouvas, Alexandros A.; Vergados, Ioannis] Univ Athens, Sch Med, Dept Ophthalmol 2, GR-11527 Athens, Greece. [Moschos, Marilita M.; Kotsolis, Athanasios; Ladas, Ioannis D.] Univ Athens, Sch Med, Dept Ophthalmol 1, GR-11527 Athens, Greece. RP Papakostas, TD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02115 USA. EM papakostas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 NR 34 TC 31 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD APR PY 2009 VL 29 IS 4 BP 536 EP 544 PG 9 WC Ophthalmology SC Ophthalmology GA 433KX UT WOS:000265203800017 PM 19190547 ER PT J AU Combe, B Swergold, G McLay, J McCarthy, T Zerbini, C Emery, P Connors, L Kaur, A Curtis, S Laine, L Cannon, CP AF Combe, Bernard Swergold, Gary McLay, James McCarthy, Timothy Zerbini, Cristiano Emery, Paul Connors, Laurine Kaur, Amarjot Curtis, Sean Laine, Loren Cannon, Christopher P. TI Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study) SO RHEUMATOLOGY LA English DT Article DE NSAIDs; Rheumatoid arthritis; Osteoarthritis; COX-2 inhibitors; Cardiovascular safety; Gastrointestinal safety; Analgesia ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; INHIBITOR ETORICOXIB; MULTINATIONAL ETORICOXIB; OSTEOARTHRITIS; METAANALYSIS; ROFECOXIB; NAPROXEN; EVENTS; COX-2 AB Objective. To compare cardiovascular (CV) and other safety and efficacy parameters of etoricoxib 60 and 90 mg, and diclofenac 150 mg. Methods. This double-blind study randomized OA patients to etoricoxib 90 mg, then to 60 mg once daily vs diclofenac 75 mg twice daily; RA patients were randomized to etoricoxib 90 mg once daily or diclofenac 75 mg twice daily. The primary endpoint was non-inferiority of etoricoxib vs diclofenac for thrombotic CV events (95 CI upper bound of hazard ratio 1.30). Other safety and efficacy parameters were evaluated in cohorts of patients based on etoricoxib dose and disease. Results. A total of 23 504 patients were randomized with mean treatment duration from 19.4 to 20.8 months. The thrombotic CV risk hazard ratio (HR) (etoricoxib to diclofenac) was 0.96 (95 CI 0.81, 1.15), consistent with non-inferiority of etoricoxib to diclofenac. The cumulative gastrointestinal (GI)/liver adverse events (AEs) discontinuation rate was significantly lower for etoricoxib than diclofenac in each patient cohort; HR (95 CI) of 0.46 (0.39, 0.54), 0.52 (0.42, 0.63) and 0.49 (0.39, 0.62) for the 60 mg OA, 90 mg OA and RA cohorts. The maximum average change in systolic blood pressure (BP) with etoricoxib was 3.43.6 mmHg (diastolic BP: 1.01.5 mmHg), while diclofenac produced a maximum average change of 0.91.9 mmHg (diastolic BP: 0.00.5 mmHg). Both agents resulted in similar efficacy regardless of etoricoxib dose. Conclusion. Long-term etoricoxib use is associated with a risk of thrombotic CV events comparable with that of diclofenac. Compared with diclofenac, etoricoxib demonstrated a greater risk of renovascular AEs, but a more favourable GI/liver tolerability profile. C1 [Combe, Bernard] Univ Montpellier 1, CHU Montpellier, Hop Lapeyronie, Serv Immunorhumatol, F-34000 Montpellier, France. [Swergold, Gary; Connors, Laurine; Kaur, Amarjot; Curtis, Sean] Merck Res Labs, Rahway, NJ USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Laine, Loren] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [McLay, James] Univ Aberdeen Polwarth Bldg, Dept Therapeut, Aberdeen, Scotland. [McLay, James] Univ Aberdeen Polwarth Bldg, Dept Med, Aberdeen, Scotland. [McCarthy, Timothy] Manitoba Clin, Winnipeg, MB, Canada. [Emery, Paul] Univ Leeds, Acad Unit Musculoskeletal Dis, Leeds, W Yorkshire, England. [Zerbini, Cristiano] Hosp Heliopolis, Serv Reumatol, Sao Paulo, Brazil. RP Combe, B (reprint author), Univ Montpellier 1, CHU Montpellier, Hop Lapeyronie, Serv Immunorhumatol, F-34000 Montpellier, France. EM b-combe@chu-montpellier.fr RI Zerbini, Cristiano/G-7566-2012 FU Merck Co., Inc.; Whitehouse Station, NJ, USA FX This work was supported by Merck & Co., Inc., Whitehouse Station, NJ, USA. NR 30 TC 30 Z9 35 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2009 VL 48 IS 4 BP 425 EP 432 DI 10.1093/rheumatology/kep005 PG 8 WC Rheumatology SC Rheumatology GA 421WM UT WOS:000264389000022 PM 19223284 ER PT J AU Wordsworth, P Buchanan, J Fleischmann, R Genovese, M Kay, J Hsia, E Doyle, M Rahman, M Han, CL Parasuraman, S AF Wordsworth, Paul Buchanan, Jacqueline Fleischmann, Roy Genovese, Mark Kay, Jonathan Hsia, Elizabeth Doyle, Mittie Rahman, Mahboob Han, Chenglong Parasuraman, Shreekant TI GOLIMUMAB SIGNIFICANTLY IMPROVES SELF-REPORTED PRODUCTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS SO RHEUMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-of-Rheumatology CY APR 28-MAY 01, 2009 CL Glasgow, SCOTLAND SP British Soc Rheumatol C1 [Buchanan, Jacqueline; Han, Chenglong; Parasuraman, Shreekant] Johnson & Johnson Pharmaceut Serv LLC, Malvern, PA USA. [Fleischmann, Roy] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Genovese, Mark] Stanford Univ, Palo Alto, CA 94304 USA. [Kay, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wordsworth, Paul] Nuffield Orthopaed Ctr, Oxford OX3 7LD, England. [Hsia, Elizabeth; Doyle, Mittie; Rahman, Mahboob] Univ Penn, Sch Med, Centocor Res & Dev Inc, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2009 VL 48 BP I83 EP I83 PG 1 WC Rheumatology SC Rheumatology GA 447NQ UT WOS:000266198600274 ER PT J AU Wordsworth, P Smolen, J Kay, J Doyle, MK Landewe, R Matteson, EL Zhou, Y Hsia, EC Rahman, MU AF Wordsworth, Paul Smolen, Josef Kay, Jonathan Doyle, Mittie K. Landewe, Robert Matteson, Eric L. Zhou, Y. Hsia, E. C. Rahman, M. U. CA GO-AFTER Study Investigators TI GOLIMUMAB, A HUMAN TNF-ALPHA mu ONOCLONAL ANTIBODY, IN RHEUMATOID ARTHRITIS PATIENTS PREVIOUSLY TREATED WITH ANTI-TNF-ALPHA AGENTS (GO-AFTER STUDY) SO RHEUMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-of-Rheumatology CY APR 28-MAY 01, 2009 CL Glasgow, SCOTLAND SP British Soc Rheumatol C1 [Wordsworth, Paul] Nuffield Orthopaed Ctr, Oxford OX3 7LD, England. [Smolen, Josef] Med Univ Vienna, Hietzing Hosp, Vienna, Austria. [Kay, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Doyle, Mittie K.; Hsia, E. C.; Rahman, M. U.] U Penn Med Sch, Centocor R&D Inc, Philadelphia, PA USA. [Landewe, Robert] Univ Hosp Maastricht, Maastricht, Netherlands. [Matteson, Eric L.] Mayo Clin, Rochester, MN USA. [Zhou, Y.; GO-AFTER Study Investigators] Centocor Res & Dev Inc, Malvern, PA USA. 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 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2009 VL 48 BP I18 EP I18 PG 1 WC Rheumatology SC Rheumatology GA 447NQ UT WOS:000266198600055 ER PT J AU Mitsiades, CS Hideshima, T Chauhan, D McMillin, DW Klippel, S Laubach, JP Munshi, NC Anderson, KC Richardson, PG AF Mitsiades, Constantine S. Hideshima, Teru Chauhan, Dharminder McMillin, Douglas W. Klippel, Steffen Laubach, Jacob P. Munshi, Nikhil C. Anderson, Kenneth C. Richardson, Paul G. TI Emerging Treatments for Multiple Myeloma: Beyond Immunomodulatory Drugs and Bortezomib SO SEMINARS IN HEMATOLOGY LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; PROTEASOME INHIBITOR BORTEZOMIB; HISTONE DEACETYLASE INHIBITOR; PHASE-I TRIAL; SOLUBLE HSP90 INHIBITOR; UNFOLDED PROTEIN RESPONSE; NF-KAPPA-B; CLINICAL-TRIAL; ANTITUMOR-ACTIVITY; THERAPEUTIC IMPLICATIONS AB The successful clinical development of thalidomide, bortezomib, and lenalidomide not only transformed the therapeutic management of multiple myeloma (MM) but also catalyzed a renewed interest in the development of additional classes of novel agents for this disease. This review focuses on I series of new therapeutics that have shown promising preclinical results, its well as encouraging safety profiles and early evidence of anti-MM activity in clinical studies, either alone or in combination with other, conventional or novel, anti-MM treatments. These agents include second-generation proteasome inhibitors and immunomodulatory agents, is well as members of other therapeutic classes, such as histone deacetylase inhibitors (HDAC), heat shock protein 90 (Hsp90) inhibitors, and the alkylphospholipid Akt inhibitor perifosine. Semin Hematol 46:166-175. (C) 2009 Published by Elsevier Inc. C1 [Mitsiades, Constantine S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Mitsiades, CS (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 Constantine_Mitsiades@dfci.harvard.edu FU NCI NIH HHS [R01 CA050947-17A1, R01 CA050947] NR 71 TC 49 Z9 50 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 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2009 VL 46 IS 2 BP 166 EP 175 DI 10.1053/j.seminhematol.2009.02.003 PG 10 WC Hematology SC Hematology GA 442BP UT WOS:000265815100008 PM 19389500 ER PT J AU Krasner, C Duska, L AF Krasner, Carolyn Duska, Linda TI Management of Women With Newly Diagnosed Ovarian Cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; PRIMARY PERITONEAL CANCER; ENDOTHELIAL GROWTH-FACTOR; OPTIMAL TUMOR CYTOREDUCTION; RANDOMIZED CLINICAL-TRIALS; DOSE INTENSITY ANALYSIS; EPITHELIAL OVARIAN; STAGE-III; INTRAPERITONEAL CISPLATIN C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Krasner, Carolyn] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. RP Krasner, C (reprint author), Massachusetts Gen Hosp, Div Med Oncol, Yawkey 9,55 Fruit St, Boston, MA 02114 USA. EM cnkrasner@partners.org NR 102 TC 3 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2009 VL 36 IS 2 BP 91 EP 105 DI 10.1053/j.seminoncol.2008.12.001 PG 15 WC Oncology SC Oncology GA 429TP UT WOS:000264943300004 PM 19332244 ER PT J AU Koulouris, CR Penson, RT AF Koulouris, Carolyn R. Penson, Richard T. TI Ovarian Stromal and Germ Cell Tumors SO SEMINARS IN ONCOLOGY LA English DT Review ID GYNECOLOGIC-ONCOLOGY-GROUP; MEDICAL-RESEARCH-COUNCIL; STAGE-I SEMINOMA; RANDOMIZED-TRIAL; PROGNOSTIC-FACTORS; CISPLATIN CHEMOTHERAPY; EUROPEAN ORGANIZATION; 2ND-LOOK LAPAROTOMY; ADJUVANT THERAPY; POOR-PROGNOSIS C1 [Koulouris, Carolyn R.; Penson, Richard T.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Yawkey 9066,32 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org NR 78 TC 13 Z9 14 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2009 VL 36 IS 2 BP 126 EP 136 DI 10.1053/j.seminoncol.2008.12.004 PG 11 WC Oncology SC Oncology GA 429TP UT WOS:000264943300007 PM 19332247 ER PT J AU Anderson, KC AF Anderson, Kenneth C. TI Proteasome Inhibitors in Multiple Myeloma SO SEMINARS IN ONCOLOGY LA English DT Review ID PHASE-I TRIAL; NF-KAPPA-B; INTRACELLULAR PROTEIN-DEGRADATION; SUBEROYLANILIDE HYDROXAMIC ACID; DEPENDENT PROTEOLYTIC SYSTEM; BONE-MARROW MICROENVIRONMENT; THERAPEUTIC APPLICATIONS; PERIFOSINE KRX-0401; REFRACTORY MYELOMA; PLUS BORTEZOMIB C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM Kenneth_Anderson@dfci.harvard.edu NR 51 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2009 VL 36 IS 2 BP S20 EP S26 DI 10.1053/j.seminoncol.2009.02.001 PG 7 WC Oncology SC Oncology GA 442YI UT WOS:000265876400004 PM 19393832 ER PT J AU Settleman, J AF Settleman, Jeff TI Cell Culture Modeling of Genotype-Directed Sensitivity to Selective Kinase Inhibitors: Targeting the Anaplastic Lymphoma Kinase (ALK) SO SEMINARS IN ONCOLOGY LA English DT Review ID GROWTH-FACTOR RECEPTOR; EML4-ALK FUSION GENE; LUNG-CANCER; ACTIVATING MUTATIONS; EGFR MUTATIONS; NEUROBLASTOMA; TUMORS; IDENTIFICATION; THERAPY; ADENOCARCINOMA C1 [Settleman, Jeff] Massachusetts Gen Hosp, Ctr Mol Therapeut, Ctr Canc, Charlestown, MA 02129 USA. [Settleman, Jeff] Harvard Univ, Sch Med, Charlestown, MA USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Mol Therapeut, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM Settleman@helix.mgh.harvard.edu NR 32 TC 11 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2009 VL 36 IS 2 BP S36 EP S41 DI 10.1053/j.seminoncol.2009.02.006 PG 6 WC Oncology SC Oncology GA 442YI UT WOS:000265876400006 PM 19393834 ER PT J AU Taylor, L Zhou, XH AF Taylor, Leslie Zhou, Xiao-Hua TI RELAXING LATENT IGNORABILITY IN THE ITT ANALYSIS OF RANDOMIZED STUDIES WITH MISSING DATA AND NONCOMPLIANCE SO STATISTICA SINICA LA English DT Article DE Causal inference; complier average causal effect; encouragement design study; flu shots; latent ignorability; missing data; noncompliance ID INSTRUMENTAL VARIABLES; CAUSAL INFERENCE; IDENTIFICATION AB In this paper we consider the problem in causal inference of estimating the local complier average causal effect (CACE) parameter in the setting of a randomized clinical trial with a binary outcome, cross-over noncompliance, and unintentional missing data on the responses. We focus oil the development of a moment estimator that relaxes the assumption of latent ignorability and incorporates sensitivity parameters that represent the relationship between potential outcomes and associated potential response indicators. If conclusions are insensitive over a range of logically possible values of the sensitivity parameters, then the number of interpretations of the data is reduced, and causal conclusions are more defensible. We illustrate our methods using a randomized encouragerne lit design study oil the effectiveness of an influenza vaccine. C1 [Taylor, Leslie] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA 98101 USA. RP Taylor, L (reprint author), Univ Washington, Dept Biostat, F-600 Hlth Sci Bldg,1705 NE Pacific St, Seattle, WA 98195 USA. EM taylorl@u.washington.edu; azhou@u.washington.edu NR 13 TC 1 Z9 1 U1 0 U2 1 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD APR PY 2009 VL 19 IS 2 BP 749 EP 764 PG 16 WC Statistics & Probability SC Mathematics GA 437EK UT WOS:000265469000019 ER PT J AU Xu, RH Vaida, F Harrington, DP AF Xu, Ronghui Vaida, Florin Harrington, David P. TI USING PROFILE LIKELIHOOD FOR SEMIPARAMETRIC MODEL SELECTION WITH APPLICATION TO PROPORTIONAL HAZARDS MIXED MODELS SO STATISTICA SINICA LA English DT Article DE Akaike information; bridge sampling; Laplace approximation; likelihood ratio test; profile likelihood; reciprocal importance sampling; testing on the boundary ID GAMMA-FRAILTY MODEL; FAILURE TIME DATA; RATIO TESTS; ASYMPTOTIC THEORY; SURVIVAL-DATA; ENVIRONMENTAL CONTRIBUTIONS; NONSTANDARD CONDITIONS; ALCOHOL DEPENDENCE; CLINICAL-TRIALS; COX REGRESSION AB We consider selection of nested and non-nested semiparametric models. Using profile likelihood we can define both a likelihood ratio statistic and an Akaike information for models with nuisance parameters. Asymptotic quadratic expansion of the log profile likelihood allows derivation of the asymptotic null distribution of the likelihood ratio statistic including the boundary cases, as well as unbiased estimation of the Akaike information by an Akaike information criterion. Our work was motivated by the proportional hazards mixed effects model (PHMM), which incorporates general random effects of arbitrary covariates and includes the frailty model as a special case. The asymptotic properties of its parameter estimate has recently been established, which enables the quadratic expansion of the log profile likelihood. For computation of the (profile) likelihood under PHMM we apply three algorithms: Laplace approximation, reciprocal importance sampling, and bridge sampling. We compare the three algorithms under different data structures, and apply the methods to a multi-center lung cancer clinical trial. C1 [Xu, Ronghui; Vaida, Florin] Univ Calif San Diego, Dept Family & Prevent Med, Div Biostat & Bioinformat, La Jolla, CA 92093 USA. [Xu, Ronghui] Univ Calif San Diego, Dept Math, La Jolla, CA 92093 USA. [Harrington, David P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Harrington, David P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Xu, RH (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, Div Biostat & Bioinformat, La Jolla, CA 92093 USA. EM rxu@ucsd.edu; vaida@ucsd.edu; dph@jimmy.harvard.edu NR 58 TC 8 Z9 8 U1 0 U2 2 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 EI 1996-8507 J9 STAT SINICA JI Stat. Sin. PD APR PY 2009 VL 19 IS 2 BP 819 EP 842 PG 24 WC Statistics & Probability SC Mathematics GA 437EK UT WOS:000265469000023 ER PT J AU Reeves, MJ Fonarow, GC Zhao, X Smith, EE Schwamm, LH AF Reeves, Mathew J. Fonarow, Gregg C. Zhao, Xin Smith, Eric E. Schwamm, Lee H. CA GWTG Stroke Steering Comm & Invest TI Quality of Care in Women With Ischemic Stroke in the GWTG Program SO STROKE LA English DT Article DE acute stroke; quality of health care; sex differences; women ID TISSUE-PLASMINOGEN ACTIVATOR; SEX-DIFFERENCES; CEREBROVASCULAR-DISEASE; CLINICAL PRESENTATION; REGISTRY; GENDER; MANAGEMENT; OUTCOMES; MORTALITY; ACCESS AB Background and Purpose-Prior studies have suggested worse poststroke outcomes in women. We sought to examine sex differences in quality of care (QOC) in the Get With The Guidelines-Stroke (GWTG-Stroke) program. Methods-We analyzed the relationships between sex and QOC as well as outcomes (in-hospital mortality and discharge home) using multivariable logistic regression models in 383 318 acute ischemic stroke admissions from 1139 hospitals that participated in the GWTG-Stroke program between 2003 to 2008. QOC was measured using 7 predefined performance measures and a defect-free cafe summary measure (defined as the proportion of patients who received all eligible interventions). Results-Compared to men, women were older and more likely to present by ambulance. They were also more likely to have a past medical history of atrial fibrillation or hypertension, and less likely to have a history of heart disease, dyslipidemia, or smoking. Although sex differences in individual performance measures were relatively modest they consistently identified women as being less likely to receive care compared to men. Overall, women received less defect-free care than men (66.3% versus 71.1%, adjusted odds ratio [aOR]=0.86; 95% confidence interval [CI] 0.85 to 0.87) and were less likely to be discharged home (41.0% versus 49.5%, aOR=0.84, 95% CI 0.83 to 0.85). Although crude mortality was higher in women (6.0% versus 5.2%), this difference was eliminated after risk adjustment (aOR= 1.03, 95% CI 0.99 to 1.06). Conclusions-Quality of care for women with ischemic stroke was lower than that for men, and women were less likely to be discharged home. Further study is warranted to identify the causes and consequences of these sex-based differences in cafe. (Stroke. 2009;40:1127-1133.) C1 [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Zhao, Xin] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Zhao, Xin] Duke Clin Res Ctr, Durham, NC USA. [Smith, Eric E.; Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. RP Reeves, MJ (reprint author), Michigan State Univ, Dept Epidemiol, B601 W Fee Hall, E Lansing, MI 48824 USA. EM reevesm@msu.edu RI Smith, Eric/C-5443-2012; OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145 FU American Stroke Association; Pfizer Inc, New York; Merck-Schering Plough Partnership FX GWTG-Stroke is funded by the AHA and the American Stroke Association. The program is also supported in part by unrestricted educational grants to the AHA by Pfizer Inc, New York, NY, and the Merck-Schering Plough Partnership (North Wales, Pa), which did not participate in the design, analysis, manuscript preparation, or approval. NR 33 TC 62 Z9 63 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP 1127 EP 1133 DI 10.1161/STROKEAHA.108.543157 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500017 PM 19211482 ER PT J AU Kiernan, TJ Yan, BP Cubeddu, RJ Rengifo-Moreno, P Gupta, V Inglessis, I Ning, M Demirjian, ZN Jaff, MR Buonanno, FS Schainfeld, RM Palacios, IF AF Kiernan, Thomas J. Yan, Bryan P. Cubeddu, Roberto J. Rengifo-Moreno, Pablo Gupta, Vishal Inglessis, Ignacio Ning, MingMing Demirjian, Zareh N. Jaff, Michael R. Buonanno, Ferdinando S. Schainfeld, Robert M. Palacios, Igor F. TI May-Thurner Syndrome in Patients With Cryptogenic Stroke and Patent Foramen Ovale An Important Clinical Association SO STROKE LA English DT Article DE PFO; May Thurner syndrome; cryptogenic stroke; iliac vein thrombosis ID PARADOXICAL EMBOLISM; ISCHEMIC-STROKE; THROMBOSIS; VEINS AB Background and Purpose-We aimed to investigate the incidence of May-Thurner syndrome in patients with cryptogenic stroke with patent foramen ovale. Methods-This was a retrospective study. All consecutive patients with cryptogenic stroke having undergone patent foramen ovale closure from January 1, 2002, to December 31, 2007, at our institute were included in this study. Pelvic magnetic resonance venography studies of all patients were reviewed to determine if features of May-Thurner syndrome were present. Medical records and invasive venography studies of all patients were reviewed when available. All patients with May-Thurner syndrome features on magnetic resonance venography were reviewed by a vascular medicine specialist to define any previous incidence of deep vein thrombosis or any signs of chronic venous insufficiency. All patients also had lower limb venous duplex performed to rule out lower limb venous thrombosis. Results-A total of 470 patients from January 1, 2002, until December 31, 2007, with cryptogenic stroke underwent patent foramen ovale closure at our institute. Thirty patients (6.3%) had features consistent with May-Thurner syndrome on magnetic resonance venography. These patients were predominantly female (80%) with a mean age of 43.6 +/- 11.9 years. Twelve patients (40%) had abnormalities in their laboratory thrombophilia evaluation and 13 females (54.1%) were taking hormone-related birth control pills. Only 2 patients had a history and signs of chronic venous insufficiency. All patent foramen ovales demonstrated right-to-left shunting on transesophageal echocardiography. Atrial septal aneurysms/hypermobile atrial septa were present in 70% of patients with May-Thurner syndrome. Conclusion-May-Thurner syndrome has an important clinical association with cryptogenic stroke and patent foramen ovale. (Stroke. 2009;40:1502-1504.) C1 [Kiernan, Thomas J.; Yan, Bryan P.; Cubeddu, Roberto J.; Rengifo-Moreno, Pablo; Gupta, Vishal; Inglessis, Ignacio; Jaff, Michael R.; Schainfeld, Robert M.; Palacios, Igor F.] Massachusetts Gen Hosp, Dept Intervent Cardiol & Vasc Med, Boston, MA 02114 USA. [Demirjian, Zareh N.] Massachusetts Gen Hosp, Hematol Unit, Dept Med, Boston, MA 02114 USA. [Ning, MingMing; Buonanno, Ferdinando S.] Massachusetts Gen Hosp, Clin Proteom Res Ctr, Dept Neurol, Boston, MA 02114 USA. [Ning, MingMing; Buonanno, Ferdinando S.] Massachusetts Gen Hosp, Cardioneurol Clin, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. RP Kiernan, TJ (reprint author), Massachusetts Gen Hosp, Dept Intervent Cardiol & Vasc Med, 55 Fruit St, Boston, MA 02114 USA. EM tjkiernan@partners.org RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 FU National Institutes of Health/National Institute of Neurological Diseases and Stroke [NS051588, NS052498] FX M.N. is supported by the National Institutes of Health/National Institute of Neurological Diseases and Stroke: NS051588 and NS052498 (M.N./Lo). NR 16 TC 12 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP 1502 EP 1504 DI 10.1161/STROKEAHA.108.527366 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500074 PM 19182088 ER PT J AU Almandoz, JED Yoo, AJ Stone, MJ Gonzalez, RG Schaefer, PW Romero, JM AF Almandoz, Josser E. Delgado Yoo, Albert J. Stone, Michael J. Gonzalez, R. Gilberto Schaefer, Pamela W. Romero, Javier M. TI Systematic Characterization Of The Spot Sign on CT Angiography Increases The Positive Predictive Value For The Identification Of Patients At Highest Risk Of Significant Hematoma Expansion And Hospital Mortality SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Almandoz, Josser E. Delgado; Yoo, Albert J.; Stone, Michael J.; Gonzalez, R. Gilberto; Schaefer, Pamela W.; Romero, Javier M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E132 EP E132 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500196 ER PT J AU Atochin, DN Gutsaeva, DR Li, Q Demchenko, IT Piantadosi, CA Huang, PL AF Atochin, Dmitriy N. Gutsaeva, Diana R. Li, Qian Demchenko, Ivan T. Piantadosi, Claude A. Huang, Paul L. TI Hypoxic Preconditioning Stimulates Mitochondrial Biogenesis and Promotes Brain Ischemic Tolerance by Akt Pathway Activation SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Atochin, Dmitriy N.; Li, Qian; Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Charlestown, MA USA. [Gutsaeva, Diana R.] Med Coll Georgia, Dept Anesthesiol & Perioperat Med, Augusta, SC USA. [Demchenko, Ivan T.; Piantadosi, Claude A.] Duke Univ, Cntr Hyperbar Med & Environm Physiol, Durham, NC USA. RI Atochin, Dmitriy/Q-3150-2016 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E139 EP E139 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500224 ER PT J AU Ay, H Sharma, P Dichgans, M Sorensen, AG Cortellini, L Arsava, EM Furie, KL Schmidt, R Fazekas, F Olugbodi, AA Sudlow, C Ballabio, E Jood, K Redfors, P Thijs, V Cole, J Kittner, S Majersilk, J Meurer, WJ Lindgren, A Norrving, B Illoh, K Worrall, BB Montaner, J Delgado, MP Rosand, J AF Ay, Hakan Sharma, Pankaj Dichgans, Martin Sorensen, A. Gregory Cortellini, Lynelle Arsava, Ethem M. Furie, Karen L. Schmidt, Reinhold Fazekas, Franz Olugbodi, Alkintomi A. Sudlow, Cathie Ballabio, Elena Jood, Katarina Redfors, Petra Thijs, Vincent Cole, John Kittner, Steven Majersilk, Jennifer Meurer, William J. Lindgren, Arne Norrving, Bo Illoh, Kachi Worrall, Bradford B. Montaner, Joan Delgado, Maria Pilar Rosand, Jonathan CA Int Stroke Genetics Consortium TI International Validation of a Computerized Algorithm for Etiologic Classification of Ischemic Stroke: The Causative Classification of Stroke System SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Ay, Hakan; Sorensen, A. Gregory; Cortellini, Lynelle; Arsava, Ethem M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sharma, Pankaj] Hammersmith Hosp, London, England. [Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, London, England. [Dichgans, Martin] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Schmidt, Reinhold; Fazekas, Franz] Med Univ Graz, Graz, Austria. [Olugbodi, Alkintomi A.] Obafemi Awolowo Univ, Ife, Osun State, Nigeria. [Sudlow, Cathie; Ballabio, Elena] Univ Edinburgh, Western Gen Hosp, Edinburgh, Midlothian, Scotland. [Jood, Katarina; Redfors, Petra] Univ Gothenburg, Gothenburg, Sweden. [Thijs, Vincent] Katholieke Univ Leuven Hosp, Louvain, Belgium. [Cole, John; Kittner, Steven] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Majersilk, Jennifer; Meurer, William J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Lindgren, Arne; Norrving, Bo] Univ Lund Hosp, S-22185 Lund, Sweden. [Illoh, Kachi] UTHSC, Houston, TX USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Montaner, Joan; Delgado, Maria Pilar] Vall Hebron Hosp, Barcelona, Spain. RI Thijs, Vincent/C-3647-2009; Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015 OI Thijs, Vincent/0000-0002-6614-8417; 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E203 EP E203 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500486 ER PT J AU Cheng, EM Cohen, SN Lee, ML Vassar, SD Chen, AY AF Cheng, Eric M. Cohen, Stanley N. Lee, Martin L. Vassar, Stefanie D. Chen, Alex Y. TI No Improvement In Overall Use of Antiplatelet or Antithrombotic Agents Among United States Stroke Survivors from 2000-2005. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Cheng, Eric M.; Lee, Martin L.; Vassar, Stefanie D.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Cohen, Stanley N.] Univ Nevada, Sch Med, Las Vegas, NV 89154 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E263 EP E263 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500730 ER PT J AU Dichgans, M Bevan, S Cole, JW Plourde, A Matarin, M Ross-Adams, H Meitinger, T Wichmann, E Mitchel, BD Furie, K Rich, SS MacLeod, MJ Meschia, J Rosand, J Kittner, SJ Markus, HS Muller-Myhsok, B Gschwendtner, A AF Dichgans, Martin Bevan, Steve Cole, John W. Plourde, Anna Matarin, Mar Ross-Adams, Helen Meitinger, Thomas Wichmann, Erich Mitchel, Braxton D. Furie, Karen Rich, Stephen S. MacLeod, Mary J. Meschia, James Rosand, Jonathan Kittner, Steve J. Markus, Hugh S. Muller-Myhsok, Betram Gschwendtner, Andreas CA Int Stroke Genetics Consortium TI Sequence Variants on Chromosome 9p21 Confer Risk of Large Vessel Stroke. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Dichgans, Martin; Gschwendtner, Andreas] Univ Munich, Dept Neurol, Klinikum Grosshadern, Munich, Germany. [Bevan, Steve; Markus, Hugh S.] Univ London, Cntr Clin Neurosci, London, England. [Cole, John W.; Kittner, Steve J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Plourde, Anna; Furie, Karen; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Matarin, Mar] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Ross-Adams, Helen] Univ Aberdeen, Dept Med & Therapeut, Aberdeen, Scotland. [Meitinger, Thomas] Inst Human Genet, Helmholtz Zentrum Munchen, Munich, Germany. [Wichmann, Erich] Inst Epidemiol, Helmholtz Zentrum Munchen, Munich, Germany. [Mitchel, Braxton D.] Univ Maryland, Dept Neurol, Sch Med, Baltimore, MD 21201 USA. [Rich, Stephen S.] Univ Virginia, Cntr Publ Hlth Genom, Charlottesville, VA USA. [MacLeod, Mary J.] Univ Aberdeen, Dept Med & Therapeut, Aberdeen, Scotland. [Meschia, James] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Muller-Myhsok, Betram] Max Planck Inst Psychiat, D-80804 Munich, Germany. RI Muller-Myhsok, Bertram/A-3289-2013; Matarin, Mar/F-1771-2016 OI Matarin, Mar/0000-0002-4717-5735 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E109 EP E109 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500110 ER PT J AU Earnshaw, SR Jackson, DL Farkouh, RA Schwamm, LH AF Earnshaw, Stephanie R. Jackson, Daniel L. Farkouh, Raymond A. Schwamm, Lee H. TI Cost-effectiveness of MRI-Based Selection of Patients for Intravenous Thrombolysis. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Earnshaw, Stephanie R.; Farkouh, Raymond A.] RTI Hlth Solut, Res Triangle Pk, NC USA. [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E192 EP E193 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500444 ER PT J AU Forster, A Gass, A Ay, H Kern, R Griebe, M Zohsel, K Hennerici, MG Szabo, K AF Foerster, Alex Gass, Achim Ay, Hakan Kern, Rolf Griebe, Martin Zohsel, Kathrin Hennerici, Michael G. Szabo, Kristina TI Acute CT In TIA Patients Is Unrevealing-A Comparative CT/MRI Study SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Foerster, Alex; Gass, Achim; Kern, Rolf; Griebe, Martin; Zohsel, Kathrin; Hennerici, Michael G.; Szabo, Kristina] Univ Klinikum Mannheim, Mannheim, Germany. [Ay, Hakan] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E195 EP E196 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500457 ER PT J AU Furie, KL Viscoli, CM Gorman, MJ Young, LH Inzucchi, SE Lovejoy, AM Horwitz, RI Kernan, WN AF Furie, Karen L. Viscoli, Catherine M. Gorman, Mark J. Young, Lawrence H. Inzucchi, Silvio E. Lovejoy, Anne M. Horwitz, Ralph I. Kernan, Walter N. CA IRIS Invest TI Lower Rates of Consent in Women Screened for Stroke Prevention Trials: The IRIS Experience SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Viscoli, Catherine M.; Young, Lawrence H.; Inzucchi, Silvio E.; Lovejoy, Anne M.; Kernan, Walter N.] Yale Univ, Sch Med, New Haven, CT USA. [Gorman, Mark J.] Univ Vermont, Coll Med, Burlington, VT USA. [Horwitz, Ralph I.] Stanford Univ, Sch Med, Stamford, CT 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E129 EP E129 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500184 ER PT J AU Goldstein, JN Espinola, J Fisher, J Pallin, DJ Camargo, CA AF Goldstein, Joshua N. Espinola, Janice Fisher, Jonathan Pallin, Daniel J. Camargo, Carlos A., Jr. TI Patient Opinion of Enrollment in a Hypothetical Stroke Trial Using Exception to Informed Consent SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Goldstein, Joshua N.; Espinola, Janice; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fisher, Jonathan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pallin, Daniel J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Pallin, Daniel/H-6382-2013; Goldstein, Joshua/H-8953-2016 OI Pallin, Daniel/0000-0002-8517-9702; 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E153 EP E153 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500284 ER PT J AU Guo, SZ Kim, WJ Lok, J Lo, EH AF Guo, Shuzhen Kim, Woo Jean Lok, Josephine Lo, Eng H. TI Disruption of Trophic Coupling in the Neurovascular Unit by Oxidative Stress. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Guo, Shuzhen; Kim, Woo Jean; Lok, Josephine; Lo, Eng H.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E256 EP E256 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500705 ER PT J AU Hammer, MD Starkman, S Burgin, WS Watson, T Nogueira, R Schwamm, L Sen, S Shuaib, A Schellinger, P Diener, HC Liebeskind, DS AF Hammer, Maxim D. Starkman, Sidney Burgin, W. S. Watson, Tim Nogueira, Raul Schwamm, Lee Sen, Souvik Shuaib, Ashfaq Schellinger, Peter Diener, Hans C. Liebeskind, David S. TI Flo 24 Stroke Trial: Safety and Efficacy of NeuroFlo in 8-24 Hour Stroke Patients. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Hammer, Maxim D.] Univ Pittsburgh, Pittsburgh, PA USA. [Starkman, Sidney; Liebeskind, David S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Burgin, W. S.] Univ Rochester, Rochester, NY USA. [Watson, Tim] Univ Calgary, Calgary, AB, Canada. [Nogueira, Raul; Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sen, Souvik] Univ N Carolina, Chapel Hill, NC USA. [Shuaib, Ashfaq] Univ Edmonton, Edmonton, AB, Canada. [Schellinger, Peter; Diener, Hans C.] Univ Klinikum Erlangen, Erlangen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E247 EP E247 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500664 ER PT J AU Hiroki, M Kumar, A Benner, T Singhal, AB Mintzopoulos, D Melinosky, C Yeo, PC Tiglias, V Fukuyama, H Sorensen, AG AF Hiroki, Masahiko Kumar, Ashok Benner, Thomas Singhal, Aneesh B. Mintzopoulos, Dionyssios Melinosky, Christopher Yeo, Priscilla C. Tiglias, Vicky Fukuyama, Hidenao Sorensen, A. G. TI Periarterial Hyperintensities in the Contralateral Striatum in Hypertensive Patients with Putaminal Hemorrhage Versus Striatal Lacunar Infarction SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Hiroki, Masahiko; Fukuyama, Hidenao] Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan. [Kumar, Ashok; Benner, Thomas; Mintzopoulos, Dionyssios; Melinosky, Christopher; Yeo, Priscilla C.; Tiglias, Vicky; Sorensen, A. G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E233 EP E233 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500608 ER PT J AU Huang, S Atochin, D Dal, G Huang, P Rosen, BR Kim, YR AF Huang, Shuning Atochin, Dmitriy Dal, Guangping Huang, Paul Rosen, Bruce R. Kim, Young R. TI Restoration Of CBV Affects BBB Integrity In Transient MCAo SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Huang, Shuning] MIT, Cambridge, MA 02139 USA. [Atochin, Dmitriy; Dal, Guangping; Huang, Paul; Rosen, Bruce R.; Kim, Young R.] Massachusetts Gen Hosp, Charlestown, MA USA. RI Atochin, Dmitriy/Q-3150-2016 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E224 EP E224 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500573 ER PT J AU Jin, G Tsuji, K Xing, CH Yang, YG Wang, XY Lo, EH AF Jin, Guang Tsuji, Kiyoshi Xing, Changhong Yang, Yongguang Wang, Xiaoying Lo, Eng H. TI Cd47 Gene Knockout Protects Against Transient Focal Cerebral Ischemia. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Jin, Guang; Tsuji, Kiyoshi; Xing, Changhong; Yang, Yongguang; Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E257 EP E257 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500709 ER PT J AU Kamalian, S Konstas, AA Kemmling, A Goldmakher, GV Gonzalez, RG Nogueira, RG Furie, KL Schaefer, PW Lev, MH AF Kamalian, Shahmir Konstas, Angelos A. Kemmling, Andre Goldmakher, Gregory V. Gonzalez, Ramon G. Nogueira, Raul G. Furie, Karen L. Schaefer, Pamela W. Lev, Michael H. TI Algorithmically Optimized Software Accounting for Contrast Arrival Time Delay Is Required For Accurate CT Cerebral Blood Volume Map Construction In Patients With Extracranial Carotid Artery Occlusion Or Atrial Fibrillation. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Kamalian, Shahmir; Konstas, Angelos A.; Kemmling, Andre; Goldmakher, Gregory V.; Gonzalez, Ramon G.; Nogueira, Raul G.; Furie, Karen L.; Schaefer, Pamela W.; Lev, Michael H.] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E192 EP E192 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500441 ER PT J AU Kemmling, A Haselgrove, C Makris, N Kamalian, S Hodge, S Kennedy, DN Caviness, VS Lev, MH AF Kemmling, Andre Haselgrove, Christian Makris, Nikos Kamalian, Shahmir Hodge, Steve Kennedy, David N. Caviness, Verne S. Lev, Michael H. TI AUTOASPECTS: Validation Of Automated Alberta Stroke Program Early CT Score In Acute Stroke DWI Images Using Brain Parcellation Software WebParc. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Haselgrove, Christian; Makris, Nikos; Hodge, Steve; Kennedy, David N.] Massachusetts Gen Hosp, Cntr Morphometr Anal, Boston, MA 02114 USA. RI Kennedy, David/H-3627-2012 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E211 EP E212 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500521 ER PT J AU Kim, HH Liu, PY Noma, K Wang, HW Hwang, SK Ahn, YJ Moskowitz, MA Liao, JK AF Kim, Hyung-Hwan Liu, Ping-Yen Noma, Kensuke Wang, Hong-Wei Hwang, Seo-Kyoung Ahn, Yong-Joo Moskowitz, Michael A. Liao, James K. TI Decrease Cerebral Ischemia and Neurological Deficits Following Clot-Embolic Stroke in Mice with Targeted Deletion of ROCK1 and ROCK2 in Bone Marrow-derived Cells SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Kim, Hyung-Hwan; Liu, Ping-Yen; Noma, Kensuke; Wang, Hong-Wei; Hwang, Seo-Kyoung; Ahn, Yong-Joo; Liao, James K.] Brigham & Womens Hosp, Cambridge, MA USA. [Moskowitz, Michael A.] Massachusetts Gen Hosp, Charlestown, MA 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E220 EP E220 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500558 ER PT J AU Kimberly, WT Gilson, A Rost, NS Rosand, J Viswanathan, A Smith, EE Greenberg, SM AF Kimberly, W. T. Gilson, Aaron Rost, Natalia S. Rosand, Jonathan Viswanathan, Anand Smith, Eric E. Greenberg, Steven M. TI Silent Ischemic Infarcts are Associated with Increased Hemorrhage Burden in Cerebral Amyloid Angiopathy SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Kimberly, W. T.; Gilson, Aaron; Rost, Natalia S.; Rosand, Jonathan; Viswanathan, Anand; Smith, Eric E.; Greenberg, Steven M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E130 EP E130 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500188 ER PT J AU Latorre, JGS Chou, SHY Nogueira, RG Singhal, AB Carter, BS Ogilvy, CS Rordorf, GA AF Latorre, Julius Gene S. Chou, Sherry Hsiang-Yi Nogueira, Raul G. Singhal, Aneesh B. Carter, Bob S. Ogilvy, Christopher S. Rordorf, Guy A. TI Effective Glucose Control with Aggressive Hyperglycemia Management Associated with Improved Outcome in Aneurysmal Subarachnoid Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Latorre, Julius Gene S.] SUNY Upstate Med Univ, Syracuse, NY USA. [Chou, Sherry Hsiang-Yi] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nogueira, Raul G.; Singhal, Aneesh B.; Carter, Bob S.; Ogilvy, Christopher S.; Rordorf, Guy A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Chou, Sherry/G-5779-2015 NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E145 EP E146 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500253 ER PT J AU Lima, FO Parides, MK Greer, DM Silva, GS Kelly, PJ Furie, KL AF Lima, Fabricio O. Parides, Michael K. Greer, David M. Silva, Gisele S. Kelly, Peter J. Furie, Karen L. TI Defining an Age Threshold for the "Young" Adult Stroke. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Lima, Fabricio O.; Greer, David M.; Silva, Gisele S.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parides, Michael K.] Columbia Univ, New York, NY USA. [Kelly, Peter J.] Mater Univ, Dublin, Ireland. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E264 EP E264 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500736 ER PT J AU Liu, J Gao, BB Clermont, AC Feener, EP AF Liu, Jia Gao, Benbo Clermont, Allen C. Feener, Edward P. TI Plasma Kallikrein Exacerbates Intracerebral Hemorrhage Expansion in Diabetic Rats Novel Role of the Contact System as Collagenase SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Liu, Jia; Gao, Benbo; Clermont, Allen C.; Feener, Edward P.] Joslin Diabet Ctr, Boston, MA 02215 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E227 EP E227 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500587 ER PT J AU Lutselp, HL Beach, K Roubin, G Leimgruber, P Lal, BK Gray, W Rosenfield, K Bergelin, R Voelks, J Longbottom, M Hobson, RW Brott, TG AF Lutselp, Helmi L. Beach, Kirk Roubin, Gary Leimgruber, Pierre Lal, Brajesh K. Gray, William Rosenfield, Kenneth Bergelin, Robert Voelks, Jenifer Longbottom, Mary Hobson, Robert W. Brott, Thomas G. CA CREST Investigators TI Carotid Luminal Diameter Changes One Year after Stenting: Results from the Lead-in Phase of CREST. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Lutselp, Helmi L.] OHSU, Oregon Stroke Cntr, Portland, OR USA. [Beach, Kirk] Univ Washington, Seattle, WA 98195 USA. [Roubin, Gary] Lenox Hill Hosp, New York, NY 10021 USA. [Leimgruber, Pierre] Deaconess Med Cntr, Spokane, WA USA. [Lal, Brajesh K.; Hobson, Robert W.] UMDNJ, Newark, NJ USA. [Gray, William] Columbia Univ, Med Cntr, New York, NY USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bergelin, Robert] Univ Washington, Seattle, WA 98195 USA. [Voelks, Jenifer] Univ Alabama, Birmingham, AL USA. [Longbottom, Mary; Brott, Thomas G.] Mayo Clin, Jacksonville, FL 32224 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E108 EP E109 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500107 ER PT J AU Masrur, S Pervez, MA El-Ghandour, A Abdullah, AR Schwamm, LH AF Masrur, Shihab Pervez, Muhammad A. El-Ghandour, Ahmed Abdullah, Abdul R. Schwamm, Lee H. TI Stroke Patients Who Pass Initial Dysphagia Screening Are Still At Risk for Aspiration Pneumonia. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Masrur, Shihab; Pervez, Muhammad A.; El-Ghandour, Ahmed; Abdullah, Abdul R.; Schwamm, Lee H.] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E266 EP E266 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500744 ER PT J AU Ning, MM Palacios, I Sena, D Inglessis, I McNamara, ME Lievens, M Demirjian, Z Cruz-Gonzalez, I Rengifo, P Cubeddu, R Schainfeld, R McMullin, D Dec, W Grabowski, E Lo, EH Buonanno, F AF Ning, Mingming Palacios, Igor Sena, Dayse Inglessis, Ignacio McNamara, Mary Ellen Lievens, Mary Demirjian, Zareh Cruz-Gonzalez, Ignacio Rengifo, Pablo Cubeddu, Robert Schainfeld, Robert McMullin, David Dec, William Grabowski, Eric Lo, Eng H. Buonanno, Ferdinando TI "Economy Class Strokes"-The Association Between Long Distance Travel And Patent Foramen Ovale. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Ning, Mingming; Palacios, Igor; Sena, Dayse; Inglessis, Ignacio; McNamara, Mary Ellen; Lievens, Mary; Demirjian, Zareh; Cruz-Gonzalez, Ignacio; Rengifo, Pablo; Cubeddu, Robert; Schainfeld, Robert; McMullin, David; Dec, William; Grabowski, Eric; Lo, Eng H.; Buonanno, Ferdinando] Massachusetts Gen Hosp, Boston, MA 02114 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E192 EP E192 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500442 ER PT J AU Nogueira, RG Rabinov, JD Baccin, C Yoo, A Carter, B Ogilvy, CS Hirsch, JA Pryor, JC AF Nogueira, Raul G. Rabinov, James D. Baccin, Carlos Yoo, Albert Carter, Bob Ogilvy, Christopher S. Hirsch, Joshua A. Pryor, Johnny C. TI Embolization of Intracranial Dural Arteriovenous Fistulas with Onyx: Single-Center Experience in a Series of 25 Patients SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Nogueira, Raul G.] Massachusetts Gen Hosp, Newton, MA USA. [Rabinov, James D.; Baccin, Carlos; Yoo, Albert; Carter, Bob; Ogilvy, Christopher S.; Hirsch, Joshua A.; Pryor, Johnny C.] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E134 EP E135 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500206 ER PT J AU Nogueira, RG Lielbeskind, DS Sung, G Duckwiler, G Smith, WS AF Nogueira, Raul G. Lielbeskind, David S. Sung, Gene Duckwiler, Gary Smith, Wade S. CA MERCI Multi MERCI Writing Comm TI Predictors of Clinical Outcomes in Acute Ischemic Stroke Patients Undergoing Thrombectomy: Pooled Analysis of the MERCI and Multi MERCI Trials SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Nogueira, Raul G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lielbeskind, David S.; Duckwiler, Gary] Univ Calif Los Angeles, Los Angeles, CA USA. [Sung, Gene] Univ So Calif, Los Angeles, CA USA. [Smith, Wade S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E131 EP E131 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500193 ER PT J AU Nozari, A Dilekozh, E Sukhotinsky, I Stein, T Eikermann-Haerter, K Liu, C Ayata, C Moskowitz, MA AF Nozari, Ala Dilekozh, Ergin Sukhotinsky, Inna Stein, Thor Eikermann-Haerter, Katharina Liu, Christina Ayata, Cenk Moskowitz, Michael A. TI Microembolization triggers Cortical Spreading Depression both with and without Microinfarcts: Implications for a Migraine-Stroke Continuum SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Nozari, Ala; Dilekozh, Ergin; Sukhotinsky, Inna; Stein, Thor; Eikermann-Haerter, Katharina; Liu, Christina; Ayata, Cenk; Moskowitz, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E217 EP E217 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500544 ER PT J AU Nystrom, K Bedard, L Schindler, J Moali, D Cusano, A Cemeno, M Viswanathan, A Schwamm, L AF Nystrom, Karin Bedard, Lisa Schindler, Joseph Moali, Daniel Cusano, Al Cemeno, Michael Viswanathan, Anand Schwamm, Lee TI Telestroke: Implementation of a HUB and SPOKE Model for Acute Stroke Care SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Nystrom, Karin; Cusano, Al; Cemeno, Michael] Yale New Haven Med Ctr, New Haven, CT 06504 USA. [Bedard, Lisa; Moali, Daniel] Lawrence Mem Hosp, New London, CT USA. [Schindler, Joseph] Yale Univ, Sch Med, New Haven, CT USA. [Viswanathan, Anand; Schwamm, Lee] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E137 EP E138 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500219 ER PT J AU Oleinilk, A Romero, J Schwab, K Lev, MH Jhawar, N Smith, EE Greenberg, SM Rosand, J Goldstein, JN AF Oleinilk, Alexandra Romero, Javier Schwab, Kristin Lev, Michael H. Jhawar, Nuipur Smith, Eric E. Greenberg, Steven M. Rosand, Jonathan Goldstein, Joshua N. TI Computed Tomography Angiography For Intracerebral Hemorrhage Does Not Increase Risk Of Nephropathy SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Oleinilk, Alexandra; Romero, Javier; Schwab, Kristin; Lev, Michael H.; Jhawar, Nuipur; Smith, Eric E.; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012; Goldstein, Joshua/H-8953-2016 OI Smith, Eric/0000-0003-3956-1668; 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E206 EP E206 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500499 ER PT J AU Ovbiagele, B Schwamm, L Smith, EE Hernandez, A Olson, D Pan, WQ Zhao, X Fonarow, G Saver, JL AF Ovbiagele, Bruce Schwamm, Lee Smith, Eric E. Hernandez, Adrian Olson, DaiWai Pan, Wenqin Zhao, Xin Fonarow, Gregg Saver, Jeffrey L. TI Influence of a Pivotal Trial on Hospital-based Assessment of Lipids and Discharge Statin Treatment-Analysis of the GWTG-Stroke Database. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Ovbiagele, Bruce] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Schwamm, Lee; Smith, Eric E.; Fonarow, Gregg; Saver, Jeffrey L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hernandez, Adrian; Olson, DaiWai; Pan, Wenqin; Zhao, Xin] Duke Clin Rsch Inst, Durham, NC USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E260 EP E260 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500720 ER PT J AU Pallast, S Arai, K Wang, XY Lo, EH van Leyen, K AF Pallast, Stefanie Arai, Ken Wang, Xiaoying Lo, Eng H. van Leyen, Klaus TI A Role for Programmed Organelle Degradation in Stroke SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Pallast, Stefanie; Arai, Ken; Wang, Xiaoying; Lo, Eng H.; van Leyen, Klaus] Massachusetts Gen Hosp, Charlestown, MA USA. RI van Leyen, Klaus/C-9126-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E150 EP E150 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500271 ER PT J AU Pervez, MA Masrur, S Rost, NS Hidalgo, R Viswanathan, A Schwamm, LH AF Pervez, Muhammad A. Masrur, Shihab Rost, Natalia S. Hidalgo, Renzo Viswanathan, Anand Schwamm, Lee H. TI Safety of "Drip and Ship" Compared to Conventionally Administered Thrombolysis in Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Pervez, Muhammad A.; Masrur, Shihab; Rost, Natalia S.; Hidalgo, Renzo; Viswanathan, Anand; Schwamm, Lee H.] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E163 EP E164 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500323 ER PT J AU Rosenthal, ES Park, S Schwamm, LH AF Rosenthal, Eric S. Park, Soojin Schwamm, Lee H. TI Accuracy of Stroke Onset Time Reported by Emergency Department Physicians Activating an Acute Stroke Alert System SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Rosenthal, Eric S.; Park, Soojin; Schwamm, Lee H.] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E205 EP E206 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500496 ER PT J AU Rost, NS Masrur, S Pervez, MA Schwamm, LH AF Rost, Natalia S. Masrur, Shihab Pervez, Muhammad A. Schwamm, Lee H. TI Unsuspected Coagulopathy Rarely Prevents IV Thrombolysis in Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Rost, Natalia S.; Masrur, Shihab; Pervez, Muhammad A.; Schwamm, Lee H.] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E165 EP E166 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500331 ER PT J AU Roubin, G Ferguson, R Chakhtoura, E Gray, W Rosenfield, K Katzen, B Hopkins, LN Morrish, W Goldstein, J Sheffet, AJ Tom, M Meschia, J Voelks, J Hobson, RW Brott, TG AF Roubin, Gary Ferguson, Robert Chakhtoura, Elie Gray, William Rosenfield, Kenneth Katzen, Barry Hopkins, L. N. Morrish, William Goldstein, Jonathan Sheffet, Alice J. Tom, MeeLee Meschia, James Voelks, Jenifer Hobson, Robert W., II Brott, Thomas G. TI Credentialing and Training of Interventionalists in the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST). SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Roubin, Gary] Lenox Hill Hosp, New York, NY 10021 USA. [Ferguson, Robert] Metro Hlth Med Cntr, Cleveland, OH USA. [Chakhtoura, Elie; Sheffet, Alice J.; Hobson, Robert W., II] UMDNJ, New Jersey Med Sch, Newark, NJ USA. [Gray, William] NY Presbyterian Hosp Columbia, New York, NY USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Katzen, Barry] Baptist Hosp Miami, Miami, FL USA. [Hopkins, L. N.] Millard Fillmore Hosp, Buffalo, NY USA. [Morrish, William] Univ Calgary, Calgary, AB, Canada. [Goldstein, Jonathan] St Michaels Med Cntr, Newark, NJ USA. [Meschia, James; Brott, Thomas G.] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Voelks, Jenifer] Univ Alabama, Birmingham, AL 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E108 EP E108 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500104 ER PT J AU Saver, JL Smith, EE Hernandez, A Olson, D Zhao, X Schwamm, L AF Saver, Jeffrey L. Smith, Eric E. Hernandez, Adrian Olson, DaiWai Zhao, Xin Schwamm, Lee TI The Golden Hour and Acute Brain Ischemia: Presenting Features and Lytic Therapy in Over 30,000 Patients Arriving within 60 Minutes of Onset at GWTG-S Hospitals SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Cntr, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Smith, Eric E.; Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hernandez, Adrian; Olson, DaiWai; Zhao, Xin] Duke Clin Rsch Inst, Durham, NC USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E113 EP E113 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500126 ER PT J AU Schaefer, P Mui, K Gonzalez, R Lev, M AF Schaefer, Pamela Mui, Kit Gonzalez, Ramon Lev, Michael TI Reversible CT Cerebral Blood Volume Lesions in Intra-arterial Thrombolytic Treatment of Acute Stroke: Evidence of Infarct Recovery, or Technical Artifact? SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Schaefer, Pamela; Mui, Kit; Gonzalez, Ramon; Lev, Michael] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E194 EP E194 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500452 ER PT J AU Schaefer, P Mui, K Yoo, A Verduzco, L Gonzalez, R AF Schaefer, Pamela Mui, Kit Yoo, Albert Verduzco, Luis Gonzalez, Ramon TI Lower Cerebral Blood Flow Thresholds for Tissue Recovery in Acute Ischemic Stroke Patients Treated with Early Reperfusion after Intra-Arterial Thrombolysis SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Schaefer, Pamela; Mui, Kit; Yoo, Albert; Verduzco, Luis; Gonzalez, Ramon] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E148 EP E148 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500263 ER PT J AU Schwamm, LH Romero, J Frey, J Demaerschalk, BM Parikh, G Burke, R Chaliki, HP Babilkian, V AF Schwamm, Lee H. Romero, Jose Frey, James Demaerschalk, Bart M. Parikh, Gunjan Burke, Robert Chaliki, Hari P. Babilkian, Viken TI Cerebral Ischemic events Associated with Agitated Saline Intravenous Injection ("Bubble Study") for Identification of Right to Left Cardiac or Pulmonary Shunts SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Romero, Jose; Babilkian, Viken] Boston Med Ctr, Boston, MA USA. [Frey, James; Parikh, Gunjan] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Demaerschalk, Bart M.; Burke, Robert; Chaliki, Hari P.] Mayo Clin, Scottsdale, AZ USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E147 EP E147 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500259 ER PT J AU Sheth, KN Kumar, MA Rahman, RM Rost, NS Gilson, A Schwab, K Cortellim, LM Goldstein, JN Smith, EE Greenberg, SM Rosand, J AF Sheth, Kevin N. Kumar, Monisha A. Rahman, Rosanna M. Rost, Natalia S. Gilson, Aaron Schwab, Kristin Cortellim, Lynelle M. Goldstein, Joshua N. Smith, Eric E. Greenberg, Steven M. Rosand, Jonathan TI Packed Red Blood Cell Transfusion and Improved Survival in Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Sheth, Kevin N.; Rahman, Rosanna M.; Rost, Natalia S.; Gilson, Aaron; Schwab, Kristin; Cortellim, Lynelle M.; Goldstein, Joshua N.; Smith, Eric E.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kumar, Monisha A.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. RI Smith, Eric/C-5443-2012; Goldstein, Joshua/H-8953-2016 OI Smith, Eric/0000-0003-3956-1668; 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E238 EP E238 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500626 ER PT J AU Silva, G Lima, F Parides, M Greer, DM Kelly, PJ Furie, KL AF Silva, Gisele Lima, Fabricio Parides, Michael Greer, David M. Kelly, Peter J. Furie, Karen L. TI Plasma Biomarkers Can Discriminate between Cervical Artery Dissection and Large Artery Atherosclerosis SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Silva, Gisele; Lima, Fabricio; Greer, David M.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parides, Michael] Columbia Univ, New York, NY USA. [Kelly, Peter J.] Mater Misericordiae Univ Hosp, Dublin, Ireland. 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E197 EP E197 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500464 ER PT J AU Silva, GS Lima, F Camargo, EC Singhal, AB Greer, DM Ay, H Halpern, EF Smith, WS Lev, MH Koroshetz, W Furie, KL AF Silva, Gisele S. Lima, Fabricio Camargo, Erica C. Singhal, Aneesh B. Greer, David M. Ay, Hakan Halpern, Elkan F. Smith, Wade S. Lev, Michael H. Koroshetz, Walter Furie, Karen L. TI Starting IV t-PA Infusions for Acute Ischemic Stroke at Community Hospitals prior to Transfer to a Regional Stroke Center is Feasible and Safe SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Silva, Gisele S.; Lima, Fabricio; Camargo, Erica C.; Singhal, Aneesh B.; Greer, David M.; Ay, Hakan; Halpern, Elkan F.; Lev, Michael H.; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Wade S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Koroshetz, Walter] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E162 EP E162 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500315 ER PT J AU Sims, JR Gharai, LR Schaefer, PW Vangel, M Rosenthal, ES Lev, MH Schwamm, LH AF Sims, John R., II Gharai, Leila Rezai Schaefer, Pamela W. Vangel, Mark Rosenthal, Eric S. Lev, Michael H. Schwamm, Lee H. TI ABC/2 for Rapid Clinical Estimate of Infarct, Perfusion and Mismatch Volumes SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Sims, John R., II; Gharai, Leila Rezai; Schaefer, Pamela W.; Vangel, Mark; Rosenthal, Eric S.; Lev, Michael H.; Schwamm, Lee H.] Massachusetts Gen Hosp, Charlestown, 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E159 EP E159 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500306 ER PT J AU Smith, EE Liang, L Hernandez, A Reeves, MJ Fonarow, GC Schwamm, LH AF Smith, Eric E. Liang, Li Hernandez, Adrian Reeves, Mathew J. Fonarow, Gregg C. Schwamm, Lee H. TI Get With the Guidelines-Stroke is Associated with Improved Processes of Care for Hemorrhagic Stroke. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Liang, Li; Hernandez, Adrian] Duke Clin Rsch Inst, Durham, NC USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E261 EP E262 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500725 ER PT J AU Sung, GY Llebeskind, DS Sanossian, N Nogueira, RG Kim, P Smith, WS Hemphill, C AF Sung, Gene Y. Llebeskind, David S. Sanossian, Nerses Nogueira, Raul G. Kim, Paul Smith, Wade S. Hemphill, Claude TI Predicting Hemorrhage After Reperfusion Therapy SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Sung, Gene Y.; Sanossian, Nerses; Kim, Paul] Univ So Calif, Los Angeles, CA USA. [Llebeskind, David S.; Smith, Wade S.; Hemphill, Claude] Univ Calif Los Angeles, Los Angeles, CA USA. [Nogueira, Raul G.] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E231 EP E232 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500604 ER PT J AU Tong, D Hernandez, A Zhao, X Fonarow, G Smith, E Schwamm, L AF Tong, David Hernandez, Adrian Zhao, Xin Fonarow, Greg Smith, Eric Schwamm, Lee TI Timing of Hospital Arrival Among GWTG Stroke Participants 2002-2007: Trends, Variations, and Implications SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Tong, David] Calif Pacific Med Ctr, San Francisco, CA USA. [Hernandez, Adrian; Zhao, Xin] Duke Clin Res Ctr, Durham, NC USA. [Fonarow, Greg] Univ Calif Los Angeles, Los Angeles, CA USA. [Smith, Eric] Univ Calgary, Calgary, AB, Canada. [Schwamm, Lee] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E235 EP E235 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500613 ER PT J AU Viscoli, CM Inzucchi, SE Young, LH Furie, KL Gorman, MJ Horwitz, RI Lovejoy, AM Kernan, WN AF Viscoli, Catherine M. Inzucchi, Silvio E. Young, Lawrence H. Furie, Karen L. Gorman, Mark J. Horwitz, Ralph I. Lovejoy, Anne M. Kernan, Walter N. CA IRIS Investigators TI Predictors of Insulin Resistance in a Large Cohort of Ischemic Stroke Patients in the IRIS Trial SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Viscoli, Catherine M.; Inzucchi, Silvio E.; Young, Lawrence H.; Lovejoy, Anne M.; Kernan, Walter N.] Yale Univ, Sch Med, New Haven, CT USA. [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gorman, Mark J.] Univ Vermont, Coll Med, Burlington, VT USA. [Horwitz, Ralph I.] Stanford Univ, Sch Med, Stanford, CA 94305 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E142 EP E142 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500240 ER PT J AU Yuzawa, I Shin, HK Sakadzic, S Nishimura, M Lee, JH Boas, DA Ay, H Moskowitz, MA Ayata, C AF Yuzawa, Izumi Shin, Hwa K. Sakadzic, Sava Nishimura, Masaki Lee, Jeong H. Boas, David A. Ay, Hakan Moskowitz, Michael A. Ayata, Cenk TI Mild Induced Hypertension Improves Blood Flow via External Carotid Collaterals in Focal Cerebral Ischemia. SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Yuzawa, Izumi; Lee, Jeong H.; Moskowitz, Michael A.; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA. [Shin, Hwa K.] Pusan Natl Univ, Med Rsch Ctr Ischem Tissue Regenerat, Pusan, South Korea. [Sakadzic, Sava; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Nishimura, Masaki] Kyoto Univ, Dept Neurosurg, Kyoto, Japan. [Ay, Hakan; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neurosci Intens Care Unit, Charlestown, MA USA. [Ay, Hakan; Ayata, Cenk] Harvard Univ, Sch Med, Stroke Serv, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E258 EP E259 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500715 ER PT J AU Ziegler, PD Glotzer, TV Daoud, EG Ezekowitz, MD Singer, DE Koehler, JL Hilker, CE AF Ziegler, Paul D. Glotzer, Taya V. Daoud, Emile G. Ezekowitz, Michael D. Singer, Daniel E. Koehler, Jodi L. Hilker, Christopher E. TI Incidence of Newly Detected Atrial Arrhythmias via Implantable Devices in Patients with a Prior History of Stroke SO STROKE LA English DT Meeting Abstract CT American-Association-International-Stroke Conference 2009 CY FEB 17-20, 2009 CL San Diego, CA SP Amer Assoc Int Stroke C1 [Ziegler, Paul D.; Koehler, Jodi L.; Hilker, Christopher E.] Medtronic, Mounds View, MN USA. [Glotzer, Taya V.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Daoud, Emile G.] Ohio State Univ, Columbus, OH 43210 USA. [Ezekowitz, Michael D.] Lankenau Inst Med Rsch, Wynnewood, PA USA. [Singer, Daniel E.] 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 0039-2499 J9 STROKE JI Stroke PD APR PY 2009 VL 40 IS 4 BP E186 EP E187 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 426LJ UT WOS:000264709500421 ER PT J AU Gopaldas, RR Atluri, PV Blaustein, AS Bakaeen, FG Huh, J Chu, D AF Gopaldas, Raja R. Atluri, Prasad V. Blaustein, Alvin S. Bakaeen, Faisal G. Huh, Joseph Chu, Danny TI Papillary Fibroelastoma of the Aortic Valve Operative Approaches upon Incidental Discovery SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE Aortic valve/pathology/surgery/utrasonography; cardiac surgical procedures/methods; echocardiography, transesophageal; fibroma/complications/pathology/surgery/ultrasonography; heart neoplasms/diagnosis/pathology/surgery/therapy/ultrasonography ID ECHOCARDIOGRAPHIC CHARACTERISTICS; EXCISION AB Papillary fibroelastomas are the most common benign neoplasms of the cardiac valvular structures, and they are being recognized more frequently because of higher-resolution imaging technology Papillary fibroelastomas are associated with substantial complications that are secondary to systemic embolism. Incidentally discovered papillary fibroelastomas are treated on the basis of their size, mobility, and associated comorbidities and symptoms. Surgical resection should be offered to all patients who have symptoms and to asymptomatic patients who have pedunculated lesions or tumors larger than 1 cm in diameter Valve-sparing excision produces good long-term results in most instances. Herein, we present the case of a patient who was scheduled for elective myocardial revasculanzation and in whom an aortic valve papillary fibroelastoma was discovered incidentally during routine intraoperative transesophageal echocardiography. The timely recognition of this asymptomatic tumor enabled a modified operative approach: the patient underwent myocardial revascularization with concomitant valve-sparing resection of the tumor We discuss the pathophysiology of fibroelastomas of the aortic valve and operative approaches to the management of these tumors when they are discovered incidentally. (Tex Heart Inst J 2009,36(2):160-3) C1 [Gopaldas, Raja R.; Bakaeen, Faisal G.; Huh, Joseph; Chu, Danny] Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Houston, TX 77030 USA. [Atluri, Prasad V.] Michael E DeBakey Vet Affairs Med Ctr, Dept Anesthesia, Houston, TX 77030 USA. [Blaustein, Alvin S.] Michael E DeBakey Vet Affairs Med Ctr, Div Cardiol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Chu, D (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchumd@gmail.com NR 19 TC 17 Z9 17 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PD APR PY 2009 VL 36 IS 2 BP 160 EP 163 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 435GL UT WOS:000265331800019 PM 19436815 ER PT J AU Bilgen, B Uygun, K Bueno, EM Sucosky, P Barabino, GA AF Bilgen, Bahar Uygun, Korkut Bueno, Ericka M. Sucosky, Philippe Barabino, Gilda A. TI Tissue Growth Modeling in a Wavy-Walled Bioreactor SO TISSUE ENGINEERING PART A LA English DT Article; Proceedings Paper CT Annual Meeting of the Biomedical-Engineering-Society CY OCT 22, 2006 CL Chicago, IL SP Biomed Engn Soc ID ENGINEERED CARTILAGE; ROTATING BIOREACTORS; ARTICULAR-CARTILAGE; POLYMER SCAFFOLD; CELL-GROWTH; IN-VITRO; CHONDROCYTE; KINETICS; ENVIRONMENT; PREDICTION AB Bioreactors have played a crucial role in recent approaches to cartilage tissue engineering, providing an environment that promotes efficient cell seeding, nutrient and waste transport, and essential physical stimuli. This study employed a wavy-walled bioreactor to investigate the effects of the hydrodynamic environment on the properties of engineered cartilage. Its unique design provides multiple hydrodynamic environments within one setting. A tissue growth model was developed to characterize the tissue growth and extracellular matrix synthesis by chondrocytes seeded and cultivated on polyglycolic acid scaffolds in the wavy-walled bioreactor for a period of 4 weeks. This model consists of four components: 1) a computational fluid dynamics model, 2) a kinetic growth model, 3) an artificial neural network that empirically correlates hydrodynamic parameters with kinetic constants, and 4) a second artificial neural network that correlates the biochemical composition of constructs with their material properties. In tandem, these components enable the prediction of the dynamics of tissue growth, as well as the final compositional and mechanical properties of engineered cartilage. The growth model methodology developed in this study serves as a tool to predict the optimal bioprocessing conditions required to achieve desired tissue properties. C1 [Sucosky, Philippe; Barabino, Gilda A.] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. [Bueno, Ericka M.] Brigham & Womens Hosp, Skeletal Biol Lab, Dept Orthoped Surg, Boston, MA 02115 USA. [Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. [Bilgen, Bahar] Brown Univ, Dept Orthopaed, Alpert Med Sch, Providence, RI 02912 USA. [Bilgen, Bahar] Rhode Isl Hosp, Providence, RI 02912 USA. [Uygun, Korkut] Shriners Hosp Children, Boston, MA USA. RP Barabino, GA (reprint author), Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, 313 Ferst Dr, Atlanta, GA 30332 USA. EM gilda.barabino@bme.gatech.edu RI Bilgen, Bahar/B-3096-2009; Sucosky, Philippe/A-7052-2013; OI Sucosky, Philippe/0000-0003-0113-5858; Bilgen, Bahar/0000-0002-7395-2315 NR 41 TC 10 Z9 10 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD APR PY 2009 VL 15 IS 4 BP 761 EP 771 DI 10.1089/ten.tea.2008.0078 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 429AA UT WOS:000264892000004 PM 18847355 ER PT J AU Radisic, M Fast, VG Sharifov, OF Iyer, RK Park, H Vunjak-Novakovic, G AF Radisic, Milica Fast, Vladimir G. Sharifov, Oleg F. Iyer, Rohin K. Park, Hyoungshin Vunjak-Novakovic, Gordana TI Optical Mapping of Impulse Propagation in Engineered Cardiac Tissue SO TISSUE ENGINEERING PART A LA English DT Article ID PLURIPOTENT STEM-CELLS; ELECTRICAL-STIMULATION; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; HUMAN FIBROBLASTS; MYOCYTE CULTURES; DEFINED FACTORS; IN-VITRO; HEART; MUSCLE AB Cardiac tissue engineering has a potential to provide functional, synchronously contractile tissue constructs for heart repair, and for studies of development and disease using in vivo-like yet controllable in vitro settings. In both cases, the utilization of bioreactors capable of providing biomimetic culture environments is instrumental for supporting cell differentiation and functional assembly. In the present study, neonatal rat heart cells were cultured on highly porous collagen scaffolds in bioreactors with electrical field stimulation. A hallmark of excitable tissues such as myocardium is the ability to propagate electrical impulses. We utilized the method of optical mapping to measure the electrical impulse propagation. The average conduction velocity recorded for the stimulated constructs (14.4 +/- 4.1 cm/s) was significantly higher than that of the nonstimulated constructs (8.6 +/- 2.3 cm/s, p=0.003). The measured electrical propagation properties correlated to the contractile behavior and the compositions of tissue constructs. Electrical stimulation during culture significantly improved amplitude of contractions, tissue morphology, and connexin-43 expression compared to the nonsimulated controls. These data provide evidence that electrical stimulation during bioreactor cultivation can improve electrical signal propagation in engineered cardiac constructs. C1 [Radisic, Milica; Iyer, Rohin K.] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada. [Vunjak-Novakovic, Gordana] Columbia Univ, Dept Biomed Engn, Vanderbilt Clin, New York, NY 10032 USA. [Fast, Vladimir G.; Sharifov, Oleg F.] Univ Alabama, Dept Biomed Engn, Birmingham, AL 35294 USA. [Park, Hyoungshin] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Park, Hyoungshin] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Radisic, M (reprint author), Univ Toronto, Inst Biomat & Biomed Engn, 164 Coll St,Room 407, Toronto, ON M5S 3G9, Canada. EM m.radisic@utoronto.ca; gv2131@columbia.edu RI vunjak-novakovic, gordana/J-9279-2012; OI Vunjak-Novakovic, Gordana/0000-0002-9382-1574 FU NSERC; NIH [R01 HL076485, P41-EB002520]; Ontario Graduate Scholarship FX This study was supported by NSERC (Discovery Grant to M. R.), NIH (R01 HL076485 and P41-EB002520 to G.V.N.), and Ontario Graduate Scholarship (to R.K.I.). NR 46 TC 29 Z9 29 U1 0 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD APR PY 2009 VL 15 IS 4 BP 851 EP 860 DI 10.1089/ten.tea.2008.0223 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 429AA UT WOS:000264892000012 PM 18847360 ER PT J AU Stowell, CP AF Stowell, Christopher P. TI All politics, and oxygenation, are local: decision making and red blood cell transfusion SO TRANSFUSION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Stowell, CP (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. EM cstowell@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2009 VL 49 IS 4 BP 620 EP 621 DI 10.1111/j.1537-2995.2009.02141.x PG 2 WC Hematology SC Hematology GA 421TA UT WOS:000264380000005 PM 19335376 ER PT J AU Marty, FM AF Marty, Francisco M. TI Strongyloides hyperinfection syndrome and transplantation: a preventable, frequently fatal infection SO TRANSPLANT INFECTIOUS DISEASE LA English DT Editorial Material ID KIDNEY-TRANSPLANT; RENAL-TRANSPLANTATION; IVERMECTIN; STERCORALIS; RECIPIENTS; CYCLOSPORINE; TRANSMISSION; PATIENT; DISEASE C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM fmarty@partners.org NR 24 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD APR PY 2009 VL 11 IS 2 BP 97 EP 99 DI 10.1111/j.1399-3062.2009.00383.x PG 3 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 430UU UT WOS:000265015600001 PM 19400809 ER PT J AU Yu, BL Bloch, KD Zapol, WM AF Yu, Binglan Bloch, Kenneth D. Zapol, Warren M. TI Hemoglobin-Based Red Blood Cell Substitutes and Nitric Oxide SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID ISCHEMIA-REPERFUSION INJURY; HEMORRHAGIC-SHOCK; INHALED NO; RESISTANCE; INFARCTION; HEMOLYSIS; MODEL; TRIAL AB Hemoglobin-based oxygen carriers (HBOCs) have been studied for decades as red blood cell substitutes. Profound vasoconstrictor effects have limited the clinical utility of HBOCs and are attributable to avid scavenging of nitric oxide (NO). Inhaling NO can charge the body's stores of NO metabolites without producing hypotension and can prevent systemic hypertension induced when HBOCs are subsequently infused. Concurrent breathing of low NO doses can prevent pulmonary vasoconstriction after HBOC infusion without augmenting plasma methemoglobinemia. (Trends Cardiovasc Med 2009; 19:103-107) (C) 2009, Elsevier Inc. C1 [Yu, Binglan; Bloch, Kenneth D.; Zapol, Warren M.] Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Massachusetts Gen Hosp,Anesthesia Ctr Crit Care R, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Massachusetts Gen Hosp,Anesthesia Ctr Crit Care R, 55 Fruit St,Thier 503, Boston, MA 02114 USA. EM wzapol@partners.org FU NHLBI NIH HHS [R01 HL042397-18] NR 30 TC 20 Z9 22 U1 2 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD APR PY 2009 VL 19 IS 3 BP 103 EP 107 AR PII S1050-1738(09)00089-9 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 489OW UT WOS:000269430900006 PM 19679268 ER PT J AU Kaufman, DS Winter, KA Shipley, WU Heney, NM Wallace, HJ Toonkel, LM Zietman, AL Tanguay, S Sandler, HM AF Kaufman, Donald S. Winter, Kathryn A. Shipley, William U. Heney, Niall M. Wallace, H. James, III Toonkel, Leonard M. Zietman, Anthony L. Tanguay, Simon Sandler, Howard M. TI Phase I-II RTOG Study (99-06) of Patients With Muscle-invasive Bladder Cancer Undergoing Transurethral Surgery, Paclitaxel, Cisplatin, and Twice-daily Radiotherapy Followed by Selective Bladder Preservation or Radical Cystectomy and Adjuvant Chemotherapy SO UROLOGY LA English DT Article ID COMBINED-MODALITY PROGRAM; ORGAN PRESERVATION; RADIATION-THERAPY; TRIAL; GEMCITABINE AB OBJECTIVES To evaluate the safety, tolerance, protocol completion rate, tumor response rate, and patient survival of chemoradiotherapy for patients with muscle-invasive operable bladder cancer. METHODS After transurethral resection of the tumor in patients with Stage T2-T4a bladder cancer, twice-daily radiotherapy with paclitaxel and cisplatin chemotherapy induction (TCI) was administered. If repeat biopsy showed less than Stage T1 disease, consolidation with TCI was given. If repeat biopsy showed greater than Stage T1 disease, cystectomy was recommended. Adjuvant gemcitabine and cisplatin were given to all patients. RESULTS A total of 80 patients met protocol eligibility. TCI resulted in 26% developing grade 3-4 acute toxicity, mainly gastrointestinal (25%). During consolidation TCI, grade 3-4 acute toxicity, all transient, was reported in 8%. Four cycles of adjuvant chemotherapy were completed per protocol or with minor deviations in 70% of the patients. Adjuvant treatment was associated with grade 3 toxicity in 46% and grade 4 in 26%. One patient had a fatal hemorrhagic stroke. Late bladder radiation toxicity was evaluated in 53 patients with 2 years of follow-up. Of these 53 patients, 3 experienced self-limited, late grade 3 bladder toxicity. The postinduction complete response rate was 81% (65/80), 36 of the 80 patients died (22 of bladder cancer). At a median follow-up of 49.4 months, the actuarial 5-year overall and disease-specific survival rate was 56% and 71%, respectively. CONCLUSIONS These favorable tumor response rates with possible increased bladder preservation rates suggest that this treatment regimen deserves further study. UROLOGY 73: 833-837, 2009. (c) 2009 Elsevier Inc. C1 [Shipley, William U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genitourinary Oncol Unit,Dept Radiat Oncol, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Radiat Therapy Oncol Grp, Dept Stat, Philadelphia, PA USA. Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. Univ Michigan, Ann Arbor, MI 48109 USA. McGill Univ, Ctr Hlth, Dept Urol Surg, Montreal, PQ, Canada. RP Shipley, WU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genitourinary Oncol Unit,Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM wshipley@partners.org FU National Institutes of Health [RTOG U10 CA21661, UIC CA32115] FX This study was supported by RTOG U10 CA21661 and UIC CA32115 grants from the National Institutes of Health. NR 15 TC 74 Z9 76 U1 0 U2 1 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 APR PY 2009 VL 73 IS 4 BP 833 EP 837 DI 10.1016/j.urology.2008.09.036 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 432CF UT WOS:000265110400042 PM 19100600 ER PT J AU Maeno, Y Shinzato, M Nagashima, S Rittling, SR Denhardt, DT Uede, T Taniguchi, K AF Maeno, Yoshimasa Shinzato, Masanori Nagashima, Shigeo Rittling, Susan R. Denhardt, David T. Uede, Toshimitsu Taniguchi, Koki TI Effect of Osteopontin on Diarrhea Duration and Innate Immunity in Suckling Mice Infected with a Murine Rotavirus SO VIRAL IMMUNOLOGY LA English DT Article ID LACKING OSTEOPONTIN; INTERFERON-GAMMA; HOST-RESISTANCE; PROTECTION; CELLS; CYTOKINE; INTEGRIN; ENTRY; EXPRESSION; CHILDREN AB We studied the role of osteopontin (OPN) in host responses against rotavirus (RV) infection. OPN knockout (OPN-KO) suckling mice were more susceptible to RV (strain EW) infection and showed prolonged diarrhea duration compared to wild-type (WT) suckling mice. OPN in the small intestine of WT mice was expressed after 48 h post-infection. On day 2 postinfection, mRNA levels of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-15 in OPN-KO mice were lower than in WT mice, although mRNA expression of Th-1- and Th-2-related cytokines in the small intestine were nearly the same between OPN-KO and WT mice. These results suggested that OPN is involved in innate responses against RV infection. C1 [Maeno, Yoshimasa; Nagashima, Shigeo; Taniguchi, Koki] Fujita Hlth Univ, Dept Virol & Parasitol, Sch Med, Aichi 4701192, Japan. [Shinzato, Masanori] Fujita Hlth Univ, Dept Pathol, Sch Hlth Sci, Aichi 4701192, Japan. [Rittling, Susan R.] Forsyth Inst, Boston, MA USA. [Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Div Life Sci, Piscataway, NJ USA. [Uede, Toshimitsu] Hokkaido Univ, Div Mol Immunol, Inst Med Genet, Sapporo, Hokkaido, Japan. RP Maeno, Y (reprint author), Fujita Hlth Univ, Dept Virol & Parasitol, Sch Med, 1-98 Kutsukake, Aichi 4701192, Japan. EM ymaeno@fujita-hu.ac.jp RI uede, toshimitsu/A-4273-2012 FU Ministry of Education, Culture, Sports, Science, and Technology of Japan FX This study was partly supported by Grants-in-Aid for Scientific Research on Priority Areas and the Open Research Center Program of Fujita Health University from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. NR 28 TC 5 Z9 5 U1 0 U2 1 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 APR PY 2009 VL 22 IS 2 BP 139 EP 144 DI 10.1089/vim.2008.0054 PG 6 WC Immunology; Virology SC Immunology; Virology GA 425KW UT WOS:000264636400008 PM 19327001 ER PT J AU Bhattacharya, D Ansari, IH Striker, R AF Bhattacharya, Dipankar Ansari, Israrul H. Striker, Rob TI The flaviviral methyltransferase is a substrate of Casein Kinase 1 SO VIRUS RESEARCH LA English DT Article DE Casein Kinase 1; Phosphorylation; Methyltransferase; RNA cap; Flavivirus ID PHOSPHORYLATION; PROTEINS; SEQUENCE; NS5; CK1; HYPERPHOSPHORYLATION; DETERMINANTS; METHYLATIONS; INHIBITORS; FAMILY AB Serine/Threonine phosphorylation of the nonstructural protein 5 (NS5) is a conserved feature of flaviviruses, but the identity and function(s) of the responsible kinase(s) remain unknown. Serine 56 in the methyltransferase domain of NS5 can be phosphorylated intracellularly, is conserved in all flaviviruses, and is a critical residue in the catalytic mechanism. A negative charge at this residue inactivates the 2'-0 methyltransferase activity necessary to form a 5' cap structure of the viral RNA. Here we show pharmacologic inhibition of Casein Kinase 1 (CK1) suppresses yellow fever virus (YFV) production. We also demonstrate the alpha isoform of Casein Kinase I (CK1 alpha), a kinase previously identified as phosphorylating Hepatitis C Virus NS5A protein, also phosphorylates serine 56 of YFV methyltransferase. Overall these results suggest CK1 activity can influence flaviviral replication. Published by Elsevier B.V. C1 [Bhattacharya, Dipankar; Ansari, Israrul H.; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. RP Striker, R (reprint author), Univ Wisconsin, Dept Med, 1550 Linden Dr, Madison, WI 53706 USA. EM rtstriker@wisc.edu FU NIH/NIAID Regional Center of Excellence for Biodefense; Emerging Infectious Diseases Research (RCE) Program; Region V 'Great Lakes' RCE [U54-AI057153]; Wisconsin Partnership Fund for a Healthy Future FX This work was sponsored by the NIH/NIAID Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) Program. The authors wish to acknowledge membership within and support from the Region V 'Great Lakes' RCE (NIH award U54-AI057153). We thank the UW Madison Biotechnology Mass Spectrometry facility and the Human Proteomics Mass Spectrometry Facility supported by the "The Wisconsin Partnership Fund for a Healthy Future" for technical assistance, Laura Hogan for editorial suggestions and Richard Kuhn for the anti NS3 YFV antibody. NR 24 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD APR PY 2009 VL 141 IS 1 BP 101 EP 104 DI 10.1016/j.virusres.2009.01.002 PG 4 WC Virology SC Virology GA 430MJ UT WOS:000264992900013 PM 19185594 ER PT J AU Yang, LD Belaguli, N Berger, DH AF Yang, Linda Belaguli, Narasimhaswamy Berger, David H. TI MicroRNA and Colorectal Cancer SO WORLD JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT Molecular Surgeon Symposium on Personalized Genomic Medicine and Surgery CY APR 12, 2008 CL Baylor Coll Med, Houston, TX HO Baylor Coll Med ID CHRONIC LYMPHOCYTIC-LEUKEMIA; COLON-CANCER; CAENORHABDITIS-ELEGANS; REGULATED MICRORNA; RNA-INTERFERENCE; BURKITT-LYMPHOMA; NUCLEAR EXPORT; GENE; EXPRESSION; CELLS AB MicroRNAs are small 19 to 22 nucleotide sequences of RNA that participate in the regulation of cell differentiation, cell cycle progression, and apoptosis. MicroRNAs act much like small interfering RNA, annealing with RISC, to cleave messenger RNA, and microRNAs exert translational inhibition that is incompletely understood. They are important factors in tumorigenesis and have been the subject of research in many types of cancers, including colon cancer. MicroRNAs may be abnormally down-regulated or up-regulated in colon-cancer tissue. Artificial dysregulation of certain microRNAs will trigger tumorigenesis or apoptosis depending on which microRNA is manipulated. Although the natural mechanisms for the dysregulation of microRNAs is still largely unknown, one theory tested in colon cancers proposes that DNA hypermethylation leads to down-regulation of certain microRNAs. Specific microRNA expression patterns help characterize specific cancers and may be used as a prognostication factor and in following patient response to 5-fluorouracil chemotherapy. This article reviews the existing literature pertaining to the study of microRNA in colorectal cancer. C1 [Yang, Linda; Belaguli, Narasimhaswamy; Berger, David H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Berger, DH (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, 112OCL,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dhb@bcm.tmc.edu FU NCI NIH HHS [R13 CA132572] NR 65 TC 71 Z9 76 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD APR PY 2009 VL 33 IS 4 BP 638 EP 646 DI 10.1007/s00268-008-9865-5 PG 9 WC Surgery SC Surgery GA 419FW UT WOS:000264205600005 PM 19123024 ER PT J AU Fox, CS Gona, P Hoffmann, U Porter, SA Salton, CJ Massaro, JM Levy, D Larson, MG D'Agostino, RB O'Donnell, CJ Manning, WJ AF Fox, Caroline S. Gona, Philimon Hoffmann, Udo Porter, Stacy A. Salton, Carol J. Massaro, Joseph M. Levy, Daniel Larson, Martin G. D'Agostino, Ralph B., Sr. O'Donnell, Christopher J. Manning, Warren J. TI Pericardial Fat, Intrathoracic Fat, and Measures of Left Ventricular Structure and Function The Framingham Heart Study SO CIRCULATION LA English DT Article DE epidemiology; magnetic resonance imaging; obesity; pericardium; risk factors ID EPICARDIAL ADIPOSE-TISSUE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; OBESE SUBJECTS; WEIGHT-LOSS; MASS; ECHOCARDIOGRAPHY; MORPHOLOGY; THICKNESS AB Background-Pericardial fat has been implicated in the pathogenesis of obesity-related cardiovascular disease. Whether the associations of pericardial fat and measures of cardiac structure and function are independent of the systemic effects of obesity and visceral adiposity has not been fully explored. Methods and Results-Participants from the Framingham Heart Study (n = 997; 54.4% women) underwent chest and abdominal computed tomography and cardiovascular magnetic resonance imaging between 2002 and 2005. Pericardial fat, intrathoracic fat, and visceral adipose tissue quantified from multidetector computed tomography, along with body mass index and waist circumference, were examined in relation to cardiovascular magnetic resonance measures of left ventricular (LV) mass, LV end-diastolic volume, and left atrial dimension. In women, pericardial fat (r = 0.20 to 0.35, P < 0.001), intrathoracic fat (r = 0.25 to 0.37, P < 0.001), visceral adipose tissue (r = 0.24 to 0.45, P < 0.001), body mass index (r = 0.36 to 0.53, P < 0.001), and waist circumference (r = 0.30 to 0.48, P < 0.001) were directly correlated with LV mass, LV end-diastolic volume, and left atrial dimension. In men, pericardial fat (r = 0.19 to 0.37, P < 0.001), intrathoracic fat (r = 0.17 to 0.31, P < 0.001), visceral adipose tissue (r = 0.19 to 0.36, P < 0.001), body mass index (r = 0.32 to 0.44, P < 0.001), and waist circumference (r = 0.34 to 0.44, P < 0.001) were directly correlated with LV mass and left atrial dimension, but LV end-diastolic volume was not consistently associated with adiposity measures. Associations persisted after multivariable adjustment but not after additional adjustment for body weight and visceral adipose tissue, except for pericardial fat and left atrial dimension in men. Conclusions-Pericardial fat is correlated with cardiovascular magnetic resonance measures, but the association is not independent of or stronger than other ectopic fat stores or proxy measures of visceral adiposity. An important exception is left atrial dimension in men. These results suggest that the systemic effects of obesity on cardiac structure and function may outweigh the local pathogenic effects of pericardial fat. (Circulation. 2009; 119: 1586-1591.) C1 [Fox, Caroline S.; Gona, Philimon; Massaro, Joseph M.; Larson, Martin G.; D'Agostino, Ralph B., Sr.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Fox, Caroline S.; Porter, Stacy A.] Harvard Univ, Sch Med, Boston, MA USA. [Gona, Philimon; Massaro, Joseph M.; Larson, Martin G.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254 FU National Heart, Lung and Blood Institute [N01-HC-25195, R01-HL70279] FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195 and R01-HL70279). NR 27 TC 99 Z9 101 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 MAR 31 PY 2009 VL 119 IS 12 BP 1586 EP 1591 DI 10.1161/CIRCULATIONAHA.108.828970 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 426LI UT WOS:000264709400005 PM 19289634 ER PT J AU Boger, RH Sullivan, LM Schwedhelm, E Wang, TJ Maas, R Benjamin, EJ Schulze, F Xanthakis, V Benndorf, RA Vasan, RS AF Boeger, Rainer H. Sullivan, Lisa M. Schwedhelm, Edzard Wang, Thomas J. Maas, Renke Benjamin, Emelia J. Schulze, Friedrich Xanthakis, Vanessa Benndorf, Ralf A. Vasan, Ramachandran S. TI Plasma Asymmetric Dimethylarginine and Incidence of Cardiovascular Disease and Death in the Community SO CIRCULATION LA English DT Article DE cardiovascular diseases; epidemiology; nitric oxide; population; risk factors ID NITRIC-OXIDE SYNTHASE; CORONARY-HEART-DISEASE; GLOMERULAR-FILTRATION-RATE; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; RISK-FACTOR; EVENTS; ARGININE; ADMA; DIMETHYLAMINOHYDROLASE AB Background-Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, induces endothelial dysfunction. Although elevated ADMA has been associated with an increased risk of cardiovascular disease events and death in referral samples, the prognostic significance of ADMA in the community has not been adequately evaluated. Methods and Results-We related plasma ADMA, L-arginine (Arg), and the ratio of Arg to ADMA to the incidence of cardiovascular disease (fatal or nonfatal myocardial infarction, coronary insufficiency, angina pectoris, stroke or transient ischemic attack, intermittent claudication, or heart failure) and death in 3320 Framingham Offspring Study participants (1769 women; mean age, 59 years). Over a follow-up period of 10.9 years, 281 individuals of 2956 free of cardiovascular disease at baseline developed incident cardiovascular disease, and 285 participants died. In multivariable models adjusting for established risk factors and other biomarkers (B-type natriuretic peptide, renin, homocysteine, urine albumin excretion, and C-reactive protein), ADMA and the ratio of Arg to ADMA were significantly associated with all-cause mortality (adjusted-hazard ratio [HR] per 1-SD increment, 1.21; 95% CI, 1.07 to 1.37; and HR per 1-SD increment, 0.80; 95% CI, 0.69 to 0.93, respectively), whereas Arg was not (HR per 1-SD increment, 0.89; 95% CI, 0.77 to 1.02). We noted effect modification by diabetes status; ADMA was associated with death in individuals without diabetes (adjusted HR per 1-SD increment, 1.30; 95% CI, 1.13 to 1.50) but not in individuals with diabetes (adjusted HR per 1-SD increment, 0.85; 95% CI, 0.62 to 1.16). ADMA, Arg, and the ratio of Arg to ADMA were not associated with cardiovascular disease incidence (P > 0.10). Conclusions-In our large community-based sample, ADMA was significantly associated with all-cause mortality, particularly in nondiabetic individuals. ( Circulation. 2009; 119: 1592-1600.) C1 [Boeger, Rainer H.; Schwedhelm, Edzard; Maas, Renke; Schulze, Friedrich; Benndorf, Ralf A.] Univ Med Ctr Hamburg Eppendorf, Inst Expt & Clin Pharmacol, Clin Pharmacol Unit, Hamburg, Germany. [Sullivan, Lisa M.; Wang, Thomas J.; Benjamin, Emelia J.; Xanthakis, Vanessa; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Sullivan, Lisa M.; Xanthakis, Vanessa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Div Cardiol, Boston, MA USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM boeger@uke.uni-hamburg.de; vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195, K23-HL074077-01, N01HV28178, 2K24HL04334]; Deutsche Forschungsgemeinschaft [Bo 1431/4-1] FX This work was supported through National Institutes of Health/National Heart, Lung, and Blood Institute contracts N01-HC-25195, K23-HL074077-01 (Dr Wang), N01HV28178, and 2K24HL04334 ( Dr Vasan) and by the Deutsche Forschungsgemeinschaft grant Bo 1431/4-1 ( Dr Boger). NR 41 TC 182 Z9 187 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 31 PY 2009 VL 119 IS 12 BP 1592 EP U65 DI 10.1161/CIRCULATIONAHA.108.838268 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 426LI UT WOS:000264709400006 PM 19289633 ER PT J AU Lewis, GD AF Lewis, Gregory D. TI The Role of the Pulmonary Vasculature in Heart Failure With Preserved Ejection Fraction Comment SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE pulmonary hypertension; heart failure; epidemiology ID DOPPLER-ECHOCARDIOGRAPHY; ARTERIAL-HYPERTENSION; EXERCISE CAPACITY; PREVALENCE; SILDENAFIL; MANAGEMENT; CATHETERIZATION; HEMODYNAMICS; PRESSURES; INSIGHTS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02114 USA. RP Lewis, GD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM glewis@partners.org NR 31 TC 6 Z9 6 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 MAR 31 PY 2009 VL 53 IS 13 BP 1127 EP 1129 DI 10.1016/j.jacc.2009.01.006 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 423SJ UT WOS:000264515700006 PM 19324257 ER PT J AU Chu-Shore, CJ Major, P Montenegro, M Thiele, E AF Chu-Shore, Catherine J. Major, Philippe Montenegro, Maria Thiele, Elizabeth TI Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex SO NEUROLOGY LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; MUTATIONAL ANALYSIS; SURGICAL-TREATMENT; CORTICAL TUBERS; PATHOGENESIS; IMPAIRMENT; SEVERITY; SURGERY; LESIONS; COUNT AB Background: Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of hamartomatous lesions in multiple organs, including tubers in the brain. The majority of patients with TSC have epilepsy. Some cortical tubers are epileptic foci, while others appear to be physiologically quiescent. It is unknown whether variations in tuber morphology may account for this difference. The objectives of this study were to determine the frequency of cyst-like tubers in patients with TSC, whether cyst-like tubers correlate with TSC genotype, and whether cyst-like cortical tubers are associated with a history of infantile spasms, epilepsy, or refractory epilepsy. Methods: A retrospective chart review was performed of 173 patients with TSC. MRI images were evaluated for the presence of at least one cyst-like cortical tuber. Patient charts were then reviewed for genetic mutation, a history of infantile spasms, epilepsy, and epilepsy refractory to more than three medications. Results: A total of 46% of patients had at least one cyst-like cortical tuber present on neuroimaging. Patients with a TSC2 mutation were more likely to have a cyst-like tuber than patients with TSC1 mutation (p = 0.002) or patients with no mutation identified (p = 0.039). Patients with at least one cyst-like cortical tuber were more likely to have a history of infantile spasms (p = 0.00005), epilepsy (p = 0.0038), and refractory epilepsy (p = 0.0007) than patients without a cyst-like cortical tuber. Conclusion: Cyst-like cortical tubers are strongly associated with TSC2 gene mutation and a more aggressive seizure phenotype in patients with tuberous sclerosis complex. Neurology (R) 2009;72:1165-1169 C1 [Chu-Shore, Catherine J.; Montenegro, Maria; Thiele, Elizabeth] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Major, Philippe] CHU St Justine, Serv Neurol, Montreal, PQ, Canada. RP Thiele, E (reprint author), Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA. EM ethiele@partners.org NR 28 TC 38 Z9 40 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 MAR 31 PY 2009 VL 72 IS 13 BP 1165 EP 1169 DI 10.1212/01.wnl.0000345365.92821.86 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 426LE UT WOS:000264709000011 PM 19332694 ER PT J AU Tam, J Duda, DG Perentes, JY Quadri, RS Fukumura, D Jain, RK AF Tam, Joshua Duda, Dan G. Perentes, Jean Y. Quadri, Rehan S. Fukumura, Dai Jain, Rakesh K. TI Blockade of VEGFR2 and Not VEGFR1 Can Limit Diet-Induced Fat Tissue Expansion: Role of Local versus Bone Marrow-Derived Endothelial Cells SO PLOS ONE LA English DT Article AB Background: We investigated if new vessel formation in fat involves the contribution of local tissue-derived endothelial cells (i.e., angiogenesis) or bone marrow-derived cells (BMDCs, i.e. vasculogenesis) and if antiangiogenic treatment by blockade of vascular endothelial growth factor (VEGF) receptors can prevent diet-induced obesity (DIO). Methodology/Principal Findings: We performed restorative bone marrow transplantation into wild-type mice using transgenic mice expressing green fluorescent protein (GFP) constitutively (driven by beta-actin promoter) or selectively in endothelial cells (under Tie2 promoter activation) as donors. The presence of donor BMDCs in recipient mice was investigated in fat tissue vessels after DIO using in vivo and ex vivo fluorescence microscopy. We investigated the roles of VEGF receptors 1 and 2 (VEGFR1/VEGFR2) by inducing DIO in mice and treating them with blocking monoclonal antibodies. We found only marginal (less than 1%) incorporation of BMDCs in fat vessels during DIO. When angiogenesis was inhibited by blocking VEGFR2 in mice with DIO, treated mice had significantly lower body weights than control animals. In contrast, blocking VEGFR1 had no discernable effect on the weight gain during DIO. Conclusions/Significance: Formation of new vessels in fat tissues during DIO is largely due to angiogenesis rather than de novo vasculogenesis. Antiangiogenic treatment by blockade of VEGFR2 but not VEGFR1 may limit adipose tissue expansion. C1 [Tam, Joshua; Duda, Dan G.; Perentes, Jean Y.; Quadri, Rehan S.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Tam, Joshua; Duda, Dan G.; Perentes, Jean Y.; Quadri, Rehan S.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Tam, Joshua] Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Perentes, Jean Y.] Ctr Hosp Univ Vaudois CHUV, Div Thorac & Vasc Surg, Lausanne, Switzerland. RP Tam, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu FU National Institutes of Health [P01CA80124, R01CA96915, R01CA115767, R01CA85140, R01CA126642] FX This study was partially supported by National Institutes of Health grants P01CA80124, R01CA96915, R01CA115767, R01CA85140, and R01CA126642. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 49 Z9 50 U1 2 U2 3 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 MAR 31 PY 2009 VL 4 IS 3 AR e4974 DI 10.1371/journal.pone.0004974 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437PR UT WOS:000265499900007 PM 19333381 ER PT J AU De Jager, PL Baecher-Allan, C Maier, LM Arthur, AT Ottoboni, L Barcellos, L McCauley, JL Sawcer, S Goris, A Saarela, J Yelensky, R Price, A Leppa, V Patterson, N de Bakker, PIW Tran, D Aubin, C Pobywajlo, S Rossin, E Hu, XL Ashley, CW Choy, E Rioux, JD Pericak-Vance, MA Ivinson, A Booth, DR Stewart, GJ Palotie, A Peltonen, L Dubois, B Haines, JL Weiner, HL Compston, A Hauser, SL Daly, MJ Reich, D Oksenberg, JR Hafler, DA AF De Jager, Philip L. Baecher-Allan, Clare Maier, Lisa M. Arthur, Ariel T. Ottoboni, Linda Barcellos, Lisa McCauley, Jacob L. Sawcer, Stephen Goris, An Saarela, Janna Yelensky, Roman Price, Alkes Leppa, Virpi Patterson, Nick de Bakker, Paul I. W. Tran, Dong Aubin, Cristin Pobywajlo, Susan Rossin, Elizabeth Hu, Xinli Ashley, Charles W. Choy, Edwin Rioux, John D. Pericak-Vance, Margaret A. Ivinson, Adrian Booth, David R. Stewart, Graeme J. Palotie, Aarno Peltonen, Leena Dubois, Benedicte Haines, Jonathan L. Weiner, Howard L. Compston, Alastair Hauser, Stephen L. Daly, Mark J. Reich, David Oksenberg, Jorge R. Hafler, David A. TI The role of the CD58 locus in multiple sclerosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetic; human; RNA; quantitative trait; inflammation ID REGULATORY T-CELLS; INTERLEUKIN-7 RECEPTOR; GENE-EXPRESSION; FOXP3; ASSOCIATION; ALEFACEPT; GENOME; PSORIASIS; TRIAL; RISK AB Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the CD58 gene region, encoding the costimulatory molecule LFA-3, are associated with risk of developing MS. We now report additional genetic evidence, as well as resequencing and fine mapping of the CD58 locus in patients with MS and control subjects. These efforts identify a CD58 variant that provides further evidence of association with MS (P = 1.1 x 10(-6), OR 0.82) and the single protective effect within the CD58 locus is captured by the rs2300747(G) allele. This protective rs2300747G allele is associated with a dose-dependent increase in CD58 mRNA expression in lymphoblastic cell lines (P = 1.1 x 10(-10)) and in peripheral blood mononuclear cells from MS subjects (P = 0.0037). This protective effect of enhanced CD58 expression on circulating mononuclear cells in patients with MS is supported by finding that CD58 mRNA expression is higher in MS subjects during clinical remission. Functional investigations suggest a potential mechanism whereby increases in CD58 expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of CD4(+)CD25(high) regulatory T cells that are defective in subjects with MS. C1 [De Jager, Philip L.; Baecher-Allan, Clare; Maier, Lisa M.; Ottoboni, Linda; Tran, Dong; Aubin, Cristin; Pobywajlo, Susan; Rossin, Elizabeth; Ashley, Charles W.; Weiner, Howard L.; Hafler, David A.] Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Boston, MA 02115 USA. [De Jager, Philip L.; de Bakker, Paul I. W.] Partners Ctr Personalized Genet Med, Boston, MA 02115 USA. [De Jager, Philip L.; Maier, Lisa M.; Ottoboni, Linda; Yelensky, Roman; Price, Alkes; Patterson, Nick; de Bakker, Paul I. W.; Tran, Dong; Aubin, Cristin; Rossin, Elizabeth; Hu, Xinli; Choy, Edwin; Rioux, John D.; Palotie, Aarno; Peltonen, Leena; Daly, Mark J.; Reich, David; Hafler, David A.] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [De Jager, Philip L.; Maier, Lisa M.; Ottoboni, Linda; Yelensky, Roman; Price, Alkes; Patterson, Nick; de Bakker, Paul I. W.; Tran, Dong; Aubin, Cristin; Rossin, Elizabeth; Hu, Xinli; Choy, Edwin; Rioux, John D.; Palotie, Aarno; Peltonen, Leena; Daly, Mark J.; Reich, David; Hafler, David A.] MIT, Cambridge, MA 02139 USA. [Arthur, Ariel T.] Univ Sydney, Dept Med, Sydney, NSW 2145, Australia. [Arthur, Ariel T.] Univ Sydney, Nerve Res Fdn, Sydney, NSW 2145, Australia. [Barcellos, Lisa] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. [McCauley, Jacob L.] Univ Miami, Miller Sch Med, Miami Inst Human Genom, Miami, FL 33136 USA. [Sawcer, Stephen; Dubois, Benedicte; Compston, Alastair] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England. [Goris, An; Palotie, Aarno; Peltonen, Leena] Univ Louvain, Sect Expt Neurol, B-3000 Louvain, Belgium. [Saarela, Janna; Leppa, Virpi] Natl Publ Hlth Inst, Dept Mol Med, Helsinki 00290, Finland. [Saarela, Janna; Leppa, Virpi] Univ Finland, Biomedicum, Program Mol Med, Helsinki 00290, Finland. [Yelensky, Roman; Choy, Edwin; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Price, Alkes] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Rioux, John D.] Montreal Heart Inst, Montreal, PQ H3C 3J7, Canada. [Rioux, John D.] Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Ivinson, Adrian] Harvard Univ, Sch Med, Harvard Neurodiscovery Ctr, Boston, MA 02115 USA. [Booth, David R.; Stewart, Graeme J.] Westmead Millenium Inst, Inst Immunol & Allergy Res, Sydney, NSW, Australia. [Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37232 USA. [Hauser, Stephen L.; Oksenberg, Jorge R.] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. [Hauser, Stephen L.; Oksenberg, Jorge R.] Univ Calif San Francisco, Sch Med, Inst Human Genet, San Francisco, CA 94143 USA. RP De Jager, PL (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Div Mol Immunol, Boston, MA 02115 USA. EM pdejager@rics.bwh.harvard.edu RI Haines, Jonathan/C-3374-2012; de Bakker, Paul/B-8730-2009; Saarela, Janna/E-5369-2014; Reich, Daniel/E-5701-2010; Goris, An/F-2943-2010; Rioux, John/A-9599-2015; Hauser, Stephen/J-2978-2016; OI Choy, Edwin/0000-0001-9896-8084; de Bakker, Paul/0000-0001-7735-7858; Reich, Daniel/0000-0002-2628-4334; Goris, An/0000-0002-1276-6682; Rioux, John/0000-0001-7560-8326; Saarela, Janna/0000-0002-0853-6219; OTTOBONI, LINDA/0000-0001-5412-7785 FU NIH [R01SN24247, P01 A039671]; National Multiple Scelrosis Society [FG-1718-Al]; National Institute of Neurological Disorders and Stroke [NS46341]; Foundation Flanders, Belgium (F.W.O.-Vlaanderen); International Multiple Sclerosis Genetics Consortium; NINDS [R01 NS43559] FX We thank the following clinicians for contributing to sample collection efforts: B.W.H. Dr. Guy Buckle, Dr. Susan Gauthier, Dr. Maria Houtchens, Dr. Sarnia Khoury, Lynn Stazzone NP. We also thank the following University of Finland clinicians for contributions to sample collection efforts: Dr. Pentti J Tienari, Dr. Marja-Liisa Surnelahti, Dr. Irina Elovaara, Dr. Keijo Koivisto, Dr. Tuula Pirttil, Dr. Mauri Reunanen. This work was supported by grants from the NIH R01SN24247, NIH P01 A039671. P.L.D. has a Harry Weaver Neuroscience Scholar Award from the National Multiple Scelrosis Society; he is also a William C. Fowler Scholar in Multiple Sclerosis Research and is supported by National Institute of Neurological Disorders and Stroke K08 grant, NS46341. DAH is a Jacob Javits Scholar of the National Institutes of Health. B.D. is a Clinical Investigator and A.G. is a Postdoctoral Fellow of the Research Foundation Flanders, Belgium (F.W.O.-Vlaanderen). J.L.M. is supported by a postdoctoral fellowship (FG-1718-Al) from the National Multiple Sclerosis Society. The International Multiple Sclerosis Genetics Consortium is supported by R01 NS049477. LP is supported by NINDS, R01 NS43559, and the Neuropromise European Union project, LSHM-CT-2005-018637. D.R. is supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences. The RNA data on MS and CIS subjects from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital study was generated as part of a collaboration with Affymetrix, Inc. NR 32 TC 97 Z9 97 U1 3 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 2009 VL 106 IS 13 BP 5264 EP 5269 DI 10.1073/pnas.0813310106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 427PG UT WOS:000264790600057 PM 19237575 ER PT J AU Kuang, FL Luo, ZH Scharff, MD AF Kuang, Fei Li Luo, Zhonghui Scharff, Matthew D. TI H3 trimethyl K9 and H3 acetyl K9 chromatin modifications are associated with class switch recombination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE activation-induced cytoside deaminase; B cells; ChIP; immunoglobulin ID ACTIVATION-INDUCED DEAMINASE; S-MU REGION; SOMATIC HYPERMUTATION; HISTONE MODIFICATIONS; LYSINE-9 METHYLATION; V(D)J RECOMBINATION; AID; TRANSCRIPTION; MUTATIONS; REARRANGEMENT AB Class switch recombination (CSR) involves a DNA rearrangement in the Ig heavy chain (IgH) gene that allows the same variable (V) region to be expressed with any one of the downstream constant region (C) genes to encode antibodies with many different effector functions. One hypothesis for how CSR is targeted to different C region genes is that histone modifications increase accessibility and/or recruit activation-induced cytosine deaminase (AID) and its associated processes to particular donor and recipient switch regions. In this work, we identified H3 acetyl K9 and H3 trimethyl K9 as histone modifications that correlate with the recombining pair of donor and recipient switch regions. The appearance of H3 trimethyl K9 is surprising because usually it is thought to mark silent genes and heterochromatin. Nevertheless, the time course of appearance of these histone modifications, the regions in IgH they associate with, and their appearance independent of AID damage suggest that both modifications play a role in targeting CSR. C1 [Kuang, Fei Li; Luo, Zhonghui; Scharff, Matthew D.] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. [Luo, Zhonghui] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Scharff, MD (reprint author), Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM scharff@aecom.yu.edu FU Albert Einstein College of Medicine Cancer Center [P30CA013330]; Medical Scientist Training Program [T32GM007288]; National Institutes of Health [R01CA72649, R01CA102705]; National Women's Division of Albert Einstein College of Medicine FX We thank members of the Scharff and Birshtein laboratories, M. Sadofsky, H. Ye, and B. Diamond for helpful discussions. We thank B. K. Birshtein and A. Skoultchi for critical reading of the manuscript, and T. Honjo for AID-deficient mice. This work was supported by the Albert Einstein College of Medicine Cancer Center Flow Cytometry Core Facility Grant P30CA013330. F.L.K. and Z.L. were supported by the Medical Scientist Training Program T32GM007288; and M.D.S. was supported by National Institutes of Health Grants R01CA72649 and R01CA102705 and by the Harry Eagle Chair provided by the National Women's Division of Albert Einstein College of Medicine. NR 40 TC 35 Z9 35 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 2009 VL 106 IS 13 BP 5288 EP 5293 DI 10.1073/pnas.0901368106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 427PG UT WOS:000264790600061 PM 19276123 ER PT J AU Sergi, MJ Fiske, AP Horan, WP Kern, RS Kee, KS Subotnik, KL Nuechterlein, KH Green, MF AF Sergi, Mark J. Fiske, Alan P. Horan, William P. Kern, Robert S. Kee, Kimmy S. Subotnik, Kenneth L. Nuechterlein, Keith H. Green, Michael F. TI Development of a measure of relationship perception in schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE Schizophrenia; Relationship perception; Relationships Across Domains; Social cognition; Relational models theory; Community functioning ID SOCIAL-PERCEPTION; NEUROCOGNITIVE DEFICITS; MODELS THEORY; COGNITION; RECOGNITION; PERFORMANCE; MEDIATOR; ERRORS; TESTS; FORMS AB Relationships Across Domains (RAD) is a new measure of competence in relationship perception that may be used to assess clinically stable persons with schizophrenia and healthy persons. The structure and content of the RAD are grounded in relational models theory, a well-validated theory of social relations. The 75-item RAD contains 25 vignettes and can be administered in approximately 35 min. The RAD requires participants to implicitly identify the relational model of a dyad described in a brief vignette and infer how the members of the dyad are likely to behave in three other social contexts. The RAD demonstrated good internal consistency in schizophrenia outpatients and healthy participants matched to the outpatients in age and education. The schizophrenia outpatients performed more poorly on the RAD than two healthy comparison groups, supporting the ability of the RAD to discriminate between clinical and non-clinical populations. The schizophrenia patients' performance on the RAD was moderately related to reading ability and several domains of community functioning. (c) 2008 Elsevier Ireland Ltd. All fights reserved. C1 [Sergi, Mark J.] Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. [Sergi, Mark J.; Horan, William P.; Kern, Robert S.; Kee, Kimmy S.; Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fiske, Alan P.] Univ Calif Los Angeles, Dept Anthropol, Ctr Culture Brain & Dev, Los Angeles, CA USA. [Fiske, Alan P.] Univ Calif Los Angeles, Ctr Behav Evolut & Culture, Los Angeles, CA USA. [Horan, William P.; Kern, Robert S.; Kee, Kimmy S.; Subotnik, Kenneth L.; Nuechterlein, Keith H.; Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Kee, Kimmy S.] Calif State Univ Channel Isl, Psychol Program, Camarillo, CA USA. [Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. RP Sergi, MJ (reprint author), Calif State Univ Northridge, Dept Psychol, 18111 Nordhoff St, Northridge, CA 91330 USA. EM mark.sergi@csun.edu FU National Institute of Mental Health Translational Research Center [MH66286]; National Institute of Mental Health [MH43292, MH65707]; Department of Veterans Affairs VISN-22 Mental Illness Research Education Clinical Center FX This research was supported by the National Institute of Mental Health Translational Research Center (MH66286; Keith H. Nuechterlein, Director), Dr. Green's grants from the National Institute of Mental Health (MH43292 and MH65707), and the Department of Veterans Affairs VISN-22 Mental Illness Research Education Clinical Center. The authors thank Jim Mintz, Ph.D., of the UCLA Sernel Neuropsychiatric Institute Biostatistical Core for his consultation regarding the construction of Relationships Across Domains. The authors thank Nicholas Haslam, Ph.D., for his advice on the development of the RAD and his comments on an earlier version of this paper. The authors also thank Karen Cornelius, Psy.D., Shauna Davidson, M.A., Mark McGee, B.A., and Poorang Nori, B.A., for their assistance with the recruitment of participants and/or the collection and coding of data. NR 40 TC 15 Z9 16 U1 1 U2 3 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 MAR 31 PY 2009 VL 166 IS 1 BP 54 EP 62 DI 10.1016/j.psychres.2008.03.010 PG 9 WC Psychiatry SC Psychiatry GA 425CT UT WOS:000264615300007 PM 19193447 ER PT J AU Haley, RW Spence, JS Carmack, PS Gunst, RF Schucany, WR Petty, F Devous, MD Bonte, FJ Trivedi, MH AF Haley, Robert W. Spence, Jeffrey S. Carmack, Patrick S. Gunst, Richard F. Schucany, William R. Petty, Frederick Devous, Michael D., Sr. Bonte, Frederick J. Trivedi, Madhukar H. TI Abnormal brain response to cholinergic challenge in chronic encephalopathy from the 1991 Gulf War SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Tomography, emission-computed, single-photon; Physostigmine; Brain diseases; Regional blood flow; Persian Gulf syndrome; Veterans ID CEREBRAL BLOOD-FLOW; US ARMY VETERANS; FUNCTIONAL STATUS; MR SPECTROSCOPY; CASE-DEFINITION; SARIN; PHYSOSTIGMINE; EXPOSURE; ILLNESS; TALAIRACH AB Several case definitions of chronic illness in veterans of the 1991 Persian Gulf War have been linked epidemiologically with environmental exposure to cholinesterase-inhibiting chemicals, which cause chronic changes in cholinergic receptors in animal models. Twenty-one chronically ill Gulf War veterans (5 with symptom complex 1, 11 with complex 2, and 5 with complex 3) and 17 age-, sex- and education-matched controls, underwent an 99mTc-HMPAO-SPECT brain scan following infusion of saline and >48 h later a second scan following infusion of physostigmine in saline. From each SPECT image mean normalized regional cerebral blood flow (nrCBF) from 39 small blocks of correlated voxels were extracted with geostatistical spatial modeling from eight deep gray matter structures in each hemisphere. Baseline nrCBF in symptom complex 2 was lower than controls throughout deep structures. The change in nrCBF after physostigmine (challenge minus baseline) was negative in complexes I and 3 and controls but positive in complex 2 in some structures. Since effects were opposite in different groups, no finding typified the entire patient sample. A hold-out discriminant model of nrCBF from 17 deep brain blocks predicted membership in the clinical groups with sensitivity of 0.95 and specificity of 0.82. Gulf War-associated chronic encephalopathy in a subset of veterans may be due to neuronal dysfunction, including abnormal cholinergic response, in deep brain structures. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Haley, Robert W.; Spence, Jeffrey S.; Carmack, Patrick S.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Epidemiol, Dallas, TX 75390 USA. [Haley, Robert W.; Spence, Jeffrey S.; Carmack, Patrick S.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Spence, Jeffrey S.; Carmack, Patrick S.; Gunst, Richard F.; Schucany, William R.] So Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA. [Petty, Frederick; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Petty, Frederick] US Dept Vet Affairs, Med Ctr, Dallas, TX USA. [Devous, Michael D., Sr.; Bonte, Frederick J.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Nucl Med Ctr, Dallas, TX 75390 USA. RP Haley, RW (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Epidemiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Robert.Haley@UTSouthwestern.edu RI Haley, Robert/P-9026-2014 OI Haley, Robert/0000-0001-8849-9579 NR 59 TC 19 Z9 21 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAR 31 PY 2009 VL 171 IS 3 BP 207 EP 220 DI 10.1016/j.pscychresns.2008.05.004 PG 14 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 426HG UT WOS:000264698000007 PM 19230625 ER PT J AU Berdichevsky, Y Sabolek, H Levine, JB Staley, KJ Yarmush, ML AF Berdichevsky, Yevgeny Sabolek, Helen Levine, John B. Staley, Kevin J. Yarmush, Martin L. TI Microfluidics and multielectrode array-compatible organotypic slice culture method SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Organotypic; Hippocampus; Multielectrode array; MEA; PDMS; Soft lithography; Microchannel; Axon ID MICROELECTRODE ARRAYS; NERVOUS-TISSUE; GROWTH; GRADIENTS; PLATFORM; CHIPS; CUES AB Organotypic brain slice cultures are used for a variety of molecular, electrophysiological, and imaging studies. However, the existing culture methods are difficult or expensive to apply in studies requiring long-term recordings with multielectrode arrays (MEAs). In this work, a novel method to maintain organotypic cultures of rodent hippocampus for several weeks on standard MEAs in an unmodified tissue culture incubator is described. Polydimethylsiloxane (Sylgard) mini-wells were used to stabilize organotypic cultures on glass and MEA surfaces. Hippocampus slices were successfully maintained within PDMS mini-wells for multiple weeks, with preserved pyramidal layer organization, connectivity, and activity. MEAs were used to record the development of spontaneous activity in an organotypic cultures for 4 weeks. This method is compatible with integration of microchannels into the culture substrate. Microchannels were incorporated into the mini-wells and applied to the guidance of axons originating within the slice, paving the way for studies of axonal sprouting using organotypic slices. (C) 2008 Elsevier B.V. All rights reserved. C1 [Berdichevsky, Yevgeny; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Engn Med, Boston, MA 02114 USA. [Sabolek, Helen; Staley, Kevin J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Levine, John B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Engn Med, 51 Blossom St,Rm 406, Boston, MA 02114 USA. EM ireis@sbi.org RI Levine, John/G-6221-2015 FU NIH [P41 E13002503, F32 MH079662] FX This work was supported in part by NIH P41 E13002503. Y.B. was supported by NIH F32 MH079662. NR 24 TC 33 Z9 34 U1 2 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAR 30 PY 2009 VL 178 IS 1 BP 59 EP 64 DI 10.1016/j.jneumeth.2008.11.016 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 416NO UT WOS:000264013000009 PM 19100768 ER PT J AU Chen, Y Aguirre, AD Ruvinskaya, L Devor, A Boas, DA Fujimoto, JG AF Chen, Yu Aguirre, Aaron D. Ruvinskaya, Lana Devor, Anna Boas, David A. Fujimoto, James G. TI Optical coherence tomography (OCT) reveals depth-resolved dynamics during functional brain activation SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Optical coherence tomography (OCT); Functional optical coherence tomography; Optical intrinsic signal imaging (OISI); Depth-resolved functional dynamics; Somatosensory cortex; Scattering change; Retrograde vessel dilation ID RAT SOMATOSENSORY CORTEX; NEURONAL-ACTIVITY; IN-VIVO; VISUAL-CORTEX; BLOOD-FLOW; NEURAL ACTIVITY; HEMODYNAMIC-CHANGES; RETINAL PHYSIOLOGY; SCATTERING CHANGES; OXYGEN-METABOLISM AB Optical intrinsic signal imaging (OISI) provides two-dimensional, depth-integrated activation maps of brain activity. Optical coherence tomography (OCT) provides depth-resolved, cross-sectional images of functional brain activation. Co-registered OCT and OISI imaging was performed simultaneously on the rat somatosensory cortex through a thinned skull during forepaw electrical stimulation. Fractional signal change measurements made by OCT revealed a functional signal that correlates well with that of the intrinsic hemodynamic signals and provides depth-resolved, layer-specific dynamics in the functional activation patterns indicating retrograde vessel dilation. OCT is a promising a new technology which provides complementary information to OISI for functional neuroimaging. (C) 2008 Elsevier B.V. All rights reserved. C1 [Chen, Yu; Aguirre, Aaron D.; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Chen, Yu; Aguirre, Aaron D.; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Aguirre, Aaron D.; Boas, David A.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Ruvinskaya, Lana; Devor, Anna; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Devor, Anna] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92093 USA. [Devor, Anna] Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA. RP Fujimoto, JG (reprint author), MIT, Elect Res Lab, 50 Vassar St,Rm 36-361, Cambridge, MA 02139 USA. EM jgfuji@mit.edu FU Air Force Office of Scientific Research Medical Free Electron Laser Program [FA9550-07-1-0101, FA9550-07-1-0014]; National Institutes of Health [R01-EB00790, R01-NS057476, R01-NS-051188, R01-EY011289-23, R01-CA75289-10, F31-EB005978-03]; Whitaker Foundation FX The authors thank Drs. Elizabeth M. Hillman, Shuai Yuan, Chao Zhou, Sava Sakadzic, Qianqian Fang, and Guangyu Zhang for helpful discussions and technical assistance. Also we thank James Jiang and Alex Cable (Thorlabs Inc.) for providing the swept-source OCT system for obtaining the Fourier-domain OCT results. This research was supported by the Air Force Office of Scientific Research Medical Free Electron Laser Program FA9550-07-1-0101 and FA9550-07-1-0014, and the National Institutes of Health R01-EB00790, R01-NS057476, R01-NS-051188, R01-EY011289-23, and R01-CA75289-10. A.D. Aguirre acknowledges support from the Whitaker Foundation and the National Institutes of Health F31-EB005978-03. NR 46 TC 32 Z9 32 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAR 30 PY 2009 VL 178 IS 1 BP 162 EP 173 DI 10.1016/j.jneumeth.2008.11.026 PG 12 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 416NO UT WOS:000264013000023 PM 19121336 ER PT J AU Rad, AM Iskander, ASM Janic, B Knight, RA Arbab, AS Soltanian-Zadeh, H AF Rad, Ali M. Iskander, A. S. M. Janic, Branislava Knight, Robert A. Arbab, Ali S. Soltanian-Zadeh, Hamid TI AC133+progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study SO BMC BIOTECHNOLOGY LA English DT Article ID ENDOTHELIAL PROGENITOR CELLS; MESENCHYMAL STEM-CELLS; BREAST-CANCER CELLS; SUPERPARAMAGNETIC IRON-OXIDE; VESICULAR STOMATITIS-VIRUS; MODIFIED CD34(+) CELLS; IN-VIVO; SUICIDE GENE; PERIPHERAL-BLOOD; GLIOMA MODEL AB Background: Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC) can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI). In this study, we used superparamagentic iron oxide (SPIO)-labeled APCs to carry the human sodium iodide symporter (hNIS) gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m) scan. Results: Three million human breast cancer (MDA-MB-231) cells were subcutaneously implanted in the right flank of nude mice. APCs, isolated from fresh human cord blood, were genetically transformed to carry the hNIS gene using adenoviral vectors and magnetically labeled with ferumoxides-protamine sulfate (FePro) complexes. Magnetically labeled genetically transformed cells were administered intravenously in tumor bearing mice when tumors reached 0.5 cm in the largest dimension. MRI and single photon emission computed tomography (SPECT) images were acquired 3 and 7 days after cell injection, with a 7 Tesla animal MRI system and a custom built micro-SPECT using Tc-99m, respectively. Expression of hNIS in accumulated cells was determined by staining with anti-hNIS antibody. APCs were efficiently labeled with ferumoxide-protamine sulfate (FePro) complexes and transduced with hNIS gene. Our study showed not only the accumulation of intravenously administered genetically transformed, magnetically labeled APCs in the implanted breast cancer, but also the expression of hNIS gene at the tumor site. Tc-99m activity ratio (tumor/non-tumor) was significantly different between animals that received non-transduced and transduced cells (P < 0.001). Conclusion: This study indicates that genetically transformed, magnetically labeled APCs can be used both as delivery vehicles and cellular probes for detecting in vivo migration and homing of cells. Furthermore, they can potentially be used as a gene carrier system for the treatment of tumor or other diseases. C1 [Rad, Ali M.; Iskander, A. S. M.; Janic, Branislava; Arbab, Ali S.; Soltanian-Zadeh, Hamid] Henry Ford Hosp, Dept Radiol, Detroit, MI 48202 USA. [Rad, Ali M.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Knight, Robert A.] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Soltanian-Zadeh, Hamid] Univ Tehran, Dept Elect & Comp Engn, Control & Intelligent Proc Ctr Excellence, Tehran, Iran. RP Soltanian-Zadeh, H (reprint author), Henry Ford Hosp, Dept Radiol, Detroit, MI 48202 USA. EM alirad@rad.hfh.edu; aiskander@rad.hfh.edu; bjanic@rad.hfh.edu; RKNIGHT1@hfhs.org; saali@rad.hfh.edu; hamids@rad.hfh.edu RI Soltanian-Zadeh, Hamid/K-2903-2016 OI Soltanian-Zadeh, Hamid/0000-0002-7302-6856 FU Department of Defense [W81XWH-06-1-0576]; National Institutes of Health (NIH) [EB002450, CA122031, NS058589] FX This work was supported in part by the Department of Defense Breast Cancer Research Program under grant number W81XWH-06-1-0576 and by the National Institutes of Health (NIH) under grant numbers EB002450, CA122031, and NS058589. NR 65 TC 16 Z9 18 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD MAR 27 PY 2009 VL 9 AR 28 DI 10.1186/1472-6750-9-28 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 439DR UT WOS:000265608300001 PM 19327159 ER PT J AU Hoe, HS Fu, ZY Makarova, A Lee, JY Lu, CY Feng, L Pajoohesh-Ganji, A Matsuoka, Y Hyman, BT Ehlers, MD Vicini, S Pak, DTS Rebeck, GW AF Hoe, Hyang-Sook Fu, Zhanyan Makarova, Alexandra Lee, Ji-Yun Lu, Congyi Feng, Li Pajoohesh-Ganji, Ahdeah Matsuoka, Yasuji Hyman, Bradley T. Ehlers, Michael D. Vicini, Stefano Pak, Daniel T. S. Rebeck, G. William TI The Effects of Amyloid Precursor Protein on Postsynaptic Composition and Activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREBELLAR GRANULE NEURONS; NMDA RECEPTOR SUBUNITS; LONG-TERM POTENTIATION; D-ASPARTATE RECEPTORS; IN-VIVO; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; DIFFERENTIAL ROLES; NR2A SUBUNIT; BETA AB The amyloid precursor protein (APP) is cleaved to produce the Alzheimer disease-associated peptide A beta, but the normal functions of uncleaved APP in the brain are unknown. We found that APP was present in the postsynaptic density of central excitatory synapses and coimmunoprecipitated with N-methyl-D-aspartate receptors (NMDARs). The presence of APP in the postsynaptic density was supported by the observation that NMDARs regulated trafficking and processing of APP; overexpression of the NR1 subunit increased surface levels of APP, whereas activation of NMDARs decreased surface APP and promoted production of A beta. We transfected APP or APP RNA interference into primary neurons and used electrophysiological techniques to explore the effects of APP on postsynaptic function. Reduction of APP decreased (and overexpression of APP increased) NMDAR whole cell current density and peak amplitude of spontaneous miniature excitatory postsynaptic currents. The increase in NMDAR current by APP was due to specific recruitment of additional NR2B-containing receptors. Consistent with these findings, immunohistochemical experiments demonstrated that APP increased the surface levels and decreased internalization of NR2B subunits. These results demonstrate a novel physiological role of postsynaptic APP in enhancing NMDAR function. C1 [Pajoohesh-Ganji, Ahdeah; Rebeck, G. William] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. [Fu, Zhanyan; Lu, Congyi; Feng, Li; Vicini, Stefano] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA. [Lee, Ji-Yun; Pak, Daniel T. S.] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20057 USA. [Matsuoka, Yasuji] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. [Makarova, Alexandra; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Disorders, Charlestown, MA 02129 USA. [Ehlers, Michael D.] Duke Univ, Med Ctr, Dept Neurobiol, Howard Hughes Med Inst, Durham, NC 27710 USA. RP Rebeck, GW (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, 3970 Reservoir Rd NW, Washington, DC 20057 USA. EM gwr2@georgetown.edu RI Feng, Li Rebekah/A-5678-2009; Lee, Ji-Yun/F-8127-2013; Lu, Congyi/G-3984-2013 FU National Institutes of Health Grants [AG14473, NS48085, AG032330] FX This work was supported, in whole or in part, by National Institutes of Health Grants AG14473 ( to G. W. R.), NS48085 ( to D. T. S. P.), NS047700 ( to S. V.), AG12406 ( to B. T. H.), AG032330 ( to H. S. H.). This work is also supported by the Alzheimer's Research Fund in memory of Bill and Marie Drach. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked " advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 48 TC 54 Z9 56 U1 2 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 MAR 27 PY 2009 VL 284 IS 13 BP 8495 EP 8506 DI 10.1074/jbc.M900141200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421ZW UT WOS:000264397800034 PM 19164281 ER PT J AU Hartong, DT Mcgee, TL Sandberg, MA Berson, EL Asselbergs, FW van der Harst, P De Vivo, I Dryja, TP AF Hartong, Dyonne T. McGee, Terri L. Sandberg, Michael A. Berson, Eliot L. Asselbergs, Folkert W. van der Harst, Pim De Vivo, Immaculata Dryja, Thaddeus P. TI Search for a correlation between telomere length and severity of retinitis pigmentosa due to the dominant rhodopsin Pro23His mutation SO MOLECULAR VISION LA English DT Article ID CLINICAL EXPRESSION; OCULAR FINDINGS; GENE; REDUCTION; DISEASE; TUMOR AB Purpose: Great variation exists in the age of onset of symptoms and the severity of disease at a given age in patients with retinitis pigmentosa ( RP). The final pathway for this disease may involve apoptotic photoreceptor cell death. Telomere length is associated with biologic aging, senescence, and apoptosis. We evaluated whether the length of telomeres in leukocytes correlated with the severity of RP in patients with the Pro23His rhodopsin mutation who have shown marked heterogeneity in disease severity. Methods: We evaluated 122 patients with the Pro23His rhodopsin mutation. The patients' retinal function was stratified according to their 30-Hz cone electroretinogram (ERG). The length of telomeres in leukocytes was measured by the quantitative real time polymerase chain reaction (qRT-PCR) method in the 15 patients with the highest age-adjusted 30Hz ERG amplitudes and in the 15 patients with the lowest amplitudes. Results: Mean leukocyte telomere length was similar in the 15 patients with the highest cone ERG amplitudes (median: 0.40 units; interquartile range 0.36-0.56) and the 15 patients with the lowest cone amplitudes (median: 0.41 units; inter quartile range 0.34-0.64; p=0.95). Conclusions: We found no evidence for an association between telomere length and the severity of RP as monitored by the cone ERG in patients with the Pro23His rhodopsin mutation. C1 [Hartong, Dyonne T.] Univ Groningen, Dept Ophthalmol, Univ Med Ctr Groningen, NL-9713 GZ Groningen, Netherlands. [Hartong, Dyonne T.; McGee, Terri L.; Dryja, Thaddeus P.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. [McGee, Terri L.; Sandberg, Michael A.; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. [Asselbergs, Folkert W.; van der Harst, Pim] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, NL-9713 GZ Groningen, Netherlands. [De Vivo, Immaculata] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. RP Hartong, DT (reprint author), Univ Groningen, Dept Ophthalmol, Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM d.t.hartong@ohk.umcg.nl FU NEI [EY00169, EY08683]; NIH [CA082838, CA132190]; Foundation Fighting Blindness FX This work was supported by NEI grants EY00169, EY08683, NIH grants CA082838 and CA132190, and the Foundation Fighting Blindness (Owing Mills, MD). NR 39 TC 3 Z9 3 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD MAR 27 PY 2009 VL 15 IS 60-62 BP 592 EP 597 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 427TM UT WOS:000264802000001 PM 19325938 ER PT J AU Dutta, D Ensminger, AW Zucker, JP Chess, A AF Dutta, Devkanya Ensminger, Alexander W. Zucker, Jacob P. Chess, Andrew TI Asynchronous Replication and Autosome-Pair Non-Equivalence in Human Embryonic Stem Cells SO PLOS ONE LA English DT Article AB A number of mammalian genes exhibit the unusual properties of random monoallelic expression and random asynchronous replication. Such exceptional genes include genes subject to X inactivation and autosomal genes including odorant receptors, immunoglobulins, interleukins, pheromone receptors, and p120 catenin. In differentiated cells, random asynchronous replication of interspersed autosomal genes is coordinated at the whole chromosome level, indicative of chromosome-pair non-equivalence. Here we have investigated the replication pattern of the random asynchronously replicating genes in undifferentiated human embryonic stem cells, using fluorescence in situ hybridization based assay. We show that allele-specific replication of X-linked genes and random monoallelic autosomal genes occur in human embryonic stem cells. The direction of replication is coordinated at the whole chromosome level and can cross the centromere, indicating the existence of autosome-pair non-equivalence in human embryonic stem cells. These results suggest that epigenetic mechanism(s) that randomly distinguish between two parental alleles are emerging in the cells of the inner cell mass, the source of human embryonic stem cells. C1 [Dutta, Devkanya; Ensminger, Alexander W.; Zucker, Jacob P.; Chess, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. RP Dutta, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. EM chess@chgr.mgh.harvard.edu FU National Institute of Health FX This work is supported by funding obtained from National Institute of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 7 Z9 7 U1 0 U2 9 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 MAR 27 PY 2009 VL 4 IS 3 AR e4970 DI 10.1371/journal.pone.0004970 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437PO UT WOS:000265499600003 PM 19325893 ER PT J AU Giblin, W Chatterji, M Westfield, G Masud, T Theisen, B Cheng, HL DeVido, J Alt, FW Ferguson, DO Schatz, DG Sekiguchi, J AF Giblin, William Chatterji, Monalisa Westfield, Gerwin Masud, Tehmina Theisen, Brian Cheng, Hwei-Ling DeVido, Jeffrey Alt, Frederick W. Ferguson, David O. Schatz, David G. Sekiguchi, JoAnn TI Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation SO BLOOD LA English DT Article ID FREE V(D)J RECOMBINATION; DOUBLE-STRAND BREAKS; CODING END SEQUENCE; T-CELL DEVELOPMENT; ATAXIA-TELANGIECTASIA; OMENN-SYNDROME; B-CELL; CHROMOSOMAL TRANSLOCATIONS; ONCOGENIC TRANSLOCATIONS; LYMPHOCYTE DEVELOPMENT AB The RAG1/2 endonuclease initiates programmed DNA rearrangements in progenitor lymphocytes by generating double-strand breaks at specific recombination signal sequences. This process, known as V(D)J recombination, assembles the vastly diverse antigen receptor genes from numerous V, D, and J coding segments. In vitro biochemical and cellular transfection studies suggest that RAG1/2 may also play postcleavage roles by forming complexes with the recombining ends to facilitate DNA end processing and ligation. In the current study, we examine the in vivo consequences of a mutant form of RAG1, RAG1-S723C, that is proficient for DNA cleavage, yet exhibits defects in postcleavage complex formation and end joining in vitro. We generated a knockin mouse model harboring the RAG1-S723C hypomorphic mutation and examined the immune system in this fully in vivo setting. RAG1-S723C homozygous mice exhibit impaired lymphocyte development and decreased V(D) J rearrangements. Distinct from RAG nullizygosity, the RAG1-S723C hypomorph results in aberrant DNA double-strand breaks within rearranging loci. RAG1-S723C also predisposes to thymic lymphomas associated with chromosomal translocations in a p53 mutant background, and heterozygosity for the mutant allele accelerates age-associated immune system dysfunction. Thus, our study provides in vivo evidence that implicates aberrant RAG1/2 activity in lymphoid tumor development and premature immunosenescence. (Blood. 2009; 113: 2965-2975) C1 [Giblin, William; Westfield, Gerwin; Sekiguchi, JoAnn] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Chatterji, Monalisa; Schatz, David G.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Westfield, Gerwin; Theisen, Brian; Ferguson, David O.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Masud, Tehmina; Sekiguchi, JoAnn] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Cheng, Hwei-Ling; Alt, Frederick W.; Schatz, David G.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Cheng, Hwei-Ling; DeVido, Jeffrey; Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst,Dept Genet, Boston, MA 02115 USA. RP Sekiguchi, J (reprint author), Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. EM sekiguch@med.umich.edu RI Schatz, David/A-6748-2013; OI Schatz, David/0000-0002-5669-1176; Sekiguchi, JoAnn/0000-0002-7178-4258 FU National Institutes of Health; University of Michigan's Cancer Center Support Grant [5 P30 CA46592]; NIH [AI063058, AI32524, AI35714]; Pew Scholars Award; Munn IDEA award FX This work was supported in part by the National Institutes of Health (NIH, Bethesda, MD) through the University of Michigan's Cancer Center Support Grant ( 5 P30 CA46592); NIH grant AI063058 (NIAID), Pew Scholars Award ( Pew Charitable Trusts, San Francisco, CA), Munn IDEA award (UM Cancer Center, Ann Arbor, MI) to J. S.; NIH grant AI32524 ( NIAID) to D. G. S.; and NIH grant AI35714 ( NIAID) to F. W. A. T. M. is a Fulbright Scholar. D. G. S. and F. W. A. are Investigators of the Howard Hughes Medical Institute. NR 72 TC 23 Z9 23 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 MAR 26 PY 2009 VL 113 IS 13 BP 2965 EP 2975 DI 10.1182/blood-2008-07-165167 PG 11 WC Hematology SC Hematology GA 424HY UT WOS:000264559000015 PM 19126872 ER PT J AU Bianchi, G Oliva, L Cascio, P Pengo, N Fontana, F Cerruti, F Orsi, A Pasqualetto, E Mezghrani, A Calbi, V Palladini, G Giuliani, N Anderson, KC Sitia, R Cenci, S AF Bianchi, Giada Oliva, Laura Cascio, Paolo Pengo, Niccolo Fontana, Francesca Cerruti, Fulvia Orsi, Andrea Pasqualetto, Elena Mezghrani, Alexandre Calbi, Valeria Palladini, Giovanni Giuliani, Nicola Anderson, Kenneth C. Sitia, Roberto Cenci, Simone TI The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition SO BLOOD LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTION FACTOR XBP-1; PLASMA-CELLS; ER STRESS; BORTEZOMIB; EXPRESSION; PATHWAY; CANCER; DIFFERENTIATION AB Proteasome inhibitors (PIs) are effective against multiple myeloma (MM), but the mechanisms of action and bases of individual susceptibility remain unclear. Recent work linked PI sensitivity to protein synthesis and proteasome activity, raising the question whether different levels of proteasome expression and workload underlie PI sensitivity in MM cells (MMCs). Exploiting human MM lines characterized by differential PI sensitivity, we report that highly sensitive MMCs express lower proteasome levels and higher proteasomal workload than relatively PI-resistant MMCs, resulting in the accumulation of polyubiquitinated proteins at the expense of free ubiquitin (proteasome stress). Manipulating proteasome expression or workload alters apoptotic sensitivity to PI, demonstrating a cause-effect relationship between proteasome stress and apoptotic responses in MMCs. Intracellular immunostaining in primary, patient-derived MMCs reveals that polyubiquitinated proteins hallmark neoplastic plasma cells, in positive correlation with immuno-globulin (Ig) content, both intra-and interpatient. Moreover, overall proteasome activity of primary MMCs inversely correlates with apoptotic sensitivity to PI. Altogether, our data indicate that the balance between proteasome workload and degradative capacity represents a critical determinant of apoptotic sensitivity of MMCs to PI, potentially providing a framework for identifying indicators of responsiveness and designing novel combination therapies. (Blood. 2009; 113: 3040-3049) C1 [Bianchi, Giada; Oliva, Laura; Pengo, Niccolo; Fontana, Francesca; Orsi, Andrea; Pasqualetto, Elena; Sitia, Roberto; Cenci, Simone] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Bianchi, Giada; Pengo, Niccolo; Fontana, Francesca; Orsi, Andrea; Sitia, Roberto; Cenci, Simone] Univ Vita Salute San Raffaele, Milan, Italy. [Bianchi, Giada; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Myeloma Res,Dept Med Oncol, Boston, MA 02115 USA. [Bianchi, Giada; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Oliva, Laura; Pengo, Niccolo; Pasqualetto, Elena; Calbi, Valeria; Sitia, Roberto; Cenci, Simone] Ist Sci San Raffaele, Myeloma Unit, I-20132 Milan, Italy. [Cascio, Paolo; Cerruti, Fulvia] Univ Turin, Dept Vet Morphophysiol, Turin, Italy. [Fontana, Francesca; Cenci, Simone] Ist Sci San Raffaele, BoNetwork, I-20132 Milan, Italy. [Mezghrani, Alexandre] CNRS, Inst Genom Fonct, Montpellier, France. [Calbi, Valeria] Ist Sci San Raffaele, Hematol & Bone Marrow Transplantat BMT Unit, I-20132 Milan, Italy. [Palladini, Giovanni] Univ Pavia, Policlin San Matteo, Fdn Ist Ricovero & Cura Carratere Sci IRCCS, Dept Biochem,Biotechnol Res Labs,Amyloidosis Ctr, I-27100 Pavia, Italy. [Giuliani, Nicola] Univ Parma, Hematol & BMT Ctr, I-43100 Parma, Italy. RP Cenci, S (reprint author), Ist Sci San Raffaele, Div Genet & Cell Biol, DiBiT 4A3 Room 68,Via Olgettina 58, I-20132 Milan, Italy. EM cenci.simone@hsr.it RI Pengo, Niccolo/K-5009-2012; Palladini, Giovanni/G-1763-2010; Cenci, Simone/J-7700-2016; OI Pengo, Niccolo/0000-0002-9249-4786; Palladini, Giovanni/0000-0001-5994-5138; Cenci, Simone/0000-0003-1215-7518; Sitia, Roberto/0000-0001-7086-4152; Giuliani, Nicola/0000-0003-3457-3774 FU Associazione Italiana per la Ricerca sul Cancro ( AIRC, Milano, Italy); Cariplo ( NoBEL project, Milano, Italy); Ministero della Sanita, Roma, Italy; MIUR ( CoFin and Center of Excellence in Physiopathology of Cell Differentiation, Roma, Italy); Telethon, Roma, Italy FX This work was supported through grants from the Associazione Italiana per la Ricerca sul Cancro ( AIRC, Milano, Italy), Cariplo ( NoBEL project, Milano, Italy), Ministero della Sanita, Roma, Italy, MIUR ( CoFin and Center of Excellence in Physiopathology of Cell Differentiation, Roma, Italy), and Telethon, Roma, Italy. NR 53 TC 106 Z9 106 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 MAR 26 PY 2009 VL 113 IS 13 BP 3040 EP 3049 DI 10.1182/blood-2008-08-172734 PG 10 WC Hematology SC Hematology GA 424HY UT WOS:000264559000023 PM 19164601 ER PT J AU Ringden, O Pavletic, SZ Anasetti, C Barrett, AJ Wang, T Wang, D Antin, JH Di Bartolomeo, P Bolwell, BJ Bredeson, C Cairo, MS Gale, RP Gupta, V Hahn, T Hale, GA Halter, J Jagasia, M Litzow, MR Locatelli, F Marks, DI McCarthy, PL Cowan, MJ Petersdorf, EW Russell, JA Schiller, GJ Schouten, H Spellman, S Verdonck, LF Wingard, JR Horowitz, MM Arora, M AF Ringden, Olle Pavletic, Steven Z. Anasetti, Claudio Barrett, A. John Wang, Tao Wang, Dan Antin, Joseph H. Di Bartolomeo, Paolo Bolwell, Brian J. Bredeson, Christopher Cairo, Mitchell S. Gale, Robert P. Gupta, Vikas Hahn, Theresa Hale, Gregory A. Halter, Jorg Jagasia, Madan Litzow, Mark R. Locatelli, Franco Marks, David I. McCarthy, Philip L. Cowan, Morton J. Petersdorf, Effie W. Russell, James A. Schiller, Gary J. Schouten, Harry Spellman, Stephen Verdonck, Leo F. Wingard, John R. Horowitz, Mary M. Arora, Mukta TI The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HOST-DISEASE; CYCLOSPORINE-A; INCREASED RISK; DOSE CYCLOSPORINE; MYELOID-LEUKEMIA; RELAPSE AB Do some patients benefit from an unrelated donor (URD) transplant because of a stronger graft-versus-leukemia (GVL) effect? We analyzed 4099 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) undergoing a myeloablative allogeneic hematopoietic cell transplantation (HCT) from an URD (8/8 human leukocyte antigen [HLA]matched, n = 941) or HLA-identical sibling donor (n = 3158) between 1995 and 2004 reported to the CIBMTR. In the Cox regression model, acute and chronic GVHD were added as time-dependent variables. In multivariate analysis, URD transplant recipients had a higher risk for transplantation-related mortality (TRM; relative risk [RR], 2.76; P < .001) and relapse (RR, 1.50; P < .002) in patients with AML, but not ALL or CML. Chronic GVHD was associated with a lower relapse risk in all diagnoses. Leukemia-free survival (LFS) was decreased in patients with AML without acute GVHD receiving a URD transplant (RR, 2.02; P < .001) but was comparable to those receiving HLA-identical sibling transplants in patients with ALL and CML. In patients without GVHD, multivariate analysis showed similar risk of relapse but decreased LFS for URD transplants for all 3 diagnoses. In conclusion, risk of relapse was the same (ALL, CML) or worse (AML) in URD transplant recipients compared with HLA-identical sibling transplant recipients, suggesting a similar GVL effect. (Blood. 2009; 113: 3110-3118) C1 [Ringden, Olle] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Div Clin Immunol,Ctr Allogene Stem & Cell Transpl, SE-14186 Stockholm, Sweden. [Pavletic, Steven Z.; Barrett, A. John] NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, BMT Program, Tampa, FL USA. [Wang, Tao; Wang, Dan; Bredeson, Christopher; Spellman, Stephen; Horowitz, Mary M.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. [Antin, Joseph H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Di Bartolomeo, Paolo] Osped Civile, Dept Haematol, Pescara, Italy. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH USA. [Cairo, Mitchell S.] Columbia Univ, Med Ctr, New York, NY USA. [Gale, Robert P.] Ctr Adv Studies Leukemia, Los Angeles, CA USA. [Gupta, Vikas] Princess Margaret Hosp, BMT Program, Toronto, ON M4X 1K9, Canada. [Hahn, Theresa; McCarthy, Philip L.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Hale, Gregory A.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Halter, Jorg] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Locatelli, Franco] Policlin San Matteo, IRCCS, I-27100 Pavia, Italy. [Marks, David I.] United Bristol Healthcare Trust, Adult BMT Unit, Bristol, Avon, England. [Cowan, Morton J.] Univ Calif San Francisco, Childrens Hosp, BMT Div, San Francisco, CA 94143 USA. [Petersdorf, Effie W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Russell, James A.] Tom Baker Canc Clin, Dept Med, Calgary, AB, Canada. [Schiller, Gary J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Schouten, Harry] Univ Hosp Maastricht, Maastricht, Netherlands. [Verdonck, Leo F.] Univ Utrecht Hosp, Utrecht, Netherlands. [Wingard, John R.] Univ Florida, Coll Med, Hlth Sci Ctr, Gainesville, FL USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. RP Ringden, O (reprint author), Karolinska Univ, Huddinge Hosp, Karolinska Inst, Div Clin Immunol,Ctr Allogene Stem & Cell Transpl, F79, SE-14186 Stockholm, Sweden. EM Olle.Ringden@ki.se RI Halter, Joerg/C-9487-2012 FU NCI NIH HHS [R01 CA100019, U24 CA076518, U24-CA76518] NR 38 TC 96 Z9 98 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 MAR 26 PY 2009 VL 113 IS 13 BP 3110 EP 3118 DI 10.1182/blood-2008-07-163212 PG 9 WC Hematology SC Hematology GA 424HY UT WOS:000264559000031 PM 19059878 ER PT J AU LaMontagne, AD Stoddard, AM Roelofs, C Sembajwe, G Sapp, AL Sorensen, G AF LaMontagne, Anthony D. Stoddard, Anne M. Roelofs, Cora Sembajwe, Grace Sapp, Amy L. Sorensen, Glorian TI A hazardous substance exposure prevention rating method for intervention needs assessment and effectiveness evaluation: the Small Business Exposure Index SO ENVIRONMENTAL HEALTH LA English DT Article ID PRECAUTIONARY PRINCIPLE; MANUFACTURING WORKSITES; OCCUPATIONAL-SAFETY; HEALTHY DIRECTIONS; WORKING-CLASS; PROGRAMS AB Aims: This paper describes the refinement and adaptation to small business of a previously developed method for systematically prioritizing needs for intervention on hazardous substance exposures in manufacturing worksites, and evaluating intervention effectiveness. Methods: We developed a checklist containing six unique sets of yes/no variables organized in a 2 x 3 matrix of exposure potential versus exposure protection at three levels corresponding to a simplified hierarchy of controls: materials, processes, and human interface. Each of the six sets of indicator variables was reduced to a high/moderate/low rating. Ratings from the matrix were then combined to generate an exposure prevention 'Small Business Exposure Index' (SBEI) Summary score for each area. Reflecting the hierarchy of controls, material factors were weighted highest, followed by process, and then human interface. The checklist administered by an industrial hygienist during walk-through inspection (N = 149 manufacturing processes/areas in 25 small to medium-sized manufacturing worksites). One area or process per manufacturing department was assessed and rated. A second hygienist independently assessed 36 areas to evaluate inter-rater reliability. Results: The SBEI Summary scores indicated that exposures were well controlled in the majority of areas assessed (58% with rating of 1 or 2 on a 6-point scale), that there was some room for improvement in roughly one-third of areas (31% of areas rated 3 or 4), and that roughly 10% of the areas assessed were urgently in need of intervention (rated as 5 or 6). Inter-rater reliability of EP ratings was good to excellent (e. g., for SBEI Summary scores, weighted kappa = 0.73, 95% CI 0.52-0.93). Conclusion: The SBEI exposure prevention rating method is suitable for use in small/medium enterprises, has good discriminatory power and reliability, offers an inexpensive method for intervention needs assessment and effectiveness evaluation, and complements quantitative exposure assessment with an upstream prevention focus. C1 [LaMontagne, Anthony D.] Univ Melbourne, McCaughey Ctr, VicHlth Ctr Promot Mental Hlth & Community Wellbe, Melbourne Sch Populat Hlth, Melbourne, Vic 3010, Australia. [Stoddard, Anne M.] New England Res Inst, Watertown, MA 02472 USA. [Roelofs, Cora] Dept Work Environm, Lowell, MA 02130 USA. [Sembajwe, Grace; Sapp, Amy L.; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP LaMontagne, AD (reprint author), Univ Melbourne, McCaughey Ctr, VicHlth Ctr Promot Mental Hlth & Community Wellbe, Melbourne Sch Populat Hlth, Melbourne, Vic 3010, Australia. EM alamonta@unimelb.edu.au; astoddard@neriscience.com; Cora_Roelofs@uml.edu; Grace_Sembajwe@dfci.harvard.edu; asapp@hsph.harvard.edu; Glorian_Sorensen@dfci.harvard.edu FU US National Cancer Institute [5 R01 CA68087]; National Institute for Occupational Safety and Health [5 R01 OH04012] FX The authors acknowledge the essential roles of Richard Youngstrom and Wes Straub, the two industrial hygienists who also participated in the development of the SBEI, and collected the SBEI data. This paper is dedicated to Richard Youngstrom, who recently retired from a career devoted to the protection and promotion of worker health. The authors additionally acknowledge the important contributions of the following collaborators and intervention staff: Elizabeth Barbeau, Candy Combe, Elizabeth Harden, Sonia Hauser, Mary Kay Hunt, Brad Kaiser, Kerry Kokkinogenis, Ruth Lederman, Nancy Lightman, Mario Maeda, Deborah McLellan, Eugenie Olson, Lorraine Wallace, and Janelle Klar. This work would not have been possible without the participating 25 small businesses and their employees. This research was supported by US National Cancer Institute Grant number 5 R01 CA68087, and the National Institute for Occupational Safety and Health Grant number 5 R01 OH04012. The authors thank the workers and managers at study sites for their participation in the Healthy Directions-Small Business study. NR 21 TC 1 Z9 1 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD MAR 26 PY 2009 VL 8 AR 10 DI 10.1186/1476-069X-8-10 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 444UB UT WOS:000266004800001 PM 19323840 ER PT J AU Goldstein, MA Goodman, A del Carmen, MG Wilbur, DC AF Goldstein, Mark A. Goodman, Annekathryn del Carmen, Marcela G. Wilbur, David C. TI A Woman with an Abnormal Papanicolaou Smear CIN 3 (severe dysplasia or carcinoma in situ) of the uterine cervix. Endocervical adenocarcinoma in situ SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS INTRAEPITHELIAL LESIONS; RANDOMIZED CONTROLLED-TRIAL; YOUNG-WOMEN; NATURAL-HISTORY; PARTICLE VACCINE; QUADRIVALENT VACCINE; RISK-FACTORS; NEOPLASIA; CANCER C1 [Goldstein, Mark A.] Massachusetts Gen Hosp, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. [Goodman, Annekathryn; del Carmen, Marcela G.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [Goodman, Annekathryn; del Carmen, Marcela G.] Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Goldstein, Mark A.] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Goodman, Annekathryn; del Carmen, Marcela G.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. [Wilbur, David C.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Goldstein, MA (reprint author), Massachusetts Gen Hosp, Div Adolescent & Young Adult Med, Boston, MA 02114 USA. NR 38 TC 9 Z9 11 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 26 PY 2009 VL 360 IS 13 BP 1337 EP 1344 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 423VP UT WOS:000264524100011 PM 19321871 ER PT J AU Barry, MJ AF Barry, Michael J. TI Screening for Prostate Cancer - The Controversy That Refuses to Die SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ANTIGEN; MEN C1 [Barry, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barry, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 182 Z9 184 U1 0 U2 12 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 MAR 26 PY 2009 VL 360 IS 13 BP 1351 EP 1354 DI 10.1056/NEJMe0901166 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 423VP UT WOS:000264524100014 PM 19297564 ER PT J AU Turenius, CI Htut, MM Prodon, DA Ebersole, PL Ngo, PT Lara, RN Wilczynski, JL Stanley, BG AF Turenius, Christine I. Htut, Myat M. Prodon, Daniel A. Ebersole, Priscilla L. Ngo, Phuong T. Lara, Raul N. Wilczynski, Jennifer L. Stanley, B. Glenn TI GABA(A) receptors in the lateral hypothalamus as mediators of satiety and body weight regulation SO BRAIN RESEARCH LA English DT Article DE GABA; Receptor; Feeding; Suppression; Lateral hypothalamus; Rat ID D-ASPARTIC ACID; ELICITS FEEDING-BEHAVIOR; NUCLEUS-ACCUMBENS SHELL; RAT HYPOTHALAMUS; FOOD-INTAKE; REVERSE MICRODIALYSIS; NEURONS; GLUTAMATE; MUSCIMOL; SYSTEMS AB In the lateral hypothalamus (LH), the inhibitory amino acid neurotransmitter, GABA, has had a long-standing presumptive role as an inhibitor of food intake. However, minimal investigation has been focused on GABA, especially as compared to the attention received by many peptide transmitters. To begin to address this deficiency in the understanding of the role of GABA in the LH and feeding, we report that antagonism of GABA(A) receptors in the rat LH elicits feeding, consistent with previous findings, and provide evidence for the behavioral selectivity of this effect. We extend previous findings that activation of LH GABA(A) receptors suppresses feeding, in particular by showing that night-time and deprivation-induced eating are dramatically suppressed. Finally, we show that chronic activation, but not blockade, of the LH GABA(A) receptors leads to a reduction in 24 h food intake with concomitant body weight loss. These data collectively suggest that activation of GABA(A) receptors plays a fundamental role in controlling food intake and body weight, a role that has previously been somewhat underestimated. Published by Elsevier B.V. C1 [Turenius, Christine I.; Stanley, B. Glenn] Univ Calif Riverside, Interdept Neurosci Grad Program, Riverside, CA 92521 USA. [Htut, Myat M.; Prodon, Daniel A.; Ebersole, Priscilla L.; Ngo, Phuong T.; Lara, Raul N.; Wilczynski, Jennifer L.; Stanley, B. Glenn] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Stanley, B. Glenn] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA. RP Turenius, CI (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM turenius@u.washington.edu NR 51 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 25 PY 2009 VL 1262 BP 16 EP 24 DI 10.1016/j.brainres.2009.01.016 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 429XY UT WOS:000264954600003 PM 19401161 ER PT J AU Dobscha, SK Corson, K Perrin, NA Hanson, GC Leibowitz, RQ Doak, MN Dickinson, KC Sullivan, MD Gerrity, MS AF Dobscha, Steven K. Corson, Kathryn Perrin, Nancy A. Hanson, Ginger C. Leibowitz, Ruth Q. Doak, Melanie N. Dickinson, Kathryn C. Sullivan, Mark D. Gerrity, Martha S. TI Collaborative Care for Chronic Pain in Primary Care A Cluster Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHRONIC NONCANCER PAIN; CLINICALLY IMPORTANT DIFFERENCE; IMPROVING PRIMARY-CARE; LOW-BACK-PAIN; DEPRESSION CARE; OUTCOME MEASURES; CHRONIC ILLNESS; SCREENING-TEST; HEALTH-STATUS; MANAGEMENT AB Context Chronic pain is common in primary care patients and is associated with distress, disability, and increased health care use. Objective To assess whether a collaborative intervention can improve chronic pain related outcomes, including comorbid depression severity, in a Department of Veterans Affairs primary care setting. Design, Setting, and Participants Cluster randomized controlled trial of a collaborative care assistance with pain treatment intervention vs treatment as usual at 5 primary care clinics of 1 Department of Veterans Affairs Medical Center. Forty-two primary care clinicians were randomized to the assistance with pain treatment intervention group or the treatment as usual group. The 401 patients had musculoskeletal pain diagnoses, moderate or greater pain intensity, and disability lasting 12 weeks or longer and were assigned to the same treatment groups as their clinicians. Recruitment occurred from January 2006 to January 2007 and follow-up concluded in January 2008. Intervention Assistance with pain treatment included a 2-session clinician education program, patient assessment, education and activation, symptom monitoring, feedback and recommendations to clinicians, and facilitation of specialty care. Main Outcome Measures Changes over 12 months in pain-related disability (Roland-Morris Disability Questionnaire, range of 0-24), pain intensity (Chronic Pain Grade [CPG] Pain Intensity subscale, range of 0-100), and depression (Patient Health Questionnaire 9 [PHQ-9], range of 0-27), measured as beta coefficients (difference in slopes in points per month). Results Intervention patients had a mean (SD) of 10.6 (4.5) contacts with the assistance with pain treatment team. Compared with the patients receiving treatment as usual, intervention patients showed greater improvements in pain-related disability (Roland-Morris Disability Questionnaire beta, -0.101 [95% confidence interval {CI}, -0.163 to -0.040]; P=.004 and CPG Pain Intensity subscale beta, -0.270 [95% CI, -0.480 to -0.061]; P=.01). Among patients with baseline depression (PHQ-9 score >= 10), there was greater improvement in depression severity in patients receiving the intervention compared with patients receiving treatment as usual (PHQ-9 beta, -0.177 [95% CI, -0.295 to -0.060]; P=.003). The differences in scores between baseline and 12 months for the assistance with pain treatment intervention group and the treatment as usual group, respectively, were -1.4 vs -0.2 for the Roland-Morris Disability Questionnaire, -4.7 vs -0.6 for the CPG Pain Intensity subscale, and -3.7 vs -1.2 for PHQ-9. Conclusion The assistance with pain treatment collaborative intervention resulted in modest but statistically significant improvement in a variety of outcome measures. Trial Registration clinicaltrials.gov Identifier: NCT00129480 C1 [Dobscha, Steven K.; Corson, Kathryn; Leibowitz, Ruth Q.; Dickinson, Kathryn C.; Gerrity, Martha S.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR 97239 USA. [Doak, Melanie N.] Portland VA Med Ctr, Div Primary Care, Portland, OR 97239 USA. [Gerrity, Martha S.] Portland VA Med Ctr, Div Hosp & Specialty Med, Portland, OR 97239 USA. [Dobscha, Steven K.; Corson, Kathryn] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Doak, Melanie N.; Gerrity, Martha S.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Perrin, Nancy A.; Hanson, Ginger C.] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97201 USA. [Sullivan, Mark D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM steven.dobscha@va.gov FU Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service [PMI 03-195, REA 06-174]; Greenwall Foundation FX Funding/Support: This research was supported by the Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service Projects PMI 03-195 and REA 06-174. Some research team members received training on chronic pain communication skills developed with a grant from the Greenwall Foundation. NR 67 TC 129 Z9 130 U1 5 U2 7 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 MAR 25 PY 2009 VL 301 IS 12 BP 1242 EP 1252 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 423JO UT WOS:000264492800024 PM 19318652 ER PT J AU Sinha, S Subramanian, S Miller, L Proctor, TM Roberts, C Burrows, GG Vandenbark, AA Offner, H AF Sinha, Sushmita Subramanian, Sandhya Miller, Lisa Proctor, Thomas M. Roberts, Chris Burrows, Gregory G. Vandenbark, Arthur A. Offner, Halina TI Cytokine Switch and Bystander Suppression of Autoimmune Responses to Multiple Antigens in Experimental Autoimmune Encephalomyelitis by a Single Recombinant T-Cell Receptor Ligand SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PROTEOLIPID PROTEIN; DENDRITIC CELLS; TRANSGENIC MICE; SJL MICE; INTERLEUKIN-10; PEPTIDE; MECHANISMS; TOLERANCE; SCLEROSIS; DESIGN AB Recombinant T-cell receptor ligands (RTLs) can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner, and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). Antigen specificity of RTL raises the question as to whether this treatment would be successful in MS patients where target antigens are unknown. Using spinal cord homogenate or combinations of two different peptides to induce disease, we found that treatment with single RTL could reverse EAE as long as targeted T-cells were present. Therapy with three different RTLs each caused a significant reduction in IL-17 and increases in IL-10 and IL-13 in peptide-activated splenocytes, reduced proliferation of both cognate and bystander specificities of lymph node cells, and reduced inflammatory lesions and secreted IL-17 and IL-2 from peptide-activated spinal cord cells. These results show that treatment with single RTLs can induce a cytokine switch in cognate T-cells that inhibits both the target and bystander T-cells, providing new evidence for the potential applicability of RTL therapy in MS. C1 [Sinha, Sushmita; Subramanian, Sandhya; Miller, Lisa; Proctor, Thomas M.; Roberts, Chris; Vandenbark, Arthur A.; Offner, Halina] Vet Affairs Med Ctr, Portland, OR 97239 USA. [Sinha, Sushmita; Subramanian, Sandhya; Miller, Lisa; Roberts, Chris; Burrows, Gregory G.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Burrows, Gregory G.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. [Proctor, Thomas M.; Burrows, Gregory G.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Tykeson Multiple Sclerosis Res Lab, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU National Multiple Sclerosis Society; National Multiple Sclerosis Society Postdoctoral Fellowship [FG1749-A-1, RG3794A, RG3468]; National Institutes of Health [NS47661, AI43960, NS41965, NS46877] FX Dr. Sinha is a Postdoctoral Fellow of the National Multiple Sclerosis Society, and this work was supported in part by National Multiple Sclerosis Society Postdoctoral Fellowship FG1749-A-1 and Grants RG3794A and RG3468; National Institutes of Health Grants NS47661, AI43960, NS41965, and NS46877; The Nancy Davis MS Center Without Walls; and the Biomedical Laboratory R&D Service, Department of Veterans Affairs. We thank Eva Niehaus for assistance in preparing the manuscript. NR 22 TC 22 Z9 23 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 25 PY 2009 VL 29 IS 12 BP 3816 EP 3823 DI 10.1523/JNEUROSCI.5812-08.2009 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 424DE UT WOS:000264544900016 PM 19321778 ER PT J AU Bakkour, A Morris, JC Dickerson, BC AF Bakkour, Akram Morris, John C. Dickerson, Bradford C. TI The cortical signature of prodromal AD Regional thinning predicts mild AD dementia SO NEUROLOGY LA English DT Article ID VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; MRI; HIPPOCAMPAL; ATROPHY; VOLUME; SEGMENTATION AB Objective: We previously used exploratory analyses across the entire cortex to determine that mild Alzheimer disease (AD) is reliably associated with a cortical signature of thinning in specific limbic and association regions. Here we investigated whether the cortical signature of AD-related thinning is present in individuals with questionable AD dementia (QAD) and whether a greater degree of regional cortical thinning predicts mild AD dementia. Methods: Participants included 49 older adults with mild impairment consistent with mild cognitive impairment (Clinical Dementia Rating [CDR] = 0.5) at the time of structural MRI scanning. Cortical thickness was measured in nine regions of interest (ROIs) identified previously from a comparison of patients with mild AD and controls. Results: Longitudinal clinical follow-up revealed that 20 participants converted to mild AD dementia (progressors) while 29 remained stable (nonprogressors) approximately 2.5 years after scanning. At baseline, QAD participants showed a milder degree of cortical thinning than typically seen in mild AD, and CDR Sum-of-Boxes correlated with thickness in temporal and parietal ROIs. Compared to nonprogressors, progressors showed temporal and parietal thinning. Using receiver operating characteristic curves, the thickness of an aggregate measure of these regions predicted progression to mild AD with 83% sensitivity and 65% specificity. Conclusions: Thinning in specific cortical areas known to be affected by Alzheimer disease (AD) is detectable in individuals with questionable AD dementia (QAD) and predicts conversion to mild AD dementia. This method could be useful for identifying individuals at relatively high risk for imminent progression from QAD to mild AD dementia, which may be of value in clinical trials. Neurology (R) 2009; 72: 1048-1055 C1 [Dickerson, Bradford C.] Massachusetts Gen Hosp, Gerontol Res Unit, Dept Neurol, Massachusetts Alzheimers Dis Res Ctr, Charlestown, MA 02129 USA. [Bakkour, Akram] Massachusetts Gen Hosp, Dept Psychiat, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Dickerson, Bradford C.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Dept Neurol, Boston, MA 02115 USA. [Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Morris, John C.] Washington Univ, Sch Med, Alzheimers Dis Res Ctr, St Louis, MO 63110 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, Dept Neurol, Massachusetts Alzheimers Dis Res Ctr, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu RI Morris, John/A-1686-2012; OI Bakkour, Akram/0000-0002-6070-4945 FU NIA [K23-AG22509, R01-AG29411, R21-AG29840, P50-AG05681, P01-AG03991, NCRR P41-RR14075, U24-RR021382]; Alzheimer's Association; Howard Hughes Medical Institute; Mental Illness and Neuroscience Discovery ( MIND) Institute FX Supported by grants from the NIA K23-AG22509, R01-AG29411, R21-AG29840, P50-AG05681, and P01-AG03991, NCRR P41-RR14075, U24-RR021382, the Alzheimer's Association, Howard Hughes Medical Institute, and the Mental Illness and Neuroscience Discovery ( MIND) Institute. NR 32 TC 114 Z9 116 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 MAR 24 PY 2009 VL 72 IS 12 BP 1048 EP 1055 DI 10.1212/01.wnl.0000340981.97664.2f PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 422VZ UT WOS:000264457100005 PM 19109536 ER PT J AU Sasportas, LS Kasmieh, R Wakimoto, H Hingtgen, S van de Water, JAJM Mohapatra, G Figueiredo, JL Martuza, RL Weissleder, R Shah, K AF Sasportas, Laura S. Kasmieh, Randa Wakimoto, Hiroaki Hingtgen, Shawn van de Water, Jeroen A. J. M. Mohapatra, Gayatry Figueiredo, Jose Luiz Martuza, Robert L. Weissleder, Ralph Shah, Khalid TI Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gliomas; in vivo imaging; TRAIL ID APOPTOSIS-INDUCING LIGAND; MARROW STROMAL CELLS; GROWTH IN-VIVO; BONE-MARROW; PROGENITOR CELLS; GENE-THERAPY; TUMOR-THERAPY; GLIOMA MODEL; S-TRAIL; MIGRATION AB The poor prognosis of patients with aggressive and invasive cancers combined with toxic effects and short half-life of currently available treatments necessitate development of more effective tumor selective therapies. Mesenchymal stem cells (MSCs) are emerging as novel cell-based delivery agents; however, a thorough investigation addressing their therapeutic potential and fate in different cancer models is lacking. In this study, we explored the engineering potential, fate, and therapeutic efficacy of human MSCs in a highly malignant and invasive model of glioblastoma. We show that engineered MSC retain their "stem-like'' properties, survive longer in mice with gliomas than in the normal brain, and migrate extensively toward gliomas. We also show that MSCs are resistant to the cytokine tumor necrosis factor apoptosis ligand (TRAIL) and, when engineered to express secreted recombinant TRAIL, induce caspase-mediated apoptosis in established glioma cell lines as well as CD133-positive primary glioma cells in vitro. Using highly malignant and invasive human glioma models and employing real-time imaging with correlative neuropathology, we demonstrate that MSC-delivered recombinant TRAIL has profound anti-tumor effects in vivo. This study demonstrates the efficacy of diagnostic and therapeutic MSC in preclinical glioma models and forms the basis for developing stem cell-based therapies for different cancers. C1 [Sasportas, Laura S.; Kasmieh, Randa; Hingtgen, Shawn; van de Water, Jeroen A. J. M.; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. [Sasportas, Laura S.; Kasmieh, Randa; Hingtgen, Shawn; van de Water, Jeroen A. J. M.; Figueiredo, Jose Luiz; Weissleder, Ralph; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CMIR,Dept Radiol, Boston, MA 02114 USA. [Wakimoto, Hiroaki; Martuza, Robert L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Syst Biol,Ctr Syst Biol, Boston, MA 02114 USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA. EM kshah@helix.mgh.harvard.edu RI van de Water, Jeroen/F-1302-2011 OI van de Water, Jeroen/0000-0001-6974-2270 FU American Brain Tumor Association; Goldhirsh Foundation; Alliance for Cancer Gene Therapy; American Cancer Society; National Institutes of Health [P50 CA86355] FX We thank Rainer Koehler for his help with intravital microscopy and Fil Swirski for his help with FACS analysis. This work was supported by grants from the American Brain Tumor Association (K.S.), Goldhirsh Foundation (K.S.), Alliance for Cancer Gene Therapy (K.S.), and American Cancer Society (K.S.), and by National Institutes of Health Grant P50 CA86355 (to R.W.). NR 47 TC 207 Z9 219 U1 3 U2 51 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 MAR 24 PY 2009 VL 106 IS 12 BP 4822 EP 4827 DI 10.1073/pnas.0806647106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 423VA UT WOS:000264522600046 PM 19264968 ER PT J AU Salvesen, HB Carter, SL Mannelqvist, M Dutt, A Getz, G Stefansson, IM Raeder, MB Sos, ML Engelsen, IB Trovik, J Wik, E Greulich, H Bo, TH Jonassen, I Thomas, RK Zander, T Garraway, LA Oyan, AM Sellers, WR Kalland, KH Meyerson, M Akslen, LA Beroukhim, R AF Salvesen, H. B. Carter, S. L. Mannelqvist, M. Dutt, A. Getz, G. Stefansson, I. M. Raeder, M. B. Sos, M. L. Engelsen, I. B. Trovik, J. Wik, E. Greulich, H. Bo, T. H. Jonassen, I. Thomas, R. K. Zander, T. Garraway, L. A. Oyan, A. M. Sellers, W. R. Kalland, K. H. Meyerson, M. Akslen, L. A. Beroukhim, R. TI Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amplification; endometrial cancer; prognosis; comparative genomic hybridization; stathmin expression ID EXPRESSION; MUTATIONS; PIK3CA; CANCERS; POPULATION; SIGNATURE; ADENOCARCINOMAS; ABERRATIONS; INHIBITOR; P110-BETA AB Although 75% of endometrial cancers are treated at an early stage, 15% to 20% of these recur. We performed an integrated analysis of genome-wide expression and copy-number data for primary endometrial carcinomas with extensive clinical and histopathological data to detect features predictive of recurrent disease. Unsupervised analysis of the expression data distinguished 2 major clusters with strikingly different phenotypes, including significant differences in disease-free survival. To identify possible mechanisms for these differences, we performed a global genomic survey of amplifications, deletions, and loss of heterozygosity, which identified 11 significantly amplified and 13 significantly deleted regions. Amplifications of 3q26.32 harboring the oncogene PIK3CA were associated with poor prognosis and segregated with the aggressive transcriptional cluster. Moreover, samples with PIK3CA amplification carried signatures associated with in vitro activation of PI3 kinase (PI3K), a signature that was shared by aggressive tumors without PIK3CA amplification. Tumors with loss of PTEN expression or PIK3CA overexpression that did not have PIK3CA amplification also shared the PI3K activation signature, high protein expression of the PI3K pathway member STMN1, and an aggressive phenotype in test and validation datasets. However, mutations of PTEN or PIK3CA were not associated with the same expression profile or aggressive phenotype. STMN1 expression had independent prognostic value. The results affirm the utility of systematic characterization of the cancer genome in clinically annotated specimens and suggest the particular importance of C1 [Salvesen, H. B.; Raeder, M. B.; Engelsen, I. B.; Trovik, J.; Wik, E.] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. [Salvesen, H. B.; Raeder, M. B.; Trovik, J.; Wik, E.] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. [Carter, S. L.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02142 USA. [Carter, S. L.; Dutt, A.; Getz, G.; Greulich, H.; Garraway, L. A.; Meyerson, M.; Beroukhim, R.] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA. [Mannelqvist, M.; Stefansson, I. M.; Oyan, A. M.; Kalland, K. H.; Akslen, L. A.] Univ Bergen, Gade Inst, Sect Pathol, N-5020 Bergen, Norway. [Dutt, A.; Greulich, H.; Garraway, L. A.; Meyerson, M.; Beroukhim, R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stefansson, I. M.; Akslen, L. A.] Haukeland Hosp, Dept Pathol, N-5020 Bergen, Norway. [Sos, M. L.; Thomas, R. K.; Zander, T.] Max Planck Inst Neurol Res, D-509315 Cologne, Germany. [Sos, M. L.; Thomas, R. K.; Zander, T.] Max Planck Soc, Klaus Joachim Zulch Labs, D-509315 Cologne, Germany. [Sos, M. L.; Thomas, R. K.; Zander, T.] Univ Cologne, Fac Med, D-509315 Cologne, Germany. [Greulich, H.; Garraway, L. A.; Beroukhim, R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Greulich, H.; Garraway, L. A.; Beroukhim, R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bo, T. H.; Jonassen, I.] Univ Bergen, Dept Informat, N-5020 Bergen, Norway. [Bo, T. H.; Jonassen, I.] Univ Bergen, Computat Biol Unit, N-5020 Bergen, Norway. [Thomas, R. K.] Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany. [Thomas, R. K.] Univ Cologne, Dept Internal Med, D-50931 Cologne, Germany. [Thomas, R. K.] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. [Garraway, L. A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Kalland, K. H.] Haukeland Hosp, Dept Microbiol & Immunol, N-5021 Bergen, Norway. [Sellers, W. R.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Meyerson, M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Salvesen, HB (reprint author), Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. EM helga.salvesen@uib.no; lars.akslen@gades.uib.no; rameen_beroukhim@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Dutt, Amit/I-1911-2013; Kalland, Karl-Henning/B-9445-2017; Akslen, Lars /C-1202-2017; salvesen, Helga/C-1187-2017; OI Dutt, Amit/0000-0002-1119-4774; Kalland, Karl-Henning/0000-0003-4486-2334; Akslen, Lars /0000-0003-2710-9543; salvesen, Helga/0000-0002-4438-8831; Jonassen, Inge/0000-0003-4110-0748 FU Helse Vest [911005, 911351, 911069]; University of Bergen; Norwegian Cancer Society [D94070/04, D00019/01, HS01-2006-0446]; Research Council of Norway [154942/V40, 163920/V50]; Department of Defense [PC040638, PC061642]; National Institutes of Health [K08CA122833] FX The authors thank Gerd Lillian Hallseth, Bendik Nordanger, Britt Edvardsen, Randi Nygaard, Beth Johannessen, and Hua My Hoang for technical assistance. This study was supported by Helse Vest Grants 911005, 911351, and 911069, the University of Bergen, the Norwegian Cancer Society Grants D94070/04, D00019/01, HS01-2006-0446 (Harald Andersens legat), the Research Council of Norway Grants 154942/V40 and 163920/V50, Department of Defense Grants PC040638 and PC061642, National Institutes of Health Grant K08CA122833, and the Dana-Farber Harvard Cancer Center Prostate Specialized Program in Research Excellence. This research was approved by the Norwegian Data Inspectorate (961478-2), Norwegian Social Sciences Data Services (15501), and local ethics committee (REKIII nr. 052.01). NR 31 TC 149 Z9 153 U1 2 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 24 PY 2009 VL 106 IS 12 BP 4834 EP 4839 DI 10.1073/pnas.0806514106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 423VA UT WOS:000264522600048 PM 19261849 ER PT J AU Chirinos, JA Franklin, SS Townsend, RR Raij, L AF Chirinos, Julio A. Franklin, Stanley S. Townsend, Raymond R. Raij, Leopoldo TI Body Mass Index and Hypertension Hemodynamic Subtypes in the Adult US Population SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PULSE-WAVE VELOCITY; ISOLATED SYSTOLIC HYPERTENSION; INCREASED ARTERIAL STIFFNESS; NUTRITION EXAMINATION SURVEY; CORONARY-HEART-DISEASE; METABOLIC SYNDROME; AORTIC STIFFNESS; BLOOD-PRESSURE; INDEPENDENT PREDICTOR; CARDIOVASCULAR MORTALITY AB Background: Obesity produces various hemodynamic abnormalities that may impact hypertension subtypes. Similarly, the study of hypertension subtypes provides important information regarding the relative importance of hemodynamic abnormalities contributing to obesity-related hypertension. Methods: Cross-sectional analysis of adults enrolled in the Third National Health and Nutrition Examination Survey (NHANES III) (n= 16 545) and NHANES 1999-2004 (n= 12 137). We examined the relationship between body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) and the risk of hypertension and hemodynamic subtypes: isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systodiastolic hypertension (SDH). Results: In NHANES 1999-2004, the odds ratio (OR) for hypertension for every 5-unit increase in BMI was 1.45 (95% confidence interval [CI], 1.39-1.52) (P <.001). However, the magnitude of the relative increase in the odds of hypertension was higher among younger adults. Among patients with hypertension, increasing BMI was a significant predictor of IDH or SDH (OR for IDH or SDH, 1.04; 95% CI, 1.02-1.06) (P <.001), as opposed to ISH. Isolated systolic hypertension represented a minority of hypertension cases in obese men (38.9%; 95% CI, 30.9-47.6) but remained the most prevalent type in obese women (62.1%; 95% CI, 52.4%-71.0%) (P <.001), despite a significant relative decrease in the frequency of ISH with increasing BMI in both sexes. Findings in NHANES III were very similar. Conclusions: Isolated diastolic hypertension and SDH account for most cases of obesity-related hypertension, suggesting that determinants of mean arterial pressure account for the major burden of obesity-related hypertension in US adult men. These findings should be considered in the design of clinical trials and therapeutic strategies for obesity-related hypertension. Further studies should assess determinants of mean arterial pressure in obesity and the role of sex in the pathogenesis of obesity-related hypertension. C1 [Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Div Cardiol, Dept Med, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Univ Penn, Sch Med, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA. [Townsend, Raymond R.] Univ Penn, Sch Med, Dept Med, Div Nephrol, Philadelphia, PA 19104 USA. [Franklin, Stanley S.] Univ Calif Irvine, Heart Dis Prevent Program, Irvine, CA 92717 USA. [Raij, Leopoldo] Univ Miami, Miller Sch Med, Dept Med, Div Cardiol, Miami, FL 33136 USA. [Raij, Leopoldo] Miami Vet Affairs Med Ctr, Miami, FL USA. RP Chirinos, JA (reprint author), Philadelphia Vet Affairs Med Ctr, Div Cardiol, Dept Med, 8B111,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu FU Cardiodynamics Inc; Atcor Medical Inc FX Dr Chirinos has received minor research support from Cardiodynamics Inc and Atcor Medical Inc, companies that manufacture devices for noninvasive hemodynamic measurements. NR 56 TC 22 Z9 24 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 MAR 23 PY 2009 VL 169 IS 6 BP 580 EP 586 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 423HO UT WOS:000264487600008 PM 19307521 ER PT J AU Ginde, AA Liu, MC Camargo, CA AF Ginde, Adit A. Liu, Mark C. Camargo, Carlos A., Jr. TI Demographic Differences and Trends of Vitamin D Insufficiency in the US Population, 1988-2004 SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; SERUM 25-HYDROXYVITAMIN-D; D DEFICIENCY; MYOCARDIAL-INFARCTION; CANCER PREVENTION; D SUPPLEMENTATION; BREAST-CANCER; RISK; MEN AB Background: Vitamin D insufficiency is associated with suboptimal health. The prevalence of vitamin D insufficiency may be rising, but population-based trends are uncertain. We sought to evaluate US population trends in vitamin D insufficiency. Methods: We compared serum 25-hydroxyvitamin D (25[OH] D) levels from the Third National Health and Nutrition Examination Survey (NHANES III), collected during 1988 through 1994, with NHANES data collected from 2001 through 2004 (NHANES 2001-2004). Complete data were available for 18 883 participants in NHANES III and 13 369 participants in NHANES 2001-2004. Results: The mean serum 25(OH) D level was 30 (95% confidence interval [CI], 29-30) ng/mL during NHANES III and decreased to 24 (23-25) ng/mL during NHANES 2001-2004. Accordingly, the prevalence of 25(OH) D levels of less than 10 ng/mL increased from 2% (95% CI, 2%-2%) to 6% (5%-8%), and 25(OH) D levels of 30 ng/mL or more decreased from 45% (43%-47%) to 23% (20%-26%). The prevalence of 25(OH) D levels of less than 10 ng/mL in non-Hispanic blacks rose from 9% during NHANES III to 29% during NHANES 2001-2004, with a corresponding decrease in the prevalence of levels of 30 ng/mL or more from 12% to 3%. Differences by age strata (mean serum 25[OH] D levels ranging from 28-32 ng/mL) and sex (28 ng/mL for women and 32 ng/mL for men) during NHANES III equalized during NHANES 20012004 (24 vs 24 ng/mL for age and 24 vs 24 ng/mL for sex). Conclusions: National data demonstrate a marked decrease in serum 25(OH) D levels from the 1988-1994 to the 2001-2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency. C1 [Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. [Liu, Mark C.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. [Liu, Mark C.] Johns Hopkins Univ, Sch Med, Div Clin Immunol & Allergy, Baltimore, MD USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Ginde, AA (reprint author), Univ Colorado, Denver Sch Med, Dept Emergency Med, 12401 E 17th Ave,Mail Stop B-215, Aurora, CO 80045 USA. EM adit.ginde@ucdenver.edu RI Osborne, Nicholas/N-4915-2015; Siry, Bonnie/D-7189-2017 OI Osborne, Nicholas/0000-0002-6700-2284; FU Massachusetts General Hospital Center [R01 HL84401]; National Institutes of Health [R01 AI63184] FX Dr Camargo was supported by the Massachusetts General Hospital Center for D-receptor Activation Research and grants R01 HL84401, and Dr Liu was supported by grant R01 AI63184 from the National Institutes of Health. NR 42 TC 502 Z9 519 U1 1 U2 20 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 MAR 23 PY 2009 VL 169 IS 6 BP 626 EP 632 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 423HO UT WOS:000264487600014 PM 19307527 ER PT J AU Chen, JJ Tsai, CH Cai, X Horhota, AT McLaughlin, LW Szostak, JW AF Chen, Jesse J. Tsai, Ching-Hsuan Cai, Xin Horhota, Allen T. McLaughlin, Larry W. Szostak, Jack W. TI Enzymatic Primer-Extension with Glycerol-Nucleoside Triphosphates on DNA Templates SO PLOS ONE LA English DT Article AB Background: Glycerol nucleic acid (GNA) has an acyclic phosphoglycerol backbone repeat-unit, but forms stable duplexes based on Watson-Crick base-pairing. Because of its structural simplicity, GNA is of particular interest with respect to the possibility of evolving functional polymers by in vitro selection. Template-dependent GNA synthesis is essential to any GNA-based selection system. Principal Findings: In this study, we investigated the ability of various DNA polymerases to use glycerol-nucleoside triphosphates (gNTPs) as substrates for GNA synthesis on DNA templates. Therminator DNA polymerase catalyzes quantitative primer-extension by the incorporation of two glyceronucleotides, with much less efficient extension up to five glyceronucleotides. Steady-state kinetic experiments suggested that GNA synthesis by Therminator was affected by both decreased catalytic rates and weakened substrate binding, especially for pyrimidines. In an attempt to improve pyrimidine incorporation by providing additional stacking interactions, we synthesized two new gNTP analogs with 5-propynyl substituted pyrimidine nucleobases. This led to more efficient incorporation of gC, but not gT. Conclusions: We suggest that directed evolution of Therminator might lead to mutants with improved substrate binding and catalytic efficiency. C1 [Chen, Jesse J.; Tsai, Ching-Hsuan; Cai, Xin; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Chen, Jesse J.; Tsai, Ching-Hsuan; Cai, Xin; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Chen, Jesse J.; Tsai, Ching-Hsuan; Cai, Xin; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Comput & Integrative Biol, Boston, MA 02114 USA. [Horhota, Allen T.; McLaughlin, Larry W.] Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02167 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Harvard Origins of Life Initiative [fellowship]; NSF [CHE 0434507, MCB 0451488]; Howard Hughes Medical Institute FX JJC was supported by a fellowship from the Harvard Origins of Life Initiative. This work was supported by NSF grants CHE 0434507 to JWS and MCB 0451488 to LWM. JWS is an Investigator of the Howard Hughes Medical Institute and CHT is a Research Associate of the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 13 Z9 13 U1 3 U2 23 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 MAR 23 PY 2009 VL 4 IS 3 AR e4949 DI 10.1371/journal.pone.0004949 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437PG UT WOS:000265498800006 PM 19305495 ER PT J AU Castoreno, A Eggert, US AF Castoreno, Adam Eggert, Ulrike S. TI Pathway-specific small molecule probes of cell division SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Castoreno, Adam; Eggert, Ulrike S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM adam_castoreno@dfci.harvard.edu; ulrike_eggert@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 22 PY 2009 VL 237 MA 15-BIOL BP 508 EP 508 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16GJ UT WOS:000207857800462 ER PT J AU Huang, WS Zhu, XT Wang, YH Azam, M Wen, D Sundaramoorthi, R Thomas, RM Liu, SY Banda, G Lentini, S Das, S Xu, QH Keats, J Wang, F Wardwell, S Ning, YY Snodgrass, JT Broudy, MI Russian, K Iuliucci, J Dalgarno, DC Clackson, TP Daley, GQ Sawyer, TK Shakespeare, WC AF Huang, Wei-Sheng Zhu, Xiaotian Wang, Yihan Azam, Mohammad Wen, David Sundaramoorthi, Raji Thomas, R. Mathew Liu, Shuangying Banda, Geeta Lentini, Scott Das, Sasmita Xu, Qihong Keats, Jeff Wang, Frank Wardwell, Scott Ning, Yaoyu Snodgrass, Joseph T. Broudy, Mark I. Russian, Karin Iuliucci, John Dalgarno, David C. Clackson, Timothy P. Daley, George Q. Sawyer, Tomi K. Shakespeare, William C. TI 6, 9-Disubstituted purines as potent dual Src/Abl tyrosine kinase inhibitors targeting the "inactive" conformation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Huang, Wei-Sheng; Zhu, Xiaotian; Wang, Yihan; Wen, David; Sundaramoorthi, Raji; Thomas, R. Mathew; Liu, Shuangying; Banda, Geeta; Lentini, Scott; Das, Sasmita; Xu, Qihong; Keats, Jeff; Wang, Frank; Wardwell, Scott; Ning, Yaoyu; Snodgrass, Joseph T.; Broudy, Mark I.; Russian, Karin; Iuliucci, John; Dalgarno, David C.; Clackson, Timothy P.; Sawyer, Tomi K.; Shakespeare, William C.] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. [Azam, Mohammad; Daley, George Q.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst,Childrens Hosp,Med Sch, Div Hematol Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. EM wei-sheng.huang@ariad.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 22 PY 2009 VL 237 MA 168-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16GJ UT WOS:000207857804489 ER PT J AU Rogers, JT Cahill, CM Cho, HH Moncaster, JA Goldstein, LE Moir, R Xie, ZC Huang, XD AF Rogers, Jack T. Cahill, Catherine M. Cho, Hyun Hee Moncaster, Juliet A. Goldstein, Lee E. Moir, Robert Xie, Zhongcong Huang, Xudong TI Alzheimer's disease drug discovery targeted to the nonamyloidogenic path of APP mRNA translation linked to Alpha-secretase (ADAM-17) expression SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rogers, Jack T.] Massachusetts Gen Hosp, Dept Pf Psychiat Neurosci, Charlestown, MA 02129 USA. [Moncaster, Juliet A.; Goldstein, Lee E.] BU, Sch Med, Charlestown, MA USA. [Moir, Robert; Xie, Zhongcong] Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. EM jrogers@partners.org; ccahill@rics.bwh.harvard.edu; hcho1@partners.org; jmon@bu.edu; lgold@bu.edu; huangx@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 22 PY 2009 VL 237 MA 150-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16GJ UT WOS:000207857804569 ER PT J AU Guise, A Woodward, D Lee, PT De Vogli, R Tillman, T Mccoy, D AF Guise, Andy Woodward, David Lee, Patrick T. De Vogli, Roberto Tillman, Taavi McCoy, David TI Engaging the health community in global economic reform SO LANCET LA English DT Editorial Material C1 [McCoy, David] UCL, Ctr Int Hlth & Dev, London WC1N 1EH, England. [Guise, Andy] London Sch Hyg & Trop Med, London WC1, England. [Lee, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mccoy, D (reprint author), UCL, Ctr Int Hlth & Dev, London WC1N 1EH, England. EM d.mccoy@ucl.ac.uk RI Tillmann, Taavi/R-6026-2016 OI Tillmann, Taavi/0000-0002-8428-3719 NR 11 TC 1 Z9 1 U1 1 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 MAR 21 PY 2009 VL 373 IS 9668 BP 987 EP 989 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 422AA UT WOS:000264398200008 PM 19304001 ER PT J AU Mao, YW Ge, XC Frank, CL Madison, JM Koehler, AN Doud, MK Tassa, C Berry, EM Soda, T Singh, KK Biechele, T Petryshen, TL Moon, RT Haggarty, SJ Tsai, LH AF Mao, Yingwei Ge, Xuecai Frank, Christopher L. Madison, Jon M. Koehler, Angela N. Doud, Mary Kathryn Tassa, Carlos Berry, Erin M. Soda, Takahiro Singh, Karun K. Biechele, Travis Petryshen, Tracey L. Moon, Randall T. Haggarty, Stephen J. Tsai, Li-Huei TI Disrupted in Schizophrenia 1 Regulates Neuronal Progenitor Proliferation via Modulation of GSK3 beta/beta-Catenin Signaling SO CELL LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; BETA-CATENIN; HIPPOCAMPAL NEUROGENESIS; DISC1; BRAIN; MICE; LITHIUM; CELLS; DISRUPTED-IN-SCHIZOPHRENIA-1; EXPRESSION AB The Disrupted in Schizophrenia 1 (DISC1) gene is disrupted by a balanced chromosomal translocation (1; 11) (q42; q14.3) in a Scottish family with a high incidence of major depression, schizophrenia, and bipolar disorder. Subsequent studies provided indications that DISC1 plays a role in brain development. Here, we demonstrate that suppression of DISC1 expression reduces neural progenitor proliferation, leading to premature cell cycle exit and differentiation. Several lines of evidence suggest that DISC1 mediates this function by regulating GSK3 beta. First, DISC1 inhibits GSK3 beta activity through direct physical interaction, which reduces beta-catenin phosphorylation and stabilizes beta-catenin. Importantly, expression of stabilized beta-catenin overrides the impairment of progenitor proliferation caused by DISC1 loss of function. Furthermore, GSK3 inhibitors normalize progenitor proliferation and behavioral defects caused by DISC1 loss of function. Together, these results implicate DISC1 inGSK3 beta/beta-catenin signaling pathways and provide a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders. C1 [Mao, Yingwei; Ge, Xuecai; Frank, Christopher L.; Soda, Takahiro; Singh, Karun K.; Biechele, Travis; Moon, Randall T.; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Mao, Yingwei; Ge, Xuecai; Frank, Christopher L.; Soda, Takahiro; Singh, Karun K.; Tsai, Li-Huei] MIT, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Mao, Yingwei] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Soda, Takahiro] Harvard Univ, Sch Med, Phd Program, Boston, MA 02115 USA. [Soda, Takahiro] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Koehler, Angela N.; Doud, Mary Kathryn; Tassa, Carlos; Berry, Erin M.; Petryshen, Tracey L.; Haggarty, Stephen J.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Koehler, Angela N.; Doud, Mary Kathryn; Tassa, Carlos; Berry, Erin M.; Petryshen, Tracey L.; Haggarty, Stephen J.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Madison, Jon M.; Berry, Erin M.; Petryshen, Tracey L.; Haggarty, Stephen J.; Tsai, Li-Huei] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA. [Madison, Jon M.; Berry, Erin M.; Petryshen, Tracey L.; Haggarty, Stephen J.; Tsai, Li-Huei] MIT, Cambridge, MA 02139 USA. [Biechele, Travis; Moon, Randall T.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. [Biechele, Travis; Moon, Randall T.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA. RP Tsai, LH (reprint author), MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. EM lhtsai@mit.edu RI Moon, Randall/B-1743-2014; OI Moon, Randall/0000-0002-9352-1408; Haggarty, Stephen J./0000-0002-7872-168X FU National Alliance for Research on Schizophrenia and Depression Young Investigator Award; Natural Sciences and Engineering Research Council Postdoctoral Award; National Institutes of Health [NS37007] FX We thank A. Sawa for providing the human DISC1 cDNA construct, C. Lois for the FUGW construct, X. He for FLAG-Dvl2, HA-GSK3 beta, FLAG-WT-beta-catenin, and SA-beta-catenin constructs, Y. Ma and M. Greenberg for Ngn2 antibodies, and F. Gage for the AHP cells. We acknowledge E. Scolnick, B. A. Samuels, Z. Xie, D. Meletis, M. Carlen, C. Bragg, J. Buchman, P. Thanawala, and M. Dobbin for technical support, helpful discussion, and critical reading of the manuscript. L.-H. T. is an investigator of the Howard Hughes Medical Institute and the director of the neurobiology program at the Stanley Center for Psychiatric Research. Y. M. is a recipient of the National Alliance for Research on Schizophrenia and Depression Young Investigator Award. K. K. S. is a recipient of a Natural Sciences and Engineering Research Council Postdoctoral Award and a Human Frontiers Science Program Research Fellowship. T. S. is a recipient of the Singleton Fellowship. This work was partially supported by a National Institutes of Health grant (NS37007) to L.-H. T. NR 46 TC 426 Z9 444 U1 6 U2 45 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 20 PY 2009 VL 136 IS 6 BP 1017 EP 1031 DI 10.1016/j.cell.2008.12.044 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 422CE UT WOS:000264403900009 PM 19303846 ER PT J AU Shulman, Z Shinder, V Klein, E Grabovsky, V Yeger, O Geron, E Montresor, A Bolomini-Vittori, M Feigelson, SW Kirchhausen, T Laudanna, C Shakhar, G Alon, R AF Shulman, Ziv Shinder, Vera Klein, Eugenia Grabovsky, Valentin Yeger, Orna Geron, Erez Montresor, Alessio Bolomini-Vittori, Matteo Feigelson, Sara W. Kirchhausen, Tomas Laudanna, Carlo Shakhar, Guy Alon, Ronen TI Lymphocyte Crawling and Transendothelial Migration Require Chemokine Triggering of High-Affinity LFA-1 Integrin SO IMMUNITY LA English DT Article ID VASCULAR ENDOTHELIUM; T-CELL; LEUKOCYTE TRANSMIGRATION; INFLAMMATORY RESPONSE; ADHERENT LEUKOCYTES; ADHESION RECEPTORS; BLOOD-VESSELS; ACTIVATION; ICAM-1; MOTILITY AB Endothelial chemokines are instrumental for integrin-mediated lymphocyte adhesion and transendothelial migration (TEM). By dissecting how chemokines trigger lymphocyte integrins to support shear-resistant motility on and across cytokine-stimulated endothelial barriers, we found a critical role for high-affinity (HA) LFA-1 integrin in lymphocyte crawling on activated endothelium. Endothelial-presented chemokines triggered HA-LFA-1 and adhesive filopodia at numerous submicron dots scattered underneath crawling lymphocytes. Shear forces applied to endothelial-bound lymphocytes dramatically enhanced filopodia density underneath crawling lymphocytes. A fraction of the adhesive filopodia invaded the endothelial cells prior to and during TEM and extended large subluminal leading edge containing dots of HA-LFA-1 occupied by subluminal ICAM-1. Memory T cells generated more frequent invasive filopodia and transmigrated more rapidly than their naive counterparts. We propose that shear forces exerted on HA-LFA-1 trigger adhesive and invasive filopodia at apical endothelial surfaces and thereby promote lymphocyte crawling and probing for TEM sites. C1 [Shulman, Ziv; Grabovsky, Valentin; Geron, Erez; Feigelson, Sara W.; Shakhar, Guy; Alon, Ronen] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. [Shinder, Vera; Klein, Eugenia; Yeger, Orna] Weizmann Inst Sci, Irving & Cherna Moskowitz Ctr Nano & Bio Nano Ima, IL-76100 Rehovot, Israel. [Montresor, Alessio; Bolomini-Vittori, Matteo; Laudanna, Carlo] Univ Verona, Div Gen Pathol, Dept Pathol, Sch Med, I-37134 Verona, Italy. [Montresor, Alessio; Bolomini-Vittori, Matteo; Laudanna, Carlo] Univ Verona, CBMC, I-37134 Verona, Italy. [Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kirchhausen, Tomas] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Alon, R (reprint author), Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. EM ronen.alon@weizmann.ac.il RI Bolomini-Vittori, Matteo/Q-5659-2016 OI Bolomini-Vittori, Matteo/0000-0002-5762-0791 FU Israel Science Foundation; Minerva Foundation,; MAIN; EU FX We thank S. Schwarzbaum for editorial assistance and O. Barreiro (University Autonoma, Madrid), P. Goichberg, and C. Luxenburg for helpful suggestions. We also thank Ishai Sher and the Weizmann Institute graphic department for graphic assistance. R.A. is the Incumbent of The Linda Jacobs Chair in Immune and Stem Cell Research. R.A. is supported by the Israel Science Foundation, by the Minerva Foundation, Germany, and by MAIN, the EU6 Program for Migration and Inflammation. NR 43 TC 134 Z9 135 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR 20 PY 2009 VL 30 IS 3 BP 384 EP 396 DI 10.1016/j.immuni.2008.12.020 PG 13 WC Immunology SC Immunology GA 422CU UT WOS:000264405500011 PM 19268609 ER PT J AU Ishii, H Du, H Zhang, Z Henderson, A Sen, R Pazin, MJ AF Ishii, Haruhiko Du, Hansen Zhang, Zhaoqing Henderson, Angus Sen, Ranjan Pazin, Michael J. TI Mi2 beta Shows Chromatin Enzyme Specificity by Erasing a DNase I-hypersensitive Site Established by ACF SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAVY-CHAIN GENE; TRANSCRIPTIONAL ACTIVATION; REMODELING COMPLEX; NUCLEOSOMAL DNA; HISTONE DEACETYLASE; FUNCTIONAL DIFFERENCES; REGULATORY PROTEINS; BINDING PROTEINS; B-CELLS; ENHANCER AB ATP-dependent chromatin-remodeling enzymes are linked to changes in gene expression; however, it is not clear how the multiple remodeling enzymes found in eukaryotes differ in function and work together. In this report, we demonstrate that the ATP-dependent remodeling enzymes ACF and Mi2 beta can direct consecutive, opposing chromatin-remodeling events, when recruited to chromatin by different transcription factors. In a cell-free system based on the immunoglobulin heavy chain gene enhancer, we show that TFE3 induces a DNase I-hypersensitive site in an ATP-dependent reaction that requires ACF following transcription factor binding to chromatin. In a second step, PU.1 directs Mi2 beta to erase an established DNase I-hypersensitive site, in an ATP-dependent reaction subsequent to PU.1 binding to chromatin, whereas ACF will not support erasure. Erasure occurred without displacing the transcription factor that initiated the site. Other tested enzymes were unable to erase the DNase I-hypersensitive site. Establishing and erasing the DNase I-hypersensitive site required transcriptional activation domains from TFE3 and PU.1, respectively. Together, these results provide important new mechanistic insight into the combinatorial control of chromatin structure. C1 [Du, Hansen; Sen, Ranjan; Pazin, Michael J.] NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA. [Ishii, Haruhiko] Brandeis Univ, Grad Program Biophys & Struct Biol, Waltham, MA 02454 USA. [Zhang, Zhaoqing; Pazin, Michael J.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Henderson, Angus] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Pazin, MJ (reprint author), NIA, Lab Cellular & Mol Biol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM pazinm@mail.nih.gov FU Intramural NIH HHS [ZIA AG000524-05]; NIGMS NIH HHS [GM38925, GM61011] NR 79 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 2009 VL 284 IS 12 BP 7533 EP 7541 DI 10.1074/jbc.M807617200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 419CB UT WOS:000264195600016 PM 19158090 ER PT J AU Brice, SE Alford, CW Cowart, LA AF Brice, Sarah E. Alford, Charlene W. Cowart, L. Ashley TI Modulation of Sphingolipid Metabolism by the Phosphatidylinositol-4-phosphate Phosphatase Sac1p through Regulation of Phosphatidylinositol in Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOMAIN PROTEINS SLM1; DE-NOVO; HEAT-STRESS; SERINE PALMITOYLTRANSFERASE; ACTIN CYTOSKELETON; LIPID PHOSPHATASE; FREE SPHINGOSINE; PLASMA-MEMBRANE; DISTINCT ROLES; YEAST AB Sphingolipids and phosphoinositides both play signaling roles in Saccharomyces cerevisiae. Although previous data indicate independent functions for these two classes of lipids, recent genetic studies have suggested interactions between phosphatidylinositol (PtdIns) phosphate effectors and sphingolipid biosynthetic enzymes. The present study was undertaken to further define the effects of phosphatidylinositol 4-phosphate (PtdIns(4)P) metabolism on cell sphingolipid metabolism. The data presented indicate that deletion of SAC1, a gene encoding a PtdIns(4) P phosphatase, increased levels of most sphingolipid species, including sphingoid bases, sphingoid base phosphates, and phytoceramide. In contrast, sac1 Delta dramatically reduced inositol phosphosphingolipids, which result from the addition of a PtdIns-derived phosphoinositol head group to ceramides through Aur1p. Deletion of SAC1 decreased PtdIns dramatically in both steady-state and pulse labeling studies, suggesting that the observed effects on sphingolipids may result from modulation of the availability of PtdIns as a substrate for Aur1p. Supporting this hypothesis, acute attenuation of PtdIns(4) P production through Stt4p immediately increased PtdIns and subsequently reduced sphingoid bases. This reduction was overcome by the inhibition of Aur1p. Moreover, modulation of sphingoid bases through perturbation of PtdIns(4) P metabolism initiated sphingolipid-dependent biological effects, supporting the biological relevance for this route of regulating sphingolipids. These findings suggest that, in addition to potential signaling effects of PtdInsP effectors on sphingolipid metabolism, PtdIns kinases may exert substantial effects on cell sphingolipid profiles at a metabolic level through modulation of PtdIns available as a substrate for complex sphingolipid synthesis. C1 [Brice, Sarah E.; Alford, Charlene W.; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Cowart, LA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM cowartl@musc.edu FU Centers of Biomedical Research Excellence in lipidomics and pathobiology at the Medical University of South Carolina FX This work was supported in part by the Centers of Biomedical Research Excellence in lipidomics and pathobiology at the Medical University of South Carolina NR 48 TC 38 Z9 40 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 2009 VL 284 IS 12 BP 7588 EP 7596 DI 10.1074/jbc.M808325200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 419CB UT WOS:000264195600021 PM 19139096 ER PT J AU Li, B Jackson, J Simon, MD Fleharty, B Gogol, M Seidel, C Workman, JL Shilatifard, A AF Li, Bing Jackson, Jessica Simon, Matthew D. Fleharty, Brian Gogol, Madelaine Seidel, Chris Workman, Jerry L. Shilatifard, Ali TI Histone H3 Lysine 36 Dimethylation (H3K36me2) Is Sufficient to Recruit the Rpd3s Histone Deacetylase Complex and to Repress Spurious Transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METHYLATION STATES; SACCHAROMYCES-CEREVISIAE; CHROMATIN MODIFICATIONS; GENOME-WIDE; TRIMETHYLATION; CHROMODOMAIN; ACETYLATION; RECOGNITION; ELONGATION; BINDING AB Histone methylation is associated with both transcription activation and repression. However, the functions of different states of methylation remain largely elusive. Here, using methyllysine analog technology, we demonstrate that the histone deacetylase complex, Rpd3S, can distinguish the nucleosomes methylated to different extents and that K36me2 is sufficient to target Rpd3S in vitro. Through a genome-wide survey, we identified a few mutants in which the level of K36me3 is significantly reduced, whereas the level of K36me2 is sustained. Transcription analysis and genome-wide histone modification studies on these mutants suggested that K36me2 is sufficient to target Rpd3S in vivo, thereby maintaining a functional Set2-Rpd3S pathway. C1 [Li, Bing; Jackson, Jessica; Fleharty, Brian; Gogol, Madelaine; Seidel, Chris; Workman, Jerry L.; Shilatifard, Ali] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Li, Bing] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA. [Simon, Matthew D.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Workman, JL (reprint author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA. EM jlw@stowers.org FU National Institutes of Health [GM047867, 2R01GM069905]; Stowers Institute for Medical Research FX This work was supported, in whole or in part, by National Institutes of Health Grant GM047867 through the NIGMS (to J. L. W.) and National Institutes of Health Grant 2R01GM069905 (to A. S.). This work was also supported by funding from the Stowers Institute for Medical Research. NR 33 TC 74 Z9 74 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 2009 VL 284 IS 12 BP 7970 EP 7976 DI 10.1074/jbc.M808220200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 419CB UT WOS:000264195600059 PM 19155214 ER PT J AU Thoreen, CC Kang, SA Chang, JW Liu, QS Zhang, JM Gao, Y Reichling, LJ Sim, TB Sabatini, DM Gray, NS AF Thoreen, Carson C. Kang, Seong A. Chang, Jae Won Liu, Qingsong Zhang, Jianming Gao, Yi Reichling, Laurie J. Sim, Taebo Sabatini, David M. Gray, Nathanael S. TI An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR 4E-BINDING PROTEIN-1; CAP-DEPENDENT TRANSLATION; INITIATION-FACTOR 4E; KINASE-ACTIVITY; AMINO-ACIDS; EARLY G1; PHOSPHORYLATION; 4E-BP1; MEDIATE; COMPLEX AB The mammalian target of rapamycin (mTOR) kinase is the catalytic subunit of two functionally distinct complexes, mTORC1 and mTORC2, that coordinately promote cell growth, proliferation, and survival. Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as an immunosuppressant and anti-cancer agent. Here we find that Torin1, a highly potent and selective ATP-competitive mTOR inhibitor that directly inhibits both complexes, impairs cell growth and proliferation to a far greater degree than rapamycin. Surprisingly, these effects are independent of mTORC2 inhibition and are instead because of suppression of rapamycin-resistant functions of mTORC1 that are necessary for cap-dependent translation and suppression of autophagy. These effects are at least partly mediated by mTORC1-dependent and rapamycin-resistant phosphorylation of 4E-BP1. Our findings challenge the assumption that rapamycin completely inhibits mTORC1 and indicate that direct inhibitors of mTORC1 kinase activity may be more successful than rapamycin at inhibiting tumors that depend on mTORC1. C1 [Thoreen, Carson C.; Kang, Seong A.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Thoreen, Carson C.; Kang, Seong A.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. [Sabatini, David M.] MIT, Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA. [Chang, Jae Won; Liu, Qingsong; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dept Canc Biol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Gao, Yi; Reichling, Laurie J.] Invitrogen Corp, Madison, WI 53719 USA. RP Sabatini, DM (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM sabatini@wi.mit.edu OI liu, qing song/0000-0002-7829-2547 FU National Institutes of Health [R01 AI47389, R01 CA103866]; Dana Farber Cancer Institute; Barr Foundation; Damon Runyon Cancer Research Foundation; Keck Foundation; LAM Foundation; Department of Defense [W81XWH-07-1-0448]; American Cancer Society FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 AI47389 and R01 CA103866. This work was also supported by start-up funding from the Dana Farber Cancer Institute, the Barr Foundation, and the Damon Runyon Cancer Research Foundation (to N. S. G.), Keck Foundation, LAM Foundation, and Department of Defense Grant W81XWH-07-1-0448 (to D. M. S.), and a fellowship from the American Cancer Society (to S. A. K.). NR 43 TC 810 Z9 826 U1 8 U2 58 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 MAR 20 PY 2009 VL 284 IS 12 BP 8023 EP 8032 DI 10.1074/jbc.M900301200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 419CB UT WOS:000264195600065 PM 19150980 ER PT J AU Sandler, AB Schiller, JH Gray, R Dimery, I Brahmer, J Samant, M Wang, LI Johnson, DH AF Sandler, Alan B. Schiller, Joan H. Gray, Robert Dimery, Isaiah Brahmer, Julie Samant, Meghna Wang, Lisa I. Johnson, David H. TI Retrospective Evaluation of the Clinical and Radiographic Risk Factors Associated With Severe Pulmonary Hemorrhage in First-Line Advanced, Unresectable Non-Small-Cell Lung Cancer Treated With Carboplatin and Paclitaxel Plus Bevacizumab SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID PHASE-II TRIAL; CARCINOMA; ENTITY AB Purpose Severe (grade >= 3) pulmonary hemorrhage (PH) in advanced non-small-cell lung cancer was observed in two prospective, randomized, phase II (N = 99) and phase III (N = 878) trials of bevacizumab plus carboplatin and paclitaxel. Retrospective case-control and cohort analyses were conducted to identify associated radiographic and clinical risk factors for PH. Patients and Methods Six patients with PH from the phase II trial, 15 potential PH patients with hemorrhage at any site from the phase III trial, and their matched controls were evaluated with review of baseline and on-treatment radiographs by an independent radiology facility, blinded to patient/control status. Patients with severe (grade >= 3) PH from each trial were matched with up to three controls based on sex, age group, histology (phase II), or sex and age group (phase III). Results Seven PH patients in the phase III trial were identified as severe PH. Six of the patients were early onset (occurred < 150 days of initiating bevacizumab) and one was late onset. Baseline tumor cavitation, not tumor location, was identified as the only potential risk factor for patients with early onset. Combined analysis of severe PH patients from the phase II and phase III trials (n = 13), compared with their pooled matched controls ( n = 42), did not identify any additional baseline radiographic or clinical variables associated with PH. Conclusion PH was an uncommon event. Based on these analyses, baseline tumor cavitation may be a potential risk factor for PH. No other baseline clinical variables were predictive for PH although the number of events was small. C1 Vanderbilt Univ, Nashville, TN USA. Univ Texas SW, Dallas, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Genentech Inc, San Francisco, CA 94080 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Sandler, AB (reprint author), Vanderbilt Ingram Canc Ctr, 2220 Pierce Ave, Nashville, TN 37232 USA. EM sandler@vanderbilt.edu FU NCI NIH HHS [P30 CA006973] NR 19 TC 94 Z9 96 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 MAR 20 PY 2009 VL 27 IS 9 BP 1405 EP 1412 DI 10.1200/JCO.2008.16.2412 PG 8 WC Oncology SC Oncology GA 447MA UT WOS:000266194000012 PM 19224857 ER PT J AU Ogino, S Nosho, K Kirkner, GJ Shima, K Irahara, N Kure, S Chan, AT Engelman, JA Kraft, P Cantley, LC Giovannucci, EL Fuchs, CS AF Ogino, Shuji Nosho, Katsuhiko Kirkner, Gregory J. Shima, Kaori Irahara, Natsumi Kure, Shoko Chan, Andrew T. Engelman, Jeffrey A. Kraft, Peter Cantley, Lewis C. Giovannucci, Edward L. Fuchs, Charles S. TI PIK3CA Mutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; KRAS MUTATIONS; CETUXIMAB; SURVIVAL; GENE; CIMP; POPULATION; EXPRESSION AB Purpose PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little is known about the prognostic role of PIK3CA mutation in colon cancer. Patients and Methods Using 450 resectable colon cancers (stage I to III) in two independent prospective cohorts, we detected PIK3CA mutation in 82 tumors (18%) by pyrosequencing. Cox proportional hazards models were used to calculate hazard ratios (HRs) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and tumoral molecular features, including the CpG island methylation phenotype, microsatellite instability (MSI), LINE-1 hypomethylation, and p53, CIMP, KRAS and BRAF mutation. Results Compared with patients with PIK3CA wild-type tumors, those with PIK3CA-mutated tumors experienced an increase in colon cancer-specific mortality according to univariate analysis (HR = 1.64; 95% CI, 0.95 to 2.86), which persisted after adjusting for other known or potential risk factors for cancer recurrence (including MSI; multivariate HR = 2.23; 95% CI, 1.21 to 4.11). The effect of PIK3CA mutation on cancer survival seemed to differ according to KRAS mutational status. Among patients with KRAS wild-type tumors, the presence of PIK3CA mutation was associated with a significant increase in colon cancer-specific mortality (HR = 3.80; 95% CI, 1.56 to 9.27). In contrast, PIK3CA mutation conferred no significant effect on mortality among patients with KRAS-mutated tumors (HR = 1.25; 95% CI, 0.52 to 2.96). Conclusion Among patients who undergo a curative resection of colon cancer, PIK3CA mutation is associated with shorter cancer-specific survival. The adverse effect of PIK3CA mutation may be potentially limited to patients with KRAS wild- type tumors. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Channing Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Syst Biol, Boston, MA 02215 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, 44 Binney St,Room JF 215C, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]; Entertainment Industry Foundation; Japanese Society for Promotion of Science FX Supported by the National Institutes of Health Grants No. P01 CA87969, P01 CA55075, P50 CA127003, and K07 CA122826 (to S.O.); the Bennett Family Fund; and the Entertainment Industry Foundation. K.N. was supported by a fellowship grant from the Japanese Society for Promotion of Science. NR 44 TC 185 Z9 190 U1 2 U2 11 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 MAR 20 PY 2009 VL 27 IS 9 BP 1477 EP 1484 DI 10.1200/JCO.2008.18.6544 PG 8 WC Oncology SC Oncology GA 447MA UT WOS:000266194000024 PM 19237633 ER PT J AU Goebel, M Stengel, A Wang, LX Lambrecht, NWG Tache, Y AF Goebel, Miriam Stengel, Andreas Wang, Lixin Lambrecht, Nils W. G. Tache, Yvette TI Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei SO NEUROSCIENCE LETTERS LA English DT Article DE Brain; Spinal cord; Immunohistochemistry; mRNA expression; Nucleobindin-2; Rat ID PARAVENTRICULAR NUCLEUS; SATIETY MOLECULE; FOS EXPRESSION; HYPOTHALAMUS; NEURONS; NUCLEOBINDIN-2; VASOPRESSIN; OXYTOCIN; RELEASE; PAIN AB Nesfatin-1 is one of the peptide products of posttranslational processing of the nucleobindin-2 (NUCB2) gene, suggested to have physiological relevance to suppress food intake and body weight gain in rats. Nesfatin-1-immunoreactive cells have been found in distinct nuclei in the rat brain related to circuitries regulating food intake. Here, we report novel yet undescribed localization of NUCB2/nesfatin-1 at the mRNA and protein level in the rat central nervous system. Immunohistochemical staining revealed the localization of NUCB2/nesfatin-1 in the piriform and insular cortex, endopiriform nucleus, nucleus accumbens, lateral septum, bed nucleus of stria terminalis, central amygdaloid nucleus, medial preoptic area, dorsal raphe nucleus, ambiguus nucleus, ventrolateral medulla and gigantocellular reticular nucleus, as well as Purkinje-cells of the cerebellum. In the spinal cord, nesfatin-1 immunoreactivity (IR) was found in both sympathetic and parasympathetic preganglionic neuronal groups and in the dorsal area X from lower thoracic to sacral segments. The immunohistochemical results were confirmed by RT-PCR in the central amygdaloid nucleus, nucleus accumbens, cerebellum and lumbar spinal cord microdissected by punch technique. The features and distributions of nesfatin-1 IR and mRNA expression in the brain and spinal cord suggest that NUCB2/nesfatin-1 could play a wider role in autonomic regulation of visceral-endocrine functions besides food intake. Published by Elsevier Ireland Ltd. C1 [Goebel, Miriam; Stengel, Andreas; Wang, Lixin; Lambrecht, Nils W. G.; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Ctr Neurovisceral Sci & Womens Hlth, Ctr Neurobiol Stress,Digest Dis Div,Dept Med,Davi, Los Angeles, CA USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, Cure Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu OI Lambrecht, Nils/0000-0002-1275-1384 FU German Research Foundation [1718/1-1, STE 1765/1-1]; VA Research Career Scientist Award, Department of Veterans Affairs Merit Award [NIHDK 33061, DK-41301] FX This work was supported by German Research Foundation grant GO 1718/1-1 (M.G.), grant STE 1765/1-1 (A.S.) and the VA Research Career Scientist Award, Department of Veterans Affairs Merit Award (Y.T.), NIHDK 33061 (Y.T.) and Center grant DK-41301 (Animal Core, Y.T.). We are grateful to Mrs. Honghui Liang for her excellent technical support. NR 25 TC 91 Z9 97 U1 2 U2 6 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 MAR 20 PY 2009 VL 452 IS 3 BP 241 EP 246 DI 10.1016/j.neulet.2009.01.064 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 425QZ UT WOS:000264653500006 PM 19348732 ER PT J AU Kiatpongsan, S Sipp, D AF Kiatpongsan, Sorapop Sipp, Douglas TI Monitoring and Regulating Offshore Stem Cell Clinics SO SCIENCE LA English DT Editorial Material C1 [Sipp, Douglas] RIKEN, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan. [Kiatpongsan, Sorapop] Chulalongkorn Univ, Fac Med, Dept Obstet & Gynecol, Bangkok 10330, Thailand. [Kiatpongsan, Sorapop] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv,Vincent Ctr Reprod, Boston, MA 02114 USA. [Kiatpongsan, Sorapop] Harvard Univ, John F Kennedy Sch Govt, Sci Technol & Publ Policy Program, Sci Technol & Globalizat Project,Belfer Ctr Sci &, Cambridge, MA 02138 USA. [Sipp, Douglas] Kyoto Univ, Ctr iPS Res & Applicat, Inst Integrated Cell Mat Sci, Kyoto 6068501, Japan. RP Sipp, D (reprint author), RIKEN, Ctr Dev Biol, Kobe, Hyogo 6500047, Japan. EM sipp@cdb.riken.jp RI Sipp, Douglas/C-9218-2017 OI Sipp, Douglas/0000-0002-5979-0938 NR 21 TC 51 Z9 52 U1 0 U2 11 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 MAR 20 PY 2009 VL 323 IS 5921 BP 1564 EP 1565 DI 10.1126/science.1168451 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 421EN UT WOS:000264342300022 PM 19299604 ER PT J AU Cornejo, MG Kharas, MG Werneck, MB Le Bras, S Moore, SA Ball, B Beylot-Barry, M Rodig, SJ Aster, JC Lee, BH Cantor, H Merlio, JP Gilliland, DG Mercher, T AF Cornejo, Melanie G. Kharas, Michael G. Werneck, Miriam B. Le Bras, Severine Moore, Sandra A. Ball, Brian Beylot-Barry, Marie Rodig, Scott J. Aster, Jon C. Lee, Benjamin H. Cantor, Harvey Merlio, Jean-Philippe Gilliland, D. Gary Mercher, Thomas TI Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models SO BLOOD LA English DT Article ID T-CELL LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MICE LACKING JAK3; MYELOPROLIFERATIVE DISEASE; MEGAKARYOBLASTIC LEUKEMIA; CHROMOSOMAL TRANSLOCATION; POLYCYTHEMIA-VERA; MYELOID LEUKEMIAS; JANUS KINASE; EXPRESSION AB The tyrosine kinase JAK3 plays a well-established role during normal lymphocyte development and is constitutively phosphorylated in several lymphoid malignancies. However, its contribution to lymphomagenesis remains elusive. In this study, we used the newly identified activating JAK3A572V mutation to elucidate the effect of constitutive JAK3 signaling on murine lymphopoiesis. In a bone marrow transplantation model, JAK3A572V induces an aggressive, fatal, and transplantable lymphoproliferative disorder characterized by the expansion of CD8(+)TCR alpha beta(+)CD44(+)CD122(+)Ly-6C(+) T cells that closely resemble an effector/memory T-cell subtype. Compared with wild-type counterparts, these cells show increased proliferative capacities in response to polyclonal stimulation, enhanced survival rates with elevated expression of Bcl-2, and increased production of interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha), correlating with enhanced cytotoxic abilities against allogeneic target cells. Of interest, the JAK3A572V disease is epidermotropic and produces intraepidermal microabscesses. Taken together, these clinical features are reminiscent of those observed in an uncommon but aggressive subset of CD8(+) human cutaneous T-cell lymphomas (CTCLs). However, we also observed a CD4(+) CTCL-like phenotype when cells are transplanted in an MHC-I-deficient background. These data demonstrate that constitutive JAK3 activation disrupts T-cell homeostasis and induces lymphoproliferative diseases in mice. (Blood. 2009;113:2746-2754) C1 [Cornejo, Melanie G.; Kharas, Michael G.; Moore, Sandra A.; Ball, Brian; Lee, Benjamin H.; Gilliland, D. Gary; Mercher, Thomas] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. [Werneck, Miriam B.; Cantor, Harvey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Le Bras, Severine] Childrens Hosp, Boston, MA 02115 USA. [Beylot-Barry, Marie; Merlio, Jean-Philippe] Univ Bordeaux 2, Pathol Dermatol Dept, F-33076 Bordeaux, France. [Beylot-Barry, Marie; Merlio, Jean-Philippe] CHU Bordeaux, EA2406, Bordeaux, France. [Rodig, Scott J.; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gilliland, D. Gary] Howard Hughes Med Inst, Boston, MA 02115 USA. [Mercher, Thomas] Univ Paris 05, Necker Hosp, INSERM, E0210, Paris, France. RP Mercher, T (reprint author), Hop Necker Tour Pasteur, INSERM, EMI0210, 149 Rue Sevres, F-75743 Paris 15, France. EM ggilliland@rics.bwh.harvard.edu; thomas.mercher@inserm.fr RI Werneck, Miriam/H-5802-2012; Mercher, Thomas/J-2446-2014 OI Mercher, Thomas/0000-0003-1552-087X FU National Institutes of Health [DK50654, CA66996]; Leukemia & Lymphoma Society FX This work was supported in part by National Institutes of Health grants DK50654 and CA66996 and by the Leukemia & Lymphoma Society to D. G. G. T. M. is a recipient of a Leukemia & Lymphoma SocietyAward. NR 50 TC 35 Z9 39 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 MAR 19 PY 2009 VL 113 IS 12 BP 2746 EP 2754 DI 10.1182/blood-2008-06-164368 PG 9 WC Hematology SC Hematology GA 421MA UT WOS:000264361800018 PM 19139084 ER PT J AU Steimer, DA Boyd, K Takeuchi, O Fisher, JK Zambetti, GP Opferman, JT AF Steimer, Desiree A. Boyd, Kelli Takeuchi, Osamu Fisher, Jill K. Zambetti, Gerard P. Opferman, Joseph T. TI Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; BCL-2 FAMILY-MEMBERS; BH3-ONLY PROTEINS; CONGENITAL NEUTROPENIA; APOPTOTIC RESPONSES; ESCHERICHIA-COLI; T-LYMPHOCYTES; SURVIVAL; MICE AB During hematopoiesis, myeloid cell leukemia-1 (MCL-1) mediates the survival of bone marrow progenitors and lymphocytes. However, its requirement during myeloid cell differentiation, development, and effector function is less clear. Lineage-specific deletion of MCL-1 in myeloid precursors results in neutropenia due to death during differentiation. The loss of mature neutrophils induced by Mcl-1 deletion was not rescued by genetic deletion of proapoptotic Bim and Puma or by exogenous cytokine treatment. However, blockade of intrinsic apoptosis by lineage-specific deletion of both multidomain proapoptotics Bax and Bak was capable of rescuing the neutropenia associated with Mcl-1 deletion. In the monocytic lineage, despite efficient Mcl-1 deletion, monocytes and macrophages undergo normal development. During the phagocytosis of extracellular bacteria, macrophages concomitantly increase the expression of both MCL-1 and BIM. However, Mcl-1-deficient macrophages exhibit increased sensitivity to death during bacterial phagocytosis that can be abolished by codeletion of Bim. These data suggest that MCL-1 may be necessary to antagonize BIM during macrophage effector responses. Thus, MCL-1 plays selective roles in myeloid development, being required for neutrophil development and setting the threshold for apoptosis during a macrophage effector response. (Blood. 2009;113:2805-2815) C1 [Steimer, Desiree A.; Zambetti, Gerard P.; Opferman, Joseph T.] St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. [Takeuchi, Osamu] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 565, Japan. [Fisher, Jill K.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Opferman, JT (reprint author), St Jude Childrens Hosp, Dept Biochem, 262 Danny Thomas Pl,D-4063C, Memphis, TN 38105 USA. EM joseph.opferman@stjude.org RI Takeuchi, Osamu/D-6007-2011 FU Pew Scholars Program in the Biomedical Sciences; American Lebanese Syrian Associated Charities (ALSAC); National Institutes of Health National Cancer Institute FX This work is supported by the Pew Scholars Program in the Biomedical Sciences, the American Lebanese Syrian Associated Charities (ALSAC), and the National Institutes of Health National Cancer Institute. NR 42 TC 51 Z9 51 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 MAR 19 PY 2009 VL 113 IS 12 BP 2805 EP 2815 DI 10.1182/blood-2008-05-159145 PG 11 WC Hematology SC Hematology GA 421MA UT WOS:000264361800024 PM 19064728 ER PT J AU Klement, GL Yip, TT Cassiola, F Kikuchi, L Cervi, D Podust, V Italiano, JE Wheatley, E Abou-Slaybi, A Bender, E Almog, N Kieran, MW Folkman, J AF Klement, Giannoula Lakka Yip, Tai-Tung Cassiola, Flavia Kikuchi, Lena Cervi, David Podust, Vladimir Italiano, Joseph E. Wheatley, Erin Abou-Slaybi, Abdo Bender, Elise Almog, Nava Kieran, Mark W. Folkman, Judah TI Platelets actively sequester angiogenesis regulators SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ALPHA-GRANULES; HUMAN MEGAKARYOCYTES; TUMOR ANGIOGENESIS; HUMAN LIPOSARCOMA; PROSTATE-CANCER; FACTOR VEGF; RELEASE; PROTEIN; ENDOSTATIN AB Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non-tumor-bearing animals. This process is selective, as platelets do not take up a proportional amount of other plasma proteins (eg, albumin), even though these may be present at higher concentrations. We also find that VEGF-enriched Matrigel pellets implanted subcutaneously into mice or the minute quantities of VEGF secreted by microscopic subcutaneous tumors (0.5-1 mm(3)) result in an elevation of VEGF levels in platelets, without any changes in its plasma levels. The profile of other angiogenesis regulatory proteins (eg, platelet-derived growth factor, basic fibroblast growth factor) sequestered by platelets also reflects the presence of tumors in vivo before they can be macroscopically evident. The ability of platelets to selectively take up angiogenesis regulators in cancer-bearing hosts may have implications for the diagnosis and management of many angiogenesis-related diseases and provide a guide for antiangiogenic therapies. (Blood. 2009;113:2835-2842) C1 [Klement, Giannoula Lakka; Cassiola, Flavia; Kikuchi, Lena; Cervi, David; Italiano, Joseph E.; Abou-Slaybi, Abdo; Bender, Elise; Almog, Nava; Kieran, Mark W.; Folkman, Judah] Childrens Hosp, Boston, MA 02115 USA. [Klement, Giannoula Lakka; Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Italiano, Joseph E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yip, Tai-Tung; Podust, Vladimir; Wheatley, Erin] Ciphergen Biosyst, Fremont, CA USA. RP Klement, GL (reprint author), Childrens Hosp, Karp Bldg 11-211,1 Blackfan Circle, Boston, MA 02115 USA. EM giannoula_klement@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Breast Cancer Research Foundation; Department of Defense [W81XWH-04-1-0316]; NASA [NNH04ZUU002N] FX This work is being dedicated to Dr Judah Folkman's memory, with many thanks for his support, guidance, and vision. NR 26 TC 120 Z9 123 U1 1 U2 8 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 MAR 19 PY 2009 VL 113 IS 12 BP 2835 EP 2842 DI 10.1182/blood-2008-06-159541 PG 8 WC Hematology SC Hematology GA 421MA UT WOS:000264361800027 PM 19036702 ER PT J AU Fraenkel, PG Gibert, Y Holzheimer, JL Lattanzi, VJ Burnett, SF Dooley, KA Wingert, RA Zon, LI AF Fraenkel, Paula G. Gibert, Yann Holzheimer, Jason L. Lattanzi, Victoria J. Burnett, Sarah F. Dooley, Kimberly A. Wingert, Rebecca A. Zon, Leonard I. TI Transferrin-a modulates hepcidin expression in zebrafish embryos SO BLOOD LA English DT Article ID HEREDITARY HEMOCHROMATOSIS PROTEIN; ANTIMICROBIAL PEPTIDE HEPCIDIN; IRON OVERLOAD; JUVENILE HEMOCHROMATOSIS; POSITIONAL CLONING; DANIO-RERIO; IN-VIVO; GENE; RECEPTOR; HFE AB The iron regulatory hormone hepcidin is transcriptionally up-regulated in response to iron loading, but the mechanisms by which iron levels are sensed are not well understood. Large-scale genetic screens in the zebrafish have resulted in the identification of hypochromic anemia mutants with a range of mutations affecting conserved pathways in iron metabolism and heme synthesis. We hypothesized that transferrin plays a critical role both in iron transport and in regulating hepcidin expression in zebrafish embryos. Here we report the identification and characterization of the zebrafish hypochromic anemia mutant, gavi, which exhibits transferrin deficiency due to mutations in transferrin-a. Morpholino knockdown of transferrin-a in wild-type embryos reproduced the anemia phenotype and decreased somite and terminal gut iron staining, while coinjection of transferrin-a cRNA partially restored these defects. Embryos with transferrin-a or transferrin receptor 2 (TfR2) deficiency exhibited low levels of hepcidin expression, however anemia, in the absence of a defect in the transferrin pathway, failed to impair hepcidin expression. These data indicate that transferrin-a transports iron and that hepcidin expression is regulated by a transferrin-a-dependent pathway in the zebrafish embryo. (Blood. 2009;113:2843-2850) C1 [Fraenkel, Paula G.; Gibert, Yann; Holzheimer, Jason L.; Lattanzi, Victoria J.; Burnett, Sarah F.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Fraenkel, Paula G.; Gibert, Yann; Holzheimer, Jason L.; Lattanzi, Victoria J.; Burnett, Sarah F.] Harvard Univ, Sch Med, Boston, MA USA. [Dooley, Kimberly A.] Broad Inst, Cambridge, MA USA. [Wingert, Rebecca A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Fraenkel, PG (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM pfraenke@bidmc.harvard.edu FU National Institutes of Health [DK61685-07, DK053298-07]; Howard Hughes Medical Institute; American Society of Hematology ScholarAward FX This work was supported by National Institutes of Health grants DK 61685-07 (P.G.F.) and DK053298-07 (L.I.Z.), Howard Hughes Medical Institute (L.I.Z.), and the American Society of Hematology ScholarAward (P.G.F.). NR 53 TC 25 Z9 27 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 MAR 19 PY 2009 VL 113 IS 12 BP 2843 EP 2850 DI 10.1182/blood-2008-06-165340 PG 8 WC Hematology SC Hematology GA 421MA UT WOS:000264361800028 PM 19047682 ER PT J AU Yi, CR Goldberg, MB AF Yi, Chae-ryun Goldberg, Marcia B. TI Putting Enterohemorrhagic E-coli on a Pedestal SO CELL HOST & MICROBE LA English DT Editorial Material ID ACTIN POLYMERIZATION; EFFECTOR; TIR; ESPF(U); PROTEIN; CELLS; WASP; NCK AB Many pathogenic bacteria exploit host cytoskeletal pathways to promote infection. In this issue of Cell Host & Microbe, Weiss et al. (2009) identify the host factor IRSp53 as the missing link that connects two intracellular bacterial proteins, thereby completing an actin cytoskeletal signaling pathway critical to enterohemorrhagic Escherichia coli pathogenesis. C1 [Yi, Chae-ryun; Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA 02139 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA 02139 USA. EM mgoldberg1@partners.org FU NIAID NIH HHS [R01 AI081724] NR 10 TC 0 Z9 0 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD MAR 19 PY 2009 VL 5 IS 3 BP 215 EP 217 DI 10.1016/j.chom.2009.03.002 PG 3 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 423UZ UT WOS:000264522500002 PM 19286129 ER PT J AU Tai, AW Benita, Y Peng, LF Kim, SS Sakamoto, N Xavier, RJ Chung, RT AF Tai, Andrew W. Benita, Yair Peng, Lee F. Kim, Sun-Suk Sakamoto, Naoya Xavier, Ramnik J. Chung, Raymond T. TI A Functional Genomic Screen Identifies Cellular Cofactors of Hepatitis C Virus Replication SO CELL HOST & MICROBE LA English DT Article ID PHOSPHATIDYLINOSITOL 4-KINASES; RNA REPLICATION; INHIBITION; INFECTION; HEPCIDIN; COMPLEX; CULTURE; GENES; COTRANSPORTER; INFLAMMATION AB Hepatitis C virus (HCV) chronically infects 3% of the world's population, and complications from HCV are the leading indication for liver transplantation. Given the need for better anti-HCV therapies, one strategy is to identify and target cellular cofactors of the virus lifecycle. Using a genome-wide si RNA library, we identified 96 human genes that support HCV replication, with a significant number of them being involved in vesicle organization and biogenesis. Phosphatidylinositol 4-kinase PI4KA and multiple subunits of the COPI vesicle coat complex were among the genes identified. Consistent with this, pharmacologic inhibitors of COPI and PI4KA blocked HCV replication. Targeting hepcidin, a peptide critical for iron homeostasis, also affected HCV replication, which may explain the known dysregulation of iron homeostasis in HCV infection. The host cofactors for HCV replication identified in this study should serve as a useful resource in delineating new targets for anti-HCV therapies. C1 [Tai, Andrew W.; Benita, Yair; Peng, Lee F.; Kim, Sun-Suk; Xavier, Ramnik J.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. [Benita, Yair; Xavier, Ramnik J.] Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sakamoto, Naoya] Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Tokyo, Japan. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. EM rtchung@partners.org RI Benita, Yair/E-3094-2012; Sakamoto, Naoya/G-2734-2012; OI Tai, Andrew/0000-0002-6877-450X FU National Institutes of Health [AI080122, AI062773, DK043351, AI069939, DK078772]; Massachusetts Biomedical Research Corporation; American Gastroenterological Association; American Liver Foundation FX Huh7.5.1, OR6, and UHCVCon57.3 cell lines were gifts from Doctor Francis Chisari (Scripps Institute; La Jolla, CA), Doctors N. Kato and M. Ikeda (Okayama University Graduate School of Medicine; Okayama, Japan), and Doctor Darius Moradpour (University of Lausanne; Lausanne, Switzerland), respectively. The JFH1 strain was a gift of Doctor T. Wakita (Tokyo Metropolitan Institute for Neuroscience; Tokyo, Japan). PI4KA constructs were obtained from Doctor Paul van Bergen en Henegouwen (Universiteit Utrecht; Netherlands). We would like to acknowledge the technical assistance provided by Doctor Caroline Shamu, Stewart Rudnicki, Sean Johnston, and David Wrobel at the ICCB-Longwood screening facility at the Harvard Medical School. This publication was made possible by grants AI080122 (to A.W.T.), AI062773 and DK043351 (to R.J.X.), and AI069939 and DK078772 (to R.T.C.) from the National Institutes of Health as well as by a Tosteson Postdoctoral Fellowship from the Massachusetts Biomedical Research Corporation (to A.W.T.) and grants from the American Gastroenterological Association and the American Liver Foundation (to L.F.P.). NR 40 TC 283 Z9 291 U1 3 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD MAR 19 PY 2009 VL 5 IS 3 BP 298 EP 307 DI 10.1016/j.chom.2009.02.001 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 423UZ UT WOS:000264522500011 PM 19286138 ER PT J AU Forcione, DG Alam, HB Kalva, SP Misdraji, J AF Forcione, David G. Alam, Hasan B. Kalva, Sanjeeva P. Misdraji, Joseph TI A Man with Massive Rectal Bleeding Diverticular disease of the jejunum with hemorrhage SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GASTROINTESTINAL HEMORRHAGE; SURGICAL SIGNIFICANCE; ILEAL DIVERTICULOSIS; FLUID RESUSCITATION; CRITICALLY-ILL; TRANSPORT; CARE; DIAGNOSIS; MORTALITY; TRAUMA C1 [Forcione, David G.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Alam, Hasan B.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Forcione, David G.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Misdraji, Joseph] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Forcione, DG (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 33 TC 13 Z9 13 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 MAR 19 PY 2009 VL 360 IS 12 BP 1239 EP 1248 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 420IU UT WOS:000264283400012 PM 19297577 ER PT J AU Bowers, AA West, N Newkirk, TL Troutman-Youngman, AE Schreiber, SL Wiest, O Bradner, JE Williams, RM AF Bowers, Albert A. West, Nathan Newkirk, Tenaya L. Troutman-Youngman, Annie E. Schreiber, Stuart L. Wiest, Olaf Bradner, James E. Williams, Robert M. TI Synthesis and Histone Deacetylase Inhibitory Activity of Largazole Analogs: Alteration of the Zinc-Binding Domain and Macrocyclic Scaffold SO ORGANIC LETTERS LA English DT Article ID CHROMOBACTERIUM-VIOLACEUM NO-968; CYCLIC TETRAPEPTIDES; TRICHOSTATIN-A; AZUMAMIDE-A; POTENT; TRAPOXIN; FR901228; DERIVATIVES; DESIGN; TUMORS AB Fourteen analogs of the marine natural product largazole have been prepared and assayed against histone deacetylases (HDACs) 1, 2, 3, and 6. Olefin cross-metathesis was used to efficiently access six variants of the side-chain zinc-binding domain, while adaptation of our previously reported modular synthesis allowed probing of the macrocyclic cap group. C1 [West, Nathan; Bradner, James E.] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. [Bowers, Albert A.; Newkirk, Tenaya L.; Troutman-Youngman, Annie E.; Williams, Robert M.] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA. [Williams, Robert M.] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. [West, Nathan; Schreiber, Stuart L.; Bradner, James E.] Broad Inst Harvard, Chem Biol Program, Cambridge, MA 02142 USA. [Williams, Robert M.] MIT, Cambridge, MA 02139 USA. [Schreiber, Stuart L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Wiest, Olaf] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Wiest, Olaf] Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA. RP Bradner, JE (reprint author), Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. EM james_bradner@dfci.harvard.edu; rmv@lamar.colostate.edu FU NIH [GM49631]; NCI [CA136283]; National Cancer Institute [1K08CA128972]; Burroughs-Wellcome Foundation FX We thank the CSU Cancer Supercluster and the NIH for financial support and for a postdoctoral fellowship for AAB (NCI Grant CA136283). Mass spectra were obtained on instruments supported by the NIH Shared Instrument Grant GM49631. We thank Ralph Mazitschek for the provision of acetylated substrate. J.E.B. acknowledges support by grants from the National Cancer Institute (1K08CA128972) and the Burroughs-Wellcome Foundation (CAMS). NR 34 TC 67 Z9 67 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD MAR 19 PY 2009 VL 11 IS 6 BP 1301 EP 1304 DI 10.1021/ol900078k PG 4 WC Chemistry, Organic SC Chemistry GA 417XF UT WOS:000264111100028 PM 19239241 ER PT J AU Phelps, AC Maciejewski, PK Nilsson, M Balboni, TA Wright, AA Paulk, ME Trice, E Schrag, D Peteet, JR Block, SD Prigerson, HG AF Phelps, Andrea C. Maciejewski, Paul K. Nilsson, Matthew Balboni, Tracy A. Wright, Alexi A. Paulk, M. Elizabeth Trice, Elizabeth Schrag, Deborah Peteet, John R. Block, Susan D. Prigerson, Holly G. TI Religious Coping and Use of Intensive Life-Prolonging Care Near Death in Patients With Advanced Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-LIFE; ILL ELDERLY-PATIENTS; TREATMENT PREFERENCES; DECISION-MAKING; AFRICAN-AMERICANS; MENTAL-HEALTH; END; QUESTIONNAIRE; ACKNOWLEDGMENT; RESUSCITATION AB Context Patients frequently rely on religious faith to cope with cancer, but little is known about the associations between religious coping and the use of intensive life-prolonging care at the end of life. Objective To determine the way religious coping relates to the use of intensive life-prolonging end-of-life care among patients with advanced cancer. Design, Setting, and Participants A US multisite, prospective, longitudinal cohort of 345 patients with advanced cancer, who were enrolled between January 1, 2003, and August 31, 2007. The Brief RCOPE assessed positive religious coping. Baseline interviews assessed psychosocial and religious/spiritual measures, advance care planning, and end-of-life treatment preferences. Patients were followed up until death, a median of 122 days after baseline assessment. Main Outcome Measures Intensive life-prolonging care, defined as receipt of mechanical ventilation or resuscitation in the last week of life. Analyses were adjusted for demographic factors significantly associated with positive religious coping and any end-of-life outcome at P < .05 (ie, age and race/ethnicity). The main outcome was further adjusted for potential psychosocial confounders (eg, other coping styles, terminal illness acknowledgment, spiritual support, preference for heroics, and advance care planning). Results A high level of positive religious coping at baseline was significantly associated with receipt of mechanical ventilation compared with patients with a low level (11.3% vs 3.6%; adjusted odds ratio [AOR], 2.81 [95% confidence interval {CI}, 1.03-7.69]; P = .04) and intensive life-prolonging care during the last week of life (13.6% vs 4.2%; AOR, 2.90 [ 95% CI, 1.14-7.35]; P = .03) after adjusting for age and race. In the model that further adjusted for other coping styles, terminal illness acknowledgment, support of spiritual needs, preference for heroics, and advance care planning (do-not-resuscitate order, living will, and health care proxy/durable power of attorney), positive religious coping remained a significant predictor of receiving intensive life-prolonging care near death (AOR, 2.90 [95% CI, 1.07-7.89]; P = .04). Conclusions Positive religious coping in patients with advanced cancer is associated with receipt of intensive life-prolonging medical care near death. Further research is needed to determine the mechanisms for this association. C1 [Phelps, Andrea C.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Phelps, Andrea C.; Maciejewski, Paul K.; Nilsson, Matthew; Balboni, Tracy A.; Wright, Alexi A.; Trice, Elizabeth; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Wright, Alexi A.; Trice, Elizabeth; Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Peteet, John R.; Block, Susan D.; Prigerson, Holly G.] Dana Farber Canc Inst, Dept Psychooncol & Palliat Care, Boston, MA 02115 USA. [Paulk, M. Elizabeth] Univ Texas SW Med Ctr Dallas, Parkland Hosp, Dallas, TX 75390 USA. [Paulk, M. Elizabeth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Maciejewski, Paul K.; Peteet, John R.; Block, Susan D.; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Block, Susan D.; Prigerson, Holly G.] 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,Room 268, Boston, MA 02115 USA. EM Holly_Prigerson@dfci.harvard.edu FU National Cancer Institute [CA 106370]; National Institute of Mental Health [MH63892]; Fetzer Institute FX This study was supported by grant CA 106370 from the National Cancer Institute, grant MH63892 from the National Institute of Mental Health, and a Fetzer Institute grant on spirituality at the end of life. NR 39 TC 167 Z9 168 U1 5 U2 22 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 MAR 18 PY 2009 VL 301 IS 11 BP 1140 EP 1147 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 419UC UT WOS:000264244200019 PM 19293414 ER PT J AU Liu, CH You, ZR Liu, CM Kim, YR Whalen, MJ Rosen, BR Liu, PK AF Liu, Christina H. You, Zerong Liu, Charng-Ming Kim, Young R. Whalen, Michael J. Rosen, Bruce R. Liu, Philip K. TI Diffusion-Weighted Magnetic Resonance Imaging Reversal by Gene Knockdown of Matrix Metalloproteinase-9 Activities in Live Animal Brains SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GLOBAL CEREBRAL-ISCHEMIA; TRANSIENT FOREBRAIN ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; CAROTID-ARTERY OCCLUSION; FOS MESSENGER-RNA; C-FOS; MATRIX METALLOPROTEINASES; CARDIAC-ARREST; ANTISENSE OLIGODEOXYNUCLEOTIDE; TRANSCRIPTION MRI AB The involvement of matrix metalloproteinase-9 (MMP-9) activities in the development of abnormal water diffusion in the brain after cardiac arrest is not fully understood. We used magnetic resonance imaging to determine the correlation between MMP-9 activity and the mechanism of abnormal water diffusion after global cerebral ischemia (GCI)-induced brain damage in C57black6 mice. We induced GCI in mice by occluding both carotid arteries for 60 min, then allowing reperfusion. We labeled a short DNA that targets mmp-9 mRNA activity [phosphorothioate-modified oligodeoxynucleotide (sODN)-mmp9] or a control probe without intracellular target (sODN-Ran) with iron-based MR contrast agent [ superparamagnetic iron oxide nanoparticle (SPION)-mmp9 or SPION-Ran] or fluorescein isothiocyanate (FITC)-sODN-mmp9 or FITC-sODN-Ran; we then delivered these probes by intracerebroventricular infusion or intraperitoneal injection within 3 h of reperfusion. At low dose (120 pmol/kg) the SPION-mmp9 probe was retained at significant levels in the striatum and cortex of living brains 10 h after GCI. Probe retention was validated by similar elevation of mmp-9 mRNA and antigens in postmortem samples taken from regions that exhibited GCI-induced hyperintensity in diffusion-weighted imaging, and a significant reduction in apparent diffusion coefficient (rADC, p = 0.0006, n = 12). At a higher dose (120 nmol/kg), the FITC-sODN-mmp9 probe revealed significant knockdown of MMP-9 activity, per zymography, and a reversal of striatal rADC (p = 0.004, n = 6). These observations were not duplicated in the control group. We conclude that expression of mmp-9 mRNA is associated with abnormal ADC after GCI. C1 [Liu, Philip K.] Massachusetts Gen Hosp, Dept Radiol, Lab Transcript Targeting Imaging & Repair, Charlestown, MA 02129 USA. [Liu, Christina H.; Liu, Charng-Ming; Kim, Young R.; Rosen, Bruce R.; Liu, Philip K.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [You, Zerong; Whalen, Michael J.] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. RP Liu, PK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Lab Transcript Targeting Imaging & Repair, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X FU National Institutes of Health [R21DA024235, R01EB002066, R01NS045845, R21NS057556, R01NS047447]; National Center for Research Resources [SP41RR14075] FX This work was supported by grants from the National Institutes of Health (R21DA024235, R01EB002066, R01NS045845, R21NS057556, R01NS047447) and the National Center for Research Resources (SP41RR14075). We appreciate Nichole Eusemann for editing and Dr. Joseph B. Mandeville for providing the in-house software for image registration (alignment). C. H. L. contributed MRI acquisition, data analysis, and animal care, and Z.Y. and M. W. performed MMP-9 zymography and MMP-9 immunohistology. C.-M. L. supplied sODN and siDNA, Y. R. K. and B. R. R. supplied SPION. P. K. L. designed sODN, conjugated, characterized, and delivered SPION-sODN, performed all surgical procedures for BCAO and probe delivery, and directed the project. C. H. L. and P. K. L. wrote this manuscript. All authors discussed the results and commented on this manuscript. Two patent applications have been submitted: (1) imaging nucleic acids (US serial no. 60/603,907and PCT/US2005/029875); and (2) matrix metalloproteinase targeting nucleic acids (US serial no. 60/959,856). NR 55 TC 9 Z9 11 U1 2 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 18 PY 2009 VL 29 IS 11 BP 3508 EP 3517 DI 10.1523/JNEUROSCI.5332-08.2009 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 421EL UT WOS:000264342100018 PM 19295156 ER PT J AU Barry, MJ Mulley, AJ AF Barry, Michael J. Mulley, Albert J., Jr. TI Why Are a High Overdiagnosis Probability and a Long Lead Time for Prostate Cancer Screening So Important? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TRIAL C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mbarry@partners.org NR 9 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 18 PY 2009 VL 101 IS 6 BP 362 EP U9 DI 10.1093/jnci/djp028 PG 2 WC Oncology SC Oncology GA 421YB UT WOS:000264393100001 PM 19276451 ER PT J AU Wolpin, BM Chan, AT Hartge, P Chanock, SJ Kraft, P Hunter, DJ Giovannucci, EL Fuchs, CS AF Wolpin, Brian M. Chan, Andrew T. Hartge, Patricia Chanock, Stephen J. Kraft, Peter Hunter, David J. Giovannucci, Edward L. Fuchs, Charles S. TI ABO Blood Group and the Risk of Pancreatic Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROUP-RELATED ANTIGENS; PHYSICAL-ACTIVITY QUESTIONNAIRE; HELICOBACTER-PYLORI INFECTION; DUCTAL ADENOCARCINOMA; EXPRESSION; DISEASE; REPRODUCIBILITY; MALIGNANCY; CARCINOMA; GENETICS AB Background Other than several rare, highly penetrant familial syndromes, genetic risk factors for sporadic pancreatic cancer are largely unknown. ABO blood type is an inherited characteristic that in previous small studies has been associated with the risk of gastrointestinal malignancies. Methods We separately examined the relationship between ABO blood type and the risk of incident pancreatic cancer in two large, independent, prospective cohort studies (the Nurses' Health Study and Health Professionals Follow-up Study) that collected blood group data on 107 503 US health professionals. Hazard ratios for pancreatic cancer by ABO blood type were calculated using Cox proportional hazards models with adjustment for other known risk factors, including age, tobacco use, body mass index, physical activity, and history of diabetes mellitus. All statistical tests were two-sided. Results During 927 995 person-years of follow-up, 316 participants developed pancreatic cancer. ABO blood type was associated with the risk of developing pancreatic cancer (P=.004; log-rank test). Compared with participants with blood group O, those with blood groups A, AB, or B were more likely to develop pancreatic cancer (adjusted hazard ratios for incident pancreatic cancer were 1.32 [95% confidence interval {CI} = 1.02 to 1.72], 1.51 [95% CI = 1.02 to 2.23], and 1.72 [95% CI = 1.25 to 2.38], respectively). The association between blood type and pancreatic cancer risk was nearly identical in the two cohorts (P(interaction)=.97). Overall, 17% of the pancreatic cancer cases were attributable to inheriting a non-O blood group (blood group A, B, or AB). The age-adjusted incidence rates for pancreatic cancer per 100 000 person-years were 27 (95% CI = 23 to 33) for participants with blood type O, 36 (95% CI = 26 to 50) for those with blood type A, 41 (95% CI = 31 to 56) for those with blood type AB, and 46 (95% CI = 32 to 68) for those with blood type B. Conclusions In two large, independent populations, ABO blood type was statistically significantly associated with the risk of pancreatic cancer. Further studies are necessary to define the mechanisms by which ABO blood type or closely linked genetic variants may influence pancreatic cancer risk. C1 [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Wolpin, Brian M.; Hunter, David J.; Fuchs, Charles S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. [Hartge, Patricia; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hunter, David J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kraft, Peter; Hunter, David J.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bwolpin@partners.org FU National Cancer Institute; National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, T32 CA09001]; Lustgarten Foundation for Pancreatic Cancer Research FX National Cancer Institute, National Institutes of Health (P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, T32 CA09001); Lustgarten Foundation for Pancreatic Cancer Research. NR 50 TC 142 Z9 150 U1 1 U2 13 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 MAR 18 PY 2009 VL 101 IS 6 BP 424 EP 431 DI 10.1093/jnci/djp020 PG 8 WC Oncology SC Oncology GA 421YB UT WOS:000264393100010 PM 19276450 ER PT J AU Brown, CJ Roth, DL Allman, RM Sawyer, P Ritchie, CS Roseman, JM AF Brown, Cynthia J. Roth, David L. Allman, Richard M. Sawyer, Patricia Ritchie, Christine S. Roseman, Jeffrey M. TI Trajectories of Life-Space Mobility After Hospitalization SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID OLDER PATIENTS; FUNCTIONAL DECLINE; MULTICOMPONENT INTERVENTION; RANDOMIZED-TRIAL; NATURAL-HISTORY; HEART-FAILURE; ACUTE-CARE; OUTCOMES; DELIRIUM; ADULTS AB Background: Life space is a measure of where a person goes, the frequency of going there, and the dependency in getting there. It may be a more accurate measure of mobility in older adults because it reflects participation in society as well as physical ability. Objective: To assess effects of hospitalization on life space in older adults, and to compare life-space trajectories associated with surgical and nonsurgical hospitalizations. Design: Prospective observational study. Setting: Central Alabama. Participants: 687 community-dwelling Medicare beneficiaries at least 65 years of age with surgical (n = 44), nonsurgical (n = 167), or no (n = 476) hospitalizations. Measurements: Life-Space Assessment (LSA) scores before and after hospitalization (range, 0 to 120; higher scores reflect greater mobility). Results: Mean age of participants was 74.6 years (SD, 6.3). Fifty percent were black, and 46% were male. Before hospitalization, adjusted LSA scores were similar in participants with surgical and nonsurgical admissions. Life-space assessment scores decreased in both groups immediately after hospitalization; however, participants with surgical hospitalizations had a greater decrease in scores (12.1 more points [95% CI, 3.6 to 20.7 points]; P = 0.005) than those with nonsurgical hospitalizations. However, participants with surgical hospitalizations recovered more rapidly over time (gain of 4.7 more points [CI, 2.0 to 7.4 points] per ln [week after discharge]; P < 0.001). Score recovery for participants with nonsurgical hospitalizations did not significantly differ from the null (average recovery, 0.7 points [CI,-0.6 to 1.9 points] per ln [week after discharge]). Limitation: Life space immediately before and after hospitalization was self-reported, often after hospital discharge. Conclusion: Hospitalization decreases life space in older adults. Surgical hospitalizations are associated with immediate marked life-space declines followed by rapid recovery, in contrast to nonsurgical hospitalizations, which are associated with more modest immediate declines and little evidence of recovery after several years of follow-up. C1 Birmingham & Atlanta Vet Affairs Geriatr Res, Birmingham, AL USA. Ctr Clin, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. RP Brown, CJ (reprint author), Birmingham Vet Affairs Med Ctr, 11G,700 S 19th St, Birmingham, AL 35233 USA. EM cbrown@aging.uab.edu; droth@uab.edu FU National Institute on Aging [R01 AG015062]; Veterans Affairs Research Career Development Award [E4-3842VA]; John A. Hartford Foundation FX Grant Support: By a Veterans Affairs Research Career Development Award (E4-3842VA) (Dr. Brown) and a John A. Hartford Foundation-funded Southeast Center of Excellence in Geriatric Medicine Special Fellows grant (Dr. Brown). The UAB Study of Aging is funded through a grant from the National Institute on Aging (R01 AG015062). NR 40 TC 58 Z9 58 U1 2 U2 6 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 MAR 17 PY 2009 VL 150 IS 6 BP 372 EP W67 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 423AJ UT WOS:000264468500002 PM 19293070 ER PT J AU Go, AS Fang, MC Udaltsova, N Chang, YC Pomernacki, NK Borowsky, L Singer, DE AF Go, Alan S. Fang, Margaret C. Udaltsova, Natalia Chang, Yuchiao Pomernacki, Niela K. Borowsky, Leila Singer, Daniel E. CA ATRIA Study Investigators TI Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study SO CIRCULATION LA English DT Article DE atrial fibrillation; kidney failure, chronic; proteinuria; risk factors; stroke ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; TISSUE-PLASMINOGEN ACTIVATOR; PULSE-WAVE VELOCITY; HEMODIALYSIS-PATIENTS; CARDIOVASCULAR-DISEASE; STROKE PREVENTION; MAINTENANCE HEMODIALYSIS; ANTITHROMBOTIC THERAPY; VONWILLEBRAND-FACTOR AB Background - Atrial fibrillation (AF) substantially increases the risk of ischemic stroke, but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown. Methods and Results - We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects the risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. During 33 165 person-years off anticoagulation among 10 908 patients with AF, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk, 1.54; 95% CI, 1.29 to 1.85), and there was a graded, increased risk of stroke associated with a progressively lower level of estimated glomerular filtration rate compared with a rate >= 60 mL . min(-1) +/- 1.73 m(-2): relative risk of 1.16 (95% CI, 0.95 to 1.40) for estimated glomerular filtration rate of 45 to 59 mL . min(-1) . 1.73 m(-2) and 1.39 (95% CI, 1.13 to 1.71) for estimated glomerular filtration rate < 45 mL . min(-1) . 1.73 m(-2) ( P = 0.0082 for trend). Conclusions - Chronic kidney disease increases the risk of thromboembolism in AF independently of other risk factors. Knowing the level of kidney function and the presence of proteinuria may improve risk stratification for decision making about the use of antithrombotic therapy for stroke prevention in AF. (Circulation. 2009; 119: 1363-1369.) C1 [Go, Alan S.; Udaltsova, Natalia; Pomernacki, Niela K.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Go, Alan S.; Fang, Margaret C.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Go, Alan S.; Fang, Margaret C.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Go, Alan S.; Fang, Margaret C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Chang, Yuchiao; Borowsky, Leila; Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Chang, Yuchiao; Borowsky, Leila; Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St,3rd Floor, Oakland, CA 94612 USA. EM Alan.S.Go@kp.org FU NIA NIH HHS [R01 AG015478-07, AG15478, R01 AG015478, R01 AG015478-04A1, R01 AG015478-05, R01 AG015478-06, R01 AG015478-08] NR 53 TC 160 Z9 170 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 17 PY 2009 VL 119 IS 10 BP 1363 EP 1369 DI 10.1161/CIRCULATIONAHA.108.816082 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700004 PM 19255343 ER PT J AU Bautista, LE Herrera, VM Casas, JP Miranda, J Perel, P Pichardo, R Gonzalez, A Sanchez, JR Ferreccio, C Aguilera, X Silva, E Orostegui, M Gomez, LF Chirinos, JA Medina-Lezama, J Perez, CM Suarez, E Ortiz, AP Rosero, L Schapochnik, N Ortiz, Z Ferrante, D Diaz, M AF Bautista, Leonelo E. Herrera, Victor M. Casas, Juan P. Miranda, Jaime Perel, Pablo Pichardo, Rafael Gonzalez, Angel Sanchez, Jose R. Ferreccio, Catterina Aguilera, Ximena Silva, Egle Orostegui, Myriam Gomez, Luis F. Chirinos, Julio A. Medina-Lezama, Josefina Perez, Cynthia M. Suarez, Erick Ortiz, Ana P. Rosero, Luis Schapochnik, Norberto Ortiz, Zulma Ferrante, Daniel Diaz, Margarita TI Obesity and Blood Pressure: Ethnicity Does Matter SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Bautista, Leonelo E.; Herrera, Victor M.] Univ Wisconsin, Madison, WI USA. [Casas, Juan P.; Miranda, Jaime; Perel, Pablo] London Sch Hyg & Trop Med, London WC1, England. [Pichardo, Rafael; Gonzalez, Angel] Inst Dominicano Cardiol, Santo Domingo, Dominican Rep. [Sanchez, Jose R.] Ctr Nacl Alimentac & Nutr, Inst Nacl Salud, Lima, Peru. [Ferreccio, Catterina] Pontificia Univ Catolica Chile, Santiago, Chile. [Aguilera, Ximena] Minist Salud Chile, Santiago, Chile. [Silva, Egle] Univ Zulia, Fac Med, Inst Invest & Estudios Enfermedades Cardiovasc, Maracaibo 4011, Venezuela. [Orostegui, Myriam] Univ Ind Santander, Epidemiol Rsch Ctr, Fac Dis Epidemiol Observ, Bucaramanga, Colombia. [Gomez, Luis F.] Fdn FES Social, Bogota, Colombia. [Chirinos, Julio A.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Medina-Lezama, Josefina] Santa Maria Catholic Univ, Arequipa, Peru. [Medina-Lezama, Josefina] Santa Maria Rsch Inst, Arequipa, Peru. [Perez, Cynthia M.; Suarez, Erick; Ortiz, Ana P.] Univ Puerto Rico, Grad Sch Publ Hlth, San Juan, PR 00936 USA. [Rosero, Luis] Univ Costa Rica, Ctr Cntramericano Poblac, San Jose, Costa Rica. [Schapochnik, Norberto] Minist Salud Prov Tierra Del Fuego, Tierra Del Fuego, Argentina. [Ortiz, Zulma] Acad Nacl Med Buenos Aires, Inst Invest Epidemiol, Buenos Aires, DF, Argentina. [Ferrante, Daniel] Minist Salud & Ambiente, Buenos Aires, DF, Argentina. [Diaz, Margarita] Med Acad, Ctr Invest, Montevideo, Uruguay. RI Herrera, Victor/C-5602-2008; Miranda, J. Jaime/A-8482-2008 OI Miranda, J. Jaime/0000-0002-4738-5468 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 MAR 17 PY 2009 VL 119 IS 10 BP E346 EP E346 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700365 ER PT J AU Finnerty, K Gaziano, JM Djousse, L AF Finnerty, Kathryn Gaziano, J. Michael Djousse, Luc TI Prehypertension and the Risk of Heart Failure in the Physicians' Health Study I SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Finnerty, Kathryn; Gaziano, J. Michael; Djousse, Luc] Brigham & Womens Hosp, Boston, MA 02115 USA. [Finnerty, Kathryn; Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 17 PY 2009 VL 119 IS 10 BP E322 EP E322 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700254 ER PT J AU Herrera, VM Casas, JP Miranda, J Perel, P Pichardo, R Gonzalez, A Sanchez, JR Ferreccio, C Aguilera, X Silva, E Orostegui, M Gomez, LF Chirinos, JA Medina-Lezama, J Perez, CM Suarez, E Ortiz, AP Rosero, L Schapochnik, N Ortiz, Z Ferrante, D Diaz, M Bautista, LE AF Herrera, Victor M. Casas, Juan P. Miranda, Jaime Perel, Pablo Pichardo, Rafael Gonzalez, Angel Sanchez, Jose R. Ferreccio, Catterina Aguilera, Ximena Silva, Egle Orostegui, Myriam Gomez, Luis F. Chirinos, Julio A. Medina-Lezama, Josefina Perez, Cynthia M. Suarez, Erick Ortiz, Ana P. Rosero, Luis Schapochnik, Norberto Ortiz, Zulma Ferrante, Daniel Diaz, Margarita Bautista, Leonelo E. TI Ethnic and Gender-Specific Effects of Fasting Glucose on Hypertension SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Herrera, Victor M.; Bautista, Leonelo E.] Univ Wisconsin, Madison, WI USA. [Casas, Juan P.; Miranda, Jaime; Perel, Pablo] London Sch Hyg & Trop Med, London WC1, England. [Pichardo, Rafael; Gonzalez, Angel] Inst Dominicano Cardiol, Santo Domingo, Dominican Rep. [Sanchez, Jose R.] Inst Nacl Salud, Ctr Nacl Alimentac & Nutr, Lima, Peru. [Ferreccio, Catterina] Pontificia Univ Catolica Chile, Santiago, Chile. [Aguilera, Ximena] Minist Salud Chile, Santiago, Chile. [Silva, Egle] Univ Zulia, Fac Med, Inst Invest & Estudios Enfermedades Cardiovac, Maracaibo 4011, Venezuela. [Orostegui, Myriam] Univ Ind Santander, Epidemiol Rsch Cntr, Cardiovasc Dis Epidemiol Observ, Bucaramanga, Colombia. [Gomez, Luis F.] Fdn FES Social, Hlth Div, Bogota, Colombia. [Chirinos, Julio A.] Univ Penn, Philadelphia VA Med Cntr, Philadelphia, PA 19104 USA. [Medina-Lezama, Josefina] Santa Maria Catholic Univ, Arequipa, Peru. [Medina-Lezama, Josefina] Santa Maria Rsch Inst, Arequipa, Peru. [Perez, Cynthia M.; Suarez, Erick; Ortiz, Ana P.] Univ Puerto Rico, Grad Sch Publ Hlth, Med Sci Campus, San Juan, PR 00936 USA. [Rosero, Luis] Univ Costa Rica, Cntr Cntramer Poblac, San Jose, Costa Rica. [Schapochnik, Norberto] Minist Salud Prov Tierra Fuego, Tierra Del Fuego, Argentina. [Ortiz, Zulma] Acad Nacl Med Buenos Aires, Inst Invest Epidemiol, Buenos Aires, DF, Argentina. [Ferrante, Daniel] Minist Salud Ambiente, Buenos Aires, DF, Argentina. [Diaz, Margarita] Med Acad, Ctr Invest, Montevideo, Uruguay. RI Herrera, Victor/C-5602-2008; Miranda, J. Jaime/A-8482-2008 OI Miranda, J. Jaime/0000-0002-4738-5468 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 MAR 17 PY 2009 VL 119 IS 10 BP E364 EP E365 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700448 ER PT J AU Kottgen, A Glazer, NL Dehghan, A Hwang, SJ Katz, R Li, M Yang, Q Kao, WHL Coresh, J Shlipak, MG Witteman, J Fox, CS AF Kottgen, Anna Glazer, Nicole L. Dehghan, Abbas Hwang, Shih-Jen Katz, Ronit Li, Man Yang, Qiong Kao, Wen Hong Linda Coresh, Josef Shlipak, Michael G. Witteman, Jacqueline Fox, Caroline S. TI Genome-Wide Association Study of Chronic Kidney Disease and Related Traits in 19,877 Participants in 4 Population-Based Studies Identifies Common Genetic Variants Conferring Disease Risk SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Kottgen, Anna; Li, Man; Kao, Wen Hong Linda; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Glazer, Nicole L.; Katz, Ronit] Univ Washington, Seattle, WA 98195 USA. [Dehghan, Abbas; Witteman, Jacqueline] Erasmus MC, Rotterdam, Netherlands. [Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Yang, Qiong] Boston Univ, Boston, MA 02215 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA 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 MAR 17 PY 2009 VL 119 IS 10 BP E283 EP E283 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700072 ER PT J AU Magnani, JW Mazzini, MJ Sullivan, L Williamson, MA Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Mazzini, Michael J. Sullivan, Lisa Williamson, Mary Ann Ellinor, Patrick T. Benjamin, Emelia J. TI Defining the Epidemiology of P-Wave Dispersion and Duration: Assessment for Quality Control and Measurement Precision SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Magnani, Jared W.; Mazzini, Michael J.; Williamson, Mary Ann; Benjamin, Emelia J.] Boston Med Cntr, Boston, MA USA. [Sullivan, Lisa] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 MAR 17 PY 2009 VL 119 IS 10 BP E316 EP E316 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700226 ER PT J AU Musunuru, K Orho-Melander, M Caulfield, MP Li, SG Salameh, WA Reitz, RE Kathiresan, S Melander, O Krauss, RM AF Musunuru, Kiran Orho-Melander, Marju Caulfield, Michael P. Li, Shuguang Salameh, Wael A. Reitz, Richard E. Kathiresan, Sekar Melander, Olle Krauss, Ronald M. TI Ion Mobility Analysis of Lipoprotein Subfractions Identifies 3 Independent Axes of Cardiovascular Risk SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, MIT, Broad Inst, Boston, MA 02114 USA. [Musunuru, Kiran; Kathiresan, Sekar] Harvard Univ, Boston, MA 02115 USA. [Orho-Melander, Marju; Melander, Olle] Lund Univ, Malmo, Sweden. [Caulfield, Michael P.; Li, Shuguang; Salameh, Wael A.; Reitz, Richard E.] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. [Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. NR 0 TC 0 Z9 0 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 MAR 17 PY 2009 VL 119 IS 10 BP E282 EP E283 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700071 ER PT J AU Newton-Cheh, C Eijgelsheim, M Rice, K de Bakker, PI Yin, XY Estrada, K Bis, J Rivadeneira, F Noseworthy, PA Sotoodehnia, N Smith, NL Rotter, JI Kors, JA Witteman, JC Hofman, A Heckbert, SR O'Donnell, CJ Uitterlinden, AG Psaty, BM Lumley, T Larson, MG Stricker, BH AF Newton-Cheh, Christopher Eijgelsheim, Mark Rice, Kenneth de Bakker, Paul I. Yin, Xiaoyan Estrada, Karol Bis, Joshua Rivadeneira, Fernando Noseworthy, Peter A. Sotoodehnia, Nona Smith, Nicholas L. Rotter, Jerome I. Kors, Jan A. Witteman, Jacqueline C. Hofman, Albert Heckbert, Susan R. O'Donnell, Christopher J. Uitterlinden, Andre G. Psaty, Bruce M. Lumley, Thomas Larson, Martin G. Stricker, Bruno H. TI Common Variants at 10 Loci Influence Myocardial Repolarization: The QTGEN Consortium SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Newton-Cheh, Christopher; Noseworthy, Peter A.] Massachusetts Gen Hosp, Ctr Human Genet Rsch, Cardiovasc Rsch Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher; de Bakker, Paul I.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Boston, MA USA. [Eijgelsheim, Mark; Estrada, Karol; Rivadeneira, Fernando; Kors, Jan A.; Witteman, Jacqueline C.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Rotterdam, Netherlands. [Smith, Nicholas L.] Univ Washington, Sch Med, Cardiovasc Hlth Rsch Unit, Seattle Epidemiol Rsch Cntr, Seattle, WA 98195 USA. [de Bakker, Paul I.] Harvard Univ, Sch Med, Partners HealthCare Cntr Genet & Genom, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Framingham, MA USA. [Yin, Xiaoyan; Larson, Martin G.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Cambridge, MA USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Cambridge, MA USA. [Uitterlinden, Andre G.] Univ Washington, Grp Hlth, Ctr Hlth Sci, Seattle, WA USA. [Stricker, Bruno H.] Inspectorate Hlth Care, Rotterdam, Netherlands. RI Rice, Kenneth/A-4150-2013; de Bakker, Paul/B-8730-2009; Rivadeneira, Fernando/O-5385-2015 OI Rice, Kenneth/0000-0001-5779-4495; de Bakker, Paul/0000-0001-7735-7858; Rivadeneira, Fernando/0000-0001-9435-9441 NR 0 TC 0 Z9 0 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 MAR 17 PY 2009 VL 119 IS 10 BP E277 EP E277 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700044 ER PT J AU Preis, SR Massaro, JM Hoffmann, U D'Agostino, RB Robins, SJ Meigs, JB Vasan, RS O'Donnell, CJ Fox, CS AF Preis, Sarah R. Massaro, Joseph M. Hoffmann, Udo D'Agostino, Ralph B. Robins, Sander J. Meigs, James B. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Neck Circumference as a Novel Measure of Cardiometabolic Risk: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Preis, Sarah R.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hoffmann, Udo; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 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 MAR 17 PY 2009 VL 119 IS 10 BP E302 EP E302 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700160 ER PT J AU Preis, SR Massaro, JM Robins, SJ Hoffmann, U Meigs, JB Vasan, RS Sutherland, P D'Agostino, RB O'Donnell, CJ Fox, CS AF Preis, Sarah R. Massaro, Joseph M. Robins, Sander J. Hoffmann, Udo Meigs, James B. Vasan, Ramachandran S. Sutherland, Patrice D'Agostino, Ralph B., Sr. O'Donnell, Christopher J. Fox, Caroline S. TI Visceral and Subcutaneous Adipose Tissue and Insulin Resistance in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Preis, Sarah R.; Sutherland, Patrice; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Hoffmann, Udo; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 9 Z9 11 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 MAR 17 PY 2009 VL 119 IS 10 BP E296 EP E296 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700131 ER PT J AU Weiner, RB Massaro, JM Vasan, RS Keyes, MJ McCabe, E Schnabel, R Levy, D Benjamin, EJ Wang, TJ AF Weiner, Rory B. Massaro, Joseph M. Vasan, Ramachandran S. Keyes, Michelle J. McCabe, Elizabeth Schnabel, Renate Levy, Daniel Benjamin, Emelia J. Wang, Thomas J. TI Abnormalities in Heart Rate Response to Exercise Are Not Associated with Risk of Atrial Fibrillation SO CIRCULATION LA English DT Meeting Abstract CT Joint Nutrition, Physical Activity and Metabolism Conference/49th Cardiovascular Disease Epidemiology and Prevention of the American-Heart-Association CY MAR 10-14, 2009 CL Palm Harbor, FL SP Amer Heart Assoc C1 [Weiner, Rory B.; Wang, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Massaro, Joseph M.; Vasan, Ramachandran S.; Keyes, Michelle J.; McCabe, Elizabeth; Schnabel, Renate; Levy, Daniel; Benjamin, Emelia J.] Framingham Heart Dis Epidemiol 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 MAR 17 PY 2009 VL 119 IS 10 BP E308 EP E308 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 419TX UT WOS:000264243700190 ER PT J AU Brilakis, ES Lichtenwalter, C de Lemos, JA Roesle, M Obel, O Haagen, D Saeed, B Gadiparthi, C Bissett, JK Sachdeva, R Voudris, VV Karyofillis, P Kar, B Rossen, J Fasseas, P Berger, P Banerjee, S AF Brilakis, Emmanouil S. Lichtenwalter, Christopher de Lemos, James A. Roesle, Michele Obel, Owen Haagen, Donald Saeed, Bilal Gadiparthi, Chiranjeevi Bissett, Joseph K. Sachdeva, Rajesh Voudris, Vassilios V. Karyofillis, Panagiotis Kar, Biswajit Rossen, James Fasseas, Panayotis Berger, Peter Banerjee, Subhash TI A Randomized Controlled Trial of a Paclitaxel-Eluting Stent Versus a Similar Bare-Metal Stent in Saphenous Vein Graft Lesions The SOS (Stenting Of Saphenous Vein Grafts) Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE bare-metal stents; coronary artery bypass graft surgery; drug-eluting stents; outcomes; percutaneous coronary intervention; saphenous vein grafts ID LONG-TERM OUTCOMES; FOLLOW-UP; INTERVENTION; IMPLANTATION; DISEASE AB Objectives The aim of this study was to compare the frequency of angiographic restenosis and clinical events between a paclitaxel-eluting stent (PES) and a similar bare-metal stent (BMS) in saphenous vein graft (SVG) lesions. Background There are conflicting and mostly retrospective data on outcomes after drug-eluting stent implantation in SVGs. Methods Patients requiring SVG lesion stenting were randomized to BMS or PES. The primary study end point was binary in-segment restenosis at 12-month follow-up quantitative coronary angiography. Secondary end points included death, myocardial infarction, ischemia-driven target vessel and lesion revascularization, and target vessel failure. Results Eighty patients with 112 lesions in 88 SVGs were randomized to a BMS (39 patients, 43 grafts, 55 lesions) or PES (41 patients, 45 grafts, 57 lesions). Binary angiographic restenosis occurred in 51% of the BMS-treated lesions versus 9% of the PES-treated lesions (relative risk: 0.18; 95% confidence interval [CI]: 0.07 to 0.48, p < 0.0001). During a median follow-up of 1.5 years the PES patients had less target lesion revascularization (28% vs. 5%, hazard ratio: 0.38; 95% CI: 0.15 to 0.74, p = 0.003) and target vessel failure (46% vs. 22%, hazard ratio: 0.65; 95% CI: 0.42 to 0.96, p = 0.03), a trend toward less target vessel revascularization (31% vs. 15%, hazard ratio: 0.66; 95% CI: 0.39 to 1.05, p = 0.08) and myocardial infarction (31% vs. 15%, hazard ratio: 0.67; 95% CI: 0.40 to 1.08, p = 0.10), and similar mortality (5% vs. 12%, hazard ratio: 1.56; 95% CI: 0.72 to 4.11, p = 0.27). Conclusions In SVG lesions, PES are associated with lower rates of angiographic restenosis and target vessel failure than BMS. (The SOS [Stenting of Saphenous Vein Grafts] Randomized-Controlled Trial; NCT00247208) (J Am Coll Cardiol 2009; 53: 919-28) (C) 2009 by the American College of Cardiology Foundation C1 [Brilakis, Emmanouil S.; Lichtenwalter, Christopher; de Lemos, James A.; Roesle, Michele; Obel, Owen; Haagen, Donald; Gadiparthi, Chiranjeevi; Banerjee, Subhash] Vet Affairs N Texas Healtchcare Syst, Dallas, TX USA. [Brilakis, Emmanouil S.; Lichtenwalter, Christopher; de Lemos, James A.; Obel, Owen; Gadiparthi, Chiranjeevi; Banerjee, Subhash] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Saeed, Bilal] Univ Toledo, Dept Internal Med, Toledo, OH 43606 USA. [Bissett, Joseph K.; Sachdeva, Rajesh] Cent Arkansas Vet Hlthcare Syst, Little Rock, AR USA. [Bissett, Joseph K.; Sachdeva, Rajesh] Univ Arkansas Med Sci, Little Rock, AR USA. [Voudris, Vassilios V.; Karyofillis, Panagiotis] Onassis Cariac Surg Ctr, Athens, Greece. [Kar, Biswajit] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Rossen, James] Iowa City Vet Affairs Med Ctr, Iowa City, IA USA. [Fasseas, Panayotis] Wheaton Franciscan Med Grp, Racine, WI USA. [Berger, Peter] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. RP Brilakis, ES (reprint author), Dallas VA Med Ctr 111A, 4500 S Lancaster Rd, Dallas, TX 75216 USA. EM esbrilakis@yahoo.com RI Brilakis, Emmanouil/B-5282-2009; OI Sachdeva, Rajesh/0000-0002-7729-6247; Brilakis, Emmanouil/0000-0001-9416-9701 NR 25 TC 119 Z9 126 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 MAR 17 PY 2009 VL 53 IS 11 BP 919 EP 928 DI 10.1016/j.jacc.2008.11.029 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 417GX UT WOS:000264065600002 PM 19281920 ER PT J AU Chitnis, T Pirko, I AF Chitnis, Tanuja Pirko, Istvan TI Sensitivity vs specificity Progress and pitfalls in defining MRI criteria for pediatric MS SO NEUROLOGY LA English DT Editorial Material ID MULTIPLE-SCLEROSIS; PROGNOSTIC-FACTORS; CHILDHOOD; RELAPSE; COHORT C1 [Pirko, Istvan] Univ Cincinnati, Dept Neurol, Waddell Ctr Multiple Sclerosis, Cincinnati, OH 45267 USA. [Chitnis, Tanuja] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA. RP Pirko, I (reprint author), Univ Cincinnati, Dept Neurol, Waddell Ctr Multiple Sclerosis, 260 Stetson St,Suite 2300,POB 670525, Cincinnati, OH 45267 USA. EM Istvan.Pirko@uc.edu NR 10 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 17 PY 2009 VL 72 IS 11 BP 952 EP 953 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 419TW UT WOS:000264243600002 PM 19289735 ER PT J AU Xia, XB Lemieux, ME Li, W Carroll, JS Brown, M Liu, XS Kung, AL AF Xia, Xiaobo Lemieux, Madeleine E. Li, Wei Carroll, Jason S. Brown, Myles Liu, X. Shirley Kung, Andrew L. TI Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ChIP-chip; hypoxia; jumonji protein; dioxygenase; epigenetics ID UBIQUITIN-PROTEASOME PATHWAY; GENOME-WIDE ANALYSIS; TRANSCRIPTION ACTIVATION; ANDROGEN RECEPTOR; CELLULAR-RESPONSE; MAMMALIAN-CELLS; FACTOR 1-ALPHA; HYPOXIA; SITES; FAMILY AB Adaptation to hypoxia is mediated through a coordinated transcriptional response driven largely by hypoxia-inducible factor 1 (HIF-1). We used ChIP-chip and gene expression profiling to identify direct targets of HIF-1 transactivation on a genome-wide scale. Several hundred direct HIF-1 targets were identified and, as expected, were highly enriched for proteins that facilitate metabolic adaptation to hypoxia. Surprisingly, there was also striking enrichment for the family of 2-oxoglutarate dioxygenases, including the jumonji-domain histone demethylases. We demonstrate that these histone demethylases are direct HIF targets, and their up-regulation helps maintain epigenetic homeostasis under hypoxic conditions. These results suggest that the coordinated increase in expression of several oxygen-dependent enzymes by HIF may help compensate for decreased levels of oxygen under conditions of cellular hypoxia. C1 [Xia, Xiaobo; Lemieux, Madeleine E.; Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Li, Wei; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Carroll, Jason S.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Li, Wei; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kung, Andrew L.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Kung, AL (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM andrew_kung@dfd.harvard.edu RI Li, Wei/A-8544-2009; OI Lemieux, Madeleine/0000-0001-6355-8691; Brown, Myles/0000-0002-8213-1658; Kung, Andrew/0000-0002-9091-488X FU Sidney Kimmel Foundation; American Cancer Society; National Institutes of Health; DFCI-Novartis Drug Discovery Program FX We thank Yang Shi and Xiaodong Li ( Harvard Medical School) for providing the JARID1B expression plasmid and protocols and Chris Fry ( Cell Signaling Technology) for JARID1B antibody. This work was supported by the Sidney Kimmel Foundation, American Cancer Society, National Institutes of Health, and the DFCI-Novartis Drug Discovery Program ( A. L. K.). NR 38 TC 183 Z9 190 U1 1 U2 14 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 MAR 17 PY 2009 VL 106 IS 11 BP 4260 EP 4265 DI 10.1073/pnas.0810067106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 420HD UT WOS:000264278800039 PM 19255431 ER PT J AU San-Cristobal, P Pacheco-Alvarez, D Richardson, C Ring, AM Vazquez, N Rafiqi, FH Chari, D Kahle, KT Leng, Q Bobadilla, NA Hebert, SC Alessi, DR Lifton, RP Gamba, G AF San-Cristobal, Pedro Pacheco-Alvarez, Diana Richardson, Ciaran Ring, Aaron M. Vazquez, Norma Rafiqi, Fatema H. Chari, Divya Kahle, Kristopher T. Leng, Qiang Bobadilla, Norma A. Hebert, Steven C. Alessi, Dario R. Lifton, Richard P. Gamba, Gerardo TI Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE angiotensin II receptor; hypertension; distal convoluted tubule; salt reabsorption; thiazide ID SODIUM-CHLORIDE COTRANSPORTER; CORTICAL COLLECTING DUCT; ALANINE-RICH KINASE; WNK KINASES; BLOOD-PRESSURE; MOLECULAR PATHOGENESIS; MUTANT WNK4; HYPERTENSION; OSR1; SPAK AB Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and high serum K(+) levels (hyperkalemia). WNK4 has distinct functional states that regulate the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter NCC and the K(+) channel ROMK. WNK4's functions could enable differential responses to intravascular volume depletion (hypovolemia) and hyperkalemia. Because hypovolemia is uniquely associated with high angiotensin II (AngII) levels, AngII signaling might modulate WNK4 activity. We show that AngII signaling in Xenopus oocytes increases NCC activity by abrogating WNK4's inhibition of NCC but does not alter WNK4's inhibition of ROMK. This effect requires AngII, its receptor AT1R, and WNK4, and is prevented by the AT1R inhibitor losartan. NCC activity is also increased by WNK4 harboring mutations found in PHAII, and this activity cannot be further augmented by AngII signaling, consistent with PHAII mutations providing constitutive activation of the signaling pathway between AT1R and NCC. AngII's effect on NCC is also dependent on the kinase SPAK because dominant-negative SPAK or elimination of the SPAK binding motif in NCC prevent activation of NCC by AngII signaling. These effects extend to mammalian cells. AngII increases phosphorylation of specific sites on SPAK and NCC that are necessary for activation of each in mpkDCT cells. These findings place WNK4 in the signaling pathway between AngII and NCC, and provide a mechanism by which hypovolemia maximizes renal salt reabsoprtion without concomitantly increasing K(+) secretion. C1 [Ring, Aaron M.; Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Chari, Divya; Leng, Qiang; Hebert, Steven C.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Kahle, Kristopher T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [San-Cristobal, Pedro; Pacheco-Alvarez, Diana; Vazquez, Norma; Bobadilla, Norma A.; Gamba, Gerardo] Univ Nacl Autonoma Mexico, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mol Physiol Unit, Mexico City 14000, DF, Mexico. [San-Cristobal, Pedro; Pacheco-Alvarez, Diana; Vazquez, Norma; Bobadilla, Norma A.; Gamba, Gerardo] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 14000, DF, Mexico. [Pacheco-Alvarez, Diana] Univ Panamer, Escuela Med, Mexico City 03920, DF, Mexico. [Richardson, Ciaran; Rafiqi, Fatema H.; Alessi, Dario R.] Univ Dundee, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. RP Lifton, RP (reprint author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. EM richard.lifton@yale.edu; gamba@biomedicas.unam.mx RI Leng, John/A-9359-2011; OI Alessi, Dario/0000-0002-2140-9185 FU National Institutes of Health [DK-64635]; El Consejo Nacional de Ciencia y Tecnologia (CONACYT-Mexico) [59992]; Foundation Leducq Transatlantic Network on Hypertension; Howard Hughes Medical Institute; U. K. Medical research Council; Dundee Camper Down Lodge and the Medical Research Council; Yale Medical Scientist Training Program; Goldwater Scholarship FX This work was supported by National Institutes of Health Grant DK-64635 (to G. G.), El Consejo Nacional de Ciencia y Tecnologia (CONACYT-Mexico) Grant 59992 (to G. G.), the Foundation Leducq Transatlantic Network on Hypertension (to R. P. L. and GG), the Howard Hughes Medical Institute (R. P. L.), the U. K. Medical research Council (to D. R. A), a scholarship from CONACYT-Mexico (to P. S.- C.), a special Fellowship from Dundee Camper Down Lodge and the Medical Research Council (to P. S.- C.), the Yale Medical Scientist Training Program (to K. T. K.), and a Goldwater Scholarship (A. M. R.). NR 40 TC 148 Z9 151 U1 0 U2 5 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 MAR 17 PY 2009 VL 106 IS 11 BP 4384 EP 4389 DI 10.1073/pnas.0813238106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 420HD UT WOS:000264278800060 PM 19240212 ER PT J AU Wang, CY Kim, HH Hiroi, Y Sawada, N Salomone, S Benjamin, LE Walsh, K Moskowitz, MA Liao, JK AF Wang, Chao-Yung Kim, Hyung-Hwan Hiroi, Yukio Sawada, Naoki Salomone, Salvatore Benjamin, Laura E. Walsh, Kenneth Moskowitz, Michael A. Liao, James K. TI Obesity Increases Vascular Senescence and Susceptibility to Ischemic Injury Through Chronic Activation of Akt and mTOR SO SCIENCE SIGNALING LA English DT Article ID REPLICATIVE LIFE-SPAN; PROTEIN-KINASE AKT; CELLULAR SENESCENCE; NITRIC-OXIDE; PATHOLOGICAL ANGIOGENESIS; POSTNATAL ANGIOGENESIS; ENDOTHELIAL-CELLS; RAPAMYCIN; GROWTH; MICE AB Obesity and age are important risk factors for cardiovascular disease. However, the signaling mechanism linking obesity with age-related vascular senescence is unknown. Here we show that mice fed a high-fat diet show increased vascular senescence and vascular dysfunction compared to mice fed standard chow and are more prone to peripheral and cerebral ischemia. All of these changes involve long-term activation of the protein kinase Akt. In contrast, mice with diet-induced obesity that lack Akt1 are resistant to vascular senescence. Rapamycin treatment of diet-induced obese mice or of transgenic mice with long-term activation of endothelial Akt inhibits activation of mammalian target of rapamycin (mTOR)-rictor complex 2 and Akt, prevents vascular senescence without altering body weight, and reduces the severity of limb necrosis and ischemic stroke. These findings indicate that long-term activation of Akt-mTOR signaling links diet-induced obesity with vascular senescence and cardiovascular disease. C1 [Wang, Chao-Yung; Kim, Hyung-Hwan; Hiroi, Yukio; Sawada, Naoki; Liao, James K.] Brigham & Womens Hosp, Vasc Med Res Unit, Cambridge, MA 02139 USA. [Wang, Chao-Yung; Kim, Hyung-Hwan; Hiroi, Yukio; Sawada, Naoki; Liao, James K.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Salomone, Salvatore; Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02139 USA. [Salomone, Salvatore; Moskowitz, Michael A.] Harvard Univ, Sch Med, Charlestown, MA 02139 USA. [Benjamin, Laura E.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Benjamin, Laura E.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Walsh, Kenneth] Boston Univ, Sch Med, Mol Cardiol Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Liao, JK (reprint author), Brigham & Womens Hosp, Vasc Med Res Unit, Cambridge, MA 02139 USA. EM jliao@rics.bwh.harvard.edu OI Walsh, Kenneth/0000-0001-7580-2276; Salomone, Salvatore/0000-0001-5307-6103; Wang, Chao-Yung/0000-0003-1546-7298 FU NHLBI NIH HHS [R01 HL052233, R01 HL052233-11, R01 HL052233-12, R01 HL052233-10, R01 HL070274-04, R01 HL070274, R01 HL070274-03, R01 HL080187-04, R01 HL070274-05, R01 HL080187, R01 HL080187-03]; NINDS NIH HHS [P50 NS010828-310036, P50 NS010828, P50 NS010828-320036, P50 NS010828-300036] NR 55 TC 64 Z9 66 U1 0 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD MAR 17 PY 2009 VL 2 IS 62 AR ra11 DI 10.1126/scisignal.2000143 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 567UW UT WOS:000275473100002 PM 19293429 ER PT J AU Means, TK Mylonakis, E Tampakakis, E Colvin, RA Seung, E Puckett, L Tai, MF Stewart, CR Pukkila-Worley, R Hickman, SE Moore, KJ Calderwood, SB Hacohen, N Luster, AD El Khoury, J AF Means, Terry K. Mylonakis, Eleftherios Tampakakis, Emmanouil Colvin, Richard A. Seung, Edward Puckett, Lindsay Tai, Melissa F. Stewart, Cameron R. Pukkila-Worley, Read Hickman, Suzanne E. Moore, Kathryn J. Calderwood, Stephen B. Hacohen, Nir Luster, Andrew D. El Khoury, Joseph TI Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CRYPTOCOCCUS-NEOFORMANS INFECTION; LOW-DENSITY LIPOPROTEINS; TOLL-LIKE RECEPTOR-2; CAENORHABDITIS-ELEGANS; CANDIDA-ALBICANS; HOST-DEFENSE; IN-VIVO; DENDRITIC CELLS; BETA-GLUCANS; INFLAMMATORY RESPONSES AB Receptors involved in innate immunity to fungal pathogens have not been fully elucidated. We show that the Caenorhabditis elegans receptors CED-1 and C03F11.3, and their mammalian orthologues, the scavenger receptors SCARF1 and CD36, mediate host defense against two prototypic fungal pathogens, Cryptococcus neoformans and Candida albicans. CED-1 and C03F11.1 mediated antimicrobial peptide production and were necessary for nematode survival after C. neoformans infection. SCARF1 and CD36 mediated cytokine production and were required for macrophage binding to C. neoformans, and control of the infection in mice. Binding of these pathogens to SCARF1 and CD36 was beta-glucan dependent. Thus, CED-1/SCARF1 and C03F11.3/CD36 are beta-glucan binding receptors and define an evolutionarily conserved pathway for the innate sensing of fungal pathogens. C1 [Means, Terry K.; Colvin, Richard A.; Seung, Edward; Puckett, Lindsay; Tai, Melissa F.; Hickman, Suzanne E.; Hacohen, Nir; Luster, Andrew D.; El Khoury, Joseph] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Means, Terry K.; Colvin, Richard A.; Seung, Edward; Puckett, Lindsay; Tai, Melissa F.; Hickman, Suzanne E.; Hacohen, Nir; Luster, Andrew D.; El Khoury, Joseph] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Means, Terry K.; Colvin, Richard A.; Seung, Edward; Puckett, Lindsay; Tai, Melissa F.; Hickman, Suzanne E.; Hacohen, Nir; Luster, Andrew D.; El Khoury, Joseph] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Mylonakis, Eleftherios; Tampakakis, Emmanouil; Pukkila-Worley, Read; Calderwood, Stephen B.; El Khoury, Joseph] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Stewart, Cameron R.; Moore, Kathryn J.] Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. [Means, Terry K.; Hacohen, Nir] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Means, TK (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. EM tmeans@partners.org; jelkhoury@partners.org RI Stewart, Cameron/E-6823-2011; OI Moore, kathryn/0000-0003-2505-2547 FU National Institutes of Health [AR051367, NS059005, AG032349, AI63084, AI075286, AI71060, AG20255]; Irvington Institute FX This work was supported by National Institutes of Health grants AR051367 (to T. K. Means), NS059005 and AG032349 (to J. El Khoury), AI63084 and AI075286 (to E. Mylonakis), AI71060 (to N. Hacohen), and AG20255 (to K. J. Moore), and an Irvington Institute grant (to T. K. Means). NR 60 TC 121 Z9 133 U1 1 U2 12 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 MAR 16 PY 2009 VL 206 IS 3 BP 637 EP 653 DI 10.1084/jem.20082109 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444VT UT WOS:000266009200013 PM 19237602 ER PT J AU Hikida, M Casola, S Takahashi, N Kaji, T Takemori, T Rajewsky, K Kurosaki, T AF Hikida, Masaki Casola, Stefano Takahashi, Noriko Kaji, Tomohiro Takemori, Toshitada Rajewsky, Klaus Kurosaki, Tomohiro TI PLC-gamma 2 is essential for formation and maintenance of memory B cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PHOSPHOLIPASE C-GAMMA-2; IMMUNOLOGICAL MEMORY; CLONAL SELECTION; AFFINITY MATURATION; GERMINAL-CENTERS; DENDRITIC CELLS; DEFICIENT MICE; ANTIGEN; GENERATION; RECEPTOR AB Resting antigen-experienced memory B cells are thought to be responsible for the more rapid and robust antibody responses after antigen reencounter, which are the hallmark of memory humoral responses. The molecular basis for the development and survival of memory B cells remains largely unknown. We report that phospholipase C (PLC) gamma 2 is required for efficient formation of germinal center (GC) and memory B cells. Moreover, memory B cell homeostasis is severely hampered by inducible loss of PLC-gamma 2. Accordingly, mice with a conditional deletion of PLC-gamma 2 in post-GC B cells had an almost complete abrogation of the secondary antibody response. Collectively, our data suggest that PLC-gamma 2 conveys a survival signal to GC and memory B cells and that this signal is required for a productive secondary immune response. C1 [Hikida, Masaki; Takahashi, Noriko; Kurosaki, Tomohiro] RIKEN, Res Ctr Allergy & Immunol, Lab Lymphocyte Differentiat, Kanagawa 2300045, Japan. [Kaji, Tomohiro; Takemori, Toshitada] RIKEN, Res Ctr Allergy & Immunol, Lab Immunol Memory, Kanagawa 2300045, Japan. [Kurosaki, Tomohiro] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Lymphocyte Differentiat, Suita, Osaka 5650871, Japan. [Casola, Stefano] FIRC Inst Mol Oncol IFOM, I-20139 Milan, Italy. [Rajewsky, Klaus] Harvard Univ, Sch Med, Inst Biomed Res, Ctr Blood Res, Boston, MA 02115 USA. [Hikida, Masaki] Kyoto Univ, Grad Sch Med, Ctr Innovat Immunoregulat Technol & Therapeut, Sakyo Ku, Kyoto 6068501, Japan. RP Kurosaki, T (reprint author), RIKEN, Res Ctr Allergy & Immunol, Lab Lymphocyte Differentiat, Kanagawa 2300045, Japan. EM kurosaki@rcai.riken.jp RI Kurosaki, Tomohiro/D-1306-2009 OI Kurosaki, Tomohiro/0000-0002-6352-304X FU Japanese Ministry of Education, Culture, Sports, Science and Technology; Naitoh Memorial Foundation; National Institutes of Health FX This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology to M. Hikida and T. Kurosaki, the Naitoh Memorial Foundation to T. Kurosaki, and grants from the National Institutes of Health to K. Rajewsky. NR 42 TC 38 Z9 40 U1 0 U2 6 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 MAR 16 PY 2009 VL 206 IS 3 BP 681 EP 689 DI 10.1084/jem.20082100 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444VT UT WOS:000266009200016 PM 19273623 ER PT J AU Goulart, BHL Clark, JW Lauwers, GY Ryan, DP Grenon, N Muzikansky, A Zhu, AX AF Goulart, Bernardo H. L. Clark, Jeffrey W. Lauwers, Gregory Y. Ryan, David P. Grenon, Nina Muzikansky, Alona Zhu, Andrew X. TI Long term survivors with metastatic pancreatic adenocarcinoma treated with gemcitabine: a retrospective analysis SO JOURNAL OF HEMATOLOGY & ONCOLOGY LA English DT Article ID HIGH-DOSE LEUCOVORIN; PROGNOSTIC-FACTORS; PHASE-III; CANCER; CARCINOMA; FLUOROURACIL; CHEMOTHERAPY; THERAPY; TRIAL; STATISTICS AB Background: Metastatic pancreatic adenocarcinoma has a short median overall survival (OS) of 5-6 months. However, a subgroup of patients survives more than 1 year. We analyzed the survival outcomes of this subgroup and evaluated clinical and pathological factors that might affect survival durations. Methods: We identified 20 patients with metastatic or recurrent pancreatic adenocarcinoma who received single-agent gemcitabine and had an OS longer than 1 year. Baseline data available after the diagnosis of metastatic or recurrent disease was categorized as: 1) clinical/demographic data (age, gender, ECOG PS, number and location of metastatic sites); 2) Laboratory data (Hematocrit, hemoglobin, glucose, LDH, renal and liver function and CA19-9); 3) Pathologic data (margins, nodal status and grade); 4) Outcomes data (OS, Time to Treatment Failure (TTF), and 2 year-OS). The lowest CA19-9 levels during treatment with gemcitabine were also recorded. We performed a univariate analysis with OS as the outcome variable. Results: Baseline logarithm of CA19-9 and total bilirubin had a significant impact on OS (HR = 1.32 and 1.31, respectively). Median OS and TTF on gemcitabine were 26.9 (95% CI = 18 to 32) and 11.5 (95% CI = 9.0 to 14.3) months, respectively. Two-year OS was 56.4%, with 7 patients alive at the time of analysis. Conclusion: A subgroup of patients with metastatic pancreatic cancer has prolonged survival after treatment with gemcitabine. Only bilirubin and CA 19-9 levels were predictive of longer survival in this population. Further analysis of potential prognostic and predictive markers of response to treatment and survival are needed. C1 [Goulart, Bernardo H. L.; Clark, Jeffrey W.; Ryan, David P.; Grenon, Nina; Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat,Div Hematol Oncol, Boston, MA 02115 USA. [Lauwers, Gregory Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat,Dept Pathol, Boston, MA USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat,Div Hematol Oncol, Boston, MA 02115 USA. EM bhg@u.washington.edu; jclark@partners.org; glauwers@partners.org; dpryan@partners.org; ngrenon@partners.org; amuzikansky@partners.org; azhu@partners.org NR 30 TC 13 Z9 13 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8722 J9 J HEMATOL ONCOL JI J. Hematol. Oncol. PD MAR 16 PY 2009 VL 2 AR 13 DI 10.1186/1756-8722-2-13 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 524JN UT WOS:000272139700001 PM 19291303 ER PT J AU Pflederer, T Marwan, M Renz, A Bachmann, S Ropers, D Kuettner, A Anders, K Bamberg, F Daniel, WG Achenbach, S AF Pflederer, Tobias Marwan, Mohamed Renz, Alexandra Bachmann, Sven Ropers, Dieter Kuettner, Axel Anders, Katharina Bamberg, Fabian Daniel, Werner G. Achenbach, Stephan TI Noninvasive Assessment of Coronary In-Stent Restenosis by Dual-Source Computed Tomography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DIAGNOSTIC-ACCURACY; ARTERY-DISEASE; CT DSCT; ANGIOGRAPHY; PATENCY AB Assessment of coronary artery stents using computed tomographic angiography has been challenging. The technology of dual-source computed tomography (DSCT) provides higher temporal resolution that may allow more accurate evaluation of coronary stents. This study evaluated the accuracy of DSCT for the assessment of coronary artery in-stent restenosis. A total of 112 patients with 150 previously implanted coronary stents (diameter >= 3.0 mm) were examined using DSCT (Definition; Siemens Medical Solutions, Forchheim, Germany) before conventional coronary angiography. Each stent was classified as assessable or not assessable. All assessable stents were further classified for the absence or presence of in-stent restenosis (>50% diameter reduction) using DSCT, and results were compared with those using quantitative coronary angiography. Mean stent diameter was 3.27 +/- 0.35 mm. Fifteen of 80 stents (19%) with a diameter of >= 3.0 mm were not assessable, and all 70 stents >3.0 mm were assessable. DSCT correctly identified 16 of 19 in-stem restenoses in 135 assessable stents, as well as the absence of in-stent restenosis in 110 of 116 stents (sensitivity 84%, specificity 95%, positive predictive value 73%, and negative predictive value 97% in assessable stents). In conclusion, DSCT may be useful to noninvasively detect in-stent restenosis, especially in stents with a relatively large diameter. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:812-817) C1 [Pflederer, Tobias; Marwan, Mohamed; Renz, Alexandra; Bachmann, Sven; Ropers, Dieter; Daniel, Werner G.; Achenbach, Stephan] Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, Erlangen, Germany. [Kuettner, Axel; Anders, Katharina] Univ Erlangen Nurnberg, Inst Diagnost Radiol, Erlangen, Germany. [Bamberg, Fabian; Achenbach, Stephan] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Bamberg, Fabian; Achenbach, Stephan] Harvard Univ, Sch Med, Boston, MA USA. RP Pflederer, T (reprint author), Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, Erlangen, Germany. EM tobiaspflederer@web.de NR 18 TC 19 Z9 24 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 2009 VL 103 IS 6 BP 812 EP 817 DI 10.1016/j.amjcard.2008.11.036 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 423RT UT WOS:000264514100011 PM 19268737 ER PT J AU Jacobs, ET Ahnen, DJ Ashbeck, EL Baron, JA Greenberg, ER Lance, P Lieberman, DA McKeown-Eyssen, G Schatzkin, A Thompson, PA Martinez, ME AF Jacobs, Elizabeth T. Ahnen, Dennis J. Ashbeck, Erin L. Baron, John A. Greenberg, E. Robert Lance, Peter Lieberman, David A. McKeown-Eyssen, Gail Schatzkin, Arthur Thompson, Patricia A. Martinez, Maria Elena TI Association Between Body Mass Index and Colorectal Neoplasia at Follow-Up Colonoscopy: A Pooling Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adenoma; body mass index; colorectal neoplasms; meta-analysis as topic; neoplasms; second primary; recurrence ID COLON-CANCER RISK; WOMEN UNITED-STATES; PHYSICAL-ACTIVITY; WAIST CIRCUMFERENCE; ADENOMA RECURRENCE; METABOLIC SYNDROME; RECTAL-CANCER; WEIGHT-GAIN; OBESITY; MEN AB A direct relation between body mass index (BMI) and risk of colorectal adenomas and cancer has been reported, but few studies have had adequate sample size for conducting stratified analyses by sex, family history, colorectal subsite, or features of metachronous lesions. Data from 8,213 participants in 7 prospective studies of metachronous colorectal adenomas were pooled to assess whether the association between BMI and metachronous neoplasia varied by these factors. A statistically significant direct association between BMI and the odds of nonadvanced adenomas (P(trend) < 0.001) was observed, while the relation for advanced adenomas was of marginal significance (P(trend) < 0.07). In sex-stratified analyses, obesity was statistically significantly associated with the odds of any metachronous lesion among men (odds ratio = 1.36, 95% confidence interval: 1.17, 1.58) but not among women (odds ratio = 1.10, 95% confidence interval: 0.89, 1.37). The associations with BMI appeared to be limited to proximal neoplasia, with statistically significant results for BMI and proximal (P(trend) < 0.001), but not distal (P(trend) < 0.85), neoplasia. Exploratory analyses indicated that BMI was significantly related to most histologic characteristics of metachronous adenomas among men but not among women. Our results provide further support for the association between BMI and metachronous colorectal adenomas, particularly among men, thereby indicating that body size may affect colorectal carcinogenesis at comparatively early stages. C1 [Jacobs, Elizabeth T.] Univ Arizona, Arizona Canc Ctr, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85724 USA. [Ahnen, Dennis J.] Denver VA Med Ctr, Denver, CO USA. [Ahnen, Dennis J.] Univ Colorado, Denver, CO 80202 USA. [Baron, John A.; Greenberg, E. Robert] Dartmouth Med Sch, Sect Biostat & Epidemiol, Lebanon, NH USA. [Greenberg, E. Robert] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lance, Peter] Univ Arizona, Coll Med, Tucson, AZ 85724 USA. [Lieberman, David A.] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. [Lieberman, David A.] Portland VA Med Ctr, Portland, OR USA. [McKeown-Eyssen, Gail] Univ Toronto, Dalla Lana Sch Publ Heath, Toronto, ON, Canada. [McKeown-Eyssen, Gail] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. [Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Thompson, Patricia A.] Univ Arizona, Dept Pathol, Tucson, AZ 85724 USA. RP Jacobs, ET (reprint author), Univ Arizona, Arizona Canc Ctr, Mel & Enid Zuckerman Coll Publ Hlth, POB 245024, Tucson, AZ 85724 USA. EM jacobse@u.arizona.edu RI Lance, Peter/I-2196-2014 OI Lance, Peter/0000-0003-2944-1881 FU National Cancer Institute [CA-41108, CA-23074, CA95060, CA37287, CA23108, CA 59005, CA 26852]; K07 Career Development Award [CA106269]; Cooperative Studies Program; Department of Veterans Affairs FX This work was supported by the National Cancer Institute ( grants CA-41108, CA-23074, CA95060, CA37287, CA37287, CA23108, CA 59005, and CA 26852). Dr. Jacobs is supported by a K07 Career Development Award ( grant CA106269) from the National Cancer Institute. Funding for the Veterans Affairs Study was supported by the Cooperative Studies Program, Department of Veterans Affairs. Conflict of interest: none declared. NR 52 TC 40 Z9 42 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 MAR 15 PY 2009 VL 169 IS 6 BP 657 EP 666 DI 10.1093/aje/kwn401 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 413ZT UT WOS:000263834400002 PM 19147743 ER PT J AU O'Reilly, EJ Chen, HL Gardener, H Gao, X Schwarzschild, MA Ascherio, A AF O'Reilly, Eilis J. Chen, Honglei Gardener, Hannah Gao, Xiang Schwarzschild, Michael A. Ascherio, Alberto TI Smoking and Parkinson's Disease: Using Parental Smoking as a Proxy to Explore Causality SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE causality; Parkinson disease; smoking; tobacco smoke pollution ID CIGARETTE-SMOKING; TOBACCO USE; RISK; METAANALYSIS; CONSUMPTION; HEALTH; WOMEN; TWINS AB In epidemiologic studies and in studies of discordant twins, cigarette smoking has been consistently associated with a lower risk of Parkinson's disease, but whether this association is causal remains controversial. Alternatively, an infectious or toxic exposure in childhood or early adulthood could affect both the reward mechanisms that determine smoking behavior and the future risk of Parkinson's disease. If so, parental smoking, commonly established before the birth of the first child, would be unlikely to be related to Parkinson's disease risk. The authors assessed the association between Parkinson's disease and parental smoking during childhood in the Nurses' Health Study and the Health Professionals Follow-up Study conducted in the United States. During 26 years and 18 years of follow-up, respectively, 455 newly diagnosed Parkinson's disease cases were documented among those who provided information on parental smoking. The age-adjusted, pooled relative rate of Parkinson's disease was 0.73 (95% confidence interval: 0.53, 1.00; P-trend = 0.04) comparing participants who reported that both parents smoked with those who reported that neither did. Adjustment for caffeine and alcohol intake did not materially change the results. If the inverse association between smoking and Parkinson's disease were due to confounding by an environmental factor or were the result of reverse causation, it is unlikely that parental smoking would predict Parkinson's disease. C1 [O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [O'Reilly, Eilis J.; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Gardener, Hannah] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA. RP O'Reilly, EJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02215 USA. EM eoreilly@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU National Institutes of Health/National Institute of Neurological Diseases and Stroke grant; National Institute of Environmental Health Sciences FX The study was supported by a National Institutes of Health/National Institute of Neurological Diseases and Stroke grant ( to A. A.) to study Parkinson's disease in the Health Professionals Follow-up Study and Nurses' Health Study cohorts and by the intramural program of the National Institutes of Health, the National Institute of Environmental Health Sciences ( to H. C.). NR 18 TC 22 Z9 24 U1 0 U2 1 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 MAR 15 PY 2009 VL 169 IS 6 BP 678 EP 682 DI 10.1093/aje/kwn388 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 413ZT UT WOS:000263834400004 PM 19131566 ER PT J AU Peralta, CA Katz, R Madero, M Sarnak, M Kramer, H Criqui, MH Shlipak, MG AF Peralta, Carmen A. Katz, Ronit Madero, Magdalena Sarnak, Mark Kramer, Holly Criqui, Michael H. Shlipak, Michael G. TI The Differential Association of Kidney Dysfunction With Small and Large Arterial Elasticity The Multiethnic Study of Atherosclerosis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE albuminuria; cystatin C; elasticity; kidney; kidney diseases ID PULSE-WAVE VELOCITY; GLOMERULAR-FILTRATION-RATE; AORTIC STIFFNESS; CARDIOVASCULAR MORTALITY; CREATININE CLEARANCE; SERUM CREATININE; CONTOUR ANALYSIS; RENAL-FUNCTION; NORMAL VALUES; DISEASE AB Vascular remodeling may be a mechanism linking chronic kidney disease to cardiovascular disease. Whether early kidney dysfunction is associated with small and large arterial remodeling is not well understood. Using multivariable linear regression, back-transforming beta-coefficients to relative difference, the authors studied the association of cystatin C, creatinine-based estimated glomerular filtration rate (GFR), and albuminuria with small (SAE) and large (LAE) arterial elasticity and aortic distensibility among 6,282 participants in the Multiethnic Study of Atherosclerosis at baseline (2000-2002). Compared with the lowest quintile, higher quintiles of cystatin C were incrementally associated with lower SAE: third quintile relative difference = -5% (95% confidence interval (CI): -8, -2); fourth quintile relative difference = -10% (95% CI: -13, -8); and highest quintile relative difference = -16% (95% CI: -20, -12). By use of creatinine, the association was observed only among those with chronic kidney disease (estimated GFR, < 60 mL/minute/1.73 m(2)): relative difference = -9% (95% CI: -13, -4). Albuminuria was significantly associated with lower SAE: relative difference = -6% (95% CI: -10, -1). Cystatin C was associated with lower LAE only at the highest quintile (relative difference = -3%, 95% CI: -6, 0) compared with the lowest quintile. By use of creatinine, chronic kidney disease was not independently associated with LAE (P = 0.912). Cystatin C, estimated GFR, and albuminuria were not associated with aortic distensibility (P = 0.26, 0.48, 0.45). Early kidney dysfunction is significantly associated with decreased arterial elasticity in smaller arteries and, to a lesser degree, in larger arteries. C1 [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Katz, Ronit] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Madero, Magdalena; Sarnak, Mark] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA. [Kramer, Holly] Loyola Univ, Med Ctr, Dept Prevent Med, Maywood, IL 60153 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med & Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94124 USA. RP Peralta, CA (reprint author), Vet Affairs Med Ctr, Gen Internal Med Sect 111A1, 4150 Clement St, San Francisco, CA 94124 USA. EM carmenalicia.peralta@ucsf.edu OI Kramer, Holly/0000-0002-6374-837X FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169]; Clinical Scientist in Nephrology Program from the American Kidney Fund; National Center for Research Resources [KL2 RR024130]; American Heart Association Established Investigator Award FX This work was supported by contracts N01-HC-95159 through N01-HC-95165 and by contract N01-HC-95169 from the National Heart, Lung, and Blood Institute. This work was also funded by the Clinical Scientist in Nephrology Program from the American Kidney Fund and by the National Center for Research Resources (KL2 RR024130 to C. A. P.), as well as by an American Heart Association Established Investigator Award to M. S. NR 32 TC 22 Z9 22 U1 0 U2 2 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 MAR 15 PY 2009 VL 169 IS 6 BP 740 EP 748 DI 10.1093/aje/kwn392 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 413ZT UT WOS:000263834400011 PM 19131564 ER PT J AU Mayer, K Kiessling, A Ott, J Schaefer, MB Hecker, M Henneke, I Schulz, R Gunther, A Wang, JD Wu, LJ Roth, J Seeger, W Kang, JX AF Mayer, Konstantin Kiessling, Almuth Ott, Juliane Schaefer, Martina Barbara Hecker, Matthias Henneke, Ingrid Schulz, Richard Guenther, Andreas Wang, Jingdong Wu, Lijun Roth, Joachim Seeger, Werner Kang, Jing X. TI Acute Lung Injury Is Reduced in fat-1 Mice Endogenously Synthesizing n-3 Fatty Acids SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE fat-1 mice; eicosapentaenoic acid; sickness behavior; inflammation; acute lung injury ID RESPIRATORY-DISTRESS-SYNDROME; GAMMA-LINOLENIC ACID; PLATELET-ACTIVATING-FACTOR; HUMAN ENDOTHELIAL-CELLS; FISH-OIL; EICOSAPENTAENOIC ACID; LIPID EMULSIONS; RESOLVIN E1; DIFFERENTIAL INFLUENCE; SYSTEMIC INFLAMMATION AB Rationale: Acute lung injury (ALI) remains an important cause of mortality in intensive care units. Inflammation is controlled by cytokines and eicosanoids derived from the n-6 fatty acid (FA) arachidonic acid (AA). The n-3 FA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and mediators derived from EPA and DHA possess reduced inflammatory potency. Objectives: To determine whether the ability of fat-1 mice to endogenously convert n-6 to n-3 FA, and thus generate an increased ratio of n-3 to n-6 FA, impacts experimental ALI. Methods: We investigated ALI induced by intratracheal instillation of endotoxin in fat-1 and wild-type (WT) mice, assessing leukocyte numbers, protein concentration, and prostaglandin and cytokine levels in bronchoalveolar lavage fluid, as well as free FA in plasma, and lung ventilator compliance. Body temperature and motor activity of mice-markers of sickness behavior-were also recorded. Measurements and Main Results: in ALI, fat-1 mice exhibited significantly reduced leukocyte invasion, protein leakage, and macrophage inflammatory protein-2 and thromboxane B-2 levels in lavage fluid compared with WT mice. Free AA levels were increased in the plasma of WT mice in response to endotoxin, whereas EPA and DHA were increased in the fat-1 group. Ventilator compliance was significantly improved in fat-1 mice. Body temperature and motor activity were decreased in ALI. fat-1 Mice recovered body temperature and motor activity faster. Conclusions: fat-1 Mice exhibited reduced features of ALI and sickness behavior. Increasing the availability of n-3 FA may thus be beneficial in critically ill patients with ALI. C1 [Mayer, Konstantin; Kiessling, Almuth; Ott, Juliane; Schaefer, Martina Barbara; Hecker, Matthias; Henneke, Ingrid; Schulz, Richard; Guenther, Andreas; Seeger, Werner] Univ Giessen, Lung Ctr, Med Clin 2, D-35392 Giessen, Germany. [Roth, Joachim] Univ Giessen, Dept Vet Physiol, D-35392 Giessen, Germany. [Wang, Jingdong; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wang, Jingdong; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Lijun] Resolvyx Pharmaceut Inc, Bedford, MA USA. RP Mayer, K (reprint author), Univ Giessen, Lung Ctr, Med Clin 2, Klin Str 36, D-35392 Giessen, Germany. EM konstantin.mayer@uglc.de RI Mayer, Konstantin/A-9539-2008 FU Deutsche Forschungsgemeinschaft, Collaborative Research Center 547; Excellence Cluster Cardio-Pulmonary System, Giessen, Germany; National Institutes of Health grant [CA113605]; University of Giessen School of Medicine (M.B.S.) FX Supported by Deutsche Forschungsgemeinschaft, Collaborative Research Center 547 "Cardiopulmonary Vascular System," Project B4 (K.M.), the Excellence Cluster Cardio-Pulmonary System, Giessen, Germany, by National Institutes of Health grant CA113605 (J.X.K.), and by a start-up grant from the University of Giessen School of Medicine (M.B.S.). NR 65 TC 33 Z9 35 U1 2 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2009 VL 179 IS 6 BP 474 EP 483 DI 10.1164/rccm.200807-1064OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 417LV UT WOS:000264078400009 PM 19136374 ER PT J AU Mani, G Feldman, MD Oh, S Agrawal, CM AF Mani, Gopinath Feldman, Marc D. Oh, Sunho Agrawal, C. Mauli TI Surface modification of cobalt-chromium-tungsten-nickel alloy using octadecyltrichlorosilanes SO APPLIED SURFACE SCIENCE LA English DT Article DE Biomaterials surfaces; Cobalt-chromium alloys; Self-assembled monolayers; Silanes ID SELF-ASSEMBLED MONOLAYERS; ATOMIC-FORCE MICROSCOPY; NATIVE-OXIDE SURFACE; ALKYLSILOXANE MONOLAYERS; TITANIUM SURFACES; INFRARED-SPECTROSCOPY; EXTERNAL REFLECTION; ORGANIC MONOLAYERS; THERMAL-STABILITY; IMPLANT MATERIALS AB Cobalt-chromium (Co-Cr) alloys have been extensively used for medical implants because of their excellent mechanical properties, corrosion resistance, and biocompatibility. This first time study reports the formation and stability of self-assembled monolayers (SAMs) on a Co-Cr-W-Ni alloy. SAMs of octadecyltrichlorosilanes (OTS) were coated on sputtered Co-Cr-W-Ni alloy thin film and bulk Co-Cr W-Ni alloy. OTS SAM coated alloy specimens were characterized using contact angle goniometry, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Contact angle analysis and FTIR suggested that ordered monolayers were coated on both sputtered and bulk alloy. XPS suggested the selective dissolution of cobalt from the alloy during the formation of OTS SAM. The bonding between the alloy and the OTS SAM was mainly attributed to Si-O-Cr and Si-O-W covalent bonds and a smaller contribution from Si-O-Co bonds. AFM images showed the distribution of islands of monolayers coated on the alloy. The height of monolayers in majority of the islands was closer to the theoretical length of fully extended OTS molecules oriented perpendicular to the surface. The stability of OTS SAM was investigated in tris-buffered saline at 37 degrees C for up to 7 days. Contact angle, FTIR, and XPS collectively confirmed that the monolayers remain ordered and bound to the alloy surface under this condition. This study shows that Co-Cr alloys can be surface modified using SAMs for potential biomedical applications. (C) 2009 Elsevier B. V. All rights reserved. C1 [Mani, Gopinath; Feldman, Marc D.; Oh, Sunho; Agrawal, C. Mauli] Univ Texas San Antonio, Dept Biomed Engn, San Antonio, TX 78249 USA. [Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA. [Feldman, Marc D.] Dept Vet Affairs S Texas Hlth Care Syst, San Antonio, TX 78229 USA. RP Agrawal, CM (reprint author), Univ Texas San Antonio, Dept Biomed Engn, 1 UTSA Circle, San Antonio, TX 78249 USA. EM Mauli.Agrawal@utsa.edu FU South Texas Technology Management FX We are grateful to Sparc POC grant program sponsored by South Texas Technology Management for financial support. NR 80 TC 37 Z9 38 U1 1 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-4332 J9 APPL SURF SCI JI Appl. Surf. Sci. PD MAR 15 PY 2009 VL 255 IS 11 BP 5961 EP 5970 DI 10.1016/j.apsusc.2009.01.046 PG 10 WC Chemistry, Physical; Materials Science, Coatings & Films; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA 414VR UT WOS:000263893800058 ER PT J AU Holt, DJ Lebron-Milad, K Milad, MR Rauch, SL Pitman, RK Orr, SP Cassidy, BS Walsh, JP Goff, DC AF Holt, Daphne J. Lebron-Milad, Kelimer Milad, Mohammed R. Rauch, Scott L. Pitman, Roger K. Orr, Scott P. Cassidy, Brittany S. Walsh, Jared P. Goff, Donald C. TI Extinction Memory Is Impaired in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Conditioning; emotion; extinction; fear; memory; schizophrenia ID VENTROMEDIAL PREFRONTAL CORTEX; FEAR EXTINCTION; CONDITIONED FEAR; PERSECUTORY DELUSIONS; NEGATIVE SYMPTOMS; D-CYCLOSERINE; ELECTRODERMAL ACTIVITY; EMOTION RECOGNITION; REALITY DISTORTION; DECLARATIVE MEMORY AB Background: Schizophrenia is associated with abnormalities in emotional processing and social cognition, which might result from disruption of the underlying neural mechanism(s) governing emotional learning and memory. To investigate this possibility, we measured the acquisition and extinction of conditioned fear responses and delayed recall of extinction in schizophrenia and control subjects. Methods: Twenty-eight schizophrenia and 18 demographically matched control subjects underwent a 2-day fear conditioning, extinction learning, and extinction recall procedure, in which skin conductance response (SCR) magnitude was used as the index of conditioned responses. Results: During fear acquisition, 83% of the control subjects and 57% of the patients showed autonomic responsivity ("responders"), and the patients showed larger SCRs to the stimulus that was not paired with the unconditioned stimulus (CS-) than the control subjects. Within the responder group, there was no difference between the patients and control subjects in levels of extinction learning; however, the schizophrenia patients showed significant impairment, relative to the control subjects, in context-dependent recall of the extinction memory. In addition, delusion severity in the patients correlated with baseline skin conductance levels. Conclusions: These data are consistent with prior evidence for a heightened neural response to innocuous stimuli in schizophrenia and elevated arousal levels in psychosis. The finding of deficient extinction recall in schizophrenia patients who showed intact extinction learning suggests that schizophrenia is associated with a disturbance in the neural processes supporting emotional memory. C1 [Holt, Daphne J.; Lebron-Milad, Kelimer; Milad, Mohammed R.; Pitman, Roger K.; Orr, Scott P.; Cassidy, Brittany S.; Walsh, Jared P.; Goff, Donald C.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Holt, Daphne J.; Lebron-Milad, Kelimer; Milad, Mohammed R.; Pitman, Roger K.; Orr, Scott P.; Cassidy, Brittany S.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. [Orr, Scott P.] Dept Vet Affairs Med Ctr, Manchester, NH USA. RP Holt, DJ (reprint author), Massachusetts Gen Hosp E, Psychiat Neuroimaging Res Program, Room 2662,149 13th St, Charlestown, MA 02129 USA. EM dholt@partners.org FU NIMH NIH HHS [K23 MH076054, K24 MH002025] NR 91 TC 68 Z9 68 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2009 VL 65 IS 6 BP 455 EP 463 DI 10.1016/j.biopsych.2008.09.017 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 414WM UT WOS:000263895900002 PM 18986648 ER PT J AU Bloushtain-Qimron, N Yao, J Shipitsin, M Maruyama, R Polyak, K AF Bloushtain-Qimron, Noga Yao, Jun Shipitsin, Michail Maruyama, Reo Polyak, Kornelia TI Epigenetic patterns of embryonic and adult stem cells SO CELL CYCLE LA English DT Article DE stem cells; epigenetics; DNA methylation; chromatin ID HUMAN MAMMARY-GLAND; HISTONE DEACETYLASE ACTIVITY; BREAST-CANCER CELLS; DNA METHYLATION; PROGENITOR CELLS; SELF-RENEWAL; DEVELOPMENTAL REGULATORS; CELLULAR-DIFFERENTIATION; POLYCOMB COMPLEXES; IN-VITRO AB Embryonic stem (ES) cells are pluripotent cells that differentiate into all cell types of the organism. In adult, multipotent tissue-specific stem cells undergo multi-lineage differentiation to preserve normal tissue homeostasis and repair potential injuries. The maintenance of stem cells and their differentiation follows defined epigenetic programs, including DNA methylation, histone modifications and small non-coding RNAs that result in gene expression, morphologic and functional changes. Recently, we reported for the first time the comprehensive characterization of the in vivo gene expression and DNA methylation profiles of four distinct populations of normal human mammary epithelial cells and the identification of cell type-specific DNA methylation patterns with clinical relevance. Our results together with other studies suggest an important role for epigenetic regulation in stem cell self-renewal, pluripotency and differentiation, and imply that abnormalities in these processes may play a role in tumor initiation and progression. C1 [Bloushtain-Qimron, Noga; Yao, Jun; Shipitsin, Michail; Maruyama, Reo; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Yao, Jun; Shipitsin, Michail; Maruyama, Reo; Polyak, Kornelia] Harvard Univ, Sch Med, Boston, MA USA. [Bloushtain-Qimron, Noga] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol & Immunol, Beer Sheva, Israel. [Bloushtain-Qimron, Noga] Ben Gurion Univ Negev, Canc Res Ctr, IL-84105 Beer Sheva, Israel. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu FU NIH [CA89393, CA116235, 5PO1CA080111]; DOD [W81XWH-07-1-0294]; ACS [RSG-05-154-01-MGO] FX This work was supported in part by NIH (CA89393, CA116235 and 5PO1CA080111), DOD (W81XWH-07-1-0294) and ACS (RSG-05-154-01-MGO) grants awarded to K. P. NR 87 TC 29 Z9 30 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 15 PY 2009 VL 8 IS 6 BP 809 EP 817 DI 10.4161/cc.8.6.7938 PG 9 WC Cell Biology SC Cell Biology GA 426KG UT WOS:000264706600007 PM 19229128 ER PT J AU Peer, D Shimaoka, M AF Peer, Dan Shimaoka, Motomu TI Systemic siRNA delivery to leukocyte-implicated diseases SO CELL CYCLE LA English DT Review DE small interfering RNA (siRNA); gene silencing; nano-medicine; clinical trial; nanoparticles; drug delivery; integrin; cyclin ID FUNCTION-ASSOCIATED ANTIGEN-1; ENDOTHELIAL GROWTH-FACTOR; IN-VIVO DELIVERY; RNA INTERFERENCE; NONHUMAN-PRIMATES; GENE DELIVERY; TUMOR-GROWTH; CYCLIN D1; THERAPEUTICS; MICE AB Short interfering RNA (siRNA), a small duplex of RNA fragment, has proved as an extremely useful research tool to interrogate gene functions in test tubes. However, the transformation of siRNAs from a functional genomic tool into a new therapeutic modality has been hindered by ineffective delivery methods for systemic administration. In this review, we will discuss the recent advances in formulating new delivery strategies that target siRNAs to specific cells following systemic administration. Special emphasis will be given to leukocytes, since siRNA delivery remains exceptionally challenging here due to the unavailability of effective delivery technologies. We will not only detail new platforms that utilize leukocyte integrins as receptor targets for siRNAs delivery, but also show how one of these strategies has been utilized for in vivo drug target validation of a novel anti-inflammatory target, cyclin D1, for inflammatory bowel diseases. C1 [Peer, Dan] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, Lab Nanomed, IL-69978 Tel Aviv, Israel. [Shimaoka, Motomu] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Shimaoka, Motomu] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Peer, D (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, Lab Nanomed, Britannia Bldg,Room 227, IL-69978 Tel Aviv, Israel. EM peer@post.tau.ac.il; shimaoka@idi.harvard.edu RI Peer, Dan/A-1785-2011 OI Peer, Dan/0000-0001-8238-0673 FU Alon Foundation; Marie Curie IRG [FP07]; European Union; Leukemia & Lymphoma Society; National Institutes of Health [AI063421, HL048675] FX We thank Ms. Ronnie Yoo for her technical assistance. This work was supported by grants from the Alon Foundation (D. P.), Marie Curie IRG FP07, European Union (D. P.), Leukemia & Lymphoma Society (M. S.), and National Institutes of Health, AI063421 and HL048675 (M. S.). NR 58 TC 23 Z9 23 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 15 PY 2009 VL 8 IS 6 BP 853 EP 859 DI 10.4161/cc.8.6.7936 PG 7 WC Cell Biology SC Cell Biology GA 426KG UT WOS:000264706600014 PM 19221492 ER PT J AU Shankar, LK den Abbeele, A Yap, J Benjamin, R Scheutze, S FitzGerald, TJ AF Shankar, Lalitha K. den Abbeele, AnnickVan Yap, Jeff Benjamin, Robert Scheutze, Scott FitzGerald, T. J. TI Considerations for the Use of Imaging Tools for Phase II Treatment Trials in Oncology SO CLINICAL CANCER RESEARCH LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; GASTROINTESTINAL STROMAL TUMORS; IMATINIB MESYLATE; NEOADJUVANT CHEMOTHERAPY; PET; CANCER; THERAPY; RECOMMENDATIONS; EFFICACY; SARCOMAS AB In the context of assessing tumor response, imaging tools have the potential to play a vital role in phase II and III treatment trials. If the imaging test is able to predict potential phase III success in a reliable fashion, it would be a useful tool in phase II trial design as it may provide for a more rapid and timely response assessment. The benefits and challenges of using anatomic imaging measures as well as the promising molecular imaging measures, primarily fluorodeoxyglucose-positron emission tomography, are discussed here. The general issues related to successful implementation of advanced imaging in the context of phase II treatment trials are discussed. C1 [Shankar, Lalitha K.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [den Abbeele, AnnickVan; Yap, Jeff] Dana Farber Canc Inst, Boston, MA 02115 USA. [Benjamin, Robert] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Scheutze, Scott] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [FitzGerald, T. J.] Qual Assurance Review Ctr, Providence, RI USA. RP Shankar, LK (reprint author), NCI, Div Canc Treatment & Diag, 6130 Execut Blvd,Room 6056, Bethesda, MD 20892 USA. EM shankarl@mail.nih.gov FU NCI NIH HHS [U10 CA029511-30, U10 CA029511] NR 31 TC 38 Z9 38 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2009 VL 15 IS 6 BP 1891 EP 1897 DI 10.1158/1078-0432.CCR-08-2030 PG 7 WC Oncology SC Oncology GA 423QO UT WOS:000264511000009 PM 19276276 ER PT J AU Han, S Polizzano, C Nielsen, GP Hornicek, FJ Rosenberg, AE Ramesh, V AF Han, Sangyeul Polizzano, Carolyn Nielsen, Gunnlaugur P. Hornicek, Francis J. Rosenberg, Andrew E. Ramesh, Vijaya TI Aberrant Hyperactivation of Akt and Mammalian Target of Rapamycin Complex 1 Signaling in Sporadic Chordomas SO CLINICAL CANCER RESEARCH LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; COMPARATIVE GENOMIC HYBRIDIZATION; FAMILIAL CHORDOMA; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; ENHANCED SENSITIVITY; CLIVUS CHORDOMA; CANCER; MTOR; MUTATIONS; CCI-779 AB Purpose: Chordomas are rare, malignant bone neoplasms in which the pathogenic mechanisms remain unknown. Interestingly, tuberous sclerosis complex (TSC) is the only syndrome in which the incidence of chordomas has been described. We previously reported the pathogenic role of the TSC genes in TSC-associated chordomas. In this study, we investigated whether aberrant TSC/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is associated with sporadic chordomas. Experimental Design: We assessed the status of mTORC1 signaling in primary tumors/cell lines of sacral chordomas and further examined upstream of mTORC1 signaling, including the PTEN (phosphatase and tensin homologue deleted on chromosome ten) tumor suppressor. We also tested the efficacy of the mTOR inhibitor rapamycin on signaling and growth of chordoma cell lines. Results: Sporadic sacral chordoma tumors and cell lines examined commonly displayed hyperactivated Akt and mTORC1 signaling. Strikingly, expression of PTEN, a negative regulator of mTORC1 signaling, was not detected or significantly reduced in chordoma-derived cell lines and primary tumors. Furthermore, rapamycin inhibited mTORC1 activation and suppressed proliferation of chordoma-derived cell line. Conclusions: Our results suggest that loss of PTEN as well as other genetic alterations that result in constitutive activation of Akt/mTORC1 signaling may contribute to the development of sporadic chordomas. More importantly, a combination of Akt and mTORC1 inhibition may provide clinical benefits to chordoma patients. C1 [Han, Sangyeul; Polizzano, Carolyn; Ramesh, Vijaya] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Sch Med, Boston, MA 02114 USA. [Nielsen, Gunnlaugur P.; Rosenberg, Andrew E.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02114 USA. [Hornicek, Francis J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Orthopaed Oncol Serv, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Han, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Sch Med, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM syhan@partners.org; ramesh@helix.mgh.harvard.edu FU NIH [NS24279]; S. Sydney De Young Foundation; NF Inc., NE FX NIH Grant NS24279, S. Sydney De Young Foundation and NF Inc., NE. NR 38 TC 31 Z9 34 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2009 VL 15 IS 6 BP 1940 EP 1946 DI 10.1158/1078-0432.CCR-08-2364 PG 7 WC Oncology SC Oncology GA 423QO UT WOS:000264511000015 PM 19276265 ER PT J AU Bertagnolli, MM Warren, RS Niedzwiecki, D Mueller, E Compton, CC Redston, M Hall, M Hahn, HP Jewell, SD Mayer, RJ Goldberg, RM Saltz, LB Loda, M AF Bertagnolli, Monica M. Warren, Robert S. Niedzwiecki, Donna Mueller, Elke Compton, Carolyn C. Redston, Mark Hall, Margaret Hahn, Hejin P. Jewell, Scott D. Mayer, Robert J. Goldberg, Richard M. Saltz, Leonard B. Loda, Massimo TI p27(Kip1) in Stage III Colon Cancer: Implications for Outcome following Adjuvant Chemotherapy in Cancer and Leukemia Group B Protocol 89803 SO CLINICAL CANCER RESEARCH LA English DT Article ID DEPENDENT KINASE INHIBITOR; UBIQUITIN LIGASE SUBUNIT; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; ALTERED EXPRESSION; MOLECULAR ANALYSIS; PROGNOSTIC ROLE; P27 EXPRESSION; CARCINOMA; ADENOCARCINOMA AB Background: In retrospective studies, loss of p27(Kip1) (p27), a cyclin-dependent kinase inhibitor, has been associated with poor prognosis following colorectal cancer treatment. In a prospective study, we validated this relationship in patients enrolled on a trial of adjuvant chemotherapy for stage III colon cancer. Methods: Cancer and Leukemia Group B protocol 89803 randomized 1,264 stage III colon cancer patients to receive weekly bolus 5-fluorouracil/leucovorin or weekly bolus irinotecan, 5-fluorouracil, and leucovorin (IFL). The primary endpoint was overall survival (OS); disease-free survival was a secondary endpoint. Expression of p27 and DNA mismatch repair proteins were determined by immunohistochemistry in primary tumor and normal tissue from paraffin blocks. Data were analyzed using log-rank test. Results: Of 601 tumors analyzed, 207 (34.4%) showed p27 loss, 377 (62.8%) retained p27, and 17 (2.8%) were indeterminate. Patients with p27-negative tumors showed reduced OS [5-year CS 66%: 95% confidence interval (95% CI), 0.59-0.72 versus 75%: 95% CI, 0.70-0.79; log-rank P = 0.021]. This relationship was not influenced by treatment arm. Combination of p27 status with mismatch repair status, however, identified a small subset of patients that may benefit from IFL (n = 36; 5-year disease-free survival 81%: 95% CI, 0.64-0.98 versus 47% 95% CI, 0.21-0.72; log-rank P = 0.042; 5-year OS 81%: 95% CI, 0.64-0.98 versus 60%: 95% CI, 0.35-0.85; log-rank P = 0.128). Conclusions: Loss of p27 is associated with reduced survival in stage III colon cancer but by itself does not indicate a significant difference in outcome between patients treated IFL or 5-fluorouracil/leucovorin. C1 [Bertagnolli, Monica M.; Mueller, Elke; Redston, Mark; Hahn, Hejin P.; Loda, Massimo] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bertagnolli, Monica M.; Mayer, Robert J.; Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Warren, Robert S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Niedzwiecki, Donna; Hall, Margaret] Duke Univ, Med Ctr, Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. [Compton, Carolyn C.] NCI, Bethesda, MD USA. [Jewell, Scott D.] Ohio State Univ, Columbus, OH 43210 USA. [Goldberg, Richard M.] Univ N Carolina, Chapel Hill, NC USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM Mbertagnolli@partners.org RI Goldberg , Richard/M-1311-2013; OI Saltz, Leonard/0000-0001-8353-4670 FU USPHS [CA31946]; National Cancer Institute, NIH, Department of Health and Human Services; CALGB Statistical Center [CA33601] FX The research for CALGB protocol 89803 was supported, in part, by USPHS grant CA31946 from the National Cancer Institute, NIH, Department of Health and Human Services, to the CALGB (Richard L. Schilsky, M.D., Chairman) and to the CALGB Statistical Center (Stephen George, Ph. D., CA33601). NR 28 TC 13 Z9 13 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2009 VL 15 IS 6 BP 2116 EP 2122 DI 10.1158/1078-0432.CCR-08-2674 PG 7 WC Oncology SC Oncology GA 423QO UT WOS:000264511000035 PM 19276255 ER PT J AU Issa, NC Fishman, JA AF Issa, Nicolas C. Fishman, Jay A. TI Infectious Complications of Antilymphocyte Therapies in Solid Organ Transplantation SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ANTI-THYMOCYTE GLOBULIN; RENAL-ALLOGRAFT RECIPIENTS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; EPSTEIN-BARR-VIRUS; RABBIT ANTITHYMOCYTE GLOBULIN; RECEPTOR MONOCLONAL-ANTIBODY; STEROID-RESISTANT REJECTION; CONTAINING TRIPLE THERAPY; ACUTE CELLULAR REJECTION; TUMOR-NECROSIS-FACTOR AB Antilymphocyte therapies are widely used for immunosuppression in solid organ transplantation. These agents have varied mechanisms of action, with resulting differences in the intensity and duration of immunosuppression and in associated infectious complications. Induction therapy with antithymocyte globulins is associated with a greater incidence of cytomegalovirus, Epstein-Barr virus, and BK polyomavirus infections, compared with therapy with interleukin (IL)-2a receptor antagonists. However, long-term experience with the IL-2a receptor antagonists is lacking. By contrast, the treatment of graft rejection with T cell-depleting antibodies is associated with an increased risk of opportunistic infections. This is likely a reflection of the intensification of immunosuppression in the treatment of graft rejection and, often, a failure to link the use of antilymphocyte agents to prophylaxis for infection. The use of T cell-depleting agents, especially in the treatment of acute graft rejection, must be linked to monitoring and risk-adjusted prophylaxis for Pneumocystis, other fungi, Epstein-Barr virus, BK polyomavirus, and cytomegalovirus infection. C1 [Issa, Nicolas C.; Fishman, Jay A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Fishman, JA (reprint author), Transplant Infect Dis & Compromised Host Program, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org FU PATH Alliance (Axiom/Astellas) FX J.A.F. has served as a consultant for Bristol-Myers Squibb, Merck, Hoffman-La Roche, T2 Biosystems, Astellas, and FDA/CBER-Xenotransplantation; has served on the scientific advisory board for Primera; has served on the speakers' bureau for Hoffman-La Roche; and has received corporate grant support from PATH Alliance (Axiom/Astellas). J.A.F. has patents for molecular cloning of antigens shared by rat- and human-derived Pneumocystis carinii (patent 5442050; GenBank accession numbers L43850, L43851, and L43852) and molecular sequence of swine retrovirus and methods of use (patent 6190861; patent cooperation treaty international patent WO07/21836; GenBank accession numbers AF038600, AF038601, and AF038599). N.C.I.: no conflicts. NR 127 TC 74 Z9 77 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 MAR 15 PY 2009 VL 48 IS 6 BP 772 EP 786 DI 10.1086/597089 PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 415QI UT WOS:000263949000014 PM 19207081 ER PT J AU Julg, B Walker, BD AF Julg, Boris Walker, Bruce D. TI The Paradox of Incomplete CD4(+) Cell Count Restoration Despite Successful Antiretroviral Treatment and the Need to Start Highly Active Antiretroviral Therapy Early SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-1 INFECTION; VIROLOGICAL SUPPRESSION; RECOVERY; INDIVIDUALS; PROGRESSION; FAILURE; COHORT; RISK; AIDS C1 [Julg, Boris; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA. [Julg, Boris; Walker, Bruce D.] Harvard, Charlestown, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Walker, BD (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA. EM bwalker@partners.org NR 18 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2009 VL 48 IS 6 BP 795 EP 797 DI 10.1086/597094 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 415QI UT WOS:000263949000016 PM 19196173 ER PT J AU Paltiel, AD Freedberg, KA Scott, CA Schackman, BR Losina, E Wang, BX Seage, GR Sloan, CE Sax, PE Walensky, RP AF Paltiel, A. David Freedberg, Kenneth A. Scott, Callie A. Schackman, Bruce R. Losina, Elena Wang, Bingxia Seage, George R., III Sloan, Caroline E. Sax, Paul E. Walensky, Rochelle P. TI HIV Preexposure Prophylaxis in the United States: Impact on Lifetime Infection Risk, Clinical Outcomes, and Cost-Effectiveness SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ACUTE-RENAL-FAILURE; ANTIRETROVIRAL THERAPY; MALE CIRCUMCISION; TENOFOVIR DF; PREVENTION; MEN; SEX; EMTRICITABINE; TRANSMISSION AB Background. The combination of tenofovir and emtricitabine shows promise as HIV preexposure prophylaxis (PrEP). We sought to forecast clinical, epidemiologic, and economic outcomes of PrEP, taking into account uncertainties regarding efficacy, the risks of developing drug resistance and toxicity, behavioral disinhibition, and drug costs. Methods. We adapted a computer simulation of HIV acquisition, detection, and care to model PrEP among men who have sex with men and are at high risk of HIV infection (i.e., 1.6% mean annual incidence of HIV infection) in the United States. Base-case assumptions included 50% PrEP efficacy and monthly tenofovir-emtricitabine costs of $753. We used sensitivity analyses to examine the stability of results and to identify critical input parameters. Results. In a cohort with a mean age of 34 years, PrEP reduced lifetime HIV infection risk from 44% to 25% and increased mean life expectancy from 39.9 to 40.7 years (21.7 to 22.2 discounted quality-adjusted life-years). Discounted mean lifetime treatment costs increased from $81,100 to $232,700 per person, indicating an incremental cost-effectiveness ratio of $298,000 per quality-adjusted life-year gained. Markedly larger reductions in lifetime infection risk (from 44% to 6%) were observed with the assumption of greater (90%) PrEP efficacy. More-favorable incremental cost-effectiveness ratios were obtained by targeting younger populations with a higher incidence of infection and by improvements in the efficacy and cost of PrEP. Conclusions. PrEP could substantially reduce the incidence of HIV transmission in populations at high risk of HIV infection in the United States. Although it is unlikely to confer sufficient benefits to justify the current costs of tenofovir-emtricitabine, price reductions and/or increases in efficacy could make PrEP a cost-effective option in younger populations or populations at higher risk of infection. Given recent disappointments in HIV infection prevention and vaccine development, additional study of PrEP-based HIV prevention is warranted. C1 [Paltiel, A. David; Schackman, Bruce R.] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. [Freedberg, Kenneth A.; Sax, Paul E.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Freedberg, Kenneth A.; Sax, Paul E.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Harvard Ctr AIDS Res, Boston, MA USA. [Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Freedberg, Kenneth A.; Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Sax, Paul E.; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. RP Paltiel, AD (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, 60 Coll St, New Haven, CT 06520 USA. EM david.paltiel@yale.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Mental Health [R01MH65869]; National Institute of Allergy and Infectious Diseases [K24AI062476, K25AI50436, R37AI42006, P30AI42851]; National Institute on Drug Abuse [K01DA17179, R01DA015612]; Doris Duke Charitable Foundation; Abbott; Bristol-Myers Squibb; Gilead; Merck; Tibotec FX P.E.S. has served as a consultant to Abbott, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, and Tibotec; has received honoraria for teaching from Abbott, Bristol-Myers Squibb, Gilead, Merck, and Tibotec; and has received grant support from Merck. All other authors: no conflicts. NR 65 TC 132 Z9 139 U1 3 U2 28 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 MAR 15 PY 2009 VL 48 IS 6 BP 806 EP 815 DI 10.1086/597095 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 415QI UT WOS:000263949000018 PM 19193111 ER PT J AU Braithwaite, RS Roberts, MS Goetz, MB Gibert, CL Rodriguez-Barradas, MC Nucifora, K Justice, AC AF Braithwaite, R. Scott Roberts, Mark S. Goetz, Matthew Bidwell Gibert, Cynthia L. Rodriguez-Barradas, Maria C. Nucifora, Kimberly Justice, Amy C. TI Do Benefits of Earlier Antiretroviral Treatment Initiation Outweigh Harms for Individuals at Risk for Poor Adherence? SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV; INFECTION; TRANSMISSION; VETERANS; OUTCOMES AB Clinicians may defer antiretroviral treatment for patients with suboptimal adherence. We used a validated computer simulation of HIV disease progression to compare alternative treatment thresholds for patients with suboptimal adherence. Earlier treatment increased life expectancy across a wide adherence range (50%-100% of doses taken). Delaying treatment for patients with suboptimal adherence may not always be appropriate. C1 [Braithwaite, R. Scott; Nucifora, Kimberly; Justice, Amy C.] Yale Univ, Dept Med, Gen Internal Med Sect, West Haven, CT USA. [Braithwaite, R. Scott; Nucifora, Kimberly; Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Roberts, Mark S.] Univ Pittsburgh, Sch Med, Dept Med, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA USA. [Roberts, Mark S.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Infect Dis Sect, Los Angeles, CA 90095 USA. [Goetz, Matthew Bidwell] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gibert, Cynthia L.] George Washington Univ, Dept Med, Infect Dis Sect, Washington, DC USA. [Gibert, Cynthia L.] Vet Affairs Med Ctr, Infect Dis Sect, Washington, DC 20422 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Braithwaite, RS (reprint author), 950 Campbell Ave,11ACSLG, New Haven, CT 06516 USA. EM ronald.braithwaite@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU National Institute of Alcohol Abuse and Alcoholism [K23 AA14483-01]; Archimedes; Monogram Biosciences FX Potential conflicts of interest. M. S. R. has received an unrestricted research grant from and consults for Archimedes. M. B. G. has received an honorarium and consultancy fees from Monogram Biosciences. R. S. B. is a methodological consultant for United BioSource. All other authors: no conflicts. NR 12 TC 19 Z9 19 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2009 VL 48 IS 6 BP 822 EP 826 DI 10.1086/596768 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 415QI UT WOS:000263949000020 PM 19210173 ER PT J AU Rosenberg, JE Hahn, WC AF Rosenberg, Jonathan E. Hahn, William C. TI Bladder cancer: modeling and translation SO GENES & DEVELOPMENT LA English DT Article DE Bladder cancer; mTOR signaling; mouse models; preclinical trials; rapamycin; tissue microarrays ID TRANSITIONAL-CELL-CARCINOMA; RADICAL CYSTECTOMY; NEOADJUVANT CHEMOTHERAPY; PELVIC LYMPHADENECTOMY; LUNG ADENOCARCINOMA; TUMOR PROGRESSION; URINARY-BLADDER; H-RAS; P53; EXPRESSION AB Transitional cell carcinoma of the bladder is a common malignancy worldwide that is associated with significant morbidity and mortality. Although superficial tumors can often be treated effectively, invasive cancers not only require invasive surgery, but are also refractory to aggressive chemotherapy and radiotherapy. In this issue of Genes & Development, Puzio-Kuter and colleagues (pp. 675-680) describe an elegant genetically engineered murine model of bladder cancer that recapitulates many of the cardinal features of the human disease. The development of such models together with the application of new approaches to enumerate the complement of genetic alterations in bladder will provide new insights into the molecular nature of this disease. Moreover, the anatomy of this urinary malignancy provides a unique opportunity for innovative translational studies. C1 [Rosenberg, Jonathan E.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA 02142 USA. RP Rosenberg, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Jonathan_Rosenberg@dfci.harvard.edu; William_Hahn@dfci.harvard.edu NR 42 TC 6 Z9 6 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2009 VL 23 IS 6 BP 655 EP 659 DI 10.1101/gad.1789109 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 421LM UT WOS:000264360400001 PM 19299556 ER PT J AU Suzuki, T Miyamoto, H Nakahari, T Inoue, I Suemoto, T Jiang, B Hirota, Y Itohara, S Saido, TC Tsumoto, T Sawamoto, K Hensch, TK Delgado-Escueta, AV Yamakawa, K AF Suzuki, Toshimitsu Miyamoto, Hiroyuki Nakahari, Takashi Inoue, Ikuyo Suemoto, Takahiro Jiang, Bin Hirota, Yuki Itohara, Shigeyoshi Saido, Takaomi C. Tsumoto, Tadaharu Sawamoto, Kazunobu Hensch, Takao K. Delgado-Escueta, Antonio V. Yamakawa, Kazuhiro TI Efhc1 deficiency causes spontaneous myoclonus and increased seizure susceptibility SO HUMAN MOLECULAR GENETICS LA English DT Article ID POTASSIUM CHANNEL GENE; FEBRILE SEIZURES; SODIUM-CHANNEL; EPILEPSY; MUTATIONS; CILIA; SCN1A; MICE; GAMMA-2-SUBUNIT; NEUROGENESIS AB Mutations in EFHC1 gene have been previously reported in patients with epilepsies, including those with juvenile myoclonic epilepsy. Myoclonin1, also known as mRib72-1, is encoded by the mouse Efhc1 gene. Myoclonin1 is dominantly expressed in embryonic choroid plexus, post-natal ependymal cilia, tracheal cilia and sperm flagella. In this study, we generated viable Efhc1-deficient mice. Most of the mice were normal in outward appearance, and both sexes were found to be fertile. However, the ventricles of the brains were significantly enlarged in the null mutants, but not in the heterozygotes. Although the ciliary structure was found intact, the ciliary beating frequency was significantly reduced in null mutants. In adult stages, both the heterozygous and null mutants developed frequent spontaneous myoclonus. Furthermore, the threshold of seizures induced by pentylenetetrazol was significantly reduced in both heterozygous and null mutants. These observations seem to further suggest that decrease or loss of function of myoclonin1 may be the molecular basis for epilepsies caused by EFHC1 mutations. C1 [Suzuki, Toshimitsu; Inoue, Ikuyo; Yamakawa, Kazuhiro] RIKEN, Neurogenet Lab, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Miyamoto, Hiroyuki; Hensch, Takao K.] RIKEN, Lab Neuronal Circuit Dev, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Suemoto, Takahiro; Saido, Takaomi C.] RIKEN, Lab Proteolyt Neurosci, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Jiang, Bin; Tsumoto, Tadaharu] RIKEN, Tsumoto Res Unit, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Itohara, Shigeyoshi] RIKEN, Lab Behav Genet, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Suzuki, Toshimitsu] RIKEN, Special Postdoctoral Researchers Program, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Nakahari, Takashi] Osaka Med Coll, Dept Physiol, Osaka 5698686, Japan. [Hirota, Yuki; Sawamoto, Kazunobu] Nagoya City Univ, Grad Sch Med Sci, Inst Mol Med, Dept Dev & Regenerat Biol, Nagoya, Aichi 4678601, Japan. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Epilepsy Program, Epilepsy Genetics Lab, Los Angeles, CA 90073 USA. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Epilepsy Program, Genom Labs, Los Angeles, CA 90073 USA. [Delgado-Escueta, Antonio V.] VA GLAHS W Los Angeles, Los Angeles, CA 90073 USA. RP Yamakawa, K (reprint author), RIKEN, Neurogenet Lab, Brain Sci Inst, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. EM yamakawa@brain.riken.jp RI Itohara, Shigeyoshi/I-8769-2012; Yamakawa, Kazuhiro/N-5050-2015; OI Itohara, Shigeyoshi/0000-0002-2410-9989; Delgado-Escueta, Antonio V./0000-0002-1581-6999; Sawamoto, Kazunobu/0000-0003-1984-5129 FU Ministry of Education, Culture, Sports, Science and Technology of Japan; RIKEN FX This work was supported in part by a grant from RIKEN Brain Science Institute (K.Y.), from the Ministry of Education, Culture, Sports, Science and Technology of Japan ( T. S.) and from RIKEN Special Postdoctoral Researchers Program ( T. S.). NR 35 TC 39 Z9 39 U1 0 U2 0 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 MAR 15 PY 2009 VL 18 IS 6 BP 1099 EP 1109 DI 10.1093/hmg/ddp006 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 413XT UT WOS:000263828100011 PM 19147686 ER PT J AU Han, SZ Kim-Howard, X Deshmukh, H Kamatani, Y Viswanathan, P Guthridge, JM Thomas, K Kaufman, KM Ojwang, J Rojas-Villarraga, A Baca, V Orozco, L Rhodes, B Choi, CB Gregersen, PK Merrill, JT James, JA Gaffney, PM Moser, KL Jacob, CO Kimberly, RP Harley, JB Bae, SC Anaya, JM Alarcon-Riquelme, ME Matsuda, K Vyse, TJ Nath, SK AF Han, Shizhong Kim-Howard, Xana Deshmukh, Harshal Kamatani, Yoichiro Viswanathan, Parvathi Guthridge, Joel M. Thomas, Kenaz Kaufman, Kenneth M. Ojwang, Joshua Rojas-Villarraga, Adriana Baca, Vicente Orozco, Lorena Rhodes, Benjamin Choi, Chan-Bum Gregersen, Peter K. Merrill, Joan T. James, Judith A. Gaffney, Patrick M. Moser, Kathy L. Jacob, Chaim O. Kimberly, Robert P. Harley, John B. Bae, Sang-Choel Anaya, Juan-Manuel Alarcon-Riquelme, Marta E. Matsuda, Koichi Vyse, Timothy J. Nath, Swapan K. TI Evaluation of imputation-based association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; REVISED CRITERIA; GENOTYPE DATA; CLASSIFICATION; POLYMORPHISM; DISEASES; TDT AB We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an association between SLE susceptibility and ITGAM or ITGAM-ITGAX region. The primary objectives of this study are to assess whether single or multiple causal variants from the same gene or any nearby gene(s) are involved in SLE susceptibility and to confirm a robust ITGAM association across nine independent data sets (n = 8211). First, we confirmed our previously reported association of rs1143679 (risk allele 'A') with SLE in EAs (P = 1.0 x 10(-8)) and Hispanic-Americans (P = 2.9 x 10(-5)). Secondly, using a comprehensive imputation-based association test, we found that ITGAM is one of the major non-human leukocyte antigen susceptibility genes for SLE, and the strongest association for EA is the same coding variant rs1143679 (log(10)Bayes factor=20, P = 6.17 x 10(-24)). Thirdly, we determined the robustness of rs1143679 association with SLE across three additional case-control samples, including UK (P = 6.2 x 10(-8)), Colombian (P = 3.6 x 10(-7)), Mexican (P = 0.002), as well as two independent sets of trios from UK (P(TDT) = 1.4 x 10(-5)) and Mexico (P(TDT) = 0.015). A meta-analysis combing all independent data sets greatly reinforces the association (P(meta) = 7.1 x 10(-50), odds ratio = 1.83, 95% confidence interval = 1.69-1.98, n = 10 046). However, this ITGAM association was not observed in the Korean or Japanese samples, in which rs1143679 is monomorphic for the non-risk allele (G). Taken together along with our earlier findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM-SLE association, especially in European- and African-derived populations, but not in Asian populations. C1 [Han, Shizhong; Kim-Howard, Xana; Deshmukh, Harshal; Viswanathan, Parvathi; Nath, Swapan K.] Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. [Han, Shizhong; Kim-Howard, Xana; Deshmukh, Harshal; Viswanathan, Parvathi; Kaufman, Kenneth M.; Ojwang, Joshua; Gaffney, Patrick M.; Moser, Kathy L.; Harley, John B.; Anaya, Juan-Manuel; Nath, Swapan K.] Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. [Guthridge, Joel M.; James, Judith A.] Oklahoma Med Res Fdn, Clin Immunol Res Program, Oklahoma City, OK 73104 USA. [Kamatani, Yoichiro; Matsuda, Koichi] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Kaufman, Kenneth M.; Harley, John B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Rojas-Villarraga, Adriana; Anaya, Juan-Manuel] Rosario Univ, Ctr Autoimmune Dis Res CREA, Bogota, Colombia. [Baca, Vicente] Pediat Hosp, IMSS, Dept Rheumatol, Ctr Med Nacl Siglo 21, Mexico City, DF, Mexico. [Orozco, Lorena] Inst Nacl Med Genom, Mexico City, DF, Mexico. [Rhodes, Benjamin; Vyse, Timothy J.] Hammersmith Hosp, Imperial Coll, Rheumatol Sect, London, England. [Choi, Chan-Bum; Bae, Sang-Choel] Hosp Rheumat Dis, Seoul, South Korea. [Gregersen, Peter K.] Feinstein Inst Med Res, Manhasset, NY USA. [James, Judith A.; Harley, John B.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. [Nath, Swapan K.] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Kimberly, Robert P.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Alarcon-Riquelme, Marta E.] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. RP Nath, SK (reprint author), Oklahoma Med Res Fdn, Genet Epidemiol Unit, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM swapan-nath@omrf.org RI Han, Shizhong/E-4084-2010; Han, Shizhong/H-5785-2011; Kamatani, Yoichiro/N-5513-2015; Rojas-Villarraga, Adriana/J-2404-2016; Anaya, Juan-Manuel/J-1960-2016; OI Matsuda, Koichi/0000-0001-7292-2686; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Rojas-Villarraga, Adriana/0000-0003-3145-2440; Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392 FU NCRR NIH HHS [RR020143]; NIAID NIH HHS [AI063622, AI24717]; NIAMS NIH HHS [AR049084, AR043274, AR048940, AR053483, AR42460, AR445650, P30 AR053483]; Wellcome Trust NR 31 TC 59 Z9 59 U1 0 U2 9 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 MAR 15 PY 2009 VL 18 IS 6 BP 1171 EP 1180 DI 10.1093/hmg/ddp007 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 413XT UT WOS:000263828100018 PM 19129174 ER PT J AU Zhang, M Ho, A Hammond, EH Suzuki, Y Bermudez, RS Lee, RJ Pilepich, M Shipley, WU Sandler, H Khor, LY Pollack, A Chakravarti, A AF Zhang, Min Ho, Alex Hammond, Elizabeth H. Suzuki, Yoshiyuki Bermudez, R. Scott Lee, R. Jeffrey Pilepich, Michael Shipley, William U. Sandler, Howard Khor, Li-Yan Pollack, Alan Chakravarti, Arnab TI PROGNOSTIC VALUE OF SURVIVIN IN LOCALLY ADVANCED PROSTATE CANCER: STUDY BASED ON RTOG 8610 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Survivin; Prostate cancer; Radiotherapy; Prognostic factor ID ANTI-APOPTOSIS GENE; SPLICE VARIANTS; HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION; GASTRIC CARCINOMAS; SECONDARY ANALYSIS; PROTEIN SURVIVIN; MESSENGER-RNA; IN-VIVO; EXPRESSION AB Purpose: To examine the prognostic value of nuclear and cytoplasmic survivin expression in men with locally advanced prostate cancer who were enrolled in Radiation Therapy Oncology Group (RTOG) protocol 8610. Methods and Materials: RTOG 8610 was a Phase III randomized study comparing the effect of radiotherapy plus short-term androgen deprivation with radiotherapy alone. Of the 456 eligible patients, 68 patients had suitably stained tumor material for nuclear survivin analysis and 65 patients for cytoplasmic survivin. Results: Compared with patients with nuclear survivin intensity scores of <= 191.2, those with intensity scores >191.2 had significantly improved prostate cancer survival (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.20-1.00, p = 0.0452). On multivariate analysis, nuclear survivin intensity scores >191.2 were significantly associated with improved overall survival (HR, 0.46; 95% CI, 0.25-0.86; p = 0.0156) and prostate cancer survival (HR, 0.36; 95% CI, 0.16-0.84; p = 0.0173). On univariate analysis, compared with patients with cytoplasmic survivin integrated optical density <= 82.7, those with an integrated optical density >82.7 showed a significantly increased risk of local progression (HR, 2.49; 95% CI, 1.03-6.0 1; p = 0.0421). Conclusion: Nuclear overexpression of survivin was associated with improved overall and prostate cancer survival on multivariate analysis, and cytoplasmic overexpression of survivin was associated with increased rate of local progression on univariate analysis in patients with locally advanced prostate cancer treated on RTOG, 8610. Our results might reflect the different functions of survivin and its splice variants, which are known to exist in distinct subcellular compartments. (C) 2009 Elsevier Inc. C1 [Chakravarti, Arnab] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ho, Alex] Amer Coll Radiol, Philadelphia, PA USA. [Hammond, Elizabeth H.; Lee, R. Jeffrey] LDS Hosp, Salt Lake City, UT USA. [Suzuki, Yoshiyuki] Gunma Univ, Gunma, Japan. [Bermudez, R. Scott] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Pilepich, Michael] Univ Calif Los Angeles, Los Angeles, CA USA. [Sandler, Howard] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Khor, Li-Yan; Pollack, Alan] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Chakravarti, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM achakravarti@partners.org FU Radiation Therapy Oncology Group [U10CA21661]; Community Clinical Oncology Program [U10CA37422]; National Cancer Institute to the Radiation Therapy Oncology Group [U10CA32115]; Pennsylvania Department of Health; [R01 CA101984-01] FX Supported by Radiation Therapy Oncology Group Grant U10CA21661, Community Clinical Oncology Program Grant U10CA37422, and Grants Stat U10CA32115 from the National Cancer Institute to the Radiation Therapy Oncology Group and the Pennsylvania Department of Health and R01 CA101984-01 (both to A. Pollack). NR 50 TC 14 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2009 VL 73 IS 4 BP 1033 EP 1042 DI 10.1016/j.ijrobp.2008.06.1489 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 419ZE UT WOS:000264257400012 PM 18977097 ER PT J AU Healy, BC Hayden, DL Sampat, MP Bakshi, R Guttmann, CRG AF Healy, Brian C. Hayden, Douglas L. Sampat, Mehul P. Bakshi, Rohit Guttmann, Charles R. G. TI Unbiased treatment effect estimates by modeling the disease process of multiple sclerosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Active/inactive disease process; Clinical trials; MRI; Multiple sclerosis; Regression to the mean ID CLINICAL-TRIALS; RANDOMIZED-TRIALS; OPEN-LABEL; REGRESSION; MRI; LESIONS; MS AB Gadolinium-enhancing lesions in the brain are commonly used as a primary outcome measure of disease activity in phase I/II clinical trials in multiple sclerosis (MS). The advent of effective therapy and the cost of clinical trials have led some researchers to adopt a one-arm study design with selection towards patients showing MRI activity. Regression to the mean is recognized as an important consideration in these trials, but the additional confounding effect of alternating active and inactive phases of disease has not been considered. Simulated data were generated from Poisson and normal distributions to mimic outcomes from phase I/II clinical trials of patients with relapsing-remitting MS under a constant or changing disease process model. in all cases, conventional comparison of pretreatment to on-treatment measurements overestimated the treatment effect. Although correction for regression to the mean provided unbiased estimates of the treatment effect under a constant disease process model, this correction also overestimated the treatment effect when disease activity changed over time. Conversely, unbiased estimates of the treatment effect under an alternating (active/inactive) disease process were obtained by correctly accounting for regression to the mean and the disease process. The implications of these results are discussed in terms of efficacy and safety. (c) 2008 Elsevier B.V. All rights reserved. C1 [Guttmann, Charles R. G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Imaging,Dept Radiol, Boston, MA 02115 USA. [Healy, Brian C.; Bakshi, Rohit; Guttmann, Charles R. G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Partners MS Ctr,Dept Neurol, Boston, MA 02115 USA. [Healy, Brian C.; Hayden, Douglas L.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Guttmann, CRG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Imaging,Dept Radiol, 221 Longwood Ave, Boston, MA 02115 USA. EM guttmann@bwh.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAR 15 PY 2009 VL 278 IS 1-2 BP 54 EP 59 DI 10.1016/j.jns.2008.11.013 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 411ZF UT WOS:000263692300010 PM 19121526 ER PT J AU Miura, T Brockman, MA Schneidewind, A Lobritz, M Pereyra, F Rathod, A Block, BL Brumme, ZL Brumme, CJ Baker, B Rothchild, AC Li, B Trocha, A Cutrell, E Frahm, N Brander, C Toth, I Arts, EJ Allen, TM Walker, BD AF Miura, Toshiyuki Brockman, Mark A. Schneidewind, Arne Lobritz, Michael Pereyra, Florencia Rathod, Almas Block, Brian L. Brumme, Zabrina L. Brumme, Chanson J. Baker, Brett Rothchild, Alissa C. Li, Bin Trocha, Alicja Cutrell, Emily Frahm, Nicole Brander, Christian Toth, Ildiko Arts, Eric J. Allen, Todd M. Walker, Bruce D. TI HLA-B57/B*5801 Human Immunodeficiency Virus Type 1 Elite Controllers Select for Rare Gag Variants Associated with Reduced Viral Replication Capacity and Strong Cytotoxic T-Lymphotye Recognition SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; CELL RESPONSES; ANTIRETROVIRAL THERAPY; LYMPHOCYTE EPITOPES; ESCAPE MUTATIONS; HIV-1 INFECTION; AMINO-ACID; P24 GAG; SUPPRESSORS; LOAD AB Human immunodeficiency virus type 1 (HIV-1) elite controllers (EC) maintain viremia below the limit of commercial assay detection (< 50 RNA copies/ml) in the absence of antiviral therapy, but the mechanisms of control remain unclear. HLA-B57 and the closely related allele B*5801 are particularly associated with enhanced control and recognize the same Gag(240-249) TW10 epitope. The typical escape mutation (T242N) within this epitope diminishes viral replication capacity in chronically infected persons; however, little is known about TW10 epitope sequences in residual replicating viruses in B57/B*5801 EC and the extent to which mutations within this epitope may influence steady-state viremia. Here we analyzed TW10 in a total of 50 B57/B*5801-positive subjects (23 EC and 27 viremic subjects). Autologous plasma viral sequences from both EC and viremic subjects frequently harbored the typical cytotoxic T-lymphocyte (CTL)-selected mutation T242N (15/23 sequences [65.2%] versus 23/27 sequences [85.1%], respectively; P = 0.18). However, other unique mutants were identified in HIV controllers, both within and flanking TW10, that were associated with an even greater reduction in viral replication capacity in vitro. In addition, strong CTL responses to many of these unique TW10 variants were detected by gamma interferon-specific enzyme-linked immunospot assay. These data suggest a dual mechanism for durable control of HIV replication, consisting of viral fitness loss resulting from CTL escape mutations together with strong CD8 T-cell immune responses to the arising variant epitopes. C1 [Miura, Toshiyuki; Brockman, Mark A.; Schneidewind, Arne; Pereyra, Florencia; Rathod, Almas; Block, Brian L.; Brumme, Zabrina L.; Brumme, Chanson J.; Baker, Brett; Rothchild, Alissa C.; Li, Bin; Trocha, Alicja; Cutrell, Emily; Frahm, Nicole; Brander, Christian; Toth, Ildiko; Allen, Todd M.; Walker, Bruce D.] Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA. [Miura, Toshiyuki; Brockman, Mark A.; Schneidewind, Arne; Pereyra, Florencia; Rathod, Almas; Block, Brian L.; Brumme, Zabrina L.; Brumme, Chanson J.; Baker, Brett; Rothchild, Alissa C.; Li, Bin; Trocha, Alicja; Cutrell, Emily; Frahm, Nicole; Brander, Christian; Toth, Ildiko; Allen, Todd M.; Walker, Bruce D.] Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Miura, Toshiyuki; Trocha, Alicja; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Miura, Toshiyuki; Brockman, Mark A.; Schneidewind, Arne; Pereyra, Florencia; Brumme, Zabrina L.; Li, Bin; Frahm, Nicole; Brander, Christian; Allen, Todd M.; Walker, Bruce D.] Harvard Univ, Sch Med, Boston, MA USA. [Lobritz, Michael; Arts, Eric J.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Miura, T (reprint author), Massachusetts Gen Hosp, Ragon Inst, 149 13th St,Room 5212, Charlestown, MA 02129 USA. EM miura523@hotmail.com; bwalker@partners.org RI Allen, Todd/F-5473-2011 FU NIAID/NIH [AI028568, AI030914]; Howard Hughes Medical Institute; Harvard University Center for AIDS Research (HU CFAR); Mark and Lisa Schwartz Foundation; IAVI; Bill and Melinda Gates Foundation; Canadian Institutes for Health Research (CIHR) FX The ideas and opinions expressed in the manuscript are solely the responsibility of the authors and are not necessarily shared by the NIH or other funding sources, Massachusetts General Hospital, or its affiliates. We declare no conflicts of interest related to this study. NR 38 TC 171 Z9 175 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR 15 PY 2009 VL 83 IS 6 BP 2743 EP 2755 DI 10.1128/JVI.02265-08 PG 13 WC Virology SC Virology GA 411LG UT WOS:000263650500033 PM 19116253 ER PT J AU Patursky-Polischuk, I Stolovich-Rain, M Hausner-Hanochi, M Kasir, J Cybulski, N Avruch, J Rueg, MA Hall, MN Meyuhas, O AF Patursky-Polischuk, Ilona Stolovich-Rain, Miri Hausner-Hanochi, Mirito Kasir, Judith Cybulski, Nadine Avruch, Joseph Ruegg, Markus A. Hall, Michael N. Meyuhas, Oded TI The TSC-mTOR Pathway Mediates Translational Activation of TOP mRNAs by Insulin Largely in a Raptor- or Rictor-Independent Manner (vol 29, pg 640, 2009) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 [Patursky-Polischuk, Ilona] Hebrew Univ Jerusalem Hadassah Hosp & Med Sch, Dept Biochem, Sch Med, IL-91120 Jerusalem, Israel. Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. Massachusetts Gen Hosp, Diabet Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Patursky-Polischuk, I (reprint author), Hebrew Univ Jerusalem Hadassah Hosp & Med Sch, Dept Biochem, Sch Med, IL-91120 Jerusalem, Israel. NR 1 TC 0 Z9 0 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 MAR 15 PY 2009 VL 29 IS 6 BP 1670 EP 1670 DI 10.1128/MCB.00104-09 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 412JB UT WOS:000263720000025 ER PT J AU Gale, JT Shields, DC Jain, FA Amirnouin, R Eskandar, EN AF Gale, John T. Shields, Donald C. Jain, Felipe A. Amirnouin, Ramin Eskandar, Emad N. TI Subthalamic nucleus discharge patterns during movement in the normal monkey and Parkinsonian patient SO BRAIN RESEARCH LA English DT Article DE Parkinson disease; Subthalamic nucleus; Basal ganglia; Movement; Oscillations ID HUMAN BASAL GANGLIA; NEURONAL-ACTIVITY; PALLIDAL NEURONS; MPTP MODEL; DISEASE; OSCILLATIONS; CORTEX; PATHOPHYSIOLOGY; DISORDERS; CIRCUITS AB The pathophysiology of Parkinson disease (PD) is characterized by derangements in the discharge rates, bursting patterns, and oscillatory activity of basal ganglia (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns in humans with PD were compared with that in the normal monkey during performance of similar volitional movements. Single-unit STN recordings were collected while PD patients and animals moved a joystick in the direction of targets presented on a monitor. When discharge rates in all PD human and normal monkey neurons were compared, no significant differences were observed. However, when neurons were classified by peri-movement response type (i.e., excited, inhibited, or unresponsive to movement) statistical differences were demonstrated - most significantly among PD excited neurons. Analysis of burst activity demonstrated inter- and intra-burst activities were greater in the PD human compared to the monkey irrespective of neuronal response type. Moreover, simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies. During movement, discharge and burst rates were positively correlated, independent of subject or neuronal response type; however, rates and oscillatory activity were more strongly correlated in the PD human than the normal monkey. Interestingly, across all domains of analysis, STN neurons in PD demonstrated reduced response variability when compared to STN neurons in the normal monkey brain. Thus, the net effect of PD maybe a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity. (C) 2009 Elsevier B.V. All rights reserved. C1 [Gale, John T.; Shields, Donald C.; Jain, Felipe A.; Amirnouin, Ramin; Eskandar, Emad N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St,ACC-021, Boston, MA 02114 USA. EM eeskandar@partners.org FU American Parkinson's Disease Association; Doris Duke Charitable Foundation; Parkinson Disease Foundation FX The authors would like to acknowledge the efforts of Jane Roberts for her help in preparing the experimental data. Funding was provided by the American Parkinson's Disease Association (JTG), Doris Duke Charitable Foundation (FAJ), and Parkinson Disease Foundation (ENE). NR 31 TC 25 Z9 25 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 13 PY 2009 VL 1260 BP 15 EP 23 DI 10.1016/j.brainres.2008.12.062 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 423RP UT WOS:000264513700003 PM 19167367 ER PT J AU Fukuda, T Kohda, M Kanomata, K Nojima, J Nakamura, A Kamizono, J Noguchi, Y Iwakiri, K Kondo, T Kurose, J Endo, K Awakura, T Fukushi, J Nakashima, Y Chiyonobu, T Kawara, A Nishida, Y Wada, I Akita, M Komori, T Nakayama, K Nanba, A Maruki, Y Yoda, T Tomoda, H Yu, PB Shore, EM Kaplan, FS Miyazono, K Matsuoka, M Ikebuchi, K Ohtake, A Oda, H Jimi, E Owan, I Okazaki, Y Katagiri, T AF Fukuda, Toru Kohda, Masakazu Kanomata, Kazuhiro Nojima, Junya Nakamura, Atsushi Kamizono, Jyunji Noguchi, Yasuo Iwakiri, Kiyofumi Kondo, Takeo Kurose, Junichi Endo, Ken-ichi Awakura, Takeshi Fukushi, Junichi Nakashima, Yasuharu Chiyonobu, Tomohiro Kawara, Akira Nishida, Yoshihiro Wada, Ikuo Akita, Masumi Komori, Tetsuo Nakayama, Konosuke Nanba, Akira Maruki, Yuichi Yoda, Tetsuya Tomoda, Hiroshi Yu, Paul B. Shore, Eileen M. Kaplan, Frederick S. Miyazono, Kohei Matsuoka, Masaru Ikebuchi, Kenji Ohtake, Akira Oda, Hiromi Jimi, Eijiro Owan, Ichiro Okazaki, Yasushi Katagiri, Takenobu TI Constitutively Activated ALK2 and Increased SMAD1/5 Cooperatively Induce Bone Morphogenetic Protein Signaling in Fibrodysplasia Ossificans Progressiva SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I RECEPTORS; HETEROTOPIC OSSIFICATION; NATURAL-HISTORY; C2C12 MYOBLASTS; MESSENGER-RNA; ACTIVIN-A; IDENTIFICATION; CELLS; DIFFERENTIATION; PATHWAY AB Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by congenital malformation of the great toes and by progressive heterotopic bone formation in muscle tissue. Recently, a mutation involving a single amino acid substitution in a bone morphogenetic protein (BMP) type I receptor, ALK2, was identified in patients with FOP. We report here that the identical mutation, R206H, was observed in 19 Japanese patients with sporadic FOP. This mutant receptor, ALK2(R206H), activates BMP signaling without ligand binding. Moreover, expression of Smad1 and Smad5 was up-regulated in response to muscular injury. ALK2(R206H) with Smad1 or Smad5 induced osteoblastic differentiation that could be inhibited by Smad7 or dorsomorphin. Taken together, these findings suggest that the heterotopic bone formation in FOP may be induced by a constitutively activated BMP receptor signaling through Smad1 or Smad5. Gene transfer of Smad7 or inhibition of type I receptors with dorsomorphin may represent strategies for blocking the activity induced by ALK2(R206H) in FOP. C1 [Fukuda, Toru; Kanomata, Kazuhiro; Nojima, Junya; Nakamura, Atsushi; Katagiri, Takenobu] Saitama Med Univ, Res Ctr Genom Med, Div Pathophysiol, Hidaka, Saitama 3501241, Japan. [Kohda, Masakazu; Okazaki, Yasushi] Saitama Med Univ, Res Ctr Genom Med, Div Translat Res, Hidaka, Saitama 3501241, Japan. [Fukuda, Toru; Akita, Masumi; Komori, Tetsuo; Nakayama, Konosuke; Nanba, Akira; Maruki, Yuichi; Yoda, Tetsuya; Tomoda, Hiroshi; Miyazono, Kohei; Ikebuchi, Kenji; Ohtake, Akira; Oda, Hiromi; Jimi, Eijiro; Owan, Ichiro; Okazaki, Yasushi; Katagiri, Takenobu] Saitama Med Univ, Project Clin & Basic Res FOP, Hidaka, Saitama 3501241, Japan. [Kamizono, Jyunji] Kitakyusyu City Yahata Hosp, Dept Pediat Emergency, Yahatahigashi Ku, Kitakyushu, Fukuoka 8058534, Japan. [Noguchi, Yasuo] Saga Prefectural Hosp Koseikan, Dept Orthoped Surg, Saga 8408571, Japan. [Iwakiri, Kiyofumi] Nagayoshi Orthoped Clin, Miyazaki 8800951, Japan. [Kondo, Takeo] Tohoku Univ, Grad Sch Med, Dept Phys Med & Rehabil, Aoba Ku, Sendai, Miyagi 9808474, Japan. [Kurose, Junichi] Senjyudo Hosp, Dept Orthoped Surg, Gifu 5008862, Japan. [Endo, Ken-ichi] Endo Clin, Kodaira, Tokyo 1870035, Japan. [Awakura, Takeshi] Awakura Clin, Wajima, Ishiwawa 9280246, Japan. [Fukushi, Junichi; Nakashima, Yasuharu] Kyushu Univ, Fac Med, Dept Orthoped Surg, Higashi Ku, Fukuoka 8128582, Japan. [Chiyonobu, Tomohiro] Akashi Municipal Hosp, Dept Pediat, Akashi, Hyogo 6738501, Japan. [Kawara, Akira] Kawara Clin, Higashinada Ku, Kobe, Hyogo 6580051, Japan. [Nishida, Yoshihiro] Nagoya Univ, Grad Sch, Dept Orthopaed Surg, Showa Ku, Nagoya, Aichi 4668550, Japan. [Nishida, Yoshihiro] Sch Med, Showa Ku, Nagoya, Aichi 4668550, Japan. [Wada, Ikuo] Nagoya City Univ Hosp, Dept Rehabil, Mizuho Ku, Nagoya, Aichi 4678602, Japan. [Nojima, Junya; Yoda, Tetsuya] Saitama Med Univ, Dept Oral & Maxillofacial Surg, Moroyama, Saitama 3500495, Japan. [Nanba, Akira] Saitama Med Univ, Dept Obstet & Gynecol, Moroyama, Saitama 3500495, Japan. [Nakayama, Konosuke] Saitama Med Univ, Dept Endocrinol & Diabet, Moroyama, Saitama 3500495, Japan. [Komori, Tetsuo] Saitama Med Univ, Dept Neurol, Moroyama, Saitama 3500495, Japan. [Oda, Hiromi] Saitama Med Univ, Dept Orthoped Surg, Moroyama, Saitama 3500495, Japan. [Ohtake, Akira] Saitama Med Univ, Dept Pediat, Moroyama, Saitama 3500495, Japan. [Matsuoka, Masaru; Ikebuchi, Kenji] Saitama Med Univ, Dept Lab Med, Moroyama, Saitama 3500495, Japan. [Akita, Masumi] Saitama Med Univ, Biomed Res Ctr, Div Morphol Sci, Moroyama, Saitama 3500495, Japan. [Maruki, Yuichi] Saitama Neuropsychiat Inst, Dept Neurol, Chuo Ku, Saitama 3388577, Japan. [Miyazono, Kohei] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, Tokyo 1130033, Japan. [Tomoda, Hiroshi] Kitasato Univ, Sch Pharmaceut Sci, Minato Ku, Tokyo 1080023, Japan. [Yu, Paul B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02129 USA. [Yu, Paul B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Boston, MA 02129 USA. [Shore, Eileen M.; Kaplan, Frederick S.] Univ Penn, Sch Med, Dept Orthoped Surg, Ctr Res Fibrodysplasia Ossificans Progress & Rela, Philadelphia, PA 19104 USA. [Jimi, Eijiro] Kyushu Dent Coll, Dept Biosci, Div Mol Signaling & Biochem, Kokurakita Ku, Kitakyushu, Fukuoka 8038580, Japan. [Owan, Ichiro] Univ Ryukyus, Fac Med, Dept Orthoped Surg, Nishihara, Okinawa 9030215, Japan. [Nakashima, Yasuharu] Minist Hlth Labour & Welf, Res Comm Fibrodysplasia Ossificans Progress, Bunkyo Ku, Tokyo 1138655, Japan. RP Katagiri, T (reprint author), Saitama Med Univ, Res Ctr Genom Med, Div Pathophysiol, 1397-1 Yamane, Hidaka, Saitama 3501241, Japan. EM katagiri@saitama-med.ac.jp RI Shore, Eileen/D-2593-2009; Nishida, Yoshihiro/I-7354-2014; OI Yu, Paul/0000-0003-2145-4944 FU NHLBI NIH HHS [K08 HL079943, K08 HL079943-04]; NIAMS NIH HHS [R01-AR41916] NR 42 TC 82 Z9 84 U1 3 U2 9 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 MAR 13 PY 2009 VL 284 IS 11 BP 7149 EP 7156 DI 10.1074/jbc.M801681200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 415FF UT WOS:000263919000062 PM 18684712 ER PT J AU Pamuklar, Z Federico, L Liu, SY Umezu-Goto, M Dong, AP Panchatcharam, M Fulerson, Z Berdyshev, E Natarajan, V Fang, XJ Van Meeteren, LA Moolenaar, WH Mills, GB Morris, AJ Smyth, SS AF Pamuklar, Zehra Federico, Lorenzo Liu, Shuying Umezu-Goto, Makiko Dong, Anping Panchatcharam, Manikandan Fulerson, Zachary Berdyshev, Evgeny Natarajan, Viswanathan Fang, Xianjun Van Meeteren, Laurens A. Moolenaar, Wouter H. Mills, Gordon B. Morris, Andrew J. Smyth, Susan S. TI Autotaxin/Lysopholipase D and Lysophosphatidic Acid Regulate Murine Hemostasis and Thrombosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; PLATELET SHAPE CHANGE; MYOSIN LIGHT-CHAIN; GLANZMANN THROMBASTHENIA; LYSOPHOSPHOLIPASE-D; AUTOTAXIN; RECEPTORS; ACTIVATION; MICE; PHOSPHORYLATION AB The lipid mediator lysophosphatidic acid (LPA) is a potent regulator of vascular cell function in vitro, but its physiologic role in the cardiovasculature is largely unexplored. To address the role of LPA in regulating platelet function and thrombosis, we investigated the effects of LPA on isolated murine platelets. Although LPA activates platelets from the majority of human donors, we found that treatment of isolated murine platelets with physiologic concentrations of LPA attenuated agonist-induced aggregation. Transgenic overexpression of autotaxin/lysophospholipase D (Enpp2), the enzyme necessary for production of the bulk of biologically active LPA in plasma, elevated circulating LPA levels and induced a bleeding diathesis and attenuation of thrombosis in mice. Intravascular administration of exogenous LPA recapitulated the prolonged bleeding time observed in Enpp2-Tg mice. Enpp2(+/-) mice, which have similar to 50% normal plasma LPA levels, were more prone to thrombosis. Plasma autotaxin associated with platelets during aggregation and concentrated in arterial thrombus, and activated but not resting platelets bound recombinant autotaxin/lysoPLD in an integrin-dependent manner. These results identify a novel pathway in which LPA production by autotaxin/lysoPLD regulates murine hemostasis and thrombosis and suggest that binding of autotaxin/lysoPLD to activated platelets may provide a mechanism to localize LPA production. C1 [Pamuklar, Zehra; Federico, Lorenzo; Dong, Anping; Panchatcharam, Manikandan; Fulerson, Zachary; Morris, Andrew J.; Smyth, Susan S.] Gill Heart Inst, Div Cardiovasc Med, Lexington, KY USA. [Federico, Lorenzo; Smyth, Susan S.] Univ Kentucky, Dept Pharmacol, Lexington, KY 40536 USA. [Morris, Andrew J.] Univ Kentucky, Dept Biochem, Lexington, KY 40536 USA. [Liu, Shuying; Umezu-Goto, Makiko; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Berdyshev, Evgeny; Natarajan, Viswanathan] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Fang, Xianjun] Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. [Van Meeteren, Laurens A.; Moolenaar, Wouter H.] Netherlands Canc Inst, Div Cellular Biochem, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands. [Smyth, Susan S.] US Dept Vet Affairs, Med Ctr, Lexington, KY 40511 USA. RP Smyth, SS (reprint author), Gill Heart Inst, Div Cardiovasc Med, 900 S Limestone St,326 CTW Bldg, Lexington, KY USA. EM SusanSmyth@uky.edu RI van Meeteren, Laurens/A-9890-2008; Morris, Andrew/B-7869-2010 OI van Meeteren, Laurens/0000-0001-9885-0668; FU National Institutes of Health [HL070304, HL078663, HL074219, CA096496, GM050388, HL79396, P30 CA16672, PO1 CA64602] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL070304, HL078663, and HL074219 ( to S. S. S.), CA096496 and GM050388 to A. J. M.), HL79396 ( to V. N.), and P30 CA16672 and PO1 CA64602 ( to G. B. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 48 TC 74 Z9 75 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 2009 VL 284 IS 11 BP 7385 EP 7394 DI 10.1074/jbc.M807820200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 415FF UT WOS:000263919000084 PM 19139100 ER PT J AU Shiotani, B Zou, L AF Shiotani, Bunsyo Zou, Lee TI Single-Stranded DNA Orchestrates an ATM-to-ATR Switch at DNA Breaks SO MOLECULAR CELL LA English DT Article ID DAMAGE RESPONSE; CELL-CYCLE; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; END RESECTION; MRE11-RAD50-NBS1 COMPLEX; SACCHAROMYCES-CEREVISIAE; CHECKPOINT ACTIVATION; HISTONE H2AX; PHOSPHORYLATION AB ATM and ATR are two master checkpoint kinases activated by double-stranded DNA breaks (DSBs). ATM is critical for the initial response and the subsequent ATR activation. Here we show that ATR activation is coupled with loss of ATM activation, an unexpected ATM-to-ATR switch during the biphasic DSB response. ATM is activated by DSBs with blunt ends or short single-stranded overhangs (SSOs). Surprisingly, the activation of ATM in the presence of SSOs, like that of ATR, relies on single- and double-stranded DNA junctions. In a length-dependent manner, SSOs attenuate ATM activation and potentiate ATR activation through a swap of DNA-damage sensors. Progressive resection of DSBs directly promotes the ATM-to-ATR switch in vitro. In cells, the ATM-to-ATR switch is driven by both ATM and the nucleases participating in DSB resection. Thus, single-stranded DNA orchestrates ATM and ATR to function in an orderly and reciprocal manner in two distinct phases of DSB response. C1 [Shiotani, Bunsyo; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu FU National Institutes of Health (NIH) [GM076388]; Susan G. Komen Foundation; Breast Cancer Alliance; Tosteson Foundation FX We thank Drs. R. Abraham, B. Chen, D. Chen, J. Chen, D. Cortez, G. U, S. Elledge, T. Paull, and L. Rasmussen for reagents; Drs. S. Elledge and N. Dyson for comments on the manuscript; and members of the Zou lab for discussions, LZ is a V Scholar and an Ellison New Scholar. This work is supported by grants from the National Institutes of Health (NIH) (GM076388), the Susan G. Komen Foundation, and the Breast Cancer Alliance. B.S. was partly supported by a fellowship from the Tosteson Foundation. NR 60 TC 168 Z9 171 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 13 PY 2009 VL 33 IS 5 BP 547 EP 558 DI 10.1016/j.molcel.2009.01.024 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 419RT UT WOS:000264237800002 PM 19285939 ER PT J AU Mirshahidi, S Kramer, VG Whitney, JB Essono, S Lee, S Dranoff, G Anderson, KS Ruprecht, RM AF Mirshahidi, Saied Kramer, Victor G. Whitney, James B. Essono, Sosthene Lee, Sandra Dranoff, Glenn Anderson, Karen S. Ruprecht, Ruth M. TI Overlapping synthetic peptides encoding TPD52 as breast cancer vaccine in mice: Prolonged survival SO VACCINE LA English DT Article DE Overlapping synthetic peptides (OSP); Vaccine; Cancer; Tumor protein 52 ID TUMOR PROTEIN D52; T-CELL IMMUNITY; ACTIVE IMMUNIZATION; PROSTATE-CANCER; OVARIAN-CANCER; CPG MOTIFS; IDENTIFICATION; LYMPHOCYTES; FAMILY; HELPER AB Peptide-based vaccines, one of several anti tumor immunization strategies currently under investigation, can elicit both MFIC Class F restricted (CD8(+)) and Class II-restricted (CD4(+)) responses. However, the need to identify specific T-cell epitopes in the context of MHC alleles has hampered the application of this approach, We have tested overlapping synthetic peptides (OSP) representing a tumor antigen as a novel approach that bypasses the need for epitope mapping, since OSP contain all possible epitopes for both CD8(+) and CD4(+) T cells. Here we report that vaccination of inbred and outbred mice with OSP representing tumor protein D52 (TPD52-OSP), a potential tumor antigen target for immunotherapy against breast, prostate, and ovarian cancer, was safe and induced specific CD8(+) and CD4* T-cell responses, as demonstrated by development of specific cytotoxic T cell (CTL) activity, proliferative responses, interferon (IFN)-gamma production and CD107a/b expression in all mice tested. In addition, TPD52-OSP-vaccinated BALB/c mice were challenged with TS/A breast carcinoma cells expressing endogenous TPD52; significant survival benefits were noted in vaccine recipients compared to unvaccinated controls (p<0.001). Our proof-of-concept data demonstrate the safety and efficacy of peptide library-based cancer vaccines that obviates the need to identify epitopes or MHC backgrounds of the vaccinees. We show that an OSP vaccination approach can assist in the disruption of self-tolerance and conclude that our approach may hold promise for immunoprevention of early-stage cancers in a general population. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Mirshahidi, Saied; Kramer, Victor G.; Whitney, James B.; Essono, Sosthene; Ruprecht, Ruth M.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Mirshahidi, Saied; Whitney, James B.; Essono, Sosthene; Dranoff, Glenn; Anderson, Karen S.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lee, Sandra] Dana Farber Canc Inst, Dept Biostat & Compuatat Biol, Boston, MA 02115 USA. [Lee, Sandra] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Dranoff, Glenn; Anderson, Karen S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 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 FU NIAID NIH HHS [P01 AI048240] NR 43 TC 10 Z9 12 U1 1 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 MAR 13 PY 2009 VL 27 IS 12 BP 1825 EP 1833 DI 10.1016/j.vaccine.2009.01.089 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 426AU UT WOS:000264680600006 PM 19201387 ER PT J AU Maddox, TM Ross, C Ho, PM Magid, D Rumsfeld, JS AF Maddox, Thomas M. Ross, Colleen Ho, P. Michael Magid, David Rumsfeld, John S. TI Impaired heart rate recovery is associated with new-onset atrial fibrillation: a prospective cohort study SO BMC CARDIOVASCULAR DISORDERS LA English DT Article ID TREADMILL EXERCISE SCORE; RISK-FACTORS; CHRONOTROPIC RESPONSE; PROGNOSTIC VALUE; MORTALITY; PREDICTOR; DISEASE; DYSFUNCTION; PREVALENCE; MANAGEMENT AB Background: Autonomic dysfunction appears to play a significant role in the development of atrial fibrillation (AF), and impaired heart rate recovery (HRR) during exercise treadmill testing (ETT) is a known marker for autonomic dysfunction. However, whether impaired HRR is associated with incident AF is unknown. We studied the association of impaired HRR with the development of incident AF, after controlling for demographic and clinical confounders. Methods: We studied 8236 patients referred for ETT between 2001 and 2004, and without a prior history of AF. Patients were categorized by normal or impaired HRR on ETT. The primary outcome was the development of AF. Cox proportional hazards modeling was used to control for demographic and clinical characteristics. Secondary analyses exploring a continuous relationship between impaired HRR and AF, and exploring interactions between cardiac medication use, HRR, and AF were also conducted. Results: After adjustment, patients with impaired HRR were more likely to develop AF than patients with normal HRR (HR 1.43, 95% confidence interval (CI) 1.06, 1.93). In addition, there was a linear trend between impaired HRR and AF (HR 1.05 for each decreasing BPM in HRR, 95% CI 0.99, 1.11). No interactions between cardiac medications, HRR, and AF were noted. Conclusion: Patients with impaired HRR on ETT were more likely to develop new-onset AF, as compared to patients with normal HRR. These findings support the hypothesis that autonomic dysfunction mediates the development of AF, and suggest that interventions known to improve HRR, such as exercise training, may delay or prevent AF. C1 [Maddox, Thomas M.; Ho, P. Michael; Rumsfeld, John S.] Denver VAMC, Cardiol Sect, Denver, CO USA. [Maddox, Thomas M.; Ho, P. Michael; Rumsfeld, John S.] Univ Colorado Denver, Dept Med Cardiol, Denver, CO USA. [Ross, Colleen; Magid, David] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. RP Maddox, TM (reprint author), Denver VAMC, Cardiol Sect, Denver, CO USA. EM thomas.maddox@va.gov; colleen.ross@kp.org; michael.ho@va.gov; david.j.magid@kp.org; john.rumsfeld@va.gov FU Institute for Health Research, Kaiser Permanente Colorado FX Funding for the cohort creation and analysis came from the Institute for Health Research, Kaiser Permanente Colorado. NR 28 TC 5 Z9 6 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2261 J9 BMC CARDIOVASC DISOR JI BMC Cardiovasc. Disord. PD MAR 12 PY 2009 VL 9 AR 11 DI 10.1186/1471-2261-9-11 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 457HT UT WOS:000266919800001 PM 19284627 ER PT J AU Eatock, RA AF Eatock, Ruth Anne TI NEUROSCIENCE Up, down, flying around SO NATURE LA English DT Editorial Material ID DROSOPHILA-MELANOGASTER; HAIR-CELLS; TRANSDUCTION; ORGAN; EAR C1 [Eatock, Ruth Anne] Harvard Univ, Sch Med, Dept Otol & Laryngol, Eaton Peabody Lab, Boston, MA 02114 USA. [Eatock, Ruth Anne] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Eatock, RA (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Eaton Peabody Lab, Boston, MA 02114 USA. EM eatock@meei.harvard.edu RI Eatock, Ruth/F-6404-2013; OI Eatock, Ruth Anne/0000-0001-7547-2051 NR 13 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 12 PY 2009 VL 458 IS 7235 BP 156 EP 157 DI 10.1038/458156a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417EQ UT WOS:000264059700029 PM 19279623 ER PT J AU Velu, V Titanji, K Zhu, BG Husain, S Pladevega, A Lai, LL Vanderford, TH Chennareddi, L Silvestri, G Freeman, GJ Ahmed, R Amara, RR AF Velu, Vijayakumar Titanji, Kehmia Zhu, Baogong Husain, Sajid Pladevega, Annette Lai, Lilin Vanderford, Thomas H. Chennareddi, Lakshmi Silvestri, Guido Freeman, Gordon J. Ahmed, Rafi Amara, Rama Rao TI Enhancing SIV-specific immunity in vivo by PD-1 blockade SO NATURE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CD8 T-CELLS; CHRONIC VIRAL-INFECTION; PROGRAMMED DEATH-1; EFFECTOR FUNCTION; EXPRESSION; LYMPHOCYTES; PERSISTENCE; EXHAUSTION; MECHANISMS AB Chronic immunodeficiency virus infections are characterized by dysfunctional cellular and humoral antiviral immune responses(1-3). As such, immune modulatory therapies that enhance and/or restore the function of virus-specific immunity may protect from disease progression. Here we investigate the safety and immune restoration potential of blockade of the co-inhibitory receptor programmed death 1 (PD-1) 4,5 during chronic simian immunodeficiency virus (SIV) infection in macaques. We demonstrate that PD-1 blockade using an antibody to PD-1 is well tolerated and results in rapid expansion of virus-specific CD8 T cells with improved functional quality. This enhanced T-cell immunity was seen in the blood and also in the gut, a major reservoir of SIV infection. PD-1 blockade also resulted in proliferation of memory B cells and increases in SIV envelope-specific antibody. These improved immune responses were associated with significant reductions in plasma viral load and also prolonged the survival of SIV-infected macaques. Blockade was effective during the early (week 10) as well as late (similar to week 90) phases of chronic infection even under conditions of severe lymphopenia. These results demonstrate enhancement of both cellular and humoral immune responses during a pathogenic immunodeficiency virus infection by blocking a single inhibitory pathway and identify a novel therapeutic approach for control of human immunodeficiency virus infections. C1 [Velu, Vijayakumar; Titanji, Kehmia; Husain, Sajid; Pladevega, Annette; Lai, Lilin; Chennareddi, Lakshmi; Ahmed, Rafi; Amara, Rama Rao] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Velu, Vijayakumar; Titanji, Kehmia; Husain, Sajid; Pladevega, Annette; Lai, Lilin; Chennareddi, Lakshmi; Amara, Rama Rao] Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Zhu, Baogong; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhu, Baogong; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Vanderford, Thomas H.; Silvestri, Guido] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Amara, RR (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. EM ramara@emory.edu OI Velu, Vijayakumar/0000-0003-4238-1924 FU NCRR NIH HHS [P51 RR000165, P51 RR00165, R24 RR016038, R24 RR16038]; NIAID NIH HHS [R01 AI074417-02, P30 AI050409, R01 AI057029, R01 AI057029-01, R01 AI057029-02, R01 AI057029-03, R01 AI057029-04, R01 AI057029-05, R01 AI071852, R01 AI074417, R01 AI074417-01A1] NR 30 TC 292 Z9 313 U1 4 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 12 PY 2009 VL 458 IS 7235 BP 206 EP U5 DI 10.1038/nature07662 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417EQ UT WOS:000264059700044 PM 19078956 ER PT J AU Guttman, M Amit, I Garber, M French, C Lin, MF Feldser, D Huarte, M Zuk, O Carey, BW Cassady, JP Cabili, MN Jaenisch, R Mikkelsen, TS Jacks, T Hacohen, N Bernstein, BE Kellis, M Regev, A Rinn, JL Lander, ES AF Guttman, Mitchell Amit, Ido Garber, Manuel French, Courtney Lin, Michael F. Feldser, David Huarte, Maite Zuk, Or Carey, Bryce W. Cassady, John P. Cabili, Moran N. Jaenisch, Rudolf Mikkelsen, Tarjei S. Jacks, Tyler Hacohen, Nir Bernstein, Bradley E. Kellis, Manolis Regev, Aviv Rinn, John L. Lander, Eric S. TI Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals SO NATURE LA English DT Article ID X-INACTIVATION CENTER; TRANSCRIPTIONAL ACTIVITY; GENE-EXPRESSION; MOUSE OOCYTES; STEM-CELLS; GENOME; CHROMOSOME; INTERFERENCE; SEQUENCES; NOISE AB There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts(1-4). However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise(5,6). Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified similar to 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NF kappa B, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes. C1 [Guttman, Mitchell; Amit, Ido; Garber, Manuel; French, Courtney; Lin, Michael F.; Huarte, Maite; Zuk, Or; Mikkelsen, Tarjei S.; Hacohen, Nir; Bernstein, Bradley E.; Kellis, Manolis; Regev, Aviv; Rinn, John L.; Lander, Eric S.] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA. [Guttman, Mitchell; Carey, Bryce W.; Cassady, John P.; Jaenisch, Rudolf; Jacks, Tyler; Regev, Aviv; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Feldser, David; Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Mikkelsen, Tarjei S.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Huarte, Maite; Rinn, John L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Cabili, Moran N.; Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Carey, Bryce W.; Cassady, John P.; Jaenisch, Rudolf; Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Bernstein, Bradley E.; Rinn, John L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rinn, JL (reprint author), MIT & Harvard, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM jrinn@broad.mit.edu RI Phelps, Steve/H-2263-2011; Mikkelsen, Tarjei/A-1306-2007; Huarte, Maite/J-6903-2014 OI Mikkelsen, Tarjei/0000-0002-8133-3135; Huarte, Maite/0000-0003-3753-6493 FU Human Frontier Science Program Organization; Beth Israel Deaconess Medical Center; National Human Genome Research Institute; Broad Institute of MIT and Harvard FX We would like to thank our colleagues at the Broad Institute, especially J. P. Mesirov for discussions and statistical insights, X. Xie for statistical help with conservation analyses, J. Robinson for visualization help, M. Ku, E. Mendenhall and X. Zhang for help generating ChIP samples, and N. Novershtern and A. Levy for providing transcription factor lists. M. Guttman is a Vertex scholar, I. A. acknowledges the support of the Human Frontier Science Program Organization. This work was funded by Beth Israel Deaconess Medical Center, National Human Genome Research Institute, and the Broad Institute of MIT and Harvard. NR 30 TC 1548 Z9 1661 U1 16 U2 220 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAR 12 PY 2009 VL 458 IS 7235 BP 223 EP 227 DI 10.1038/nature07672 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417EQ UT WOS:000264059700048 PM 19182780 ER PT J AU Singhal, AB Kimberly, W T Schaefer, PW Hedley-Whyte, ET AF Singhal, Aneesh B. Kimberly, W. Taylor Schaefer, Pamela W. Hedley-Whyte, E. Tessa TI Case 8-2009: A 36-Year-Old Woman with Headache, Hypertension, and Seizure 2 Weeks Post Partum. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY; CEREBRAL VASOCONSTRICTION SYNDROMES; PLACENTAL GROWTH-FACTOR; SUBARACHNOID HEMORRHAGE; POSTPARTUM ANGIOPATHY; THUNDERCLAP HEADACHE; TYROSINE KINASE-1; RISK-FACTORS; PREECLAMPSIA C1 [Singhal, Aneesh B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Partners Neurol Residency Program, Boston, MA 02114 USA. [Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Singhal, Aneesh B.; Kimberly, W. Taylor] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Schaefer, Pamela W.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 44 TC 38 Z9 39 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 12 PY 2009 VL 360 IS 11 BP 1126 EP 1137 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 417BW UT WOS:000264051000012 PM 19279345 ER PT J AU Basu, U Franklin, A Alt, FW AF Basu, Uttiya Franklin, Andrew Alt, Frederick W. TI Post-translational regulation of activation-induced cytidine deaminase SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE activation-induced cytidine deaminase; class switch recombination; evolution; phosphorylation; somatic hypermutation ID CLASS-SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; ANTIBODY DIVERSIFICATION ENZYME; KINASE-A PHOSPHORYLATION; SOMATIC HYPERMUTATION; GENE CONVERSION; TARGETED DNA; B-CELLS; AID; IMMUNOGLOBULIN AB The assembled immunoglobulin genes in the B cells of mice and humans are altered by distinct processes known as class switch recombination (CSR) and somatic hypermutation, leading to diversification of the antibody repertoire. These two DNA modification processes are initiated by the B cell-specific protein factor activation-induced cytidine deaminase ( AID). AID is post-translationally modified by phosphorylation at multiple sites, although functional significance during CSR has been implicated only for phosphorylation at serine-38 (S38). Although multiple laboratories have demonstrated that AID function is regulated via phosphorylation at S38, the precise biological role of S38 phosphorylation has been a topic of debate. Here, we discuss our interpretation of the significance of AID regulation via phosphorylation and also discuss how this form of AID regulation may have evolved in higher organisms. C1 [Basu, Uttiya; Franklin, Andrew; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Basu, Uttiya; Franklin, Andrew; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Basu, Uttiya; Franklin, Andrew; Alt, Frederick W.] Immune Dis Inst, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU NIH FX The authors would like to thank the members of the Alt laboratory for helpful discussions about many of the topics covered in this manuscript. U. B. is a fellow of the Irvington Institute of Immunology program of the Cancer Research Institute. This work was supported by an NIH grant to F. W. A. F. W. A. is an investigator of the Howard Hughes Medical Institute. NR 57 TC 8 Z9 8 U1 0 U2 0 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD MAR 12 PY 2009 VL 364 IS 1517 BP 667 EP 673 DI 10.1098/rstb.2008.0194 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 400VR UT WOS:000262898000014 PM 19010772 ER PT J AU Weinstock, DM Zuccotti, G AF Weinstock, David M. Zuccotti, Gianna TI The Evolution of Influenza Resistance and Treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID LIVE ATTENUATED VACCINES; A H3N2 VIRUSES; ADAMANTANE RESISTANCE; SEASONAL INFLUENZA; UNITED-STATES; OSELTAMIVIR; WORLDWIDE; SURVEILLANCE; PREVENTION C1 [Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zuccotti, Gianna] Brigham & Womens Hosp, Div Infect Dis, Dept Med, Boston, MA 02115 USA. [Weinstock, David M.; Zuccotti, Gianna] Harvard Univ, Sch Med, Boston, MA USA. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,DA510B, Boston, MA 02115 USA. EM weinstock@dfci.harvard.edu NR 27 TC 67 Z9 72 U1 1 U2 5 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 MAR 11 PY 2009 VL 301 IS 10 BP 1066 EP 1069 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 416OQ UT WOS:000264015800033 PM 19255112 ER PT J AU Schillace, RV Miller, CL Pisenti, N Grotzke, JE Swarbrick, GM Lewinsohn, DM Carr, DW AF Schillace, Robynn V. Miller, Casey L. Pisenti, Neal Grotzke, Jeff E. Swarbrick, Gwendolyn M. Lewinsohn, David M. Carr, Daniel W. TI A-Kinase Anchoring in Dendritic Cells Is Required for Antigen Presentation SO PLOS ONE LA English DT Article AB Background: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E-2, cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase anchoring proteins (AKAPs). Here we present evidence for the existence and functional importance of AKAPs in human DC. Methodology/Principal Findings: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin. We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-IS. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-gamma production from antigen specific CD4(+) T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-alpha and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b, slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. Conclusions: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology. C1 [Schillace, Robynn V.; Miller, Casey L.; Pisenti, Neal; Lewinsohn, David M.; Carr, Daniel W.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Schillace, Robynn V.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Grotzke, Jeff E.] Oregon Hlth & Sci Univ, Dept Microbiol & Mol Immunol, Portland, OR 97201 USA. [Swarbrick, Gwendolyn M.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Pulmonary Med, Portland, OR 97201 USA. [Carr, Daniel W.] Oregon Hlth & Sci Univ, Dept Endocrinol, Portland, OR 97201 USA. RP Schillace, RV (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. EM carrd@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research & Development Service FX This research was supported by Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research & Development Service (DWC). VA Merit Review. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 10 Z9 12 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 11 PY 2009 VL 4 IS 3 AR e4807 DI 10.1371/journal.pone.0004807 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437OF UT WOS:000265496100024 PM 19277197 ER PT J AU Cheng, S Morrow, DA Sloan, S Antman, EM Sabatine, MS AF Cheng, Susan Morrow, David A. Sloan, Sarah Antman, Elliott M. Sabatine, Marc S. TI Predictors of Initial Nontherapeutic Anticoagulation With Unfractionated Heparin in ST-Segment Elevation Myocardial Infarction SO CIRCULATION LA English DT Article DE anticoagulants; coronary disease; heparin; myocardial infarction; pharmacology ID ACUTE CORONARY SYNDROMES; PARTIAL THROMBOPLASTIN TIME; GLYCOPROTEIN IIB/IIIA INHIBITORS; MOLECULAR-WEIGHT HEPARIN; THROMBOLYTIC THERAPY; AMERICAN-COLLEGE; XA ACTIVITY; TASK-FORCE; GUSTO-IIB; NOMOGRAM AB Background-Although weight-based nomograms have improved the efficacy and safety of dosing unfractionated heparin in ST-segment elevation myocardial infarction, achieving therapeutic anticoagulation in practice remains challenging. Methods and Results-In the Enoxaparin and Thrombolysis in Reperfusion for Acute Myocardial Infarction Treatment Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study, 20 506 patients with ST-segment elevation myocardial infarction were randomized to enoxaparin or unfractionated heparin, the latter dosed according to the American College of Cardiology/American Heart Association weight-based nomogram with centrally monitored activated partial thromboplastin times (aPTTs). A total of 6055 patients received study unfractionated heparin and a fibrin-specific lytic and had an initial aPTT drawn within 4 to 8 hours of starting therapy. Despite close adherence to recommended dosing, only 33.8% of initial aPTTs were therapeutic (1.50 to 2.00 times control); 13.2% were markedly low (<1.25 times); and 16.3% were markedly high (>= 2.75 times). Markedly high aPTTs were more likely in patients who were older (adjusted risk ratio [RR(adj)], 1.14 per decade; P = 0.001), were female (RR(adj), 1.46; P < 0.001), were of lower weight (RR(adj), 1.19 per 10-kg decrease; P < 0.001) or had renal dysfunction (RRadj, 1.08 per 0.2-mg/dL increase in serum creatinine; P = 0.006). Markedly high aPTTs were associated with increased risk of TIMI major or minor bleeding by 48 hours (odds ratio, 2.11; P = 0.004); markedly low aPTTs tended to be associated with increased risk of fatal or nonfatal reinfarction by 48 hours (odds ratio, 2.19; P = 0.057). Conclusions-Despite the use of a standard weight-based unfractionated heparin nomogram in ST-segment elevation myocardial infarction, nontherapeutic anticoagulation is frequent and more likely among certain vulnerable patient groups, with excess anticoagulation associated with increased bleeding and inadequate anticoagulation associated with reinfarction. These findings should be considered when dosing unfractionated heparin in support of fibrinolytic therapy. (Circulation. 2009; 119: 1195-1202.) C1 [Cheng, Susan; Morrow, David A.; Sloan, Sarah; Antman, Elliott M.; Sabatine, Marc S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,TIMI Study Grp, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org FU Sanofi-Aventis FX Dr Morrow has served as a consultant for and received honoraria for educational presentations from Sanofi-Aventis. Dr Antman has received research grant support and honoraria for educational presentations from Sanofi-Aventis. Dr Sabatine has received research grant support and honoraria for educational presentations and consulting from Sanofi-Aventis. The other authors report no conflicts. NR 37 TC 21 Z9 22 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 MAR 10 PY 2009 VL 119 IS 9 BP 1195 EP U7 DI 10.1161/CIRCULATIONAHA.108.814996 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 416KK UT WOS:000264004800005 PM 19237657 ER PT J AU Parikh, NI Gona, P Larson, MG Fox, CS Benjamin, EJ Murabito, JM O'Donnell, CJ Vasan, RS Levy, D AF Parikh, Nisha I. Gona, Philimon Larson, Martin G. Fox, Caroline S. Benjamin, Emelia J. Murabito, Joanne M. O'Donnell, Christopher J. Vasan, Ramachandran S. Levy, Daniel TI Long-Term Trends in Myocardial Infarction Incidence and Case Fatality in the National Heart, Lung, and Blood Institute's Framingham Heart Study SO CIRCULATION LA English DT Article DE biomarkers; electrocardiography; epidemiology; myocardial infarction ID HOSPITAL CARDIAC-ARREST; 4 US COMMUNITIES; DISEASE MORTALITY; TEMPORAL TRENDS; CORONARY-DISEASE; UNITED-STATES; MEDICAL-CARE; RISK-FACTORS; EVENT RATES; DECLINE AB Background-Whereas the prevalence of coronary heart disease risk factors has declined over the past decades in the United States, acute myocardial infarction (AMI) rates have been steady. We hypothesized that this paradox is due partly to the advent of increasingly sensitive biomarkers for AMI diagnosis. Methods and Results-In Framingham Heart Study participants over 4 decades, we compared the incidence and survival rates of initial AMI diagnosis by ECG (AMI-ECG) regardless of biomarkers with those based exclusively on infarction biomarkers (AMI-marker). We used Poisson regression to calculate annual incidence rates of first AMI over 4 decades (1960 to 1969, 1970 to 1979, 1980 to 1989, and 1990 to 1999) and compared rates of AMI-ECG with rates of AMI-marker. Cox proportional-hazards analysis was used to compare AMI case fatality over 4 decades. In 9824 persons (54% women; follow-up, 212 539 person-years; age, 40 to 89 years), 941 AMIs occurred, including 639 AMI-ECG and 302 AMI-marker events. From 1960 to 1999, rates of AMI-ECG declined by approximate to 50% and rates of AMI-marker increased approximate to 2-fold. Crude 30-day, 1-year, and 5-year case fatality rates in 1960 to 1969 and 1990 to 1999 were 0.20 and 0.14, 0.24 and 0.21, and 0.45 and 0.41, respectively. Age-and sex-adjusted 30-day, 1-year, and 5-year AMI case fatality declined by 60% in 1960 to 1999 (P for trend <0.001), with parallel declines noted after AMI-ECG and AMI-marker. Conclusions-Over the past 40 years, rates of AMI-ECG have declined by 50%, whereas rates of AMI-marker have doubled. Our findings offer an explanation for the apparently steady national AMI rates in the face of improvements in primary prevention. (Circulation. 2009; 119: 1203-1210.) C1 [Parikh, Nisha I.; Gona, Philimon; Larson, Martin G.; Fox, Caroline S.; Benjamin, Emelia J.; Murabito, Joanne M.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Parikh, Nisha I.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Benjamin, Emelia J.; Murabito, Joanne M.; Vasan, Ramachandran S.; Levy, Daniel] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Benjamin, Emelia J.; Murabito, Joanne M.; Vasan, Ramachandran S.; Levy, Daniel] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Fox, Caroline S.; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM levyd@nih.gov OI Larson, Martin/0000-0002-9631-1254; Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195] FX This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute contract N01-HC-25195. NR 39 TC 93 Z9 97 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 10 PY 2009 VL 119 IS 9 BP 1203 EP 1210 DI 10.1161/CIRCULATIONAHA.108.825364 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 416KK UT WOS:000264004800006 PM 19237656 ER PT J AU van Kimmenade, RRJ Januzzi, JL Bakker, JA Houben, AJ Rennenberg, R Kroon, AA Crijns, HJGM van Dieijen-Visser, MP de Leeuw, PW Pinto, YM AF van Kimmenade, Roland R. J. Januzzi, James L., Jr. Bakker, Jaap A. Houben, Alphonse J. Rennenberg, Roger Kroon, Abraham A. Crijns, Harry J. G. M. van Dieijen-Visser, Marja P. de Leeuw, Peter W. Pinto, Yigal M. TI Renal Clearance of B-Type Natriuretic Peptide and Amino Terminal Pro-B-Type Natriuretic Peptide A Mechanistic Study in Hypertensive Subjects SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; MOLECULAR-WEIGHT PROTEINS; CHRONIC KIDNEY-DISEASE; STAGE HEART-FAILURE; NT-PROBNP; EMERGENCY-DEPARTMENT; ARTERY STENOSIS; ASSIST DEVICE; BLOOD-FLOW; BNP AB Objectives This study sought to compare the renal clearance mechanisms of B-type natriuretic peptide (BNP) and amino terminal pro-B-type natriuretic peptide (NT-proBNP). Background The small molecular weight proteins (SMWPs) BNP and NT-proBNP both inversely correlate with glomerular filtration rate (GFR). Whether this association is causal or confounding is unknown and has been the basis of widespread speculation. Methods We combined measurements of BNP and NT-proBNP concentrations in the renal arteries and veins of 165 subjects undergoing renal arteriography with invasive renal plasma flow (RPF) measurements and echocardiography. Fractional extraction (FE) of BNP and NT-proBNP was computed. Results The BNP and NT-proBNP concentrations correlated similarly to GFR (r = -0.35 and r = -0.30, respectively; p < 0.001 for both) but the NT-proBNP/BNP serum ratio was negatively associated with GFR (r = -0.21, p = 0.008). Median FEBNP was 0.21 (interquartile range [IQR] 0.16 to 0.22) for left and 0.22 (IQR 0.17 to 0.29) for right kidneys. Median FE(NT-proBNP) was 0.16 (IQR 0.09 to 20) for left and 0.18 (IQR 0.12 to 0.22) for right kidneys. The FE(BNP) correlated with GFR (left: r = 0.26, p = 0.008; right: r = 0.21, p = 0.03) as did FE(NT-proBNP) (left: r = 0.25, p = 0.005; right: r = 0.20, p = 0.02). Although FE(BNP) and FE(NT-proBNP) correlated strongly with each other (left: r = 0.66; right: r = 0.60; p = 0.001 for both), left and right FE(NT-proBNP/BNP) ratios were not influenced by GFR (r = 0.10, p = 0.30 and r = 0.08, p = 0.43, respectively). Multivariate analyses confirmed that FE was not independently associated with BNP or NT-proBNP concentrations. Conclusions Contrary to widespread belief (but in line with the renal physiology of SMWP), BNP and NT-proBNP are equally dependent on renal function for their clearance. (J Am Coll Cardiol 2009; 53: 884-90) (C) 2009 by the American College of Cardiology Foundation C1 [van Kimmenade, Roland R. J.; Crijns, Harry J. G. M.] Univ Hosp Maastricht, Dept Cardiol, NL-6202 AZ Maastricht, Netherlands. [Bakker, Jaap A.; van Dieijen-Visser, Marja P.] Univ Hosp Maastricht, Dept Clin Chem, NL-6202 AZ Maastricht, Netherlands. [Houben, Alphonse J.; Rennenberg, Roger; Kroon, Abraham A.; de Leeuw, Peter W.] Univ Hosp Maastricht, Dept Internal Med, NL-6202 AZ Maastricht, Netherlands. [Januzzi, James L., Jr.; Bakker, Jaap A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Pinto, Yigal M.] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, NL-1105 AZ Amsterdam, Netherlands. RP van Kimmenade, RRJ (reprint author), Univ Hosp Maastricht, Dept Cardiol, POB 5800, NL-6202 AZ Maastricht, Netherlands. EM rolandvank@hotmail.com RI houben, b/C-1913-2014; Kimmenade, R.R.J./L-4432-2015; OI Bakker, Jaap A./0000-0002-2918-7361 NR 47 TC 74 Z9 74 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP 884 EP 890 DI 10.1016/j.jacc.2008.11.032 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LC UT WOS:000263864100012 PM 19264247 ER PT J AU Ajijola, OA McCarty, D Barrett, CD Barantke, M Heist, EK Riedl, LR Upadhyay, G Orencole, M Picard, M Dec, GW Ruskin, JN Singh, JP AF Ajijola, Olujimi A., II McCarty, David Barrett, Conor D. Barantke, Melanie Heist, E. Kevin Riedl, Lindsay R. Upadhyay, Gaurav Orencole, Mary Picard, Michael Dec, G. William Ruskin, Jeremy N. Singh, Jagmeet P. TI Inpatient Versus Elective Outpatient Cardiac Resynchronization Therapy Device Implantation and Long Term Clinical Outcome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A126 EP A126 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200524 ER PT J AU Baggish, AL Fulco, CS Muza, S Rock, PB Beidleman, B Cymerman, A Yared, K Systrom, D Wood, MJ Weyman, AE Picard, MH Harris, NS AF Baggish, Aaron L. Fulco, Charles S. Muza, Stephen Rock, Paul B. Beidleman, Beth Cymerman, Allen Yared, Kibar Systrom, David Wood, Malissa J. Weyman, Arthur E. Picard, Michael H. Harris, N. Stuart TI Impact of Moderate Altitude Staging on Pulmonary Arterial Pressure During Ascent to High Altitude SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. USA, Environm Med Res Inst, Natick, MA 01760 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A449 EP A449 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201864 ER PT J AU Blankstein, R Bamberg, F Nichols, JH Rogers, IS Truong, QA Nagurney, JT Brady, TJ Gazelle, GS Hoffmann, U AF Blankstein, Ron Bamberg, Fabian Nichols, John H. Rogers, Ian S. Truong, Quynh A. Nagurney, John T. Brady, Thomas J. Gazelle, G. Scott Hoffmann, Udo TI Cost and Resource Utilization Associated with Use of Cardiac CT for the Evaluation of Chest Pain in the Emergency Department SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A391 EP A391 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201622 ER PT J AU Boylston, WH Venkatachalam, K Prabhu, SD Valente, AJ Chandrasekar, B AF Boylston, William H. Venkatachalam, Kaliyamurthi Prabhu, Sumanth D. Valente, Anthony J. Chandrasekar, Bysani TI Neutralization of Interleukin (IL)-18 Ameliorates Ischemia/Reperfusion-Induced Myocardial Injury SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. Univ Texas Hlth Sci Ctr San Antonio, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A310 EP A311 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201287 ER PT J AU Chan, SY Zhang, YY Loscalzo, J AF Chan, Stephen Y. Zhang, Ying-Yi Loscalzo, Joseph TI Regulation and Function of Hypoxia-Inducible MicroRNA in Human Pulmonary Arterial Endothelial Cells SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A468 EP A468 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201939 ER PT J AU Chia, S Van Cott, EM Raffel, OC Jang, IK AF Chia, Stanley Van Cott, Elizabeth M. Raffel, O. Christopher Jang, Ik-Kyung TI Comparison of Activated Clotting Times Obtained Using Hemochron and Medtronic Analyzers in Patients Receiving Anti-Thrombin Therapy During Cardiac Catheterization SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Chia, Stanley; Van Cott, Elizabeth M.; Raffel, O. Christopher; Jang, Ik-Kyung] 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A371 EP A371 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201540 ER PT J AU Dash, R Chan, T Yamada, M Paningbatan, M Myagmar, BE Swigart, PM Yang, PC Simpson, PC AF Dash, Rajesh Chan, Trevor Yamada, Mayumi Paningbatan, Marietta Myagmar, Bat-Erdene Swigart, Philip M. Yang, Phillip C. Simpson, Paul C., Jr. TI Magnetic Resonance Imaging With Targeted Iron-Oxide Labeling Detects Differential Cardiac Cell Survival After Doxorubicin and Myocardial Infarction in Culture and In Vivo SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 San Francisco VA Med Ctr, San Francisco, CA USA. Stanford Univ, Stanford, CA 94305 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A304 EP A304 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201261 ER PT J AU Depta, JP Cannon, CP Fonarow, GC Zhao, X Bhatt, DL AF Depta, Jeremiah P. Cannon, Christopher P. Fonarow, Gregg C. Zhao, Xin Bhatt, Deepak L. TI Patient Characteristics Associated With the Choice of Triple Antithrombotic Therapy in the Setting of Acute Coronary Syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Cleveland Clin, Cleveland, OH 44106 USA. VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A323 EP A323 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201341 ER PT J AU Ferencik, M Schlett, CL Bamberg, F Nichols, JH Pena, AJ Shapiro, MD Rogers, IS Seneviratne, S Truong, QA Parry, BA Cury, RC Chae, CU Brady, TJ Brown, DF Nagurney, JT Hoffmann, U AF Ferencik, Maros Schlett, Christopher L. Bamberg, Fabian Nichols, John H. Pena, Antonio J. Shapiro, Michael D. Rogers, Ian S. Seneviratne, Sujith Truong, Quynh A. Parry, Blair Alden Cury, Ricardo C. Chae, Claudia U. Brady, Thomas J. Brown, David F. Nagurney, John T. Hoffmann, Udo TI Cardiovascular Risk Scores and Coronary Plaque Burden as Detected by Computed Tomography for Detection of Acute Coronary Syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Ferencik, Maros; Schlett, Christopher L.; Bamberg, Fabian; Nichols, John H.; Pena, Antonio J.; Shapiro, Michael D.; Rogers, Ian S.; Seneviratne, Sujith; Truong, Quynh A.; Parry, Blair Alden; Cury, Ricardo C.; Chae, Claudia U.; Brady, Thomas J.; Brown, David F.; Nagurney, John T.; Hoffmann, Udo] 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A264 EP A264 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201098 ER PT J AU Gavin, CM Thakur, R Gaziano, JM Kaufman, J Bhatt, D AF Gavin, Cara McLaughlin Thakur, Ranjan Gaziano, J. Michael Kaufman, James Bhatt, Deepak TI The Relationship Between Renal Function and All-Cause Mortality Among Veterans Receiving Implantable Cardioverter Defibrillators SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Boston VA Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A136 EP A136 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200565 ER PT J AU Isselbacher, E Nienaber, CA Trimarchi, S Evangelista, A Cooper, JV Froehlich, JB Erlich, M Oh, J Januzzi, JL O'Gara, P Sundt, T Harris, KM Bossone, E Pyeritz, RE Eagle, KA AF Isselbacher, Eric Nienaber, Christoph A. Trimarchi, Santi Evangelista, Arturo Cooper, Jeanna V. Froehlich, James B. Erlich, Marek Oh, Jae Januzzi, James L. O'Gara, Patrick Sundt, Thoralf Harris, Kevin M. Bossone, Eduardo Pyeritz, Reed E. Eagle, Kim A. CA IRAD Investigators TI The IRAD Classification System-A Modern Method for Characterizing Mortality Risk of Aortic Dissection Based on Time From Symptom Onset, Dissection Location, and Treatment Rendered SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A447 EP A447 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201856 ER PT J AU Klein, AJ Kim, MS Westfall, JM Masoudi, FA Rumsfeld, JS Carroll, JD Jaynes, CL Messenger, JC AF Klein, Andrew J. Kim, Michael S. Westfall, John M. Masoudi, Frederick A. Rumsfeld, John S. Carroll, John D. Jaynes, Cathy L. Messenger, John C. TI Medical Simulation Training to Improve Acute Myocardial Infarction Care for Rural Hospitals SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Univ Colorado Denver, Aurora, CO USA. Denver VA Med Ctr, Denver, CO 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A401 EP A401 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201663 ER PT J AU Korngold, EC Januzzi, JL Gantzer, ML Moorthy, MV Cook, NR Albert, CM AF Korngold, Ethan C. Januzzi, James L., Jr. Gantzer, Mary Lou Moorthy, M. V. Cook, Nancy R. Albert, Christine M. TI Amino-Terminal Pro-B Type Natriuretic Peptide and hsCRP as Predictors of Sudden Cardiac Death Among Women SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A120 EP A120 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200500 ER PT J AU Maddox, T Ho, PM Roe, M Dai, D Tsai, T Rumsfeld, JS AF Maddox, Thomas Ho, P. Michael Roe, Matthew Dai, David Tsai, Tom Rumsfeld, John S. TI Secondary Prevention Therapies Among Patients With Non-Obstructive CAD: Insights From the NCDR Cath-PCI Registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Denver VAMC, Denver, CO USA. Univ Colorado, Denver, CO 80202 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A468 EP A468 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201937 ER PT J AU Maddox, T Ho, PM Wang, TY Ou, FS Tsai, T Wiviott, SD Rumsfeld, JS AF Maddox, Thomas Ho, P. Michael Wang, Tracy Y. Ou, Fang-Shu Tsai, Tom Wiviott, Stephen D. Rumsfeld, John S. TI Clopidogrel Use Among Medically-Managed NSTEMI Patients: Insights From the NCDR ACTION Registry - GWTG SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Denver VAMC, Denver, CO USA. Univ Colorado, Denver, CO 80202 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A374 EP A374 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201552 ER PT J AU Mahabadi, AA Bamberg, F Toepker, M Shapiro, MD Rogers, IS Nagurney, JT Brady, TJ Hoffmann, U Truong, QA AF Mahabadi, Amir A. Bamberg, Fabian Toepker, Michael Shapiro, Michael D. Rogers, Ian S. Nagurney, John T. Brady, Thomas J. Hoffmann, Udo Truong, Quynh A. TI Aortic Valve Calcification Is Associated With the Presence, Extent and Composition of Coronary Artery Plaque: ROMICAT Substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Mahabadi, Amir A.; Bamberg, Fabian; Toepker, Michael; Shapiro, Michael D.; Rogers, Ian S.; Nagurney, John T.; Brady, Thomas J.; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI PET CT Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 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 MAR 10 PY 2009 VL 53 IS 10 BP A410 EP A410 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201701 ER PT J AU Merchant, FM Noseworthy, P Weiner, R Singh, S Ruskin, JN Reddy, VY AF Merchant, Faisal M. Noseworthy, Peter Weiner, Rory Singh, Sheldon Ruskin, Jeremy N. Reddy, Vivek Y. TI Terminal QRS Notching Distinguishes Between Benign and Malignant Variants of Early Repolarization SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Miami, FL 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A141 EP A141 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200586 ER PT J AU Merchant, FM Noseworthy, P Weiner, R Singh, S Ruskin, JN Reddy, VY AF Merchant, Faisal M. Noseworthy, Peter Weiner, Rory Singh, Sheldon Ruskin, Jeremy N. Reddy, Vivek Y. TI Early Repolarization Associated With Idiopathic Ventricular Tachycardia/Ventricular Fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Miami, FL 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A121 EP A121 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200503 ER PT J AU Mohammed, AA Agnihotri, A van Kimmenade, RRJ Martinez-Rumayor, A Green, S Quiroz, R Januzzi, JL AF Mohammed, Asim A. Agnihotri, Arvind van Kimmenade, Roland R. J. Martinez-Rumayor, Abelardo Green, Sandy Quiroz, Rene Januzzi, James L., Jr. TI Should Use of Troponin Measurement for the Diagnosis of Myocardial Infarction After Coronary Artery Bypass Graft Surgery Be Reconsidered? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Mohammed, Asim A.; Agnihotri, Arvind; van Kimmenade, Roland R. J.; Martinez-Rumayor, Abelardo; Green, Sandy; Quiroz, Rene; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kimmenade, R.R.J./L-4432-2015 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A350 EP A350 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201451 ER PT J AU Mohammed, AA Agnihotri, A van Kimmenade, RRJ Martinez-Rumayor, A Green, S Quiroz, R Januzzi, JL AF Mohammed, Asim A. Agnihotri, Arvind van Kimmenade, Roland R. J. Martinez-Rumayor, Abelardo Green, Sandy Quiroz, Rene Januzzi, James L., Jr. TI Causes and Importance of Troponin Elevation After Coronary Artery Bypass Graft Surgery: Prospective Analysis of 847 Patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Mohammed, Asim A.; Agnihotri, Arvind; van Kimmenade, Roland R. J.; Martinez-Rumayor, Abelardo; Green, Sandy; Quiroz, Rene; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kimmenade, R.R.J./L-4432-2015 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A352 EP A352 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201460 ER PT J AU Mohammed, AA van Kimmenade, RRJ Uthamalingam, S van der Meer, P Felker, M Januzzi, JL AF Mohammed, Asim A. van Kimmenade, Roland R. J. Uthamalingam, Shanmugam van der Meer, Peter Felker, Michael Januzzi, James L., Jr. TI Red Cell Distribution Width and One-Year Mortality in Acute Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hosp, Maastricht, Netherlands. RI Kimmenade, R.R.J./L-4432-2015 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A159 EP A159 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200659 ER PT J AU Murphy, MK Blankstein, R Nasir, K Gazell, GS Mamuya, F Abbara, S Lee, TH Brady, TJ AF Murphy, Meagan K. Blankstein, Ron Nasir, Khuram Gazell, G. Scott Mamuya, Fred Abbara, Suhny Lee, Thomas H. Brady, Thomas J. TI Appropriateness and Utilization of Cardiac Computed Tomography: Implications for Development and Implementation of Future Guidelines SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Partners Community Healthcare Inc, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A390 EP A390 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201618 ER PT J AU O'Donoghue, M Morrow, DA Jiang, ST Rifai, N Bode, C Gibson, CM Gerszten, RE Cannon, CP Sabatine, MS AF O'Donoghue, Michelle Morrow, David A. Jiang, Songtao Rifai, Nader Bode, Christoph Gibson, C. Michael Gerszten, Robert E. Cannon, Christopher P. Sabatine, Marc S. TI Serial Inflammatory Biomarkers to Predict Angiographic and Clinical Outcomes in Patients With STEMI Undergoing Fibrinolysis: A CLARITY-TIMI 28 Substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 MAR 10 PY 2009 VL 53 IS 10 BP A344 EP A344 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201426 ER PT J AU Refaat, M Heist, EK Dindy, D Ruskin, J Mansour, M AF Refaat, Marwan Heist, E. Kevin Dindy, Daniel Ruskin, Jeremy Mansour, Moussa TI Electrocardiographic Characteristics in Right Ventricular Versus Biventricular Pacing in Patients With a Right Bundle Branch Block QRS Pattern SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A129 EP A129 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200538 ER PT J AU Rigotti, NA Pipe, A Garza, D Arteaga, C Benowitz, NL Tonstad, S AF Rigotti, Nancy A. Pipe, Andrew Garza, Dahlia Arteaga, Carmen Benowitz, Neal L. Tonstad, Serena TI Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease: A Randomized Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Ottawa, Inst Heart, Minto Prevent & Rehabil Ctr, Ottawa, ON, Canada. NR 0 TC 3 Z9 3 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 MAR 10 PY 2009 VL 53 IS 10 BP A224 EP A224 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200933 ER PT J AU Rocha-Filho, JA Shturman, L Rogers, IS Blankstein, R Okada, DR Mamuya, WS Bezerra, HG Sarwar, A Hoffmann, U Feuchtner, G Brady, TJ Cury, RC AF Rocha-Filho, Jose A. Shturman, Leon Rogers, Ian S. Blankstein, Ron Okada, David R. Mamuya, Wilfred S. Bezerra, Hiram G. Sarwar, Ammar Hoffmann, Udo Feuchtner, Gudrun Brady, Thomas J. Cury, Ricardo C. TI Incremental Value of Adenosine-Induced Stress Myocardial Perfusion Imaging Using Dual Source Computed Tomography on Coronary Computed Tomography Angiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Rocha-Filho, Jose A.; Shturman, Leon; Rogers, Ian S.; Blankstein, Ron; Okada, David R.; Mamuya, Wilfred S.; Bezerra, Hiram G.; Sarwar, Ammar; Hoffmann, Udo; Feuchtner, Gudrun; Brady, Thomas J.; Cury, Ricardo C.] 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A259 EP A259 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201076 ER PT J AU Rogers, IS Massaro, JM Truong, QA Mahabadi, AA Fox, CS Isselbacher, EM Hoffmann, U O'Donnell, CJ AF Rogers, Ian S. Massaro, Joseph M. Truong, Quynh A. Mahabadi, Amir A. Fox, Caroline S. Isselbacher, Eric M. Hoffmann, Udo O'Donnell, Christopher J. TI Determinants of Thoracic and Abdominal Aortic Diameter by Computed Tomography in the Framingham Heart Study: The Influence of Gender, Age, and Body Surface Area SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A456 EP A456 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201893 ER PT J AU Rogers, IS Blankstein, R Sarwar, A Shturman, L Soni, AV Loureiro, R Bezerra, H Petranovic, M Okada, DR Brady, TJ Mamuya, WS Cury, RC AF Rogers, Ian S. Blankstein, Ron Sarwar, Ammar Shturman, Leon Soni, Anand V. Loureiro, Ricardo Bezerra, Hiram Petranovic, Milena Okada, David R. Brady, Thomas J. Mamuya, Wilfred S. Cury, Ricardo C. TI Stress Perfusion Cardiac CT Permits Simultaneous Evaluation of the Coronary Arteries, Myocardial Perfusion, and Left Ventricular Function With Similar Radiation Exposure to Rest/Stress Single Photon Emission Computed Tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Rogers, Ian S.; Blankstein, Ron; Sarwar, Ammar; Shturman, Leon; Soni, Anand V.; Loureiro, Ricardo; Bezerra, Hiram; Petranovic, Milena; Okada, David R.; Brady, Thomas J.; Mamuya, Wilfred S.; Cury, Ricardo C.] 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A275 EP A275 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201144 ER PT J AU Sakhuja, R Keebler, M Lai, TS Gavin, CM Thakur, R Bhatt, DL AF Sakhuja, Rahul Keebler, Mary Lai, Tai-Shaun Gavin, Cara McLaughlin Thakur, Ranjan Bhatt, Deepak L. TI Mortality in Dialysis Patients With a Defibrillator: A Quantitative Meta-Analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A131 EP A131 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200547 ER PT J AU Schwartz, GG Draznin, B Reusch, JEB Leitner, JW Lu, L Xu, Y Greyson, CR Wang, CCL AF Schwartz, Gregory G. Draznin, Boris Reusch, Jane E. B. Leitner, J. Wayne Lu, Li Xu, Ya Greyson, Clifford R. Wang, Cecilia C. L. TI Insulin-Stimulated PI 3-Kinase Activity Is Blunted, but Akt Pphosphorylation Is Preserved in Aortas of Pigs With Diet-Induced Obesity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado Denver, Sch Med, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A435 EP A435 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201806 ER PT J AU Scirica, BM Morrow, DA Karwatowska-Prokopczuk, E Hedgepeth, CM Wang, W Qin, J Belardinelli, L Braunwald, E AF Scirica, Benjamin M. Morrow, David A. Karwatowska-Prokopczuk, Ewa Hedgepeth, Chester M., III Wang, Whedy Qin, Jie Belardinelli, Luiz Braunwald, Eugene TI Ventricular Arrhythmias Following Non-ST Segment Elevation ACS and the Relationship With Sudden Cardiac Death in the MERLIN-TIMI 36 Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Scirica, Benjamin M.; Morrow, David A.; Karwatowska-Prokopczuk, Ewa; Hedgepeth, Chester M., III; Wang, Whedy; Qin, Jie; Belardinelli, Luiz; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A121 EP A121 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200506 ER PT J AU Setoguchi, S Higgins, JM Mootha, VK Mogun, H Avorn, J AF Setoguchi, Soko Higgins, John M. Mootha, Vamsi K. Mogun, Helen Avorn, Jerry TI Propranolol and the Risk of Severe Myopathy Among the Elderly SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 MAR 10 PY 2009 VL 53 IS 10 BP A205 EP A205 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200852 ER PT J AU Shah, RV van Kimmenade, RRJ Chen-Tournoux, A Januzzi, JL AF Shah, Ravi V. van Kimmenade, Roland R. J. Chen-Tournoux, Annabel Januzzi, James L. TI The Novel Interleukin Receptor Family Member ST2 Correlates With Cardiac Structure, Function, and Prognosis: Results From the PRIDE Echocardiographic Substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Shah, Ravi V.; van Kimmenade, Roland R. J.; Chen-Tournoux, Annabel; Januzzi, James L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kimmenade, R.R.J./L-4432-2015 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A185 EP A185 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200772 ER PT J AU Singh, JP Solis-Martin, J McCarty, D Tournoux-Chen, A Orencole, M Picard, MH Hung, JH AF Singh, Jagmeet P. Solis-Martin, Jorge McCarty, David Tournoux-Chen, Annabel Orencole, Mary Picard, Michael H. Hung, Judy H. TI Targeting the Electrically Delayed Segment Improves the Mitral Regurgitant Volume in Patients Receiving Cardiac Resynchronization Therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 [Singh, Jagmeet P.; Solis-Martin, Jorge; McCarty, David; Tournoux-Chen, Annabel; Orencole, Mary; Picard, Michael H.; Hung, Judy H.] 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A124 EP A124 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200515 ER PT J AU Sweeney, AW Hage, F Aqel, R Phillips, G Perry, G Zogbi, G Calhoun, D AF Sweeney, Aaron W. Hage, Fadi Aqel, Raed Phillips, George Perry, Gilbert Zogbi, Gilbert Calhoun, David TI Percutaneous Renal Artery Revascularization versus Medical Therapy for Renal Artery Stenosis: A Prospective Randomized Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Univ Alabama, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Div Cardiol, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A87 EP A87 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200361 ER PT J AU Truong, QA Cannon, CP Zakai, NA Rogers, IS Giugliano, RP Wiviott, SD McCabe, CH Morrow, DA Braunwald, E AF Truong, Quynh A. Cannon, Christopher P. Zakai, Neil A. Rogers, Ian S. Giugliano, Robert P. Wiviott, Stephen D. McCabe, Carolyn H. Morrow, David A. Braunwald, Eugene CA TIMI Study Grp TI TIMI Risk Index Predicts Long-Term Mortality in Patients With ST-Elevation Myocardial Infarction in the TIMI-II Clinical Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 MAR 10 PY 2009 VL 53 IS 10 BP A333 EP A333 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201380 ER PT J AU Tsai, TT Ho, PM Carroll, NM Shetterly, SM Xu, S Powers, JD Go, AS Margolis, K Magid, DJ AF Tsai, Thomas T. Ho, P. Michael Carroll, Nikki M. Shetterly, Susan M. Xu, Stanley Powers, J. David Go, Alan S. Margolis, Karen Magid, David J. TI Two Year Outcomes Following Off-Label Use of Drug-Eluting Stents in the Real-World: Insights from the HMO Research Network-Stent Registry (HMORN-Stent) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Denver, CO 80202 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 BP A16 EP A16 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864200065 ER PT J AU Van der Meer, P Domian, IJ Chiravuri, M Feinberg, AF Wu, SM Parker, KK Chien, KR AF Van der Meer, Peter Domian, Ibrahim J. Chiravuri, Murali Feinberg, Adam F. Wu, Sean M. Parker, Kevin K. Chien, Kenneth R. TI Committed Ventricular Progenitors in the Islet-1 Lineage Expand and Assemble Into Functional Ventricular Heart Muscle SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. RI Feinberg, Adam/A-7103-2009 OI Feinberg, Adam/0000-0003-3338-5456 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 SU 1 BP A468 EP A468 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201940 ER PT J AU Venkatachalam, K Boylston, WH Bailey, SR Chandrasekar, B AF Venkatachalam, Kaliyamurthi Boylston, William H. Bailey, Steven R. Chandrasekar, Bysani TI AMPK Activation Blocks Interleukin-18-Mediated IKK/NF-B/PTEN Activation and Endothelial Cell Death SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 58th Annual Scientific Session of the American-College-of-Cardiology CY MAR 28-31, 2009 CL Orlando, FL SP Amer Coll Cardiol C1 S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. Univ Texas Hlth Sci Ctr San Antonio, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 10 PY 2009 VL 53 IS 10 SU 1 BP A430 EP A430 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 414LD UT WOS:000263864201786 ER PT J AU Reyes, S Viswanathan, A Godin, O Dufouil, C Benisty, S Hernandez, K Kurtz, A Jouvent, E O'Sullivan, M Czernecki, V Bousser, MG Dichgans, M Chabriat, H AF Reyes, S. Viswanathan, A. Godin, O. Dufouil, C. Benisty, S. Hernandez, K. Kurtz, A. Jouvent, E. O'Sullivan, M. Czernecki, V. Bousser, M. G. Dichgans, M. Chabriat, H. TI Apathy A major symptom in CADASIL SO NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PARKINSONS-DISEASE; NEUROPSYCHIATRIC INVENTORY; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; PSYCHOPATHOLOGY; COGNITION; SPECTRUM; MOOD AB Objective: The frequency and impact of apathy in subcortical ischemic vascular dementia (SIVD) remain undetermined. The frequency, clinical, neuropsychological, and imaging correlates of apathy were assessed in a large cohort of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a genetic model of SIVD. Methods: Apathy was diagnosed based on Neuropsychiatric Inventory assessment. Degree of disability was assessed by modified Rankin scale, cognitive impairment by Mattis Dementia Rating Scale (MDRS) and Mini-Mental State Examination (MMSE), autonomy by the Instrumental Activities of Daily Living (IADL) scale, and quality of life by SEP-59 self-questionnaire. Validated imaging methods were used to determine the total burden of cerebral lesions. Results: Among 132 patients, 54 (41%) were apathetic. Apathetic patients were older than nonapathetic subjects, had a lower MMSE and MDRS score, had more global disability, and were more limited in IADL. Apathetic patients were more frequently depressed compared to nonapathetic patients and more frequently presented additional neuropsychiatric symptoms. Multiple regression modeling showed a significant and independent association between apathy and a lower score of overall quality of life and between apathy and a higher load of white matter and lacunar lesions. Conclusions: The results suggest that apathy is common in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), appears in association with cognitive impairment, global functional disability, and severe neuropsychiatric symptoms during the course of the disease, and can occur separately from depression. Apathy has an independent impact on the overall quality of life in CADASIL. Neurology (R) 2009; 72: 905-910 C1 [Bousser, M. G.; Chabriat, H.] INSERM, U740, F-75654 Paris 13, France. [Reyes, S.; Viswanathan, A.; Hernandez, K.; Kurtz, A.; Jouvent, E.] Assistance Publ Hop Paris, CHU Lariboisiere, Dept Neurol, Paris, France. [Benisty, S.] Assistance Publ Hop Paris, CHU Lariboisiere, Dept Geriatr, Paris, France. [Viswanathan, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Viswanathan, A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Trials Unit, Boston, MA USA. [Godin, O.; Dufouil, C.] Univ Paris 06, INSERM, U708, Paris, France. [O'Sullivan, M.] Univ Munich, Dept Neurol, Klinikum Grosshadern, D-8000 Munich, Germany. [Czernecki, V.; Dichgans, M.] Hop La Pitie Salpetriere, INSERM, U610, Paris, France. RP Chabriat, H (reprint author), Hop Lariboisiere, Serv Neurol, 2 Rue Ambroise Pare, F-75010 Paris, France. EM hugues.chabriat@lrb.ap-hop-paris.fr RI Dufouil, Carole/J-4968-2012; O'Sullivan, Michael/A-1796-2010; Jouvent, Eric/B-4320-2014; Chabriat, Hugues/G-5699-2010 OI Jouvent, Eric/0000-0001-7797-2236; Chabriat, Hugues/0000-0001-8436-6074 FU PHRC [AOR 02-001]; Company Bouygues FX Supported by PHRC grant AOR 02-001 (DRC/APHP) and performed with the help of ARNEVA (Association de Recherche en Neurologie Vasculaire), Hospital Lariboisiere, France, with a sponsorship of the Company Bouygues. NR 36 TC 42 Z9 45 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 10 PY 2009 VL 72 IS 10 BP 905 EP 910 DI 10.1212/01.wnl.0000344166.03470.f8 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 416KM UT WOS:000264005000009 PM 19273824 ER PT J AU Herzog, AG Blum, AS Farina, EL Maestri, XE Newman, J Garcia, E Krishnamurthy, KB Hoch, DB Replansky, S Fowler, KM Smithson, SD Dworetzky, BA Bromfield, EB AF Herzog, A. G. Blum, A. S. Farina, E. L. Maestri, X. E. Newman, J. Garcia, E. Krishnamurthy, K. B. Hoch, D. B. Replansky, S. Fowler, K. M. Smithson, S. D. Dworetzky, B. A. Bromfield, E. B. TI Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use SO NEUROLOGY LA English DT Article ID CATAMENIAL EPILEPSY; PLASMA-LEVELS; PHARMACOKINETICS; WOMEN; SEIZURES; HORMONES; DRUGS AB Objective: To determine whether 1) combined oral contraceptive (COC) use affects serum levels of valproate (VPA) as well as lamotrigine (LTG) and 2) the naturally occurring high (mid-luteal) and low (early-mid follicular) reproductive steroid level phases of the menstrual cycle might affect antiepileptic drug levels as well. Methods: This investigation compared serum antiepileptic drug levels at two timepoints during a single menstrual cycle in four groups of women with epilepsy: 12 on VPA, 12 on VPA plus COC (VPA-COC), 12 on LTG, and 12 on LTG plus COC (LTG-COC). Results: Both VPA and LTG levels were lower (p < 0.01) on active COC than on inactive pill with median declines of 23.4% for the VPA-COC group and 32.6% for the LTG-COC group. Serum LTG levels showed a notable but not significant 31.3% median decline during the mid-luteal phase compared to the early-mid follicular phase in the non-COC group. The non-COC valproate group showed the least change of any group between the two measured timepoints with a decline of 8.3% (p = NS). Conclusions: The findings suggest that valproate (VPA), like lamotrigine (LTG), has substantially and significantly lower serum levels while women take active combined oral contraceptives as compared to inactive pills. Larger sample sizes will be required to determine whether LTG levels may drop significantly also during the luteal (high steroid) phase of natural menstrual cycles and whether VPA levels may show greater stability in levels across the phases of the menstrual cycle. Neurology (R) 2009; 72: 911-914 C1 [Herzog, A. G.; Farina, E. L.; Krishnamurthy, K. B.; Fowler, K. M.; Smithson, S. D.] Beth Israel Deaconess Med Ctr, Harvard Neuroendocrine Unit, Boston, MA 02215 USA. [Blum, A. S.; Maestri, X. E.; Newman, J.] Rhode Isl Hosp, Dept Neurol, Providence, RI USA. [Garcia, E.] Newton Wellesley Hosp, Dept Neurol, Wellesley, MA USA. [Hoch, D. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Replansky, S.; Dworetzky, B. A.; Bromfield, E. B.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Herzog, AG (reprint author), Beth Israel Deaconess Med Ctr, Harvard Neuroendocrine Unit, 330 Brookline Ave, Boston, MA 02215 USA. EM aherzog@bidmc.harvard.edu OI Hoch, Daniel/0000-0002-4294-024X; Dworetzky, Barbara/0000-0002-3364-2347; Fowler, Kristen/0000-0003-0196-5747 NR 20 TC 30 Z9 30 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 MAR 10 PY 2009 VL 72 IS 10 BP 911 EP 914 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 416KM UT WOS:000264005000010 PM 19273825 ER PT J AU Worobey, CC Fisher, NDL Cox, D Forman, JP Curhan, GC AF Worobey, Cynthia Cooper Fisher, Naomi D. L. Cox, David Forman, John P. Curhan, Gary C. TI Genetic Polymorphisms and the Risk of Accelerated Renal Function Decline in Women SO PLOS ONE LA English DT Article AB Background: Reduced glomerular filtration rate is an important predictor of cardiovascular disease and death. Genetic polymorphisms, particularly in genes involved in the renin-angiotensin system (RAS), may influence the rate of renal function decline. Methodology/Principal Findings: We examined the relation between specific single nucleotide polymorphisms (SNPs), including those in the RAS, apolipoprotein E and alpha-adducin, and renal function decline assessed by estimated glomerular filtration rate (eGFR) over an 11-year period in 2578 Caucasian participants of the Nurses' Health Study. Logistic regression was used to examine the associations between genotype and risk of eGFR decline of >= 25%. Results: After 11 years between creatinine measurements, the eGFR declined by >= 25% in 423 of 2578 (16%) women. The angiotensinogen (AGT) A-20C polymorphism was associated with a higher risk of renal function decline when two risk alleles were present than if one or no alleles were present (CC vs AA and AC) OR 1.83 (95% CI 1.02-3.26; p = 0.04). The angiotensin II type 1 receptor (AT(1)R) A1166C polymorphism was marginally associated with a higher risk of renal function decline when two risk alleles were present (CC vs AA, OR = 1.41; 95% CI 0.98-2.01; p = 0.06). The alpha-adducin G460W polymorphism was associated with a lower risk of renal function decline when any number of risk alleles were present (WG vs GG, OR = 0.78, 95% CI 0.61-0.99, p = 0.04; WW vs GG, OR = 0.46; 95% CI 0.20-1.07, p = 0.07). Linear regression analysis with change in eGFR as the outcome showed a larger decline of 3.5 (95% CI 0.5 to 6.4, p = 0.02) ml/min/1.73 m(2) in AGT A-20C CC homozygotes. No other polymorphisms were significantly associated with renal function decline or absolute change in eGFR over the study period. Conclusions: Genetic variants in the angiotensinogen, angiotensin II type 1 receptor and alpha-adducin genes may contribute to loss of renal function in the general female Caucasian population. C1 [Worobey, Cynthia Cooper] Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. [Fisher, Naomi D. L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA USA. [Cox, David; Forman, John P.; Curhan, Gary C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Forman, John P.; Curhan, Gary C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Renal Div, Boston, MA USA. [Curhan, Gary C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Worobey, CC (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. EM gcurhan@partners.org RI Cox, David/A-2023-2009 OI Cox, David/0000-0002-2152-9259 FU National Institutes of Health [DK66574, CA87969, DK07791] FX The research was supported by Grants DK66574, CA87969 and DK07791 from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 7 Z9 7 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 MAR 10 PY 2009 VL 4 IS 3 AR e4787 DI 10.1371/journal.pone.0004787 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437OE UT WOS:000265496000023 ER PT J AU Yang, J Bielenberg, DR Rodig, SJ Doiron, R Clifton, MC Kung, AL Strong, RK Zurakowski, D Moses, MA AF Yang, Jiang Bielenberg, Diane R. Rodig, Scott J. Doiron, Robert Clifton, Matthew C. Kung, Andrew L. Strong, Roland K. Zurakowski, David Moses, Marsha A. TI Lipocalin 2 promotes breast cancer progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE epithelial to mesenchymal transition; biomarker; estrogen receptor ID GELATINASE-ASSOCIATED LIPOCALIN; EPITHELIAL-MESENCHYMAL TRANSITIONS; CELL-LINES; E-CADHERIN; ESTROGEN-RECEPTOR; EXPRESSION; NGAL; METASTASIS; APOPTOSIS; INVASION AB Here, we report that lipocalin 2 (Lcn2) promotes breast cancer progression, and we identify the mechanisms underlying this function. We first found that Lcn2 levels were consistently associated with invasive breast cancer in human tissue and urine samples. To investigate the function of Lcn2 in breast cancer progression, Lcn2 was overexpressed in human breast cancer cells and was found to up-regulate mesenchymal markers, including vimentin and fibronectin, down-regulate the epithelial marker E-cadherin, and significantly increase cell motility and invasiveness. These changes in marker expression and cell motility are hallmarks of an epithelial to mesenchymal transition (EMT). In contrast, Lcn2 silencing in aggressive breast cancer cells inhibited cell migration and the mesenchymal phenotype. Furthermore, reduced expression of estrogen receptor (ER) alpha and increased expression of the key EMT transcription factor Slug were observed with Lcn2 expression. Overexpression of ER alpha in Lcn2-expressing cells reversed the EMT and reduced Slug expression, suggesting that ER alpha negatively regulates Lcn2-induced EMT. Finally, orthotopic studies demonstrated that Lcn2-expressing breast tumors displayed a poorly differentiated phenotype and showed increased local tumor invasion and lymph node metastasis. Taken together, these in vitro, in vivo, and human studies demonstrate that Lcn2 promotes breast cancer progression by inducing EMT through the ER alpha/Slug axis and may be a useful biomarker of breast cancer. C1 [Yang, Jiang; Bielenberg, Diane R.; Doiron, Robert; Moses, Marsha A.] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Yang, Jiang; Bielenberg, Diane R.; Doiron, Robert; Moses, Marsha A.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Zurakowski, David] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Yang, Jiang; Bielenberg, Diane R.; Doiron, Robert; Zurakowski, David; Moses, Marsha A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Strong, Roland K.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Moses, MA (reprint author), Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. EM marsha.moses@childrens.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [CA 118732-01A1, K01 CA118732, R01 CA118764] NR 39 TC 139 Z9 146 U1 1 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 MAR 10 PY 2009 VL 106 IS 10 BP 3913 EP 3918 DI 10.1073/pnas.0810617106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 416WT UT WOS:000264036900049 PM 19237579 ER PT J AU Koffie, RM Meyer-Luehmann, M Hashimoto, T Adams, KW Mielke, ML Garcia-Alloza, M Micheva, KD Smith, SJ Kim, ML Lee, VM Hyman, BT Spires-Jones, TL AF Koffie, Robert M. Meyer-Luehmann, Melanie Hashimoto, Tadafumi Adams, Kenneth W. Mielke, Matthew L. Garcia-Alloza, Monica Micheva, Kristina D. Smith, Stephen J. Kim, M. Leo Lee, Virginia M. Hyman, Bradley T. Spires-Jones, Tara L. TI Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Alzheimer; array tomography; neurodegeneration; synaptotoxicity ID ALZHEIMERS-DISEASE; NATURAL OLIGOMERS; DENDRITIC SPINES; TRANSGENIC MICE; MEMORY; ABNORMALITIES; HIPPOCAMPUS; DEPRESSION; MICROSCOPY; DEPOSITION AB Synapse loss correlates with a cognitive decline in Alzheimer's disease (AD), but whether this is caused by fibrillar deposits known as senile plaques or soluble oligomeric forms of amyloid beta(A beta) is controversial. By using array tomography, a technique that combines ultrathin sectioning of tissue with immunofluorescence, allowing precise quantification of small structures, such as synapses, we have tested the hypothesis that oligomeric A beta surrounding plaques contributes to synapse loss in a mouse model of AD. We find that senile plaques are surrounded by a halo of oligomeric A beta. Analysis of > 14,000 synapses (represented by PSD95-stained excitatory synapses) shows that there is a 60% loss of excitatory synapses in the halo of oligomeric A beta surrounding plaques and that the density increases to reach almost control levels in volumes further than 50 mu m from a plaque in an approximately linear fashion (linear regression, r(2) = 0.9; P < 0.0001). Further, in transgenic cortex, microdeposits of oligomeric A beta associate with a subset of excitatory synapses, which are significantly smaller than those not in contact with oligomeric A beta. The proportion of excitatory synapses associated with A beta correlates with decreasing density (correlation, -0.588; P < 0.0001). These data show that senile plaques are a potential reservoir of oligomeric A beta, which colocalizes with the postsynaptic density and is associated with spine collapse, reconciling the apparently competing schools of thought of "plaque'' vs. "oligomeric A beta as the synaptotoxic species in the brain of AD patients. C1 [Koffie, Robert M.; Meyer-Luehmann, Melanie; Hashimoto, Tadafumi; Adams, Kenneth W.; Mielke, Matthew L.; Garcia-Alloza, Monica; Hyman, Bradley T.; Spires-Jones, Tara L.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Meyer-Luehmann, Melanie] Univ Munich, Dept Biochem, Lab Neurodegenerat Dis Res, D-80336 Munich, Germany. [Micheva, Kristina D.; Smith, Stephen J.] Stanford Univ, Dept Mol & Cellular Biol, Sch Med, Stanford, CA 94305 USA. [Kim, M. Leo; Lee, Virginia M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Spires-Jones, TL (reprint author), Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. EM tspires@partners.org RI Hashimoto, Tadafumi/A-7723-2013; OI Meyer-Luehmann, Melanie/0000-0003-3661-2220 FU Massachusetts Alzheimer's Disease Research Center National Institutes of Health (NIH) [2 P50 AG0513424]; John D. French Alzheimer's Foundation; Alzheimer's Drug Discovery Foundation; NIH [AG08487] FX We thank Dr. Dennis Selkoe, Brigham and Women's Hospital, Boston for providing antibodiesandDr. Phill Jones, MGH, Boston for aid with image analysis. This work was supported by the Massachusetts Alzheimer's Disease Research Center National Institutes of Health (NIH) Grant 2 P50 AG0513424, a John D. French Alzheimer's Foundation Fellowship, an Alzheimer's Drug Discovery Foundation grant, and NIH Grant AG08487. NR 30 TC 308 Z9 309 U1 5 U2 36 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 MAR 10 PY 2009 VL 106 IS 10 BP 4012 EP 4017 DI 10.1073/pnas.0811698106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 416WT UT WOS:000264036900066 PM 19228947 ER PT J AU Sawada, N Kim, HH Moskowitz, MA Liao, JK AF Sawada, Naoki Kim, Hyung-Hwan Moskowitz, Michael A. Liao, James K. TI Rac1 Is a Critical Mediator of Endothelium-Derived Neurotrophic Activity SO SCIENCE SIGNALING LA English DT Article ID BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; TGF-BETA; SIGNALING PATHWAYS; CEREBRAL-ISCHEMIA; HEAT-SHOCK; NEURONS; FAMILY; GROWTH; GDNF AB The therapeutic potential of neurotrophic factors has been hampered by their inability to achieve adequate tissue penetration. Brain blood vessels, however, could be an alternative target for neuro-salvage therapies by virtue of their close proximity to neurons. Here we show that hemizygous deletion of Rac1 in mouse endothelial cells (ECs) attenuates brain injury and edema after focal cerebral ischemia. Microarray analysis of Rac1(+/-) ECs revealed enrichment of stress response genes, basement membrane components, and neurotrophic factors that could affect neuronal survival. Consistent with these expression profiles, endothelial Rac1 hemizygosity enhanced antioxidative and endothelial barrier capacities and potentiated paracrine neuroprotective activities through the up-regulation of the neurotrophic factor, artemin. Endothelial Rac1, therefore, could be an important therapeutic target for promoting endothelial barrier integrity and neurotrophic activity. C1 [Sawada, Naoki; Kim, Hyung-Hwan; Liao, James K.] Brigham & Womens Hosp, Cambridge, MA 02139 USA. [Moskowitz, Michael A.] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Liao, JK (reprint author), Brigham & Womens Hosp, 65 Landsdowne St,Room 275, Cambridge, MA 02139 USA. EM jliao@rics.bwh.harvard.edu FU NHLBI NIH HHS [R01 HL080187-02, R01 HL080187-03, R01 HL070274-05, R01 HL080187, R01 HL052233-05, R01 HL052233-12, R01 HL052233-10, R01 HL070274-04, R01 HL070274, R01 HL080187-04, R01 HL052233-09, R01 HL052233-11, R01 HL052233]; NIDDK NIH HHS [R01 DK062729-05, R01 DK062729] NR 55 TC 13 Z9 14 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD MAR 10 PY 2009 VL 2 IS 61 AR ra10 DI 10.1126/scisignal.2000162 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 567UV UT WOS:000275473000003 PM 19278959 ER PT J AU Zhang, BH Wright, AA Huskamp, HA Nilsson, ME Maciejewski, ML Earle, CC Block, SD Maciejewski, PK Prigerson, HG AF Zhang, Baohui Wright, Alexi A. Huskamp, Haiden A. Nilsson, Matthew E. Maciejewski, Matthew L. Earle, Craig C. Block, Susan D. Maciejewski, Paul K. Prigerson, Holly G. TI Health Care Costs in the Last Week of Life Associations With End-of-Life Conversations SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PATIENT PREFERENCES; ADVANCE DIRECTIVES; PROPENSITY SCORE; INTENSIVE-CARE; MEDICAL-CARE; TRENDS; EXPENDITURES; CANCER; DEATH AB Background: Life-sustaining medical care of patients with advanced cancer at the end of life (EOL) is costly. Patient-physician discussions about EOL wishes are associated with lower rates of intensive interventions. Methods: Funded by the National Institute of Mental Health and the National Cancer Institute, Coping With Cancer is a longitudinal multi-institutional study of 627 patients with advanced cancer. Patients were interviewed at baseline and were followed up through death. Costs for intensive care unit and hospital stays, hospice care, and life-sustaining procedures (eg, mechanical ventilator use and resuscitation) received in the last week of life were aggregated. Generalized linear models were applied to test for cost differences in EOL care. Propensity score matching was used to reduce selection biases. Results: Of 603 participants, 188 (31.2%) reported EOL discussions at baseline. After propensity score matching, the remaining 415 patients did not differ in socio-demographic characteristics, recruitment sites, illness acknowledgment, or treatment preferences. Further analyses, adjusted by quintiles of propensity scores and significant confounders, revealed that the mean (SE) aggregate costs of care (in 2008 US dollars) were $1876 ($177) for patients who reported EOL discussions compared with $2917 ($285) for patients who did not, a cost difference of $1041 (35.7% lower among patients who reported EOL discussions) (P=.002). Patients with higher costs had worse quality of death in their final week (Pearson production moment correlation partial r=-0.17, P=.006). Conclusions: Patients with advanced cancer who reported having EOL conversations with physicians had significantly lower health care costs in their final week of life. Higher costs were associated with worse quality of death. C1 [Zhang, Baohui; Nilsson, Matthew E.; Block, Susan D.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Wright, Alexi A.; Earle, Craig C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Earle, Craig C.] Dana Farber Canc Inst, Dept Populat Sci, Boston, MA 02115 USA. [Huskamp, Haiden A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Block, Susan D.; Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA. [Block, Susan D.; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Maciejewski, Matthew L.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Univ N Carolina, Div Pharmaceut Outcomes & Policy, Eshelman Sch Pharmacy, Chapel Hill, NC USA. [Maciejewski, Paul K.] Yale Univ, Sch Med, Dept Psychiat, Womens Hlth Res & Magnet Resonance Res Ctr, New Haven, CT USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Smith 268,44 Binney St, Boston, MA 02115 USA. EM Holly_Prigerson@dfci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370]; Center for Psycho-Oncology and Palliative Care Research; Dana-Farber Cancer Institute FX This study was supported in part by grant MH63892 from the National Institute of Mental Health, by grant CA106370 from the National Cancer Institute, and by the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute (all to Dr Prigerson). NR 28 TC 286 Z9 286 U1 11 U2 35 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 MAR 9 PY 2009 VL 169 IS 5 BP 480 EP 488 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 416EX UT WOS:000263989500009 PM 19273778 ER PT J AU Ganzini, L Goy, ER Dobscha, SK AF Ganzini, Linda Goy, Elizabeth R. Dobscha, Steven K. TI Oregonians' Reasons for Requesting Physician Aid in Dying SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MENTAL STATUS QUESTIONNAIRE; TERMINALLY-ILL PATIENTS; ASSISTED SUICIDE; HASTENED DEATH; DESIRE; EXPERIENCES; EUTHANASIA; ATTITUDES; CANCER AB Background: Oregon is the only US jurisdiction with a legal process, the Oregon Death with Dignity Act, that allows terminally ill patients to obtain physician aid in dying ( PAD). Methods: Fifty-six Oregonians who either requested PAD or contacted a PAD advocacy organization completed a survey indicating the importance of 29 reasons for their interest in PAD on a scale where 1 was not important and 5 was very important; 28% of people referred from the PAD advocacy organization enrolled in the study. Results: Forty-one patients died by the end of the study; 18 received a prescription for medication under the Oregon Death with Dignity Act, and 9 died by lethal dose of medication. The most important reasons for requesting PAD, all with median scores of 5, were wanting to control the circumstances of death and die at home; loss of independence; and concerns about future pain, poor quality of life, and inability to care for one's self. All physical symptoms (eg, pain, dyspnea, and fatigue) at the time of the interview were rated as unimportant (median score, 1), but concerns about physical symptoms in the future were rated at a median score of 3 or higher. Lack of social support and depressed mood were rated as unimportant reasons for requesting PAD. Conclusions: At the time they express initial interest in PAD, Oregonians are motivated by worries about future physical discomfort and losses of autonomy and function. When confronted with a request for PAD, health care providers should first work to bolster the patient's sense of control and to educate and reassure the patient regarding management of future symptoms. C1 Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Hlth Serv Res & Dev Serv, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Ganzini, L (reprint author), Portland VA Med Ctr, Res Serv, Mail Code R&D 66,POB 1034, Portland, OR 97239 USA. EM Linda.Ganzini@va.gov FU Department of Veterans' Affairs Health Services Research and Development Service FX This study was supported by a grant from the Northwest Health Foundation and Career Development Awards from the Department of Veterans' Affairs Health Services Research and Development Service (Drs Goy and Dobscha). NR 22 TC 42 Z9 43 U1 3 U2 18 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 MAR 9 PY 2009 VL 169 IS 5 BP 489 EP 492 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 416EX UT WOS:000263989500010 PM 19273779 ER PT J AU Benarafa, C Lecuyer, TE Remold-O'Donnell, E AF Benarafa, C. Lecuyer, T-E Remold-O'Donnell, E. TI SerpinB1 regulates the size of the neutrophil reservoir in the bone marrow independently of neutrophil elastase SO SWISS MEDICAL WEEKLY LA English DT Meeting Abstract C1 [Benarafa, C.; Lecuyer, T-E; Remold-O'Donnell, E.] Harvard Univ, Sch Med, Dept Pediat, Immune Dis Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU E M H SWISS MEDICAL PUBLISHERS LTD PI MUTTENZ PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND SN 1424-7860 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD MAR 7 PY 2009 VL 139 IS 9-10 BP 12S EP 12S PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 417YB UT WOS:000264113300050 ER PT J AU Habbel, P Weylandt, KH Lichopoj, K Nowak, J Purschke, M Wang, JD He, CW Baumgart, DC Kang, JX AF Habbel, Piet Weylandt, Karsten H. Lichopoj, Katja Nowak, Johannes Purschke, Martin Wang, Jing-Dong He, Cheng-Wei Baumgart, Daniel C. Kang, Jing X. TI Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Colorectal carcinoma; Colon cancer; Omega-3; Omega-6; Polyunsaturated fatty acids; Arachidonic acid; Docosahexaenoic acid; Prostaglandin E-2; Cyclooxygenase-2; Apoptosis ID POLYUNSATURATED FATTY-ACIDS; COLORECTAL-CANCER RISK; NITRIC-OXIDE SYNTHASE; PROSTAGLANDIN E-2; TRANSGENIC MICE; N-3; APOPTOSIS; CYCLOOXYGENASE-2; EXPRESSION; GROWTH AB AIM: To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell growth. METHODS: The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death, flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (COX-2), p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E-2 (PGE(2)) generation in the presence of AA and DHA was measured using a PGE(2)-ELISA. RESULTS: AA increased cell growth, whereas DHA reduced viability of LS 174T cells in a time- and dose-dependent manner. Furthermore, DHA down-regulated mRNA of bcl-2 and up-regulated p21. Interestingly, DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE(2) formation. DHA also down-regulated COX-2 expression. In addition to the effect on PGE(2) formation, DHA directly reduced PGE(2)-induced cell proliferation in a dose-dependent manner. CONCLUSION: These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE(2). (C) 2009 The WJG Press and Baishideng. All rights reserved. C1 [Habbel, Piet; Weylandt, Karsten H.; Lichopoj, Katja; Nowak, Johannes; Purschke, Martin; Wang, Jing-Dong; He, Cheng-Wei; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Habbel, Piet; Weylandt, Karsten H.; Lichopoj, Katja; Nowak, Johannes; Purschke, Martin; Wang, Jing-Dong; He, Cheng-Wei; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Habbel, Piet; Weylandt, Karsten H.; Lichopoj, Katja; Nowak, Johannes; Baumgart, Daniel C.] Humboldt Univ, Sch Med, Div Gastroenterol & Hepatol, Virchow Hosp,Charite Med Ctr, D-13344 Berlin, Germany. RP Weylandt, KH (reprint author), Massachusetts Gen Hosp, Dr Kangs Lab, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM karsten.weylandt@gmx.de FU PHS HHS [R01 113605] NR 30 TC 18 Z9 20 U1 1 U2 4 PU BAISHIDENG PUBL GRP CO LTD PI WANCHAI PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG 100025, PEOPLES R CHINA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAR 7 PY 2009 VL 15 IS 9 BP 1079 EP 1084 DI 10.3748/wjg.15.1079 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 418MM UT WOS:000264152300008 PM 19266600 ER PT J AU Hammell, CM Lubin, I Boag, PR Blackwell, TK Ambros, V AF Hammell, Christopher M. Lubin, Isabella Boag, Peter R. Blackwell, T. Keith Ambros, Victor TI nhl-2 Modulates MicroRNA Activity in Caenorhabditis elegans SO CELL LA English DT Article ID MEDIATED TRANSLATIONAL REPRESSION; PHYSIOLOGICAL GERMLINE APOPTOSIS; C-ELEGANS; RING FINGER; IN-VITRO; P-BODIES; RNA; GW182; PROTEIN; COMPLEX AB TRIM-NHL proteins represent a large class of metazoan proteins implicated in development and disease. We demonstrate that a C. elegans TRIM-NHL protein, NHL-2, functions as a cofactor for the microRNA-induced silencing complex (miRISC) and thereby enhances the posttranscriptional repression of several genetically verified microRNA targets, including hbl-1 and let-60/Ras (by the let-7 family of microRNAs) and cog-1 (by the lsy-6 microRNA). NHL-2 is localized to cytoplasmic P-bodies and physically associates with the P-body protein CGH-1 and the core miRISC components ALG-1/2 and AIN-1. nhl-2 and cgh-1 mutations compromise the repression of microRNA targets in vivo but do not affect microRNA biogenesis, indicating a role for an NHL-2: CGH-1 complex in the effector phase of miRISC activity. We propose that the NHL-2: CGH-1 complex functions in association with mature miRISC to modulate the efficacy of microRNA: target interactions in response to physiological and developmental signals, thereby ensuring the robustness of genetic regulatory pathways regulated by microRNAs. C1 [Hammell, Christopher M.; Lubin, Isabella; Ambros, Victor] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Boag, Peter R.; Blackwell, T. Keith] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dept Pathol,Joslin Diabet Ctr, Boston, MA 02215 USA. RP Ambros, V (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. EM victor.ambros@umassmed.edu OI Hammell, Christopher/0000-0002-5961-0976 FU NIH [F32 GM69186]; National Institutes of Health [GM30428, GM63826] FX Thanks to members of the Ambros laboratory and M. Hammell for thoughtful critiques of the data and the manuscript. We thank C. Mello and M. Han for antisera and worm strains and the Caenorhabditis Genetics Center for worm strains. C. M. H. was supported by an NIH postdoctoral fellowship (F32 GM69186). P. R. B. was supported by a fellowship from the M. R. Reinhard Family Foundation. V. A. and T. K. B. were supported by grants from the National Institutes of Health (GM30428 and GM63826, respectively). NR 40 TC 97 Z9 113 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 6 PY 2009 VL 136 IS 5 BP 926 EP 938 DI 10.1016/j.cell.2009.01.053 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 415JU UT WOS:000263930900015 PM 19269369 ER PT J AU Blaya, C Moorjani, P Salum, GA Goncalves, L Weiss, LA Leistner-Segal, S Manfro, GG Smoller, JW AF Blaya, Carolina Moorjani, Priya Salum, Giovanni Abrahao Goncalves, Leonardo Weiss, Lauren A. Leistner-Segal, Sandra Manfro, Gisele G. Smoller, Jordan W. TI Preliminary evidence of association between EFHC2, a gene implicated in fear recognition, and harm avoidance SO NEUROSCIENCE LETTERS LA English DT Article DE Harm-avoidance; Panic; EFHC2 ID WHOLE-GENOME ASSOCIATION; TURNER-SYNDROME; PANIC DISORDER; PHOBIC ANXIETY; PERSONALITY; TEMPERAMENT; NEUROTICISM AB Genetic variation at the EF-hand domain containing 2 gene (EFHC2) locus has been associated with fear recognition in Turner syndrome. The aim of this study was to examine whether EFHC2 variants are associated with non-syndromic anxiety-related traits [harm avoidance (HA) and behavioral inhibition (BI)] and with panic disorder (PD). Our sample comprised 127 PD patients and 132 controls without psychiatric disorder. We genotyped nine SNPs within the EFHC2 locus and used PLINK to perform association analyses. An intronic SNP (rs1562875) was associated with HA (permuted p = 0.031) accounting alone for over 3% of variance in this trait. This same SNP was nominally, but not empirically, associated with BI (r(2) = 0.022; nominal p = 0.022) and PD (OR = 2.64; nominal p = 0.009). The same association was found in a subsample of only females. In sum, we observed evidence of association between a variant in EFHC2, a gene previously associated with the processing of fear and social threat, and HA. Larger studies are warranted to confirm this association. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Blaya, Carolina; Salum, Giovanni Abrahao; Goncalves, Leonardo; Leistner-Segal, Sandra; Manfro, Gisele G.] Univ Fed Rio Grande do Sul, Dept Psychiat, Postgrad Program Med Sci Psychiat, Hosp Clin Porto Alegre,Anxiety Disorders Program, BR-90470280 Porto Alegre, RS, Brazil. [Moorjani, Priya; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Human Genet Res, Psychiat Genet Program Mood & Anxiety Diorders, Boston, MA 02114 USA. [Moorjani, Priya; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Weiss, Lauren A.] Broad Inst Harvard, Cambridge, MA USA. [Weiss, Lauren A.] MIT, Cambridge, MA 02139 USA. [Weiss, Lauren A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weiss, Lauren A.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. RP Manfro, GG (reprint author), Univ Fed Rio Grande do Sul, Dept Psychiat, Postgrad Program Med Sci Psychiat, Hosp Clin Porto Alegre,Anxiety Disorders Program, Luiz Manoel Gonzaga 630-11, BR-90470280 Porto Alegre, RS, Brazil. EM gmanfro@portoweb.com.br RI Leistner-Segal, Sandra/B-2858-2008; Manfro, Gisele/B-7020-2009; Salum, Giovanni/A-7849-2010 OI Leistner-Segal, Sandra/0000-0003-3792-6168; Salum, Giovanni/0000-0002-7537-7289 FU Fundacao de Incentivo a Pesquisa; CAPES; CNPq FX Funding was provided by Fundacao de Incentivo a Pesquisa, CAPES, CNPq, Rose and Eugene Kleiner Family Foundation and Ruth L. Kirschstein National Research Service Award. Authors thank Dr. Luis Augusto Rohde for his contribution. NR 19 TC 9 Z9 10 U1 2 U2 5 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 MAR 6 PY 2009 VL 452 IS 1 BP 84 EP 86 DI 10.1016/j.neulet.2009.01.036 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 417QT UT WOS:000264092100020 PM 19429002 ER PT J AU Di Carlo, D Edd, JF Humphry, KJ Stone, HA Toner, M AF Di Carlo, Dino Edd, Jon F. Humphry, Katherine J. Stone, Howard A. Toner, Mehmet TI Particle Segregation and Dynamics in Confined Flows SO PHYSICAL REVIEW LETTERS LA English DT Article ID POISEUILLE FLOW; INERTIAL MIGRATION; REYNOLDS-NUMBER; FRACTIONATION; SEPARATION; SPHERE; LIFT AB Nonlinearity in finite-Reynolds-number flow results in particle migration transverse to fluid streamlines, producing the well-known "tubular pinch effect" in cylindrical pipes. Here we investigate these nonlinear effects in highly confined systems where the particle size approaches the channel dimensions. Experimental and numerical results reveal distinctive dynamics, including complex scaling of lift forces with channel and particle geometry. The unique behavior described in this Letter has broad implications for confined particulate flows. C1 [Di Carlo, Dino; Edd, Jon F.; Toner, Mehmet] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Di Carlo, Dino; Edd, Jon F.; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Humphry, Katherine J.; Stone, Howard A.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Humphry, Katherine J.; Stone, Howard A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Di Carlo, D (reprint author), Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. EM dicarlo@seas.ucla.edu; jonedd2@gmail.com RI Humphry, Katherine/C-1948-2008; OI Humphry, Katherine/0000-0002-9098-6402 FU NIBIB [P41 EB002503]; American Cancer Society [PF-07-237-01-CCE]; NIH [F32 EB007901] FX The authors acknowledge support from the NIBIB (P41 EB002503), D. D. was supported by the American Cancer Society (PF-07-237-01-CCE), and J.F.E. was supported by NIH through the NIBIB (F32 EB007901). NR 19 TC 153 Z9 154 U1 7 U2 65 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAR 6 PY 2009 VL 102 IS 9 AR 094503 DI 10.1103/PhysRevLett.102.094503 PG 4 WC Physics, Multidisciplinary SC Physics GA 415CM UT WOS:000263911900028 PM 19392526 ER PT J AU Bussel, JB Kuter, DJ Pullarkat, V Lyons, RM Guo, M Nichol, JL AF Bussel, James B. Kuter, David J. Pullarkat, Vinod Lyons, Roger M. Guo, Matthew Nichol, Janet L. TI Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP SO BLOOD LA English DT Article ID INTRAVENOUS GAMMA-GLOBULIN; PLATELET PRODUCTION; BONE-MARROW; AUTOIMMUNE THROMBOCYTOPENIA; THROMBOPOIETIN LEVELS; ADULT PATIENTS; IN-VITRO; PURPURA; SPLENECTOMY; AMG-531 AB Chronic immune thrombocytopenic purpura (ITP) is characterized by low platelet counts and mucocutaneous bleeding. In previous studies romiplostim (AMG531), a thrombopoiesis-stimulating protein, increased platelet counts in most patients with chronic ITP. This ongoing, long-term open-label, single-arm study investigated safety and efficacy in patients who completed a previous romiplostim study and had platelet counts less than 5 x 10(9)/L. One hundred forty-two patients were treated for up to 156 weeks (mean, 69 weeks). Platelet responses (platelet count >= 50 x 10(9)/L and double baseline) were observed in 87% of all patients and occurred on average 67% of the time in responding patients. In 77% of patients, the romiplostim dose remained within 2 mu g/kg of their most frequent dose at least 90% of the time. Ninety patients (63%) received treatment by self-administration. Treatment-related serious adverse events were reported in 13 patients (9%). Bone marrow reticulin was observed in 8 patients; marrows were not routinely performed in this study, so the true incidence of this event cannot be determined. Severe bleeding events were reported in 12 patients (9%). Thrombotic events occurred in 7 patients (5%). In conclusion, romiplostim increased platelet counts in most patients for up to 156 weeks without tachyphylaxis and had an acceptable safety profile. (ClinicalTrials-.gov Identifier NCT00116688). (Blood. 2009; 113: 2161-2171) C1 [Bussel, James B.] New York Presbyterian Hosp, Dept Pediat, Div Hematol, New York, NY USA. [Bussel, James B.] New York Presbyterian Hosp, Dept Med, Div Hematol, New York, NY USA. [Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pullarkat, Vinod] City Hope Natl Med Ctr, Div Hematol, Duarte, CA USA. [Lyons, Roger M.] Canc Care Ctr S Texas US Oncol, San Antonio, TX USA. [Guo, Matthew; Nichol, Janet L.] Amgen Inc, Thousand Oaks, CA USA. RP Bussel, JB (reprint author), Cornell Univ, Weill Med Coll, P609,525 East 68th St, New York, NY 10065 USA. EM jbussel@med.cornell.edu FU Amgen FX The authors thank the study investigators, coordinators, nurses, and patients and their families for their invaluable contributions to this study. In addition to the authors, the following investigators participated in the study: Louis Aledort, Mount Sinai Hospital (New York, NY); James George, University of Oklahoma Health Sciences Center, Hematology Oncology Section (Oklahoma City, OK); Jeffery Wasser, DeQuattro Community Cancer Center (Manchester, CT); Terry Gernsheimer, Puget Sound Blood Center (Seattle, WA); Alan E. Lichtin, The Cleveland Clinic Foundation, Department of Hematology/Oncology (Cleveland, OH); Jeffrey Andrey, Scripps Clinic (San Diego, CA); Ronald Go, Gundersen Lutheran Health System (La Crosse, WI); M. S. Murali, Central Indiana Cancer Centers-Rama (Indianapolis, IN); Howard Liebman, USC Keck School of Medicine, Division of Hematology (Los Angeles, CA); Robert Redner, University of Pittsburgh Department of Medicine, Hillman Cancer Center (Pittsburgh, PA); Craig Kessler, Georgetown University Medical Center (Washington, DC); Michael Tarantino, Comprehensive Bleeding Disorders Center (Peoria, IL); Gail Macik, University of Virginia Health System (Charlottesville, VA); Solomon Hamburg, Tower Cancer Research Foundation (Beverly Hills, CA); Frank Slovick, Heartland Hematology Oncology Associates (Kansas City, MO); Maria Tirona, Marshall University (Huntington, WV); Gow Arepally, Duke University Medical Center (Durham, NC); Troy Guthrie, Regional Consultants in Hematology and Oncology, Baptist Cancer Institute (Jacksonville, FL); Lawrence Rice, Baylor College of Medicine (Houston, TX); Frank M. Senecal, Northwest Medical Specialties (Tacoma, WA); Barry Firstenberg, Arlington Cancer Center (Arlington, TX); Howard Terebelo, Newland Medical Associates (Southfield, MI); Usha Sunkara, Alta Bates Comprehensive Cancer Center (Berkeley, CA); Emmanuelle Bourgeois, Service des Maladies du Sang, CHRU Claude Huriet (Lille, France); Francois Lefrere, Service d'Hematologie Adulte, Hopital Necker (Paris, France); MC Kappers-Klunne, Erasmus MC (Rotterdam, The Netherlands); Adrian Newland, Department of Hematology, The Royal London Hospital (London, United Kingdom); Martin R. Schipperus, Ziekenhuis Leyenburg, Hematology (Den Haag, The Netherlands); Edo Vellenga, Universitair Medisch centrum Groningen (Groningen, The Netherlands); Carlos Grande, Hospital 12 de Octubre (Madrid, Spain); Miguel Sanz, Hospital La Fe (Valencia, Spain); Jean-Francois Viallard, Medecine Interne-Maladies Infectieuses, Hopital Haut-Leveque (Pessac, France); Jose Tongol, Phoebe Cancer Center (Albany, GA); and Robert Hermann, Northwest Georgia Oncology Centers PC (Marietta, GA).; This study was supported in part by research funding from Amgen. James O'Kelly, an employee of Amgen, and Mary Royer, a paid consultant to Amgen, assisted with preparation of the manuscript. NR 44 TC 197 Z9 211 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 5 PY 2009 VL 113 IS 10 BP 2161 EP 2171 DI 10.1182/blood-2008-04-150078 PG 11 WC Hematology SC Hematology GA 415EZ UT WOS:000263918400008 PM 18981291 ER PT J AU Shammas, MA Reis, RJS Koley, H Batchu, RB Li, C Munshi, NC AF Shammas, Masood A. Reis, Robert J. Shmookler Koley, Hemanta Batchu, Ramesh B. Li, Cheng Munshi, Nikhil C. TI Dysfunctional homologous recombination mediates genomic instability and progression in myeloma SO BLOOD LA English DT Article ID CULTURED-MAMMALIAN-CELLS; MULTIPLE-MYELOMA; DNA-REPAIR; TELOMERASE INHIBITION; ADENOCARCINOMA CELLS; GENE AMPLIFICATION; HUMAN-FIBROBLASTS; GROWTH ARREST; LUNG-CANCER; T-ANTIGEN AB A prominent feature of most if not all cancers is a striking genetic instability, leading to ongoing accrual of mutational changes, some of which underlie tumor progression, including acquisition of invasiveness, drug resistance, and metastasis. Thus, the molecular basis for the generation of this genetic diversity in cancer cells has important implications in understanding cancer progression. Here we report that homologous recombination (HR) activity is elevated in multiple myeloma (MM) cells and leads to an increased rate of mutation and progressive accumulation of genetic variation over time. We demonstrate that the inhibition of HR activity in MM cells by small inhibitory RNA(siRNAs) targeting recombinase leads to significant reduction in the acquisition of new genetic changes in the genome and, conversely, the induction of HR activity leads to significant elevation in the number of new mutations over time and development of drug resistance in MM cells. These data identify dysregulated HR activity as a key mediator of DNA instability and progression of MM, with potential as a therapeutic target. (Blood. 2009; 113: 2290-2297) C1 [Shammas, Masood A.; Li, Cheng; Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Shammas, Masood A.; Koley, Hemanta; Batchu, Ramesh B.; Munshi, Nikhil C.] VA Hlth Care Syst, Dept Med, Boston, MA USA. [Shammas, Masood A.; Koley, Hemanta; Batchu, Ramesh B.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA. [Reis, Robert J. Shmookler] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. [Reis, Robert J. Shmookler] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Reis, Robert J. Shmookler] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,M1B28, Boston, MA 02115 USA. EM Nikhil_Munshi@DFCI.Harvard.edu RI Shmookler Reis, Robert/C-4112-2009 FU National Institutes of Health [1RO1CA125711-01A2]; Multiple Myeloma Research Foundation; Department of Veterans Affairs [NIH-P50-100007]; NIH [RO1-124929, P50-100007, PO1-78 378]; Department of Veterans Affairs FX This work was supported in part by grants from National Institutes of Health (Bethesda, MD; 1RO1CA125711-01A2), the Multiple Myeloma Research Foundation (Norwalk, CT) and NIH-P50-100007 Developmental Research Award to M. A. S. and from the Department of Veterans Affairs (Washington, DC) Merit Review Awards and NIH grants RO1-124929, P50-100007, and PO1-78 378 to N.C.M. The work also was supported in part by grants from the Department of Veterans Affairs (Merit Review and Research Career Scientist Award) to R.J.S.R. NR 53 TC 47 Z9 47 U1 1 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 MAR 5 PY 2009 VL 113 IS 10 BP 2290 EP 2297 DI 10.1182/blood-2007-05-089193 PG 8 WC Hematology SC Hematology GA 415EZ UT WOS:000263918400022 PM 19050310 ER PT J AU Meng, YA Yu, Y Cupples, LA Farrer, LA Lunetta, KL AF Meng, Yan A. Yu, Yi Cupples, L. Adrienne Farrer, Lindsay A. Lunetta, Kathryn L. TI Performance of random forest when SNPs are in linkage disequilibrium SO BMC BIOINFORMATICS LA English DT Article ID VARIABLE IMPORTANCE; ASSOCIATION; TRAITS AB Background: Single nucleotide polymorphisms (SNPs) may be correlated due to linkage disequilibrium (LD). Association studies look for both direct and indirect associations with disease loci. In a Random Forest (RF) analysis, correlation between a true risk SNP and SNPs in LD may lead to diminished variable importance for the true risk SNP. One approach to address this problem is to select SNPs in linkage equilibrium (LE) for analysis. Here, we explore alternative methods for dealing with SNPs in LD: change the tree-building algorithm by building each tree in an RF only with SNPs in LE, modify the importance measure (IM), and use haplotypes instead of SNPs to build a RF. Results: We evaluated the performance of our alternative methods by simulation of a spectrum of complex genetics models. When a haplotype rather than an individual SNP is the risk factor, we find that the original Random Forest method performed on SNPs provides good performance. When individual, genotyped SNPs are the risk factors, we find that the stronger the genetic effect, the stronger the effect LD has on the performance of the original RF. A revised importance measure used with the original RF is relatively robust to LD among SNPs; this revised importance measure used with the revised RF is sometimes inflated. Overall, we find that the revised importance measure used with the original RF is the best choice when the genetic model and the number of SNPs in LD with risk SNPs are unknown. For the haplotype-based method, under a multiplicative heterogeneity model, we observed a decrease in the performance of RF with increasing LD among the SNPs in the haplotype. Conclusion: Our results suggest that by strategically revising the Random Forest method tree-building or importance measure calculation, power can increase when LD exists between SNPs. We conclude that the revised Random Forest method performed on SNPs offers an advantage of not requiring genotype phase, making it a viable tool for use in the context of thousands of SNPs, such as candidate gene studies and follow-up of top candidates from genome wide association studies. C1 [Meng, Yan A.; Yu, Yi; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. [Cupples, L. Adrienne; Farrer, Lindsay A.; Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Meng, Yan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Meng, Yan A.] Broad Inst Harvard, Cambridge, MA USA. [Meng, Yan A.] MIT, Cambridge, MA 02139 USA. RP Meng, YA (reprint author), Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. EM ymeng@broad.mit.edu; yy79@bu.edu; adrienne@bu.edu; farrer@bu.edu; klunetta@bu.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Farrer, Lindsay/0000-0001-5533-4225; Lunetta, Kathryn/0000-0002-9268-810X FU Canadian Institutes of Health Research; Fonds de la Recherche en Sante; National Institutes of Health [R01-AG09029, R01-AG25259, R01-AG17173]; NIH NCRR [1S10RR163736] FX This work was supported by grants from the Canadian Institutes of Health Research (Y.A.M), Fonds de la Recherche en Sante (Y.A.M), and the National Institutes of Health (R01-AG09029, R01-AG25259, and R01-AG17173 to L. A. F), and utilized the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the NIH NCRR Shared Instrumentation grant (1S10RR163736). We thank LinGA System Administrator Andi Broka for facilitating the parallel computation on LinGA and Kristin Nicodemus for sharing her results during revision of this manuscript. NR 19 TC 44 Z9 47 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAR 5 PY 2009 VL 10 AR 78 DI 10.1186/1471-2105-10-78 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 439DB UT WOS:000265606700001 PM 19265542 ER PT J AU Habib, SL AF Habib, Samy L. TI Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients SO MOLECULAR CANCER LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; 3-KINASE/AKT PATHWAY; KIDNEY TUMORS; RENAL TUMORS; OGG1; PROTEIN; REPAIR; GENE; EXPRESSION; CARCINOGENESIS AB Background: The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. Loss of heterozygosity at the 8-oxoG-DNA glycosylase (OGG1) allele is found in human kidney clear cell carcinoma identifying loss of OGG1 function as a possible contributor to tumorigenesis in the kidney. Tuberin regulates OGG1 through the transcription factor NF-YA in cultured cells. The purpose of this study is to determine the effect of tuberin-deficiency on OGG1 protein and mRNA levels as well as on 8-oxodG levels in kidney tumors from patients with TSC. In addition we evaluated the phophorylation level of downstream targets of mTOR, phospho-S70K, in kidney tumor tissue from TSC patients. Results: Kidney angiomyolipoma tissue from TSC patients expresses significant levels of phophotuberin and low levels of tuberin compared to control kidney tissue. The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. The decrease OGG1 expression is also associated with significant decrease in the transcription factor, NF-YA, expression in tumor samples compared to normal tissues. In addition, the levels of 8-oxodG are 4-fold higher in tumors compared to control samples. The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. Cyclin D1 expression is also 3-fold higher in increase in the tumor tissues compared to normal kidney tissues. Conclusion: These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. These data suggest that tuberin and OGG1 are important proteins in the pathogenesis of angiomyolipoma in TSC patients. C1 [Habib, Samy L.] S Texas Vet Healthcare Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. [Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), S Texas Vet Healthcare Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. EM habib@uthscsa.edu FU NIH [P50DK061597]; NIDDK; George M. O'Brien Development and Feasibility Project; American Diabetes Association Research Grant; New Investigator Award from the South Texas Veterans Healthcare System FX The author would like to acknowledge the Morphology Core, George O'Brien Kidney Center for help with fluorescence microscopy (P50DK061597 NIH, NIDDK). Dr. H. E. Abboud for reading the manuscript. This work is supported in part by George M. O'Brien Development and Feasibility Project, American Diabetes Association Research Grant and a New Investigator Award from the South Texas Veterans Healthcare System ( to S. L. H.). NR 30 TC 8 Z9 8 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD MAR 5 PY 2009 VL 8 AR 13 DI 10.1186/1476-4598-8-13 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 424WZ UT WOS:000264600300001 PM 19265534 ER PT J AU Desai, NR Cheng, S Nohria, A Halperin, F Giugliano, RP AF Desai, Nihar R. Cheng, Susan Nohria, Anju Halperin, Florencia Giugliano, Robert P. TI When Past Is Prologue SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TRAUMATIC BRAIN-INJURY; CHRONIC HEART-FAILURE; GROWTH-HORMONE; CARDIOMYOPATHY; HYPOTHYROIDISM; DEFICIENCY; DISEASE; MEN C1 [Giugliano, Robert P.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. [Halperin, Florencia] Brigham & Womens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Dept Med, 350 Longwood Ave,1st Fl Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 17 TC 3 Z9 3 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 MAR 5 PY 2009 VL 360 IS 10 BP 1016 EP 1022 DI 10.1056/NEJMcps0805508 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 413WX UT WOS:000263824500011 PM 19264691 ER PT J AU Ho, PM Maddox, TM Wang, L Fihn, SD Jesse, RL Peterson, ED Rumsfeld, JS AF Ho, P. Michael Maddox, Thomas M. Wang, Li Fihn, Stephan D. Jesse, Robert L. Peterson, Eric D. Rumsfeld, John S. TI Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; OF-FUNCTION POLYMORPHISM; MEDICATION NONADHERENCE; ANTIPLATELET ACTION; TRIAL; ATORVASTATIN; THERAPY; ASPIRIN; RESISTANCE; REGRESSION AB Context Prior mechanistic studies reported that omeprazole decreases the platelet inhibitory effects of clopidogrel, yet the clinical significance of these findings is not clear. Objective To assess outcomes of patients taking clopidogrel with or without a proton pump inhibitor (PPI) after hospitalization for acute coronary syndrome (ACS). Design, Setting, and Patients Retrospective cohort study of 8205 patients with ACS taking clopidogrel after discharge from 127 Veterans Affairs hospitals between October 1, 2003, and January 31, 2006. Vital status information was available for all patients through September 30, 2006. Main Outcome Measures All-cause mortality or rehospitalization for ACS. Results Of 8205 patients taking clopidogrel after discharge, 63.9% (n = 5244) were prescribed PPI at discharge, during follow-up, or both and 36.1% (n = 2961) were not prescribed PPI. Death or rehospitalization for ACS occurred in 20.8% (n = 615) of patients taking clopidogrel without PPI and 29.8% (n = 1561) of patients taking clopidogrel plus PPI. In multivariable analyses, use of clopidogrel plus PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without PPI ( adjusted odds ratio [AOR], 1.25; 95% confidence interval [CI], 1.11-1.41). Among patients taking clopidogrel after hospital discharge and prescribed PPI at any point during follow-up (n = 5244), periods of use of clopidogrel plus PPI ( compared with periods of use of clopidogrel without PPI) were associated with a higher risk of death or rehospitalization for ACS (adjusted hazard ratio, 1.27; 95% CI, 1.10-1.46). In analyses of secondary outcomes, patients taking clopidogrel plus PPI had a higher risk of hospitalizations for recurrent ACS compared with patients taking clopidogrel without PPI (14.6% vs 6.9%; AOR, 1.86 [ 95% CI, 1.57-2.20]) and revascularization procedures (15.5% vs 11.9%; AOR, 1.49 [ 95% CI, 1.30-1.71]), but not for all-cause mortality (19.9% vs 16.6%; AOR, 0.91 [ 95% CI, 0.80-1.05]). The association between use of clopidogrel plus PPI and increased risk of adverse outcomes also was consistent using a nested case-control study design (AOR, 1.32; 95% CI, 1.14-1.54). In addition, use of PPI without clopidogrel was not associated with death or rehospitalization for ACS among patients not taking clopidogrel after hospital discharge (n = 6450) ( AOR, 0.98; 95% CI, 0.85-1.13). Conclusion Concomitant use of clopidogrel and PPI after hospital discharge for ACS was associated with an increased risk of adverse outcomes than use of clopidogrel without PPI, suggesting that use of PPI may be associated with attenuation of benefits of clopidogrel after ACS. C1 [Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Wang, Li; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Fihn, Stephan D.; Jesse, Robert L.] VA Cent Off, Washington, DC USA. [Jesse, Robert L.] Richmond VA Med Ctr, Richmond, VA USA. [Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. RP Ho, PM (reprint author), Dept Cardiol 111B, 1055 Clermont St, Denver, CO 80220 USA. EM michael.ho@va.gov FU Quality Enhancement Research Initiative of the US Department of Veterans Affairs; VA Health Services Research and Development Career Development Award; National Institute on Aging and from an Agency for Healthcare Research and Quality Center for Education and Research on Therapeutics [RO1] FX This study was supported by the Quality Enhancement Research Initiative of the US Department of Veterans Affairs. Dr Ho is supported by VA Health Services Research and Development Career Development Award. Dr Peterson is supported by an RO1 grant from the National Institute on Aging and from an Agency for Healthcare Research and Quality Center for Education and Research on Therapeutics. NR 34 TC 587 Z9 645 U1 3 U2 26 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 MAR 4 PY 2009 VL 301 IS 9 BP 937 EP 944 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 413HQ UT WOS:000263784600023 PM 19258584 ER PT J AU Bowers, AA Greshock, TJ West, N Estiu, G Schreiber, SL Wiest, O Williams, RM Bradner, JE AF Bowers, Albert A. Greshock, Thomas J. West, Nathan Estiu, Guillermina Schreiber, Stuart L. Wiest, Olaf Williams, Robert M. Bradner, James E. TI Synthesis and Conformation-Activity Relationships of the Peptide Isosteres of FK228 and Largazole SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; CHROMOBACTERIUM-VIOLACEUM NO-968; AZUMAMIDE-A; POTENT; DEPSIPEPTIDE; FR901228; DESIGN; TRICHOSTATIN; TRAPOXIN; DOCKING AB The peptide isosteres (110 and 11) of the naturally occurring and potent histone deacetylase (HDAC) inhibitors FK228 and largazole have been synthesized and evaluated side-by-side with FK228, largazole, and SAHA for inhibition of the class I HDACs 1, 2, 3, and 6. C1 [Estiu, Guillermina; Wiest, Olaf] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. [Williams, Robert M.] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. [Bowers, Albert A.; Greshock, Thomas J.; Williams, Robert M.] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA. [West, Nathan; Bradner, James E.] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. [West, Nathan; Schreiber, Stuart L.; Bradner, James E.] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA 02142 USA. [Schreiber, Stuart L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Wiest, O (reprint author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. EM james_bradner@dfci.harvard.edu FU NCI NIH HHS [K08 CA128972, 1K08CA128972, K08 CA128972-01A1, CA136283, F32 CA136283]; NIGMS NIH HHS [GM49631] NR 32 TC 72 Z9 73 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 4 PY 2009 VL 131 IS 8 BP 2900 EP 2905 DI 10.1021/ja807772w PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 427PX UT WOS:000264792300044 PM 19193120 ER PT J AU Polli, FE Wright, CI Milad, MR Dickerson, BC Vangel, M Barton, JJS Rauch, SL Manoach, DS AF Polli, Frida E. Wright, Christopher I. Milad, Mohammed R. Dickerson, Bradford C. Vangel, Mark Barton, Jason J. S. Rauch, Scott L. Manoach, Dara S. TI Hemispheric differences in amygdala contributions to response monitoring SO NEUROREPORT LA English DT Article DE amygdala; anterior cingulate cortex; antisaccade; emotion; errors; limbic system; reinforcement learning; response monitoring ID ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; RHESUS-MONKEY; FMRI; PERSPECTIVES; ACQUISITION; PERFORMANCE; EXTINCTION; ACTIVATION; DEPRESSION AB The amygdala detects aversive events and coordinates with the rostral anterior cingulate cortex to adapt behavior. We assessed error-related activation in these regions and its relation to task performance using functional MRI and a saccadic paradigm. Both amygdalae showed increased activation during error versus correct antisaccade trials that was correlated with error-related activation in the corresponding rostral anterior cingulate cortex. Together, activation in the right amygdala and right rostral anterior cingulate cortex predicted greater accuracy. In contrast, the left amygdala activation predicted a higher error rate. These findings support a role for the amygdala in response monitoring. Consistent with proposed specializations of the right and left amygdala in aversive conditioning, we hypothesize that right amygdala-rostral anterior cingulate cortex interactions mediate learning to avoid errors, whereas left error-related amygdala activation underpins detrimental negative affect. NeuroReport 20:398-402 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Polli, Frida E.; Wright, Christopher I.; Milad, Mohammed R.; Dickerson, Bradford C.; Rauch, Scott L.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Dickerson, Bradford C.; Vangel, Mark] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dickerson, Bradford C.; Manoach, Dara S.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Wright, Christopher I.; Dickerson, Bradford C.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Polli, Frida E.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Barton, Jason J. S.] Univ British Columbia, Dept Neurol, Vancouver, BC V5Z 1M9, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Ophthalmol, Vancouver, BC V5Z 1M9, Canada. [Barton, Jason J. S.] Univ British Columbia, Dept Visual Sci, Vancouver, BC V5Z 1M9, Canada. RP Manoach, DS (reprint author), 149 13th St,Room 2608, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012 FU NIMH [F31 MH72120, R01 MH67720]; NARSAD; MIND Institute [DOE DE-FG02 99ER62764, NCRR 5 P41 RR14075 A 05]; [K08 NS01920] FX With gratitude to Matt Cain, Katy Thakkar, Bruce Fischl, and Doug Greve. This study was supported by NIMH F31 MH72120 (FET); R01 MH67720 (D.S.M.); NARSAD (D.S.M.); K08 NS01920 (J.J.S.B.); MIND Institute (DOE DE-FG02 99ER62764; NCRR 5 P41 RR14075 A 05). NR 26 TC 13 Z9 13 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 4 PY 2009 VL 20 IS 4 BP 398 EP 402 DI 10.1097/WNR.0b013e328324edb8 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 423ST UT WOS:000264516700010 PM 19218865 ER PT J AU Grandpre, LE Duke-Cohan, JS Ewald, BA Devoy, C Barouch, DH Letvin, NL Reinherz, EL Baden, LR Dolin, R Seaman, MS AF Grandpre, Lauren E. Duke-Cohan, Jonathan S. Ewald, Bonnie A. Devoy, Colleen Barouch, Dan H. Letvin, Norman L. Reinherz, Ellis L. Baden, Lindsey R. Dolin, Raphael Seaman, Michael S. TI Immunogenicity of recombinant Modified Vaccinia Ankara following a single or multi-dose vaccine regimen in rhesus monkeys SO VACCINE LA English DT Article DE MVA; Vaccinia virus; Vaccine; Neutralizing antibody; Rhesus monkey ID SMALLPOX VACCINE; LETHAL MONKEYPOX; VIRUS CHALLENGE; RESPIRATORY CHALLENGE; DRYVAX(R) CHALLENGE; PROTECTS MICE; STRAIN MVA; ANTIBODIES; INFECTION; RESPONSES AB Modified Vaccinia Ankara (MVA) is a replication-defective strain of vaccinia virus (VV) that is being investigated in humans as an alternative vaccine against smallpox. Understanding the parameters of a MVA vaccine regimen that can effectively enhance protective immunity will be important for clinical development. The present studies utilize cohorts of rhesus monkeys immunized with recombinant MVA (rMVA) or recombinant VV (rVV) vaccine vectors to investigate the magnitude, breadth, and durability of anti-VV immunity elicited by a single or multi-dose vaccine regimen. These data demonstrate that a single immunization with rMVA elicits weaker cellular and humoral immunity compared to a single inocuiation with rVV. However, vaccine-elicited antibody responses, but not T cell responses, are significantly enhanced with repeated immunizations of rMVA. Importantly, only monkeys receiving up to four inoculations with rMVA generated neutralizing antibody (NAb) responses that were comparable in magnitude and durability to those elicited in monkeys receiving two inoculations with rVV. These data also show that the breadth of antibody responses against protein antigens associated with two antigenically distinct forms of infectious VV are similar in rMVA- and rVV-immunized monkeys. Together, these studies suggest that a multi-dose vaccine regimen utilizing up to four inoculations of MVA generates robust and durable antibody-mediated immunity comparable to that elicited by replication-competent VV. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Grandpre, Lauren E.; Ewald, Bonnie A.; Devoy, Colleen; Barouch, Dan H.; Letvin, Norman L.; Baden, Lindsey R.; Dolin, Raphael; Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Duke-Cohan, Jonathan S.; Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. [Duke-Cohan, Jonathan S.; Reinherz, Ellis L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Baden, Lindsey R.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Duke-Cohan, Jonathan S.; Barouch, Dan H.; Letvin, Norman L.; Reinherz, Ellis L.; Baden, Lindsey R.; Dolin, Raphael; Seaman, Michael S.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. RP Seaman, MS (reprint author), Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, 330 Brookline Ave,E CLS 1001, Boston, MA 02215 USA. EM mseaman@bidmc.harvard.edu OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NIH [A1057330, A102042, NOI -A130033] FX We thank Sampa Santra for generous assistance and reagents. This work was supported by NIH grants A1057330, A102042 (E.L.R. and J.S.D.) and NIH contract NOI -A130033 (N.L.). NR 37 TC 17 Z9 17 U1 0 U2 2 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 MAR 4 PY 2009 VL 27 IS 10 BP 1549 EP 1556 DI 10.1016/j.vaccine.2009.01.010 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 420BY UT WOS:000264264600011 PM 19168105 ER PT J AU Spertus, JA Jones, PG Masoudi, FA Rumsfeld, JS Krumholz, HM AF Spertus, John A. Jones, Philip G. Masoudi, Frederick A. Rumsfeld, John S. Krumholz, Harlan M. TI Factors Associated With Racial Differences in Myocardial Infarction Outcomes SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; CORONARY-ARTERY-DISEASE; HEALTH-STATUS; PROPENSITY-SCORE; CLINICAL-TRIALS; HEART-FAILURE; PRIMARY-CARE; END-POINTS; RACE; REVASCULARIZATION AB Background: Little information is available about factors associated with racial differences across a broad spectrum of post-myocardial infarction outcomes, including patients' symptoms and quality of life. Objective: To determine racial differences in mortality, rehospitalization, angina, and quality of life after myocardial infarction and identify the factors associated with these differences. Design: Prospective cohort study. Setting: 10 hospitals in the United States. Patients: 1849 patients who had myocardial infarction, 28% of whom were black. Measurements: Demographic, economic, clinical, psychosocial, and treatment characteristics and outcomes were prospectively collected. Outcomes included time to 2-year all-cause mortality, 1-year rehospitalization, and Seattle Angina Questionnaire-assessed angina and quality of life. Results: Black patients had higher unadjusted mortality (19.9% vs. 9.3%; P < 0.001) and rehospitalization rates (45.4% vs. 40.4%; P = 0.130), more angina (28.0% vs. 17.8%; P < 0.001), and worse mean quality of life (80.6 [SD, 22.5] vs. 85.9 [SD, 17.2]; P < 0.001). After adjustment for patient characteristics, black patients trended toward greater mortality (hazard ratio, 1.29 [95% CI, 0.92 to 1.81]; P = 0.142), fewer rehospitalizations (hazard ratio, 0.82 [CI, 0.66 to 1.02]; P = 0.071), and higher likelihood of angina at 1 year (odds ratio, 1.41 [CI, 1.03 to 1.94]; P = 0.032) but similar quality of life (mean difference, -0.6 [CI, -3.4 to 2.2]). Adjustment for site of care further attenuated mortality differences (hazard ratio, 1.04 [CI, 0.71 to 1.52]; P = 0.84). Adjustment for treatments had minimal effect on any association. Limitation: Residual confounding and missing data may have introduced bias. Conclusion: Although black patients with myocardial infarction have worse outcomes than white patients, these differences did not persist after adjustment for patient factors and site of care. Further adjustment for treatments received minimally influenced observed differences. Strategies that focus on improving baseline cardiac risk and hospital factors may do more than treatment-focused strategies to attenuate racial differences in myocardial infarction outcomes. C1 [Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Univ Missouri, Kansas City, MO 64110 USA. Univ Colorado, Denver Hlth Med Ctr, Hlth Sci Ctr, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Yale New Haven Med Ctr, New Haven, CT 06504 USA. Yale Univ, Sch Med, New Haven, CT USA. RP Spertus, JA (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 4401 Wornall Rd,5th Floor, Kansas City, MO 64111 USA. EM Spertusj@umkc.edu FU The National Heart, Lung, and Blood Institute; Cardiac Dysfunction and Disease; CV Therapeutics; Cardiovascular Outcomes FX Funding: The National Heart, Lung, and Blood Institute Specialized Center of Clinically Oriented Research in Cardiac Dysfunction and Disease, CV Therapeutics, and Cardiovascular Outcomes. NR 55 TC 29 Z9 29 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 MAR 3 PY 2009 VL 150 IS 5 BP 314 EP + PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 417CC UT WOS:000264051700003 PM 19258559 ER PT J AU Atlas, SJ Grant, RW Ferris, TG Chang, YC Barry, MJ AF Atlas, Steven J. Grant, Richard W. Ferris, Timothy G. Chang, Yuchiao Barry, Michael J. TI Patient-Physician Connectedness and Quality of Primary Care SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PAY-FOR-PERFORMANCE; HEALTH-CARE; UNITED-STATES; RACIAL/ETHNIC DISPARITIES; PATIENTS EXPERIENCES; PREVENTIVE SERVICES; GLYCEMIC CONTROL; CONTROLLED-TRIAL; INSURANCE STATUS; AMBULATORY-CARE AB Background: Valid measurement of physician performance requires accurate identification of patients for whom a physician is responsible. Among all patients seen by a physician, some will be more strongly connected to their physician than others, but the effect of connectedness on measures of physician performance is not known. Objective: To determine whether patient-physician connectedness affects measures of clinical performance. Design: Population-based cohort study. Setting: Academic network of 4 community health centers and 9 hospital-affiliated primary care practices. Patients: 155 590 adults with 1 or more visits to a study practice from 2003 to 2005. Measurements: A validated algorithm was used to connect patients to either 1 of 181 physicians or 1 of 13 practices in which they received most of their care. Performance measures included breast, cervical, and colorectal cancer screening in eligible patients; hemoglobin A(1c) measurement and control in patients with diabetes; and low-density lipoprotein cholesterol measurement and control in patients with diabetes and coronary artery disease. Results: Overall, 92 315 patients (59.3%) were connected to a specific physician, whereas 53 669 patients (34.5%) were connected only to a specific practice and 9606 patients (6.2%) could not be connected to a physician or practice. The proportion of patients in a practice who could be connected to a physician varied markedly (45.6% to 71.2% of patients per practice; P < 0.001). Physician-connected patients were significantly more likely than practice-connected patients to receive guideline-consistent care (for example, adjusted mammography rates were 78.1% vs. 65.9% [P < 0.001] and adjusted hemoglobin A1c rates were 90.3% vs. 74.9% [P < 0.001]). Receipt of preventive care varied more by whether patients were more or less connected to a physician than by race or ethnicity. Limitation: Patient-physician connectedness was assessed in 1 primary care network. Conclusion: Patients seen in primary care practices seem to be variably connected with a specific physician, and less connected patients are less likely to receive guideline-consistent care. C1 [Atlas, Steven J.] Harvard Univ, Div Gen Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Atlas, SJ (reprint author), Harvard Univ, Div Gen Med, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM satlas@partners.org OI Grant, Richard/0000-0002-6164-8025 FU National Cancer Institute FX Funding: National Cancer Institute. NR 54 TC 89 Z9 90 U1 0 U2 6 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 MAR 3 PY 2009 VL 150 IS 5 BP 325 EP + PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 417CC UT WOS:000264051700004 PM 19258560 ER PT J AU Cody, V Pace, J Makin, J Piraino, J Queener, SF Rosowsky, A AF Cody, Vivian Pace, Jim Makin, Jennifer Piraino, Jennifer Queener, Sherry F. Rosowsky, Andre TI Correlations of Inhibitor Kinetics for Pneumocystis jirovecii and Human Dihydrofolate Reductase with Structural Data for Human Active Site Mutant Enzyme Complexes SO BIOCHEMISTRY LA English DT Article ID METHOTREXATE-RESISTANT VARIANTS; MACROMOLECULAR CRYSTALLOGRAPHY; CRYSTAL-STRUCTURE; CARINII; SUBSTITUTIONS; PNEUMONIA; MUTATIONS; INFECTION; INSIGHTS; SYSTEM AB To understand the role of specific active site residues in conferring selective dihydrofolate reductase (DHFR) inhibition from pathogenic organisms such as Pneumocystis carinii (pc) or Pneumocystis jirovecii (pj), the causative agent in AIDS pneumonia, it is necessary to evaluate the role of these residues in the human enzyme. We report the first kinetic parameters for DHFR from pjDHFR and pcDHFR with methotrexate (MTX), trimethoprim (TMP), and its potent analogue, PY957. We also report the mutagenesis and kinetic analysis of active site mutant proteins at positions 35 and 64 of human (h) DHFR and the crystal structure determinations of hDHFR ternary complexes of NADPH and PY957 with the wild-type DHFR enzyme, the single mutant protein, GIn35Lys, and two double mutant proteins, GIn35Ser/Asn64Ser and GIn35Ser/Asn64Phe. These substitutions place into human DHFR amino acids found at those sites in the opportunistic pathogens pcDHFR (Q35K/N64F) and pjDHFR (Q35S/N64S). The K(i) inhibition constant for PY957 showed greatest potency of the compound for the N64F single mutant protein (5.2 nM), followed by wild-type pcDHFR (K(i) 22 nM) and then wild-type hDHFR enzyme (K(i) 230 nM). Structural data reveal significant conformational changes in the binding interactions of PY957 in the hDHFR Q35S/N64F mutant protein complex compared to the other hDHFR mutant protein complexes and the pcDHFR ternary complex. The conformation of PY957 in the wild-type DHFR is similar to that observed for the single mutant protein. These data support the hypothesis that the enhanced selectivity of PY957 for pcDHFR is in part due to the contributions at positions 37 and 69 (pcDHFR numbering). This insight will help in the design of more selective inhibitors that target these opportunistic pathogens. C1 [Cody, Vivian; Pace, Jim; Makin, Jennifer; Piraino, Jennifer] Hauptman Woodward Med Res Inst, Dept Biol Struct, Buffalo, NY 14203 USA. [Cody, Vivian] SUNY Buffalo, Sch Biol & Med Sci, Dept Biol Struct, Buffalo, NY 14260 USA. [Queener, Sherry F.] Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. [Rosowsky, Andre] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cody, V (reprint author), Hauptman Woodward Med Res Inst, Dept Biol Struct, 700 Ellicott St, Buffalo, NY 14203 USA. EM cody@hwi.buffalo.edu FU National Institutes of Health [GM51670] FX This work was supported in part by a grant from the National Institutes of Health (GM51670 to V.C.). NR 33 TC 12 Z9 13 U1 3 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 3 PY 2009 VL 48 IS 8 BP 1702 EP 1711 DI 10.1021/bi801960h PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 412BD UT WOS:000263697300005 PM 19196009 ER PT J AU Ianari, A Natale, T Calo, E Ferretti, E Alesse, E Screpanti, I Haigis, K Gulino, A Lees, JA AF Ianari, Alessandra Natale, Tiziana Calo, Eliezer Ferretti, Elisabetta Alesse, Edoardo Screpanti, Isabella Haigis, Kevin Gulino, Alberto Lees, Jacqueline A. TI Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein SO CANCER CELL LA English DT Article ID ONCOGENE-INDUCED SENESCENCE; DNA-DAMAGE; CELL-CYCLE; RB FAMILY; APOPTOSIS; PRB; MECHANISMS; DIFFERENTIATION; PROLIFERATION; TRANSCRIPTION AB The retinoblastoma protein (pRB) tumor suppressor blocks cell proliferation by repressing the E2F transcription factors. This inhibition is relieved through mitogen-induced phosphorylation of pRB, triggering E2F release and activation of cell-cycle genes. E2F1 can also activate proapoptotic genes in response to genotoxic or oncogenic stress. However, pRB's role in this context has not been established. Here we show that DNA damage and E1A-induced oncogenic stress promote formation of a pRB-E2F1 complex even in proliferating cells. Moreover, pRB is bound to proapoptotic promoters that are transcriptionally active, and pRB is required for maximal apoptotic response in vitro and in vivo. Together, these data reveal a direct role for pRB in the induction of apoptosis in response to genotoxic or oncogenic stress. C1 [Ianari, Alessandra; Natale, Tiziana; Ferretti, Elisabetta; Screpanti, Isabella; Gulino, Alberto] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy. [Ianari, Alessandra; Calo, Eliezer; Lees, Jacqueline A.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Alesse, Edoardo] Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. [Haigis, Kevin] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA. [Gulino, Alberto] Neuromed Inst, I-86077 Pozzilli, Italy. RP Gulino, A (reprint author), Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy. EM alberto.gulino@uniroma1.it; jalees@mit.edu RI Ferretti, Elisabetta/G-5413-2013 OI Ferretti, Elisabetta/0000-0001-7265-6429 FU Associazione Italiana per la Ricerca sul Cancro; Telethon [GGP07118]; Istituto Pasteur Cenci Bolognetti; Ministero dell'Istruzione, Universita a della Ricerca; Italian Ministry of Health; NIH [2-P01-CA42063]; American-Italian Cancer Foundation; Marie Curie Outgoing International Fellowship; Ludwig Scholar at MIT FX Vectors and cell lines were kindly provided by F. Stegmeier (pPRIME-CMV-GFP and pPRIME-CMV-GFP-shRB) and S. Lowe (pBabe-hygro, pBabeE1A-hygro, and U2OS rtTA RB.670). We thank K. Hilgendorf and A. Cheung for technical help and M. Levrero, Koch Institute colleagues, and members of the Gulino and Lees laboratories for helpful discussions throughout this work. This project was supported by grants from the Associazione Italiana per la Ricerca sul Cancro; Telethon (GGP07118); Istituto Pasteur Cenci Bolognetti; Ministero dell'Istruzione, Universita a della Ricerca; the Italian Ministry of Health; and the Rome Oncogenomic Center to A.G. and from the NIH (2-P01-CA42063) to J.A.L. A.I. was supported by postdoctoral fellowships from the American-Italian Cancer Foundation and from the Marie Curie Outgoing International Fellowship. J.A.L. is a Ludwig Scholar at MIT. NR 41 TC 78 Z9 80 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR 3 PY 2009 VL 15 IS 3 BP 184 EP 194 DI 10.1016/j.ccr.2009.01.026 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 416IC UT WOS:000263998200006 PM 19249677 ER PT J AU Dhingra, R Pencina, MJ Schrader, P Wang, TJ Levy, D Pencina, K Siwik, DA Colucci, WS Benjamin, EJ Vasan, RS AF Dhingra, Ravi Pencina, Michael J. Schrader, Peter Wang, Thomas J. Levy, Daniel Pencina, Karol Siwik, Deborah A. Colucci, Wilson S. Benjamin, Emelia J. Vasan, Ramachandran S. TI Relations of Matrix Remodeling Biomarkers to Blood Pressure Progression and Incidence of Hypertension in the Community SO CIRCULATION LA English DT Article DE hypertension; collagen; epidemiology; metalloproteinases; risk factors ID CARBOXY-TERMINAL PROPEPTIDE; CARDIOVASCULAR RISK-FACTORS; LEFT-VENTRICULAR STRUCTURE; PROCOLLAGEN TYPE-I; TISSUE INHIBITOR; HEART-DISEASE; METALLOPROTEINASE-1 LEVELS; ANTIHYPERTENSIVE THERAPY; MYOCARDIAL FIBROSIS; MATRIX-METALLOPROTEINASE-9 AB Background Biomarkers of extracellular matrix remodeling are associated with prevalent hypertension in cross-sectional studies, but their relations to longitudinal changes in blood pressure (BP) and hypertension incidence are unknown. Methods and Results We evaluated 595 nonhypertensive Framingham Offspring Study participants (mean age 55 years; 360 women) without prior heart failure or myocardial infarction who underwent routine measurements of plasma tissue inhibitor of metalloproteinase-1 (TIMP-1), metalloproteinase-9 (MMP-9), and procollagen III N-terminal peptide. We related plasma TIMP-1, procollagen III N-terminal peptide, and MMP-9 to the incidence of hypertension and progression of BP by >= 1 category (defined on the basis of the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). On follow-up (4 years), 81 participants (51 women) developed hypertension, and 198 (114 women) progressed to a higher BP category. In multivariable models, a 1-SD increment of log-TIMP-1 was associated with a 50% higher incidence of hypertension (95% CI 1.08 to 2.08) and a 21% (95% CI 1.00 to 1.47) higher risk of BP progression. Individuals in the top TIMP-1 tertile had a 2.15-fold increased risk of hypertension (95% CI 0.99 to 4.68) and 1.68-fold (95% CI 1.05 to 2.70) increased risk of BP progression relative to the lowest tertile. Individuals with detectable MMP-9 had a 1.97-fold higher risk of BP progression (95% CI 1.06 to 3.64) than those with undetectable levels. Plasma procollagen III N-terminal peptide was not associated with hypertension incidence or BP progression. Conclusions In the present community-based sample, higher TIMP-1 and MMP-9 concentrations were associated with BP progression on follow-up. Additional studies are warranted to confirm our findings. (Circulation. 2009; 119: 1101-1107.) C1 [Dhingra, Ravi; Pencina, Michael J.; Wang, Thomas J.; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Dhingra, Ravi] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. [Dhingra, Ravi] Alice Peck Day Mem Hosp, Dept Med, Lebanon, NH USA. [Pencina, Michael J.; Schrader, Peter; Pencina, Karol] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Siwik, Deborah A.; Colucci, Wilson S.] Boston Univ, Sch Med, Myocardial Biol Unit, Boston, MA 02118 USA. [Colucci, Wilson S.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Siwik, Deborah/0000-0002-7166-327X; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [RO1 HL67288, HL080124, 2K24HL04334, 1R01AG028321, RO1HL076784] FX This work was supported through National Heart, Lung, and Blood Institute contracts RO1 HL67288, HL080124, and 2K24HL04334 (Dr Vasan) and 1R01AG028321 and RO1HL076784 (Dr Benjamin). NR 44 TC 31 Z9 36 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 MAR 3 PY 2009 VL 119 IS 8 BP 1101 EP U62 DI 10.1161/CIRCULATIONAHA.108.821769 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 413DC UT WOS:000263772100007 PM 19221217 ER PT J AU Frankel, DS Vasan, RS D'Agostino, RB Benjamin, EJ Levy, D Wang, TJ Meigs, JB AF Frankel, David S. Vasan, Ramachandran S. D'Agostino, Ralph B., Sr. Benjamin, Emelia J. Levy, Daniel Wang, Thomas J. Meigs, James B. TI Resistin, Adiponectin, and Risk of Heart Failure The Framingham Offspring Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE heart failure; resistin; adiponectin; adipokines; epidemiology ID CORONARY-ARTERY-DISEASE; BODY-MASS INDEX; INSULIN-RESISTANCE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; PLASMA ADIPONECTIN; OXIDATIVE STRESS; ADIPOSE-TISSUE; SERUM RESISTIN; OBESITY AB Objectives We tested the association of the adipokines resistin and adiponectin with incident heart failure. Background Abnormal concentrations of adipokines may partially explain the association between obesity and heart failure. Methods We related circulating adipokine concentrations to the incidence of heart failure in 2,739 participants in the Framingham Offspring Study. Results During 6 years of follow-up, 58 participants developed new-onset heart failure. In proportional hazards models ( adjusting for age, sex, blood pressure, antihypertensive treatment, diabetes, smoking, total/high-density lipoprotein cholesterol ratio, prevalent coronary heart disease, valvular heart disease, left ventricular hypertrophy, and estimated glomerular filtration rate) using the lowest third of the resistin distribution as the referent, the hazard ratios for heart failure in the middle and top thirds were 2.89 (95% confidence interval [CI]: 1.05 to 7.92) and 4.01 ( 95% CI: 1.52 to 10.57), respectively ( p = 0.004 for trend). Additional adjustment for body mass index, insulin resistance ( measured with the homeostasis model), C-reactive protein, and B-type natriuretic peptide did not substantively weaken this association ( multivariable hazard ratios [HRs]: 2.62 and 3.74, p = 0.007). In the maximally adjusted model, each SD increment in resistin (7.45 ng/ml) was associated with a 26% increase in heart failure risk ( 95% CI: 1% to 60%). Concentrations of adiponectin were not associated with heart failure ( multivariable HRs: 0.87 and 0.97, p = 0.9). Conclusions Increased circulating concentrations of resistin were associated with incident heart failure, even after accounting for prevalent coronary heart disease, obesity, and measures of insulin resistance and inflammation. The findings suggest a role for resistin in human disease and a novel pathway to heart failure. (J Am Coll Cardiol 2009; 53: 754-62) (C) 2009 by the American College of Cardiology Foundation C1 [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Vasan, Ramachandran S.; D'Agostino, Ralph B., Sr.; Benjamin, Emelia J.; Levy, Daniel; Wang, Thomas J.; Meigs, James B.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; American Diabetes Association; GlaxoSmithKline; Lilly; [2K24HL404334]; [RO1 HL076784]; [1R01 AG028321] FX Supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study ( contract no. N01-HC-25195), 2K24HL404334 (Dr. Vasan), RO1 HL076784 ( Dr. Benjamin), 1R01 AG028321 ( Dr. Benjamin), and an American Diabetes Association Career Development Award ( Dr. Meigs). Dr. D'Agostino has received honoraria from Sanofi-Aventis and serves on advisory boards for Pfizer and Bayer. Dr. Meigs currently has research grants from GlaxoSmithKline and serves on safety boards for GlaxoSmithKline and Lilly. The funding agencies had no influence over the content or conduct of the analysis or the decision to publish the findings. Dr. Frankel had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 47 TC 135 Z9 141 U1 0 U2 4 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 MAR 3 PY 2009 VL 53 IS 9 BP 754 EP 762 DI 10.1016/j.jacc.2008.07.073 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 411RH UT WOS:000263667200004 PM 19245965 ER PT J AU Bourdette, D Simon, J AF Bourdette, Dennis Simon, Jack TI The radiologically isolated syndrome Is it very early multiple sclerosis? SO NEUROLOGY LA English DT Editorial Material ID DIAGNOSTIC-CRITERIA C1 [Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Simon, Jack] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97239 USA. [Bourdette, Dennis; Simon, Jack] Portland VA Med Ctr, Portland, OR USA. RP Bourdette, D (reprint author), Oregon Hlth & Sci Univ, Dept Neurol L226, Portland, OR 97239 USA. EM bourdett@ohsu.edu NR 10 TC 13 Z9 15 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 MAR 3 PY 2009 VL 72 IS 9 BP 780 EP 781 DI 10.1212/01.wnl.0000337255.89622.ce PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 413CZ UT WOS:000263771800001 PM 19073944 ER PT J AU Perez, VI Buffenstein, R Masamsetti, V Leonard, S Salmon, AB Mele, J Andziak, B Yang, T Edrey, Y Friguet, B Ward, W Richardson, A Chaudhuri, A AF Perez, Viviana I. Buffenstein, Rochelle Masamsetti, Venkata Leonard, Shanique Salmon, Adam B. Mele, James Andziak, Blazej Yang, Ting Edrey, Yael Friguet, Bertrand Ward, Walter Richardson, Arlan Chaudhuri, Asish TI Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cysteine oxidation; Heterocephalus glaber; mechanisms of aging; proteasome activity; protein homeostasis ID AGE-RELATED-CHANGES; HYDROGEN-PEROXIDE; DISULFIDE BONDS; LIFE-SPAN; MICE; PROTEASOME; METABOLISM; EXPLAIN; THIOREDOXIN; REDUCTION AB The widely accepted oxidative stress theory of aging postulates that aging results from accumulation of oxidative damage. Surprisingly, data from the longest-living rodent known, naked molerats [MRs; mass 35 g; maximum lifespan (MLSP) > 28.3 years], when compared with mice (MLSP 3.5 years) exhibit higher levels of lipid peroxidation, protein carbonylation, and DNA oxidative damage even at a young age. We hypothesize that age-related changes in protein structural stability, oxidation, and degradation are abrogated over the lifespan of the MR. We performed a comprehensive study of oxidation states of protein cysteines [both reversible (sulfenic, disulfide) and indirectly irreversible (sulfinic/sulfonic acids)] in liver from young and old C57BL/6 mice (6 and 28 months) and MRs (2 and >24 years). Furthermore, we compared interspecific differences in urea-induced protein unfolding and ubiquitination and proteasomal activity. Compared with data from young mice, young MRs have 1.6 times as much free protein thiol groups and similar amounts of reversible oxidative damage to cysteine. In addition, they show less urea-induced protein unfolding, less protein ubiquitination, and higher proteasome activity. Mice show a significant age-related increase in cysteine oxidation and higher levels of ubiquitination. In contrast, none of these parameters were significantly altered over 2 decades in MRs. Clearly MRs have markedly attenuated age-related accrual of oxidation damage to thiol groups and age-associated up-regulation of homeostatic proteolytic activity. These pivotal mechanistic interspecies differences may contribute to the divergent aging profiles and strongly implicate maintenance of protein stability and integrity in successful aging. C1 [Perez, Viviana I.; Buffenstein, Rochelle; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Chaudhuri, Asish] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Buffenstein, Rochelle; Mele, James; Ward, Walter] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Perez, Viviana I.; Buffenstein, Rochelle; Masamsetti, Venkata; Leonard, Shanique; Salmon, Adam B.; Mele, James; Ward, Walter; Richardson, Arlan; Chaudhuri, Asish] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Richardson, Arlan; Chaudhuri, Asish] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. [Friguet, Bertrand] Univ Paris 07, Lab Biol & Biochim Cellulaire Vieillissement, EA 3106, IFR 117, F-75251 Paris 05, France. [Buffenstein, Rochelle; Andziak, Blazej; Yang, Ting; Edrey, Yael] CUNY, Grad Sch, Dept Biol, New York, NY 10016 USA. RP Buffenstein, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. EM buffenstein@uthscsa.edu; chaudhuria@uthscsa.edu FU American Federation for Aging Research (V.I.P.); National Institutes of Health/National Institute on Aging [K07 AG025063 04, AG-022891, AG025362, AG23843, R37 AG26557] FX This work was supported by the American Federation for Aging Research (V.I.P.), and National Institutes of Health/National Institute on Aging Grants K07 AG025063 04 (to A.C.), AG-022891 (to R.B.), AG025362 (to W.W.), AG23843 (to A.R.), and R37 AG26557 (to A.R. and A.C.). NR 43 TC 164 Z9 167 U1 1 U2 41 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 MAR 3 PY 2009 VL 106 IS 9 BP 3059 EP 3064 DI 10.1073/pnas.0809620106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 414DM UT WOS:000263844100018 PM 19223593 ER PT J AU Fogg, MH Wirth, LJ Posner, M Wang, F AF Fogg, Mark H. Wirth, Lori J. Posner, Marshall Wang, Fred TI Decreased EBNA-1-specific CD8+T cells in patients with Epstein-Barr virus-associated nasopharyngeal carcinoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; cytotoxic T lymphocytes; immunotherapy ID NUCLEAR ANTIGEN EBNA1; REGULATORY T-CELLS; ADOPTIVE TRANSFER; EBV; CD4(+); LYMPHOCYTES; EXPRESSION; INHIBITION; RESPONSES; LYMPHOMA AB The Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) is potentially a universal target for immune recognition of EBV-infected normal or malignant cells. EBNA-1-specific CD8+ T-cell responses have been assessed against a few epitopes presented on a limited number of HLA class I alleles. We now assess CD8+ T-cell responses to a complete panel of EBNA-1 peptides in an HLA-characterized population. We detected EBNA-1-specific CD8+ T cells in 10 of 14 healthy donors by analysis of peripheral blood mononuclear cells and EBV-specific T-cell lines. The frequent detection of CD8+ T-cell responses was confirmed by mapping EBNA-1 epitopes and demonstrating HLA class I presentation to CD8+ T cells in 6 of 6 donors, including 2 new EBNA-1 epitopes presented by HLA A0206 and A6802. Importantly, EBNA-1 specific CD8+ T cells were significantly less frequent in EBV-specific T-cell lines from patients with EBV-associated nasopharyngeal carcinoma (3 out of 22, P = 0.0003), whereas the frequency of LMP2-specific responses (14 out of 22) was not significantly different from healthy donors (11 out of 14). EBNA-1-specific CD8+ T-cell responses were rescued in approximately half of nasopharyngeal carcinoma patients by peptide and cytokine stimulation of peripheral blood mononuclear cells, suggesting these EBNA-1-specific CD8+ T cells were functionally defective in their response to EBV-infected cells. These results indicate that humans normally mount a significant EBNA-1-specific CD8+ T-cell response to EBV infection, but the immune response to this tumor antigen has been significantly altered in nasopharyngeal carcinoma patients. Overcoming this defect in EBV-specific immunity may prevent or enhance treatment of EBV-associated nasopharyngeal carcinoma. C1 [Fogg, Mark H.; Wang, Fred] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wirth, Lori J.; Posner, Marshall] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Wang, F (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. EM fwang@rics.bwh.harvard.edu FU National Institutes of Health [CA68051]; Dana-Farber Cancer Institute Friends of Head and Neck Cancer Research Award FX We thank Rosemary Costello and Sonia Kim for managing the clinical sample collection, Christian Brander and Nicole Frahm for providing peptidesandtechnical advice, EllisReinherzandRebeccaHusseyfor providing 721.221 cells expressing individual HLA class I alleles, Yi Li for assistance with the statistical analyses, the Brigham and Women's Hospital Tissue Typing Laboratory for HLA class I typing, and Ashok Khatri at the Massachusetts General Hospital peptide core facility for peptide synthesis. This work was supported by grants from the National Institutes of Health (CA68051) and a Dana-Farber Cancer Institute Friends of Head and Neck Cancer Research Award. NR 28 TC 31 Z9 31 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 2009 VL 106 IS 9 BP 3318 EP 3323 DI 10.1073/pnas.0813320106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 414DM UT WOS:000263844100062 PM 19211798 ER PT J AU Hua, M Peluffo, G Chen, HY Gelman, R Schnitt, S Polyak, K AF Hua, Min Peluffo, Guillermo Chen, Haiyan Gelman, Rebecca Schnitt, Stuart Polyak, Kornelia TI Role of COX-2 in epithelial-stromal cell interactions and progression of ductal carcinoma in situ of the breast SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast cancer; stroma; tumor progression; DCIS; celecoxib ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; KAPPA-B ACTIVATION; CANCER DEVELOPMENT; CYCLOOXYGENASE-2 EXPRESSION; TUMOR PROGRESSION; PREVENTION; MICROENVIRONMENT; ANGIOGENESIS; INHIBITION; TRANSITION AB Epithelial-stromal cell interactions have an important role in breast tumor progression, but the molecular mechanisms underlying these effects are just beginning to be understood. We previously described that fibroblasts promote, whereas normal myoepithelial cells inhibit, the progression of ductal carcinoma in situ (DCIS) to invasive breast carcinomas by using a xenograft model of human DCIS. Here, we report that the tumor growth and progression-promoting effects of fibroblasts are at least in part due to increased COX-2 expression in tumor epithelial cells provoked by their interaction with fibroblasts. Up-regulation of COX-2 in DCIS xenografts resulted in increased VEGF and MMP14 expression, which may contribute to the larger weight and invasive histology of COX-2-expressing tumors. Administration of celecoxib, a selective COX-2 inhibitor, to tumor-bearing mice decreased xenograft tumor weight and inhibited progression to invasion. Coculture of fibroblasts with DCIS epithelial cells enhanced their motility and invasion, and this change was associated with increased MMP14 expression and MMP9 protease activity. We identified the NF-kappa B pathway as one of the mediators of stromal fibroblast-derived signals regulating COX-2 expression in tumor epithelial cells. Inhibition of NF-kappa B and COX-2 activity and down-regulation of MMP9 expression attenuated the invasion-promoting effects of fibroblasts. These findings support a role for COX-2 in promoting the progression of DCIS to invasive breast carcinomas, and suggest that therapeutic targeting of the NF-kappa B and prostaglandin signaling pathways might be used for the treatment and prevention of breast cancer. C1 [Hua, Min; Peluffo, Guillermo; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Haiyan; Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hua, Min; Schnitt, Stuart; Polyak, Kornelia] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Haiyan; Gelman, Rebecca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Peluffo, Guillermo] Univ Buenos Aires, Angel Honorio Roffo Oncol Inst, Buenos Aires, DF, Argentina. [Schnitt, Stuart] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kornelia.polyak@dfci.harvard.edu FU National Institutes of Health [CA89393, CA94074, CA116235, NO2-CO-41101]; Department of Defense [W81XWH-07-1-0294]; American Cancer Society [RSG-05-154-01-MGO]; Susan G. Komen Breast Cancer Foundation Fellowship [PDF042234]; International Union Against Cancer International Cancer Technology Transfer fellowship FX We thank Natasha Pliss for help with immunohistochemistry; Dr. Jerry Shay (University of Texas Southwestern Medical Center, Dallas, TX) for HME50 cells; Drs. John Mountz (University of Alabama, Birmingham, AL), and Steven Goldring (Beth-Israel Deaconess Medical Center, Boston, MA) for providing us with primary cultures derived from rheumatoid arthritis patients; Dr. Mark Ewen (Dana-Farber Cancer Institute, Boston, MA) for his generous gift of the I kappa B*-expressing adenoviral vector; and the Broad Institute TRC for shRNA constructs. This work was supported in part by National Institutes of Health Grants CA89393, CA94074, and CA116235, Department of Defense Grant W81XWH-07-1-0294, and American Cancer Society Grant RSG-05-154-01-MGO (to K. P.); the Susan G. Komen Breast Cancer Foundation Fellowship PDF042234 (to M. H.); and an International Union Against Cancer International Cancer Technology Transfer fellowship and National Institutes of Health Grant NO2-CO-41101 (to G. P.). NR 33 TC 5 Z9 5 U1 1 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 MAR 3 PY 2009 VL 106 IS 9 BP 3372 EP 3377 DI 10.1073/pnas.0813306106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 414DM UT WOS:000263844100071 ER PT J AU Kruger, B Krick, S Dhillon, N Lerner, SM Ames, S Bromberg, JS Lin, M Walsh, L Vella, J Fischereder, M Kramer, BK Colvin, RB Heeger, PS Murphy, BT Schroppel, B AF Krueger, Bernd Krick, Stefanie Dhillon, Navdeep Lerner, Susan M. Ames, Scott Bromberg, Jonathan S. Lin, Marvin Walsh, Liron Vella, John Fischereder, Michael Kraemer, Bernhard K. Colvin, Robert B. Heeger, Peter S. Murphy, Barbara T. Schroeppel, Bernd TI Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE delayed graft function; high mobility group box-1 ID DELAYED GRAFT FUNCTION; RENAL-TRANSPLANTATION; ISCHEMIA/REPERFUSION INJURY; LIVER ISCHEMIA; IMMUNE-SYSTEM; TLR4; TOLL-LIKE-RECEPTOR-4; POLYMORPHISMS; INFLAMMATION; PROTEIN AB While studies in animal models have linked Toll-like receptor (TLR) 4 signaling to kidney injury induced by ischemia and reperfusion, the relevance of TLR4 activation to allograft injury in human kidney transplants is unknown. Here we show that TLR4 is constitutively expressed within all donor kidneys but is significantly higher in deceased-, compared with living-donor organs. Tubules from deceased- but not living-donor kidneys also stained positively for high-mobility group box-1 (HMGB1), a known endogenous TLR4 ligand. In vitro stimulation of human tubular cells with HMGB1, in a TLR4-dependent system, confirmed that HMGB1 can stimulate proinflammatory responses through TLR4. To assess the functional significance of TLR4 in human kidney transplantation, we determined whether TLR4 mutations that confer diminished affinity for HMGB1 influence intragraft gene-expression profiles and immediate graft function. Compared with kidneys expressing WT alleles, kidneys with a TLR4 loss-of-function allele contained less TNF alpha, MCP-1, and more heme oxygenase 1 (HO-1), and exhibited a higher rate of immediate graft function. These results represent previously undetected evidence that donor TLR4 contributes to graft inflammation and sterile injury following cold preservation and transplantation in humans. Targeting TLR4 signaling may have value in preventing or treating postischemic acute kidney injury after transplantation. C1 [Krueger, Bernd; Krick, Stefanie; Dhillon, Navdeep; Lin, Marvin; Walsh, Liron; Heeger, Peter S.; Murphy, Barbara T.; Schroeppel, Bernd] Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA. [Lerner, Susan M.; Ames, Scott; Bromberg, Jonathan S.; Heeger, Peter S.; Murphy, Barbara T.; Schroeppel, Bernd] Mt Sinai Sch Med, Inst Transplantat, New York, NY 10029 USA. [Vella, John] Maine Med Ctr, Div Nephrol, Portland, ME 04102 USA. [Fischereder, Michael] Univ Munich, Med Poliklin Innenstadt Munchen, Munich, Germany. [Krueger, Bernd; Kraemer, Bernhard K.] Klinikum Ruhr Univ Bochum, Med Klin 1, Marienhosp Herne, Bochum, Germany. [Colvin, Robert B.] Pathol Res Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schroppel, B (reprint author), Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA. EM bernd.schroppel@mssm.edu RI Kruger, Bernd/F-5781-2011; OI Ames, Scott/0000-0002-2331-4972 FU Satellite Healthcare; National Institutes of Health [UOI AI070107-01] FX For their assistance in enrollment and sample collection, the authors thank the surgical members of the Mount Sinai transplant institute: Benoit Blondeau, Ana Carolina del Pozo, Pablo Uva, and Hiroshi Sogawa. We thank Dr. Detlef Schlondorff for the support in writing the manuscript. This work is supported by a Satellite Healthcare research grant (to B. S.) and a National Institutes of Health research grant to B. T. M. (UOI AI070107-01). NR 45 TC 168 Z9 185 U1 0 U2 15 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 MAR 3 PY 2009 VL 106 IS 9 BP 3390 EP 3395 DI 10.1073/pnas.0810169106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 414DM UT WOS:000263844100074 PM 19218437 ER PT J AU Goldberg, BD Nezam, SMRM Jillella, P Bouma, BE Tearney, GJ AF Goldberg, Brian D. Nezam, S. M. Reza Motaghian Jillella, Priyanka Bouma, Brett E. Tearney, Guillermo J. TI Miniature swept source for point of care Optical Frequency Domain Imaging SO OPTICS EXPRESS LA English DT Article ID FINE-NEEDLE ASPIRATION; PALPABLE BREAST MASSES; COHERENCE TOMOGRAPHY; SEMICONDUCTOR-LASER; SPEED; SENSITIVITY; NM AB Point of care (POC) medical technologies require portable, small, robust instrumentation for practical implementation. In their current embodiment, optical frequency domain imaging (OFDI) systems employ large form-factor wavelength-swept lasers, making them impractical in the POC environment. Here, we describe a first step toward a POC OFDI system by demonstrating a miniaturized swept-wavelength source. The laser is based on a tunable optical filter using a reflection grating and a miniature resonant scanning mirror. The laser achieves 75 nm of bandwidth centered at 1340 nm, a 0.24 nm instantaneous line width, a 15.3 kHz repetition rate with 12 mW peak output power, and a 30.4 kHz A-line rate when utilizing forward and backward sweeps. The entire laser system is approximately the size of a deck of cards and can operate on battery power for at least one hour. (C) 2009 Optical Society of America C1 [Goldberg, Brian D.; Nezam, S. M. Reza Motaghian; Jillella, Priyanka; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Goldberg, Brian D.; Nezam, S. M. Reza Motaghian; Jillella, Priyanka; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Goldberg, Brian D.; Bouma, Brett E.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM gtearney@partners.org FU Medical Free Electron Laser Program [FA9550-041- 0079]; Physical Sciences Inc. (NIH) [1 R43 CA114896-01]; NIH [1 F31 EB005141-01]; Terumo Corporation FX Funding for this work was provided by the Medical Free Electron Laser Program (FA9550-041- 0079), Physical Sciences Inc. (NIH 1 R43 CA114896-01), the NIH (1 F31 EB005141-01), and Terumo Corporation. The authors would also like to thank Ben Vakoc and William Oh for their guidance in OFDI imaging and swept-source laser design. Currently SM Reza Motaghianezam is with the Department of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125. NR 38 TC 15 Z9 16 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD MAR 2 PY 2009 VL 17 IS 5 BP 3619 EP 3629 DI 10.1364/OE.17.003619 PG 11 WC Optics SC Optics GA 417QJ UT WOS:000264090900065 PM 19259202 ER PT J AU Liteplo, AS Marill, KA Villen, T Miller, RM Murray, AF Croft, PE Capp, R Noble, VE AF Liteplo, Andrew S. Marill, Keith A. Villen, Tomas Miller, Robert M. Murray, Alice F. Croft, Peter E. Capp, Roberta Noble, Vicki E. TI Emergency Thoracic Ultrasound in the Differentiation of the Etiology of Shortness of Breath (ETUDES): Sonographic B-lines and N-terminal Pro-brain-type Natriuretic Peptide in Diagnosing Congestive Heart Failure SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Convention of the American-Institute-of-Ultrasound-in-Medicine CY MAR 13-15, 2008 CL San Diego, CA SP Amer Inst Ultrasound Med DE ultrasound; emergency; dyspnea; congestive heart failure; NT-ProBNP; comet tails ID EXTRAVASCULAR LUNG WATER; ALVEOLAR-INTERSTITIAL SYNDROME; COMET-TAIL ARTIFACT; BODY-MASS INDEX; PULMONARY-EDEMA; DEPARTMENT PRIDE; ACUTE DYSPNEA; SIGN; DISEASE; BNP AB Sonographic thoracic B-lines and N-terminal pro-brain-type natriuretic peptide (NT-ProBNP) have been shown to help differentiate between congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD). The authors hypothesized that ultrasound (US) could be used to predict CHF and that it would provide additional predictive information when combined with NT-ProBNP. They also sought to determine optimal two- and eight-zone scanning protocols when different thresholds for a positive scan were used. This was a prospective, observational study of a convenience sample of adult patients presenting to the emergency department (ED) with shortness of breath. Each patient had an eight-zone thoracic US performed by one of five sonographers, and serum NT-ProBNP levels were measured. Chart review by two physicians blinded to the US results served as the criterion standard. The operating characteristics of two- and eight-zone thoracic US alone, compared to, and combined with NT-ProBNP test results for predicting CHF were calculated using both dichotomous and interval likelihood ratios (LRs). One-hundred patients were enrolled. Six were excluded because of incomplete data. Results of 94 patients were analyzed. A positive eight-zone US, defined as at least two positive zones on each side, had a positive likelihood ratio (LR+) of 3.88 (99% confidence interval [CI] = 1.55 to 9.73) and a negative likelihood ratio (LR-) of 0.5 (95% CI = 0.30 to 0.82), while the NT-ProBNP demonstrated a LR+ of 2.3 (95% CI = 1.41 to 3.76) and LR- of 0.24 (95% CI = 0.09 to 0.66). Using interval LRs for the eight-zone US test alone, the LR for a totally positive test (all eight zones positive) was infinite and for a totally negative test (no zones positive) was 0.22 (95% CI = 0.06 to 0.80). For two-zone US, interval LRs were 4.73 (95% CI = 2.10 to 10.63) when inferior lateral zones were positive bilaterally and 0.3 (95% CI = 0.13 to 0.71) when these were negative. These changed to 8.04 (95% CI = 1.76 to 37.33) and 0.11 (95% CI = 0.02 to 0.69), respectively, when congruent with NT-ProBNP. Bedside thoracic US for B-lines can be a useful test for diagnosing CHF. Predictive accuracy is greatly improved when studies are totally positive or totally negative. A two-zone protocol performs similarly to an eight-zone protocol. Thoracic US can be used alone or can provide additional predictive power to NT-ProBNP in the immediate evaluation of dyspneic patients presenting to the ED. C1 [Liteplo, Andrew S.; Marill, Keith A.; Villen, Tomas; Miller, Robert M.; Murray, Alice F.; Croft, Peter E.; Capp, Roberta; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Ultrasound, Boston, MA 02114 USA. RP Liteplo, AS (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Ultrasound, Boston, MA 02114 USA. EM aliteplo@partners.org NR 39 TC 85 Z9 87 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2009 VL 16 IS 3 BP 201 EP 210 DI 10.1111/j.1553-2712.2008.00347.x PG 10 WC Emergency Medicine SC Emergency Medicine GA 414HZ UT WOS:000263855800002 PM 19183402 ER PT J AU Lopez, L Katz, JT AF Lopez, Lenny Katz, Joel T. TI Perspective: Creating an Ethical Workplace: Reverberations of Resident Work Hours Reform SO ACADEMIC MEDICINE LA English DT Article ID DUTY HOURS REGULATIONS; INTERNAL-MEDICINE; PATIENT-CARE; BURNOUT; SATISFACTION; EDUCATION; EMPATHY; PROGRAM; IMPACT; PERCEPTIONS AB Medical professionals are a community of highly educated individuals with a commitment to a core set of ideals and principles. This community provides both technical and ethical socialization. The development of ethical physicians is highly linked to experiences in the training period. Moral traits are situation-sensitive psychological and behavioral dispositions. The consequence of long duty hours on the moral development of physicians is less understood. The clinical environment of medical training programs can be so intense as to lead to conditions that may actually deprofessionalize trainees. The dynamic relationship between individual character traits and the situational dependence of their expression suggests that a systems approach will help promote and nurture moral development. Ethical behavior can be supported by systems that make it more difficult to veer from the ideal. Work hours limits are a structural change that will help preserve public safety by preventing physicians from taking the moral shortcuts that can occur with increasing work and time pressures. Work hours rules are beneficial but insufficient to optimize an ethical work and training environment. Additional measures need to be put in place to ensure that ethical tensions are not created between the patient's well-being and the resident's adherence to work hours rules. The ethical ideals of physician autonomy, selflessness, and accountability to the patient must be protected through the judicious and flexible use of work hours limits, physician extenders, census caps, nonteaching services, and high-quality handoffs. C1 [Lopez, Lenny] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny; Katz, Joel T.] Harvard Univ, Sch Med, Boston, MA USA. [Lopez, Lenny; Katz, Joel T.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM llopez1@partners.org FU Institutional National Research Service Award [5 T32 HP11001-19] FX Dr. Lopez acknowledges the Support of an Institutional National Research Service Award #5 T32 HP11001-19. NR 41 TC 10 Z9 10 U1 0 U2 5 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 MAR PY 2009 VL 84 IS 3 BP 315 EP 319 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 466IP UT WOS:000267655100012 PM 19240437 ER PT J AU Fortuna, RJ Ting, DY Kaellber, DC Simon, SR AF Fortuna, Robert J. Ting, David Y. Kaellber, David C. Simon, Steven R. TI Characteristics of Medicine-Pediatrics Practices: Results From the National Ambulatory Medical Care Survey SO ACADEMIC MEDICINE LA English DT Article ID COMBINED INTERNAL-MEDICINE; PHYSICIANS; PROGRAMS; CHILDREN; TRENDS AB Background Combined medicine-pediatrics (med-peds) training has existed for 40 years, yet little is known about national med-peds practices. A more comprehensive understanding of med-peds practices is important to inform medical students and guide evolving curricula and accreditation standards. Method The authors used data from the National Ambulatory Medical Care Survey from 2000 to 2006 to characterize the age distribution and types of visits seen by med-peds, internal medicine, pediatric, and family physicians. Results Forty-three percent of visits to med-peds physicians were from children <= 18 years of age. Compared with family physicians, med-peds physicians saw a higher proportion of infants and toddlers <= 2 years of age (21.0% versus 3.7%; P = .002) and children <= 18 years of age (42.9% versus 15.5%; P = .002), but they treated fewer adults age 65 or older (13.8% versus 21.3%; P = .013). Compared with internists, med-peds physicians saw a greater percentage of visits from adults 19 to 64 years of age (75.8% versus 61.2%) and fewer visits from patients age 65 or older (24.2% versus 38.8%; P = .006). Med-peds physicians, like family physicians and pediatricians, most commonly treated patients for acute problems and reported high levels of continuity of care for patients-pediatric (93.6%) and adult (94.6%). Conclusions Med-peds physicians care for a considerable proportion of pediatric patients while maintaining high levels of continuity of care for adult and pediatric patients. Within their practices, med-peds physicians treat a larger percentage of pediatric patients than do family physicians, but they see a smaller percentage of elderly patients. C1 [Ting, David Y.] Massachusetts Gen Hosp, Harvard Massachusetts Gen Hosp, Med Pediat Residency Program, Boston, MA 02114 USA. [Kaellber, David C.] Case Western Reserve Univ, MetroHlth Syst, Cleveland, OH 44106 USA. [Simon, Steven R.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Simon, Steven R.] Harvard Pilgrim Hlth Care, Boston, MA USA. EM rfortuna@post.harvard.edu FU Institutional National Research Service Award [5 T32 HP11001-18] FX An Institutional National Research Service Award, #5 T32 HP11001-18, supported Dr. Fortuna. NR 12 TC 4 Z9 4 U1 0 U2 0 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 MAR PY 2009 VL 84 IS 3 BP 396 EP 401 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 466IP UT WOS:000267655100025 PM 19240455 ER PT J AU Zuckerman, KE Boudreau, AA Lipstein, EA Kuhlthau, KA Perrin, JM AF Zuckerman, Katharine E. Boudreau, Alexy Arauz Lipstein, Ellen A. Kuhlthau, Karen A. Perrin, James M. TI Household Language, Parent Developmental Concerns, and Child Risk for Developmental Disorder SO ACADEMIC PEDIATRICS LA English DT Article DE assessment; behavior; development; disparities; Hispanic; language ID HEALTH-CARE NEEDS; YOUNG-CHILDREN; ENGLISH PROFICIENCY; US CHILDREN; SERVICES; ACCESS; DISPARITIES; HOME; SURVEILLANCE; INSURANCE AB Background.-Provider elicitation of parent developmental and behavioral (DB) concerns is the foundation of DB surveillance. Language differences may affect whether providers assess parental DB concerns. Objective.-The aim of this study was to compare children in English versus Spanish primary language households by risk for DB disorder and provider elicitation of parental developmental and behavioral concerns. Methods.-The 2003 National Survey of Children's Health was used to compare 29 692 children, aged 0 to 71 months, who received preventive care in the previous 12 months and were in English versus Spanish primary language households. Using logistic regression, we tested the association of household primary language with child risk of developmental and behavioral disorder and parent-reported elicitation of developmental and behavioral concerns at health care visits. Results.-After adjusting for sociodemographic differences, children in Spanish primary language households were less likely than children in English primary language households to be at risk for DB disorder (40.5% vs 40.8%; AOR [adjusted odds ratio] 0.68, 95% confidence interval [CI], 0.55-0.85). Parents in Spanish primary language households reported less provider elicitation of developmental and behavioral concerns compared to all English primary language households (31.0% vs 43.7%; AOR 0.70, 95% CI, 0.57-0.85), but similar rates of elicitation compared to Hispanic English primary language households. Among households with children at moderate/high risk for DB disorder, parents in Spanish primary language households reported less elicitation of concerns than parents in English primary language households (AOR 0.63, 95% CI, 0.41-0.96). Conclusion.-Parents in Spanish primary language households reported lower child risk for developmental and behavioral disorder and less provider elicitation of developmental and behavioral concerns. These findings suggest that primary language may affect risk for developmental and behavioral disorder and likelihood of DB Surveillance in children. C1 [Zuckerman, Katharine E.; Boudreau, Alexy Arauz; Lipstein, Ellen A.; Kuhlthau, Karen A.; Perrin, James M.] Harvard Univ, Sch Med, Dept Pediat,MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02115 USA. RP Zuckerman, KE (reprint author), 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM kzuckerman@partners.org FU Health Resources and Services Administration, Department of Health and Human Services [T32 HP10018] FX This work was supported in part by a National Research Service Award (T32 HP10018) from the Health Resources and Services Administration, Department of Health and Human Services, to the Harvard Pediatcic Health Services Research Fellowship. We thank Jonathan Winickoff, MD. for his comments and manuscript review and the Child and Adolescent Health Measurement Intiative Data Resource Center at Oregon Health & Science University for use of their dataset. NR 31 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAR-APR PY 2009 VL 9 IS 2 BP 97 EP 105 PG 9 WC Pediatrics SC Pediatrics GA 573KZ UT WOS:000275913600007 PM 19329100 ER PT J AU Keene, CD Chang, RC Leverenz, JB Kopyov, O Perlman, S Hevner, R Born, DE Bird, TD Montine, TJ AF Keene, C. Dirk Chang, Rubens C. Leverenz, James B. Kopyov, Oleg Perlman, Susan Hevner, Robert F. Born, Donald E. Bird, Thomas D. Montine, Thomas J. TI A patient with Huntington's disease and long-surviving fetal neural transplants that developed mass lesions SO ACTA NEUROPATHOLOGICA LA English DT Article DE Huntington's disease; Human fetal neural transplantation; Graft survival and differentiation; Transplant overgrowth; Peripheral nerve co-graft ID AUTOLOGOUS ADRENAL-MEDULLA; PARKINSONS-DISEASE; INTRASTRIATAL COGRAFTS; PERIPHERAL-NERVE; FOLLOW-UP; ALLOGRAFTS; PATHOLOGY; SAFETY; NEUROTRANSPLANTATION; STRIATUM AB Transplantation of human fetal neural tissue into adult neostriatum is an experimental therapy for Huntington's disease (HD). Here we describe a patient with HD who received ten intrastriatal human fetal neural transplants and, at one site, an autologous sural nerve co-graft. Although initially clinically stable, she developed worsening asymmetric upper motor neuron symptoms in addition to progression of HD, and ultimately died 121 months post transplantation. Eight neural transplants, up to 2.9 cm, and three ependymal cysts, up to 2.0 cm, were identified. The autologous sural nerve co-graft was found adjacent to the largest mass lesion, which, along with the ependymal cyst, exhibited pronounced mass effect on the internal capsules bilaterally. Grafts were composed of neurons and glia embedded in disorganized neuropil; robust Y chromosome labeling was present in a subset of grafts and cysts. The graft-host border was discrete, and there was no evidence of graft rejection or HD pathologic changes within donor neurons. This report, for the first time, highlights the potential for graft overgrowth in a patient receiving fetal neural transplantation. C1 [Keene, C. Dirk; Chang, Rubens C.; Hevner, Robert F.; Born, Donald E.; Montine, Thomas J.] Univ Washington, Med Ctr, Harborview Med Ctr, Dept Pathol,Div Neuropathol, Seattle, WA 98104 USA. [Leverenz, James B.; Bird, Thomas D.] Univ Washington, Med Ctr, Dept Neurol, VA Puget Sound Hlth Care Syst, Seattle, WA 98104 USA. [Hevner, Robert F.] Univ Washington, Med Ctr, Dept Neurosurg, Seattle Childrens Hosp, Seattle, WA 98104 USA. [Hevner, Robert F.] Reg Med Ctr, Seattle, WA 98104 USA. [Kopyov, Oleg] St Johns Reg Med Ctr, Inst Neurosci, Oxnard, CA 93030 USA. [Perlman, Susan] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. RP Keene, CD (reprint author), Univ Washington, Med Ctr, Harborview Med Ctr, Dept Pathol,Div Neuropathol, Box 359791, Seattle, WA 98104 USA. EM cdkeene@u.washington.edu RI Keene, Christopher/N-1806-2015 FU NIA NIH HHS [T32 AG000238, P50-AG005136, 5T32-AG000238, P50 AG005136, P50 AG005136-25] NR 27 TC 42 Z9 45 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAR PY 2009 VL 117 IS 3 BP 329 EP 338 DI 10.1007/s00401-008-0465-0 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 409YA UT WOS:000263540500010 PM 19057918 ER PT J AU Nemeth, T Kovacs, M Kertesz, Z Szabo, M Settleman, J Mocsai, A AF Nemeth, T. Kovacs, M. Kertesz, Zs Szabo, M. Settleman, J. Mocsai, A. TI The role of p190RhoGAP in neutrophils SO ACTA PHYSIOLOGICA HUNGARICA LA English DT Meeting Abstract C1 [Nemeth, T.; Kovacs, M.; Kertesz, Zs; Szabo, M.; Mocsai, A.] Semmelweis Univ, Dept Physiol, Budapest, Hungary. [Settleman, J.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Settleman, J.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AKADEMIAI KIADO RT PI BUDAPEST PA PRIELLE K U 19, PO BOX 245,, H-1117 BUDAPEST, HUNGARY SN 0231-424X J9 ACTA PHYSIOL HUNG JI Acta Physiol. Hung. PD MAR PY 2009 VL 96 IS 1 BP 109 EP 109 PG 1 WC Physiology SC Physiology GA 413LK UT WOS:000263794400065 ER PT J AU Portugal, R Oliva, E AF Portugal, Raque Oliva, Esther TI Calretinin Diagnostic Utility in the Female Genital Tract SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE calretinin; female genital tract; differential diagnosis; immunohistochemistry ID CORD-STROMAL TUMORS; USEFUL IMMUNOHISTOCHEMICAL MARKER; EPITHELIAL MEMBRANE ANTIGEN; SEROUS PAPILLARY CARCINOMA; NORMAL ENDOMETRIAL STROMA; PROBABLE WOLFFIAN ORIGIN; GRANULOSA-CELL TUMORS; SMOOTH-MUSCLE TUMORS; MESONEPHRIC ADENOCARCINOMA; CLINICOPATHOLOGICAL ANALYSIS AB The utility of calretinin was first described in the diagnosis of mesothelioma. In the female genital tract, calretinin was initially reported in Wolffian remnants and related lesions and later used in the diagnosis of sex cord stromal tumors of the ovary, endometrial stromal tumors with sex cord-like differentiation, and uterine tumors resembling sex cord tumors of the ovary. This review discusses calretinin expression in normal tissues of the female genital tract and highlights its potential utility ill the diagnosis of these subsets of neoplasms with emphasis to tumors that may constitute a problem in their differential diagnosis. In particular, the limited utility of calretinin in the diagnosis of sex cord stromal tumors of the ovary, in the differential diagnosis between mesothelioma and serous tumors involving the ovary and/or peritoneum, and in the differential diagnosis between Wolffian lesions and endometrial carcinoma are addressed. C1 [Portugal, Raque; Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM raquelvpt@hotmail.com NR 115 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD MAR PY 2009 VL 16 IS 2 BP 118 EP 124 PG 7 WC Pathology SC Pathology GA 412AV UT WOS:000263696500005 PM 19550372 ER PT J AU Argyrakopoulou, G Doupis, J AF Argyrakopoulou, Georgia Doupis, John TI DPP4 inhibitors: from sitagliptin monotherapy to the new alogliptin-pioglitazone combination therapy SO ADVANCES IN THERAPY LA English DT Review DE alogliptin; diabetes mellitus; DPP4 inhibitors; incretin; metformin; pioglitazone; saxagliptin; sitagliptin; vildagliptin ID DIPEPTIDYL PEPTIDASE-4 INHIBITOR; GLUCAGON-LIKE PEPTIDE-1; IMPROVES GLYCEMIC CONTROL; DRUG-NAIVE PATIENTS; DEPENDENT INSULINOTROPIC POLYPEPTIDE; BETA-CELL FUNCTION; DOUBLE-BLIND; RENAL-INSUFFICIENCY; INCRETIN HORMONES; DIABETIC-PATIENTS AB Diabetes mellitus (DM) is currently considered to be an epidemic disease. A safe and effective treatment has long been sought by scientists. Incretin mimetics and dipeptidyl peptidase-4 (DPP4) inhibitors represent a new class of agents that have recently been included as antidiabetic drugs. Although only a limited number of studies exist regarding the treatment of DM based on the incretin effect, DPP4 inhibitors have so far proved to be safe and effective, both when administered alone or in combination with other antidiabetic medication. This review focuses on incretin-effect physiology, as well as the DPP4 inhibitors, from sitagliptin to the new alogliptin-pioglitazone combination agent, given as monotherapy and in combination with other antidiabetic agents. C1 [Doupis, John] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Argyrakopoulou, Georgia] Kapodistriakon Univ, Sch Med, Laikon Hosp, Athens, Greece. RP Doupis, J (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM John.Doupis@joslin.harvard.edu NR 47 TC 3 Z9 5 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0741-238X J9 ADV THER JI Adv. Ther. PD MAR PY 2009 VL 26 IS 3 BP 272 EP 280 DI 10.1007/s12325-009-0009-6 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 432OT UT WOS:000265144300003 PM 19259628 ER PT J AU Trief, PM Teresi, JA Eimicke, JP Shea, S Weinstock, RS AF Trief, Paula M. Teresi, Jeanne A. Eimicke, Joseph P. Shea, Steven Weinstock, Ruth S. TI Improvement in diabetes self-efficacy and glycaemic control using telemedicine in a sample of older, ethnically diverse individuals who have diabetes: the IDEATel project SO AGE AND AGEING LA English DT Article DE diabetes; self-efficacy; glycaemic control; elderly ID COLUMBIA-UNIVERSITY INFORMATICS; PSYCHOMETRIC PROPERTIES; CASE-MANAGEMENT; CARE; EDUCATION; OUTCOMES; ADULTS; TRIAL; INTERVENTION; PREVALENCE AB Background: with increasing prevalence of diabetes in older people, it is important to understand factors that affect their outcomes. The Informatics for Diabetes Education and Telemedicine (IDEATel) project is a demonstration project to evaluate the feasibility and effectiveness of telemedicine with diverse, medically underserved, older diabetes patients. Subjects were randomised to telemedicine case management or usual care. This intervention has been shown to result in improved medical outcomes and self-efficacy. Self-efficacy refers to one's belief that (s)he can successfully engage in a behaviour. Self-efficacy has been shown to relate to behaviour change and glycaemic control in middle-aged individuals, but not studied in older individuals. Objectives: to assess whether (a) diabetes self-efficacy relates to the primary medical outcome of glycaemic control, and to secondary outcomes (blood pressure and cholesterol), and (b) whether, after an intervention, change in diabetes self-efficacy relates to change in these medical outcomes in a group of older, ethnically diverse individuals. Methods: three waves of longitudinal data from participants in IDEATel were analysed. Results: diabetes self-efficacy at baseline correlated with glycaemic control, blood pressure and cholesterol. An increase in diabetes self-efficacy over time was related to an improvement in glycaemic control (P < 0.0001), but not in blood pressure and lipid levels. The intervention was significantly related to improved self-efficacy over time (P < 0.0001), and both directly (P = 0.022) and indirectly through self-efficacy (P < 0.001) to improved glycaemic control. The mediation effect of self-efficacy was also significant (P < 0.004). Conclusions: diabetes self-efficacy is a relevant construct for older diabetes patients. Thus, interventions that target enhanced self-efficacy may also result in improved glycaemic control. C1 [Trief, Paula M.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Trief, Paula M.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. [Teresi, Jeanne A.] Columbia Univ, Stroud Ctr, Bronx, NY 10471 USA. [Teresi, Jeanne A.] New York State Psychiat Inst & Hosp, Div Res, Hebrew Home Aged Riverdale, Bronx, NY 10471 USA. [Shea, Steven] Columbia Univ, Mailman Sch Publ Hlth, Dept Med & Publ Hlth, New York, NY 10032 USA. [Weinstock, Ruth S.] Joslin Diabet Ctr, Dept Med, Syracuse, NY 13210 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Vet Affairs Med Ctr, Syracuse, NY 13210 USA. RP Trief, PM (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM triefp@upstate.edu NR 34 TC 49 Z9 49 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD MAR PY 2009 VL 38 IS 2 BP 219 EP 225 DI 10.1093/ageing/afn299 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 410UD UT WOS:000263602900016 PM 19171951 ER PT J AU Rousseau, CM Lockhart, DW Listgarten, J Maley, SN Kadie, C Learn, GH Nickle, DC Heckerman, DE Deng, W Brander, C Ndung'u, T Coovadia, H Goulder, PJR Korber, BT Walker, BD Mullins, JI AF Rousseau, Christine M. Lockhart, David W. Listgarten, Jennifer Maley, Stephen N. Kadie, Carl Learn, Gerald H. Nickle, David C. Heckerman, David E. Deng, Wenjie Brander, Christian Ndung'u, Thumbi Coovadia, Hoosen Goulder, Philip J. R. Korber, Bette T. Walker, Bruce D. Mullins, James I. TI Rare HLA Drive Additional HIV Evolution Compared to More Frequent Alleles SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTE ESCAPE VARIANTS; CLASS-I SUPERTYPES; TYPE-1 INFECTION; CTL ESCAPE; VIRAL LOAD; DISEASE PROGRESSION; IMMUNE ESCAPE; TRANSMISSION; GAG AB HIV-1 can evolve HLA-specific escape variants in response to HLA-mediated cellular immunity. HLA alleles that are common in the host population may increase the frequency of such escape variants at the population level. When loss of viral fitness is caused by immune escape variation, these variants may revert upon infection of a new host who does not have the corresponding HLA allele. Furthermore, additional escape variants may appear in response to the nonconcordant HLA alleles. Because individuals with rare HLA alleles are less likely to be infected by a partner with concordant HLA alleles, viral populations infecting hosts with rare HLA alleles may undergo a greater amount of evolution than those infecting hosts with common alleles due to the loss of preexisting escape variants followed by new immune escape. This hypothesis was evaluated using maximum likelihood phylogenetic trees of each gene from 272 full-length HIV-1 sequences. Recent viral evolution, as measured by the external branch length, was found to be inversely associated with HLA frequency in nef (p < 0.02), env (p < 0.03), and pol (p <= 0.05), suggesting that rare HLA alleles provide a disproportionate force driving viral evolution compared to common alleles, likely due to the loss of preexisting escape variants during early stages postinfection. C1 [Rousseau, Christine M.] Univ Washington, Dept Microbiol, Sustainable Sci Inst, Seattle, WA 98103 USA. [Lockhart, David W.] Univ Washington, Dept Biostat, Seattle, WA 98103 USA. [Listgarten, Jennifer; Kadie, Carl; Heckerman, David E.] Microsoft Res, eSci Res Grp, Redmond, WA 98052 USA. [Brander, Christian; Ndung'u, Thumbi; Goulder, Philip J. R.; Walker, Bruce D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Ndung'u, Thumbi; Coovadia, Hoosen; Goulder, Philip J. R.; Walker, Bruce D.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, HIV Pathogenesis Program, Durban, South Africa. [Goulder, Philip J. R.] Nuffield Dept Med, Dept Pediat, Oxford, England. [Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM 87544 USA. [Korber, Bette T.] Santa Fe Inst, Santa Fe, NM 87501 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Mullins, James I.] Univ Washington, Dept Med, Washington, DC 98103 USA. RP Rousseau, CM (reprint author), Univ Washington, Dept Microbiol, Sustainable Sci Inst, 3515 Ashworth Ave N, Seattle, WA 98103 USA. EM crousseau@ssilink.org OI Brander, Christian/0000-0002-0548-5778; Ndung'u, Thumbi/0000-0003-2962-3992; Korber, Bette/0000-0002-2026-5757 FU University of Washington Center For AIDS Research [AI27757, AI047734] FX The authors would like to thank all of the participants who contributed time, information, and blood samples for the study. Funding for this research was provided by University of Washington Center For AIDS Research (AI27757), including a New Investigator Award (AI047734) to C. M. R., by Puget Sound Partners in Global Health (to C. M. R.), and by Microsoft Research (to J. L., C. K., and D. E. H.). This work was previously presented in part at the 14th Conference on Retroviruses and Opportunistic Infections, 2007. NR 38 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 2009 VL 25 IS 3 BP 297 EP 303 DI 10.1089/aid.2008.0208 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 425KV UT WOS:000264636300007 PM 19327049 ER PT J AU Yuan, W Li, X Kasterka, M Gorny, MK Zolla-Pazner, S Sodroski, J AF Yuan, Wen Li, Xing Kasterka, Marta Gorny, Miroslaw K. Zolla-Pazner, Susan Sodroski, Joseph TI Oligomer-Specific Conformations of the Human Immunodeficiency Virus (HIV-1) gp41 Envelope Glycoprotein Ectodomain Recognized by Human Monoclonal Antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID BROADLY NEUTRALIZING ANTIBODIES; TYPE-1 GP41; TRANSMEMBRANE PROTEIN; AIDS PATIENTS; HTLV-III; EPITOPE; BINDING; MOLECULES; REGION; SERA AB Trimerization of the human immunodeficiency virus (HIV-1) envelope glycoproteins is mediated by the ecto-domain of the gp41 transmembrane glycoprotein. Here we investigate oligomer-specific conformations of gp41 by using monoclonal antibodies (MAbs) from HIV-1-infected humans. Human MAbs directed against the cluster I region of gp41 recognized trimeric, dimeric, and monomeric forms of soluble envelope glycoproteins; thus, the integrity of the cluster I epitopes is minimally affected by the oligomeric state. In contrast, human MAbs to the cluster II region were all oligomers specific. One cluster II MAb, 126-6, recognized exclusively the trimeric form of envelope glycoproteins, whereas the others recognized both trimeric and dimeric forms. Thus, a distinct trimer-specific conformation exists in the cluster II region of gp41. Analysis of soluble envelope glycoprotein mutants revealed that gp41 sequences immediately N-terminal to isoleucine 646 contribute to the formation of both the trimer and the trimer-specific conformational epitope. C1 [Yuan, Wen; Kasterka, Marta] Univ Virginia, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. [Yuan, Wen] Univ Virginia, Myles H Thaler Ctr AIDS & Human Retrovirus Res, Charlottesville, VA 22908 USA. [Li, Xing; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. [Li, Xing; Sodroski, Joseph] Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. [Li, Xing; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. [Gorny, Miroslaw K.; Zolla-Pazner, Susan] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Zolla-Pazner, Susan] Vet Affairs Med Ctr, New York, NY 10010 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Yuan, W (reprint author), Univ Virginia, Dept Med, Div Infect Dis & Int Hlth, POB 800734, Charlottesville, VA 22908 USA. EM wy5e@virginia.edu RI Li, Xing/D-3852-2009; OI Gorny, Miroslaw/0000-0002-2714-8780 FU NIH [AI24755, AI39420, AI40895, HL59725, AI36085]; Center for HIV/AIDS Vaccine Immunology [AI67854]; Center for AIDS Research [AI42848, AI27742]; Bristol- Myers Squibb Foundation; International AIDS Vaccine Initiative; Department of Veterans Affairs; Department of Medicine, University of Virginia FX We thank Ms. Yvette McLaughlin and Ms. Elizabeth Carpelan for manuscript preparation. This work was supported by NIH grants [AI24755, AI39420, and AI40895 (J. S.) and HL59725 and AI36085 (S. Z. P.)], by a Center for HIV/AIDS Vaccine Immunology grant (AI67854), by Center for AIDS Research grants [AI42848 (DFCI) and AI27742 (NYU)], by an unrestricted research grant from the Bristol- Myers Squibb Foundation, by a gift from the late William F. McCartyCooper, by funds from the International AIDS Vaccine Initiative and the Department of Veterans Affairs, and by funds from the Department of Medicine, University of Virginia. NR 53 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 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 2009 VL 25 IS 3 BP 319 EP 328 DI 10.1089/aid.2008.0213 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 425KV UT WOS:000264636300010 PM 19292593 ER PT J AU Scibelli, AC Phillips, TJ AF Scibelli, Angela C. Phillips, Tamara J. TI Combined Scopolamine and Ethanol Treatment Results in a Locomotor Stimulant Response Suggestive of Synergism That is Not Blocked by Dopamine Receptor Antagonists SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Dopamine; Ethanol; Locomotor Activity; Muscarinic Receptor; Selected Line ID CONDITIONED PLACE PREFERENCE; SUBTYPE-SPECIFIC ANTIBODIES; QUANTITATIVE TRAIT LOCUS; SLOW MOUSE LINES; MUSCARINIC ACETYLCHOLINE; NUCLEUS-ACCUMBENS; REVERSE SELECTION; GENETIC INFLUENCE; KNOCKOUT MICE; TREATED RATS AB Muscarinic acetylcholine receptors (mAChRs) are well positioned to mediate ethanol's stimulant effects. To investigate this possibility, we examined the effects of scopolamine, a receptor subtype nonselective mAChR antagonist, on ethanol-induced stimulation in genotypes highly sensitive to this effect of ethanol. We also investigated whether the dopamine D1-like receptor antagonist, SCH-23390 or the dopamine D2-like receptor antagonist, haloperidol, could block the extreme stimulant response found following co-administration of scopolamine and ethanol. Scopolamine (0, 0.0625, 0.125, 0.25, or 0.5 mg/kg) was given 10 minutes prior to saline or ethanol (0.75 to 2 g/kg) to female FAST (Experiment I) or DBA/2J (Experiment II) mice that were then tested for locomotion for 30 minutes. In Experiments III and IV, respectively, SCH-23390 (0, 0.015, or 0.03 mg/kg) was given 10 minutes prior, and haloperidol (0, 0.08, or 0.16 mg/kg) was given 2 minutes prior, to scopolamine (0 or 0.5 mg/kg), followed 10 minutes later by saline or ethanol (1.5 g/kg) and female DBA/2J mice were tested for locomotion for 30 minutes. FAST and DBA/2J mice displayed a robust enhancement of the locomotor effects of ethanol following pretreatment with scopolamine that was suggestive of synergism. SCH-23390 had no effect on the response to the scopolamine + ethanol drug combination, nor did it attenuate ethanol- or scopolamine-induced locomotor activity. Haloperidol, while attenuating the effects of ethanol, was not able to block the effects of scopolamine or the robust response to the scopolamine-ethanol drug combination. These results suggest that while muscarinic receptor antagonism robustly enhances acute locomotor stimulation to ethanol, dopamine receptors are not involved in the super-additive interaction of scopolamine and ethanol treatment. They also suggest that in addition to cautions regarding the use of alcohol when scopolamine is clinically prescribed due to enhanced sedative effects, enhanced stimulation may also be a concern. C1 [Scibelli, Angela C.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. [Scibelli, Angela C.; Phillips, Tamara J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR USA. RP Phillips, TJ (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, 3710 SW US Vet Hosp Rd,R&D-32, Portland, OR 97239 USA. EM phillipt@ohsu.edu FU National Institute on Alcohol Abuse and Alcoholism [P60AA010760]; National Institute on Drug Abuse [T32DA07262]; Department of Veterans Affairs FX This work was supported by a National Institute on Alcohol Abuse and Alcoholism grant P60AA010760, a grant from the National Institute on Drug Abuse T32DA07262, and a grant from the Department of Veterans Affairs. NR 77 TC 6 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2009 VL 33 IS 3 BP 435 EP 447 DI 10.1111/j.1530-0277.2008.00854.x PG 13 WC Substance Abuse SC Substance Abuse GA 409PN UT WOS:000263518400007 PM 19120057 ER PT J AU Thomsen, SF Ferreira, MAR Kyvik, KO Fenger, M Backer, V AF Thomsen, S. F. Ferreira, M. A. R. Kyvik, K. O. Fenger, M. Backer, V. TI A quantitative genetic analysis of intermediate asthma phenotypes SO ALLERGY LA English DT Article DE airway obstruction; airway responsiveness; asthma; exhaled nitric oxide; genetics; IgE; twin study ID EXHALED NITRIC-OXIDE; AIRWAY RESPONSIVENESS; SAMPLE; SYMPTOMS; TWINS; AGE AB To study the relative contribution of genetic and environmental factors to the correlation between exhaled nitric oxide (FeNO), airway responsiveness, airway obstruction, and serum total immunoglobulin E (IgE). Within a sampling frame of 21 162 twin subjects, 20-49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins) who either themselves and/or their co-twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Traits were measured using standard techniques. Latent factor models were fitted to the observed data using maximum likelihood methods. Additive genetic factors explained 67% of the variation in FeNO, 43% in airway responsiveness, 22% in airway obstruction, and 81% in serum total IgE. In general, traits had genetically and environmentally distinct variance structures. The most substantial genetic similarity was observed between FeNO and serum total IgE, genetic correlation (rho(A)) = 0.37, whereas the strongest environmental resemblance was observed between airway responsiveness and airway obstruction, specific environmental correlation (rho(E)) = -0.46, and between FeNO and airway responsiveness, rho(E) = 0.34. Asthma is a complex disease characterized by a set of etiologically heterogeneous biomarkers, which likely constitute diverse targets of intervention. C1 [Thomsen, S. F.; Backer, V.] Bispebjerg Hosp, Dept Resp Med, DK-2400 Copenhagen NV, Denmark. [Ferreira, M. A. R.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ferreira, M. A. R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Kyvik, K. O.] Univ So Denmark, Danish Twin Registry, Odense, Denmark. [Fenger, M.] Hvidovre Univ Hosp, Dept Clin Biochem, Copenhagen, Denmark. RP Thomsen, SF (reprint author), Bispebjerg Hosp, Dept Resp Med, DK-2400 Copenhagen NV, Denmark. RI Ferreira, Manuel/D-3609-2013; Backer, Vibeke/I-9573-2014; Kyvik, Kirsten /K-5680-2016 OI Backer, Vibeke/0000-0002-7806-7219; Kyvik, Kirsten /0000-0003-2981-0245 NR 15 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-4538 J9 ALLERGY JI Allergy PD MAR PY 2009 VL 64 IS 3 BP 427 EP 430 DI 10.1111/j.1398-9995.2008.01850.x PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 411UL UT WOS:000263676500013 PM 19175595 ER PT J AU Long, AA AF Long, Aidan A. TI Immunomodulators in the treatment of asthma SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article CT Postconference Symposium for the Eastern Allergy Conference CY MAY 04, 2008 CL Naples, FL DE Airway inflammation; asthma; cytokine blockers; dendritic cell; IgE; immunomodulators; monoclonal antibodies; omalizumab; T(H)1 cells; T(H)2 cells ID NECROSIS-FACTOR-ALPHA; ANTI-IGE ANTIBODY; SEVERE PERSISTENT ASTHMA; HUMAN EPITHELIAL-CELLS; IL-5 RECEPTOR-ALPHA; AIRWAY HYPERRESPONSIVENESS; MONOCLONAL-ANTIBODY; ALLERGIC-ASTHMA; DENDRITIC CELLS; ANTI-INTERLEUKIN-5 ANTIBODY AB Asthma represents a syndrome of airway inflammatory diseases with a complex pathology. The immunologic pathogenesis is being increasingly revealed and provides opportunity for targeted biological intervention. This study was designed to describe current experience with immunomodulators as targeted therapy in asthma. A literature review was performed. Targeted therapies have included strategies to activate dendritic cells through the Toll-like receptor (TLR) 9 receptors, to interrupt the action of T(H)2 cytokines with cytokine blockers and monoclonal antibodies, to promote development of T(H)1 responses, to interrupt mast cell signaling, to block IgE mediated pathways, and to block TNF-alpha. Omalizumab is the only biological therapy that has an approved indication in asthma at this time. Improved understanding of the heterogeneity of asthma should allow for specific targeting of different disease phenotype-specific therapies including immunomodulators. (Allergy Asthma Proc 30:109-119, 2009; doi: 10.2500/aap.2009.30.3203) C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Long, AA (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Cox 201,55 Fruit St, Boston, MA 02114 USA. EM aalong@mgh.harvard.edu NR 78 TC 13 Z9 14 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 2009 VL 30 IS 2 BP 109 EP 119 DI 10.2500/aap.2009.30.3203 PG 11 WC Allergy SC Allergy GA 440YP UT WOS:000265735900002 PM 19463201 ER PT J AU Brener, SJ Bhatt, DL AF Brener, Sorin J. Bhatt, Deepak L. TI The pain and the gain of treating patients with acute coronary syndromes-can the two be separated? SO AMERICAN HEART JOURNAL LA English DT Article ID ACUITY TRIAL; MORTALITY C1 [Brener, Sorin J.] New York Methodist Hosp, Brooklyn, NY USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Brener, SJ (reprint author), NY Methodist Hosp, New York, NY 11215 USA. EM sjb9005@nyp.org NR 11 TC 2 Z9 2 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 MAR PY 2009 VL 157 IS 3 BP 399 EP 401 DI 10.1016/j.ahj.2008.11.012 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419JD UT WOS:000264214700001 PM 19249407 ER PT J AU Bushnell, C Zimmer, L Schwamm, L Goldstein, LB Clapp-Channing, N Harding, T Drew, L Zhao, X Peterson, E AF Bushnell, Cheryl Zimmer, Louise Schwamm, Lee Goldstein, Larry B. Clapp-Channing, Nancy Harding, Tina Drew, Laura Zhao, Xin Peterson, Eric TI The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) Registry: Design, rationale, and baseline patient characteristics SO AMERICAN HEART JOURNAL LA English DT Article ID MEDICATION ADHERENCE; CEREBRAL INFARCTION; OLDER-PEOPLE; PRIMARY-CARE; RISK-FACTORS; SELF-REPORT; PREVENTION; POPULATION; ATTACK; 1ST AB Background Approximately one third of the 780,000 people in the United States who have a stroke each year have recurrent events. Although efficacious secondary prevention measures are available, levels of adherence to these strategies in patients who have had stroke are largely unknown. Understanding medication-taking behavior in this population is an important step to optimizing the appropriate use of proven secondary preventive therapies and reducing the risk of recurrent stroke. Methods The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry is a prospective study of adherence to stroke prevention medications from hospital discharge to 1 year in patients admitted with stroke or transient ischemic attack. The primary outcomes are medication usage as determined by patient interviews after 3 and 12 months. Potential patient-, provider-, and system-level barriers to persistence of medication use are also collected. Secondary outcomes include the rates of recurrent stroke or transient ischemic attack, vascular events, and rehospitalization and functional status as measured by the modified Rankin score. Results The AVAIL enrolled about 2,900 subjects from 106 hospitals from July 2006 through July 2008. The 12-month follow-up will be completed in August 2009. Conclusions The AVAIL registry will document the current state of adherence and persistence to stroke prevention medications among a nationwide sample of patients. These data will be used to design interventions to improve the quality of care post acute hospitalization and reduce the risks of future stroke and cardiovascular events. (Am Heart J 2009; 157:428-35.) C1 [Bushnell, Cheryl] Wake Forest Univ Hlth Sci, Winston Salem, NC 27157 USA. [Zimmer, Louise; Goldstein, Larry B.; Clapp-Channing, Nancy; Harding, Tina; Drew, Laura; Zhao, Xin; Peterson, Eric] Duke Univ, Med Ctr, Durham, NC USA. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bushnell, C (reprint author), Wake Forest Univ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM cbushnel@wfubmc.edu OI Schwamm, Lee/0000-0003-0592-9145 NR 34 TC 21 Z9 24 U1 1 U2 5 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 MAR PY 2009 VL 157 IS 3 BP 428 EP 435 DI 10.1016/j.ahj.2008.11.002 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419JD UT WOS:000264214700005 PM 19249411 ER PT J AU Giraldez, RR Sabatine, MS Morrow, DA Mohanavelu, S McCabe, CH Antman, EM Braunwald, E AF Giraldez, Roberto R. Sabatine, Marc S. Morrow, David A. Mohanavelu, Satishkumar McCabe, Carolyn H. Antman, Elliott M. Braunwald, Eugene TI Baseline hemoglobin concentration and creatinine clearance composite laboratory index improves risk stratification in ST-elevation myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; UNFRACTIONATED HEPARIN; CLINICAL-OUTCOMES; INTRAVENOUS NPA; MORTALITY; SCORE; THROMBOLYSIS; FIBRINOLYSIS; ASSOCIATION; REPERFUSION AB Background Hemoglobin (Hgb) and creatinine clearance (CrCl) are readily-available, routinely-obtained laboratory parameters that predict acute coronary syndrome outcomes. We sought to develop a laboratory index (LI) to predict early mortality in ST-elevation myocardial infarction (STEMI) and determine the additional risk stratification offered by adding the LI to the TIMI Risk Score (TRS) for STEMI. Methods and Results The association between Hgb and CrCl values obtained at hospitalization and 30-day mortality was evaluated in 14,373 STEMI patients undergoing fibrinolysis in Intravenous NPA for the Treatment of Infarcting Myocardium Early II-Thrombolysis In Myocardial Infarction-17 (InTIME II-TIMI 17). Logistic regression models determined the optimal combination of laboratory variables into a LI. Prognostic utility of the LI was validated in 18,427 STEMI patients from Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment (ExTRACT)-TIMI 25. In InTIME II, Hqb levels <15.0 g/dL and CrCl <100 mL/min were significantly and independently associated with increased risk of death (OR(adj) 1.22, 95% Cl 1.15-1.29 for each I g/dL decrease in Hgb, P < .001, and OR(adj) 1.23, 95% Cl 1.17-1.29 for each 10 mL/min decrease in CrCl, P < .001, respectively). In multivariable analysis, the optimal weighting of Hqb and CrCl to form an LI to predict mortality was (15-Hgb) + (100-CrCl)/8. The LI revealed a 10-fold increase in death across prespecified groups (P < .001). The LI offered additional risk stratification across all TRS groups and improved the discriminatory ability of the TRS (c-statistic from 0.755 to 0.789, P < .001). External validation in ExTRACT showed similar enhancement of the prognostic capacity of the TRS (c-statistic from 0.747 to 0.777, P < .001). Conclusions The LI is a simple, powerful tool to predict death in STEMI, either separately or with the TRS. (Am Heart J 2009; 157:517-24.) C1 [Giraldez, Roberto R.; Sabatine, Marc S.; Morrow, David A.; Mohanavelu, Satishkumar; McCabe, Carolyn H.; Antman, Elliott M.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,TIMI Study Grp,Cardiovasc Div, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM msabatine@partners.org NR 15 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 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2009 VL 157 IS 3 BP 517 EP 524 DI 10.1016/j.ahj.2008.10.021 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419JD UT WOS:000264214700018 PM 19249423 ER PT J AU Decker, C Ahmad, H Moreng, KL Maddox, TM Reid, KJ Jones, PG Spertus, JA AF Decker, Carole Ahmad, Homaa Moreng, Kate Louise Maddox, Thomas M. Reid, Kimberly J. Jones, Philip G. Spertus, John A. TI Risk factor management after myocardial infarction: Reported adherence and outcomes SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; CARDIAC REHABILITATION; LIFE-STYLE; SECONDARY PREVENTION; HEALTH-STATUS; CARE; MEDICATION; VALIDITY; THERAPY; QUALITY AB Background Providing patients with documented discharge instructions is a performance measure of health care quality. It is not well known how often cardiac patients comply with the list of instructions or what their association is with health status outcomes after an acute myocardial infarction. Methods Acute myocardial infarction patients (N = 2,498) were prospectively enrolled into a 19-center study and asked, at I month, if they had recalled receiving instructions at discharge on any of the 13 secondary prevention behaviors (eg, exercise, medications, diet, and smoking). Adherence, defined as the percentage of relevant activities patients reported adhering to at 1 month, was grouped into 4 categories: poor (0%-49%), partial (50%-74%), careful (75%-99%), and very careful (100%). Results A total of 2,046 patients completed 1-month interviews and received instruction on at least 1 risk factor management (RFM) behavior. Very careful adherence at I-month was reported most frequently with "taking medications as prescribed" (94%). In multivariable-adjusted models, patients who reported being poorly adherent were 58% more likely to report angina at I year as compared with those who very carefully followed RFM (relative risk 1.58, 95% CI 1.05-2.37). There was no independent association between RFM behavior and quality of life, physical functioning, rehospitalization, or mortality. Conclusions There is substantial variation in the types of RFM to which acute myocardial infarction patients adhere. In aggregate, stronger adherence was associated with less angina at I year. More research is needed to understand adherence patterns and its association with outcomes. (Am Heart J 2009; 157:556-62.) C1 [Decker, Carole; Reid, Kimberly J.; Jones, Philip G.; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Decker, Carole; Moreng, Kate Louise; Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Ahmad, Homaa] Univ Chicago Hosp, Cardiol Sect, Chicago, IL 60637 USA. [Maddox, Thomas M.] Univ Colorado, Hlth Sci Ctr, Denver VAMC, Denver, CO USA. RP Decker, C (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 4401 Warnall Rd, Kansas City, MO 64111 USA. EM cldecker@saint-lukes.org NR 32 TC 9 Z9 9 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2009 VL 157 IS 3 BP 556 EP 562 DI 10.1016/j.ahj.2008.11.022 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 419JD UT WOS:000264214700023 PM 19249428 ER PT J AU Chaudhry, S Arena, R Wasserman, K Hansen, JE Lewis, GD Myers, J Chronos, N Baden, WE AF Chaudhry, Sundeep Arena, Ross Wasserman, Karlman Hansen, James E. Lewis, Gregory D. Myers, Jonathan Chronos, Nicolas Baden, William E. TI Exercise-Induced Myocardial Ischemia Detected by Cardiopulmonary Exercise Testing SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; CHRONIC HEART-FAILURE; NORMAL CORONARY ANGIOGRAMS; OXYGEN PULSE; STROKE VOLUME; DISEASE; RECOMMENDATIONS; PERFORMANCE; STATEMENT; WOMEN AB Cardiopulmonary exercise testing (CPET) is a well-accepted physiologic evaluation technique in patients diagnosed with heart failure and in patients presenting with unexplained dyspnea on exertion. Several variables obtained during CPET, including oxygen consumption relative to heart rate and work rate provide consistent, quantitative patterns of abnormal physiologic responses to graded exercise when left ventricular dysfunction is caused by myocardial ischemia. This concept report describes both the methodology and clinical application of CPET associated with myocardial ischemia. Initial evidence indicates left ventricular dysfunction induced by myocardial ischemia may be accurately detected by an abnormal CPET response. CPET testing may complement current noninvasive testing modalities that elicit inducible ischemia. It provides a physiologic quantification of the work rate, heart rate, and O(2) uptake at which myocardial ischemia develops. In conclusion, adding CPET with gas exchange measurements is likely to be of value in diagnosing and quantifying both overt and occult myocardial ischemia and its reversibility with treatment. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:615-619) C1 [Chaudhry, Sundeep] Met Test Inc, Dept Res & Dev, Atlanta, GA USA. [Arena, Ross] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23284 USA. [Arena, Ross] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA 23284 USA. [Wasserman, Karlman; Hansen, James E.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Resp & Crit Care Physiol & Med, Torrance, CA 90509 USA. [Lewis, Gregory D.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Myers, Jonathan] Stanford Univ, Div Cardiol, VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Chronos, Nicolas] St Josephs Hosp, St Joseph Translat & Res Inst, Atlanta, GA USA. [Baden, William E.] SUNY Buffalo, Div Cardiovasc Med, Sch Med, Buffalo, NY 14260 USA. [Baden, William E.] SUNY Buffalo, Div Cardiovasc Med, Sch Publ Hlth, Buffalo, NY 14260 USA. RP Chaudhry, S (reprint author), Met Test Inc, Dept Res & Dev, Atlanta, GA USA. EM schaudhry@mettest.net RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 FU NHLBI NIH HHS [K23 HL091106-01A1, K23 HL091106] NR 19 TC 22 Z9 24 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2009 VL 103 IS 5 BP 615 EP 619 DI 10.1016/j.amjcard.2008.10.034 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 416DV UT WOS:000263986500008 PM 19231322 ER PT J AU Bamberg, F Schlett, CL Truong, QA Rogers, IS Koenig, W Nagurney, JT Seneviratne, S Lehman, SJ Cury, RC Abbora, S Butler, J Lee, H Brady, TJ Hoffmann, U AF Bamberg, Fabian Schlett, Christopher L. Truong, Quynh A. Rogers, Ian S. Koenig, Wolfgang Nagurney, John T. Seneviratne, Sujith Lehman, Sam J. Cury, Ricardo C. Abbora, Suhny Butler, Javed Lee, Hang Brady, Thomas J. Hoffmann, Udo TI Presence and Extent of Coronary Artery Disease by Cardiac Computed Tomography and Risk for Acute Coronary Syndrome in Cocaine Users Among Patients With Chest Pain SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE; SCIENTIFIC STATEMENT; INCREASED PREVALENCE; CLINICAL CARDIOLOGY; INTRAVENOUS COCAINE; ASSOCIATION; COMMITTEE; VASOCONSTRICTION AB Cocaine users represent an emergency department (ED) population that has been shown to be at increased risk for acute coronary syndrome (ACS); however, there is controversy about whether this higher risk is mediated through advanced atherosclerosis. Thus, we aimed to determine whether history of cocaine use is associated with ACS and coronary artery disease. In this matched cohort study, we selected patients with a history of cocaine use and age- and gender-matched controls from a large cohort of consecutive patients who presented with acute chest pain to the ED. Coronary atherosclerotic plaque as detected by 64-slice coronary computed tomography was compared between the groups. Among 412 patients, 44 had a history of cocaine use (9%) and were matched to 132 controls (mean age 46 +/- 6 years, 86% men). History of cocaine use was associated with a sixfold higher risk for ACS (odds ratio 5.79, 95% confidence interval 1.24 to 27.02, p = 0.02), but was not associated with a higher prevalence of any plaque, calcified plaque, or noncalcified plaque (all p>0.58) or the presence of significant stenosis (p = 0.09). History of cocaine use was also not associated with the extent of any, calcified, or noncalcified plaque (all p>0.12). These associations persisted after adjustment for other cardiovascular risk factors. In conclusion, in patients presenting to the emergency department with acute chest pain, history of cocaine use is associated with an increase in risk for ACS; however, this was not attributable to a higher presence or extent of coronary atherosclerotic plaque. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:620-625) C1 [Bamberg, Fabian; Schlett, Christopher L.; Truong, Quynh A.; Rogers, Ian S.; Seneviratne, Sujith; Lehman, Sam J.; Cury, Ricardo C.; Abbora, Suhny; Butler, Javed; Brady, Thomas J.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Bamberg, Fabian; Schlett, Christopher L.; Truong, Quynh A.; Rogers, Ian S.; Nagurney, John T.; Seneviratne, Sujith; Lehman, Sam J.; Cury, Ricardo C.; Abbora, Suhny; Butler, Javed; Lee, Hang; Brady, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Koenig, Wolfgang] Univ Ulm, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. EM uhoffmann@partners.org FU National Institutes of Health [R0-1HL0800-53, T32HL076136]; Siemens Medical Solutions, Forcheim, Germany; General Electric, Milwaukee, Wisconsin FX This work was supported by Grant R0-1HL0800-53 from the National Institutes of Health and in part supported by Siemens Medical Solutions, Forcheim, Germany, and General Electric, Milwaukee, Wisconsin. Drs. Rogers and Truong received support from NIH grant T32HL076136. NR 28 TC 6 Z9 6 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2009 VL 103 IS 5 BP 620 EP 625 DI 10.1016/j.amjcard.2008.11.011 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 416DV UT WOS:000263986500009 PM 19231323 ER PT J AU Sakhuja, R Keebler, M Lai, TS Gavin, CM Thakur, R Bhatt, DL AF Sakhuja, Rahul Keebler, Mary Lai, Tai-Shuan Gavin, Cara McLaughlin Thakur, Ranjan Bhatt, Deepak L. TI Meta-Analysis of Mortality in Dialysis Patients With an Implantable Cardioverter Defibrillator SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; RENAL-INSUFFICIENCY; SUDDEN-DEATH; SURVIVAL; RECIPIENTS; IMPACT; RISK; PREVENTION; THERAPY; FAILURE AB Patients receiving dialysis are at high risk for sudden cardiac death. Although clinical trials have shown that implantable cardioverter-defibrillators (ICDs) are effective in improving survival in a variety of populations, dialysis patients have been routinely excluded from these analyses. The purpose of this meta-analysis was to synthesize the available evidence regarding the effectiveness of ICD therapy in patients receiving dialysis. Medline, EMBASE, Web of Science, and Google Scholar were searched for pertinent studies published from 1999 to 2008. In addition, hand searches of the relevant annual scientific sessions and major scientific meetings in North America and Europe from 2000 to 2008 were performed. All clinical reports describing outcomes of ICD therapy in relation to renal function were eligible. Four investigators independently extracted the data in a standardized manner. Seven studies were identified, with a total of 2,516 patients and 89 patients receiving dialysis. Despite having ICDs, patients receiving dialysis had a 2.7-fold higher mortality compared with those not receiving dialysis. The results were similar in fixed- and random-effects models. Comparing patients receiving dialysis and those with chronic kidney disease but not receiving dialysis, there was no significant difference in mortality (risk ratio 1.62, 95% confidence interval 0.84 to 3.14). No evidence of publication bias was found. In conclusion, this meta-analysis suggests that even in those with ICDs, there is still a 2.7-fold increased mortality risk in patients who receive dialysis compared with those who do not. Beta blockers may be less cardioprotective in patients with ICDs who are on dialysis. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;103:735-741) C1 [Gavin, Cara McLaughlin; Bhatt, Deepak L.] VA Boston Healthcare Syst & Brigham & Womens Hosp, Boston, MA 02115 USA. [Sakhuja, Rahul; Keebler, Mary] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lai, Tai-Shuan] Natl Taiwan Univ Hosp, Div Nephrol, Yun Lin Branch, Touliu, Taiwan. [Thakur, Ranjan] Michigan State Univ, Thorac & Cardiovasc Inst, Lansing, MI USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst & Brigham & Womens Hosp, Boston, MA 02115 USA. EM dlbhattmd@alum.mit.edu NR 23 TC 53 Z9 55 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2009 VL 103 IS 5 BP 735 EP 741 DI 10.1016/j.amjcard.2008.11.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 416DV UT WOS:000263986500030 PM 19231344 ER PT J AU Harris, B Hwang, U Lee, WS Richardson, LD AF Harris, Ben Hwang, Ula Lee, Won S. Richardson, Lynne D. TI Disparities in use of computed tomography for patients presenting with headache SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys ID EMERGENCY-DEPARTMENT; SUBARACHNOID HEMORRHAGE; ETHNIC DISPARITIES; HEALTH-CARE; CHEST-PAIN; STROKE; GENDER; RACE AB Objective: Headache is a common presenting complaint in the emergency department (ED). Physicians may choose to screen for causes of headache using computed tomography (CT). It is not known whether patient characteristics influence this decision. This study sought to identify patient demographic factors associated with CT evaluation for adult patients with headache. Methods: This study used a retrospective cohort review at an academic, urban ED. Study eligibility was based on chief complaint of headache and final diagnosis of the same. Detailed demographic (age, sex, race/ethnicity, insurance) and clinical (Emergency Severity Index [ESI], Charlson comorbidity score, pain score) data were abstracted from the ED medical record. The main outcome studied was whether a head CT was part of clinical evaluation. Results: One hundred fifty-five patients were reviewed. Mean age was 42 years (SD, +/- 18 years); 75% female, 17% white, 41% black, and 33% Hispanic; 73% were insured; mean ESI was 3.06 (SD, +/- 0.64); and Charlson score was 0.60 (SD, +/- 1.55). Thirty-seven percent of patients underwent head CT. In multivariable analyses, patients were more likely to undergo head CT if they had greater acuity (ESI :! 3; odds ratio [OR], 5.11; P < .01) but were less likely to undergo head CT if they were black (OR, 0.21; P < .01) when adjusting for each other as well as older age, sex, comorbidity, insurance status, and history of migraine. Conclusion: In this study, patients who were black were significantly less likely to undergo head CT during their ED evaluation for headache, independent of clinical and demographic factors. Published by Elsevier Inc. C1 [Harris, Ben; Hwang, Ula; Richardson, Lynne D.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Hwang, Ula] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Lee, Won S.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Hwang, U (reprint author), Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. EM ulahwang@yahoo.com FU NHLBI NIH HHS [R01 HL073387-03, R01 HL073387] NR 20 TC 9 Z9 10 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAR PY 2009 VL 27 IS 3 BP 333 EP 336 DI 10.1016/j.ajem.2008.03.041 PG 4 WC Emergency Medicine SC Emergency Medicine GA 432SN UT WOS:000265154500014 PM 19328379 ER PT J AU Campa, OM Melrose, RJ Harwood, DG Mandelkern, MA Sultzer, DL Walston, AK AF Campa, Olivia M. Melrose, Rebecca J. Harwood, Dylan G. Mandelkern, Mark A. Sultzer, David L. Walston, Amy K. TI Depressive Symptoms and Regional Cortical Metabolism in Patients with Alzheimer's Disease: An FDG-PET Study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Melrose, Rebecca J.; Harwood, Dylan G.; Sultzer, David L.; Walston, Amy K.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Mandelkern, Mark A.] Univ Calif Los Angeles, Dept Phys, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 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 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2009 VL 17 IS 3 SU 1 BP A73 EP A73 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YW UT WOS:000207905900087 ER PT J AU Dunn, LB Feil, D Meeks, T Misra, S AF Dunn, Laura B. Feil, Denise Meeks, Thomas Misra, Sahana TI Tough Love: Ways to Make the Difficult Decisions When Caring for Dementia Patients SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Dunn, Laura B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Feil, Denise] Univ Calif Los Angeles, W Los Angeles VA, Los Angeles, CA USA. [Meeks, Thomas] Univ Calif San Diego, San Diego, CA 92103 USA. [Misra, Sahana] Oregon Hlth & Sci Univ, Portland, OR 97201 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 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2009 VL 17 IS 3 SU 1 BP A12 EP A12 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YW UT WOS:000207905900005 ER PT J AU German, ME Athappilly, GK Llorente, M Martinez, M McGahee, S AF German, Maria E. Athappilly, Geena K. Llorente, Maria Martinez, Moises McGahee, Shunda TI Underrepresentation of Elderly Minority in Antidepressant Trials SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [German, Maria E.; Athappilly, Geena K.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Llorente, Maria] Miami Vet Adm, Miami, FL USA. [Martinez, Moises] Columbia Univ, New York, NY USA. [McGahee, Shunda] 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 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2009 VL 17 IS 3 SU 1 BP A120 EP A121 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YW UT WOS:000207905900169 ER PT J AU Kasckow, J Brown, C Bensasi, S Houck, P Thomas, S Ford, A Reynolds, C AF Kasckow, John Brown, Charlotte Bensasi, Salem Houck, Patty Thomas, Stephen Ford, Angela Reynolds, Charles TI Racial Preferences for Participation in a Depression Prevention Research Intervention SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Brown, Charlotte; Bensasi, Salem; Reynolds, Charles] Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Houck, Patty] UPMC Hlth Syst, Pittsburgh, PA USA. [Thomas, Stephen; Ford, Angela] Ctr Minor Hlth, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2009 VL 17 IS 3 SU 1 BP A65 EP A66 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YW UT WOS:000207905900074 ER PT J AU Kyomen, HH Lebowitz, BD Nelson, RJ Trinh, NHT AF Kyomen, Helen H. Lebowitz, Barry D. Nelson, Randy J. Trinh, Nhi-Ha T. TI Evaluating and Managing Aggressive Behaviors in Geropsychiatric Patients SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Kyomen, Helen H.] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. [Lebowitz, Barry D.] Univ Calif San Diego, San Diego, CA 92103 USA. [Nelson, Randy J.] Ohio State Univ, Columbus, OH 43210 USA. [Trinh, Nhi-Ha T.] 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 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2009 VL 17 IS 3 SU 1 BP A17 EP A18 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YW UT WOS:000207905900014 ER PT J AU Lanouette, NM Kaskow, JW Fellows, I Patterson, TL Golshan, S Zisook, S AF Lanouette, Nicole M. Kaskow, John W. Fellows, Ian Patterson, Thomas L. Golshan, Shahrokh Zisook, Sidney TI Subsyndromal Depressive Symptoms in Schizophrenia: Effect of Treatment Response on Functional Outcomes SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Lanouette, Nicole M.; Fellows, Ian; Patterson, Thomas L.; Golshan, Shahrokh; Zisook, Sidney] Univ Calif San Diego, San Diego, CA 92103 USA. [Kaskow, John W.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Kaskow, John W.] Univ Pittsburgh, Pittsburgh, PA USA. [Fellows, Ian; Golshan, Shahrokh; Zisook, Sidney] VA San Diego Hlth Care Syst, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2009 VL 17 IS 3 SU 1 BP A128 EP A129 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YW UT WOS:000207905900182 ER PT J AU Melrose, RJ Harwood, DG Campa, O Mandelkern, MA Bussel, N Sultzer, DL AF Melrose, Rebecca J. Harwood, Dylan G. Campa, Olivia Mandelkern, Mark A. Bussel, Natalya Sultzer, David L. TI Neurobiological Correlates of Instrumental Activities of Daily Living in Alzheimer's Disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Melrose, Rebecca J.; Harwood, Dylan G.; Campa, Olivia; Bussel, Natalya; Sultzer, David L.] Univ Calif Los Angeles, VA Greater Healthcare Syst, Los Angeles, CA USA. [Melrose, Rebecca J.; Harwood, Dylan G.; Sultzer, David L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Mandelkern, Mark A.] Univ Calif Irvine, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2009 VL 17 IS 3 SU 1 BP A82 EP A82 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YW UT WOS:000207905900101 ER PT J AU Sultzer, DL Davis, SM Tariot, PN Dagerman, KS Lebowitz, BD Lyketsos, CG Rosenheck, RA Hsiao, JK Lieberman, JA Schneider, LS AF Sultzer, David L. Davis, Sonia M. Tariot, Pierre N. Dagerman, Karen S. Lebowitz, Barry D. Lyketsos, Constantine G. Rosenheck, Robert A. Hsiao, John K. Lieberman, Jeffrey A. Schneider, Lon S. TI Antipsychotic Medication Treatment Response in Alzheimer's Disease (CATIE-AD): Patient Symptoms, Function, and Life Quality, and Caregiver Well-being SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 [Sultzer, David L.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Sultzer, David L.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Davis, Sonia M.] Quintiles, Res Triangle Pk, NC USA. [Tariot, Pierre N.] Banner Alzheimers Inst, Phoenix, AZ USA. [Dagerman, Karen S.] USC, Dept Psychiat, Keck Sch Med, Los Angeles, CA USA. [Lebowitz, Barry D.] UCSD, Div Geriatr Psychiat, La Jolla, CA USA. [Lyketsos, Constantine G.] Johns Hopkins Bayview Med Ctr, Dept Psychiat, Baltimore, MD USA. [Rosenheck, Robert A.] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, New Haven, CT USA. [Hsiao, John K.] NIMH, Bethesda, MD 20892 USA. [Lieberman, Jeffrey A.] Columbia Univ, New York, NY USA. [Schneider, Lon S.] USC, Dept Psychiat, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2009 VL 17 IS 3 SU 1 BP A74 EP A75 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA V16YW UT WOS:000207905900090 ER PT J AU Lopez, L Cook, EF Horng, MS Hicks, LS AF Lopez, Lenny Cook, E. Francis Horng, Mark S. Hicks, LeRoi S. TI Lifestyle Modification Counseling for Hypertensive Patients: Results From the National Health and Nutrition Examination Survey 1999-2004 SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID HIGH BLOOD-PRESSURE; UNITED-STATES; CARDIOVASCULAR-DISEASE; WEIGHT-LOSS; PREVALENCE; PREVENTION; PHYSICIAN; AWARENESS; EXERCISE; ADVICE AB BACKGROUND Lifestyle modification is recommended for all patients with the diagnosis of hypertension. METHODS We examined 3,497 adult hypertensive participants (representing 42 million Americans), from the National Health and Nutrition Examination Survey (NHANES) 1999-2004.We analyzed the rate, demographic, and clinical factors of participants who reported receiving lifestyle counseling and their adherence. RESULTS Of the 3,497 participants with hypertension, 84% reported receiving lifestyle modification counseling. After adjustment for demographic and clinical characteristics, non-Hispanic blacks were more likely to report receiving counseling (odds ratio (OR), 2.5; P < 0.001) when compared to whites. Men (OR, 1.5; P=0.02) reported receiving counseling more often than women as well as those with Medicare insurance (OR, 1.5; P= 0.02) compared to the privately insured. Participants who were hypercholesterolemic (OR, 1.7; P < 0.001), diabetic (OR, 3.5; P < 0.001), overweight (OR, 1.5; P < 0.001), or obese (OR 3.0; P < 0.001) reported receiving lifestyle counseling more often than those without these conditions. Of those receiving counseling, 88% reported adhering to those recommendations. After adjustment for demographic and clinical characteristics, only non-Hispanic blacks (OR, 2.8; P < 0.001) and those aged >60 (OR, 1.9; P=0.04) were more likely to report adhering when advised. CONCLUSIONS High cardiovascular risk hypertensive patients had high rates of lifestyle counseling. However, gaps exist in lifestyle counseling for young and low cardiovascular risk hypertensive patients. In addition, differences in rates of adherence exist especially in those with high cardiovascular risk comorbid conditions. Future work is needed to increase adherence to lifestyle counseling for all hypertensive patients. C1 [Lopez, Lenny] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lopez, Lenny; Hicks, LeRoi S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Brigham & Womens Faulkner Hosp Program,Dept Med, Boston, MA 02115 USA. [Cook, E. Francis; Hicks, LeRoi S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Cook, E. Francis] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Horng, Mark S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Hicks, LeRoi S.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. EM llopez1@partners.org FU Institutional National Research Service Award [5T32HP11001-19] FX Dr Lopez acknowledges the support of an Institutional National Research Service Award #5T32HP11001-19.This article was presented as an oral presentation at the March 2007 New England Regional Society of General Internal Medicine (SGIM) meeting and as a poster at the April 2007 National SGIM meeting. Dr Hicks acknowledges being supported by Project Export grant #P20 MD00537 from NCMHD and the Robert Wood Johnson Harold Amos Medical Faculty Development Program. NR 39 TC 15 Z9 16 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAR PY 2009 VL 22 IS 3 BP 325 EP 331 DI 10.1038/ajh.2008.348 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 410LZ UT WOS:000263580100019 PM 19096366 ER PT J AU Kooienga, L Fried, L Scragg, R Kendrick, J Smits, G Chonchol, M AF Kooienga, Laura Fried, Linda Scragg, Robert Kendrick, Jessica Smits, Gerard Chonchol, Michel TI The Effect of Combined Calcium and Vitamin D(3) Supplementation on Serum Intact Parathyroid Hormone in Moderate CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Vitamin D(3); chronic kidney disease; secondary hyperparathyroidism ID CHRONIC KIDNEY-DISEASE; BONE-MINERAL DENSITY; SECONDARY HYPERPARATHYROIDISM; D DEFICIENCY; HEMODIALYSIS-PATIENTS; CALCIDIOL DEFICIENCY; ERGOCALCIFEROL; PARICALCITOL; PREVALENCE; WOMEN AB Background: Studies addressing the effects of vitamin D(3) supplementation on secondary hyperparathyroidism in patients with moderate chronic kidney disease are scarce. Study Design: Post hoc analysis of the randomized clinical trial Vitamin D, Calcium, Lyon Study II (DECALYOS II) to assess effects according to baseline estimated glomerular filtration rate (eGFR). Setting & Participants: Multicenter, randomized, double-blinded, placebo-controlled study of 639 elderly women randomly assigned to calcium-vitamin D(3) fixed combination; calcium plus vitamin D(3) separate combination, or placebo. Interventions: Placebo or calcium (1,200 mg) and vitamin D(3) (800 IU) in fixed or separate combination. Outcomes & Measurements: Proportion of participants with a mean decrease in intact parathyroid hormone (iPTH) level of 30% or greater. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and categorized as 60 or greater, 45 to 59, and less than 45 mL/min/1.73 m(2). Results: 610 participants had an eGFR at baseline: 288 (47.2%), 222 (36.4%), and 100 (16.4%) were in each decreasing eGFR category. Across decreasing eGFR groups, 88%, 86%, and 89% had 25-hydroxyvitamin D (25[OH]D) levels less than 15 ng/mL at baseline. On treatment, similar improvements in the proportion of participants achieving 25(OH)D levels greater than 30 ng/mL at 6 months were seen in all kidney function groups (43%, 49%, and 41%, respectively). Active regimens versus placebo increased mean 25(OH)D levels from baseline in all eGFR groups at all times (P < 0.001 for all). The proportion with a 30% or greater decrease in iPTH level at 6 months was 50% in all eGFR groups on treatment versus 6% to 9% for placebo (P < 0.001 for all). The effects of the intervention on iPTH levels did not differ according to baseline eGFR (interaction P > 0.1 for all times). Limitations: This study included only elderly white women. Conclusion: Vitamin D3 was effective in increasing 25(OH)D and decreasing iPTH levels in patients with moderate chronic kidney disease. C1 [Kooienga, Laura; Kendrick, Jessica; Smits, Gerard; Chonchol, Michel] Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Denver, CO 80262 USA. [Fried, Linda] Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Scragg, Robert] Univ Auckland, Sch Populat Hlth, Epidemiol & Biostat Sect, Auckland 1, New Zealand. RP Chonchol, M (reprint author), Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Box C-280, Denver, CO 80262 USA. EM michel.chonchol@uchsc.edu OI Scragg, Robert/0000-0003-0013-2620 NR 30 TC 25 Z9 27 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2009 VL 53 IS 3 BP 408 EP 416 DI 10.1053/j.ajkd.2008.09.020 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 414DJ UT WOS:000263843800010 PM 19185400 ER PT J AU Kashner, TM Trivedi, MH Wicker, A Fava, M Greist, JH Mundt, JC Shores-Wilson, K Rush, AJ Wisniewski, SR AF Kashner, T. Michael Trivedi, Madhukar H. Wicker, Annie Fava, Maurizio Greist, John H. Mundt, James C. Shores-Wilson, Kathy Rush, A. John Wisniewski, Stephen R. TI Voice Response System to Measure Healthcare Costs: A STAR*D Report SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; MEDICATION ALGORITHM PROJECT; REPORT QIDS-SR; SELF-REPORT; DEPRESSIVE SYMPTOMATOLOGY; TELEPHONE INTERVIEW; PROVIDER RECORDS; QUICK INVENTORY; RATING-SCALE; PSYCHOMETRIC EVALUATION AB To evaluate a telephone-operated, voice response (IVR) system designed collect use-of-care data from patients with depression (UAC-IVR). Study Design: Patient self-reports from repeated IVR surveys were compared with provider records 3789 patients with major depression at 41 clinical sites participating in the Sequenced Alternatives to Relieve Depression (STAR*D) trial. Methods: UAC-IVR responses were examined for consistency and compared with provider records compute reporting biases and intraclass correlation coefficients. Predictors of inconsistent and reporting biases were based on mixed logistic and regression models adjusted for and predisposing and enabling covariates, and corrected for nesting and repeated measures. Results: Inconsistent responses were found 10% of calls and 21% of patients. Under-reporting biases (-20%) and moderate agreement (intraclass correlation of 68%) were found UAC-IVR responses were compared with records. IVR reporting biases were less patients after 3 calls or more (experience), for patients with severe baseline symptoms (motivation), and for patients who gave consistent IVR (reliability). Bias was unrelated to treatment outcomes or demographic factors. Conclusion: Clinical managers should use IVR to collect service histories only after patients are properly trained and responses monitored for consistency and reporting biases. C1 [Kashner, T. Michael; Trivedi, Madhukar H.; Wicker, Annie; Shores-Wilson, Kathy; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Kashner, T. Michael] Vet Hlth Adm, Washington, DC USA. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greist, John H.; Mundt, James C.] Healthcare Technol Syst Inc, Madison, WI USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Kashner, TM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM michael.kashner@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU National Institute of Mental Health, National Institutes of Health [N01-MH-90003] FX This project was funded in whole or in part with federal funds from the National Institute of Mental Health, National Institutes of Health, under contract N01-MH-90003 (A.J. Rush, MD, Principal Investigator). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services or the Department of Veterans Affairs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. NR 57 TC 4 Z9 5 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAR PY 2009 VL 15 IS 3 BP 153 EP 162 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 426LF UT WOS:000264709100001 PM 19298096 ER PT J AU Ta, S Goldzweig, C Juzba, M Lee, M Wenger, N Yano, EM Asch, S AF Ta, Sony Goldzweig, Caroline Juzba, Michael Lee, Martin Wenger, Neil Yano, Elizabeth M. Asch, Steve TI Addressing Physician Concerns About Performance Profiling: Experience With a Local Veterans Affairs Quality Evaluation Program SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE veterans' administration; diabetes mellitus; quality of care; clinical performance ID HEALTH-CARE FACILITIES; PAY-FOR-PERFORMANCE; DIABETES CARE; OF-CARE; CHRONIC DISEASE; DISPARITIES; MELLITUS AB The Authors investigated the addition of novel quality indicators, patient risk adjustment, and simple statistics in an ongoing clinician feedback initiative that profiles diabetes care for 13 Veterans Affairs (VA) clinics. Data were extracted from a computerized database for calendar years 2004 to 2005. Performance was assessed with 4 monitoring measures, 3 intermediate outcomes, and 3 appropriate treatment measures. Attainment rates for each indicator were calculated by clinic. The effect of risk adjustment and the significance of clinic performance variation were determined with multivariate logistic models. Analysis of the 10 quality measures revealed lower attainment and greater clinic-level variation for the less familiar indicators. Statistically significant performance variations were detected among clinics, with several being of a clinically important magnitude. Risk adjustment did not substantially change performance. The addition of clinically relevant quality measures and simple statistics appeared to enhance the characterization of performance by this profiling program. (Am J Med Qual 2009;24:123-131) C1 [Ta, Sony; Wenger, Neil] Univ Calif Los Angeles, Dept Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90096 USA. [Goldzweig, Caroline; Lee, Martin; Yano, Elizabeth M.; Asch, Steve] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Juzba, Michael] Long Beach VA Healthcare Syst, Long Beach, CA USA. RP Ta, S (reprint author), Univ Calif Los Angeles, Dept Gen Internal Med & Hlth Serv Res, 911 Broxton Ave,3rd Floor, Los Angeles, CA 90096 USA. EM sonyta@med-net.ucla.edu FU VA Health Services Research and Development Center of Excellence for the Study of Healthcare Provider Behavior; National Research Service Award [T32HP19001]; University of California Los Angeles Department of General Internal Medicine and Health Services Research FX Dr Ta and Dr Wenger are with the UCLA Department of General Internal Medicine. and Health Services Research, Los Angeles, CA; Dr Goldzweig, Dr Lee, Dr Yano, and Dr Asch are with the Greater Los Angeles VA Healthcare System, Los Angeles, CA; and Dr Juzba is with the Long Beach VA Healthcare System, Long Beach, CA. This research was funded by a local grant from the VA Health Services Research and Development Center of Excellence for the Study of Healthcare Provider Behavior, and by a National Research Service Award grant (T32HP19001) from the University of California Los Angeles Department of General Internal Medicine and Health Services Research. The authors' have no financial interests involving this research and this work was not supported by any commercial entity. The views expressed in this article are those of the authors and do not necessarily represent the views of the organizations with which they are affiliated. Corresponding author Sony Ta, MD, MPH, UCLA Department of General Internal Medicine and Health Services Research, 911 Broxton Avenue, 3rd Floor, Los Angeles, CA 90096 (email: sonyta@mednet.ucla.edu). NR 25 TC 2 Z9 2 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR-APR PY 2009 VL 24 IS 2 BP 123 EP 131 DI 10.1177/1062860608330828 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 423KJ UT WOS:000264494900005 PM 19228893 ER PT J AU Fox, AJ Millar, J Raymond, J Pryor, JC Roy, D Tomlinson, GA McKay, JP Molyneux, AJ AF Fox, A. J. Millar, J. Raymond, J. Pryor, J. C. Roy, D. Tomlinson, G. A. McKay, J. P. Molyneux, A. J. TI Dangerous Advances in Measurements from Digital Subtraction Angiography: When Is a Millimeter Not a Millimeter? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Neuroradiology CY JUN 09-11, 2007 CL Chicago, IL SP Amer Soc Neuroradiol ID UNRUPTURED INTRACRANIAL ANEURYSMS; CAROTID STENOSIS; SYMPTOMATIC PATIENTS; CT ANGIOGRAPHY; ANGIOPLASTY; PATIENT; ARTERY; STENT AB Aneurysms need accurate millimeters (mm), Direct millimeters were lost with digital subtraction angiography (DSA) years ago, with measurements in pixels. Advances in DSA can now give inherent millimeters. The Cerecyte aneurysm coiling trial's angiographic core lab assesses images from compact disc (CD). External fiducials for millimeter calibration are required, Of 25 cases with two 10 mm fiducials, near and far from the intensifier, the midline mean is between 9 "mm" to 15 "mm". Yet 10 mm must be 10 mm. This variance is potentially dangerous. Proprietary software seems to prohibit calibration transfer via CD to another vendor's system. C1 [Fox, A. J.; McKay, J. P.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Neuroradiol, Toronto, ON M4N 3M5, Canada. [Millar, J.] Southampton Gen Hosp, Wessex Neurol Ctr, Dept Neuroradiol, Southampton SO9 4XY, Hants, England. [Raymond, J.; Roy, D.] Univ Montreal, Hop Notre Dame, Dept Neuroradiol, Montreal, ON, Canada. [Pryor, J. C.] Harvard Univ, Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02115 USA. [Tomlinson, G. A.] Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. [Molyneux, A. J.] Univ Oxford, Oxford Neurovasc & Neuroradiol Res Unit, Oxford, England. RP Fox, AJ (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Neuroradiol, 2075 Bayview Ave,Room AG31b, Toronto, ON M4N 3M5, Canada. EM allan.fox@sunnybrook.ca RI Raymond, Jean/D-3940-2011; Tomlinson, George/L-5432-2016 OI Tomlinson, George/0000-0002-9328-6399 NR 20 TC 8 Z9 10 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2009 VL 30 IS 3 BP 459 EP 461 DI 10.3174/ajnr.A1381 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 419WF UT WOS:000264249700005 PM 19039047 ER PT J AU Desikan, RS Cabral, HJ Fischl, B Guttmann, CRG Blacker, D Hyman, BT Albert, MS Killiany, RJ AF Desikan, R. S. Cabral, H. J. Fischl, B. Guttmann, C. R. G. Blacker, D. Hyman, B. T. Albert, M. S. Killiany, R. J. TI Temporoparietal MR Imaging Measures of Atrophy in Subjects with Mild Cognitive Impairment That Predict Subsequent Diagnosis of Alzheimer Disease SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ENTORHINAL CORTEX NEURONS; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; COORDINATE SYSTEM; RHESUS-MONKEY; WORK GROUP; DEMENTIA; SEGMENTATION; HIPPOCAMPAL; ASSOCIATION AB BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) represents a transitional state between normal aging and Alzheimer disease (AD). Our goal was to determine if specific temporoparietal regions can predict the time to progress from MCI to AD. MATERIALS AND METHODS: MR images from 129 individuals with MCI were analyzed to identify the volume of 14 neocortical and 2 non-neocortical brain regions, comprising the temporal and parietal lobes. In addition, 3 neuropsychological test scores were included to determine whether they would provide independent information. After a mean follow-up time of 5 years, 44 of these individuals had progressed to a diagnosis of AD. RESULTS: Cox proportional hazards models demonstrated significant effects for 6 MR imaging regions with the greatest differences being the following: the entorhinal cortex (hazard ratio [HR] = 0.54, P <.001), inferior parietal lobule (hazard ratio [HR] = 0.64, P <.005), and middle temporal gyrus (HR = 0.64, P <.004), indicating decreased risk with larger volumes. A multivariable model showed that a combination of the entorhinal cortex (HR = 0.60, P <.001) and the inferior parietal lobule (HR = 0.62, P <.01) was the best predictor of time to progress to AD. A multivariable model reiterated the importance of including both MR imaging and neuropsychological variables in the final model. CONCLUSIONS: These findings reaffirm the importance of the entorhinal cortex and present evidence for the importance of the inferior parietal lobule as a predictor of time to progress from MCI to AD. The inclusion of neuropsychological performance in the final model continues to highlight the importance of using these measures in a complementary fashion. C1 [Killiany, R. J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Ctr Biomed Imaging, Boston, MA 02118 USA. [Cabral, H. J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Killiany, R. J.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA. [Fischl, B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Blacker, D.; Killiany, R. J.] Massachusetts Gen Hosp, Dept Psychiat, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Hyman, B. T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fischl, B.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Guttmann, C. R. G.; Killiany, R. J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Albert, M. S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Killiany, RJ (reprint author), Boston Univ, Sch Med, Dept Anat & Neurobiol, Ctr Biomed Imaging, 700 Albany St,W701, Boston, MA 02118 USA. EM killiany@bu.edu OI Cabral, Howard/0000-0002-1185-8331 FU National Institute on Aging [P01-AG04953]; National Center for Research Resources [P41-RR14075, R01-RR16594, U24-RRO21382]; National Institute for Biomedical Imaging and Bioengineering [R01-EB001550]; National Institute for Neurological Diseases and Stroke. FX This work was supported by grants from the National Institute on Aging (P01-AG04953), the National Center for Research Resources (P41-RR14075, R01-RR16594, U24-RRO21382), the National Institute for Biomedical Imaging and Bioengineering (R01-EB001550), and the National Institute for Neurological Diseases and Stroke. NR 54 TC 45 Z9 45 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2009 VL 30 IS 3 BP 532 EP 538 DI 10.3174/ajnr.A1397 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 419WF UT WOS:000264249700019 PM 19112067 ER PT J AU Stefancyk, AL AF Stefancyk, Amanda L. TI Leading the Way SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM astefancyk@partners.org 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 0002-936X J9 AM J NURS JI Am. J. Nurs. PD MAR PY 2009 VL 109 IS 3 BP 68 EP 69 PG 2 WC Nursing SC Nursing GA 414TW UT WOS:000263889100032 ER PT J AU Jakobiec, FA Nguyen, J Mandell, K Fay, A AF Jakobiec, Frederick A. Nguyen, John Mandell, Kenneth Fay, Aaron TI Complex Palpebral Odontogenic Choristoma: A Reappraisal of the Origin of Teeth-bearing Periocular Lesions SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PHAKOMATOUS-CHORISTOMA; DENTIGEROUS CYST; RESPIRATORY EPITHELIUM; ORBITAL TERATOMA; MAXILLARY ANTRUM; FORDYCE NODULES; MEMBRANE GRAFT; TUMOR; KERATOCYST; TOOTH AB PURPOSE: To describe the findings observed in a congenital ectopic tooth of the lower inner eyelid and explain its origin. DESIGN: Retrospective and interventional clinicopathologic study. METHODS: Histopathologic evaluation of sequentially excised specimens over 4 years and radiographic study of and associated dental abnormalities, compared with critical reevaluation of similar reported cases in the literature. RESULTS: The ectopic eyelid tooth clinically created a dome-shaped mass and microscopically displayed advanced cytodifferentiation but incomplete morphogenesis with clearly identifiable ameloblasts, enamel, odontoblasts, and dentin, surrounded by an intact dental sac. Swollen oral mucosal epithelium with associated sebaceous Fordyce nodules, residual ciliated odontogenic epithelium, embryonic epithelial rests, and accessory mucinous and sero-mucinous accessory salivary glands were discovered in place of normal conjunctiva. The tarsus with meibomian glands was absent but islands of cartilage were present. CONCLUSIONS: Because of the variety of the ectopic tissues that were exhibited, a causative displacement of oral embryonic epithelium with extensive differentiating potentialities is posited. Two previously reported palpebral dental choristomas also had identical locations in the inferomedial eyelid. This is the site where the phakomatous choristoma may be encountered, but this unencapsulated mass creates an eyelid thickening without a globoid configuration and infiltrates the inferior orbit. After a careful re-appraisal of published reports of orbital cysts bearing a tooth that were formerly diagnosed as "teratomas," we have concluded that they developed from similar embryonic oral (buccal) epithelial displacements rather than from aberrant germ cells, based on the cysts' linings and the associated accessory salivary glands in their walls. This view is further supported by the absence of heterologous teratomatous elements of endodermal or neuroectodermal derivation. A clinical and surgical approach to management and a new diagnostic schema for odontogenic choristomas are proposed. (Am J Ophthalmol 2009;147:531-543. (C) 2009 by Elsevier Inc. All rights reserved.) C1 [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Nguyen, John; Fay, Aaron] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Oculoplast & Reconstruct Surg, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Room 321, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 46 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2009 VL 147 IS 3 BP 531 EP 543 DI 10.1016/j.ajo.2008.09.033 PG 13 WC Ophthalmology SC Ophthalmology GA 411ON UT WOS:000263659000027 PM 19217956 ER PT J AU Dempsey, EC Wick, MJ Karoor, V Barr, EJ Tallman, DW Wehling, CA Walchak, SJ Laudi, S Le, M Oka, M Majka, S Cool, CD Fagan, KA Klemm, DJ Hersh, LB Gerard, NP Gerard, C Miller, YE AF Dempsey, Edward C. Wick, Marilee J. Karoor, Vijaya Barr, Erica J. Tallman, Dustin W. Wehling, Carol A. Walchak, Sandra J. Laudi, Sven Le, Mysan Oka, Masahiko Majka, Susan Cool, Carlyne D. Fagan, Karen A. Klemm, Dwight J. Hersh, Louis B. Gerard, Norma P. Gerard, Craig Miller, York E. TI Neprilysin Null Mice Develop Exaggerated Pulmonary Vascular Remodeling in Response to Chronic Hypoxia SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROTEIN-KINASE-C; ANGIOTENSIN-CONVERTING ENZYME; NEUROENDOCRINE CELL SYSTEM; ENDOPEPTIDASE EC 3.4.24.11; SMOOTH-MUSCLE-CELLS; NEUTRAL ENDOPEPTIDASE; ENDOCRINE-CELLS; BRONCHOPULMONARY DYSPLASIA; VASOPEPTIDASE INHIBITORS; ARTERIAL-HYPERTENSION AB Neprilysin is a transmembrane metalloendopeptidase that degrades neuropeptides that are important for both growth and contraction. In addition to promoting carcinogenesis, decreased levels of neprilysin increases inflammation and neuroendocrine cell hyperplasia, which may predispose to vascular remodeling. Early pharmacological studies showed a decrease in chronic hypoxic pulmonary hypertension with neprilysin inhibition. We used a genetic approach to test the alternate hypothesis that neprilysin depletion increases chronic hypoxic pulmonary hypertension. Loss of neprilysin had no effect on baseline airway or alveolar wall architecture, vessel density, cardiac function, hematocrit, or other relevant peptidases. Only lung neuroendocrine cell hyperplasia and a subtle neuropeptide imbalance were found. After chronic hypoxia, neprilysin-null mice exhibited exaggerated pulmonary hypertension and striking increases in muscularization of distal vessels. Subtle thickening of proximal media/adventitia not typically seen in mice was also detected. In contrast, adaptive right ventricular hypertrophy was less than anticipated. Hypoxic wild-type pulmonary vessels displayed close temporal and spatial relationships between decreased neprilysin and increased cell growth. Smooth muscle cells from neprilysin-null pulmonary arteries had increased proliferation compared with controls, which was decreased by neprilysin replacement. These data suggest that neprilysin may be protective against chronic hypoxic pulmonary hypertension in the lung, at least in part by attenuating the growth of smooth muscle cells. Lung-targeted strategies to increase neprilysin levels could have therapeutic benefits in the treatment of this disorder. (Am J Pathol 2009, 174:782-796; DOI: 10.2353/ajpath.2009.080345) C1 [Dempsey, Edward C.; Wick, Marilee J.; Karoor, Vijaya; Barr, Erica J.; Tallman, Dustin W.; Walchak, Sandra J.; Oka, Masahiko; Majka, Susan; Fagan, Karen A.; Klemm, Dwight J.; Hersh, Louis B.] Univ Colorado Denver & Hlth Sci Ctr, Cardiovasc Pulm Res Lab, Denver, CO USA. [Laudi, Sven] Univ Colorado Denver & Hlth Sci Ctr, Dept Anesthesiol, Denver, CO 80202 USA. [Cool, Carlyne D.] Univ Colorado Denver & Hlth Sci Ctr, Dept Pathol, Denver, CO 80202 USA. [Dempsey, Edward C.; Wick, Marilee J.; Barr, Erica J.; Wehling, Carol A.; Le, Mysan; Klemm, Dwight J.; Miller, York E.] Denver VA Med Ctr, Pulm & Crit Care Sect, Denver, CO USA. [Cool, Carlyne D.] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA. [Hersh, Louis B.] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gerard, Norma P.; Gerard, Craig] Childrens Hosp, Dept Pediat, Div Pulm, Boston, MA USA. [Dempsey, Edward C.] Univ Colorado Denver & Hlth Sci Ctr, Univ Colorado Canc Ctr, Denver, CO USA. RP Dempsey, EC (reprint author), Univ Colorado Denver, Cardiovasc Pulm Res Lab, B-133,12700 E 19th Ave, Aurora, CO 80046 USA. EM edward.dempsey@ucdenver.edu FU National Heart Lung and Blood Institute PPG [HL14985, RO-1, HL078927] FX Supported by grants from the National Heart Lung and Blood Institute PPG #HL14985 and RO-1 #HL078927 to E.C.D. NR 71 TC 22 Z9 22 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 2009 VL 174 IS 3 BP 782 EP 796 DI 10.2353/ajpath.2009.080345 PG 15 WC Pathology SC Pathology GA 410XW UT WOS:000263612600008 PM 19234135 ER PT J AU Rigor, DL Bodyak, N Bae, S Choi, JH Zhang, L Ter-Ovanesyan, D He, ZH McMullen, JR Shioi, T Izumo, S King, GL Kang, PM AF Rigor, Debra L. Bodyak, Natalya Bae, Soochan Choi, Jun H. Zhang, Li Ter-Ovanesyan, Dmitry He, Zhiheng McMullen, Julie R. Shioi, Tetsuo Izumo, Seigo King, George L. Kang, Peter M. TI Phosphoinositide 3-kinase Akt signaling pathway interacts with protein kinase C beta 2 in the regulation of physiologic developmental hypertrophy and heart function SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE transgenic mice; constitutive active; dominant negative; protein kinase B ID CARDIAC-HYPERTROPHY; CLASS-I; ACTIVATION; INDUCTION; FAILURE; MYOCARDIUM; GROWTH; SIZE; OVEREXPRESSION; CONTRACTILITY AB Rigor DL, Bodyak N, Bae S, Choi JH, Zhang L, Ter-Ovanesyan D, He Z, McMullen JR, Shioi T, Izumo S, King GL, Kang PM. Phosphoinositide 3-kinase Akt signaling pathway interacts with protein kinase C beta 2 in the regulation of physiologic developmental hypertrophy and heart function. Am J Physiol Heart Circ Physiol 296: H566-H572, 2009. First published January 2, 2009; doi:10.1152/ajpheart.00562.2008.-The phosphoinositide 3-kinase (PI3-kinase)-protein kinase B (Akt) signaling pathway is essential in the induction of physiological cardiac hypertrophy. In contrast, protein kinase C beta 2 (PKC beta 2) is implicated in the development of pathological cardiac hypertrophy and heart failure. Thus far, no clear association has been demonstrated between these two pathways. In this study, we examined the potential interaction between the PI3-kinase and PKC beta 2 pathways by crossing transgenic mice with cardiac specific expression of PKC beta 2, constitutively active (ca) PI3-kinase, and dominant-negative (dn) PI3-kinase. In caPI3-kinase/PKC beta 2 and dnPI3-kinase/PKC beta 2 double-transgenic mice, the heart weight-to-body weight ratios and cardiomyocyte sizes were similar to those observed in caPI3-kinase and dnPI3-kinase transgenic mice, respectively, suggesting that the regulation of physiological developmental hypertrophy via modulation of cardiomyocyte size proceeds through the PI3-kinase pathway. In addition, we observed that caPI3-kinase/PKC beta 2 mice showed improved cardiac function while the function of dnPI3-kinase/PKC beta 2 mice was similar to that of the PKC beta 2 group. PKC beta 2 protein levels in both dnPI3-kinase/PKC beta 2 and PKC beta 2 mice were significantly upregulated. Interestingly, however, PKC beta 2 protein expression was significantly attenuated in caPI3-kinase/PKC beta 2 mice. PI3-kinase activity measured by Akt phosphorylation was not affected by PKC beta 2 overexpression. These data suggest a potential interaction between these two pathways in the heart, where PI3-kinase is predominantly responsible for the regulation of physiological developmental hypertrophy and may act as an upstream modulator of PKC beta 2 with the potential for rescuing the pathological cardiac dysfunction induced by overexpression of PKC beta. C1 [Rigor, Debra L.; Bodyak, Natalya; Bae, Soochan; Choi, Jun H.; Zhang, Li; Ter-Ovanesyan, Dmitry; McMullen, Julie R.; Shioi, Tetsuo; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Rigor, Debra L.; Bodyak, Natalya; Bae, Soochan; Choi, Jun H.; Zhang, Li; Ter-Ovanesyan, Dmitry; McMullen, Julie R.; Shioi, Tetsuo; Kang, Peter M.] Harvard Univ, Sch Med, Boston, MA USA. [He, Zhiheng; King, George L.] Joslin Diabet Ctr, Dept Vasc Res, Boston, MA 02215 USA. [Izumo, Seigo] Novartis Inst Biomed Res, Cambridge, MA USA. RP Kang, PM (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, 3 Blackfan Circle,Rm 910, Boston, MA 02215 USA. EM pkang@bidmc.harvard.edu RI Bae, Soochan/H-1315-2011 FU National Heart, Lung, and Blood Institute [RO1-HL-65742] FX This study was supported, in part, by National Heart, Lung, and Blood Institute Grant RO1-HL-65742 (P. M. Kang). NR 34 TC 12 Z9 12 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 MAR PY 2009 VL 296 IS 3 BP H566 EP H572 DI 10.1152/ajpheart.00562.2008 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 412SY UT WOS:000263745700006 PM 19122165 ER PT J AU Blevins, JE Morton, GJ Williams, DL Caldwell, DW Bastian, LS Wisse, BE Schwartz, MW Baskin, DG AF Blevins, James E. Morton, Gregory J. Williams, Diana L. Caldwell, David W. Bastian, Lloyd S. Wisse, Brent E. Schwartz, Michael W. Baskin, Denis G. TI Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8 SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE paraventricular nucleus; retrograde tracer; cholecystokinin ID MELANOCYTE-STIMULATING HORMONE; CORTICOTROPIN-RELEASING HORMONE; AGOUTI-RELATED PROTEIN; REDUCES FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; LEPTIN ACTION; MEAL SIZE; FEEDING INHIBITION; AREA POSTREMA; RECEPTOR AB Blevins JE, Morton GJ, Williams DL, Caldwell DW, Bastian LS, Wisse BE, Schwartz MW, Baskin DG. Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8. Am J Physiol Regul Integr Comp Physiol 296: R476-R484, 2009. First published December 24, 2008; doi:10.1152/ajpregu.90544.2008. Melanocortin 4 receptors (MC4R) are hypothesized to mediate the central nervous system actions of leptin to enhance the satiety effects of cholecystokinin (CCK). To further elucidate this mechanism, we confirmed that peripheral administration of CCK-8 is less effective in producing this effect in MC4R-deficient mice ( MC4R(-/-)). Whereas intraperitoneal (ip) CCK-8 at 0.75 nmol/kg lean body mass (lbm) suppressed food intake in wild-type mice, CCK-8 doses of 7.5 nmol/kg lbm were required to attenuate food intake in MC4R(-/-) mice. To determine whether melanocortin signaling in the hypothalamic paraventricular nucleus (PVN) participates in regulating this CCK satiety response, we administered the MC3/MC4R antagonist, SHU9119, into the PVN of rats before ip CCK-8 administration. PVN administration of SHU9119 attenuated the ability of CCK-8 to reduce 30-min food intake by 20%. To determine whether MC4R are expressed by PVN neurons that project directly to hindbrain nuclei involved in the satiety response to ip CCK-8, the retrograde tracer fluorescent cholera toxin subunit B was injected into the nucleus tractus solitarius (NTS) of the hindbrain. After 4 days, labeled PVN neurons were collected by laser capture microdissection and found to express MC4R mRNA by quantitative RT-PCR analysis. These data provide evidence for a neuroanatomical link between hypothalamic melanocortin signaling in the PVN and NTS neurons that regulate food intake. These findings highlight the contribution of melanocortin signaling in the PVN toward regulating the satiety effects of CCK-8 while acknowledging that melanocortin-dependent pathways in other brain regions and/or melanocortin-independent mechanisms are also important in this mechanism. C1 [Blevins, James E.; Caldwell, David W.; Bastian, Lloyd S.; Baskin, Denis G.] VA Puget Sound Hlth Care Syst, Off Res & Dev, Dept Vet Affairs Med Ctr, Med Res Serv, Seattle, WA 98108 USA. [Blevins, James E.; Morton, Gregory J.; Williams, Diana L.; Wisse, Brent E.; Schwartz, Michael W.; Baskin, Denis G.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Baskin, Denis G.] Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA. RP Blevins, JE (reprint author), VA Puget Sound Hlth Care Syst, Off Res & Dev, Dept Vet Affairs Med Ctr, Med Res Serv, Mail stop S-151,1660 S Columbian Way, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu RI Schwartz, Michael/H-9950-2012; Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU University of Washington; CNRU; NIH [DK-17047, P30DK-035816, P30 DK-017047-31, P30 DK017047 -31689, P30 DK-035816, PO1 DK-068384] FX This material is based on work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs including the VA Career Development Program, Merit Review Research Program, Research Enhancement Award Program, and Career Scientist Program. D. G. Baskin is the recipient of a Department of Veterans Affairs Senior Research Career Scientist Award at the VA Puget Sound Health Care System. The research was also supported by the biomedical research core programs,particularly the Cellular and Molecular Imaging Core of the National Institutes of Health (NIH) Diabetes Endocrinology Research Center and NIH CNRU at the University of Washington. Grant support for the research was provided by a Pilot and Feasibility grant from the University of Washington CNRU and NIH Grants DK-17047, P30DK-035816, P30 DK-017047 -31, P30 DK017047 -31689, P30 DK-035816, and PO1 DK-068384. NR 53 TC 38 Z9 39 U1 0 U2 3 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 MAR PY 2009 VL 296 IS 3 BP R476 EP R484 DI 10.1152/ajpregu.90544.2008 PG 9 WC Physiology SC Physiology GA 412ST UT WOS:000263745200002 PM 19109369 ER PT J AU Vagin, O Kraut, JA Sachs, G AF Vagin, Olga Kraut, Jeffrey A. Sachs, George TI Role of N-glycosylation in trafficking of apical membrane proteins in epithelia SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE apical sorting; apical membrane retention; H-K-ATPase beta-subunit; lectin ID DARBY CANINE KIDNEY; INFLUENZA-VIRUS HEMAGGLUTININ; H,K-ATPASE BETA-SUBUNIT; POLARIZED MDCK CELLS; L-TYPE LECTINS; PLASMA-MEMBRANE; LIPID RAFTS; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; TRANSMEMBRANE DOMAIN AB Vagin O, Kraut JA, Sachs G. Role of N-glycosylation in trafficking of apical membrane proteins in epithelia. Am J Physiol Renal Physiol 296: F459-F469, 2009. First published October 29, 2008; doi: 10.1152/ajprenal.90340.2008.- Polarized distribution of plasma membrane transporters and receptors in epithelia is essential for vectorial functions of epithelia. This polarity is maintained by sorting of membrane proteins into apical or basolateral transport containers in the trans-Golgi network and/or endosomes followed by their delivery to the appropriate plasma membrane domains. Sorting depends on the recognition of sorting signals in proteins by specific sorting machinery. In the present review, we summarize experimental evidence for and against the hypothesis that N-glycans attached to the membrane proteins can act as apical sorting signals. Furthermore, we discuss the roles of N-glycans in the apical sorting event per se and their contribution to folding and quality control of glycoproteins in the endoplasmic reticulum or retention of glycoproteins in the plasma membrane. Finally, we review existing hypotheses on the mechanism of apical sorting and discuss the potential roles of the lectins, VIP36 and galectin-3, as putative apical sorting receptors. C1 [Vagin, Olga; Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. [Vagin, Olga; Kraut, Jeffrey A.; Sachs, George] Univ Calif Los Angeles, Membrane Biol Lab, Los Angeles, CA 90073 USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles Hlth Care Syst, Div Nephrol, Los Angeles, CA USA. RP Vagin, O (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Bldg 113,Rm 324,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM olgav@ucla.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-077149, DK-58333, DK-053642] FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-077149, DK-58333, and DK-053642. Downloaded from ajprenal. physiology. org on February 23, 2009 NR 95 TC 75 Z9 77 U1 0 U2 8 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 MAR PY 2009 VL 296 IS 3 BP F459 EP F469 DI 10.1152/ajprenal.90340.2008 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 410CB UT WOS:000263552400001 PM 18971212 ER PT J AU Rongey, CA Kanwal, F Hoang, T Gifford, AL Asch, SM AF Rongey, Catherine A. Kanwal, Fasiha Hoang, Tuyen Gifford, Allen L. Asch, Steven M. TI Viral RNA Testing in Hepatitis C Antibody-Positive Veterans SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID INJECTION-DRUG USERS; VIRUS-INFECTION; UNITED-STATES; ANTIVIRAL THERAPY; PLUS RIBAVIRIN; LIVER FIBROSIS; CIRRHOSIS; AMINOTRANSFERASE; MULTICENTER; ELIGIBILITY AB Background: Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the U.S. population. As up to 30% of HCV-antibody (anti-HCV)-positive patients leave negative HCV ribonucleic acid (RNA), indicating resolution of infection, VA (Veterans Affairs) guidelines recommend RNA testing on all anti-HCV-positive patients. As HCV RNA testing is a prequel to treatment, perceived eligibility for treatment may influence the decision to order an RNA test. This study was designed to determine the patient and healthcare facility factors associated with patient receipt of HCV RNA testing. Methods: Two logistic regression analyses were conducted in anti-HCV-positive patients, including the entire sample and then on a subsample excluding sites with routine HCV RNA testing policies, using data stored in the VA Southern California Network data warehouse. Significant patient- and site-level predictors of patient receipt of HCV RNA testing were determined. Results: Of the 13,257 antibody-positive patients, 76% received HCV RNA testing. Excluding sites with routine HCV RNA testing, patients aged >65 years (RR=0.79) and illicit drug users (RR=0.94) were significantly less likely to receive HCV RNA testing. Patients with abnormal transaminases (RR=1.14), presence of non-HCV hepatitis (RR=1.08), or decompensated liver disease (RR=1.22) were significantly more likely to receive HCV RNA testing. Conclusions: Without policies for routine RNA testing, patients with hepatitic C who either are aged >65 years or are illicit: drug users are less likely to be tested. Also, patient receipt of RNA testing becomes dependent on clinical cites of hepatic decompensation or inflammation. The results Support the implementation of routine RNA testing for anti-HCV-positive patients. C1 [Rongey, Catherine A.] Univ Calif Los Angeles, Robert Wood Johnson Clin Schloars Program, Los Angeles, CA 90024 USA. [Kanwal, Fasiha] Univ Calif Los Angeles, Ctr Outcomes Res & Educ, Los Angeles, CA 90024 USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Los Angeles, CA 90095 USA. [Rongey, Catherine A.; Hoang, Tuyen; Asch, Steven M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Rongey, Catherine A.] Univ So Calif, Div Gastroenterol, Los Angeles, CA 90033 USA. [Kanwal, Fasiha] St Louis Univ, Div Gastroenterol, St Louis, MO 63103 USA. [Gifford, Allen L.] Boston Univ, Dept Internal Med, Boston, MA 02215 USA. RP Rongey, CA (reprint author), Univ So Calif, Dept Med, GI Liver Div, Sch Med, 1200 N State St,LAC Room 12-137, Los Angeles, CA 90033 USA. EM rongey@usc.edu FU VA HIV-Hepatitis Quality Enhancement Research Initiative FX Dr. Rongey is supported by the Robert Wood Johnson Clinical Scholars and Foundation. This research was also supported by the VA HIV-Hepatitis Quality Enhancement Research Initiative. NR 28 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAR PY 2009 VL 36 IS 3 BP 235 EP 238 DI 10.1016/j.amepre.2008.10.013 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 409XE UT WOS:000263538300007 PM 19162434 ER PT J AU Medoff, BD Landry, AL Wittbold, KA Sandall, BP Derby, MC Cao, ZF Adams, JC Xavier, RJ AF Medoff, Benjamin D. Landry, Aimee L. Wittbold, Kelley A. Sandall, Barry P. Derby, Merran C. Cao, Zhifang Adams, Joe C. Xavier, Ramnik J. TI CARMA3 Mediates Lysophosphatidic Acid-Stimulated Cytokine Secretion by Bronchial Epithelial Cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE bronchial epithelial cells; asthma; lysophosphatidic acid; thymic stromal lymphopoietin; CARMA3 ID NF-KAPPA-B; THYMIC STROMAL LYMPHOPOIETIN; ALLERGIC AIRWAY INFLAMMATION; DENDRITIC CELLS; T-CELLS; GENE-EXPRESSION; IMMUNE-SYSTEM; MURINE MODEL; ACTIVATION; ASTHMA AB NF-kappa B activation in bronchial epithelial cells is important for the development of allergic airway inflammation, and may control the expression of critical mediators of allergic inflammation such as thymic stromal lymphopoietin (TSLP) and the chemokine CCL20. Members of the caspase recruitment domain (CARD) family of proteins are differentially expressed in tissue and help mediate NF-kappa B activity in response to numerous stimuli. Here we demonstrate that CARMA3 (CARD10) is specifically expressed in human airway epithelial cells, and that expression of CARMA3 in these cells leads to activation of NF-kappa B. CARMA3 has recently been shown to mediate NF-kappa B activation in embryonic fibroblasts after stimulation with lysophosphatidic acid (LPA), a bioactive lipid-mediator that is elevated in the lungs of individuals with asthma. Consistent with this, we demonstrate that stimulation of airway epithelial cells with LPA leads to increased expression of TSLP and CCL20. We then show that inhibition of CARMA3 activity in airway epithelial cells reduces LPA-mediated NF-kappa B activity and the production of TSLP and CCL20. In conclusion, these data demonstrate that LPA stimulates TSLP and CCL20 expression in bronchial epithelial cells via CARMA3-mediated NF-kappa B activation. C1 [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Gastrointestinal Unit, Boston, MA 02114 USA. [Medoff, Benjamin D.; Wittbold, Kelley A.; Sandall, Barry P.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Medoff, Benjamin D.; Wittbold, Kelley A.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Cao, Zhifang; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. [Adams, Joe C.] Harvard Univ, Sch Med, Otopathol Lab, Boston, MA USA. [Adams, Joe C.] Harvard Univ, Sch Med, Dept Otolaryngol, MA Eye & Ear Infirm, Boston, MA 02115 USA. [Adams, Joe C.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Gastrointestinal Unit, Simches Res Bldg,Room 7222,185 Cambridge St, Boston, MA 02114 USA. EM bmedoff@partners.org; xavier@molbio.mgh.harvard.edu FU American Thoracic Society Unrestricted Research Award; National Institutes of Health [A1062773, HL088297] FX This work was supported by an American Thoracic Society Unrestricted Research Award to B.D.M., and by National Institutes of Health grants A1062773 to R.J.X. and HL088297 to B.D.M. and R.J.X. NR 64 TC 24 Z9 26 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 2009 VL 40 IS 3 BP 286 EP 294 DI 10.1165/rcmb.2008-0129OC PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 412PC UT WOS:000263735700005 PM 18757306 ER PT J AU Kolliputi, N Waxman, AB AF Kolliputi, Narasaiah Waxman, Aaron B. TI IL-6 Cytoprotection in Hyperoxic Acute Lung Injury Occurs via Suppressor of Cytokine Signaling-1-Induced Apoptosis Signal-Regulating Kinase-1 Degradation SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE IL-6; apoptosis signal-regulating kinase-1; suppressor of cytokine signaling-1; lung injury; tumor necrosis factor receptor-1 ID NECROSIS-FACTOR RECEPTOR; CELL-DEATH; INDUCED ACTIVATION; ENDOTHELIAL-CELLS; IN-VIVO; ASK1; SOCS3; PROTECTS; THIOREDOXIN; INHIBITOR AB Hyperoxic acute lung injury (HALI) is characterized by a cell death response that is inhibited by IL-6. Suppressor of cytokine signaling-1 (SOCS-1) is an antiapoptotic negative regulator of the IL-6-mediated Janus kinase-signal transducer and activator of transcription signaling pathway. We hypothesized that SOCS-1 is a critical regulator and key mediator of IL-6-induced cytoprotection in HALI. To test this hypothesis, we characterized the expression of SOCS-1 and downstream apoptosis signal-regulating kinase (ASK)-1-Jun N-terminal kinase signaling molecules in small airway epithelial cells in the presence of H(2)O(2), which induces oxidative stress. We also examined these molecules in wild-type and lung-specific IL-6 trans genic (Tg(+)) mice exposed to 100% oxygen for 72 hours. In control small airway epithelial cells exposed to H(2)O(2) or in wild-type mice exposed to 100% oxygen, a marked induction of ASK-1 and plun N-terminal kinase was observed. Both IL-6-stimulated endogenous SOCS-1 and SOCS-1 overexpression abolished H(2)O(2)-induced ASK-1 activation. In addition, IL-6 Tg+ mice exposed to 100% oxygen exhibited reduced ASK-1 levels and enhanced SOCS-1 expression compared with wild-type mice. Interestingly, no significant changes in activation of the key ASK-1 activator, tumor necrosis factor receptor-1//tumor necrosis factor receptor-associated factor-2 were observed between wild-type and IL-6 Tg(+) mice. Furthermore, the interaction between SOCS-1 and ASK-1 promotes ubiquitin-mediated degradation both in vivo and in vitro. These studies demonstrate that SOCS-1 is an important regulator in IL-6-induced cytoprotection against HALL C1 [Kolliputi, Narasaiah; Waxman, Aaron B.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Pulm Crit Care Unit, Boston, MA 02114 USA. RP Waxman, AB (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Pulm Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM abwaxman@Partners.org RI Kolliputi, Narasaiah/I-6050-2012 OI Kolliputi, Narasaiah/0000-0002-2654-1900 FU National Institutes of Health [R01 HL074859] FX This work was supported by National Institutes of Health grant R01 HL074859 (A.B.W.). NR 50 TC 29 Z9 30 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 2009 VL 40 IS 3 BP 314 EP 324 DI 10.1165/rcmb.2007-0287OC PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 412PC UT WOS:000263735700008 PM 18776134 ER PT J AU Tamashiro, E Xiong, GX Anselmo-Lima, WT Kreindler, JL Palmer, JN Cohen, NA AF Tamashiro, Edwin Xiong, Guoxiang Anselmo-Lima, Wilma T. Kreindler, James L. Palmer, James N. Cohen, Noam A. TI Cigarette smoke exposure impairs respiratory epithelial ciliogenesis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article; Proceedings Paper CT 54th Annual Fall Meeting of the American-Rhinologic-Society CY SEP 20, 2008 CL Chicago, IL SP Amer Rhinol Soc DE Cigarette; cilia; ciliogenesis; concentrate; rhinosinusitis; tobacco; transepithelial resistance ID ENDOSCOPIC SINUS SURGERY; RAT TRACHEAL EPITHELIUM; LIQUID INTERFACE CULTURES; CILIARY BEAT FREQUENCY; NECROSIS-FACTOR-ALPHA; CHRONIC RHINOSINUSITIS; MECHANICAL INJURY; OXYGEN RADICALS; TOBACCO-SMOKE; EX-SMOKERS AB Background: Cigarette smoke exposure is considered an important negative prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no clear mechanistic evidence implicating cigarette smoke exposure in the poor clinical evolution of the disease or in the maintenance of the inflammatory state characterizing CRS. This study aimed to evaluate the effects of cigarette smoke exposure on respiratory cilia differentiation. Methods: Monse nasal septal epithelium cultures grown at an air-liquid interface were used as a model of respiratory epithelium. After 5 days of cell growth, cultures were exposed to air on the apical surface. Additionally, cigarette smoke condensate (CSC; the particulate phase of tobacco smoke) or cigarette smoke extract (CSE; the volatile phase) Were diluted in the basolateral compartment in different concentrations. After 15 days of continuous exposure, scanning electron microscopy and immunofluorescence for type IV tubulin were used to determine presence and maturation of cilia. Transepithelial resistance was also recorded to evaluate confluence and physiological barrier integrity. Results: CSC and CSE impair ciliogenesis in a dose-dependent manner with notable effects in concentrations higher than 30 mu g/mL, yielding >70% nonciliation and shorter cilia compared With control. No statistical difference on transepithelial resistance was evident. Conclusion: CSC and CSE exposure negatively impacts ciliogenesis of respiratory cells at concentrations not effecting transepithelial resistance. The impairment on ciliogenesis reduce the mucociliary clearance apparatuts after injury and/or infection and may explain the poor response to therapy for CRS patients exposed to tobacco smoke. C1 [Palmer, James N.; Cohen, Noam A.] Univ Penn Hlth Syst, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA USA. [Palmer, James N.; Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Dept Surg, Philadelphia, PA USA. [Tamashiro, Edwin; Anselmo-Lima, Wilma T.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Ophthalmol Otorhinolaryngol & Head & Neck Su, BR-05508 Sao Paulo, Brazil. [Xiong, Guoxiang; Kreindler, James L.] Univ Penn Hlth Syst, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Div Rhinol, 5th Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu RI Tamashiro, Edwin/C-5062-2012; OI Tamashiro, Edwin/0000-0002-3153-6292; Cohen, Noam/0000-0002-9462-3932 NR 45 TC 53 Z9 53 U1 2 U2 39 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AMJ RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAR-APR PY 2009 VL 23 IS 2 BP 117 EP 122 DI 10.2500/ajra.2009.23.3280 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 431IV UT WOS:000265055900001 PM 19401033 ER PT J AU Pandharipande, PV Choy, G del Carmen, MG Gazelle, GS Russell, AH Lee, SI AF Pandharipande, Pari V. Choy, Garry del Carmen, Marcela G. Gazelle, G. Scott Russell, Anthony H. Lee, Susanna I. TI MRI and PET/CT for Triaging Stage IB Clinically Operable Cervical Cancer to Appropriate Therapy: Decision Analysis to Assess Patient Outcomes SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cervical cancer; decision analysis; PET/CT; pelvic MRI ID GYNECOLOGIC-ONCOLOGY-GROUP; EXTENDED-FIELD IRRADIATION; PELVIC RADIATION-THERAPY; RADICAL HYSTERECTOMY; PRETREATMENT EVALUATION; AMERICAN-COLLEGE; CARCINOMA; IIA; RADIOTHERAPY; LYMPHADENECTOMY AB OBJECTIVE. We evaluated the ability of pretreatment MRI and PET/CT to improve outcomes for patients with clinically staged International Federation of Gynecology and Obstetrics (FIGO) IB cervical cancer. MATERIALS AND METHODS. We developed a decision-analytic model to predict outcomes for a hypothetical patient cohort with FIGO IB cervical cancer who underwent pretreatment MRI, PET/CT, MRI and PET/CT, or no further imaging (direct pursuance of surgery). The model incorporated imaging performance, underlying parametrial extension and lymph node involvement, surgery and chemoradiation treatment options, and survival penalties from incorrect assessment of disease extent. Three outcomes were compared: 5-year overall survival, percentage of patients receiving correct primary therapy, and percentage of patients spared "trimodality therapy" (surgery followed by chemoradiation). Sensitivity analysis was performed to assess the effects of model uncertainty on outcomes. RESULTS. The preferred imaging strategy depended on the outcome studied. Five-year overall survival was comparable across strategies but was highest with the noimaging strategy (92.37%) and with PET/CT (92.36%) and lowest with MRI (92.30%). Triage to correct primary therapy was highest with PET/CT (89.27%) and lowest with MRI (68.21%). Avoidance of trimodality therapy was highest with combined MRI and PET/CT (95.01%) and lowest with the noimaging strategy (82.32%). Results were somewhat sensitive to imaging test performance characteristics but stable across most parameter ranges tested. CONCLUSION. Pretreatment imaging of FIGO IB cervical cancer patients can optimize triage to appropriate therapy. Although imaging does not appear to improve survival, PET/CT maximizes patient triage to correct therapy, and combined MRI and PET/CT spares the most patients unnecessary trimodality therapy. C1 [Pandharipande, Pari V.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Choy, Garry; del Carmen, Marcela G.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. [Russell, Anthony H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lee, Susanna I.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pari@mgh-ita.org NR 30 TC 21 Z9 21 U1 0 U2 5 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 MAR PY 2009 VL 192 IS 3 BP 802 EP 814 DI 10.2214/AJR.08.1224 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 416KT UT WOS:000264005700037 PM 19234280 ER PT J AU Cai, WL Tabbara, M Takata, N Yoshida, H Harris, GJ Novelline, RA de Moya, M AF Cai, Wenli Tabbara, Malek Takata, Noboru Yoshida, Hiroyuki Harris, Gordon J. Novelline, Robert A. de Moya, Marc TI MDCT for Automated Detection and Measurement of Pneumothoraces in Trauma Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE computerized volumetry; emergency radiology; occult pneumothorax; pneumothorax; quantifying pneumothorax ID THORACIC COMPUTED-TOMOGRAPHY; SEVERELY INJURED PATIENTS; BLUNT CHEST TRAUMA; OCCULT; SIZE; CT AB OBJECTIVE. The size of a pneumothorax is an important index to guide the emergency treatment of trauma patients-chest tube drainage. The purpose of this study was to develop and validate an automated computer-aided volumetry scheme for detection and measurement of pneumothoraces for trauma patients imaged with MDCT. MATERIALS AND METHODS. Three pigs and 68 trauma patients with at least one diagnosed occult pneumothorax (23 women and 45 men; age range, 14-89 years; mean age, 41 +/- 19 years) were selected for the development and validation of our computer-aided volumetry scheme for pneumothorax. Computer-aided volumetry of pneumothorax consisted of five automated steps: extraction of pleural region, detection of pneumothorax candidates, delineation of the detected pneumothorax candidates, reduction of false-positive findings, and report of the volumetric measurement of pneumothoraces. RESULTS. In the animal study, our computer-aided volumetry scheme yielded a mean value of 24.27 +/- 0.64 mL (SD) compared with 25 mL of air volume manually injected in each scan. The correlation coefficients were 0.999 and 0.997 for the in vivo and ex vivo comparison, respectively. In the patient study, the sensitivity of our computer-aided volumetry scheme was 100% with a false-positive rate of 0.15 per case for 32 occult pneumothoraces = 25 mL. The correlation coefficient was 0.999 for manual volumetry comparison. This automated computer-aided volumetry scheme took approximately 3 minutes to finish the detection and measurement per case. CONCLUSION. The results show that our computer-aided volumetry scheme provides an automated method for accurate and efficient detection and measurement of pneumothoraces in MDCT images of trauma patients. C1 [Cai, Wenli; Takata, Noboru; Yoshida, Hiroyuki; Harris, Gordon J.; Novelline, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli; Tabbara, Malek; Takata, Noboru; Yoshida, Hiroyuki; Harris, Gordon J.; Novelline, Robert A.; de Moya, Marc] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tabbara, Malek; de Moya, Marc] Harvard Univ, Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Cai, WL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,400C, Boston, MA 02114 USA. EM cai.wenli@mgh.harvard.edu OI Tabbara, Malek/0000-0003-1046-7803 NR 22 TC 13 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2009 VL 192 IS 3 BP 830 EP 836 DI 10.2214/AJR.08.1339 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 416KT UT WOS:000264005700040 PM 19234283 ER PT J AU Shi, AA Lee, SI AF Shi, Ann A. Lee, Susanna I. TI Radiological Reasoning: Algorithmic Workup of Abnormal Vaginal Bleeding with Endovaginal Sonography and Sonohysterography (vol 191, pg S68, 2008) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Correction C1 [Shi, Ann A.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Lee, Susanna I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shi, AA (reprint author), Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. NR 1 TC 0 Z9 0 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 MAR PY 2009 VL 192 IS 3 BP S62 EP S62 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 413LL UT WOS:000263794500009 ER PT J AU Kozanek, M Fu, EC Van de Velde, SK Gill, TJ Li, G AF Kozanek, Michal Fu, Eric C. Van de Velde, Samuel K. Gill, Thomas J. Li, Guoan TI Posterolateral Structures of the Knee in Posterior Cruciate Ligament Deficiency SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE posterior cruciate ligament (PCL); lateral collateral ligament popliteus; posterolateral knee structures; PCL injury ID SIMULATED MUSCLE LOADS; LATERAL COLLATERAL LIGAMENTS; ARTHROSCOPIC EVALUATION; POPLITEUS TENDON; NATURAL-HISTORY; JOINT; FLEXION; RECONSTRUCTION; INJURIES; ANTERIOR AB Background: In vitro data suggest that injury to the posterior cruciate ligament stresses the posterolateral structures of the knee, placing them at greater risk of secondary injury. However, it is not known how isolated posterior cruciate ligament deficiency affects these soft tissue stabilizers of the knee joint in vivo. Hypothesis: Posterior cruciate ligament deficiency will alter the apparent length patterns of the lateral collateral ligament (LCL) and popliteus. Study Design: Controlled laboratory study. Methods: The apparent length changes in the lateral collateral ligament and popliteus muscle-tendon unit during weightbearing knee flexion were studied in 14 patients with isolated, unilateral posterior cruciate ligament deficiency using magnetic resonance imaging, dual-orthogonal fluoroscopy, and 3-dimensional modeling. Data of the injured and uninjured contralateral sides were compared. Results: Posterior cruciate ligament deficiency caused significant increases in the apparent length of both posterolateral structures (P < .05). The differences between injured and uninjured contralateral side were greatest at 120 of knee flexion in the lateral collateral ligament (48.2 +/- 6.1 mm and 51.6 +/- 6.1 mm, respectively) and at 30 of knee flexion in the popliteus (101.2 +/- 9.3 mm and 110.4 +/- 10.2 mm, respectively). Conclusion: Deficiency of the posterior cruciate ligament alters the length patterns of posterolateral structures in vivo and might place them at greater risk of secondary injury. Clinical Relevance: Reestablishment of normal kinematics after posterior cruciate ligament injury is critical for restoring normal function of posterolateral structures of the knee. C1 [Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Li, G (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institutes of Health [R01 AR 052408]; National Football League Charities Foundation FX The authors gratefully acknowledge the financial support of the National Institutes of Health (R01 AR 052408) and National Football League Charities Foundation. We would also like to thank the patients for their participation in this study and Ramprasad Papannagari, Louis E. DeFrate, Kyung Wook Nha, Jong Keun Seon, and Bijoy Thomas for technical assistance. NR 39 TC 10 Z9 10 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 MAR PY 2009 VL 37 IS 3 BP 534 EP 541 DI 10.1177/0363546508325664 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 419KJ UT WOS:000264218000011 PM 19088056 ER PT J AU Mathisen, DJ AF Mathisen, Douglas J. TI 2008 Midwest Surgical Association Harridge Lecture SO AMERICAN JOURNAL OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Cardiothorac Surg, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Dept Cardiothorac Surg, Boston, MA 02114 USA. EM dmathisen@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAR PY 2009 VL 197 IS 3 BP 275 EP 278 DI 10.1016/j.amjsurg.2008.12.001 PG 4 WC Surgery SC Surgery GA 420GP UT WOS:000264277400002 PM 19245900 ER PT J AU Irving, JA Young, RH AF Irving, Julie A. Young, Robert H. TI Microcystic Stromal Tumor of the Ovary Report of 16 Cases of a Hitherto Uncharacterized Distinctive Ovarian Neoplasm SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-07, 2008 CL Denver, CO SP US & Canadian Acad Pathol DE ovary; neoplasm; microcystic stromal tumor ID LEYDIG-CELL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; DIFFERENTIAL-DIAGNOSIS AB We have encountered 16 ovarian neoplasms of probable stromal origin whose most distinctive feature is microcystic change, which is usually conspicuous. Oil the basis or our extensive experience with ovarian tumors, the neoplasm is unique and warrants separate categorization; we have elected to designate it "microcystic stromal tumor" because of its most striking feature. The patients ranged from 26 to 63 (mean 45) years of age and typically presented with it pelvic mass. Hormonal manifestations were possibly present in only 2. All tumors were unilateral with it mean size of 8.7 (range: 2 to 27)cm and none had evidence of extraovarian spread. The tumors were solid-cystic (11 cases), solid (3 cases), or predominantly cystic (2 cases). The solid component was usually firm and tun or white-tan, but in 1 case was yellowish; soft foci were present in 3 cases and small foci of hemorrhage. necrosis, or both. in 3. Oil microscopic examination the appearance of the tumors varied according to the relative prominence of their 3 fundamental components: microcysts, solid cellular regions, and fibrous stroma. Microcysts dominated in 9 cases, were roughly equal to noncystic morphology in 5 cases and were minor in 2. The microcystic pattern was characterized by small rounded to oval cystic spaces, in areas coalescing to larger irregular channels; intracytoplasmic vacuoles were also frequently present. The solid cellular areas were usually focally intersected by fibrous bands and hyaline plaques reminiscent of thecoma. The cells contained moderately conspicuous finely granular, lightly cosinophilic cytoplasm, with generally bland, round to oval or spindle-shaped nuclei with tine chromatin rind small indistinct nucleoli, loci of bizarre nuclei were, however, present in 10 cases. Mitotic rate was low in all cases, ranging front 0 to 2 mitoses/10 high-power fields. Immunohistochemcial results were as follows: CD10, 16/16 cases positive; vimentin, 16/16 eases positive: inhibin, 1/16 cases weakly positive; calretinin, 1/16 cases positive; cytokeratin, 4/6 cases focally positive; and epithelial membrane antigen, 0; 16 cases positive. Microcystic change can be observed in a wide variety of ovarian tumors and the broad potential differential diagnosis is discussed in the text. For tumors which have been well sampled and exhibit (1) a microcystic pattern and regions with lobulated cellular masses with intervening, sometimes hyalinized fibrous stroma, (2) ail absence of morphologic features enabling any other specific diagnosis in the sex cord-stromal category, (3) an absence of epithelial elements, and (4) an absence of teratomatous or other germ cell elements, we propose the designation "microcystic stromal tumor." The characteristic immunophenotype is CD10(+)/vimentin+/epithelial membrane antigen-, with focal cytokeralin-positivity in one-quarter of cases; inhibin and/or calretinin are usually negative. Seven patients with available follow-up are without evidence of disease at a mean of 4.25 years (range: 1.5 to 12.5y) from the time of initial diagnosis. These tumors, to date, have occurred over a wide age range in Postpubertal females, are characteristically unilateral, and confined to the ovary at presentation. They represent, in addition to the sclerosing stromal tumor (segregated out 3 decades ago), it distinctive subtype of ovarian tumor, likely also belonging to the stromal category based on current evidence. C1 [Irving, Julie A.] Royal Jubilee Hosp, Dept Lab Med Pathol & Med Genet, Victoria, BC V8R 1J8, Canada. [Irving, Julie A.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. [Young, Robert H.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Irving, JA (reprint author), Royal Jubilee Hosp, Dept Lab Med Pathol & Med Genet, 1952 Bay St, Victoria, BC V8R 1J8, Canada. EM Julie.Irving@viha.ca NR 28 TC 28 Z9 33 U1 0 U2 4 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 MAR PY 2009 VL 33 IS 3 BP 367 EP 375 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 413AR UT WOS:000263765800005 PM 18971779 ER PT J AU Green, SM Green, JA Januzzi, JL AF Green, Sandy M. Green, Jamie A. Januzzi, James L., Jr. TI Natriuretic Peptide Testing for Heart Failure Therapy Guidance in the Inpatient and Outpatient Setting SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Review DE acutely destabilized heart; hospital readmission rates; mortality; cardiac biomarkers; B-type natriuretic peptide; N-terminal fragment; NT-proBNP ID EMERGENCY-DEPARTMENT PRIDE; AMINO-TERMINAL PROBNP; NT-PROBNP; HOSPITAL LENGTH; ACUTE DYSPNEA; HIGH-RISK; BNP; DIAGNOSIS; MANAGEMENT; TRIAL AB Acutely destabilized heart failure is one of the most common diagnoses in the modern health care system. It has high hospital readmission rates and significant short-, medium-, and long-term mortality, likely due to misdiagnosis or failure to assess adequate treatment before discharge. Cardiac biomarkers such as B-type natriuretic peptide and its amino terminal cleavage equivalent N-terminal fragment have rapidly become one of the key tools in the diagnosis and guidance of heart failure therapy. In this article, we shall review the data on the current use of the natriuretic peptides for the diagnosis, prognosis, and management of heart failure in both the Outpatient and inpatient settings. C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Januzzi, James L., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Green, Sandy M.; Green, Jamie A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 39 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD MAR-APR PY 2009 VL 16 IS 2 BP 171 EP 177 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 423KS UT WOS:000264495800011 PM 19300043 ER PT J AU Saban, DR Chauhan, SK Zhang, X El Annan, J Jin, Y Dana, R AF Saban, D. R. Chauhan, S. K. Zhang, X. El Annan, J. Jin, Y. Dana, R. TI 'Chimeric' Grafts Assembled from Multiple Allodisparate Donors Enjoy Enhanced Transplant Survival SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Allograft rejection; allosensitization; corneal allograft; immune regulation; Th1; tolerance ID ORTHOTOPIC CORNEAL ALLOGRAFTS; T-CELLS; EPITHELIUM; REJECTION; MICE; IMMUNOLOGY; EXPRESSION; ANTIGENS; CD4(+); SHEETS AB Certain components of a graft that provoke alloimmunity may not be vital for graft function or critical as targets of rejection. Corneal transplantation is an example of this, because graft epithelium plays a role in allosensitization, whereas corneal graft endothelium-which shares the same alloantigens-is the critical target in allorejection. In this study, we found that exploiting this biology by replacing donor epithelium of an allograft with an allodisparate third-party epithelium yields a marked enhancement in transplant survival. Such 'chimeric' allografts consisted of a C3H/He (H-2(k)) corneal epithelium over a C57BL/6 (H-2(b)) epithelial-denuded cornea (or v.v.) and orthotopically placed on BALB/c (H-2(d)) hosts. Conventional corneal allografts (C3H/He or C57BL/6) or isografts (BALB/c) were also transplanted on BALB/c hosts. Alloreactive T-cell frequencies (CD4(+) interferon [IFN]-gamma(+)) primed to the graft endothelium were strongly diminished in chimeric hosts relative to conventionally allografted hosts. This was corroborated by a decreased T-cell infiltration (p = 0.03) and a marked enhancement of allograft survival (p = 0.001). Our results represent the first successful demonstration of chimeric tissue, epithelial-denuded allograft plus third-party allodisparate epithelium, in the promotion of allograft survival. Moreover, chimeric grafting can be readily performed clinically, whereby corneal allograft rejection remains a significant problem particularly in inflamed graft beds. C1 [Saban, D. R.; Chauhan, S. K.; Zhang, X.; El Annan, J.; Jin, Y.; Dana, R.] Schepens Eye Res Inst, Boston, MA USA. [Dana, R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Saban, D. R.; Chauhan, S. K.; Zhang, X.; El Annan, J.; Jin, Y.; Dana, R.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Dana, R (reprint author), Schepens Eye Res Inst, Boston, MA USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health [EYRO1-12963, EYT32-07156]; Fight for Sight and American Society of Cataract and Refractive Surgeons [PD06009] FX The authors would like to thank Drs. Ammon Peck and Sharmila Masli for their excellent discussions during the development of this study. This work was funded in part by the National Institutes of Health grants EYRO1-12963 (RD) and EYT32-07156 (DRS) as well as by a joint grant funded by the Fight for Sight and American Society of Cataract and Refractive Surgeons (PD06009; DRS). NR 24 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2009 VL 9 IS 3 BP 473 EP 482 DI 10.1111/j.1600-6143.2008.02535.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 409PS UT WOS:000263518900006 PM 19260831 ER PT J AU Bannerman, DD Rinaldi, M Vinyard, BT Laihia, J Leino, L AF Bannerman, Douglas D. Rinaldi, Manuela Vinyard, Bryan T. Laihia, Jarmo Leino, Lasse TI Effects of intramammary infusion of cis-urocanic acid on mastitis-associated inflammation and tissue injury in dairy cows SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID BETA-D-GLUCOSAMINIDASE; ENDOTOXIN-INDUCED MASTITIS; EPITHELIAL-CELL DAMAGE; NECROSIS-FACTOR-ALPHA; BOVINE MAMMARY-GLAND; ESCHERICHIA-COLI; CLINICAL MASTITIS; LACTATE-DEHYDROGENASE; STAPHYLOCOCCUS-AUREUS; BACTERIAL LIPOPOLYSACCHARIDE AB Objective-To evaluate the effects of cis-urocanic acid (cis-UCA) on mammary gland (MG) inflammation and injury associated with Escherichia coli-induced mastitis in dairy cows. Animals-12 lactating dairy cows (36 MGs). Procedures-At 7-week intervals, a different MG in each cow was experimentally inoculated with E coli. At 6-hour intervals from 6 to 36 hours after inoculation, the inoculated MG in each cow was infused with 40 mL of saline (0.9% NaCl) solution, 12.5mM cis-UCA, or 25mM cis-UCA (4 cows/group); ultimately, each cow received each treatment. Immediately prior to and at various time points after inoculation and treatment, milk samples were collected. Bacterial CFUs, somatic cell counts (SCCs), N-acetyl-beta-D-glucosaminidase (NAGase) and lactate dehydrogenase (LDH) activities, and concentrations of bovine serum albumin, tumor necrosis factor-alpha, and cis-UCA were quantified in each milk sample. Results-Compared with findings in saline solution-treated MGs, NAGase and LDH activities in milk samples from cis-UCA-treated MGs were lower. Cis-UCA had no effect on milk SCCs and milk concentrations of bovine serum albumin and tumor necrosis factor-alpha. Furthermore, cis-UCA had no adverse effect on bacterial clearance; CFUS of E coli in MGs treated with saline solution or cis-UCA were equivalent. Conclusions and Clinical Relevance-In cows, milk NAGase and LDH activities were both lower in E coli-infected MGs infused with cis-UCA than in those infused with saline solution, which suggests that cis-UCA reduced mastitis-associated tissue damage. Furthermore, these data indicated that therapeutic concentrations of cis-UCA in milk can be achieved via intramammary infusion. (Am J Vet Res 2009,-70:373-382) C1 [Bannerman, Douglas D.; Rinaldi, Manuela] ARS, Bovine Funct Genom Lab, USDA, BARC E, Beltsville, MD 20705 USA. [Vinyard, Bryan T.] ARS, Biometr Consulting Serv, USDA, BARC W, Beltsville, MD 20705 USA. [Laihia, Jarmo; Leino, Lasse] BioCis Pharma Ltd, Turku 20520, Finland. RP Bannerman, DD (reprint author), US Dept Vet Affairs, Off Res Oversight, 810 Vermont Ave NW 10R, Washington, DC 20420 USA. NR 72 TC 7 Z9 8 U1 0 U2 4 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD MAR PY 2009 VL 70 IS 3 BP 373 EP 382 PG 10 WC Veterinary Sciences SC Veterinary Sciences GA 419FL UT WOS:000264204400009 PM 19254150 ER PT J AU Martyn, JAJ Fagerlund, MJ Eriksson, LI AF Martyn, J. A. J. Fagerlund, M. Jonsson Eriksson, L. I. TI Basic principles of neuromuscular transmission SO ANAESTHESIA LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; BOTULINUM TOXIN; BLOCKING-AGENTS; SUBUNITS CONTRIBUTE; MUSCLE-RELAXANTS; SUCCINYLCHOLINE; DENERVATION; ACTIVATION; EXPRESSION; MATURATION AB Neuromuscular transmission at the skeletal muscle occurs when a quantum of acetylcholine from the nerve endings is released and binds to the nicotinic acetylcholine receptors on the postjunctional muscle membrane. The nicotinic acetylcholine receptors on the endplate respond by opening channels for the influx of sodium ions and subsequent endplate depolarisation leads to muscle contraction. The acetylcholine immediately detaches from the receptor and is hydrolysed by acetylcholinesterase enzyme. Suxamethonium is a cholinergic agonist stimulating the muscle nicotinic acetylcholine receptors prior to causing neuromuscular block. Non-depolarising neuromuscular blocking drugs bind to the nicotinic acetylcholine receptors preventing the binding of acetylcholine. Non-depolarising neuromuscular blocking drugs also inhibit prejunctional alpha 3 beta 2 nicotinic acetylcholine autoreceptors, which can be seen in the clinical settings as train-of-four fade. In some pathological states such as denervation, burns, immobilisation, inflammation and sepsis, there is expression of other subtypes of nicotinic acetylcholine receptors with upregulation of these receptors throughout the muscle membrane. The responses of these receptors to suxamethonium and non-depolarising neuromuscular blocking drugs are different and explain some of the aberrant responses to neuromuscular blocking drugs. C1 [Martyn, J. A. J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Martyn, J. A. J.] Massachusetts Gen Hosp, Dept Anesthesiol, Clin & Biol Pharmacol Lab, Boston, MA 02114 USA. [Martyn, J. A. J.] Shriners Hosp Children, Boston, MA USA. [Fagerlund, M. Jonsson] Karolinska Inst, Dept Anesthesiol, Stockholm, Sweden. [Eriksson, L. I.] Karolinska Univ Hosp, Stockholm, Sweden. RP Martyn, JAJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM jmartyn@etherdome.mgh.harvard.edu FU National Institute of Health, Bethesda [GM55082]; Swedish Kesearch Council Medicine [K2008-53X13405-09-3] FX Work described was supported ill part by Grants GM31569, GM21500-Project IV, GM55082 from the National Institute of Health, Bethesda, MD (to IAJM), Swedish Kesearch Council Medicine (K2008-53X13405-09-3, to LIE), Karolinska li Stockholm City Council Stockholm, Sweden (to MJF and LIE) aiid fi-om Shriners Hospitals Philanthropy, Tampa, FL (to JAJM). NR 38 TC 24 Z9 25 U1 3 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD MAR PY 2009 VL 64 BP 1 EP 9 PG 9 WC Anesthesiology SC Anesthesiology GA 473CL UT WOS:000268182700002 PM 19222426 ER PT J AU Kopman, AF Eikermann, M AF Kopman, A. F. Eikermann, M. TI Antagonism of non-depolarising neuromuscular block: current practice SO ANAESTHESIA LA English DT Article ID POSTOPERATIVE RESIDUAL CURARIZATION; POSTANESTHESIA CARE-UNIT; PULMONARY COMPLICATIONS; INTRAVENOUS NEOSTIGMINE; NERVE-STIMULATION; D-TUBOCURARINE; RECOVERY; VECURONIUM; ATRACURIUM; TRAIN-OF-4 AB There is now mounting evidence that even small degrees of postoperative residual neuromuscular block increases the incidence of adverse respiratory events in the Post Anaesthesia Care Unit and may increase longer-term morbidity as well. In the absence Of quantitative neuromuscular monitoring, residual block is easily missed. A very strong case can be made for the routine administration of a non-depolarising antagonist unless it can be objectively demonstrated that complete recovery has occurred spontaneously. However, the use of acetylcholinesterase inhibitors is associated with the potential for cardiovascular and respiratory side-effects, so there are cogent reasons for using low closes when the level of neuromuscular block is not intense. As little as 0.015-0.025 mg.kg(-1) of neostigmine is required at a train-of-four count Of four With minimal fade, whereas 0.04-0.05 mg.kg(-1) is needed at a train-of-four count of two or three. If only a single twitch or none at all can be evoked, neostigmine should not be expected to promptly reverse neuromuscular block, and antagonism is best delayed till a train-of-four-count of two is achieved. C1 [Kopman, A. F.] Weill Cornell Med Coll, Dept Anesthesiol, New York, NY USA. [Eikermann, M.] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Eikermann, M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Kopman, AF (reprint author), Weill Cornell Med Coll, Dept Anesthesiol, New York, NY USA. EM akopman@nyc.rr.com NR 66 TC 35 Z9 40 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD MAR PY 2009 VL 64 BP 22 EP 30 PG 9 WC Anesthesiology SC Anesthesiology GA 473CL UT WOS:000268182700004 PM 19222428 ER PT J AU Epstein, RH Dexter, F Ehrenfeld, JM Sandberg, WS AF Epstein, Richard H. Dexter, Franklin Ehrenfeld, Jesse M. Sandberg, Warren S. TI Implications of Event Entry Latency on Anesthesia Information Management Decision Support Systems SO ANESTHESIA AND ANALGESIA LA English DT Article ID OPERATING-THEATER; DOCUMENTATION; INTERRUPTION; DISTRACTION; CONFIDENCE; DISPLAYS; SURGERY AB BACKGROUND: Decision support systems (DSSs) are being developed to use events entered in anesthesia information management systems (AIMS) for quality of care, compliance, billing, documentation, and management purposes. DSS performance is impacted by latency from the actual time an event occurs to when it is written to the database, as well as how often the database is queried. Such latencies may result in poor DSS recommendations. METHODS: We analyzed approximately 48,000 cases at Hospital A for latency of two DSS prototype events, Beginh and Surgery End. Each latency was measured from 1) the time that the event was recorded in the AIMS database as having taken place to 2) the time when the first DSS query would have been executed after the documentation of that event by the provider. The effects on latency of 1, 5, and 10 min query intervals were determined. Latencies for Surgery Begin and Surgery End were compared with those of Hospital B, where a different AIMS was used. RESULTS: Network delays and the event processing time of the AIMS contributed <1 s and 30 s, respectively, to latency. Average latencies for the two studied events were approximately half of the query interval, the expected value if the events occurred randomly within each interval. However, the longest 5% of latencies exceeded the query interval. This was not due to providers editing the times of the Begin or End Surgery events, as each occurred in only 0.7%, of cases. Although the median latencies for the two events were longer at Hospital B than Hospital A by a few minutes, the 90th and 95th percentiles of the latencies were much longer at Hospital B (8-30 min, depending on the query interval and the percentile). CONCLUSIONS: DSS performance is influenced by the timeliness of documentation, the incidence of missing documentation and the query interval. Facilities using a DSS, including electronic whiteboards showing patient status, should assess the latencies of the measured events and critique the influence of the latencies on clinical and managerial decisions. C1 [Epstein, Richard H.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Anesthesiol, Philadelphia, PA 19107 USA. [Dexter, Franklin] Univ Iowa, Div Management Consulting, Dept Anesthesia, Iowa City, IA USA. [Dexter, Franklin] Univ Iowa, Div Management Consulting, Dept Hlth Management & Policy, Iowa City, IA USA. [Ehrenfeld, Jesse M.; Sandberg, Warren S.] Harvard Univ, Sch Med, Dept Anaesthesia, Cambridge, MA 02138 USA. [Ehrenfeld, Jesse M.; Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. RP Epstein, RH (reprint author), Thomas Jefferson Univ Hosp, 111 S 11th St,Suite 5480G, Philadelphia, PA 19107 USA. EM richard.epstein@jefferson.edu OI Epstein, Richard/0000-0001-8466-3845; Ehrenfeld, Jesse/0000-0003-3427-0140; Sandberg, Warren/0000-0002-9246-777X NR 16 TC 32 Z9 32 U1 1 U2 2 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 MAR PY 2009 VL 108 IS 3 BP 941 EP 947 DI 10.1213/ane.0b013e3181949ae6 PG 7 WC Anesthesiology SC Anesthesiology GA 409WU UT WOS:000263537300043 PM 19224807 ER PT J AU Lee, C Gianos, M Klaustermeyer, WB AF Lee, Christina Gianos, Mary Klaustermeyer, William B. TI Diagnosis and management of hypersensitivity reactions related to common cancer chemotherapy agents SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CARBOPLATIN-HYPERSENSITIVITY; L-ASPARAGINASE; ESCHERICHIA-COLI; IDIOSYNCRATIC REACTIONS; RAPID DESENSITIZATION; FLUID RETENTION; OVARIAN-CANCER; BREAST-CANCER; OXALIPLATIN AB Objectives: To review clinical hypersensitivity reactions related to common cancer chemotherapy agents and to discuss potential management strategies. Data Sources: PubMed searches were performed for articles published from 1970 to 2008 regarding hypersensitivity to cancer chemotherapy and related agents using the keywords hypersensitivity, allergy, chemotherapy, platinums, taxanes, asparaginase, epipodophyllotoxins, and procarbazine. Retrieved articles were surveyed for additional citations. Study Selection: Articles were reviewed for relevance to the subject matter, and the most pertinent articles were included in this review. Results: Hypersensitivity reactions are commonly associated with the use of certain cancer chemotherapy drugs, including platinums, taxanes, asparaginase, procarbazine, and epipodophyllotoxins. Platinum agents (cisplatin, carboplatin, oxaliplatin) are associated with IgE-mediated hypersensitivity reactions, and skin testing may be indicated. Taxane (paclitaxel, docetaxel)-related reactions are generally non-IgE mediated, and premedication with corticosteroids and antihistamines is usually effective. Asparaginase has a high rate of hypersensitivity reactions that are likely IgE mediated or related to complement activation. Skin testing has been recommended but has not been validated for asparaginase. Procarbazine reactions call be IgE mediated but are also associated with a type III reaction manifested by pulmonary toxicity and cutaneous reactions. Hypersensitivity reactions related to epipodophyllotoxins may involve both immunologic and nonimmunologic factors that may be avoided with a slow infusion and premedication. Conclusion: With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. Knowledge of the presentations of these reactions and management options give the treating physician the means to make all informed decision of how best to proceed. C1 [Lee, Christina; Gianos, Mary; Klaustermeyer, William B.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Allergy & Immunol 111R, Los Angeles, CA 90024 USA. RP Lee, C (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Allergy & Immunol 111R, 11301 Wilshire Blvd, Los Angeles, CA 90024 USA. EM christina.h.lee@hotmail.com NR 79 TC 59 Z9 63 U1 3 U2 16 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAR PY 2009 VL 102 IS 3 BP 179 EP 187 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 420GM UT WOS:000264277000003 PM 19354063 ER PT J AU Pollack, CV Varon, J Garrison, NA Ebrahimi, R Dunbar, L Peacock, WF AF Pollack, Charles V. Varon, Joseph Garrison, Norman A. Ebrahimi, Ramin Dunbar, Lala Peacock, W. Frank TI Clevidipine, an Intravenous Dihydropyridine Calcium Channel Blocker, Is Safe and Effective for the Treatment of Patients With Acute Severe Hypertension SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Scientific Assembly of the American-College-of-Emergency-Physicians CY OCT 18-19, 2007 CL Seattle, WA SP Amer Coll Emergency Phys ID BLOOD-PRESSURE; HEALTHY-VOLUNTEERS; MANAGEMENT; ANTAGONIST; CRISES; EMERGENCIES; EFFICACY; SURGERY AB Study objective: We assess the safety and efficacy of intravenous clevidipine for treating patients with acute severe increase in blood pressure by using prespecified, non-weight-based titration dosing, with continuous maintenance infusion for 18 hours or longer. Methods: Prospective, open-label, single-arm evaluation of patients aged 18 years or older and presenting in the emergency department or ICU with severe hypertension (systolic blood pressure >180 mm Hg and/or diastolic blood pressure >115 mm Hg) and treated with clevidipine to achieve a predetermined, patient-specific systolic blood pressure target range. Clevidipine was initiated at 2 mg per hour and titrated as needed in doubling increments every 3 minutes to a maximum of 32 mg per hour, during 30 minutes, and then continued for a total duration of 18 to 96 hours. Results: Study patients Commonly presented with both acute hypertension and end-organ injury; 81% (102/126) had demonstrable end-organ injury at baseline. Within 30 minutes of starting clevidipine, 88.9% (104/117) of patients achieved target range. Median time to target range was 10.9 minutes. No concomitant intravenous antihypertensives were needed in 92.3% (108/117) of patients receiving 18 hours or more of clevidipine infusion. Clevidipine was well tolerated with successful transition to oral antihypertensive therapy after infusion to a defined blood pressure target in 91.3% (115/126) of patients. Conclusion: Clevidipine, dosed in a non-weight-based manner, was safe and effective in a cohort of patients with severe hypertension at a Starting dose of 2 mg per hour, followed by simple titration during 18 hours or more of continuous infusion. Patients were effectively managed via simple blood pressure cuff monitoring throughout. (Ann Emerg Med. 2009;53:329-338.] C1 [Pollack, Charles V.] Univ Penn, Dept Emergency Med, Penn Hosp, Philadelphia, PA 19107 USA. [Varon, Joseph] Univ Texas Med Sch, Univ Texas Hlth Sci Ctr Houston, St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. Univ Texas Med Branch Galveston, Galveston, TX USA. [Garrison, Norman A.] Jackson Hosp, Montgomery, AL USA. [Ebrahimi, Ramin] Univ Calif Los Angeles, Los Angeles, CA USA. [Ebrahimi, Ramin] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. [Dunbar, Lala] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Peacock, W. Frank] Cleveland Clin, Dept Emergency Med, Cleveland, OH 44106 USA. RP Pollack, CV (reprint author), Univ Penn, Dept Emergency Med, Penn Hosp, 800 Spruce St,2 Pine E, Philadelphia, PA 19107 USA. EM pollackc@pahosp.com OI Varon, Joseph/0000-0002-7622-9974 NR 26 TC 30 Z9 33 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2009 VL 53 IS 3 BP 329 EP 338 DI 10.1016/j.annemergmed.2008.04.025 PG 10 WC Emergency Medicine SC Emergency Medicine GA 422VK UT WOS:000264455600008 PM 18534716 ER PT J AU Shelley, BM Sussman, AL Williams, RL Segal, AR Crabtree, BF AF Shelley, Brian M. Sussman, Andrew L. Williams, Robert L. Segal, Alissa R. Crabtree, Benjamin. F. CA RIOS Net Clinicians TI 'They Don't Ask Me So I Don't Tell Them': Patient-Clinician Communication About Traditional, Complementary, and Alternative Medicine SO ANNALS OF FAMILY MEDICINE LA English DT Article DE Patient-physician relations; communication; complementary therapies; practice-based research; primary health care; traditional medicine ID PRIMARY-CARE CLINICIAN; CANCER-PATIENTS; NATIONAL-SURVEY; BREAST-CANCER; UNITED-STATES; PHYSICIAN; THERAPIES; RACE/ETHNICITY; PERSPECTIVES; PERCEPTIONS AB PURPOSE Although high rates of traditional medicine and complementary and alternative medicine (TM/CAM) use have been well documented, there has been less attention to the factors influencing communication between patients and their primary care clinicians about TM/CAM. Such communication can be important in anticipating possible drug-herb interactions and in assuring agreement about therapeutic plans. METHODS We used sequential, multistage, qualitative methods, including focus groups, in-depth interviews, and a video vignette, to explore communication about TM/CAM between patients and their primary care clinicians. The study was conducted in RIOS Net (Research Involved in Outpatient Settings Network), a Southwestern US practice-based research network, situated largely in Hispanic and American Indian communities where TM/CAM is an important part of self-care. RESULTS One hundred fourteen patients, 41 clinic staff members, and 19 primary care clinicians in 8 clinic sites participated. The degree and nature of TM/CAM communication is based on certain conditions in the clinical encounter. We categorized these findings into 3 themes: acceptance/nonjudgment, initiation of communication, and safety/efficacy. Perceived clinician receptivity to and initiation of discussion about TM/CAM strongly influenced patients' decisions to communicate; perceived clinician expertise in TM/CAM was less important. Clinicians' comfort with patients' self-care approaches and their level of concern about lack of scientific evidence of effectiveness and safety of TM/CAM influenced their communication about TM/CAM with patients. CONCLUSIONS Specific communication barriers limit patient-clinician communication about TM/CAM. Clinicians who wish to communicate more effectively with their patients about these topics and better integrate the types of care their patients use can change the communication dynamic with simple strategies designed to overcome these barriers. C1 [Shelley, Brian M.] First Choice Community Healthcare, S Valley Family Hlth Commons, Albuquerque, NM 87105 USA. [Shelley, Brian M.; Sussman, Andrew L.; Williams, Robert L.] Univ New Mexico, Dept Family & Community Med, Albuquerque, NM 87131 USA. [Segal, Alissa R.] Massachusetts Coll Pharm & Hlth Sci, Dept Pharm Practice, Boston, MA USA. [Segal, Alissa R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Crabtree, Benjamin. F.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Family Med, New Brunswick, NJ USA. RP Shelley, BM (reprint author), First Choice Community Healthcare, S Valley Family Hlth Commons, 2001 N Ctr Familiar SW, Albuquerque, NM 87105 USA. EM bshelley@salud.unm.edu FU National Center for Complementary and Alternative Medicine (NCCAM) [1 R21 AT 2323-01]; National Institutes of Health FX This publication was made possible by grant No. 1 R21 AT 2323-01 from the National Center for Complementary and Alternative Medicine (NCCAM). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, or the National Institutes of Health. NR 46 TC 80 Z9 81 U1 5 U2 10 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD MAR-APR PY 2009 VL 7 IS 2 BP 139 EP 147 DI 10.1370/afm.947 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 425UP UT WOS:000264663200008 PM 19273869 ER PT J AU Camposano, SE Greenberg, E Kwiatkowski, DJ Thiele, EA AF Camposano, S. E. Greenberg, E. Kwiatkowski, D. J. Thiele, E. A. TI Distinct clinical characteristics of Tuberous Sclerosis Complex patients with no mutation identified SO ANNALS OF HUMAN GENETICS LA English DT Article DE tuberous sclerosis complex; no mutation identified; mosaicism; lymphangioleiomyomatosis; angiomyolipoma ID GENOTYPE-PHENOTYPE CORRELATIONS; SOMATIC MOSAICISM; MISSENSE MUTATION; TSC2 GENES; LYMPHANGIOLEIOMYOMATOSIS; DISEASE; MANIFESTATIONS; DIAGNOSIS; SEVERITY; FAMILIES AB Tuberous Sclerosis Complex (TSC) is a multi-system disorder that is highly variable in its clinical presentation. Current molecular diagnostic methods permit identification of mutations in either TSC1 or TSC2 in 75-85% of TSC patients. Here we examine the clinical characteristics of those TSC patients who have no mutation identified (NMI). A retrospective review of our patient population that had comprehensive testing for mutations in TSC1/TSC2 identified 23/157 (15%) that were NMI. NMI patients had a lower incidence of brain findings on imaging studies, neurological features, and renal findings than those with TSC2 mutations. In contrast, NMI patients had a lower incidence of seizures than TSC patients with TSC1 mutations, but had a higher incidence of both renal angiomyolipomas and pulmonary lymphangioleiomyomatosis. This distinct constellation of findings suggest that NMI patients may have a unique molecular pathogenesis, different from that seen in TSC patients with the usual mutations in TSC1 and TSC2. We suggest that the mechanisms of disease in these patients include both mosaicism for a TSC2 mutation, and unusual non-coding region mutations in TSC2. C1 [Camposano, S. E.; Greenberg, E.; Thiele, E. A.] Massachusetts Gen Hosp, Carol & James Herscot Ctr, Dept Neurol, Boston, MA 02114 USA. [Kwiatkowski, D. J.] Brigham & Womens Hosp, Div Translat Med, Boston, MA 02115 USA. RP Camposano, SE (reprint author), Massachusetts Gen Hosp, Carol & James Herscot Ctr, Dept Neurol, Tuberous Sclerosis Complex,175 Cambridge St,Suite, Boston, MA 02114 USA. EM scamposano@partners.org FU NIH NINDS [R01 NS31535] FX This work was supported by the Carol and James Herscot Center for Tuberous Sclerosis Complex, and NIH NINDS R01 NS31535. The authors are thankful to Elkan Halpern for his statistical expertise, and to Elisabeth Winterkorn and Kerry Conant for reviewing the manuscript. NR 26 TC 19 Z9 19 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAR PY 2009 VL 73 BP 141 EP 146 DI 10.1111/j.1469-1809.2008.00496.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 408QC UT WOS:000263448700002 PM 19133941 ER PT J AU Ruddy, KJ Partridge, AH AF Ruddy, K. J. Partridge, A. H. TI Adherence with adjuvant hormonal therapy for breast cancer SO ANNALS OF ONCOLOGY LA English DT Editorial Material ID TAMOXIFEN; WOMEN C1 [Ruddy, K. J.; Partridge, A. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ruddy, KJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM Ann_Partridge@dfci.harvard.edu NR 7 TC 19 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2009 VL 20 IS 3 BP 401 EP 402 DI 10.1093/annonc/mdp039 PG 2 WC Oncology SC Oncology GA 413ZU UT WOS:000263834500002 PM 19246419 ER PT J AU Enzinger, PC Ryan, DP Clark, JW Muzikansky, A Earle, CC Kulke, MH Meyerhardt, JA Blaszkowsky, LS Zhu, AX Fidias, P Vincitore, MM Mayer, RJ Fuchs, CS AF Enzinger, P. C. Ryan, D. P. Clark, J. W. Muzikansky, A. Earle, C. C. Kulke, M. H. Meyerhardt, J. A. Blaszkowsky, L. S. Zhu, A. X. Fidias, P. Vincitore, M. M. Mayer, R. J. Fuchs, C. S. TI Weekly docetaxel, cisplatin, and irinotecan (TPC): results of a multicenter phase II trial in patients with metastatic esophagogastric cancer SO ANNALS OF ONCOLOGY LA English DT Article DE chemotherapy; cisplatin; docetaxel; esophageal cancer; gastric cancer; irinotecan ID ADVANCED GASTRIC-CANCER; GASTROESOPHAGEAL JUNCTION; ESOPHAGEAL CANCER; PLUS CISPLATIN; COMBINATION; ADENOCARCINOMA; CAPECITABINE; CARCINOMA; 1ST-LINE AB Background: Recent studies have examined the addition of docetaxel to fluorouracil and cisplatin in advanced esophagogastric cancer. Patients and methods: We carried out a phase I dose-escalation study of weekly docetaxel, cisplatin, and irinotecan (TPC), given on days 1 and 8 every 3 weeks, in patients with chemonaive solid tumors. Subsequently, we completed a multiinstitutional phase II study of TPC in patients with previously untreated, metastatic esophagogastric cancer. Results: Thirty-nine patients were enrolled in the phase I trial; a weekly schedule of TPC was well tolerated. On that basis, docetaxel 30 mg/m(2), cisplatin 25 mg/m(2), and irinotecan 65 mg/m(2) were selected for the phase II trial, where in the first 18 patients irinotecan 65 mg/m(2) caused too much diarrhea and was reduced to 50 mg/m(2). Among 56 eligible patients with previously untreated, metastatic esophagogastric cancer enrolled in the phase II trial, three complete and 27 partial responses were observed (overall response rate = 54%), and 15 patients (30%) had stable disease. Median progression-free survival was 7.1 months, and median survival was 11.9 months. At the final irinotecan dose of 50 mg/m(2), grade 3 or higher toxicity included diarrhea (26%), neutropenia (21%), nausea (18%), fatigue (16%), anorexia (13%), and thrombosis/embolism (13%). Conclusions: Weekly TPC is an active and well-tolerated regimen for patients with esophagogastric cancer. C1 [Enzinger, P. C.; Earle, C. C.; Kulke, M. H.; Meyerhardt, J. A.; Vincitore, M. M.; Mayer, R. J.; Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, C. S.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Muzikansky, A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Ryan, D. P.; Clark, J. W.; Blaszkowsky, L. S.; Zhu, A. X.; Fidias, P.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Enzinger, PC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM peter_enzinger@dfci.harvard.edu FU Pfizer Oncology; Sanofi-Aventis; National Institutes of Health [P50 CA127003] FX Pfizer Oncology; Sanofi-Aventis; National Institutes of Health (P50 CA127003). NR 22 TC 16 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2009 VL 20 IS 3 BP 475 EP 480 DI 10.1093/annonc/mdn658 PG 6 WC Oncology SC Oncology GA 413ZU UT WOS:000263834500014 PM 19139178 ER PT J AU Furniss, CS McClean, MD Smith, JF Bryan, J Applebaum, KM Nelson, HH Posner, MR Kelsey, KT AF Furniss, C. S. McClean, M. D. Smith, J. F. Bryan, J. Applebaum, K. M. Nelson, H. H. Posner, M. R. Kelsey, K. T. TI Human papillomavirus 6 seropositivity is associated with risk of head and neck squamous cell carcinoma, independent of tobacco and alcohol use SO ANNALS OF ONCOLOGY LA English DT Article DE epidemiology; head and neck squamous cell carcinoma; human papillomavirus; risk factors; serology ID VIRUS-LIKE PARTICLES; MAJOR CAPSID PROTEIN; SACCHAROMYCES-CEREVISIAE; CERVICAL-CANCER; NEUTRALIZING EPITOPES; SEXUAL-BEHAVIOR; ORAL-CANCER; HPV DNA; INFECTION; TYPE-16 AB Background: The risk of head and neck squamous cell carcinoma (HNSCC) associated with common human papillomavirus types has not been well defined. Methods: We conducted a case-control study of 1034 individuals (486 incident cases diagnosed with HNSCC and 548 population-based controls matched to cases by age, gender, and town of residence) in Greater Boston, MA. Sera were tested for antibodies to human papillomavirus (HPV)6, HPV11, HPV16, and HPV18 L1. Results: HPV6 antibodies were associated with an increased risk of pharyngeal cancer [odds ratio (OR) = 1.6, 1.0-2.5], controlling for smoking, drinking, and HPV16 seropositivity. In HPV16-seronegative subjects, high HPV6 titer was associated with an increased risk of pharyngeal cancer (OR = 2.3, 1.1-4.8) and oral cancer (OR = 1.9, 1.0-3.6), suggesting that the cancer risk associated with HPV6 is independent of HPV16. There was no association between smoking and alcohol use and HPV6 serostatus. Further, the risk of pharyngeal cancer associated with heavy smoking was different among HPV6-seronegative (OR 3.1, 2.0-4.8) and HPV6-seropositive subjects (OR = 1.6, 0.7-3.5), while heavy drinking also appears to confer differing risk among HPV6-negative (OR 2.3, 1.5-3.7) and -positive subjects (OR = 1.3, 0.6-2.9). Conclusions: There may be interactions between positive serology and drinking and smoking, suggesting that the pathogenesis of human papillomavirus in HNSCC involves complex interactions with tobacco and alcohol exposure. C1 [Furniss, C. S.; Applebaum, K. M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [McClean, M. D.] Boston Univ, Dept Environm Hlth, Boston, MA 02215 USA. [Nelson, H. H.] Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. [Posner, M. R.] Dana Farber Canc Inst, Dept Med Oncol Solid Tumor Oncol, Boston, MA 02115 USA. [Kelsey, K. T.] Brown Univ, Div Biol & Med, Dept Community Hlth & Lab Med & Pathol, Providence, RI 02912 USA. [Smith, J. F.; Bryan, J.] Merck & Co Inc, Dept Vaccine & Biol Res, West Point, NY USA. [Nelson, H. H.] Univ Minnesota, Ctr Canc, Minneapolis, MN USA. EM karl_kelsey@Brawn.edu RI Kelsey, Karl/I-1252-2014; OI McClean, Michael/0000-0002-3902-8823 FU National Institutes of Health [CA100679, CA78609, T32ES07155] FX National Institutes of Health (CA100679, CA78609, T32ES07155). NR 37 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2009 VL 20 IS 3 BP 534 EP 541 DI 10.1093/annonc/mdn643 PG 8 WC Oncology SC Oncology GA 413ZU UT WOS:000263834500024 PM 19087986 ER PT J AU Kwo, EC Kamat, P Steinman, MA AF Kwo, Elizabeth C. Kamat, Priya Steinman, Michael A. TI Physician Use of Brand Versus Generic Drug Names in 1993-1994 and 2003-2004 SO ANNALS OF PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 02-06, 2007 CL Seattle, WA SP Amer Geriatr Soc DE brand names; generic names; pharmaceutical industry ID POTENTIAL SAVINGS; MEDICATION USE; TRADE NAMES; PHARMACEUTICALS; SUBSTITUTION; BENEFIT AB BACKGROUND: Physicians often refer to drugs by their brand names, which can result in brand name drugs being dispensed even when bioequivalent generic alternatives are available. As a result, use of brand-name terminology may result in increased drug costs. OBJECTIVE: To evaluate how often physicians use brand and generic names of drugs, how the use of terminology changes over time, and factors associated with this change. METHODS: This was a serial cross-sectional study using data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey in 1993/1994 and 2003/2004. Over the 4 study years, data were collected on 376,383 subjects. Using forms completed by physicians that described medication regimens, we determined the proportion of drug names that were recorded using brand vs nonproprietary (ie, generic) terminology. RESULTS: In 1993/1994, the 25 most commonly mentioned drugs were referred to by their brand names a median of 89% of the time. Over the ensuing decade, use of brand-name terminology decreased by a median of 11%. Drugs that first faced generic competition within 10 years of the baseline study year had large declines in brand-name use (43-58% decline), whereas drugs that first faced generic competition more than 10 years before or after the baseline study year had minimal change in brand-name use (2-3% decline; p = 0.02 for difference in rate of decline among drug groups). Year of drug introduction, baseline rate of brand-name use, clinical setting, and national region were not associated with reductions in brand-name use. CONCLUSIONS: Brand-name terminology is commonly used and decreases over time with the introduction of generic competition. Interventions that standardize medication-naming practices may hasten this decline and increase use of nonproprietary terminology in medicine. C1 [Kamat, Priya; Steinman, Michael A.] Univ Calif San Francisco, San Francisco VA Med Ctr, Div Geriatr, No Calif Inst Res & Educ, San Francisco, CA 94121 USA. [Kwo, Elizabeth C.] Univ Calif San Francisco, Aging Res Program, San Francisco, CA 94143 USA. [Kwo, Elizabeth C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Steinman, MA (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Div Geriatr, No Calif Inst Res & Educ, 4150 Clement St,Box 181-G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu RI Mendoza, Elvia/A-9361-2012 NR 35 TC 6 Z9 6 U1 0 U2 3 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAR PY 2009 VL 43 IS 3 BP 459 EP 468 DI 10.1345/aph.1L502 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 419IK UT WOS:000264212700007 PM 19261956 ER PT J AU Fritz, S Fernandez-del Castillo, C Mino-Kenudson, M Crippa, S Deshpande, V Lauwers, GY Warshaw, AL Thayer, SP Iafrate, AJ AF Fritz, Stefan Fernandez-del Castillo, Carlos Mino-Kenudson, Mari Crippa, Stefano Deshpande, Vikram Lauwers, Gregory Y. Warshaw, Andrew L. Thayer, Sarah P. Iafrate, A. John TI Global Genomic Analysis of Intraductal Papillary Mucinous Neoplasms of the Pancreas Reveals Significant Molecular Differences Compared to Ductal Adenocarcinoma SO ANNALS OF SURGERY LA English DT Article DE intraductal papillary mucinous neoplasms; comparative genomic hybridization; genetic characterization; chromosomal aberrations; KRAS ID K-RAS MUTATIONS; CLINICOPATHOLOGICAL CHARACTERISTICS; CHROMOSOMAL-ABERRATIONS; SYMPTOMATIC PATIENTS; EVOLUTIONARY STAGES; UPDATED EXPERIENCE; CYSTIC NEOPLASMS; LONG ARM; TUMORS; HYBRIDIZATION AB Objective: To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). Summary Background Data: The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. Methods: 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. Results: While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. Conclusions: This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis. C1 [Mino-Kenudson, Mari; Deshpande, Vikram; Lauwers, Gregory Y.; Iafrate, A. John] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Fritz, Stefan; Fernandez-del Castillo, Carlos; Crippa, Stefano; Warshaw, Andrew L.; Thayer, Sarah P.] Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Iafrate, AJ (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Warren 501c, Boston, MA 02114 USA. EM aiafrate@partners.org FU Karin Grunebaum Cancer Research Foundation; German Research Foundation (DFG) FX This work was supported by funding from the Karin Grunebaum Cancer Research Foundation and the German Research Foundation (DFG). NR 57 TC 46 Z9 46 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2009 VL 249 IS 3 BP 440 EP 447 DI 10.1097/SLA.0b013e31819a6e16 PG 8 WC Surgery SC Surgery GA 413QT UT WOS:000263808300015 PM 19247032 ER PT J AU Tolaney, SM Krop, IE AF Tolaney, Sara M. Krop, Ian E. TI Mechanisms of Trastuzumab Resistance in Breast Cancer SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; HERCEPTIN-INDUCED INHIBITION; TYROSINE KINASE INHIBITORS; ADVANCED SOLID TUMORS; MONOCLONAL-ANTIBODY; PHASE-I; MOLECULAR-MECHANISMS; DOWN-REGULATION; LUNG-CANCER; CELL-LINES AB Amplification of the HER2/neu gene occurs in approximately 20-25% of invasive breast cancers and is associated with poor patient outcome. The development of trastuzumab, a humanized monoclonal antibody that binds to the extracellular domain of HER2, has led to a significant improvement in outcomes of patients with HER2-positive breast cancer. However, many patients with HER2-positive metastatic breast cancer do not respond to trastuzumab, or eventually become resistant to it. In addition, approximately 15% of patients treated with trastuzumab-based therapy in the adjuvant setting relapse. In this review, we discuss the mechanisms of antitumor activity of trastuzumab, potential mechanisms contributing to its resistance, and novel therapeutic agents that may provide a means to overcome trastuzumab resistance. C1 [Tolaney, Sara M.; Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krop, IE (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 2, Boston, MA 02115 USA. EM ikrop@partners.org NR 86 TC 18 Z9 18 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD MAR PY 2009 VL 9 IS 3 BP 348 EP 355 PG 8 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 431RD UT WOS:000265079900007 PM 19275526 ER PT J AU Pivtoraiko, VN Stone, SL Roth, KA Shacka, JJ AF Pivtoraiko, Violetta N. Stone, Sara L. Roth, Kevin A. Shacka, John J. TI Oxidative Stress and Autophagy in the Regulation of Lysosome-Dependent Neuron Death SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID CATHEPSIN-D DEFICIENCY; MOUSE PERITONEAL-MACROPHAGES; SPORADIC ALZHEIMERS-DISEASE; LIPID-PEROXIDATION PRODUCTS; CULTURED RAT HEPATOCYTES; AMYLOID-BETA-PROTEIN; AGE-RELATED-CHANGES; INDUCED CELL-DEATH; INDUCED APOPTOSIS; HYDROGEN-PEROXIDE AB Lysosomes critically regulate the pH-dependent catabolism of extracellular and intracellular macromolecules delivered from the endocytic/heterophagy and autophagy pathways, respectively. The importance of lysosomes to cell survival is underscored not only by their unique ability effectively to degrade metalloproteins and oxidatively damaged macromolecules, but also by the distinct potential for induction of both caspase-dependent and -independent cell death with a compromise in the integrity of lysosome function. Oxidative stress and free radical damage play a principal role in cell death induced by lysosome dysfunction and may be linked to several upstream and downstream stimuli, including alterations in the autophagy degradation pathway, inhibition of lysosome enzyme function, and lysosome membrane damage. Neurons are sensitive to lysosome dysfunction, and the contribution of oxidative stress and free radical damage to lysosome dysfunction may contribute to the etiology of neurodegenerative disease. This review provides a broad overview of lysosome function and explores the contribution of oxidative stress and autophagy to lysosome dysfunction-induced neuron death. Putative signaling pathways that either induce lysosome dysfunction or result from lysosome dysfunction or both, and the role of oxidative stress, free radical damage, and lysosome dysfunction in pediatric lysosomal storage disorders (neuronal ceroid lipofuscinoses or NCL/Batten disease) and in Alzheimer's disease are emphasized. Antioxid. Redox Signal. 11, 481-496. C1 [Pivtoraiko, Violetta N.; Stone, Sara L.; Roth, Kevin A.; Shacka, John J.] Univ Alabama, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. [Shacka, John J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Shacka, JJ (reprint author), SC 843A,1530 3rd Ave S, Birmingham, AL 35294 USA. EM shacka@uab.edu OI Roth, Kevin/0000-0002-0643-995X FU National Institutes of Health [NS35107, NS41962]; UAB Alzheimer's Disease Research Center; Birmingham VA Medical Center FX We thank Angela Schmeckebier and Barry Bailey for expert technical assistance in preparation of the manuscript. We also thank the UAB Neuroscience Core Facilities (NS47466 and NS57098) for technical assistance. This work is supported by grants from the National Institutes of Health (NS35107 and NS41962), a pilot grant from the UAB Alzheimer's Disease Research Center, and a VISN7 Career Development Award from the Birmingham VA Medical Center. NR 174 TC 46 Z9 47 U1 1 U2 13 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD MAR PY 2009 VL 11 IS 3 BP 481 EP 496 DI 10.1089/ars.2008.2263 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 399VD UT WOS:000262826500008 PM 18764739 ER PT J AU Goldstein, G AF Goldstein, Gerald TI Neuropsychology in New York City (1930-1960)(dagger) SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Editorial Material C1 [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM ggold@nb.net NR 18 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAR PY 2009 VL 24 IS 2 BP 137 EP 143 DI 10.1093/arclin/acp023 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA 454TL UT WOS:000266705500002 PM 19435732 ER PT J AU Hilsabeck, RC Sutker, PB AF Hilsabeck, Robin C. Sutker, Patricia B. TI Using an Implicit Memory Task to Estimate Premorbid Memory SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Premorbid IQ; Premorbid cognitive functioning; Dementia; Brain injury; Mild cognitive impairment ID ALZHEIMERS-DISEASE; ABILITY; PERFORMANCE; INTELLIGENCE; TESTS; INFORMATION; VALIDATION; EXPLICIT; SAMPLE; AGE AB Clinicians are often asked to determine if significant memory loss has occurred. Clinical judgment figures prominently in making these determinations, because there is no accepted, objective method for estimating premorbid memory. Two studies were designed to explore the utility of an implicit memory task, Anagrams Solutions, for estimating premorbid memory ability. A secondary goal was to identify predictors of immediate and delayed memory measured by the Repeatable Battery for the Assessment of Neuropsychological Status using selected intellectual (IQ) and demographic variables. Participants in both studies were administered the implicit memory task, explicit memory measures, and IQ estimate. Results revealed that Anagrams Solutions was not a useful estimate of premorbid memory and that a combination of IQ and demographic variables accounted for 24-31% of the variance in measured memory performances. Findings point to the need for caution in interpreting scores on these variables as valid estimates of premorbid memory functioning. C1 [Hilsabeck, Robin C.] S Texas Vet Hlth Care Syst, Psychol Serv 116B, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.; Sutker, Patricia B.] Texas Tech Univ Hlth Sci Ctr, Lubbock, TX 79430 USA. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Hilsabeck, RC (reprint author), S Texas Vet Hlth Care Syst, Psychol Serv 116B, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM robin.hilsabeck@va.gov FU National Academy of Neuropsychology Clinical Research; Research and Education Center at Carillon Senior Living Campus FX This research was supported by grants from the National Academy of Neuropsychology Clinical Research Grants Program, and The Research and Education Center at Carillon Senior Living Campus. NR 42 TC 3 Z9 3 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAR PY 2009 VL 24 IS 2 BP 179 EP 191 DI 10.1093/arclin/acp024 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA 454TL UT WOS:000266705500006 PM 19435733 ER PT J AU Markland, AD Gerety, MB Goode, PS Kraus, SR Cornell, J Hazuda, HP AF Markland, Alayne D. Gerety, Meghan B. Goode, Patricia S. Kraus, Stephen R. Cornell, John Hazuda, Helen P. TI Urinary incontinence in community-dwelling older Mexican American and European American women SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE Urinary incontinence; Fecal incontinence; Epidemiology of urinary incontinence; Risk factors ID AFRICAN-AMERICAN; NATURAL-HISTORY; HISPANIC WOMEN; RISK-FACTORS; PREVALENCE; HEALTH; WHITE; EPIDEMIOLOGY; DEPRESSION; SEVERITY AB The aim was to measure prevalence and correlates of urinary incontinence in community-dwelling Mexican American (MA) and European American (EA) women from a cross-sectional analysis of baseline data from a longitudinal cohort. Participants were MA and EA women, aged 65 years and older, in the San Antonio Longitudinal Study of Aging (SALSA), of whom 421 (97.4%) responded to the question "How often do you have difficulty holding your urine until you can get to a toilet." Measurements included sociodemographic, functional, cognitive, psychosocial, and clinical status variables derived from bilingual interviews and performance-based tests. Urinary incontinence prevalence was 36.6% (n = 154). MA women reported less incontinence than did EAs (29% versus 45%, p = 0.001). in multivariable analyses in MA women, urinary incontinence correlated with the presence of fecal incontinence (OR 4.0, 95% CI 1.1-14.0) and more dependency in activities of daily living (1.4, 1.1-1.8) after controlling for significant sociodemographic factors. In EA women, only age >75 (4.2, 1.4-12.4) was associated with urinary incontinence. MA women were less likely to report incontinence compared to EAs, despite MAs having increased number of children, less education, higher BMI, and more diabetes. Further research is needed to evaluate risk factors for urinary incontinence among MA women. Published by Elsevier Ireland Ltd. C1 [Markland, Alayne D.; Goode, Patricia S.] Univ Alabama, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Div Gerontol & Geriatr Med,Dept Med, Birmingham Vet Affairs Med Ctr,VAMC GRECC, Birmingham, AL 35294 USA. [Gerety, Meghan B.] New Mexico VA Healthcare Syst, Dept Vet Affairs, Albuquerque, NM 87108 USA. [Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Kraus, Stephen R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Gerety, Meghan B.; Cornell, John] S Texas Vet Hlth Care Adm, San Antonio, TX 78229 USA. [Gerety, Meghan B.; Cornell, John] Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Markland, AD (reprint author), Univ Alabama, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Div Gerontol & Geriatr Med,Dept Med, Birmingham Vet Affairs Med Ctr,VAMC GRECC, 11-G Room 8221,1350 3rd Ave S, Birmingham, AL 35294 USA. EM amarkland@aging.uab.edu OI Markland, Alayne/0000-0002-6567-6744 FU National Institute of Aging [RO1 AG 10444, 16518] FX Work supported by National Institute of Aging Grants RO1 AG 10444 and 16518. The authors would like to thank Kathryn L. Burgio, PhD, for reviewing the manuscript. NR 33 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD MAR-APR PY 2009 VL 48 IS 2 BP 232 EP 237 DI 10.1016/j.archger.2008.01.013 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 411IK UT WOS:000263642800022 PM 18313155 ER PT J AU Yaffe, K Weston, AL Blackwell, T Krueger, KA AF Yaffe, Kristine Weston, Andrea L. Blackwell, Terri Krueger, Kathryn A. TI The Metabolic Syndrome and Development of Cognitive Impairment Among Older Women SO ARCHIVES OF NEUROLOGY LA English DT Article ID VASCULAR RISK-FACTORS; BODY-MASS INDEX; ALZHEIMER-DISEASE; BLOOD-PRESSURE; DEMENTIA; DECLINE; POPULATION; OBESITY; ADULTS; OSTEOPOROSIS AB Background: Several studies support a role for cardiovascular risk factors in cognitive aging. The metabolic syndrome, a constellation of cardiovascular risk factors, is common in elderly people. A growing but conflicting body of literature suggests that the metabolic syndrome may be associated with cognitive impairment. Objective: To investigate the association between the metabolic syndrome and its components and incident cognitive impairment in older women. Design: We prospectively determined if the metabolic syndrome and its components were associated with a 4-year risk of developing cognitive impairment (dementia, mild cognitive impairment, or low global cognitive test score). Setting: The study was conducted at 180 clinical centers in 25 countries. Participants: A total of 4895 older women (mean age, 66.2 years) with osteoporosis who were part of an ancillary study to determine clinically relevant cognitive impairment were included in this study. These women were free of baseline cognitive impairment and had metabolic syndrome component measures. Main Outcome Measures: Clinically significant cognitive impairment was defined to include women with clinically adjudicated dementia or MCI and women who had a Short Blessed test score greater than 6 (consistent with impairment), but whose cases were not clinically adjudicated. Logistic regression analysis was used to examine the association between presence of the metabolic syndrome and development of clinically significant cognitive impairment. Results: A total of 497 women (10.2%) had the metabolic syndrome and, of these, 36 (7.2%) developed cognitive impairment compared with 181 (of 4398 or 4.1%) without the syndrome (age-adjusted odds ratio, 1.66; 95% confidence interval, 1.14-2.41). The mean (SD) number of metabolic syndrome components for all women was 1.0 (1.1); 518 women (10.6%) were obese, 895 (18.3%) had hypertriglyceridemia, 1200 (24.5%) had low high-density lipoprotein cholesterol levels, 1944 (39.7%) had high blood pressure, and 381 (7.8%) had high fasting blood glucose levels. There was a 23.0% age-adjusted increase in the risk of developing cognitive impairment (odds ratio, 1.23; 95% confidence interval, 1.09-1.39) per unit increase in the number of components. Further multivariable adjustment somewhat reduced the effect. Conclusion: We found an association between the metabolic syndrome and the number of components and risk of developing cognitive impairment in older women. Additional studies are needed to determine if screening and close management of these at-risk elderly women would diminish the incidence of cognitive impairment. C1 [Yaffe, Kristine; Weston, Andrea L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Yaffe, Kristine; Weston, Andrea L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Blackwell, Terri] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Krueger, Kathryn A.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Campus Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM Kristine.yaffe@ucsf.edu FU National Institute on Aging [AG031155]; Eli Lilly and Company FX DrYaffe is supported in part by National Institute on Aging grant AG031155. Dr Krueger receives a full salary from Eli Lilly and Company. Ms Blackwell receives partial salary support from Eli Lilly and Company. The parent trial was funded by Eli Lilly and Company. NR 36 TC 105 Z9 110 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2009 VL 66 IS 3 BP 324 EP 328 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 416EY UT WOS:000263989600007 PM 19273750 ER PT J AU Qin, WP Haroutunian, V Katsel, P Cardozo, CP Ho, L Buxbaum, JD Pasinetti, GM AF Qin, Weiping Haroutunian, Vahram Katsel, Pavel Cardozo, Christopher P. Ho, Lap Buxbaum, Joseph D. Pasinetti, Giulio M. TI PGC-1 alpha Expression Decreases in the Alzheimer Disease Brain as a Function of Dementia SO ARCHIVES OF NEUROLOGY LA English DT Article ID CEREBRAL GLUCOSE-METABOLISM; ENERGY-METABOLISM; GENE-EXPRESSION; HEPATIC GLUCONEOGENESIS; AMYLOID NEUROPATHOLOGY; CALORIE RESTRICTION; TRANSCRIPTIONAL COACTIVATOR; COGNITIVE DECLINE; INSULIN-RECEPTOR; TRANSGENIC MICE AB Objectives: To explore mechanisms through which altered peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) expression may influence Alzheimer disease (AD) amyloid neuropathology and to test the hypothesis that promotion of PGC-1 alpha expression in neurons might be developed as a novel therapeutic strategy in AD. Design: Case-control. Patients: Human postmortem brain (hippocampal formation) samples from AD cases and age-matched non-AD cases. Results: Using genome-wide complementary DNA microarray analysis, we found that PGC-1 alpha messenger RNA expression was significantly decreased as a function of progression of clinical dementia in the AD brain. Following confirmatory real-time polymerase chain reaction assay, we continued to explore the role of PGC-1 alpha in clinical dementia and found that PGC-1 alpha protein content was negatively associated with both AD-type neuritic plaque pathology and beta-amyloid (A beta)(X-42) contents. Moreover, we found that the predicted elevation of amyloidogenic A beta(1-42) and A beta(1-40) peptide accumulation in embryonic cortico-hippocampal neurons derived from Tg2576 AD mice under hyperglycemic conditions (glucose level, 182-273 mg/dL) coincided with a dose-dependent attenuation in PGC-1 alpha expression. Most importantly, we found that the reconstitution of exogenous PGC-1 alpha expression in Tg2576 neurons attenuated the hyperglycemic-mediated beta-amyloidogenesis through mechanisms involving the promotion of the "nonamyloidogenic" alpha-secretase processing of amyloid precursor protein through the attenuation of the forkheadlike transcription factor 1 (FoxO3a) expression. Conclusion: Therapeutic preservation of neuronal PGC-1 alpha expression promotes the nonamyloidogenic processing of amyloid precursor protein precluding the generation of amyloidogenic A beta peptides. C1 [Qin, Weiping; Haroutunian, Vahram; Katsel, Pavel; Buxbaum, Joseph D.; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Ho, Lap; Buxbaum, Joseph D.; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Ho, Lap; Pasinetti, Giulio M.] Ctr Geriatr Res Educ & Clin, Bronx, NY USA. [Ho, Lap; Pasinetti, Giulio M.] James J Peters VA Med Ctr, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Qin, Weiping/0000-0002-5763-5846 FU Atkins Foundation; National Institutes of Health [AG14766]; Dana Foundation for Brain Research Initiative, Merit Review; Department of Veterans Affairs Rehabilitation Research and Development Service [B4162C] FX These studies were supported by the Dr Robert C. Atkins Foundation, National Institutes of Health grant AG14766, the Dana Foundation for Brain Research Initiative, Merit Review (Dr Pasinetti), and grant B4162C from the Department of Veterans Affairs Rehabilitation Research and Development Service. NR 60 TC 126 Z9 126 U1 5 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9942 EI 1538-3687 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2009 VL 66 IS 3 BP 352 EP 361 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 416EY UT WOS:000263989600011 PM 19273754 ER PT J AU Klimstra, DS Pitman, MB Hruban, RH AF Klimstra, David S. Pitman, Martha B. Hruban, Ralph H. TI An Algorithmic Approach to the Diagnosis of Pancreatic Neoplasms SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ACINAR-CELL-CARCINOMA; PAPILLARY MUCINOUS NEOPLASMS; SOLID-PSEUDOPAPILLARY TUMOR; NEURON-SPECIFIC ENOLASE; DUCTAL ADENOCARCINOMAS; ENDOCRINE NEOPLASMS; LOW-GRADE; FEATURES; CYSTADENOCARCINOMA; EXPRESSION AB Context. - The pancreas gives rise to an array of distinct neoplasms that can be solid, cystic, or intraductal and can recapitulate the various lines of differentiation present in the normal gland. Objective. - To develop an algorithmic approach to the diagnosis of pancreatic neoplasms that simplifies their pathologic evaluation. Data Sources. - We reviewed literature related to the classification of pancreatic neoplasms on the basis of their gross, histologic, and immunohistochemical features. Conclusions. - By using a series of dichotomous decisions, the differential diagnosis of a pancreatic neoplasm can be narrowed, and in cases of the more common neoplasms, accurate classification can be achieved. Uncommon neoplasms not accounted for by this approach are also discussed, and the additional diagnostic information needed for complete pathologic reporting is presented. C1 [Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hruban, Ralph H.] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. RP Klimstra, DS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA. EM klimstrd@mskcc.org NR 48 TC 38 Z9 41 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2009 VL 133 IS 3 BP 454 EP 464 PG 11 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 415PQ UT WOS:000263946900016 PM 19260750 ER PT J AU Turner, AP Kivlahan, DR Haselkorn, JK AF Turner, Aaron P. Kivlahan, Daniel R. Haselkorn, Jodie K. TI Exercise and Quality of Life Among People With Multiple Sclerosis: Looking Beyond Physical Functioning to Mental Health and Participation in Life SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Exercise; Health status; Mental health; Multiple sclerosis; Quality of life; Rehabilitation ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; WAR VETERANS ILLNESSES; AEROBIC EXERCISE; UNITED-STATES; OUTPATIENT REHABILITATION; BEHAVIORAL ACTIVATION; DEPRESSIVE SYMPTOMS; ACTIVITY LEVEL; DISABILITY AB Objective: To describe the prevalence of exercise in a national sample of veterans with multiple sclerosis (MS) and the association of exercise with quality of life, including physical health, mental health, and participation restriction. Design: Cross-sectional cohort study linking computerized medical records to mailed survey data from 1999. Setting: Veterans Health Administration. Participants: Veterans with MS (N=2995; 86.5% men) who received services in the Veterans Health Administration and returned survey questionnaires. Interventions: Not applicable. Main Outcome Measures: Demographic information, Veteran RAND 36-Item Health Survey (VR-36), self-reported exercise frequency. Results: Among all survey respondents with MS, only 28.6% (95% confidence interval, 26.9-30.2) endorsed any exercise. In adjusted logistic regression, exercise was associated with younger age, more education, living alone, lower levels of bodily pain, and higher body mass index. After adjusting for demographic variables and medical comorbidities, exercise was associated with better physical and mental health. People who exercised reported they had better social functioning and better role functioning (participation in life despite physical and emotional difficulties). Conclusions: Exercise in veterans with MS is uncommon. In the context of chronic illness care, the identification of exercise patterns and promotion of physical activity may represent an important opportunity to improve mental health and quality of life among people with MS. Intervention should address factors associated with lower rates of exercise including age. education, and pain. C1 [Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. [Turner, Aaron P.; Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI Turner, Aaron/0000-0001-6897-8003 FU Department of Veterans Affairs Rehabilitation Research; Development Service Career Development Award [B4927W] FX Supported by Department of Veterans Affairs Rehabilitation Research and Development Service Career Development Award (grant no. B4927W). Veterans Affairs Center of Excellence in Substance Abuse Treatment and Education, the Veterans Affairs Multiple Sclerosis Center of Excellence West. and the Veterans Affairs Office of Quality and Performance. NR 73 TC 36 Z9 36 U1 4 U2 14 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 MAR PY 2009 VL 90 IS 3 BP 420 EP 428 DI 10.1016/j.apmr.2008.09.558 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 421YW UT WOS:000264395200008 PM 19254606 ER PT J AU Weaver, FM Burns, SP Evans, CT Rapacki, LM Goldstein, B Hammond, MC AF Weaver, Frances M. Burns, Stephen P. Evans, Charlesnika T. Rapacki, Lauren M. Goldstein, Barry Hammond, Margaret C. TI Provider Perspectives on Soldiers With New Spinal Cord Injuries Returning From Iraq and Afghanistan SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Health personnel; Rehabilitation; Spinal cord injuries; Veterans ID TRAUMATIC BRAIN-INJURY; COMBAT; WAR; REHABILITATION; CASUALTIES; RISK AB Objective: The military conflicts in Iraq and Afghanistan have resulted in many soldiers returning with serious combat injuries, including spinal cord injuries (SCIs). The purpose of this study was to query providers regarding any unique problems or needs in a cohort of these soldiers treated in Veterans Health Administration (VHA) SCI Centers. Design: Semi structured questionnaire. Setting: Seventeen VHA SCI Centers. Participants: Thirty-eight providers, including physicians, nurses, therapists, social workers, and psychologists who volunteered to return completed questionnaires. Interventions: Not applicable. Main Outcome Measures: Identification of medical and psychosocial issues, rehabilitation delays, therapy and vocational needs, social support, and discharge planning. Results: Providers identified several injuries and conditions beyond SCI that were experienced by these soldiers including fractures, pressure ulcers, traumatic brain injuries, posttraumatic stress disorder, and resistant infections. Rehabilitation was often delayed because these problems needed to be addressed first. Soldiers' family and friends provide considerable support. Vocational needs include use of technology, especially computers; education; and participation in sports. Although most return to the community after discharge, many soldiers are still active duty, and some return to military base housing. Conclusions: Combat soldiers returning with SCI often have additional medical and psychosocial problems that require appropriate and timely intervention. They have strong support from family and friends and are motivated to integrate back into the community after discharge. C1 [Weaver, Frances M.; Evans, Charlesnika T.; Rapacki, Lauren M.] Edward Hines Jr VA Hosp, Ctr Complex Chron Care, Hines, IL 60141 USA. [Weaver, Frances M.; Evans, Charlesnika T.; Rapacki, Lauren M.] Edward Hines Jr VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. [Weaver, Frances M.; Evans, Charlesnika T.] Northwestern Univ, Inst Healthcare Studies, Chicago, IL 60611 USA. [Weaver, Frances M.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Burns, Stephen P.; Goldstein, Barry; Hammond, Margaret C.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Burns, Stephen P.; Goldstein, Barry; Hammond, Margaret C.] Univ Washington, Dept Rehabil, Seattle, WA 98195 USA. [Burns, Stephen P.; Goldstein, Barry; Hammond, Margaret C.] Univ Washington, Harborview Med Ctr, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. [Goldstein, Barry; Hammond, Margaret C.] Dept Vet Affairs, Spinal Cord Injury & Disorders Serv, Seattle, WA USA. RP Weaver, FM (reprint author), VA Hosp, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM Frances.Weaver@va.gov FU Spinal Cord Injury Quality Enhancement Research Initiative (QUERI) in the Department of Veterans Affairs [SC198-001] FX Supported by the Spinal Cord Injury Quality Enhancement Research Initiative (QUERI) in the Department of Veterans Affairs (grant no. SC198-001). NR 14 TC 24 Z9 25 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2009 VL 90 IS 3 BP 517 EP 521 DI 10.1016/j.apmr.2008.09.560 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 421YW UT WOS:000264395200023 PM 19254621 ER PT J AU Henneman, D Chang, Y Hodin, RA Berger, DL AF Henneman, Daniel Chang, Yuchiao Hodin, Richard A. Berger, David L. TI Effect of Laparoscopy on the Indications for Adrenalectomy SO ARCHIVES OF SURGERY LA English DT Article ID INCIDENTALOMAS; STANDARD; TRENDS AB Background: Laparoscopic adrenalectomy is now the criterion standard for removal of most benign adrenal lesions and may be used for malignant lesions as well. At the same time, improved imaging has led to an increase in the number of incidentally detected adrenal masses. The aim of this study was to determine whether the introduction of laparoscopy has changed the indications for adrenalectomy. Design: Retrospective cohort study of patients operated on for primary adrenal disease between September 1, 1987, and August 17, 2007. Setting: Academic hospital. Patients: Sixty-six patients treated before (group 1) and 203 treated after (group 2) introduction of laparoscopic adrenalectomy. Main Outcome Measures: Patient characteristics, comorbidity, tumor size, indication, and time between diagnosis and surgery. Results: Group 2 had more patients in American Society of Anesthesiologists class III with gastrointestinal and metabolic-endocrine comorbidities. Tumor size did not change, and, despite an increase in the number of adrenalectomies, indications for surgery remained consistent over time. Conclusion: Despite an increased volume of procedures, the introduction of laparoscopic adrenalectomy in our hospital did not change the indications for surgical intervention. C1 [Chang, Yuchiao; Hodin, Richard A.; Berger, David L.] Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. [Henneman, Daniel] Univ Amsterdam, Amsterdam, Netherlands. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, 15 Parkman St,Wang 465, Boston, MA 02114 USA. EM dberger@partners.org NR 19 TC 7 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAR PY 2009 VL 144 IS 3 BP 255 EP 259 PG 5 WC Surgery SC Surgery GA 419KQ UT WOS:000264218700013 PM 19289665 ER PT J AU Ray, KK Cannon, CP Cairns, R Morrow, DA Ridker, PM Braunwald, E AF Ray, Kausik K. Cannon, Christopher P. Cairns, Richard Morrow, David A. Ridker, Paul M. Braunwald, Eugene TI Prognostic Utility of ApoB/AI, Total Cholesterol/HDL, Non-HDL Cholesterol, or hs-CRP as Predictors of Clinical Risk in Patients Receiving Statin Therapy After Acute Coronary Syndromes Results From PROVE IT-TIMI 22 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE statins; apolipoprotein; inflammation; CRP; CHD ID C-REACTIVE PROTEIN; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; APOLIPOPROTEIN-B; LIPID MEASURES; HEART-DISEASE; A-I; WOMEN; TRIAL AB Objectives-The purpose of this study was to compare the prognostic utility of apoB/AI, total cholesterol/HDL (TC/HDL) ratio, non-HDL cholesterol (non-HDL-C), or hs-CRP as predictors of clinical risk among patients receiving statin therapy after acute coronary syndromes (ACS). Methods and Results-Patients with ACS were randomized in the PROVE IT-TIMI 22 trial to either pravastatin 40 mg or atorvastatin 80 mg. Cox regression models adjusting for confounders were used to assess the relationship between on-treatment lipids or hs-CRP and risk of death or acute coronary events. At 4 months a 1 SD increment in apoB/AI (HR 1.10, 95% CI 1.01 to 1.20), TC/HDL (HR 1.12, 95% CI 1.01 to 1.24), and non-HDL-C (HR 1.20, 95% CI 1.07 to 1.35) predicted events to a similar extent as LDL-C (HR 1.20, 95% CI 1.07 to 1.35) with neither apoB/AI, TC/HDL, nor non-HDL-C improving risk prediction models which included LDL-C. In contrast, the addition of hs-CRP significantly improved risk prediction models irrespective of the lipid parameters included, with a 29% to 30% increased risk observed per 1 SD increment in log CRP. Conclusion-In the present study of ACS patients receiving statin therapy, on-treatment apoB/AI, TC/HDL, and non-HDL-C offered similar prognostic information to LDL-C. However, the addition of hs-CRP to lipid-based measurements significantly improved risk prediction. On treatment CRP measurement may therefore offer additive prognostic information to lipids in ACS patients. (Arterioscler Thromb Vasc Biol. 2009;29:424-430.) C1 [Cannon, Christopher P.; Morrow, David A.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,TIMI Study Grp, Boston, MA 02115 USA. [Cannon, Christopher P.; Morrow, David A.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Ray, Kausik K.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Ridker, Paul M.] Brigham & Womens Hosp, Donald W Reynolds Ctr Cardiovasc Res, Boston, MA 02115 USA. [Ridker, Paul M.] Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org FU British Heart Foundation NR 17 TC 79 Z9 86 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2009 VL 29 IS 3 BP 424 EP D6 DI 10.1161/ATVBAHA.108.181735 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 409NY UT WOS:000263513700025 PM 19122170 ER PT J AU Gordon, AT Land, RM AF Gordon, Assaf T. Land, Rebekah M. TI Transtibial Prosthesis Suspension Failure During Skydiving Freefall: A Case Report SO ASSISTIVE TECHNOLOGY LA English DT Article DE failure; prosthesis; skydiving; suspension system; transtibial amputation AB This report describes the unusual case of an everyday-use prosthesis suspension system failure during the freefall phase of a skydiving jump. The case individual was a 53-year-old male with a left transtibial amputation secondary to trauma. He used his everyday prosthesis, a transtibial endoskeleton with push-button, plunger-releasing, pin-locking silicon liner suction suspension and a neoprene knee suspension sleeve, for a standard recreational tandem skydive. Within seconds of exiting the plane, the suspension systems failed, resulting in the complete prosthesis floating away. Several factors may have led to suspension system failure, including an inadequate seal and material design of the knee suspension sleeve and liner, lack of auxiliary suspension mechanisms, and lack of a safety cover overlying the push-button release mechanism. This is the first report, to our knowledge, to discuss prosthetic issues specifically related to skydiving. While amputees are to be encouraged to participate in this extreme sport, special modifications to everyday components may be necessary to reduce the possibility of prosthesis failure during freefall, parachute deployment, and landing. C1 [Gordon, Assaf T.] Univ Calif Los Angeles, Dept Phys Med & Rehabil, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Land, Rebekah M.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Med Ctr, Pittsburgh, PA 15213 USA. RP Gordon, AT (reprint author), Capital Spine Ctr, 2800 Shirlington Rd,Suite 102, Arlington, VA 22206 USA. EM gordonat@gmail.com NR 6 TC 1 Z9 1 U1 0 U2 3 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SPR PY 2009 VL 21 IS 1 BP 25 EP 27 DI 10.1080/10400430902945827 PG 3 WC Rehabilitation SC Rehabilitation GA 521XZ UT WOS:000271961200003 PM 19719060 ER PT J AU Cohen, LJ Fitzgerald, SG Lane, S Boninger, ML Minkel, J McCue, M AF Cohen, Laura J. Fitzgerald, Shirley G. Lane, Suzanne Boninger, Michael L. Minkel, Jean McCue, Michael TI Validation of the Seating and Mobility Script Concordance Test SO ASSISTIVE TECHNOLOGY LA English DT Article DE clinical competence; educational measurement; professional practice; rehabilitation; validation ID DIAGNOSTIC KNOWLEDGE; CAPACITY AB The purpose of this study was to develop the scoring system for the Seating and Mobility Script Concordance Test (SMSCT), obtain and appraise internal and external structure evidence, and assess the validity of the SMSCT. The SMSCT purpose is to provide a method for testing knowledge of seating and mobility prescription. A sample of 106 therapists and 15 spinal cord injury experts contributed to the development of the scoring system. Validity evidence was obtained using 15 seating and mobility experts, 10 orthopedic experts, and 66 therapists with varying levels of seating and mobility expertise. Proxy measures of clinical expertise were used for external validity evidence since no criterion measures exist. The SMSCT was found to differentiate between seating and mobility experts' and orthopedic experts' intervention subtest scores (p = 0.04). The proxy measure of clinical expertise, seating and mobility hours/week, was found to predict SMSCT intervention scores (p = 0.002). The internal structure of the SMSCT may include evidence of reduced item performance but satisfactory convergent and discriminate evidence by construct definition. Although the SMSCT may be a promising approach for measuring seating and mobility expertise, limitations exist in the corrected content. Future application of the SMSCT should only be used after further development of the tool occurs. C1 [Cohen, Laura J.] Shepherd Ctr, Crawford Res Inst, Atlanta, GA USA. [Fitzgerald, Shirley G.] James A Haley Tampa VA, Tampa, FL USA. [Lane, Suzanne] Univ Pittsburgh, Sch Educ, Dept Educ Psychol, Pittsburgh, PA 15260 USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Sch Med, Pittsburgh, PA 15260 USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Minkel, Jean] Minkel Consulting, New Windsor, NY USA. [McCue, Michael] Univ Pittsburgh, Dept Rehabil Sci & Technol, Sch Hlth & Rehabil Sci, Pittsburgh, PA 15260 USA. RP Fitzgerald, SG (reprint author), HSR&D REAP, 8900 Grand Oak Circle 118 M, Tampa, FL 33637 USA. EM Shirley.Fitzgerald@va.gov OI Boninger, Michael/0000-0001-6966-919X NR 19 TC 1 Z9 1 U1 0 U2 2 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SPR PY 2009 VL 21 IS 1 BP 47 EP 56 DI 10.1080/10400430902945546 PG 10 WC Rehabilitation SC Rehabilitation GA 521XZ UT WOS:000271961200006 PM 19719063 ER PT J AU Medland, SE Neale, MC Eaves, LJ Neale, BM AF Medland, Sarah E. Neale, Michael C. Eaves, Lindon J. Neale, Benjamin M. TI A Note on the Parameterization of Purcell's G x E Model for Ordinal and Binary Data SO BEHAVIOR GENETICS LA English DT Article DE Genotype by environment interaction; Structural equation model; Twin data; Ordinal data; G x E ID TWIN AB Following the publication of Purcell's approach to the modeling of gene by environment interaction in 2002, the interest in G x E modeling in twin and family data increased dramatically. The analytic techniques described by Purcell were designed for use with continuous data. Here we explore the re-parameterization of these models for use with ordinal and binary outcome data. Analysis of binary and ordinal data within the context of a liability threshold model traditionally requires constraining the total variance to unity to ensure identification. Here, we demonstrate an alternative approach for use with ordinal data, in which the values of the first two thresholds are fixed, thus allowing the total variance to change as function of the moderator. We also demonstrate that when using binary data, constraining the total variance to unity for a given value of the moderator is sufficient to ensure identification. Simulation results indicate that analyses of ordinal and binary data can recover both the raw and standardized patterns of results. However, the scale of the results is dependent on the specification of (threshold or variance) constraints rather than the underlying distribution of liability. Example Mx scripts are provided. C1 [Medland, Sarah E.; Neale, Michael C.; Eaves, Lindon J.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Medland, Sarah E.] Queensland Inst Med Res, Genet Epidemiol Unit, Brisbane, Qld 4006, Australia. [Neale, Michael C.; Eaves, Lindon J.] Virginia Commonwealth Univ, Dept Psychiats, Richmond, VA 23298 USA. [Neale, Michael C.; Eaves, Lindon J.] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA. [Neale, Michael C.] Free Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Neale, Benjamin M.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London, England. [Neale, Benjamin M.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Neale, Benjamin M.] Harvard Univ, Cambridge, MA 02138 USA. [Neale, Benjamin M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. RP Medland, SE (reprint author), Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, POB 980126 MCV, Richmond, VA 23298 USA. EM sarahMe@qimr.edu.au RI Medland, Sarah/C-7630-2013 OI Medland, Sarah/0000-0003-1382-380X FU Australian NHMRC Sidney Sax Fellowship [443036]; NIH [DA-18673, MH-65322]; NIMH [R01MH081803, R01MH062873] FX The authors would like to thank Sophie van der Sluis, Dorret Boomsma, Lannie Ligthart and the reviewers for their helpful comments. SEM is supported by an Australian NHMRC Sidney Sax Fellowship (443036). MCN is supported in part by NIH grants DA-18673, MH-65322. BMN is supported in part by NIMH grants R01MH081803 and R01MH062873 to SV Faraone. NR 8 TC 18 Z9 18 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD MAR PY 2009 VL 39 IS 2 BP 220 EP 229 DI 10.1007/s10519-008-9247-7 PG 10 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 403WX UT WOS:000263113800011 PM 19083089 ER PT J AU Beck, JG Coffey, SF Foy, DW Keane, TM Blanchard, EB AF Beck, J. Gayle Coffey, Scott F. Foy, David W. Keane, Terence M. Blanchard, Edward B. TI Group Cognitive Behavior Therapy for Chronic Posttraumatic Stress Disorder: An Initial Randomized Pilot Study SO BEHAVIOR THERAPY LA English DT Article ID MOTOR-VEHICLE ACCIDENT; NATIONAL COMORBIDITY SURVEY; CHRONIC PAIN PATIENTS; PSYCHOMETRIC PROPERTIES; PROCESSING THERAPY; EXPOSURE; INVENTORY; SURVIVORS; PTSD; PSYCHOPHYSIOLOGY AB Individuals with posttraumatic stress disorder (PTSD) related to a serious motor vehicle accident were randomly assigned to either group cognitive behavioral treatment (GCBT) or a minimum contact comparison group (MCC). Compared to the MCC participants (n = 16), individuals who completed GCBT (n = 17) showed significant reductions in PTSD symptoms, whether assessed using clinical interview or a self-report measure. Among treatment completers, 88.3% of GCBT participants did not satisfy criteria for PTSD at posttreatment assessment, relative to 31.3% of the MCC participants. Examination of anxiety, depression, and pain measures did not show a unique advantage of GCBT. Treatment-related gains were maintained over a 3-month follow-up interval. Patients reported satisfaction with GCBT, and attrition from this treatment was comparable with individually administered CBTs. Results are discussed in light of modifications necessitated by the group treatment format, with suggestions for future study of this group intervention. C1 [Beck, J. Gayle] SUNY Buffalo, Buffalo, NY 14260 USA. [Coffey, Scott F.] Univ Mississippi, University, MS 38677 USA. [Foy, David W.] Pepperdine Univ, Malibu, CA 90263 USA. [Keane, Terence M.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02215 USA. [Blanchard, Edward B.] SUNY Albany, Albany, NY 12222 USA. RP Beck, JG (reprint author), Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. EM jgbeck@memphis.edu FU NIMH NIH HHS [MH64777, R21 MH064777] NR 52 TC 36 Z9 38 U1 4 U2 15 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD MAR PY 2009 VL 40 IS 1 BP 82 EP 92 DI 10.1016/j.beth.2008.01.003 PG 11 WC Psychology, Clinical SC Psychology GA 409LR UT WOS:000263507700008 PM 19187819 ER PT J AU Shanahan, NA Pierz, KAH Masten, VL Waeber, C Ansorge, M Gingrich, JA Geyer, MA Hen, R Dulawa, SC AF Shanahan, Nancy A. Pierz, Kerri A. Holick Masten, Virginia L. Waeber, Christian Ansorge, Mark Gingrich, Jay A. Geyer, Mark A. Hen, Rene Dulawa, Stephanie C. TI Chronic Reductions in Serotonin Transporter Function Prevent 5-HT1B-Induced Behavioral Effects in Mice SO BIOLOGICAL PSYCHIATRY LA English DT Article DE 5-HTT; 5-HT1B receptor; antidepressant; OCD; PPI ID OBSESSIVE-COMPULSIVE DISORDER; SENSORIMOTOR GATING DEFICITS; GROWTH-HORMONE RESPONSE; PREPULSE INHIBITION; LOCOMOTOR-ACTIVITY; SUMATRIPTAN CHALLENGE; RECEPTOR AGONIST; CHRONIC FLUOXETINE; AUTISTIC DISORDER; DOPAMINE RELEASE AB Background: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts, images, or impulses and/or repetitive stereotypical behavior. Obsessive-compulsive disorder patients exhibit reduced prepulse inhibition (PPI) and symptom exacerbation after challenge with 5-HT1B