FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Geyer, MB Ricci, AM Jacobson, JS Majzner, R Duffy, D Van de Ven, C Ayello, J Bhatia, M Garvin, JH George, D Satwani, P Harrison, L Morris, E Semidei-Pomales, M Schwartz, J Alobeid, B Baxter-Lowe, LA Cairo, MS AF Geyer, Mark B. Ricci, Angela M. Jacobson, Judith S. Majzner, Robbie Duffy, Deirdre Van de Ven, Carmella Ayello, Janet Bhatia, Monica Garvin, James H., Jr. George, Diane Satwani, Prakash Harrison, Lauren Morris, Erin Semidei-Pomales, Mildred Schwartz, Joseph Alobeid, Bachir Baxter-Lowe, Lee Ann Cairo, Mitchell S. TI T cell depletion utilizing CD34(+) stem cell selection and CD3(+) addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE paediatrics; T cell depletion; allogeneic stem cell transplantation ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVAL; MISMATCHED PARENTAL DONORS; PERIPHERAL-BLOOD; REDUCED-INTENSITY; NONMALIGNANT DISEASES; IMMUNE RECONSTITUTION; CORD BLOOD; HEMATOLOGIC MALIGNANCIES AB CD34-selected haploidentical and unrelated donor allogeneic stem cell transplantation (AlloSCT) in paediatric recipients is associated with sustained engraftment and low risk of acute graft-versus-host disease (aGVHD), but limited by delayed immune reconstitution and increased risk of viral and fungal infection. The optimal dose of donor T cells to prevent graft failure and minimize risk of early opportunistic infection and post-transplant lymphoproliferative disorder (PTLD), while avoiding severe aGVHD, remains unknown. We prospectively studied CD34-selected 810/10 human leucocyte antigen (HLA)-matched unrelated donor (MUD) peripheral blood stem cell transplantation (PBSCT) in a cohort of 19 paediatric AlloSCT recipients with malignant (n=13) or non-malignant (n=6) diseases. T cells were added back to achieve total dose 1.0-2.5 similar to x similar to 10(5)similar to CD3+/kg. GVHD pharmacoprophylaxis consisted only of tacrolimus. All patients engrafted neutrophils. Probabilities of grade IIIV aGVHD, limited chronic GVHD (cGVHD), and extensive cGVHD were 15.8%, 23.3%, and 0%, respectively. One patient developed PTLD. One-year infection-related mortality was 5.6%. T cell immune reconstitution was delayed. One-year overall survival was 82.3%. Five patients with malignant disease ultimately died from progressive disease. CD34-selected MUD PBSCT using a defined dose of T cell add-back resulted in high rates of engraftment and low risk of grade IIIV aGVHD, early transplantation-related mortality, and extensive cGVHD. C1 [Geyer, Mark B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Ricci, Angela M.; Majzner, Robbie; Bhatia, Monica; Garvin, James H., Jr.; George, Diane; Satwani, Prakash] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Jacobson, Judith S.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Duffy, Deirdre; Van de Ven, Carmella; Ayello, Janet; Harrison, Lauren; Morris, Erin; Semidei-Pomales, Mildred; Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. [Schwartz, Joseph; Alobeid, Bachir] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Baxter-Lowe, Lee Ann] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Cairo, Mitchell S.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA. RP Cairo, MS (reprint author), New York Med Coll, Maria Fareri Childrens Hosp, Westchester Med Ctr, Dept Pediat Med Pathol Microbiol & Immunol, Munger Pavil Room 110A, Valhalla, NY 10595 USA. EM mitchell_cairo@nymc.edu OI Geyer, Mark/0000-0001-5248-9117 FU Pediatric Cancer Research Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R21 AR49330]; Dreaming for Discovery and Cure Fund; Marisa Fund; Sonia Scaramella Fund; Paul Luisi Foundation; Brittany Barron Fund; Doris Duke Charitable Foundation FX This work was supported in part by grants from the Pediatric Cancer Research Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21 AR49330; MSC), Dreaming for Discovery and Cure Fund, Marisa Fund, Sonia Scaramella Fund, Paul Luisi Foundation, Brittany Barron Fund, and the Doris Duke Charitable Foundation. Presented in part at the BMT Tandem Meetings, February, 2010, Orlando, Florida and the Pediatric Academic Societies Meeting, May, 2010, Vancouver, British Columbia, Canada. The authors would like to thank the patients and their families who participated in these trials and the inpatient and outpatient bedside nurses who provided expert care on a daily basis to these patients at our institution. NR 59 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2012 VL 157 IS 2 BP 205 EP 219 DI 10.1111/j.1365-2141.2012.09048.x PG 15 WC Hematology SC Hematology GA 915YF UT WOS:000302062800009 PM 22313507 ER PT J AU Michaelson, MD AF Michaelson, M. Dror TI Combination of targeted agents in metastatic renal cell carcinoma SO CANCER LA English DT Editorial Material ID PHASE-III TRIAL; INTERFERON-ALPHA; SUNITINIB; TEMSIROLIMUS; BEVACIZUMAB; EVEROLIMUS C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM dmichaelson1@partners.org NR 21 TC 4 Z9 4 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2012 VL 118 IS 7 BP 1744 EP 1746 DI 10.1002/cncr.26427 PG 3 WC Oncology SC Oncology GA 910NR UT WOS:000301647000004 PM 21898374 ER PT J AU Wu, Y Posner, MR Schumaker, LM Nikitakis, N Goloubeva, O Tan, M Lu, CW Iqbal, S Lorch, J Sarlis, NJ Haddad, RI Cullen, KJ AF Wu, Yin Posner, Marshall R. Schumaker, Lisa M. Nikitakis, Nikolaos Goloubeva, Olga Tan, Ming Lu, Changwan Iqbal, Sana Lorch, Jochen Sarlis, Nicholas J. Haddad, Robert I. Cullen, Kevin J. TI Novel Biomarker Panel Predicts Prognosis in Human Papillomavirus-Negative Oropharyngeal Cancer SO CANCER LA English DT Article DE prognostic markers; in human papilloma virus; negative; oropharyngeal cancer ID SQUAMOUS-CELL CARCINOMA; S-TRANSFERASE-PI; NECK-CANCER; NEOADJUVANT CHEMOTHERAPY; TUMOR RESPONSE; BREAST-CANCER; ORAL-CAVITY; HEAD; SURVIVAL; CISPLATIN AB BACKGROUND: New treatment strategies for locally advanced head and neck squamous cell carcinoma combine induction chemotherapy and chemoradiation. Identifying the predictors of outcome in sequentially treated patients is critical for focusing therapeutic research. In this analysis, the authors evaluated human papillomavirus type 16 (HPV-16) status and the expression levels of a defined set of biomarkers to identify predictors of response to this treatment modality. METHODS: In total, 114 patients with oropharyngeal cancer (OPC) who were treated on the TAX 324 trial (cisplatin and fluorouracil with or without docetaxel in patients with locally advanced head and neck squamous cell carcinoma) had pretreatment biopsy specimens that were evaluable for HPV-16 DNA and immunohistochemical expression of the following biomarkers: beta-tubulin II (beta T-II), glutathione S-transferase (GST-pi), p53, and B-cell lymphoma 2 (Bcl-2). Patients were categorized into risk groups based on their HPV status and biomarker expression levels. RESULTS: Patients with high-risk OPC were defined by HPV-negative status and either elevated expression of beta T-II or levels of at least 2 of the other 3 adverse markers (elevated GST-pi, elevated p53, or low Bcl-2). All other HPV-negative patients were categorized as moderate risk. In total, 55 patients were HPV-positive, and 59 patients were HPV-negative, with 34 were categorized as high risk and 25 categorized as moderate risk. The median survival for HPV-positive patients was not reached. The median survival was 44.2 months for moderate-risk patients (95% confidence interval, 20.9 months to not reached) and 12.1 months for high-risk patients (95% confidence interval, 7.5-19.7 months). The 24-month survival rate was 89% for HPV-positive patients, 67% for moderate-risk patients, and 29% for high-risk patients (P < .0001). CONCLUSIONS: The molecular data set in this study readily differentiated between 2 distinct groups of patients with locally advanced, HPV-negative OPC. This risk-stratification strategy may serve as a guide for treatment selection. Cancer 2012;118:1811-7. (C) 2011 American Cancer Society. C1 [Wu, Yin; Schumaker, Lisa M.; Nikitakis, Nikolaos; Goloubeva, Olga; Tan, Ming; Lu, Changwan; Iqbal, Sana; Cullen, Kevin J.] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Expt Therapeut Program, Baltimore, MD 21201 USA. [Posner, Marshall R.; Lorch, Jochen; Haddad, Robert I.] Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. [Posner, Marshall R.; Lorch, Jochen; Haddad, Robert I.] Harvard Univ, Sch Med, Boston, MA USA. [Sarlis, Nicholas J.] Sanofi Aventis US, Bridgewater, NJ USA. RP Cullen, KJ (reprint author), Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Expt Therapeut Program, 22 S Greene St,Room N9E17, Baltimore, MD 21201 USA. EM kcullen@umm.edu OI Schumaker, Lisa/0000-0002-8454-9660 FU Sanofi-Aventis US; Sanofi-Aventis Groupe [TAX324]; State of Maryland Cigarette Restitution Fund Program; Orokawa Foundation FX This work was supported by Sanofi-Aventis US (the parent trial TAX324 was sponsored by Sanofi-Aventis Groupe), the State of Maryland Cigarette Restitution Fund Program, and the Orokawa Foundation. NR 44 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2012 VL 118 IS 7 BP 1811 EP 1817 DI 10.1002/cncr.26485 PG 7 WC Oncology SC Oncology GA 910NR UT WOS:000301647000012 PM 22009819 ER PT J AU Hoffner, B Bauer-Wu, S Hitchcock-Bryan, S Powell, M Wolanski, A Joffe, S AF Hoffner, Brianna Bauer-Wu, Susan Hitchcock-Bryan, Suzanne Powell, Mark Wolanski, Andrew Joffe, Steven TI "Entering a Clinical Trial: Is it Right For You?" SO CANCER LA English DT Article DE informed consent; clinical trials; patient decision making; patient-provider communication; patient education; multi-media technology ID INFORMED-CONSENT; RANDOMIZATION; PARTICIPANTS; INFORMATION; BENEFITS; ONCOLOGY; QUALITY AB PURPOSE: This randomized study was designed to assess the utility of an educational video in preparing cancer patients for decisions about clinical trial participation. The study assessed the effect of the video on patients' understanding and perceptions of clinical trials, its impact on decision making and patient-provider communication, and patients' satisfaction with the video. METHODS: Ninety adults considering cancer clinical trials were randomized to receive (n = 45) or not receive (n = 45) the video. Using the validated Quality of Informed Consent (QuIC), respondents' knowledge about clinical trial participation was assessed. All subjects completed additional questions about satisfaction with the video, decision making, and patient-provider communication. Data were analyzed using the Wilcoxon rank-sum test, regression model, and descriptive statistics. RESULTS: Although intent-to-treat analysis found no significant group differences in objective understanding between those randomized to view or not view the video, the majority of participants reported favorable experiences with regard to watching the video: 85% found the video was an important source of information about clinical trials; 81% felt better prepared to discuss the trial with their physician; 89% of those who watched the video with family indicated that it helped family better understand clinical trials; and 73% indicated it helped family accept their decision about participation. CONCLUSIONS: Although the video did not measurably improve patients' knowledge about clinical trials, it was an important source of information, helped educate families, and enhanced patient communication with their oncology providers. Cancer 2012;118:1877-83. (C) 2011 American Cancer Society. C1 [Hoffner, Brianna] Univ Colorado, Sch Med, Univ Colorado Hosp, Denver, CO USA. [Bauer-Wu, Susan] Emory Univ, Atlanta, GA 30322 USA. [Hitchcock-Bryan, Suzanne; Powell, Mark; Wolanski, Andrew] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. [Joffe, Steven] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Dept Med,Childrens Hosp, Boston, MA 02115 USA. RP Hoffner, B (reprint author), Univ Colorado, Univ Colorado Hosp, Sch Med, 9019 E Panorama Circle,415, Centennial, CO 80112 USA. EM bhoffner@gmail.com FU Dana-Farber Cancer Institute; NIH [2S07RR18207-02] FX The authors gratefully acknowledge colleagues and departments at the Dana-Farber Cancer Institute whose essential support made this study possible: Christina Parker, MD, Joseph Paul Eder, MD, Geoffrey Shapiro, MD, The Phyllis F. Cantor Center for Nursing Research (where S. B. W. was the former director, S. H. B. was a clinical scholar, and B. H. was formerly on staff) and the Department of Biostatistics and Computational Biology (where M. P. was formerly affiliated). Other support was received from the Georgia Cancer Coalition Distinguished Scholars program (S. B. W.). Also, during implementation of this study, S. H. B. was a clinical research nurse in the Early Drug Development Center at Dana-Farber Cancer Institute and M. P. was a statistician in the Department of Biostatistics and Computational Biology at Dana-Farber Cancer Institute.; NIH Grant 2S07RR18207-02. NR 17 TC 15 Z9 15 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2012 VL 118 IS 7 BP 1877 EP 1883 DI 10.1002/cncr.26438 PG 7 WC Oncology SC Oncology GA 910NR UT WOS:000301647000019 PM 22009665 ER PT J AU Reardon, DA Wen, PY Yung, WKA Berk, L Narasimhan, N Turner, CD Clackson, T Rivera, VM Vogelbaum, MA AF Reardon, David A. Wen, Patrick Y. Yung, W. K. Alfred Berk, Lori Narasimhan, Narayana Turner, Christopher D. Clackson, Timothy Rivera, Victor M. Vogelbaum, Michael A. TI Ridaforolimus for patients with progressive or recurrent malignant glioma: a perisurgical, sequential, ascending-dose trial SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Malignant glioma; Mammalian target of rapamycin; Ridaforolimus; Pharmacodynamics; Immunohistochemistry ID PHASE-I TRIAL; MAMMALIAN TARGET; GLIOBLASTOMA-MULTIFORME; DEFOROLIMUS AP23573; SIGNALING PATHWAY; MTOR INHIBITOR; TEMSIROLIMUS; CANCER; THERAPY; CCI-779 AB Purpose This perisurgical phase 1 study evaluated the pharmacokinetics, pharmacodynamics, and safety of the mammalian target of rapamycin (mTOR) inhibitor ridaforolimus in patients (N = 10) with progressive or recurrent primary grade IV malignant glioma, who failed standard therapy. The primary objective of the study was to determine the maximum tolerated dose (MTD) of ridaforolimus. Methods Treatment was administered intravenously at doses of 12.5 mg (N = 7) or 15 mg (N = 3) once daily for 4 days prior to surgical resection, then resumed for 5 consecutive days every 2 weeks until disease progression or unacceptable toxicity, following a postsurgical recovery period. Results The MTD was not determined because the trial was suspended early due to slower than expected patient accrual and postsurgical drug administration challenges. Pharmacokinetic and pharmacodynamic analyses showed that ridaforolimus concentrations declined slowly during the 24-h dosing interval and remained detectable for 10 days after the last infusion in whole blood samples. In peripheral blood mononuclear cells, median levels of the mTOR downstream effector p4E-BP1 were reduced by >80% compared with baseline by 4 h after dosing. Resected brain specimens showed reduced levels of pS6, another mTOR downstream effector, while nuclear staining for p27(kip1), a protein that functions as a cell cycle inhibitor, increased after treatment. No dose-limiting toxicities were observed, and the reported adverse events were consistent with the previously established safety profile for ridaforolimus. One of 3 patients evaluable for efficacy had stable disease as best response. Conclusion Results suggest that ridaforolimus can cross the blood-brain barrier in areas of tumor involvement, and may inhibit mTOR activity in advanced gliomas based on decreased pS6 levels. This perisurgical trial design should serve as a template for evaluating intratumoral pharmacokinetics and pharmacodynamics of other targeted agents in this patient population. C1 [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. [Yung, W. K. Alfred] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Berk, Lori; Narasimhan, Narayana; Turner, Christopher D.; Clackson, Timothy; Rivera, Victor M.] ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. [Vogelbaum, Michael A.] Cleveland Clin, Dept Neurosurg, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave SW G460F, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu FU Merck Co., Inc.; Merck; Amgen; AstraZeneca; Sanofi-aventis; Genentech; MedImmune; Vascular Biogenics FX The authors would like to thank Jason Scozzafava, MSc, and Joseph J. Abrajano, PhD, of Integrus Scientific, a division of Medicus International New York, for editorial assistance in the preparation of this manuscript. Editorial support was funded by Merck & Co., Inc. The authors were fully responsible for all content and editorial decisions and received no financial support or other compensation related to the development of the paper.; D.A.R. has received remuneration from Merck/Schering, Roche/Genentech, and EMD Serono and has acted as a consultant/advisor for Merck/Schering and Roche/Genentech. P.Y.W. has acted as a consultant/advisor for Novartis and Stemline Therapeutics and has received funding from Merck, Amgen, AstraZeneca, Sanofi-aventis, Genentech, MedImmune, and Vascular Biogenics. N.N. has received remuneration from ARIAD Pharmaceuticals. C.D.T. is an employee of, has received remuneration from, and owns stock in ARIAD Pharmaceuticals, Inc. T. C. has received remuneration from and owns stock in ARIAD Pharmaceuticals, Inc. V. M. R. has received remuneration from and owns stock in ARIAD Pharmaceuticals. M.A.V. has acted as a consultant/advisor for Merck. W.K.A.Y. and L.B. have no conflicts of interest to report. NR 37 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2012 VL 69 IS 4 BP 849 EP 860 DI 10.1007/s00280-011-1773-y PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 919LF UT WOS:000302327300001 PM 22037923 ER PT J AU DuBois, SG Shusterman, S Reid, JM Ingle, AM Ahern, CH Baruchel, S Glade-Bender, J Ivy, P Adamson, PC Blaney, SM AF DuBois, Steven G. Shusterman, Suzanne Reid, Joel M. Ingle, Ashish M. Ahern, Charlotte H. Baruchel, Sylvain Glade-Bender, Julia Ivy, Percy Adamson, Peter C. Blaney, Susan M. TI Tolerability and pharmacokinetic profile of a sunitinib powder formulation in pediatric patients with refractory solid tumors: a Children's Oncology Group study SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Sunitinib; Pediatric; Pharmacokinetics; Formulation ID TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; ANTITUMOR-ACTIVITY; PHASE-I; MALATE SU11248; GROWTH-FACTOR; IMATINIB; CANCER; VIVO AB Purpose Sunitinib is an oral tyrosine kinase inhibitor of VEGF, PDGF, c-KIT, and flt-3 receptors. A pediatric phase I study of sunitinib capsules identified the maximum tolerated dose as 15 mg/m(2)/day. This study was conducted to evaluate sunitinib given as a powder formulation. Methods Sunitinib 15 mg/m(2) was administered orally daily for 4 weeks on/2 weeks off to patients <21 years old with refractory solid tumors. Sunitinib capsules were opened, and the powder sprinkled onto applesauce or yogurt. Plasma levels of sunitinib and an active metabolite, SU12662, were measured, and pharmacokinetic parameters were estimated. Results 12 patients, median age 13 (range 4-21) years, were treated. The most common first-cycle toxicities were leucopenia (n = 6), fatigue (n = 5), neutropenia (n = 4), and hypertension (n = 4). Three patients had dose-limiting toxicities (DLTs) in cycle 1 (dizziness/back pain, hand-foot syndrome, and intratumoral hemorrhage/hypoxia). A median peak plasma sunitinib concentration of 21 (range 636) ng/ml was reached at a median of 4 (range 4-8) h after the first dose. The median exposure (AUC(0-48)) was 585 (range 196-1,059) h ng/l. The median half-life was 23 (range 13-36) h. The median trough concentration measured before day 14 dosing was 32 (range 12-58) ng/ml. Conclusions The pharmacokinetic profile of sunitinib appears similar between a powder formulation and published data using capsules. The powder formulation allows patients unable to swallow capsules to receive sunitinib. C1 [DuBois, Steven G.] UCSF Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Shusterman, Suzanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Dept Pediat, Boston, MA 02115 USA. [Reid, Joel M.] Mayo Coll Med, Dept Pharmacol, Rochester, MN USA. [Ingle, Ashish M.] Childrens Oncol Grp Operat Ctr, Arcadia, CA USA. [Ahern, Charlotte H.] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Baruchel, Sylvain] Hosp Sick Children, Dept Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Glade-Bender, Julia] Columbia Univ, Dept Pediat, Morgan Stanley Childrens Hosp, Sch Med, New York, NY 10027 USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Adamson, Peter C.] Univ Penn, Childrens Hosp Philadelphia, Dept Oncol, Philadelphia, PA 19104 USA. [Blaney, Susan M.] Baylor Coll Med, Dept Pediat, Texas Childrens Canc Ctr, Houston, TX 77030 USA. RP DuBois, SG (reprint author), UCSF Sch Med, Dept Pediat, 505 Parnassus Ave,M646, San Francisco, CA 94143 USA. EM duboiss@peds.ucsf.edu FU Campini Foundation; Pfizer; NIH/NCRR/OD UCSF-CTSI [KL2 RR024130]; NCI [U01 CA97452] FX This study was supported by the Campini Foundation, Pfizer, NIH/NCRR/OD UCSF-CTSI Grant Number KL2 RR024130, and NCI U01 CA97452. Pfizer provided partial support for the analyses of sunitinib pharmacokinetics. NR 18 TC 13 Z9 14 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2012 VL 69 IS 4 BP 1021 EP 1027 DI 10.1007/s00280-011-1798-2 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 919LF UT WOS:000302327300020 PM 22179104 ER PT J AU Meisel, JL Domchek, SM Vonderheide, RH Giobbie-Hurder, A Lin, NU Winer, EP Partridge, AH AF Meisel, Jane L. Domchek, Susan M. Vonderheide, Robert H. Giobbie-Hurder, Anita Lin, Nancy U. Winer, Eric P. Partridge, Ann H. TI Quality of Life in Long-Term Survivors of Metastatic Breast Cancer SO CLINICAL BREAST CANCER LA English DT Article DE Advanced breast cancer; Metastatic breast cancer; Quality of life; Survivorship ID RANDOMIZED CONTROLLED-TRIAL; EXPRESSIVE GROUP-THERAPY; DEPRESSION SCALE; HOSPITAL ANXIETY; ALTERNATIVE MEDICINE; WOMEN; CHEMOTHERAPY; IMPACT; POPULATION; SUPPORT AB Little is known about the quality of life of women living long term with metastatic breast cancer. We conducted a survey of women living with metastatic breast cancer for 5 years or longer. Although overall quality of life appeared quite favorable, some women reported substantial depression and/or anxiety about their disease. Ongoing work to address the needs of this growing population is warranted. Introduction: Psychosocial distress is common after a diagnosis of breast cancer. Little is known about the psychosocial adjustment of women living long term with metastatic breast cancer. Methods: We conducted a cross-sectional survey of women living with metastatic breast cancer for 5 years or longer. The survey included demographic and medical history, the Hospital Anxiety and Depression Scale (HADS), the Revised Impact of Events Scale (IES-R), the Functional Assessment of Cancer Therapy-Breast (FACT-Breast), and the Duke-University of North Carolina (UNC) Functional Social Support (DUFSS) Questionnaire. Demographic and disease characteristics were assessed by using the Wilcoxon rank sum test and the Fisher exact test. The relationships between IES-A, DUFSS, and the HADS were assessed by using the Spearman correlation coefficients. Statistical tests were 2-sided, with significance defined as P <= .05. Results: Eighteen (64%) of 28 eligible women completed the survey. Women who completed the survey were more likely to have had node-positive disease (2P = .0007), to had taken adjuvant therapy (2P = .01), and to have had hormone-receptor positive disease than women who did not (2P = .04). Among those who completed the survey, data from the FACT-Breast and the DUFSS indicated that women are physically functioning well but still face significant emotional challenges. Results from the HADS indicated that 2 (11.1%) of 18 women were depressed and that 2 (11.1%) of 18 women were anxious. Six (33%) of 18 women had scores on the IES-R Scale that indicated a powerful impact of traumatic stress on the ability to function. In the total sample of 18, the IES-R was significantly correlated with the HADS-Anxiety score (Spearman correlation, 0.81; 2P = .0002) but not with the HADS-Depression score (Spearman correlation, 0.40; 2P = .12). Conclusions: Although overall quality of life is good in this population of women living long term with metastatic breast cancer, there is a subset of women who are dealing with significant anxiety and depression, and a larger group who are experiencing burdensome sadness, hopelessness, and apprehension about their disease. Ongoing work to address the needs of this population is warranted. C1 [Giobbie-Hurder, Anita; Lin, Nancy U.; Winer, Eric P.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meisel, Jane L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Domchek, Susan M.; Vonderheide, Robert H.] Hosp Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ahpartridge@partners.org NR 40 TC 7 Z9 7 U1 1 U2 5 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD APR PY 2012 VL 12 IS 2 BP 119 EP 126 DI 10.1016/j.clbc.2012.01.010 PG 8 WC Oncology SC Oncology GA 917VQ UT WOS:000302207100006 PM 22444718 ER PT J AU Lawson, EA Miller, KK Blum, JI Meenaghan, E Misra, M Eddy, KT Herzog, DB Klibanski, A AF Lawson, Elizabeth A. Miller, Karen K. Blum, Justine I. Meenaghan, Erinne Misra, Madhusmita Eddy, Kamryn T. Herzog, David B. Klibanski, Anne TI Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum, independent of body fat SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ANOREXIA-NERVOSA; PSYCHIATRIC COMORBIDITY; HYPOTHALAMIC AMENORRHEA; BEHAVIORAL-RESPONSES; ANXIETY DISORDERS; MEMORY RETENTION; PLASMA GHRELIN; SERUM LEPTIN; RATING-SCALE; OBESITY AB Objective Leptin is anorexigenic, and levels are markedly decreased in women with low body weight and high in women with obesity. Ghrelin opposes leptin effects on appetite and is negatively associated with body mass index. These appetite-regulating hormones may have opposing effects on mood and stress pathways. Women with anorexia nervosa (AN), hypothalamic amenorrhoea (HA) and obesity are at increased risk of depression and anxiety. It is unknown whether dysregulation of leptin or ghrelin contributes to the development of depression and/or anxiety in these disorders. We investigated the relationship between leptin and ghrelin levels and symptoms of depression, anxiety and perceived stress in women across the weight spectrum. Design Cross-sectional. Patients 64 women: 15 with AN, 12 normal-weight with HA, 17 overweight or obese (OB) and 20 normal-weight in good health (HC). Measurements Fasting serum leptin and plasma ghrelin levels were measured. Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the Perceived Stress Scale were administered. Results Leptin levels were inversely associated with HAM-D, HAM-A and Perceived Stress scores. The negative relationships between leptin and severity of symptoms of both depression and anxiety remained significant after controlling for body fat or weight. There was no relationship between ghrelin and symptoms of depression or anxiety. Although ghrelin levels were positively associated with the degree of perceived stress, this relationship was not significant after controlling for body fat or weight. Conclusions Leptin may mediate depressive symptoms across the weight spectrum. Further investigation of the role of leptin in modulating mood will be important. C1 [Lawson, Elizabeth A.; Miller, Karen K.; Blum, Justine I.; Meenaghan, Erinne; Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lawson, EA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM ealawson@partners.org FU Bioenvision; NIH [M01 RR01066, UL1 RR025758]; NIH Office of Research in Women's Health (ORWH) [K12 HD0519599] FX We thank the nurses and bionutritionists in the Massachusetts General Hospital Clinical Research Center and the subjects who participated in the study. This work was supported in part by the following grants: Investigator-initiated grant from Bioenvision. NIH: M01 RR01066 and UL1 RR025758. EA Lawson was funded by the Harvard K12 HD0519599 Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program supported by NIH Office of Research in Women's Health (ORWH). The authors have no conflicts to declare. NR 46 TC 39 Z9 41 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD APR PY 2012 VL 76 IS 4 BP 520 EP 525 DI 10.1111/j.1365-2265.2011.04182.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 904DY UT WOS:000301175400011 PM 21781144 ER PT J AU Zhang, J Hedden, T Chia, A AF Zhang, Jun Hedden, Trey Chia, Adrian TI Perspective-Taking and Depth of Theory-of-Mind Reasoning in Sequential-Move Games SO COGNITIVE SCIENCE LA English DT Article DE Game theory; Rationality; Recursive reasoning; Iterated reasoning; Reflexive reasoning; Intention; Belief-desire psychology; Mental model; Working memory; First-person perspective; Third-person perspective ID COMMON KNOWLEDGE; PLAYERS MODELS; CENTIPEDE GAME; RATIONALITY; LIMITATIONS; DOMINANCE AB Theory-of-mind (ToM) involves modeling an individuals mental states to plan ones action and to anticipate others actions through recursive reasoning that may be myopic (with limited recursion) or predictive (with full recursion). ToM recursion was examined using a series of two-player, sequential-move matrix games with a maximum of three steps. Participants were assigned the role of Player I, controlling the initial and the last step, or of Player II, controlling the second step. Appropriate for the assigned role, participants either anticipated or planned Player IIs strategy at the second step, and then determined Player Is optimal strategy at the first step. Participants more readily used predictive reasoning as Player II (i.e., planning ones own move) than as Player I (i.e., anticipating an opponents move), although they did not differ when translating reasoning outcome about the second step to optimal action in the first step. Perspective-taking influenced likelihood of predictive reasoning, but it did not affect the rate at which participants acquired it during the experimental block. We conclude that the depth of ToM recursion (related to perspective-taking mechanisms) and rational application of beliefdesire to action (instrumental rationality) constitute separate cognitive processes in ToM reasoning. C1 [Zhang, Jun; Chia, Adrian] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Hedden, Trey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Zhang, J (reprint author), Univ Michigan, Dept Psychol, 530 Church St, Ann Arbor, MI 48109 USA. EM junz@umich.edu NR 45 TC 6 Z9 6 U1 1 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-0213 J9 COGNITIVE SCI JI Cogn. Sci. PD APR PY 2012 VL 36 IS 3 BP 560 EP 573 DI 10.1111/j.1551-6709.2012.01238.x PG 14 WC Psychology, Experimental SC Psychology GA 919TY UT WOS:000302353400008 PM 22436023 ER PT J AU Preer, G Sorrentino, D Newton, AW AF Preer, Genevieve Sorrentino, Deborah Newton, Alice W. TI Child abuse pediatrics: prevention, evaluation, and treatment SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE abusive head trauma; child abuse; child maltreatment; child sexual abuse; shaken baby syndrome ID HEAD TRAUMA; SEXUAL-ABUSE; FORENSIC EVIDENCE; SKELETAL SURVEYS; MALTREATMENT; PREVALENCE; RISK; COLLECTION; PROTECTION; FRACTURES AB Purpose of review This review is designed to update the general pediatrician with information about current child maltreatment literature. The authors have selected salient articles, which inform daily practice of any professional involved in the care of children who may be at risk of child abuse. Recent findings The field of child abuse pediatrics continues to engender controversy in both medical journals and courtrooms. As scrutiny about the basis for the diagnosis increases, clinicians and researchers work to build a solid base of scientific evidence with thorough and well-designed studies. This is most evident with regards to abusive head trauma, wherein both lay and scientific press challenge the possibility that infants can be severely injured or killed by shaking, blunt force trauma, or both. Summary Child abuse pediatrics is a well-established and credible medical field. Although child physical and sexual abuse are age-old problems, public acknowledgement and intervention models are relatively new, and medical literature continues to reflect an increasing and deeper understanding of the impact of abuse throughout the world. C1 [Sorrentino, Deborah; Newton, Alice W.] Childrens Hosp, Child Protect Program, Boston, MA 02115 USA. [Preer, Genevieve] Boston Univ, Sch Med, Dept Pediat, Child Protect Program,Boston Med Ctr, Boston, MA 02118 USA. [Newton, Alice W.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp,Child Protect Program,Chil, Boston, MA 02115 USA. RP Newton, AW (reprint author), Childrens Hosp, Child Protect Program, 300 Longwood Ave, Boston, MA 02115 USA. EM alice.newton@childrens.harvard.edu OI Preer, Genevieve/0000-0001-8264-3541 NR 41 TC 2 Z9 2 U1 3 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2012 VL 24 IS 2 BP 266 EP 273 DI 10.1097/MOP.0b013e328350674d PG 8 WC Pediatrics SC Pediatrics GA 917AG UT WOS:000302143700020 PM 22426158 ER PT J AU Bray, GA Edelstein, SL Crandall, JP Aroda, VR Franks, PW Fujimoto, W Horton, E Jeffries, S Montez, M Mudaliar, S Pi-Sunyer, FX White, NH Knowler, WC AF Bray, George A. Edelstein, Sharon L. Crandall, Jill P. Aroda, Vanita R. Franks, Paul W. Fujimoto, Wilfred Horton, Edward Jeffries, Susan Montez, Maria Mudaliar, Sunder Pi-Sunyer, F. Xavier White, Neil H. Knowler, William C. CA Diabet Prevention Program Res Grp TI Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study SO DIABETES CARE LA English DT Article ID ACTIVATED PROTEIN-KINASE; LIFE-STYLE INTERVENTION; TYPE-2; EXERCISE; MELLITUS; THERAPY; OBESITY; MUSCLE; DIET AB OBJECTIVE-Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up. RESEARCH DESIGN AND METHODS-The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference. RESULTS-No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 +/- 5.65% vs. 0.02 +/- 5.52%, P < 0.001, and waist circumference by 2.13 +/- 7.06 cm vs. 0.79 +/- 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001). CONCLUSIONS-Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment. C1 [Bray, George A.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Edelstein, Sharon L.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Aroda, Vanita R.] Medstar Hlth Res Inst, Hyattsville, MD USA. [Franks, Paul W.] Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Fujimoto, Wilfred] Univ Washington, Seattle, WA 98195 USA. [Horton, Edward] Joslin Diabet Ctr, Boston, MA 02215 USA. [Jeffries, Susan] Univ Pittsburgh, Pittsburgh, PA USA. [Montez, Maria] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Mudaliar, Sunder] Univ Calif San Diego, San Diego, CA 92103 USA. [Pi-Sunyer, F. Xavier] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. [White, Neil H.] Washington Univ, Sch Med, St Louis, MO USA. [Knowler, William C.] NIDDK, Phoenix, AZ USA. RP Bray, GA (reprint author), Pennington Biomed Res Ctr, Baton Rouge, LA USA. OI Franks, Paul/0000-0002-0520-7604 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; National Institute of Child Health and Human Development; National Institute on Aging; National Eye Institute; National Heart, Lung, and Blood Institute; Office of Research on Women's Health; National Institute on Minority Health and Health Disparities; Centers for Disease Control and Prevention; American Diabetes Association; Bristol-Myers Squibb; Parke-Davis; Novo Nordisk; Swedish Heart-Lung Foundation; Swedish Diabetes Association; Swedish Research Council FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the DPP Coordinating Center for the design and conduct of the study, and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development; the National Institute on Aging; the National Eye Institute; the National Heart, Lung, and Blood Institute; the Office of Research on Women's Health; the National Institute on Minority Health and Health Disparities; the Centers for Disease Control and Prevention; and the American Diabetes Association.; Bristol-Myers Squibb and Parke-Davis provided additional funding and material support during the DPP. Lipha (Merck-Sante) provided medication, and Life Scan Inc. donated materials during the DPP and the DPPOS. P.W.F. was supported in part by grants from Novo Nordisk, the Swedish Heart-Lung Foundation, the Swedish Diabetes Association, and the Swedish Research Council. No other potential conflicts of interest relevant to this article were reported. NR 22 TC 53 Z9 54 U1 2 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2012 VL 35 IS 4 BP 731 EP 737 DI 10.2337/dc11-1299 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914OB UT WOS:000301959600013 ER PT J AU Ortiz-Lopez, C Lomonaco, R Orsak, B Finch, J Chang, Z Kochunov, VG Hardies, J Cusi, K AF Ortiz-Lopez, Carolina Lomonaco, Romina Orsak, Beverly Finch, Joan Chang, Zhi Kochunov, Valeria G. Hardies, Jean Cusi, Kenneth TI Prevalence of Prediabetes and Diabetes and Metabolic Profile of Patients With Nonalcoholic Fatty Liver Disease (NAFLD) SO DIABETES CARE LA English DT Article ID INSULIN-RESISTANCE; HEPATIC STEATOSIS; MELLITUS; STEATOHEPATITIS; SECRETION; OBESITY; GLUCOSE; LIPOTOXICITY; PATHOGENESIS; POPULATION AB OBJECTIVE-Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be common and associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). However, no previous study has systematically screened this population. RESEARCH DESIGN AND METHODS-We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects without NAFLD matched for age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity (euglycemic insulin clamp with 3-[H-3]glucose); and 4) indexes of insulin resistance (IR) at the level of the liver (HIRi=endogenous glucose production X fasting plasma insulin [FPI]) and adipose tissue (Adipo-IRi=fasting FFA X FPI). RESULTS-Prediabetes and T2DM was present in 85% versus 30% in controls (P < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were IR at the level of the adipose tissue, liver, and muscle (all P < 0.01-0.001). Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001) and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P < 0.0001). CONCLUSIONS-Patients with NAFLD may benefit from early screening for T2DM, because the prevalence of abnormal glucose metabolism is much higher than previously appreciated. Regardless of glucose tolerance status, severe IR is common. In patients with T2DM, adipose tissue IR appears to play a major role in the severity of NAFLD. C1 [Ortiz-Lopez, Carolina; Orsak, Beverly; Chang, Zhi; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA. [Lomonaco, Romina; Cusi, Kenneth] Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL USA. [Finch, Joan; Cusi, Kenneth] Audie L Murphy Vet Adm Med Ctr, San Antonio, TX USA. [Kochunov, Valeria G.; Hardies, Jean] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. [Cusi, Kenneth] Malcolm Randall Vet Adm Med Ctr, Gainesville, FL USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA. EM cusi@uthscsa.edu FU Burroughs Wellcome Fund; American Diabetes Association [1-08-CR-08]; Veterans Affairs Medical Research Fund; National Center for Research Resources [UL 1RR025767] FX This work was supported by the Burroughs Wellcome Fund (K.C.), by the American Diabetes Association (1-08-CR-08; K.C.), by the Veterans Affairs Medical Research Fund, and by Award Number UL 1RR025767 from the National Center for Research Resources. NR 38 TC 67 Z9 72 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2012 VL 35 IS 4 BP 873 EP 878 DI 10.2337/dc11-1849 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914OB UT WOS:000301959600037 PM 22374640 ER PT J AU Lee, CC Bloem, CJ Kasa-Vubu, JZ Liang, LJ AF Lee, C. C. Bloem, C. J. Kasa-Vubu, J. Z. Liang, L. -J. TI Effect of oral phytoestrogen on androgenicity and insulin sensitivity in postmenopausal women SO DIABETES OBESITY & METABOLISM LA English DT Article DE androgenicity insulin sensitivity; phytoestrogen; postmenopausal women; transdermal oestrogen ID RED-CLOVER; ESTROGEN; SOY; ISOFLAVONES; METABOLISM; BINDING; HUMANS; LIPIDS AB Aim: The aim of this study was to determine and compare the effect of treatment with transdermal oestrogen and phytoestrogen on insulin sensitivity and sex hormone-binding globulin (SHBG) levels in healthy postmenopausal women. Methods: Forty-three healthy postmenopausal women aged 68 +/- 7 (mean +/- SD) years who were not receiving hormonal replacement therapy completed a 3 month randomized drug therapy study. The participants were randomized to one of four groups: 0.05 mg or 0.1 mg transdermal oestrogen/ day, or 40 or 80 mg oral phytoestrogen (Promensil)/day insulin sensitivity was indirectly measured using the quantitative insulin sensitivity check index (QUICKI). SHBG, total testosterone, oestradiol, and fasting glucose and insulin levels for calculation of insulin sensitivity were obtained at baseline and at monthly intervals during the 3 months of therapy. Results: In healthy nondiabetic postmenopausal women, the rate of change in QUICKI was significantly different between the red clover based phytoestrogen and transdermal oestrogen groups, so that after three months of therapy, QUICKI with red clover based phytoestrogen therapy was lower than that in the transdermal oestrogen group, p = 0.01. Red clover based phytoestrogen therapy was not associated with any changes in SHBG levels whereas transdermal estrogen therapy significantly increased SHBG levels, p = 0.05. Conclusions: In contrast to transdermal oestrogen therapy, oral phytoestrogen therapy does not decrease androgenicity and is associated with a decrease in insulin sensitivity. These effects are similar to those of raloxifene and consistent with phytoestrogen's selective oestrogen receptor modulator properties. C1 [Lee, C. C.] Ctr Geriatr Res Educ & Clin, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Lee, C. C.; Liang, L. -J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Bloem, C. J.] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. [Kasa-Vubu, J. Z.] Univ Michigan Hlth Syst, Dept Pediat, Div Pediat Endocrinol, Ann Arbor, MI USA. RP Lee, CC (reprint author), Ctr Geriatr Res Educ & Clin, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,GRECC 11-G, Los Angeles, CA 90073 USA. EM cathy.c.lee@ucla.edu FU NCRR NIH HHS [RR-00042]; NIA NIH HHS [AG 08808]; NIDDK NIH HHS [P60DK2572] NR 15 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD APR PY 2012 VL 14 IS 4 BP 315 EP 319 DI 10.1111/j.1463-1326.2011.01532.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903LD UT WOS:000301117100004 PM 22077482 ER PT J AU Rhodes, ET Prosser, LA Hoerger, TJ Lieu, T Ludwig, DS Laffel, LM AF Rhodes, E. T. Prosser, L. A. Hoerger, T. J. Lieu, T. Ludwig, D. S. Laffel, L. M. TI Estimated morbidity and mortality in adolescents and young adults diagnosed with Type 2 diabetes mellitus SO DIABETIC MEDICINE LA English DT Article DE adolescence; microvascular disease; modelling; mortality; Type 2 diabetes ID INTENSIVE GLYCEMIC CONTROL; AMERICAN YOUTH PREVALENCE; BLOOD-GLUCOSE CONTROL; QUALITY-OF-LIFE; CLINICAL CHARACTERISTICS; COST-EFFECTIVENESS; AFRICAN-AMERICAN; UNITED-STATES; RISK-FACTORS; SEARCH AB Aims To estimate remaining life expectancy (RLE), quality-adjusted life expectancy (QALE), causes of death and lifetime cumulative incidence of microvascular/macrovascular complications of diabetes for youths diagnosed with Type 2 diabetes. Methods A Markov-like computer model simulated the life course for a hypothetical cohort of adolescents/young adults in the USA, aged 1524 years, newly diagnosed with Type 2 diabetes following either conventional or intensive treatment based on the UK Prospective Diabetes Study. Outcomes included RLE, discounted QALE in quality-adjusted life years (QALYs), cumulative incidence of microvascular/macrovascular complications and causes of death. Results Compared with a mean RLE of 58.6 years for a 20-year-old in the USA without diabetes, conventional treatment produced an average RLE of 43.09 years and 22.44 discounted QALYs. Intensive treatment afforded an incremental 0.98 years and 0.44 discounted QALYs. Intensive treatment led to lower lifetime cumulative incidence of all microvascular complications and lower mortality from microvascular complications (e.g. end-stage renal disease (ESRD) death 19.4% vs. 25.2%). Approximately 5% with both treatments had ESRD within 25 years. Lifetime cumulative incidence of coronary heart disease (CHD) increased with longer RLE and greater severity of CHD risk factors. Incorporating disutility (loss in health-related quality of life) of intensive treatment resulted in net loss of QALYs. Conclusions Adolescents/young adults with Type 2 diabetes lose approximately 15 years from average RLE and may experience severe, chronic complications of Type 2 diabetes by their 40s. The net clinical benefit of intensive treatment may be sensitive to preferences for treatment. A comprehensive management plan that includes early and aggressive control of cardiovascular risk factors is likely needed to reduce lifetime risk of CHD. C1 [Rhodes, E. T.; Ludwig, D. S.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Rhodes, E. T.; Ludwig, D. S.; Laffel, L. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Prosser, L. A.] Univ Michigan, Div Gen Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI 48109 USA. [Prosser, L. A.; Lieu, T.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Ctr Child Hlth Care Studies, Boston, MA USA. [Hoerger, T. J.] RTI Int, RTI UNC Ctr Excellence Hlth Promot Econ, Res Triangle Pk, NC USA. [Lieu, T.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. [Laffel, L. M.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Rhodes, ET (reprint author), Childrens Hosp, Div Endocrinol, 333 Longwood Ave,6th Floor, Boston, MA 02115 USA. EM erinn.rhodes@childrens.harvard.edu FU New Balance Foundation; Centers for Disease Control and Prevention (CDC) [K01DP000089]; National Institute of Diabetes and Digestive and Kidney Diseases [K24DK082730] FX E.T.R. received salary support from an unrestricted, philanthropic grant from the New Balance Foundation and was formerly Chief Medical Officer for Pediatric Weight Management Centers, LLC's Great Moves! Program, a company privately owned and operated in collaboration with the physicians of Children's Hospital Boston. E. T. R. provided contracted clinical and administrative services for the company but neither had nor has equity or other economic interest in the business. E. T. R. has also disclosed that her spouse owns stock in Bristol Myers Squibb and Pfizer. L. M. L. is a consultant for Lilly, Bristol Myers Squibb, Menarini, Sanofi-Aventis, Johnson & Johnson and Astra Zeneca, and receives grant support from Bayer. The remaining authors have nothing to declare.; The study was supported by the Centers for Disease Control and Prevention (CDC) grant K01DP000089 (to E. T. R). Additional support to investigators included the Katherine Adler Astrove Youth Education Fund (L. M. L.), Maria Griffin Drury Fund (L. M. L.) and National Institute of Diabetes and Digestive and Kidney Diseases grant K24DK082730 (D. S. L.). The CDC Diabetes Cost Effectiveness Model used in this study was developed under Contracts 200-97-0621 and 200-2002-00776 from the CDC to RTI International. The CDC approved the use of the CDC Diabetes Cost Effectiveness Model for the study. Neither the CDC nor the funders were involved in the design or conduct of the study, the collection, management, analysis or interpretation of the data, or preparation, review, decision to publish or approval of the manuscript. The authors thank the members of our Expert Panel including Sonia Caprio MD (Yale University School of Medicine), Robert Lustig MD (University of California, San Francisco), Thomas Songer PhD (University of Pittsburgh Graduate School of Public Health), Marc WeigensbergMD (University of Southern California) and Ruth Weinstock MD PhD (State University of New York Upstate) for their valuable input, Roula Zoghbi MPH for technical assistance with the Expert Panel proceedings and Melissa Putman MD for assistance with the systematic review. NR 42 TC 43 Z9 46 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD APR PY 2012 VL 29 IS 4 BP 453 EP 463 DI 10.1111/j.1464-5491.2011.03542.x PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906LB UT WOS:000301345600005 PM 22150528 ER PT J AU Markowitz, JT Laffel, LMB AF Markowitz, J. T. Laffel, L. M. B. TI Transitions in care: support group for young adults with Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article DE support groups; Type 1 diabetes; young adults ID HEALTH-CARE; ADOLESCENTS; SERVICE AB Aims Young adulthood is a challenging period for patients with Type 1 diabetes as developmental changes complicate Type 1 diabetes management and gaps in care may arise as patients transition from paediatric to adult providers. This period has been associated with worsening diabetes outcomes. One approach to aid young adults during this transition period could entail professionally led support groups to enhance self-motivation and facilitate peer-to-peer interactions. We implemented and evaluated a support group for young adults with Type 1 diabetes as a pilot project. Methods Young adults with Type 1 diabetes (1830 years) participated in monthly, professionally led support groups for 5 months. Questionnaires were completed pre- and post-group and chart review data were collected regarding glycaemic control and visit frequency in the year before and after group participation. Results Participation in the group was associated with improvement in HbA1c and decreased self-reported diabetes burden, along with a trend for an increase in diabetes-related self-care behaviours. Frequency of visits did not vary from pre- to post-group. Discussion topics identified by participants included managing diabetes in day-to-day life, experiences and interactions with others who do not have diabetes and emotions related to diabetes. Participants identified that they sought a diabetes care team that offers knowledge, support and a multidisciplinary team. Conclusions Professionally led support groups may have utility for increasing social support and optimizing diabetes outcomes in young adults with Type 1 diabetes. C1 [Markowitz, J. T.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Markowitz, JT (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM jessica.markowitz@joslin.harvard.edu FU NIH [T32 DK007260]; National Institute of Diabetes and Digestive and Kidney Diseases [DK-46887, 1K12DK094721]; Charles H. Hood Foundation; Maria Griffin Drury Pediatric Fund; Katherine Adler Astrove Youth Education Fund FX This work was supported in part by NIH Training Grant no. T32 DK007260, grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-46887; 1K12DK094721), the Charles H. Hood Foundation, the Maria Griffin Drury Pediatric Fund and the Katherine Adler Astrove Youth Education Fund. NR 17 TC 23 Z9 24 U1 1 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD APR PY 2012 VL 29 IS 4 BP 522 EP 525 DI 10.1111/j.1464-5491.2011.03537.x PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906LB UT WOS:000301345600015 PM 22150392 ER PT J AU Markowitz, JT Volkening, LK Butler, DA Antisdel-Lomaglio, J Anderson, BJ Laffel, LMB AF Markowitz, J. T. Volkening, L. K. Butler, D. A. Antisdel-Lomaglio, J. Anderson, B. J. Laffel, L. M. B. TI Re-examining a measure of diabetes-related burden in parents of young people with Type 1 diabetes: the Problem Areas in Diabetes Survey - Parent Revised version (PAID-PR) SO DIABETIC MEDICINE LA English DT Article DE adolescence; Type 1 diabetes ID GLYCEMIC CONTROL; FAMILY CONFLICT; ADOLESCENTS; IMPACT; YOUTH; ADHERENCE; MELLITUS; INTERVENTION; RELIABILITY; INVOLVEMENT AB Aims In a pediatric patients, the burden of diabetes lies within the family. In the current era of intensive insulin therapy, perceived parental burden may affect the familys efforts at effective diabetes management. The aims of this study were to re-examine and revise a measure of perceived parental burden associated with caring for a child with diabetes in the current era. Methods A geographically diverse population of young people (N = 376) with Type 1 diabetes and their parents included participants in the Juvenile Diabetes Research Foundation continuous glucose monitoring study and patients from the Joslin Diabetes Center. Participants provided data on demographics, diabetes management, diabetes-specific family conflict, and quality of life at baseline and after 6 months of follow-up. Results Young people were 12.9 +/- 2.7 years old with diabetes duration of 6.3 +/- 3.5 years. Mean HbA1C was 8.0 +/- 1.2%(64 mmol/mol), 58% received insulin pump therapy, and young people monitored blood glucose 5.2 +/- 2.3 times/day. Factor analysis yielded two factors, Immediate Burden and Theoretical Burden. The Problem Areas in Diabetes Survey Parent Revised version (PAID-PR) demonstrated excellent internal consistency (Cronbachs a = 0.87; factor 1 a = 0.78; factor 2 a = 0.83). Greater parental burden was associated with more frequent blood glucose monitoring, higher HbA1C levels, greater diabetes-specific family conflict, and lower quality of life. Testretest analysis was acceptable (r = 0.62). Conclusions The PAID-PR demonstrated excellent internal consistency, good test-retest reliability, and associations with diabetes-specific family conflict and quality of life. This brief measure may have both clinical and research utility in the management of young people with Type 1 diabetes. C1 [Markowitz, J. T.; Volkening, L. K.; Butler, D. A.; Laffel, L. M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Antisdel-Lomaglio, J.] Childrens Mem Hosp, Dept Child & Adolescent Psychiat, Chicago, IL 60614 USA. [Anderson, B. J.] Texas Childrens Hosp, Baylor Coll Med, Psychol Sect, Houston, TX 77030 USA. [Anderson, B. J.] Texas Childrens Hosp, Baylor Coll Med, Endocrinol Sect, Houston, TX 77030 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU Charles H. Hood Foundation; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund; NIH [T32 DK007260] FX This work was supported in part by the Charles H. Hood Foundation, the Katherine Adler Astrove Youth Education Fund, the Maria Griffin Drury Pediatric Fund and NIH Training Grant No. T32 DK007260. We would also like to acknowledge the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group for the use of their public dataset. NR 18 TC 11 Z9 12 U1 5 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD APR PY 2012 VL 29 IS 4 BP 526 EP 530 DI 10.1111/j.1464-5491.2011.03434.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906LB UT WOS:000301345600016 PM 21883443 ER PT J AU Gendron, M Lindquist, KA Barsalou, L Barrett, LF AF Gendron, Maria Lindquist, Kristen A. Barsalou, Lawrence Barrett, Lisa Feldman TI Emotion Words Shape Emotion Percepts SO EMOTION LA English DT Article DE emotion perception; perceptual priming; linguistic relativity; words; conceptual knowledge ID ANTERIOR TEMPORAL-LOBES; FACIAL EXPRESSIONS; SEMANTIC SATIATION; CATEGORICAL PERCEPTION; LANGUAGE COMPREHENSION; REPETITION SUPPRESSION; FMRI ADAPTATION; VISUAL-CORTEX; RECOGNITION; CONTEXT AB People believe they see emotion written on the faces of other people. In an instant, simple facial actions are transformed into information about another's emotional state. The present research examined whether a perceiver unknowingly contributes to emotion perception with emotion word knowledge. We present 2 studies that together support a role for emotion concepts in the formation of visual percepts of emotion. As predicted, we found that perceptual priming of emotional faces (e.g., a scowling face) was disrupted when the accessibility of a relevant emotion word (e.g., anger) was temporarily reduced, demonstrating that the exact same face was encoded differently when a word was accessible versus when it was not. The implications of these findings for a linguistically relative view of emotion perception are discussed. C1 [Gendron, Maria] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Gendron, Maria; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Shenyang, Peoples R China. [Lindquist, Kristen A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Lindquist, Kristen A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Lindquist, Kristen A.] Harvard Univ, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Barsalou, Lawrence] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Mass Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Mass Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RP Gendron, M (reprint author), Boston Coll, Dept Psychol, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM gendroma@bc.edu FU NIH HHS [DP1 OD003312, DP1OD003312] NR 88 TC 40 Z9 44 U1 7 U2 116 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD APR PY 2012 VL 12 IS 2 BP 314 EP 325 DI 10.1037/a0026007 PG 12 WC Psychology, Experimental SC Psychology GA 917SX UT WOS:000302200000015 PM 22309717 ER PT J AU Chun, KH Araki, K Jee, Y Lee, DH Oh, BC Huang, H Park, KS Lee, SW Zabolotny, JM Kim, YB AF Chun, Kwang-Hoon Araki, Kazushi Jee, Yuna Lee, Dae-Ho Oh, Byung-Chul Huang, Hu Park, Kyong Soo Lee, Sam W. Zabolotny, Janice M. Kim, Young-Bum TI Regulation of Glucose Transport by ROCK1 Differs from That of ROCK2 and Is Controlled by Actin Polymerization SO ENDOCRINOLOGY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; GTP-BINDING PROTEINS; RHO-KINASE-II; 3T3-L1 ADIPOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE; LIM-KINASE; GLUT4 TRANSLOCATION; CORTICAL ACTIN; RAT ADIPOCYTES; MUSCLE-CELLS AB A role of Rho-associated coiled-coil-containing protein kinase (ROCK) 1 in regulating whole-body glucose homeostasis has been reported. However, cell-autonomous effects of ROCK1 on insulin-dependent glucose transport in adipocytes and muscle cells have not been elucidated. To determine the specific role of ROCK1 in glucose transport directly, ROCK1 expression in 3T3-L1 adipocytes and L6 myoblasts was biologically modulated. Here, we show that small interfering RNA-mediated ROCK1 depletion decreased insulin-induced glucose transport in adipocytes and myoblasts, whereas adenovirus-mediated ROCK1 expression increased this in a dose-dependent manner, indicating that ROCK1 is permissive for glucose transport. Inhibition of ROCK1 also impaired glucose transporter 4 translocation in 3T3-L1 adipocytes. Importantly, the ED50 of insulin for adipocyte glucose transport was reduced when ROCK1 was expressed, leading to hypersensitivity to insulin. These effects are dependent on actin cytoskeleton remodeling, because inhibitors of actin polymerization significantly decreased ROCK1's effect to promote insulin-stimulated glucose transport. Unlike ROCK2, ROCK1 binding to insulin receptor substrate (IRS)-1 was not detected by immunoprecipitation, although cell fractionation demonstrated both ROCK isoforms localize with IRS-1 in low-density microsomes. Moreover, insulin's ability to increase IRS-1 tyrosine 612 and serine 632/635 phosphorylation was attenuated by ROCK1 suppression. Replacing IRS-1 serine 632/635 with alanine reduced insulin-stimulated phosphatidylinositol 3-kinase activation and glucose transport in 3T3-L1 adipocytes, indicating that phosphorylation of these serine residues of IRS-1, which are substrates of the ROCK2 isoform in vitro, are crucial for maximal stimulation of glucose transport by insulin. Our studies identify ROCK1 as an important positive regulator of insulin action on glucose transport in adipocytes and muscle cells. (Endocrinology 153: 1649-1662, 2012) C1 [Chun, Kwang-Hoon; Araki, Kazushi; Lee, Dae-Ho; Huang, Hu; Zabolotny, Janice M.; Kim, Young-Bum] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Med, Boston, MA 02216 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. [Chun, Kwang-Hoon; Jee, Yuna] Gachon Univ, Coll Pharm, Inchon 406799, South Korea. [Oh, Byung-Chul; Kim, Young-Bum] Gachon Univ, Lee Gil Ya Canc & Diabet Inst, Inchon 406799, South Korea. [Park, Kyong Soo] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea. [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Kim, YB (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Med, 330 Brookline Ave,CLS-736, Boston, MA 02216 USA. EM ykim2@bidmc.harvard.edu RI Park, Kyong Soo/C-2265-2008 OI Park, Kyong Soo/0000-0003-3597-342X FU National Institutes of Health [1R01DK083567, 5R01CA127247]; American Diabetes Association [1-09-RA-87]; Korea Science and Engineering Foundation [M10642140004-06N4214-0040]; Ministry of Education, Science and Technology [11-2008-18-001-00] FX This work was supported by National Institutes of Health Grants 1R01DK083567 (to Y.-B.K.) and 5R01CA127247 (to S.W.L.), the American Diabetes Association Grant 1-09-RA-87 (to Y.-B.K.), the Korea Science and Engineering Foundation Grant M10642140004-06N4214-0040 (to K.S.P.), and the 21C Frontier Microbial Genomics and Applications Center Program from the Ministry of Education, Science and Technology Grant 11-2008-18-001-00 (to B.-C.O.). NR 56 TC 26 Z9 26 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2012 VL 153 IS 4 BP 1649 EP 1662 DI 10.1210/en.2011-1036 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 917JG UT WOS:000302169800014 PM 22355071 ER PT J AU Braunwald, E AF Braunwald, Eugene TI The rise of cardiovascular medicine SO EUROPEAN HEART JOURNAL LA English DT Article DE Heart failure; Myocardial infarction; Arrhythmias ID ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; CORONARY-ARTERY-DISEASE; SAPHENOUS-VEIN GRAFT; CARDIAC-DISEASE; FOLLOW-UP; MORTALITY; THERAPY; ANGIOPLASTY; TRIAL AB Modern cardiology was born at the turn of the nineteenth to twentieth centuries with three great discoveries: the X ray, the sphygmomanometer, and the electrocardiograph. This was followed by cardiac catheterization, which led to coronary angiography and to percutaneous coronary intervention. The coronary care units and early reperfusion reduced the early mortality owing to acute myocardial infarction, and the discovery of coronary risk factors led to the development of Preventive Cardiology. Other major advances include several cardiac imaging techniques, the birth and development of cardiac surgery, and the control of cardiac arrhythmias. The treatment of heart failure, although greatly improved, remains a challenge. Current cardiology practice is evidence-based and global in scope. Research and practice are increasingly conducted in cardiovascular centres and institutes. It is likely that in the future, a greater emphasis will be placed on prevention, which will be enhanced by genetic information. C1 [Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 65 TC 27 Z9 28 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD APR PY 2012 VL 33 IS 7 BP 838 EP + DI 10.1093/eurheartj/ehr452 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 921SM UT WOS:000302497800015 PM 22416074 ER PT J AU Ragnarsson, O Hoybye, C Jonsson, PJ Feldt-Rasmussen, U Johannsson, G Biller, BMK Koltowska-Haggstrom, M AF Ragnarsson, Oskar Hoybye, Charlotte Jonsson, Peter J. Feldt-Rasmussen, Ulla Johannsson, Gudmundur Biller, Beverly M. K. Koltowska-Haggstrom, Maria TI Comorbidity and cardiovascular risk factors in adult GH deficiency following treatment for Cushing's disease or non-functioning pituitary adenomas during childhood SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE-SECRETION; TRANSSPHENOIDAL SURGERY; CLINICAL PRESENTATION; YOUNG ADULTHOOD; ADOLESCENTS; CHILDREN; CHOLESTEROL; DIAGNOSIS; ONSET; CURE AB Objective: Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood. Design, patients and methods: This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Background characteristics, anthropometry and comorbidity were studied in 47 patients diagnosed with childhood-onset (CO)-CD and 62 patients with CO-NFPA. Data from 100 ACTH-sufficient patients with CO-idiopathic hypopituitarism (CO-Idio) were used for comparison. Cardiovascular risk profile was analysed at baseline and at 1 year on GH treatment in a subgroup of patients (17 CO-CD, 24 CO-NFPA and 55 CO-Idio) not receiving GH treatment at study entry. Results: The median age at diagnosis of pituitary tumour was 14.0 years (range 10-17) in patients with CO-CD and 13.7 years (range 8-17) in CO-NFPA. In addition to GHD, 41% of patients with CO-CD had three or four other pituitary hormone deficiencies compared with 78% of patients with CO-NFPA (P < 0.001). Eighty-nine per cent of patients with CO-CD had height SDS lower than 0 compared with 61% of patients with CO-NFPA (P = 0.002). Hypertension was more common in CO-CD compared with CO-Idio (23 vs 9%, P = 0.018). At 1 year on GH treatment, total-and low-density lipoprotein-cholesterol decreased significantly in CO-CD but not in CO-NFPA. Conclusion: Adult patients with GHD following treatment for paediatric CD and NFPA have long-term adverse consequences. Despite more severe hypopituitarism in CO-NFPA, patients with CO-CD have more frequently compromised final stature. C1 [Ragnarsson, Oskar; Johannsson, Gudmundur] Sahlgrens Univ Hosp, Dept Endocrinol, SE-41345 Gothenburg, Sweden. [Ragnarsson, Oskar; Johannsson, Gudmundur] Univ Gothenburg, SE-41345 Gothenburg, Sweden. [Hoybye, Charlotte] Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, Stockholm, Sweden. [Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Endocrine Care, KIMS Med Outcomes, Sollentuna, Sweden. [Feldt-Rasmussen, Ulla] Univ Copenhagen, Rigshosp, Dept Med Endocrinol, DK-2100 Copenhagen, Denmark. [Biller, Beverly M. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA USA. RP Ragnarsson, O (reprint author), Sahlgrens Univ Hosp, Dept Endocrinol, Grona Straket 8, SE-41345 Gothenburg, Sweden. EM oskar.ragnarsson@medic.gu.se OI Ragnarsson, Oskar/0000-0003-0204-9492 FU Pfizer; Novo Nordisk; Otsuka; Ipsen; Merck Serono; Novartis; Eli Lilly; Pfizer, Inc. FX O Ragnarsson is a KIMS investigator and has received lecture fees from Pfizer. C Hoybye is a KIMS investigator and member of Pfizer's Swedish study advisory board, has received lecture fees from Pfizer and Novo Nordisk and Otsuka and research grants from Pfizer, Novo Nordisk and Ipsen. P J Jonsson and M Koltowska-Haggstrom are permanent employees of Pfizer Health AB. U Feldt-Rasmussen is a KIMS investigator and member of KIMS Strategic advisory board, has received lecture fees from Pfizer, Novo Nordisk, Merck Serono and Otsuka and research grants from Pfizer, Novo Nordisk, Novartis and Ipsen. G Johannsson owns stock in DuoCort AB and has received lecture fees from Novo Nordisk, Eli Lilly, Merck Serono and Pfizer. B M K Biller has received research grants from Eli Lilly, Novartis, Novo Nordisk and Pfizer and consulting honoraria from DuoCort, Novo Nordisk, Novartis and Pfizer.; The authors thank the KIMS investigators and their patients for the data provided. KIMS (Pfizer International Metabolic Database) is sponsored by Pfizer, Inc. NR 35 TC 2 Z9 2 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD APR PY 2012 VL 166 IS 4 BP 593 EP 600 DI 10.1530/EJE-11-0942 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 919QO UT WOS:000302343500004 PM 22258111 ER PT J AU Bredella, MA Lin, E Brick, DJ Gerweck, AV Harrington, LM Torriani, M Thomas, BJ Schoenfeld, DA Breggia, A Rosen, CJ Hemphill, LC Wu, ZD Rifai, N Utz, AL Miller, KK AF Bredella, Miriam A. Lin, Eleanor Brick, Danielle J. Gerweck, Anu V. Harrington, Lindsey M. Torriani, Martin Thomas, Bijoy J. Schoenfeld, David A. Breggia, Anne Rosen, Clifford J. Hemphill, Linda C. Wu, Zida Rifai, Nader Utz, Andrea L. Miller, Karen K. TI Effects of GH in women with abdominal adiposity: a 6-month randomized, double-blind, placebo-controlled trial SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE DEFICIENCY; CARDIOVASCULAR RISK-FACTORS; BODY-COMPOSITION; VISCERAL FAT; PREMENOPAUSAL WOMEN; REPLACEMENT THERAPY; INSULIN SENSITIVITY; RESONANCE SPECTROSCOPY; WAIST CIRCUMFERENCE; OBESE WOMEN AB Objective: Abdominal adiposity is associated with increased cardiovascular risk and decreased GH secretion. The objective of our study was to determine the effects of GH on body composition and cardiovascular risk markers in abdominally obese women. Materials and methods: In this randomized, double-blind, placebo-controlled study, 79 obese premenopausal women received GH vs placebo for 6 months. Primary endpoints were i) total abdominal (total abdominal adipose tissue, TAT) fat by computed tomography (CT) (body composition) and ii) high-sensitivity C-reactive protein (hsCRP) (cardiovascular risk marker). Body composition was assessed by CT, dual-energy X-ray absorptiometry, and proton MR spectroscopy. Serum cardiovascular risk markers, carotid intima-media thickness, and endothelial function were measured. Results: Mean 6-month GH dose was 1.7 +/- 0.1 mg/day, resulting in a mean IGF1 SDS increase from -1.7 +/- 0.08 to -0.1 +/- 0.3 in the GH group. GH administration decreased TAT and hsCRP compared with placebo. In addition, it increased thigh muscle mass and lean body mass and decreased subcutaneous abdominal and trunk fat, tissue plasminogen activator, apoB, and apoB/low-density lipoprotein compared with placebo. Visceral adipose tissue (VAT) decreased and intramyocellular lipid increased within the GH group. Six-month change in IGF1 levels was negatively associated with 6-month decrease in TAT and VAT. One subject had a 2 h glucose > 200 mg/ml at 3 months; four subjects, three of whom were randomized to GH, had 2 h glucose levels > 200 mg/ml at the end of the study. Conclusion: GH administration in abdominally obese premenopausal women exerts beneficial effects on body composition and cardiovascular risk markers but is associated with a decrease in glucose tolerance in a minority of women. C1 [Bredella, Miriam A.; Torriani, Martin; Thomas, Bijoy J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lin, Eleanor; Brick, Danielle J.; Gerweck, Anu V.; Harrington, Lindsey M.; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Hemphill, Linda C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Breggia, Anne; Rosen, Clifford J.] Maine Med Ctr Res Inst, Scarborough, ME 04074 USA. [Hemphill, Linda C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Wu, Zida] Charite, Dept Med, D-10117 Berlin, Germany. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Utz, Andrea L.] Vanderbilt Univ, Nashville, TN 37232 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org FU National Institutes of Health [RO1 HL-077674, UL1 RR025758, K23 RR-23090] FX This work was supported in part by National Institutes of Health Grants RO1 HL-077674, UL1 RR025758, and K23 RR-23090. Only study medication and placebo were supplied by Genentech, Inc. Clinical trials registration number: NCT00131378. NR 44 TC 20 Z9 20 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD APR PY 2012 VL 166 IS 4 BP 601 EP 611 DI 10.1530/EJE-11-1068 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 919QO UT WOS:000302343500005 PM 22275471 ER PT J AU Hill, M Crumlish, N Whitty, P Clarke, M Browne, S Gervin, M Kinsella, A Waddington, JL Larkin, C O'Callaghan, E AF Hill, M. Crumlish, N. Whitty, P. Clarke, M. Browne, S. Gervin, M. Kinsella, A. Waddington, J. L. Larkin, C. O'Callaghan, E. TI The relationship between insight and neurological dysfunction in first-episode psychosis SO EUROPEAN PSYCHIATRY LA English DT Article DE Psychosis; First-episode; Insight; Neurology ID SOFT SIGNS; CHRONIC-SCHIZOPHRENIA; NEUROPSYCHOLOGICAL FUNCTION; EPISODE SCHIZOPHRENIA; POOR INSIGHT; ILLNESS; UNAWARENESS; SYMPTOMS; SCALE; NEUROCOGNITION AB Purpose: Impaired insight is commonly seen in psychosis and some studies have proposed that is a biologically based deficit. Support for this view comes from the excess of neurological soft signs (NSS) observed in patients with psychoses and their neural correlates which demonstrate a degree of overlap with the regions of interest implicated in neuroimaging studies of insight. The aim was to examine the relationship between NSS and insight in a sample of 241 first-episode psychosis patients. Method: Total scores and subscale scores from three insight measures and two NSS scales were correlated in addition to factors representing overall insight and NSS which we created using principal component analysis. Results: There were only four significant associations when we controlled for symptoms. "Softer" Condensed Neurological Evaluation (CNE) signs were associated with our overall insight factor (r = 0.19, P = 0.02), with total Birchwood (r = -0.24, P < 0.01), and the Birchwood subscales: recognition of mental illness (r = -0.24, P < 0.01) and need for treatment (r = -0.18, P = 0.02). Total Neurological Evaluation Scale (NES) and recognition of the achieved effects of medication were also weakly correlated (r = 0.14, P = 0.04). Conclusion: This study does not support a direct link between neurological dysfunction and insight in psychosis. Our understanding of insight as a concept remains in its infancy. (C) 2011 Published by Elsevier Masson SAS. C1 [Hill, M.; Crumlish, N.; Whitty, P.; Clarke, M.; Browne, S.; Gervin, M.; Waddington, J. L.; Larkin, C.; O'Callaghan, E.] St John God Adult Psychiat Serv, Cluain Mhuire Family Ctr, Stanley Res Unit, Dublin, Ireland. [Hill, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hill, M.] Harvard Univ, Sch Med, Boston, MA USA. [Crumlish, N.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland. [Whitty, P.; Clarke, M.; Browne, S.; Gervin, M.; Larkin, C.; O'Callaghan, E.] Univ Coll Dublin, Sch Med, Dept Psychiat, Dublin 2, Ireland. [Kinsella, A.; O'Callaghan, E.] DELTA DETECT Early Intervent Psychosis Serv, Blackrock, Co Dublin, Ireland. [Waddington, J. L.; Larkin, C.] Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin 2, Ireland. RP O'Callaghan, E (reprint author), St John God Adult Psychiat Serv, Cluain Mhuire Family Ctr, Stanley Res Unit, Dublin, Ireland. EM eadbhard@gmail.com RI Waddington, John/C-6299-2012 FU Stanley Research Unit; Health Research Board (HRB) of Ireland FX The work presented in the manuscript was supported by grants from the Stanley Research Unit and the Health Research Board (HRB) of Ireland. The authors would like to thank all the patients and their families for participation in this study. NR 42 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD APR PY 2012 VL 27 IS 3 BP 200 EP 205 DI 10.1016/j.eurpsy.2011.01.002 PG 6 WC Psychiatry SC Psychiatry GA 921ZL UT WOS:000302516500007 PM 21392944 ER PT J AU Liu, CH Ren, JQ You, ZR Yang, JS Liu, CM Uppal, R Liu, PK AF Liu, Christina H. Ren, Jia Q. You, Zerong Yang, Jinsheng Liu, Charng-Ming Uppal, Ritika Liu, Philip K. TI Noninvasive detection of neural progenitor cells in living brains by MRI SO FASEB JOURNAL LA English DT Article DE angiogenesis; drug delivery; pericyte; pharmacokinetics ID FOREBRAIN ISCHEMIA-REPERFUSION; ENDOTHELIAL GROWTH-FACTOR; FOCAL CEREBRAL-ISCHEMIA; CARDIOPULMONARY-RESUSCITATION; GENE TRANSCRIPTS; CARDIAC-ARREST; LIVE ANIMALS; IN-VIVO; MICE; RAT AB The presence of pericytes in brain regions undergoing repair is evident of the recruitment of bone marrow-derived multipotent regenerative cells to the neurovascular unit during angiogenesis. At present, post mortem sampling is the only way to identify them. Therefore, such cell typing is inadequate for preserving neural progenitor cells for any meaningful stem cell therapy. We aimed to target cerebral pericytes in vivo using dual gene transcript-targeted MRI (GT-tMRI) in male C57black6 mice after a 60-min bilateral carotid artery occlusion (BCAO). We attached super-paramagnetic iron oxide nanoparticles (SPIONs) to phosphorothioate-modified micro-DNA that targets actin or nestin mRNA. Because BCAO compromises the blood-brain barrier (BBB) and induces expression of alpha-smooth muscle (alpha SM)-actin and nestin antigens by pericytes in new vessels, we delivered pericyte-specific magnetic resonance contrast agents (SPION-actin or SPION-nestin at 4 mg Fe/kg) by i.p. injection to C57black6 mice that had experienced BCAO. We demonstrated that the surge in cerebral iron content by inductively coupled plasma-mass spectrometry matched the increase in the frequency of relaxivity. We also found that SPION-nestin was colocalized in alpha SM-actin- and nestin-expressing pericytes in BCAO-treated C57black6 or transgenic mice [B6.Cg-Tg(CAG-mRFP1) 1F1Hadj/J, expressing red fluorescent protein by actin promoter]. We identified pericytes in the repair patch in living brains after BCAO with a voxel size of 0.03 mm(3). The presence of electron-dense nanoparticles in vascular pericytes in the region of BBB injury led us to draw the conclusion that GT-tMRI can noninvasively reveal neural progenitor cells during vascularization.-Liu, C. H., Ren, J. Q., You, Z., Yang, J., Liu, C.-M., Uppal, R., Liu, P. K. Noninvasive detection of neural progenitor cells in living brains by MRI. FASEB J. 26, 1652-1662 (2012). www.fasebj.org C1 [Liu, Christina H.; Ren, Jia Q.; Yang, Jinsheng; Liu, Charng-Ming; Uppal, Ritika; Liu, Philip K.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [You, Zerong] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA. RP Liu, PK (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM philipl@nmr.mgh.harvard.edu OI Liu, Christina/0000-0002-5723-177X FU American Heart Association [2060416]; U.S. National Institutes of Health [AT004974, DA026108, DA029889, EB013768] FX The authors thank M. McKee for assistance in TEM and N. Eusemann for help with editing. This project was supported by grants from the American Heart Association (grant 2060416) and the U.S. National Institutes of Health (grant AT004974 to J.Q.R. and grants DA026108, DA029889, and EB013768 to P.K.L.). NR 38 TC 15 Z9 15 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 IS 4 BP 1652 EP 1662 DI 10.1096/fj.11-199547 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 919VS UT WOS:000302359700026 PM 22198388 ER PT J AU Chan, KSK Xu, J Wardan, H McColl, B Orkin, S Vadolas, J AF Chan, Kasey S. K. Xu, Jian Wardan, Hady McColl, Bradley Orkin, Stuart Vadolas, Jim TI Generation of a genomic reporter assay system for analysis of gamma- and beta-globin gene regulation SO FASEB JOURNAL LA English DT Article ID SICKLE-CELL-DISEASE; FETAL-HEMOGLOBIN INDUCTION; SOLUBLE GUANYLYL CYCLASE; ERYTHROID-CELLS; EXPRESSION; BCL11A; HYDROXYUREA; THALASSEMIA; LOCUS; MICE AB A greater understanding of the regulatory mechanisms that govern gamma-globin expression in humans, especially the switching from gamma- to beta-globin, which occurs after birth, would help to identify new therapeutic targets for patients with beta-hemoglobinopathy. To further elucidate the mechanisms involved in gamma-globin expression, a novel fluorescent-based cellular reporter assay system was developed. Using homologous recombination, two reporter genes, DsRed and EGFP, were inserted into a 183-kb intact human beta-globin locus under the control of (G)gamma- or (A)gamma-globin promoter and beta-globin promoter, respectively. The modified constructs were stably transfected into adult murine erythroleukaemic (MEL) cells and human embryonic or fetal erythroleukemic (K562) cells, allowing for rapid and simultaneous analysis of fetal and adult globin gene expression according to their developmental stage-specific expression. To demonstrate the utility of this system, we performed RNA interference (RNAi)-mediated knockdown of BCL11A in the presence or absence of known fetal hemoglobin inducers and demonstrated functional derepression of a gamma-globin-linked reporter in an adult erythroid environment. Our results demonstrate that the cellular assay system represents a promising approach to perform genetic and functional genomic studies to identify and evaluate key factors associated with gamma-globin gene suppression.-Chan, K. S. K., Xu, J., Wardan, H., McColl, B., Orkin, S., Vadolas, J. Generation of a genomic reporter assay system for analysis of gamma- and beta-globin gene regulation. FASEB J. 26, 1736-1744 (2012). www.fasebj.org C1 [Chan, Kasey S. K.; Wardan, Hady; McColl, Bradley; Vadolas, Jim] Royal Childrens Hosp, Murdoch Childrens Res Inst, Cell & Gene Therapy Res Grp, Parkville, Vic 3052, Australia. [Chan, Kasey S. K.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Chan, Kasey S. K.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Xu, Jian; Orkin, Stuart] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Xu, Jian; Orkin, Stuart] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vadolas, J (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Cell & Gene Therapy Grp, Flemington Rd, Parkville, Vic 3052, Australia. EM jim.vadolas@mcri.edu.au FU Australia National Health and Medical Research Council; Murdoch Childrens Research Institute; Victorian Government; Thalassaemia Australia FX The Australia National Health and Medical Research Council, the Murdoch Childrens Research Institute, the Victorian Government's Operational Infrastructure Support Program, and Thalassaemia Australia supported this work. The authors declare no conflicts of interest. NR 37 TC 12 Z9 12 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2012 VL 26 IS 4 BP 1736 EP 1744 DI 10.1096/fj.11-199356 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 919VS UT WOS:000302359700034 PM 22267339 ER PT J AU Canto, MI Hruban, RH Fishman, EK Kamel, IR Schulick, R Zhang, Z Topazian, M Takahashi, N Fletcher, J Petersen, G Klein, AP Axilbund, J Griffin, C Syngal, S Saltzman, JR Mortele, KJ Lee, J Tamm, E Vikram, R Bhosale, P Margolis, D Farrell, J Goggins, M AF Canto, Marcia Irene Hruban, Ralph H. Fishman, Elliot K. Kamel, Ihab R. Schulick, Richard Zhang, Zhe Topazian, Mark Takahashi, Naoki Fletcher, Joel Petersen, Gloria Klein, Alison P. Axilbund, Jennifer Griffin, Constance Syngal, Sapna Saltzman, John R. Mortele, Koenraad J. Lee, Jeffrey Tamm, Eric Vikram, Raghunandan Bhosale, Priya Margolis, Daniel Farrell, James Goggins, Michael CA Amer Canc Pancreas Screening CAPS TI Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals SO GASTROENTEROLOGY LA English DT Article DE IPMN; PanIN; Surveillance; Familial Pancreatic Cancer ID PAPILLARY MUCINOUS NEOPLASMS; FAMILY-HISTORY; ENDOSCOPIC ULTRASONOGRAPHY; UPDATED EXPERIENCE; CANCER KINDREDS; BRCA2 MUTATIONS; PREVALENCE; PALB2; DIAGNOSIS; CONSENSUS AB BACKGROUND & AIMS: The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs). METHODS: We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS: Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias. CONCLUSIONS: Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. C1 [Canto, Marcia Irene; Goggins, Michael] Johns Hopkins Med Inst, Dept Med, Sol Goldman Pancreat Canc Res Ctr, Div Gastroenterol, Baltimore, MD 21205 USA. [Hruban, Ralph H.] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Fishman, Elliot K.; Kamel, Ihab R.] Johns Hopkins Med Inst, Dept Radiol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Schulick, Richard] Johns Hopkins Med Inst, Dept Surg, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Zhang, Zhe] Johns Hopkins Med Inst, Dept Biostat, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Topazian, Mark] Mayo Clin, Dept Med, Div Gastroenterol, Rochester, MN USA. [Takahashi, Naoki; Fletcher, Joel] Mayo Clin, Dept Radiol, Rochester, MN USA. [Petersen, Gloria] Mayo Clin, Dept Epidemiol, Rochester, MN USA. [Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance] Johns Hopkins Med Inst, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.] Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Jeffrey] Univ Texas MD Anderson Canc Ctr, Dept Med, Div Gastroenterol, Houston, TX 77030 USA. [Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Margolis, Daniel] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. [Farrell, James] Univ Calif Los Angeles, Dept Med, Div Gastroenterol, Los Angeles, CA 90024 USA. RP Canto, MI (reprint author), Johns Hopkins Univ, Div Gastroenterol, Sol Goldman Pancreat Canc Res Ctr, 1830 E Monument St,Room 427, Baltimore, MD 21205 USA. EM mcanto@jhmi.edu OI fishman, elliot/0000-0002-2567-1658 FU National Cancer Institute [2 P50 CA62924]; Lustgarten Foundation for Pancreatic Cancer Research; Michael Rolfe Foundation; Olympus Corporation; Cook Medical; Karp Family H. H. M. Metals, Inc; Fund for Cancer Research; ChiRhoClin FX Supported by the National Cancer Institute Specialized Program in Research Excellence Clinical Intervention Supplement 2 P50 CA62924, the Lustgarten Foundation for Pancreatic Cancer Research, the Michael Rolfe Foundation, Olympus Corporation, Cook Medical, Karp Family H. H. & M. Metals, Inc, Fund for Cancer Research, and ChiRhoClin. NR 39 TC 169 Z9 177 U1 0 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2012 VL 142 IS 4 BP 796 EP 804 DI 10.1053/j.gastro.2012.01.005 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 919BU UT WOS:000302296400029 PM 22245846 ER PT J AU Nishida, A Lau, CW Zhang, M Andoh, A Shi, HN Mizoguchi, E Mizoguchi, A AF Nishida, Atsushi Lau, Cindy W. Zhang, Mei Andoh, Akira Shi, Hai Ning Mizoguchi, Emiko Mizoguchi, Atsushi TI The Membrane-Bound Mucin Muc1 Regulates T Helper 17-Cell Responses and Colitis in Mice SO GASTROENTEROLOGY LA English DT Article DE Susceptibility; Risk Factor; Mouse Model; Immune Regulation ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; ALPHA-MUTANT MICE; CROHNS-DISEASE; INTESTINAL INFLAMMATION; SUSCEPTIBILITY LOCI; ULCERATIVE-COLITIS; MOUSE MODEL; TCR-ALPHA; RECEPTOR AB BACKGROUND & AIMS: T helper (Th) 17 cells produce the effector cytokine interleukin (IL)-17, along with IL-22, which stimulates colonic epithelial cells to produce a membrane-bound mucin, Muc1. Muc1 is a component of the colonic mucus, which functions as a lubricant and a physiologic barrier between luminal contents and mucosal surface. The gene MUC1 has been associated with susceptibility to inflammatory bowel disease; we investigated the role of Muc1 in development of colitis in mice. METHODS: Muc1 and RAG1 were disrupted in mice (Muc/RAG double knockout mice); Th1-mediated colitis was induced by intravenous injection of CD4(+)CD45RB(high) T cells. We also studied Th2-mediated colitis using mice with disruptions in Muc1 and T-cell receptor alpha chain (Muc/TCR double knockout mice). RESULTS: Muc1 deficiency led to the development of more severe forms of Th1- and Th2-induced colitis than controls. Loss of Muc1 increased colonic permeability and the Th17-cell, but not Th2 or Th1 cell, response in the inflamed colon. Loss of Muc1 also promoted expansion of an innate lymphoid cell population (Lin(-) ckit(-) Thy1(+) Sca1(+)) that produces IL-17. The expansion of Th17 adaptive immune cells and innate lymphoid cells required the commensal microbiota. CONCLUSIONS: Muc1, which is up-regulated by Th17 signaling, functions in a negative feedback pathway that prevents an excessive Th17 cell response in inflamed colons of mice. Disruption of this negative feedback pathway, perhaps by variants in Muc1, might contribute to inflammatory bowel disease in patients. C1 [Nishida, Atsushi; Lau, Cindy W.; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Nishida, Atsushi; Mizoguchi, Atsushi] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zhang, Mei; Shi, Hai Ning] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Zhang, Mei; Shi, Hai Ning] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Andoh, Akira] Shiga Univ Med Sci, Div Mucosal Immunol, Grad Sch Med, Shiga, Japan. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mizoguchi, Emiko] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mizoguchi, Emiko; Mizoguchi, Atsushi] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, CNY149-6024,13th St, Charlestown, MA 02129 USA. EM amizoguchi@partners.org FU Harry B. and Leona Helmsley Charitable Trust; Crohn's and Colitis Foundation of America; NIH [RO1AI081807, RC1DK086242, RO1DK080070, R01DK082427] FX Supported by the Harry B. and Leona Helmsley Charitable Trust; Crohn's and Colitis Foundation of America; and NIH RO1AI081807, NIH RC1DK086242 (A. M), NIH RO1DK080070 (to E. M), and NIH R01DK082427 (to H.N.S.). NR 47 TC 24 Z9 24 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2012 VL 142 IS 4 BP 865 EP U321 DI 10.1053/j.gastro.2011.12.036 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 919BU UT WOS:000302296400036 PM 22202458 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Focus and relevance in the management of GI bleeding SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97201 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2012 VL 75 IS 4 BP 861 EP 863 DI 10.1016/j.gie.2011.12.006 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 917NZ UT WOS:000302186100023 PM 22325810 ER PT J AU Mohr, DC Young, GJ Burgess, JF AF Mohr, David C. Young, Gary J. Burgess, James F., Jr. TI Employee turnover and operational performance: the moderating effect of group-oriented organisational culture SO HUMAN RESOURCE MANAGEMENT JOURNAL LA English DT Article ID UNIT-LEVEL; PATIENT SATISFACTION; VOLUNTARY TURNOVER; PRIMARY-CARE; HEALTH-CARE; KNOWLEDGE; VALUES; METAANALYSIS; TECHNOLOGY; NURSES AB This study investigates the relationship between overall employee turnover and operational performance and whether organisational culture is a moderator. Using a sample of 114 outpatient centres from a health-care system, we found a strong negative relationship between employee turnover and operational performance. Additionally, we found that organisations with a relatively stronger group-oriented organisational culture did not experience lower operational performance in the presence of high turnover. These findings contribute to the literature on the relationship between turnover and performance. Organisations with persistent high levels of turnover may want to consider developing and adopting practices that are consistent with a group-oriented organisational culture. C1 VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. RP Mohr, DC (reprint author), VA Boston Healthcare Syst 152M, 150 S Huntington Ave, Boston, MA 02130 USA. EM david.mohr2@va.gov NR 85 TC 11 Z9 11 U1 12 U2 42 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-5395 J9 HUM RESOUR MANAG J JI Hum. Resour. Manag. J. PD APR PY 2012 VL 22 IS 2 BP 216 EP 233 DI 10.1111/j.1748-8583.2010.00159.x PG 18 WC Industrial Relations & Labor; Management SC Business & Economics GA 918BR UT WOS:000302224400007 ER PT J AU Mitchell, KS Mazzeo, SE Schlesinger, MR Brewerton, TD Smith, BN AF Mitchell, Karen S. Mazzeo, Suzanne E. Schlesinger, Michelle R. Brewerton, Timothy D. Smith, Brian N. TI Comorbidity of partial and subthreshold ptsd among men and women with eating disorders in the national comorbidity survey-replication study SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE eating disorders; PTSD; gender; trauma ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; MEDIATING ROLE; NCS-R; ALEXITHYMIA; DEPRESSION; SYMPTOMS; ASSOCIATION AB Objective: The comorbidity of posttraumatic stress disorder (PTSD) and eating disorders (EDs) is high among women but has been understudied in men. Little is known about the association between partial or subthreshold PTSD and EDs among women or men. Method: This study included PTSD and ED data from male (n = 2,382) and female (n = 3,310) National Comorbidity Survey- Replication study participants. Results: The vast majority of women and men with anorexia nervosa, bulimia nervosa (BN), and binge eating disorder (BED) reported a history of interpersonal trauma. Rates of PTSD were significantly higher among women and men with BN and BED. Subthreshold PTSD was more prevalent than threshold PTSD among women with BN and women and men with BED. Discussion: Interpersonal forms of trauma, PTSD, and subthreshold/partial PTSD, were prevalent among men and women with EDs. Findings highlight the importance of assessing for trauma and PTSD in ED patients. VVC 2011 by Wiley Periodicals, Inc.* C1 [Mitchell, Karen S.; Smith, Brian N.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. [Mitchell, Karen S.; Smith, Brian N.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Mazzeo, Suzanne E.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Mazzeo, Suzanne E.] Virginia Commonwealth Univ, Dept Pediat, Richmond, VA 23284 USA. [Schlesinger, Michelle R.] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Brewerton, Timothy D.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Mitchell, KS (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr Posttraumat Stress Disorder, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM ksmitche@bu.edu FU National Institutes of Health [MH-068520] FX Supported by MH-068520 from the National Institutes of Health Grant. NR 55 TC 34 Z9 34 U1 7 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD APR PY 2012 VL 45 IS 3 BP 307 EP 315 DI 10.1002/eat.20965 PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 904VX UT WOS:000301227900001 PM 22009722 ER PT J AU Sperduto, PW Kased, N Roberge, D Xu, ZY Shanley, R Luo, XH Sneed, PK Chao, ST Weil, RJ Suh, J Bhatt, A Jensen, AW Brown, PD Shih, HA Kirkpatrick, J Gaspar, LE Fiveash, JB Chiang, V Knisely, JPS Sperduto, CM Lin, N Mehta, M AF Sperduto, Paul W. Kased, Norbert Roberge, David Xu, Zhiyuan Shanley, Ryan Luo, Xianghua Sneed, Penny K. Chao, Samuel T. Weil, Robert J. Suh, John Bhatt, Amit Jensen, Ashley W. Brown, Paul D. Shih, Helen A. Kirkpatrick, John Gaspar, Laurie E. Fiveash, John B. Chiang, Veronica Knisely, Jonathan P. S. Sperduto, Christina Maria Lin, Nancy Mehta, Minesh TI EFFECT OF TUMOR SUBTYPE ON SURVIVAL AND THE GRADED PROGNOSTIC ASSESSMENT FOR PATIENTS WITH BREAST CANCER AND BRAIN METASTASES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Breast cancer; Brain metastases; Prognosis; Radiation therapy; Stereotactic radiosurgery; Estrogen; Progesterone; HER2; Outcomes ID NERVOUS-SYSTEM METASTASES; PARTITIONING ANALYSIS RPA; RANDOMIZED PHASE-III; STEREOTACTIC RADIOSURGERY; ADJUVANT CHEMOTHERAPY; CEREBRAL METASTASES; DISTANT RECURRENCE; ESTROGEN-RECEPTOR; RADIOTHERAPY; CARCINOMA AB Purpose: The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. Methods and Materials: A multi-institutional retrospective database of 400 breast cancer patients treated for newly diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. Results: Significant prognostic factors by multivariate Cox regression and RPA were Karnofsky performance status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60 to 80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR positive improved MST from 6.4 to 9.7 months, whereas in HER2-positive patients, being ER/PR positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA vs. 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision making and stratification in clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone. (C) 2012 Elsevier Inc. C1 [Sperduto, Paul W.] Univ Minnesota Gamma Knife, Minneapolis, MN USA. [Kased, Norbert; Sneed, Penny K.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Roberge, David] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Xu, Zhiyuan; Weil, Robert J.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. [Shanley, Ryan; Luo, Xianghua] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Luo, Xianghua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Chao, Samuel T.; Suh, John] Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Bhatt, Amit] Univ Wisconsin, Dept Human Oncol, Madison, WI USA. [Jensen, Ashley W.; Brown, Paul D.] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Shih, Helen A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Kirkpatrick, John] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Gaspar, Laurie E.] Univ Colorado, Sch Med, Dept Radiat Oncol, Aurora, CO USA. [Fiveash, John B.] Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. [Chiang, Veronica] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Chiang, Veronica; Knisely, Jonathan P. S.] Yale Canc Ctr, New Haven, CT USA. [Knisely, Jonathan P. S.] Yale Univ, Sch Med, Dept Radiat Oncol, New Haven, CT USA. [Sperduto, Christina Maria] Dartmouth Coll, Hanover, NH 03755 USA. [Lin, Nancy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mehta, Minesh] Northwestern Univ, Dept Radiat Oncol, Chicago, IL 60611 USA. RP Sperduto, CM (reprint author), 560 S Maple St,Suite 10, Waconia, MN 55387 USA. EM psperduto@mropa.com RI Xu, Zhiyuan/J-8698-2013; OI Kirkpatrick, John/0000-0002-4019-0350; mehta, minesh/0000-0002-4812-5713 FU U.S. Department of Defense [W81XWH-062-0033]; National Institutes of Health [P30-CA77598] FX This research was supported in part by Grant W81XWH-062-0033 from the U.S. Department of Defense Breast Cancer Research Program (to R.J.W.), and by National Institutes of Health Grant P30-CA77598 using the services of the Biostatistics and Bioinformatics Core, Masonic Cancer Center, University of Minnesota shared resource. NR 55 TC 80 Z9 83 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2012 VL 82 IS 5 BP 2111 EP 2117 DI 10.1016/j.ijrobp.2011.02.027 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 913QA UT WOS:000301891300093 PM 21497451 ER PT J AU Khanfir, K Kallel, A Villette, S Belkacemi, Y Vautravers, C Nguyen, T Miller, R Li, YX Taghian, AG Boersma, L Poortmans, P Goldberg, H Vees, H Senkus, E Igdem, S Ozsahin, M Sozzi, WJ AF Khanfir, Kaouthar Kallel, Adel Villette, Sylviane Belkacemi, Yazid Vautravers, Claire TanDat Nguyen Miller, Robert Li, Ye Xiong Taghian, Alphonse G. Boersma, Liesbeth Poortmans, Philip Goldberg, Hadassah Vees, Hansjorg Senkus, Elzbieta Igdem, Sefik Ozsahin, Mahmut Sozzi, Wendy Jeanneret TI MANAGEMENT OF ADENOID CYSTIC CARCINOMA OF THE BREAST: A RARE CANCER NETWORK STUDY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Adenoid cystic carcinoma; Breast cancer; Radiotherapy; Surgery AB Background: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC. Methods: Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy). Results: With a median follow-up of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT. Conclusion: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery. (C) 2012 Elsevier Inc. C1 [Khanfir, Kaouthar] Hop Sion, CHCVs, Dept Radiat Oncol, CH-1950 Sion, Switzerland. [Kallel, Adel] Inst Gustave Roussy, Villejuif, France. [Villette, Sylviane] Ctr Rene Huguenin, Paris, France. [Belkacemi, Yazid] CHU Henri Mondor, Ctr Oscar Lambret, Lille, France. [Vautravers, Claire] Ctr George Francois Leclerc, Dijon, France. [TanDat Nguyen] Inst Jean Gaudinot, Reims, France. [Miller, Robert] Mayo Clin, Rochester, MN USA. [Li, Ye Xiong] Peking Union Med Coll, Beijing 100021, Peoples R China. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boersma, Liesbeth] Maastricht Univ, Med Ctr, MAASTRO Clin, Maastricht, Netherlands. [Poortmans, Philip] Dr Bernard Verbeeten Inst, Tilburg, Netherlands. [Goldberg, Hadassah] Western Galilee Hosp Nahariya, Nahariyya, Israel. [Vees, Hansjorg] Hop Univ Geneve, Geneva, Switzerland. [Senkus, Elzbieta] Med Univ Gdansk, Gdansk, Poland. [Igdem, Sefik; Ozsahin, Mahmut] Istanbul Bilim Univ, Istanbul, Turkey. [Sozzi, Wendy Jeanneret] CHU Vaudois, Lausanne, Switzerland. RP Khanfir, K (reprint author), Hop Sion, CHCVs, Dept Radiat Oncol, Grand Champsec 80, CH-1950 Sion, Switzerland. EM kaouthar.khanfir@rsv-gnw.ch RI Poortmans, P.M.P./L-4581-2015; OI Senkus, Elzbieta/0000-0001-6855-397X NR 27 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2012 VL 82 IS 5 BP 2118 EP 2124 DI 10.1016/j.ijrobp.2010.12.008 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 913QA UT WOS:000301891300094 PM 21570212 ER PT J AU Wattson, DA Chen, MH Moul, JW Moran, BJ Dosoretz, DE Robertson, CN Polascik, TJ Braccioforte, MH Salenius, SA D'Amico, AV AF Wattson, Daniel A. Chen, Ming-Hui Moul, Judd W. Moran, Brian J. Dosoretz, Daniel E. Robertson, Cary N. Polascik, Thomas J. Braccioforte, Michelle H. Salenius, Sharon A. D'Amico, Anthony V. TI The Number of High-Risk Factors and the Risk of Prostate Cancere-Specific Mortality After Brachytherapy: Implications for Treatment Selection SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Prostatic neoplasms; Prostate cancer mortality; Risk stratification; High-risk prostate cancer; Brachytherapy ID RADICAL PROSTATECTOMY; PREOPERATIVE NOMOGRAM; DISEASE RECURRENCE; RADIATION-THERAPY; COMPETING RISK; MEN; INTERMEDIATE; ONCOLOGY; DEATH AB Purpose: To determine whether an increasing number of high-risk factors is associated with higher prostate cancerespecific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk. Methods and Materials: We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage >= T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment. Results: The median follow-up time was 4.3 years. The number of men with at least two high-risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p(trend) < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8 (95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRT and AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001). Conclusions: Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk. (C) 2012 Elsevier Inc. C1 [Wattson, Daniel A.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moul, Judd W.; Robertson, Cary N.; Polascik, Thomas J.] Duke Univ, Med Ctr, Dept Surg, Div Urol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Prostate Ctr, Durham, NC USA. [Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Westmont, IL USA. [Dosoretz, Daniel E.; Salenius, Sharon A.] 21st Century Oncol, Ft Myers, FL USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wattson, DA (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM dwattson@partners.org NR 20 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2012 VL 82 IS 5 BP E773 EP E779 DI 10.1016/j.ijrobp.2011.11.023 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 913QA UT WOS:000301891300010 PM 22300573 ER PT J AU Choi, HR von Knoch, F Kandil, AO Zurakowski, D Moore, S Malchau, H AF Choi, Ho-Rim von Knoch, Fabian Kandil, Abdurrahman O. Zurakowski, David Moore, Slade Malchau, Henrik TI Retention treatment after periprosthetic total hip arthroplasty infection SO INTERNATIONAL ORTHOPAEDICS LA English DT Article ID PROSTHETIC-JOINT INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; DEBRIDEMENT; REPLACEMENT; COMPONENTS; RISK AB The purpose of this study was to compare infection control rates between implant retention and two-stage revision and assess the effectiveness of retention treatment in THA. Twenty-eight debridements with implant retention (retention group) and 65 staged revisions (removal group) were retrospectively analysed and risk factors that can contribute to failure of infection control were explored. For the retention and removal groups, infection control rates were 50% and 78% after initial treatment, and 68% and 82% at latest follow-up, respectively. There were no significant differences in the number of additional operative procedures, total length of hospital stay, and duration of treatment between groups. Infection of revision THA, polybacterial and S. aureus infection were identified as risk factors for infection control. Retention treatment can be considered an initial treatment option in selected cases of primary THA, with a single organism, non-S. aureus infection with 50% chance of infection control and no disadvantages in terms of additional procedure, hospital stay, and treatment duration. C1 [Choi, Ho-Rim; von Knoch, Fabian; Kandil, Abdurrahman O.; Moore, Slade; Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthoped Surg, Harris Orthoped Lab, Boston, MA 02114 USA. [von Knoch, Fabian] Schulthess Clin, Dept Orthopaed Surg, Zurich, Switzerland. [Zurakowski, David] Harvard Univ, Sch Med, Dept Surg, Childrens Hosp Boston, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Anesthesiol, Childrens Hosp Boston, Boston, MA USA. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Harris Orthoped Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM hmalchau@partners.org NR 24 TC 11 Z9 11 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD APR PY 2012 VL 36 IS 4 BP 723 EP 729 DI 10.1007/s00264-011-1324-5 PG 7 WC Orthopedics SC Orthopedics GA 917JP UT WOS:000302171000006 PM 21792609 ER PT J AU Hosseini, A Lodhia, P Van de Velde, SK Asnis, PD Zarins, B Gill, TJ Li, GA AF Hosseini, Ali Lodhia, Parth Van de Velde, Samuel K. Asnis, Peter D. Zarins, Bertram Gill, Thomas J. Li, Guoan TI Tunnel position and graft orientation in failed anterior cruciate ligament reconstruction: a clinical and imaging analysis SO INTERNATIONAL ORTHOPAEDICS LA English DT Article ID 3-DIMENSIONAL COMPUTED-TOMOGRAPHY; CARTILAGE CONTACT DEFORMATION; PATELLAR TENDON AUTOGRAFT; FOLLOW-UP EVALUATION; KNEE FLEXION; 11 OCLOCK; KINEMATICS; PLACEMENT; DEFICIENCY; ELONGATION AB It has been reported that technical error in positioning the graft tunnel is the most common problem in anterior cruciate ligament (ACL) reconstruction. The objective of this study was to quantitatively evaluate femoral and tibial tunnel positions and intra-articular graft orientation of primary ACL reconstruction in patients who had undergone revision ACL reconstruction. We postulated that this patient cohort had a nonanatomically positioned tunnel and graft orientation. Twenty-six patients who had undergone a revision ACL were investigated. Clinical magnetic resonance (MR) images prior to revision were analysed. Three-dimensional models of bones and tunnels on the femur and tibia were created. Intra-articular graft orientation was measured in axial, sagittal and coronal planes. Graft positions were measured on the tibial plateau as a percentage from anterior to posterior and medial to lateral; graft positions on the femur were measured using the quadrant method. Sagittal elevation angle for failed ACL reconstruction graft (69.6A degrees A +/- 13.4A degrees) was significantly greater (p < 0.05) than that of the native anteromedial (AM) and posterolateral (PL) bundles of the ACL (AM 56.2A degrees A +/- 6.1A degrees, PL 55.5A degrees A +/- 8.1A degrees). In the transverse plane, the deviation angle of the failed graft (37.3A degrees A +/- 21.0A degrees) was significantly greater than native ACL bundles. The tibial tunnel in this patient cohort was placed posteromedially and medially to the anatomical AM and PL bundles, respectively. The femoral tunnel was placed anteriorly to the anatomical AM and PL bundles. This study reveals that both the tibial and femoral tunnel positions and consequently the intra-articular graft orientation in this patient group with failed ACL reconstruction were nonanatomical when compared with native ACL values. The results can be used to improve tunnel placement in ACL reconstruction. C1 [Hosseini, Ali; Lodhia, Parth; Van de Velde, Samuel K.; Asnis, Peter D.; Zarins, Bertram; Gill, Thomas J.; Li, Guoan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. [Lodhia, Parth] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institute of Health [5R01AR055612-04, F32 AR056451] FX The authors thank Dr. Bijoy Thomas, Dr. Michael Kozanek, and Mr. Hemanth Gadikota for their technical assistance. This study was supported by National Institute of Health (5R01AR055612-04 and F32 AR056451). NR 38 TC 14 Z9 14 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD APR PY 2012 VL 36 IS 4 BP 845 EP 852 DI 10.1007/s00264-011-1333-4 PG 8 WC Orthopedics SC Orthopedics GA 917JP UT WOS:000302171000024 PM 21826407 ER PT J AU Ruiter, B Shreffler, WG AF Ruiter, Bert Shreffler, Wayne G. TI The role of dendritic cells in food allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Dendritic cells; food allergy; innate immunity; T(H)2 differentiation; T(H)2 adjuvant; sensitization; tolerance; allergen-specific immunotherapy; Toll-like receptors; C-type lectin receptors ID ANTIGEN-PRESENTING CELLS; HELPER TYPE-2 RESPONSE; REGULATORY T-CELLS; DUST MITE ALLERGEN; ORAL TOLERANCE; IMMUNE-RESPONSES; EPITHELIAL-CELLS; RETINOIC-ACID; AUTOIMMUNE ENCEPHALOMYELITIS; SUBLINGUAL ROUTE AB In recent years, our understanding of the initiation of T(H)2-type immunity has increased significantly, yet the mechanism behind the induction of T(H)2 responses and allergic sensitization to food antigens largely remains an enigma. Dendritic cells (DCs) were first described almost 4 decades ago and have since been recognized as the most important antigen-presenting cells and crucial in the induction of T-cell differentiation. Here we discuss our current knowledge of the role of DCs in food allergy. In both murine models and allergic patients, characteristics of DCs have been identified that might play a role in sensitization to food and enhance susceptibility to food allergy. In addition, it has now been shown that several allergens, including some from foods, can directly activate DCs to induce T(H)2 skewing. Other cell types with innate immune functions, such as epithelial cells and basophils, might also be involved in sensing of food allergens in human subjects, and interaction of DCs with these cells might facilitate sensitization. DCs appear to play an important role in allergen-specific immunotherapy and could be an attractive target for tolerance induction in patients with food allergy. Further characterization of differences in DC responses between human food-allergic and nonallergic subjects is necessary to gain a better insight into the role of DCs in sensitization and tolerance to food allergens. (J Allergy Clin Immunol 2012;129:921-8.) C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Ruiter, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bruiter@partners.org; wshreffler@partners.org FU NCI NIH HHS [L40 CA117818] NR 91 TC 31 Z9 31 U1 0 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2012 VL 129 IS 4 BP 921 EP 928 DI 10.1016/j.jaci.2012.01.080 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 917AP UT WOS:000302144600005 PM 22464669 ER PT J AU Jiang, B Larson, JC Drapala, PW Perez-Luna, VH Kang-Mieler, JJ Brey, EM AF Jiang, Bin Larson, Jeffery C. Drapala, Pawel W. Perez-Luna, Victor H. Kang-Mieler, Jennifer J. Brey, Eric M. TI Investigation of lysine acrylate containing poly(N-isopropylacrylamide) hydrogels as wound dressings in normal and infected wounds SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE poly(N-isopropylacrylamide); wound dressings; antimicrobial agents; hydrogels; wound infection ID POLYHEXAMETHYLENE BIGUANIDE; CELL-ADHESION; DETACHMENT; ATTACHMENT; DELIVERY; CHITOSAN; COLLAGEN AB The design of materials for cutaneous wound dressings has advanced from passive wound covers to bioactive materials that promote skin regeneration and prevent infection. Crosslinked poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogels have been investigated for a number of biomedical applications. While these materials can be used for drug delivery, limited cell interactions restrict their biological activity. In this article, acryoyl-lysine (A-Lys) was incorporated into poly(ethylene glycol) crosslinked PNIPAAm to enhance biological activity. A-Lys could be incorporated into the hydrogels to improve cellular interaction in vitro, while maintaining swelling properties and thermoresponsive behavior. Polyhexamethylene biguanide, an antimicrobial agent, could be encapsulated and released from the hydrogels and resulted in decreased bacteria counts within 2 hours. Two in vivo animal wound models were used to evaluate the hydrogel wound dressing. First, application of the hydrogels to a rodent cutaneous wound healing model resulted in significant increase in healing rate when compared with controls. Moreover, the hydrogels were also able to decrease bacteria levels in an infected wound model. These results suggest that PNIPAAm hydrogels containing A-Lys are promising wound dressings due to their ability to promote healing and deliver active antimicrobial drugs to inhibit infection. (c) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012. C1 [Jiang, Bin; Larson, Jeffery C.; Kang-Mieler, Jennifer J.; Brey, Eric M.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA. [Jiang, Bin; Larson, Jeffery C.; Brey, Eric M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Drapala, Pawel W.; Perez-Luna, Victor H.] IIT, Dept Chem & Biol Engn, Chicago, IL 60616 USA. RP Brey, EM (reprint author), IIT, Dept Biomed Engn, Chicago, IL 60616 USA. EM brey@iit.edu OI Jiang, Bin/0000-0003-2390-4312 FU CIS Pharma FX Contract grant sponsors: CIS Pharma NR 24 TC 9 Z9 9 U1 4 U2 33 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD APR PY 2012 VL 100B IS 3 BP 668 EP 676 DI 10.1002/jbm.b.31991 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 901RE UT WOS:000300983700009 PM 22121043 ER PT J AU Oral, E Ghali, BW Neils, A Muratoglu, OK AF Oral, Ebru Ghali, Bassem W. Neils, Andrew Muratoglu, Orhun K. TI A new mechanism of oxidation in ultrahigh molecular weight polyethylene caused by squalene absorption SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE lipid; synovial fluid; polyethylene; crosslinked; wear ID CROSS-LINKED POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; IN-VIVO; FREE-RADICALS; GAMMA-STERILIZATION; KNEE ARTHROPLASTY; UNITED-STATES; UHMWPE; PRODUCTS; LINKING AB Although synovial fluid lipids were found to absorb in ultrahigh molecular weight polyethylene (UHMWPE) total joint implants in vivo, their effect on the oxidation of the polymer was not known. Current understanding of the oxidation and oxidative stability of UHMWPE joint implants is focused on the presence or elimination of radiation-induced free radicals, which are long-lived and can react with oxygen over the long term. Recently, we found unexplained oxidation in irradiated and melted UHMWPE components that were exposed to bodily fluids then stored on the shelf despite being free of detectable free radicals at the time of implantation. Thus, we hypothesized that lipids absorbed from the synovial fluid in vivo could initiate and accelerate oxidation of UHMWPE even in the absence of detectable residual free radicals. We found that squalene, a precursor in cholesterol synthesis and a synovial fluid lipid with unsaturated bonds, accelerated oxidation in irradiated and melted UHMWPE under in vitro accelerated aging conditions. This result represents a paradigm shift in our understanding of oxidative stability of UHMWPE and prompts further investigation of in vivo oxidation mechanisms as well as the development of relevant in vitro aging models. (c) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012. C1 [Oral, Ebru; Ghali, Bassem W.; Neils, Andrew; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. EM omuratoglu@partners.org FU Laboratory Funds FX Contract grant sponsor: Laboratory Funds NR 45 TC 38 Z9 39 U1 1 U2 21 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD APR PY 2012 VL 100B IS 3 BP 742 EP 751 DI 10.1002/jbm.b.32507 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 901RE UT WOS:000300983700018 PM 22190411 ER PT J AU Pataquiva-Mateus, AY Wu, HC Lucchesi, C Ferraz, MP Monteiro, FJ Spector, M AF Pataquiva-Mateus, A. Y. Wu, H-C. Lucchesi, C. Ferraz, M. P. Monteiro, F. J. Spector, M. TI Supplementation of collagen scaffolds with SPARC to facilitate mineralization SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE collagen; mineralization; stem cells; biomaterials; bone ID SMOOTH-MUSCLE ACTIN; CROSS-LINKING; GLYCOSAMINOGLYCAN SCAFFOLDS; GENE DELIVERY; GAG SCAFFOLDS; IN-VITRO; BONE; COMPOSITE; MATRIX; PROLIFERATION AB The extracellular matrix-associated protein, SPARC (Secreted Protein Acidic and Rich in Cysteine) is known to play a role in the mineralization of collagen in bone formation. The objectives of this study were to determine: 1) if SPARC supplementation of type 1 collagen scaffolds in vitro facilitated the binding of pre-formed HA nanoparticles added to the scaffolds; 2) if SPARC supplementation of the scaffolds enhanced the uptake of calcium and phosphorus from calcium phosphate solutions; and 3) if pretreatment in a calcium phosphate solution enhanced the subsequent binding of the nanoparticles. A related objective was to begin to determine the behavior of mesenchymal stem cells in the scaffolds when the constructs were grown in osteogenic medium. The calcium and phosphorus contents of the scaffolds were evaluated by inductively coupled plasma analysis, and the elastic modulus of the scaffolds determined by unconfined compression testing. Scaffolds were seeded with goat bone marrow-derived mesenchymal stem cells and the cell-seeded constructs grown in osteogenic medium. Supplementation of the scaffolds with as little as 0.008 % SPARC (by wt. of collagen) resulted in an increase in the binding of hydroxyapatite nanoparticles to the scaffold, but had no effect on incorporation of calcium or phosphorus from a calcium phosphate solution. The incorporation of hydroxyapatite nanoparticles into the scaffolds did not result in an increase in modulus. Supplementation of the scaffolds with SPARC and the increase in the binding of hydroxyapatite nanoparticles did not affect the proliferation of mesenchymal stem cells. (C) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012 C1 [Pataquiva-Mateus, A. Y.; Wu, H-C.; Lucchesi, C.; Spector, M.] VA Boston Healthcare Syst, Boston, MA USA. [Pataquiva-Mateus, A. Y.; Monteiro, F. J.] INEB Inst Engn Biomed, Lab Biomat, Oporto, Portugal. [Pataquiva-Mateus, A. Y.; Monteiro, F. J.] Univ Porto, Fac Engn, Dept Met & Mat Engn, P-4100 Oporto, Portugal. [Wu, H-C.] Tatung Univ, Dept Mat Engn, Taipei 104, Taiwan. [Ferraz, M. P.] Univ Fernando Pessoa, Oporto, Portugal. [Spector, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM mspector@rics.bwh.harvard.edu RI Monteiro, Fernando/K-5872-2013; Ferraz, Maria/M-6316-2013; OI Ferraz, Maria/0000-0002-0274-106X; Monteiro, Fernando/0000-0002-1361-4605 FU Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/16616/2004]; Rehabilitation Research and Development Service of U.S. Department of Veterans Affairs FX Contract grant sponsor: Portuguese Foundation for Science and Technology (FCT); contract grant number: SFRH/BD/16616/2004; Contract grant sponsor: Rehabilitation Research and Development Service of U.S. Department of Veterans Affairs NR 35 TC 7 Z9 8 U1 0 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD APR PY 2012 VL 100B IS 3 BP 862 EP 870 DI 10.1002/jbm.b.32650 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 901RE UT WOS:000300983700031 PM 22279000 ER PT J AU Brachtel, E Yagi, Y AF Brachtel, Elena Yagi, Yukako TI Digital imaging in pathology - current applications and challenges SO JOURNAL OF BIOPHOTONICS LA English DT Article DE pathology; digital image analysis; whole slide imaging ID VIRTUAL SLIDE TELEPATHOLOGY; MULTISITE-PERFORMANCE; TISSUE SPECIMENS; HUM PATHOL; IMAGES; MICROSCOPY; QUALITY; QUANTIFICATION; OPTIMIZATION; DIAGNOSIS AB Conventional histopathology is rapidly shifting towards digital integration. Will microscopes (and pathologists) soon be obsolete? Or are we dealing with just another image modality that leaves the core of tissue diagnosis intact? This article provides an overview of current digital pathology applications and research with emphasis on whole slide imaging (WSI). Static or interactive digital pathology work stations already can be used for many purposes, e.g. telepathology expert consultations, frozen section diagnosis in remote areas, cytology screening, quality assurance, diagnostic validations for clinical trials, quantitation of hormone receptor or HER2 studies in breast cancer, or three-dimensional visualization of anatomical structures, among others. Changes of workflow in histology laboratories are beginning to enable digital image acquisition and WSI in a routine setting. WSI plays an increasing role in pathology education, glass slide boxes in medical schools are being replaced by digital slide collections; digital slide seminars and virtual microscopy are used for postgraduate and continuing medical education in pathology. Research and efforts to validate WSI systems for diagnostic settings are ongoing. (C) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) C1 [Brachtel, Elena; Yagi, Yukako] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Brachtel, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN2, Boston, MA 02114 USA. EM ebrachtel@partners.org NR 55 TC 15 Z9 15 U1 1 U2 18 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1864-063X J9 J BIOPHOTONICS JI J. Biophotonics PD APR PY 2012 VL 5 IS 4 SI SI BP 327 EP 335 DI 10.1002/jbio.201100103 PG 9 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA 916BP UT WOS:000302071900007 PM 22213680 ER PT J AU Basile, JN Bloch, MJ AF Basile, Jan N. Bloch, Michael J. TI NHANES Data Highlight the Clinical Characteristics of Those With Poorly Controlled Hypertension SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article C1 [Bloch, Michael J.] Univ Nevada, Sch Med, SC & MedSchool Associates N, Reno, NV 89557 USA. [Basile, Jan N.] Med Univ S Carolina, Seinsheimer Cardiovasc Hlth Program, Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Bloch, MJ (reprint author), Univ Nevada, Sch Med, MedSch Associates N, 1500 E 2nd St,Suite 302, Reno, NV 89557 USA. EM mbloch@aol.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD APR PY 2012 VL 14 IS 4 BP 267 EP 268 DI 10.1111/j.1751-7176.2012.00596.x PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 916BV UT WOS:000302072500013 PM 22458751 ER PT J AU Anstead, GM Sutton, DA Graybill, JR AF Anstead, Gregory M. Sutton, Deanna A. Graybill, John R. TI Adiaspiromycosis Causing Respiratory Failure and a Review of Human Infections Due to Emmonsia and Chrysosporium spp. SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PULMONARY ADIASPIROMYCOSIS; DIMORPHIC FUNGUS; CRESCENS; PATIENT; DISEASE; PATHOGEN; ZONATUM; REGION; AGENTS; LUNG AB We report a case of a 27-year-old male who presented with respiratory distress that required mechanical ventilation. Transbronchial biopsy revealed adiaspores of the fungus Emmonsia crescens within granulomata, a condition known as adiaspiromycosis. The patient received amphotericin products and corticosteroids, followed by itraconazole, and made a full recovery. Emmonsia crescens is a saprobe with a wide distribution that is primarily a rodent pathogen. The clinical characteristics of the 20 cases of human pulmonary adiaspiromycosis reported since the last comprehensive case review in 1993 are described here, as well as other infections recently reported for the genus Emmonsia. Pulmonary adiaspiromycosis has been reported primarily in persons without underlying host factors and has a mild to severe course. It remains uncertain if the optimal management of severe pulmonary adiaspiromycosis is supportive or if should consist of antifungal treatment, corticosteroids, or a combination of the latter two. The classification of fungi currently in the genus Emmonsia has undergone considerable revision since their original description, including being grouped with the genus Chrysosporium at one time. Molecular genetics has clearly differentiated the genus Emmonsia from the Chrysosporium species. Nevertheless, there has been a persistent confusion in the literature regarding the clinical presentation of infection with fungi of these two genera; to clarify this matter, the reported cases of invasive Chrysosporium infections were reviewed. Invasive Chrysosporium infections typically occur in impaired hosts and can have a fatal course. Based on limited in vitro susceptibility data for Chrysosporium zonatum, amphotericin B is the most active drug, itraconazole susceptibility is strain-dependent, and fluconazole and 5-fluorocytosine are not active. C1 [Anstead, Gregory M.; Graybill, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Sutton, Deanna A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA. [Anstead, Gregory M.] S Texas Vet Healthcare Syst, Div Infect Dis, Dept Med, San Antonio, TX USA. RP Anstead, GM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. EM anstead@uthscsa.edu NR 73 TC 25 Z9 28 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2012 VL 50 IS 4 BP 1346 EP 1354 DI 10.1128/JCM.0226-11 PG 9 WC Microbiology SC Microbiology GA 917CC UT WOS:000302148700034 PM 22259200 ER PT J AU Cohen, HJ Lan, L Archer, L Kornblith, AB AF Cohen, Harvey Jay Lan, Lan Archer, Laura Kornblith, Alice B. CA Canc Leukemia Grp B TI Impact of age, comorbidity and symptoms on physical function in long-term breast cancer survivors (CALGB 70803) SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Cancer survivors; Physical function; Comorbidity; Symptoms; Elderly ID QUALITY-OF-LIFE; GERIATRIC ASSESSMENT; EORTC QLQ-C30; OLDER; HEALTH; CHEMOTHERAPY; LIMITATIONS; POPULATION; CARCINOMA; ONCOLOGY AB Objective: The purpose of this study was to assess the impact of aging, comorbidities and symptoms on physical function in patients surviving 20 years since adjuvant treatment for breast cancer. Patients and methods: Patients were originally treated on CALGB 7581 (from 1975 to 1980), a randomized trial of three adjuvant therapies and reassessed (153 of 193 eligible survivors) 20 years from the onset of therapy for physical function and symptoms by the EORTC QLQ-C30 and comorbidities by the OARS questionnaire. Results: The average age at reassessment was 64.5 years. 66% of patients had at least two comorbidities and 22% had four or more, but relatively little interference with activities. Older patients had greater multimorbidity. Physical function was generally high and comparable to matched population norms. Older patients had greater difficulty with strenuous activities. For every increase in number of comorbidities, physical function score decreased by 5.1 (p<.001). Symptoms were also frequent (80%) and correlated strongly with decreases in function (0-100 u scale) (p<.001), to an even greater degree than comorbidities. Conclusion: Very long-term cancer survivors have changes in physical function and symptoms largely consistent with their aging suggesting that the impact of cancer and its treatment is attenuated over time and largely replaced by the impact of age-related comorbidities and functional decline. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Cohen, Harvey Jay] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. [Lan, Lan; Archer, Laura] Duke Univ, Med Ctr, CALGB Stat Ctr, Raleigh, NC USA. [Kornblith, Alice B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cohen, HJ (reprint author), Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, 201 Trent Dr,Box 3003, Durham, NC 27710 USA. EM harvey.cohen@duke.edu FU National Cancer Institute [CA31946, CA33601]; Duke Claude Pepper OAIC [P30-AG-028716]; [CA37447]; [CA45418]; [CA32291]; [CA04326]; [CA47577]; [CA29165]; [CA45389]; [CA35113]; [CA35279]; [CA77651]; [CA114558-02]; [CA45564]; [CA04457]; [CA35421]; [CA86726]; [CA59518]; [CA45808]; [CA21060]; [CA77658]; [CA11789]; [CA41287]; [CA31983]; [CA37135]; [CA16450]; [CA12046]; [CA47559]; [CA77406]; [CA03927]; [CA26806]; [CA77440]; [CA07968] FX The research for CALGB 70803 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Monica M. Bertagnolli, M.D., Chair) and to the CALGB Statistical Center (Daniel J. Sargent, Ph.D., CA33601). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.; We also acknowledge the support of the Duke Claude Pepper OAIC (Harvey Jay Cohen, M.D., P30-AG-028716).; The following institutions participated in this study:; University of Oklahoma, Oklahoma, OK - Howard Ozer, M.D., supported by CA37447; Christiana Care Health Services, Inc. CCOP, Wilmington, DE - Stephen Grubbs, M.D., supported by CA45418; Dana-Farber Cancer Institute, Boston, MA - Harold J Burstein, M.D., supported by CA32291; Dartmouth Medical School - Norris Cotton Cancer Center, Lebanon, NH - Konstantin Dragnev, M.D., supported by CA04326; Duke University Medical Center, Durham, NC - Jeffrey Crawford, M.D., supported by CA47577; Grand Rapids Clinical Oncology Program, Grand Rapids, MI - Martin) Bury, M.D.; Cancer Centers of the Carolinas, Greenville, SC - Jeffrey K. Giguere, M.D, supported by CA29165; Hematology-Oncology Associates of Central New York CCOP, Syracuse, NY - Jeffrey Kirshner, M.D., supported by CA45389; Illinois Oncology Research Association, Peoria, IL - John W. Kugler, M.D., supported by CA35113; Long Island Jewish Medical Center, Lake Success, NY - Kanti R. Rai, M.D., supported by CA35279; Memorial Sloan-Kettering Cancer Center, New York, NY - Clifford A. Hudis, M.D., supported by CA77651.; Missouri Baptist Medical Center, St. Louis, MO - Alan P. Lyss, M.D., supported by CA114558-02; Missouri Valley Consortium-Ccop, Omaha, NE - Gamini S. Soon, M.D.; Mount Sinai Medical Center, Miami, FL - Rogerio C. Lilenbaum, M.D., supported by CA45564; Mount Sinai School of Medicine, New York, NY - Lewis R. Silverman, M.D., supported by CA04457; Nevada Cancer Research Foundation CCOP, Las Vegas, NV - John A. Ellerton, M.D., supported by CA35421; Northern Indiana Cancer Research Consortium CCOP, South Bend, IN - Rafat Ansari, M.D., supported by CA86726; Roswell Park Cancer Institute, Buffalo, NY - Ellis Levine, M.D., supported by CA59518; Southeast Cancer Control Consortium Inc. CCOP, Goldsboro, NC - James N. Atkins, M.D., supported by CA45808; State University of New York Upstate Medical University, Syracuse, NY - Stephen L. Graziano, M.D., supported by CA21060; The Ohio State University Medical Center, Columbus, OH - Clara D Bloomfield, M.D., supported by CA77658; University of California at San Diego, San Diego, CA - Barbara A. Parker, M.D., supported by CA11789; University of Chicago, Chicago, IL - Hedy L Kindler, M.D., supported by CA41287; University of Maryland Greenebaum Cancer Center, Baltimore, MD - Martin Edelman, M.D., supported by CA31983; University of Massachusetts Medical School, Worcester, MA - William V. Walsh, M.D., supported by CA37135; University of Minnesota, Minneapolis, MN - Bruce A Peterson, M.D., supported by CA16450; University of Missouri/Ellis Fischel Cancer Center, Columbia, MO - Michael C Perry, M.D., supported by CA12046; University of North Carolina at Chapel Hill, Chapel Hill, NC - Thomas C. Shea, M.D., supported by CA47559; University of Vermont, Burlington, VT - Steven M Grunberg, M.D., supported by CA77406; Wake Forest University School of Medicine, Winston-Salem, NC - David D Hurd, M.D., supported by CA03927; Walter Reed Army Medical Center, Washington, DC - Brendan M Weiss, M.D., supported by CA26806; Washington University School of Medicine, St. Louis, MO - Nancy Bartlett, M.D., supported by CA77440; Weill Medical College of Cornell University, New York, NY - John Leonard, M.D., supported by CA07968; Western Pennsylvania Cancer Institute, Pittsburgh, PA - Dr. John Lister, M.D.; The funding source played no role in preparation of this manuscript.; All authors have participated in this research and preparation of this manuscript. LL and LA also provided statistical analysis. NR 37 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD APR PY 2012 VL 3 IS 2 BP 82 EP 89 DI 10.1016/j.jgo.2012.01.005 PG 8 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA 918UO UT WOS:000302276800002 PM 22707996 ER PT J AU Aoyama, A Tonsho, M Yamada, Y Millington, TM Boskovic, S Lee, S Smith, RN Madsen, JC Kawai, T Allan, JS AF Aoyama, A. Tonsho, M. Yamada, Y. Millington, T. M. Boskovic, S. Lee, S. Smith, R. -N. Madsen, J. C. Kawai, T. Allan, J. S. TI In Vivo Expansion of Regulatory T Cells with ATG and Inhibition of IL-6 Prolongs Non-Human Primate Lung Allografts Survival SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation/Meeting of the ISHLT Academy - Core Competencies in Mechanical Circulatory Support CY APR 17-21, 2012 CL Prague, CZECH REPUBLIC SP Int Soc Heart & Lung Transplantat (ISHLT), Int Soc Heart & Lung Transplantat Acad (ISHLT) C1 [Madsen, J. C.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2012 VL 31 IS 4 SU S MA 355 BP S126 EP S126 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 917VY UT WOS:000302207900355 ER PT J AU Ueno, T Yeung, MY Jung, K Dutta, P Nahrendorf, M Yun, SH Weissleder, R AF Ueno, T. Yeung, M. Y. Jung, K. Dutta, P. Nahrendorf, M. Yun, S. H. Weissleder, R. TI The Importance of DC (Dendritic Cell) - T Cell Interplay in Cardiac Transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation/Meeting of the ISHLT Academy - Core Competencies in Mechanical Circulatory Support CY APR 17-21, 2012 CL Prague, CZECH REPUBLIC SP Int Soc Heart & Lung Transplantat (ISHLT), Int Soc Heart & Lung Transplantat Acad (ISHLT) C1 [Ueno, T.; Dutta, P.; Nahrendorf, M.; Weissleder, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Ueno, T.; Yeung, M. Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA. [Jung, K.; Yun, S. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2012 VL 31 IS 4 SU S MA 408 BP S144 EP S145 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 917VY UT WOS:000302207900408 ER PT J AU Tonti, E Fedeli, M Napolitano, A Iannacone, M von Andrian, UH Guidotti, LG Abrignani, S Casorati, G Dellabona, P AF Tonti, Elena Fedeli, Maya Napolitano, Anna Iannacone, Matteo von Andrian, Ulrich H. Guidotti, Luca G. Abrignani, Sergio Casorati, Giulia Dellabona, Paolo TI Follicular Helper NKT Cells Induce Limited B Cell Responses and Germinal Center Formation in the Absence of CD4(+) T Cell Help SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIBODY-PRODUCTION; COGNATE HELP; IN-VIVO; ANTIGEN; RECEPTOR; MICE; GALACTOSYLCERAMIDE; IDENTIFICATION; LYMPHOCYTES; MOLECULES AB B cells require MHC class II (MHC II)-restricted cognate help and CD40 engagement by CD4(+) T follicular helper (T-FII) cells to form germinal centers and long-lasting Ab responses. Invariant NKT (iNKT) cells are innate-like lymphocytes that jumpstart the adaptive immune response when activated by the CD1d-restricted lipid alpha-galactosylceramide (alpha GalCer). We previously observed that immunization of mice lacking CD4(+) T cells (MHC II-/-) elicits specific IgG responses only when protein Ags are mixed with alpha GalCer. In this study, we investigated the mechanisms underpinning this observation. We find that induction of Ag-specific Ab responses in MHC II-/- mice upon immunization with protein Ags mixed with alpha GalCer requires CD1d expression and CD40 engagement on B cells, suggesting that iNKT cells provide CD1d-restricted cognate help for B cells. Remarkably, splenic iNKT cells from immunized MHC II-/- mice display a typical CXCR5(hi)programmed death-1(hi)ICOS(hi)Bcl-6(hi)T(FH) phenotype and induce germinal centers. The specific IgG response induced in MHC II-/- mice has shorter duration than that developing in CD4-competent animals, suggesting that iNKT(FH) cells preferentially induce transient rather than long-lived Ab responses. Together, these results suggest that iNKT cells can be co-opted into the follicular helper function, yet iNKT(FH) and CD4(+) T-FH cells display distinct helper features, consistent with the notion that these two cell subsets play nonredundant functions throughout immune responses. The Journal of Immunology, 2012, 188: 3217-3222. C1 [Tonti, Elena; Fedeli, Maya; Napolitano, Anna; Casorati, Giulia; Dellabona, Paolo] Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, Expt Immunol Unit, I-20132 Milan, Italy. [Iannacone, Matteo] Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, Dynam Immune Responses Unit, I-20132 Milan, Italy. [Iannacone, Matteo; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Div Immunol, Immune Dis Inst, Boston, MA 02115 USA. [Iannacone, Matteo; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Guidotti, Luca G.] Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, Immunopathogenesis Liver Infect Unit, I-20132 Milan, Italy. [Guidotti, Luca G.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Abrignani, Sergio] Ist Nazl Genet Mol, I-20122 Milan, Italy. RP Casorati, G (reprint author), Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, Expt Immunol Unit, Via Olgettina 58, I-20132 Milan, Italy. EM casorati.giulia@hsr.it; dellabona.paolo@hsr.it RI Dellabona, Paolo/G-5416-2012; von Andrian, Ulrich/A-5775-2008; OI Guidotti, Luca G./0000-0002-0205-2678; Iannacone, Matteo/0000-0002-9370-2671; Dellabona, Paolo/0000-0002-1414-633X; Casorati, Giulia/0000-0002-5102-4112 FU Cariplo Foundation; Regione Lombardia; Associazione Italiana per la Ricerca sul Cancro [IG5804] FX This work was supported by grants from the Cariplo Foundation (Vaccine Program) (to S.A. and P.D.), Regione Lombardia (International Cooperation Project) (to L.G.G., G.C., and P.D.), and Associazione Italiana per la Ricerca sul Cancro (IG5804 to G.C.). NR 31 TC 41 Z9 44 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2012 VL 188 IS 7 BP 3217 EP 3222 DI 10.4049/jimmunol.1103501 PG 6 WC Immunology SC Immunology GA 917CP UT WOS:000302150300036 PM 22379027 ER PT J AU Xia, ZQ Liu, QQ Berger, CT Keenan, BT Kaliszewska, A Cheney, PC Srivastava, GP Castillo, IW De Jager, PL Alter, G AF Xia, Zongqi Liu, Qingquan Berger, Christoph T. Keenan, Brendan T. Kaliszewska, Anna Cheney, Patrick C. Srivastava, Gyan P. Castillo, Irene Wood De Jager, Philip L. Alter, Galit TI A 17q12 Allele Is Associated with Altered NK Cell Subsets and Function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; T-BET; MULTIPLE-SCLEROSIS; INHIBITORY RECEPTORS; LINEAGE COMMITMENT; INNATE; GROWTH; PATHOGENESIS; CD94/NKG2A; INFECTION AB NK cells play an important role in innate immunity. A previous genome-wide association study demonstrated an association between a 17q12 allele (rs9916629(C)) and lower frequency of CD3(-)CD56(+) NK cells in peripheral blood. We performed an analysis that not only replicates the original result of the genome-wide association study (p = 0.036) but also defines the specific cell subpopulations and functions that are modulated by the rs9916629 polymorphism in a cohort of 96 healthy adult subjects using targeted multiparameter flow cytometric profiling of NK cell phenotypes and functions. We found that rs9916629(C) is associated with alterations in specific NK cell subsets, including lower frequency of predominantly cytotoxic CD56(dim) NK cells (p = 0.011), higher frequency of predominantly regulatory CD56(bright) NK cells (p = 0.019), and a higher proportion of NK cells expressing the inhibitory NKG2A receptor (p = 0.0002). Functionally, rs9916629(C) is associated with decreased secretion of macrophage inflammatory protein-1 beta by NK cells in the context of Ab-dependent cell-mediated cytotoxicity (p = 0.039) and increased degranulation in response to MHC class I-deficient B cells (p = 0.017). Transcriptional profiling of NK cells suggests that rs9916629 influences the expression of transcription factors such as TBX21, which has a role in NK cell differentiation, offering a possible mechanism for the phenotypic and functional differences between the different alleles. The rs9916629(C) allele therefore has a validated effect on the proportion of NK cells in peripheral blood and skews NK cells toward a specific phenotypic and functional profile, potentially influencing the impact that these innate immune cells have on infection and autoimmunity. The Journal of Immunology, 2012, 188: 3315-3322. C1 [Xia, Zongqi; Keenan, Brendan T.; Kaliszewska, Anna; Srivastava, Gyan P.; Castillo, Irene Wood; De Jager, Philip L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci, Dept Neurol & Psychiat, Boston, MA 02115 USA. [Xia, Zongqi; Keenan, Brendan T.; Kaliszewska, Anna; Srivastava, Gyan P.; Castillo, Irene Wood; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Xia, Zongqi; Liu, Qingquan; Berger, Christoph T.; Keenan, Brendan T.; Kaliszewska, Anna; Cheney, Patrick C.; Srivastava, Gyan P.; Castillo, Irene Wood; De Jager, Philip L.; Alter, Galit] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Liu, Qingquan; Berger, Christoph T.; Cheney, Patrick C.; Alter, Galit] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02129 USA. [Liu, Qingquan; Berger, Christoph T.; Cheney, Patrick C.; Alter, Galit] Harvard Univ, Boston, MA 02129 USA. RP De Jager, PL (reprint author), Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Dept Neurol, 77 Ave Louis Pasteur,NRB 168C, Boston, MA 02115 USA. EM pdejager@rics.bwh.harvard.edu; galter@partners.org FU Ragon Institute; National Multiple Sclerosis Society; American Academy of Neurology; Pfizer, Inc.; Merck Co.; University of Basel, Basel, Switzerland FX This work was partially supported by a Ragon Institute pilot study grant (to P.L.D.J. and G.A.). Z.X. is a recipient of the Clinician Scientist Development award from the National Multiple Sclerosis Society and the American Academy of Neurology and is a fellow in the Clinical Investigator Training Program (Beth Israel Deaconess Medical Center-Harvard Medical School, in collaboration with Pfizer, Inc. and Merck & Co.). P.L.D.J. is a Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society. C.T.B. is partially supported by a grant from the University of Basel, Basel, Switzerland. NR 36 TC 14 Z9 14 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2012 VL 188 IS 7 BP 3315 EP 3322 DI 10.4049/jimmunol.1102775 PG 8 WC Immunology SC Immunology GA 917CP UT WOS:000302150300045 PM 22345646 ER PT J AU Simpson, TL Moore, SA Luterek, J Varra, AA Hyerle, L Bush, K Mariano, MJ Liu, CF Kivlahan, DR AF Simpson, Tracy L. Moore, Sally A. Luterek, Jane Varra, Alethea A. Hyerle, Lynne Bush, Kristen Mariano, Mary Jean Liu, Chaun-Fen Kivlahan, Daniel R. TI Psychiatric Correlates of Medical Care Costs Among Veterans Receiving Mental Health Care SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE mental health and violence; violence exposure; war ID POSTTRAUMATIC-STRESS-DISORDER; EXTREME STRESS; STRUCTURED INTERVIEW; PHYSICAL HEALTH; TRAUMA EXPOSURE; COMPLEX PTSD; WOMEN; SYMPTOMS; SOMATIZATION; ASSOCIATION AB Research on increased medical care costs associated with posttraumatic sequelae has focused on posttraumatic stress disorder (PTSD). However, the provisional diagnosis of Disorders of Extreme Stress Not Otherwise Specified (DESNOS) encompasses broader trauma-related difficulties and may be uniquely related to medical costs. We investigated whether DESNOS severity was associated with greater nonmental health medical care costs in veterans receiving mental health care. Participants were 106 men and 105 women receiving VA outpatient mental health treatment. A standardized interview assessed DESNOS severity. The dependent variables consisted of primary and specialty medical treatment costs. Sequential zero-inflated negative binomial regression was used to evaluate the variance in medical costs accounted for by DESNOS severity, controlling for PTSD severity and established predisposing, enabling, and need-based health care factors. Contrary to our hypothesis, in fully adjusted models, DESNOS severity independently added a significant amount of variance to lower specialty medical care costs, whereas PTSD did not consistently account for significant variance in medical care costs. Greater DESNOS severity appears to be associated with lower specialty medical care costs but not primary care costs. These findings may indicate that patients with DESNOS symptoms are at risk for being underreferred for specialty care. C1 [Simpson, Tracy L.; Bush, Kristen] VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA 98108 USA. [Simpson, Tracy L.; Moore, Sally A.; Luterek, Jane; Varra, Alethea A.; Mariano, Mary Jean; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Liu, Chaun-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Luterek, Jane] VA Puget Sound Hlth Care Syst, Seattle Div, Womens Trauma & Recovery Ctr, Seattle, WA 98108 USA. [Varra, Alethea A.] VA Puget Sound Hlth Care Syst, PTSD Inpatient Program, Seattle, WA 98108 USA. [Liu, Chaun-Fen] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Div, Seattle, WA 98108 USA. RP Simpson, TL (reprint author), VA Puget Sound Hlth Care Syst, CESATE, 1660 S Columbian Way,116-WTRC, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov NR 38 TC 0 Z9 0 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD APR PY 2012 VL 27 IS 6 BP 1005 EP 1022 DI 10.1177/0886260511424496 PG 18 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 917NY UT WOS:000302186000002 PM 22203617 ER PT J AU So, K Koralek, AC Ganguly, K Gastpar, MC Carmena, JM AF So, Kelvin Koralek, Aaron C. Ganguly, Karunesh Gastpar, Michael C. Carmena, Jose M. TI Assessing functional connectivity of neural ensembles using directed information SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID GRANGER CAUSALITY; NETWORKS AB Neurons in the brain form highly complex networks through synaptic connections. Traditionally, functional connectivity between neurons has been explored using methods such as correlations, which do not contain any notion of directionality. Recently, an information-theoretic approach based on directed information theory has been proposed as a way to infer the direction of influence. However, it is still unclear whether this new approach provides any additional insight beyond conventional correlation analyses. In this paper, we present a modified procedure for estimating directed information and provide a comparison of results obtained using correlation analyses on both simulated and experimental data. Using physiologically realistic simulations, we demonstrate that directed information can outperform correlation in determining connections between neural spike trains while also providing directionality of the relationship, which cannot be assessed using correlation. Secondly, applying our method to rodent and primate data sets, we demonstrate that directed information can accurately estimate the conduction delay in connections between different brain structures. Moreover, directed information reveals connectivity structures that are not captured by correlations. Hence, directed information provides accurate and novel insights into the functional connectivity of neural ensembles that are applicable to data from neurophysiological studies in awake behaving animals. C1 [So, Kelvin; Ganguly, Karunesh; Gastpar, Michael C.; Carmena, Jose M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. [Koralek, Aaron C.; Ganguly, Karunesh; Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Ganguly, Karunesh] San Francisco VA Med Ctr, San Francisco, CA USA. [Gastpar, Michael C.] Ecole Polytech Fed EPFL, Sch Comp & Commun Sci, Lausanne, Switzerland. [Carmena, Jose M.] Univ Calif Berkeley, UCB UCSF Joint Grad Grp Bioengn, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif Berkeley, Program Cognit Sci, Berkeley, CA 94720 USA. RP So, K (reprint author), Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. EM carmena@eecs.berkeley.edu OI Koralek, Aaron/0000-0001-5205-0171 FU National Science Foundation CDI; Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development; American Heart Association/American Stroke Association FX The research reported here was supported by the National Science Foundation CDI Type-I grant to MCG and JMC, and the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development, and the American Heart Association/American Stroke Association to KG. NR 28 TC 13 Z9 13 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD APR PY 2012 VL 9 IS 2 AR 026004 DI 10.1088/1741-2560/9/2/026004 PG 13 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 917AK UT WOS:000302144100004 PM 22328616 ER PT J AU Canolty, RT Cadieu, CF Koepsell, K Ganguly, K Knight, RT Carmena, JM AF Canolty, Ryan T. Cadieu, Charles F. Koepsell, Kilian Ganguly, Karunesh Knight, Robert T. Carmena, Jose M. TI Detecting event-related changes of multivariate phase coupling in dynamic brain networks SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE neuronal oscillations; phase-locking value; functional networks; multivariate analysis ID COHERENCE; MECHANISM AB Canolty RT, Cadieu CF, Koepsell K, Ganguly K, Knight RT, Carmena JM. Detecting event-related changes of multivariate phase coupling in dynamic brain networks. J Neurophysiol 107: 2020-2031, 2012. First published January 12, 2011; doi: 10.1152/jn. 00610.2011.Oscillatory phase coupling within large-scale brain networks is a topic of increasing interest within systems, cognitive, and theoretical neuroscience. Evidence shows that brain rhythms play a role in controlling neuronal excitability and response modulation (Haider B, McCormick D. Neuron 62: 171-189, 2009) and regulate the efficacy of communication between cortical regions (Fries P. Trends Cogn Sci 9: 474-480, 2005) and distinct spatiotemporal scales (Canolty RT, Knight RT. Trends Cogn Sci 14: 506-515, 2010). In this view, anatomically connected brain areas form the scaffolding upon which neuronal oscillations rapidly create and dissolve transient functional networks (Lakatos P, Karmos G, Mehta A, Ulbert I, Schroeder C. Science 320: 110-113, 2008). Importantly, testing these hypotheses requires methods designed to accurately reflect dynamic changes in multivariate phase coupling within brain networks. Unfortunately, phase coupling between neurophysiological signals is commonly investigated using suboptimal techniques. Here we describe how a recently developed probabilistic model, phase coupling estimation (PCE; Cadieu C, Koepsell K Neural Comput 44: 3107-3126, 2010), can be used to investigate changes in multivariate phase coupling, and we detail the advantages of this model over the commonly employed phase-locking value (PLV; Lachaux JP, Rodriguez E, Martinerie J, Varela F. Human Brain Map 8: 194-208, 1999). We show that the N-dimensional PCE is a natural generalization of the inherently bivariate PLV. Using simulations, we show that PCE accurately captures both direct and indirect (network mediated) coupling between network elements in situations where PLV produces erroneous results. We present empirical results on recordings from humans and nonhuman primates and show that the PCEestimated coupling values are different from those using the bivariate PLV. Critically on these empirical recordings, PCE output tends to be sparser than the PLVs, indicating fewer significant interactions and perhaps a more parsimonious description of the data. Finally, the physical interpretation of PCE parameters is straightforward: the PCE parameters correspond to interaction terms in a network of coupled oscillators. Forward modeling of a network of coupled oscillators with parameters estimated by PCE generates synthetic data with statistical characteristics identical to empirical signals. Given these advantages over the PLV, PCE is a useful tool for investigating multivariate phase coupling in distributed brain networks. C1 [Canolty, Ryan T.; Ganguly, Karunesh; Carmena, Jose M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. [Canolty, Ryan T.; Cadieu, Charles F.; Koepsell, Kilian; Ganguly, Karunesh; Knight, Robert T.; Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Cadieu, Charles F.; Koepsell, Kilian] Univ Calif Berkeley, Redwood Ctr Theoret Neurosci, Berkeley, CA 94720 USA. [Ganguly, Karunesh] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Ganguly, Karunesh; Knight, Robert T.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Knight, Robert T.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif Berkeley, Program Cognit Sci, Berkeley, CA 94720 USA. RP Carmena, JM (reprint author), Univ Calif Berkeley, Dept Elect Engn & Comp Sci, 754 Sutardja Dai Hall,MC 1764, Berkeley, CA 94720 USA. EM carmena@eecs.berkeley.edu FU DARPA [N66001-10-C-2008]; National Science Foundation [CBET-0954243, IIS-0917342]; National Institute of Neurological Disorders and Stroke [NIH-R01-NS21135] FX This work was supported by DARPA Contract N66001-10-C-2008 (to J. M. Carmena), National Science Foundation Grant CBET-0954243 (to J. M. Carmena), National Science Foundation Grant IIS-0917342 (to C. F. Cadieu and K. Koepsell), and National Institute of Neurological Disorders and Stroke Grant NIH-R01-NS21135 (to R. T. Knight). NR 25 TC 13 Z9 13 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2012 VL 107 IS 7 BP 2020 EP 2031 DI 10.1152/jn.00610.2011 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 922GG UT WOS:000302534600022 PM 22236706 ER PT J AU Van den Abbeele, AID Gatsonis, C De Vries, DJ Melenevsky, Y Szot-Barnes, A Yap, JT Godwin, AK Rink, L Huang, M Blevins, M Sicks, J Eisenberg, B Siegel, BA AF Van den Abbeele, Annick D. Gatsonis, Constantine de Vries, Daniel J. Melenevsky, Yulia Szot-Barnes, Agnieszka Yap, Jeffrey T. Godwin, Andrew K. Rink, Lori Huang, Min Blevins, Meridith Sicks, JoRean Eisenberg, Burton Siegel, Barry A. TI ACRIN 6665/RTOG 0132 Phase II Trial of Neoadjuvant Imatinib Mesylate for Operable Malignant Gastrointestinal Stromal Tumor: Monitoring with F-18-FDG PET and Correlation with Genotype and GLUT4 Expression SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE GIST; FDG-PET; GLUT4; genotype; therapeutic response ID POSITRON-EMISSION-TOMOGRAPHY; BONE-SARCOMA-GROUP; EORTC-SOFT-TISSUE; EARLY PREDICTION; FDG-PET; MUTATIONS; GIST; THERAPY; KIT; MANAGEMENT AB We investigated the correlation between metabolic response by F-18-MG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib rnesylate therapy. Methods: F-18-FDG PET was performed at baseline, 1-7 d, and 4 or 8 wk after imatinib mesylate initiation. Best objective response was defined by version 1.0 of the Response Evaluation Criteria in Solid Tumors (RECIST). Mutational analysis and tumor GLUT4 expression by immunohistochemistry were done on tissue obtained at baseline or surgery. Results: F-18-FDG PET showed high baseline tumor glycolytic activity (mean SUVmax, 14.2; range, 1.3-53.2), decreasing after 1 wk of imatinib mesylate (mean, 5.5; range, -0.5-47.7, P < 0.001, n = 44), and again before surgery (mean, 3.0; range, -0.5-36.1, P < 0.001, n = 40). At week 1, there were 3 patients with complete metabolic response (CMR), 33 with partial metabolic response (PMR), 6 with stable metabolic disease (SMD), and 2 with progressive metabolic disease (PMD). Before surgery, there were 3 with CMR, 33 with PMR, 4 with SMD, and none with PMD. The best response according to RECIST was 2 with partial response, 36 with stable disease, and 1 with progressive disease (n = 39). Of the patients with a posttreatment decrease in GLUT4 expression, 1 had CMR, 15 had PMR, 2 had SMD, and 1 had PMD at week 1, whereas before surgery 1 patient had CMR, 16 had PMR, 2 had SMD, and none had PMD. Among 27 patients with KIT exon 11 mutations, 1 had CMR, 22 had PMR, 3 had SMD, and 1 had PMD at week 1, whereas 1 had CMR, 22 had PMR, 2 had SMD, and 2 were unknown before surgery; among 4 patients with a wild-type genotype, 2 had PMR and 2 SMD at week 1, whereas 1 had CMR, 2 had PMR, and 1 had SMD before surgery. Conclusion: After imatinib mesylate initiation, metabolic response by F-18-FDG PET was documented earlier (1-7 d) and was of much greater magnitude (36/44) than that documented by RECIST (2/39). Immunohistochemistry data suggest that GLUT4 may play a role in F-18-FDG uptake in gastrointestinal stromal tumor, GLUT4 levels decrease after imatinib mesylate therapy in most patients with PMR, and the biologic action of imatinib mesylate interacts with glycolysis and GLUT4 expression. A greater than 85% metabolic response was observed as early as days 1-7 in patients with exon 11 mutations. C1 [Van den Abbeele, Annick D.; de Vries, Daniel J.; Melenevsky, Yulia; Szot-Barnes, Agnieszka; Yap, Jeffrey T.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Van den Abbeele, Annick D.; de Vries, Daniel J.; Melenevsky, Yulia; Szot-Barnes, Agnieszka; Yap, Jeffrey T.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Gatsonis, Constantine; Blevins, Meridith; Sicks, JoRean] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Rink, Lori; Huang, Min] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Eisenberg, Burton] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Siegel, Barry A.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Div Nucl Med, St Louis, MO USA. [Siegel, Barry A.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. RP Van den Abbeele, AID (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St,Dana 101, Boston, MA 02115 USA. EM abbeele@dfci.harvard.edu OI Blevins, Meridith/0000-0002-3861-9859 FU Department of Health and Human Services; National Cancer Institute [U01 CA079778, U01 CA080098, R01 CA106588] FX We thank all the patients who generously volunteered to participate in this study, the study team staffs at the participating institutions, and ACRIN. We acknowledge the contributions of Ramsey Badawi, and we recognize the pioneering work of George Demetri and his team in bringing novel therapies to patients with GISTs. This project was funded in part by the Department of Health and Human Services and the National Cancer Institute through grants U01 CA079778, U01 CA080098, and R01 CA106588. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor is endorsement by the U.S. government implied. This study was presented in part at the 2008 annual meeting of the American College of Radiology Imaging Network and at the 2009 annual meeting of the American Society of Clinical Oncology. No other potential conflict of interest relevant to this article was reported. NR 38 TC 20 Z9 21 U1 0 U2 6 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 BP 567 EP 574 DI 10.2967/jnumed.111.094425 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300038 PM 22381410 ER PT J AU Graham, MM Jacene, HA AF Graham, Michael M. Jacene, Heather A. TI Molecular Imaging Training for Nuclear Medicine Residents SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article C1 [Graham, Michael M.] Univ Iowa, Dept Radiol, Div Nucl Med, Iowa City, IA 52242 USA. [Jacene, Heather A.] Dana Farber Canc Inst, Dept Imaging, Div Nucl Med, Boston, MA 02115 USA. RP Graham, MM (reprint author), Univ Iowa, Dept Radiol, Div Nucl Med, 3863 JPP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM michael-graham@uiowa.edu NR 1 TC 2 Z9 2 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 BP 655 EP 657 DI 10.2967/jnumed.112.103994 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300051 PM 22410460 ER PT J AU Blomberg, BA Gharavi, MH Saboury, B Werner, TJ Torigian, D Cheng, G Lim, E Akers, SR Alavi, A AF Blomberg, B. A. Gharavi, M. H. Saboury, B. Werner, T. J. Torigian, D. Cheng, G. Lim, E. Akers, S. R. Alavi, A. TI Effect of aging and smoking on FDG-uptake in atherosclerotic plaques assessed by multiple-time-point PET/CT imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 3rd Symposium on Multimodality Cardiovascular Molecular Imaging CY APR 19-21, 2012 CL Natl Inst Hlth (NIH), Bethesda, MD HO Natl Inst Hlth (NIH) C1 [Blomberg, B. A.; Gharavi, M. H.; Saboury, B.; Werner, T. J.; Torigian, D.; Alavi, A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Cheng, G.; Lim, E.; Akers, S. R.] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 MA 3 BP 665 EP 665 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300057 ER PT J AU Saboury, B Blomberg, BA Gharavi, MH Werner, TJ Lim, E Torigian, D Cheng, G Akers, SR Alavi, A AF Saboury, B. Blomberg, B. A. Gharavi, M. H. Werner, T. J. Lim, E. Torigian, D. Cheng, G. Akers, S. R. Alavi, A. TI Optimized visual assessment of atherosclerotic plaque burden by delayed-time-point FDG-PET/CT imaging: a new observation SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 3rd Symposium on Multimodality Cardiovascular Molecular Imaging CY APR 19-21, 2012 CL Natl Inst Hlth (NIH), Bethesda, MD HO Natl Inst Hlth (NIH) C1 [Saboury, B.; Blomberg, B. A.; Gharavi, M. H.; Werner, T. J.; Torigian, D.; Alavi, A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Lim, E.; Cheng, G.; Akers, S. R.] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2012 VL 53 IS 4 MA 19 BP 670 EP 670 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 920BV UT WOS:000302377300073 ER PT J AU Loo, SK Shtir, C Doyle, AE Mick, E McGough, JJ McCracken, J Biederman, J Smalley, SL Cantor, RM Faraone, SV Nelson, SF AF Loo, Sandra K. Shtir, Corina Doyle, Alysa E. Mick, Eric McGough, James J. McCracken, James Biederman, Joseph Smalley, Susan L. Cantor, Rita M. Faraone, Stephen V. Nelson, Stanley F. TI Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE cognitive ability; genetics; SNPs; ADHD; haplotype ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; QUANTITATIVE TRAIT LOCUS; COGNITIVE-ABILITY; CONVERGING EVIDENCE; MAXIMUM-LIKELIHOOD; CHRM2 GENE; SCHIZOPHRENIA; SCAN; POLYMORPHISM; LINKAGE AB Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally homogeneous family sample of 656 individuals with at least one child affected by attention-deficit/hyperactivity disorder (ADHD). Results: Haplotype trend regression analysis with sliding four-SNP windows identified haplotypes of genome-wide significance in genes involved in synaptic signaling (KIF16B; p = 1.27E-08) and neurodevelopment (PAX5; p = 3.58E-08), and highlight findings from a recent genetic study of cognitive ability (RXRA; p = 7.7E-08; GYPC; p = 2.5E-07). Further interrogation of SNPs within top haplotypes reveals that the minor alleles are associated with higher intelligence, whereas others are associated with relatively lower (but still average range) intelligence. Effects of the eight genes are additive, as a greater number of the associated genotypes in a given individual predict higher intelligence (p = 5.36E-08) and account for 8% of variance in intelligence. Conclusions: Analyses that examine additive genetic effects may be useful in identifying regions where the additive effects of SNPs have a significant effect on phenotype. These results describe novel variants and additive effects of genes involved in brain development on variability in intelligence within an ADHD sample. The precise mechanisms of these loci in relation to determining individual differences in general cognitive ability require further investigation. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(4):432-440. C1 [Loo, Sandra K.; McGough, James J.; McCracken, James; Smalley, Susan L.; Cantor, Rita M.; Nelson, Stanley F.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Shtir, Corina] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 1TN, England. [Doyle, Alysa E.; Biederman, Joseph] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mick, Eric] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, New York, NY USA. RP Loo, SK (reprint author), 760 Westwood Plaza Ste 47-406, Los Angeles, CA 90024 USA. EM Sloo@mednet.ucla.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU National Institute of Health [MH059126, MH085518, MH01966, MH071852, MH058277, NS54124]; UCLA Informatics Center for Neurogenetics and Neurogenomics; [NS062691] FX This work was supported by National Institute of Health grants MH059126, MH085518, MH01966, MH071852, MH058277, and NS54124. We acknowledge the support and advice regarding study analyses provided by the UCLA Informatics Center for Neurogenetics and Neurogenomics funded by grant NS062691. NR 48 TC 2 Z9 2 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2012 VL 51 IS 4 BP 432 EP 440 DI 10.1016/j.jaac.2012.01.006 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 918SQ UT WOS:000302271800014 PM 22449649 ER PT J AU Chandra, R AF Chandra, Rohit TI The Deadly Dinner Party and Other Medical Detective Stories SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Chandra, Rohit] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chandra, R (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rchandra@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2012 VL 51 IS 4 BP 444 EP 445 DI 10.1016/j.jaac.2012.02.006 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 918SQ UT WOS:000302271800017 ER PT J AU Gordon, KB Kimball, A Chau, D Kricorian, G AF Gordon, Kenneth B. Kimball, Alexa Chau, Dina Kricorian, Gregory TI AMG 827, an anti-interleukin-17 receptor antibody, improves psoriasis symptoms: Results from a randomized, controlled, phase II study SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) CY MAR 16-20, 2012 CL San Diego, CA SP Amer Acad Dermatol (AAD) C1 [Gordon, Kenneth B.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Kimball, Alexa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kimball, Alexa] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chau, Dina; Kricorian, Gregory] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 SU S BP AB184 EP AB184 PG 1 WC Dermatology SC Dermatology GA 919JF UT WOS:000302319800733 ER PT J AU Kimball, A Kricorian, G Gelfand, JM Creamer, K AF Kimball, Alexa Kricorian, Gregory Gelfand, Joel M. Creamer, Kara TI OBSERVE-5 long-term surveillance registry of patients receiving etanercept for psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) CY MAR 16-20, 2012 CL San Diego, CA SP Amer Acad Dermatol (AAD) C1 [Kimball, Alexa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kimball, Alexa] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kricorian, Gregory; Creamer, Kara] Amgen Inc, Thousand Oaks, CA 91320 USA. [Gelfand, Joel M.] Univ Penn Hlth Syst, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 SU S BP AB197 EP AB197 PG 1 WC Dermatology SC Dermatology GA 919JF UT WOS:000302319800783 ER PT J AU Lagana, F Tran, TN AF Lagana, Frances Thanh Nga Tran TI Viable alternative treatment for symptomatic onychomycosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) CY MAR 16-20, 2012 CL San Diego, CA SP Amer Acad Dermatol (AAD) C1 [Lagana, Frances] UMass Mem Med Ctr, Worcester, MA USA. [Thanh Nga Tran] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 SU S BP AB102 EP AB102 PG 1 WC Dermatology SC Dermatology GA 919JF UT WOS:000302319800403 ER PT J AU Shetti, M Schmults, C Berg, D Parvathaneni, U AF Shetti, Madhu Schmults, Chrysalyne Berg, Daniel Parvathaneni, Upendra TI Parallel uncertainty for adjuvant radiotherapy indications in cutaneous squamous cell carcinoma (CSCC) with perineural invasion (PNI) among radiation oncologists and Mohs surgeons SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) CY MAR 16-20, 2012 CL San Diego, CA SP Amer Acad Dermatol (AAD) C1 [Shetti, Madhu; Berg, Daniel; Parvathaneni, Upendra] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Schmults, Chrysalyne] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 SU S BP AB155 EP AB155 PG 1 WC Dermatology SC Dermatology GA 919JF UT WOS:000302319800618 ER PT J AU Vleugels, F Schmults, C Buzney, E Wang, L AF Vleugels, Frank Schmults, Chrysalyne Buzney, Elizabeth Wang, Linda TI Metastatic eccrine porocarcinoma 2 years after Mohs micrographic surgery SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) CY MAR 16-20, 2012 CL San Diego, CA SP Amer Acad Dermatol (AAD) C1 [Vleugels, Frank] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Schmults, Chrysalyne; Buzney, Elizabeth] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Wang, Linda] Dana Farber Canc Inst, Ctr Cutaneous Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 SU S BP AB154 EP AB154 PG 1 WC Dermatology SC Dermatology GA 919JF UT WOS:000302319800612 ER PT J AU Yong, M Kimball, A Schenfeld, J Anthony, M AF Yong, Mellissa Kimball, Alexa Schenfeld, Jennifer Anthony, Mary TI Incidence rates of malignancies and hospitalized infectious events in psoriasis patients with or without treatment and a general population in the United States: 2005-2009 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 70th Annual Meeting of the American-Academy-of-Dermatology (AAD) CY MAR 16-20, 2012 CL San Diego, CA SP Amer Acad Dermatol (AAD) C1 [Yong, Mellissa; Schenfeld, Jennifer; Anthony, Mary] Amgen Inc, Thousand Oaks, CA 91320 USA. [Kimball, Alexa] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 SU S BP AB6 EP AB6 PG 1 WC Dermatology SC Dermatology GA 919JF UT WOS:000302319800025 ER PT J AU Brown, CJ Foley, KT Lowman, JD Allman, RM Roth, DL AF Brown, C. J. Foley, K. T. Lowman, J. D. Allman, R. M. Roth, D. L. TI Impact of a Hospital Mobility Program on Function after Discharge SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Brown, C. J.; Allman, R. M.] Birmingham VAMC, Birmingham, AL USA. [Foley, K. T.; Lowman, J. D.] UAB, Sch Hlth Profess, Birmingham, AL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S5 EP S5 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800014 ER PT J AU Brown, RT Kiely, DK Bharel, M Patel, M Ard, KL Blazey-Martin, D Mitchell, SL AF Brown, R. T. Kiely, D. K. Bharel, M. Patel, M. Ard, K. L. Blazey-Martin, D. Mitchell, S. L. TI Use of Health Services in Older Homeless Adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Brown, R. T.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Brown, R. T.] San Francisco VA Med Ctr, San Francisco, CA USA. [Kiely, D. K.; Mitchell, S. L.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Bharel, M.] Boston Healthcare Homeless Program, Boston, MA USA. [Patel, M.] St Elizabeths Med Ctr, Dept Med, Boston, MA USA. [Ard, K. L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Blazey-Martin, D.] Tufts Med Ctr, Dept Med, Boston, MA USA. [Mitchell, S. L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S49 EP S49 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800141 ER PT J AU Brown, RT Kiely, DK Bharel, M Mitchell, SL AF Brown, R. T. Kiely, D. K. Bharel, M. Mitchell, S. L. TI Factors Associated with Geriatric Syndromes in Older Homeless Adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Brown, R. T.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Brown, R. T.] San Francisco VA Med Ctr, San Francisco, CA USA. [Kiely, D. K.; Mitchell, S. L.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Bharel, M.] Boston Healthcare Homeless Program, Boston, MA USA. [Mitchell, S. L.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S47 EP S47 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800135 ER PT J AU Chongkrairatanakul, N Hesse, K AF Chongkrairatanakul, N. Hesse, K. TI Improving Management of Osteoporosis at the Rehabilitation Center. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Chongkrairatanakul, N.; Hesse, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chongkrairatanakul, N.] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S69 EP S69 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800201 ER PT J AU Edes, T Levy, C Goedken, D Kinosian, B AF Edes, T. Levy, C. Goedken, D. Kinosian, B. TI Where Heroes Meet Angels: the Medical Foster Home. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Kinosian, B.] Univ PA, Philadelphia, PA USA. [Kinosian, B.] Philadelphia VAMC, CHERP, Philadelphia, PA USA. [Edes, T.; Goedken, D.] US Dept Vet Affairs, Washington, DC USA. [Levy, C.] Denver VAMC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S112 EP S113 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800326 ER PT J AU Engel, PA Morgan, A Spencer, J AF Engel, P. A. Morgan, A. Spencer, J. TI Geriatrics in Primary Care: Integrating Comprehensive Geriatric Care into the Medical Home. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Engel, P. A.; Morgan, A.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Engel, P. A.; Spencer, J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S55 EP S55 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800158 ER PT J AU Espinoza, S Hazuda, H AF Espinoza, S. Hazuda, H. TI Lower Extremity Function Mediates the Association between Diabetes and Frailty. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Espinoza, S.; Hazuda, H.] S Texas Vet Healthcare Syst, San Antonio, TX USA. [Espinoza, S.; Hazuda, H.] UT Hlth Sci Ctr, Div Clin Epidemiol, San Antonio, TX USA. [Espinoza, S.; Hazuda, H.] UT Hlth Sci Ctr, Div Geriatr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S219 EP S219 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800637 ER PT J AU Espinoza, S Darvin, K Halade, D Breeding, L Richardson, A AF Espinoza, S. Darvin, K. Halade, D. Breeding, L. Richardson, A. TI Protein Biomarkers for Frailty. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Espinoza, S.; Darvin, K.; Halade, D.; Breeding, L.; Richardson, A.] UT Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX USA. [Espinoza, S.; Richardson, A.] S Texas Vet Healthcare Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S218 EP S219 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800636 ER PT J AU Fung, CH Martin, J Jouldjian, S Josephson, K Alessi, C AF Fung, C. H. Martin, J. Jouldjian, S. Josephson, K. Alessi, C. TI Difficulty with Use of Positive Airway Pressure Equipment among Older Adults with Sleep Apnea. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Fung, C. H.; Martin, J.; Jouldjian, S.; Josephson, K.; Alessi, C.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. [Fung, C. H.; Martin, J.; Alessi, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S127 EP S127 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800369 ER PT J AU Garcia, CH Espinoza, S Hazuda, H AF Garcia, C. H. Espinoza, S. Hazuda, H. TI Strong Association Between Low Health Literacy and Poor Health Status among Hispanic Elderly Patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Garcia, C. H.; Espinoza, S.; Hazuda, H.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Espinoza, S.; Hazuda, H.] S Texas Vet Healthcare Syst, Med, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S164 EP S164 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800477 ER PT J AU Goodson, W Bloch, A Santos-Modesitt, W Yaffe, K King, AC Barnes, DE AF Goodson, W. Bloch, A. Santos-Modesitt, W. Yaffe, K. King, A. C. Barnes, D. E. TI The Effects of Aerobic Exercise and Stretching on Self-Reported Sleep Quality in Community Dwelling Older Adults with Cognitive Complaints: A Randomized, Controlled Trial. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Goodson, W.; Santos-Modesitt, W.; Yaffe, K.; Barnes, D. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goodson, W.; Santos-Modesitt, W.; Yaffe, K.; Barnes, D. E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Bloch, A.] Alliant Univ, San Francisco, CA USA. [King, A. C.] Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S67 EP S67 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800194 ER PT J AU Hanson, AJ Bayer-Carter, JL Green, PS Montine, TJ Baker, LD Watson, GS Bonner, LM Callaghan, M Leverenz, JB Walter, BK Tsai, EC Wilkinson, CW Zhang, J Craft, S AF Hanson, A. J. Bayer-Carter, J. L. Green, P. S. Montine, T. J. Baker, L. D. Watson, G. S. Bonner, L. M. Callaghan, M. Leverenz, J. B. Walter, B. K. Tsai, E. C. Wilkinson, C. W. Zhang, J. Craft, S. TI Lipid-depleted apolipoproteins and amyloid peptides are influenced by APOE genotype and cognitive diagnosis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Hanson, A. J.; Bayer-Carter, J. L.; Green, P. S.; Montine, T. J.; Baker, L. D.; Watson, G. S.; Leverenz, J. B.; Tsai, E. C.; Wilkinson, C. W.; Zhang, J.; Craft, S.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Hanson, A. J.; Bayer-Carter, J. L.; Green, P. S.; Montine, T. J.; Baker, L. D.; Watson, G. S.; Bonner, L. M.; Callaghan, M.; Leverenz, J. B.; Walter, B. K.; Tsai, E. C.; Wilkinson, C. W.; Craft, S.] VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S7 EP S7 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800019 ER PT J AU Howe, JL Griffith, JL AF Howe, J. L. Griffith, J. L. TI A Training Model to Strengthen Team-based Primary Care for Older Rural Veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Howe, J. L.; Griffith, J. L.] Mt Sinai Sch Med, New York, NY USA. [Howe, J. L.; Griffith, J. L.] James J Peter VAMC, GRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S205 EP S206 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800598 ER PT J AU Huang, DL Chan, KC Young, BA AF Huang, D. L. Chan, K. C. Young, B. A. TI Poor Oral Health and Quality of Life in US Older Adults with Diabetes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Huang, D. L.; Young, B. A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Huang, D. L.] Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Young, B. A.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S185 EP S185 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800538 ER PT J AU Huang, DL Rosenberg, DE Petz, SD Belza, B AF Huang, D. L. Rosenberg, D. E. Petz, S. D. Belza, B. TI Food Access in Aging Adults with Impaired Mobility. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Huang, D. L.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Huang, D. L.] Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Rosenberg, D. E.] Grp Hlth Res Inst, Seattle, WA USA. [Petz, S. D.; Belza, B.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Belza, B.] Univ Washington, Hlth Promot Res Ctr, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S169 EP S169 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800491 ER PT J AU Hughes, M Wey, M Bai, X Martinez, A Fernandez, E Strong, R AF Hughes, M. Wey, M. Bai, X. Martinez, A. Fernandez, E. Strong, R. TI Effect of rapamycin in a mouse model of synucleinopathy. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Hughes, M.] UTHSCSA, Sch Med, San Antonio, TX USA. [Wey, M.; Bai, X.; Martinez, A.; Fernandez, E.; Strong, R.] Barshop Inst Longev & Aging Studies, San Antonio, TX USA. [Fernandez, E.; Strong, R.] S Texas Vet Hlth Care Network, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S115 EP S115 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800334 ER PT J AU Hung, WW Dunn, CM Moodhe, NE Gottesman, EM Morano, B Boockvar, KS AF Hung, W. W. Dunn, C. M. Moodhe, N. E. Gottesman, E. M. Morano, B. Boockvar, K. S. TI Improving quality of care for older veterans through a RHIO-enhanced Care Transitions Intervention (CTI). SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Hung, W. W.; Dunn, C. M.; Moodhe, N. E.; Gottesman, E. M.; Morano, B.; Boockvar, K. S.] James J Peters VA Med Ctr, GRECC, Bronx, NY USA. [Hung, W. W.; Morano, B.; Boockvar, K. S.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S59 EP S59 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800171 ER PT J AU Jawad, M Villarreal, D Sanchez-Reilly, S Ross, J Lee, S Restrepo, M Tidwell, J AF Jawad, M. Villarreal, D. Sanchez-Reilly, S. Ross, J. Lee, S. Restrepo, M. Tidwell, J. TI Geriatric Palliative Care and Medical Intensive Care teams Collaborating to increase Geriatric Palliative Care Services for Older Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Jawad, M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Villarreal, D.; Sanchez-Reilly, S.; Ross, J.; Lee, S.; Restrepo, M.; Tidwell, J.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S231 EP S231 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800673 ER PT J AU Kinosian, B Edes, T Hossain, M AF Kinosian, B. Edes, T. Hossain, M. TI Veterans Using Primary Care Housecalls Outside the VA: Still Better than Expected SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Kinosian, B.] Philadelphia VAMC, CHERP, Philadelphia, PA USA. [Kinosian, B.] Univ PA, Philadelphia, PA USA. [Edes, T.; Hossain, M.] Dept Vet Affairs, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S4 EP S4 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800011 ER PT J AU Kostas, TR Paquin, A Rudolph, JL AF Kostas, T. R. Paquin, A. Rudolph, J. L. TI Medication Discrepancies Upon Discharge: Systems Failures. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Kostas, T. R.; Paquin, A.; Rudolph, J. L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Kostas, T. R.; Rudolph, J. L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Paquin, A.] VA Boston Healthcare Syst, Dept Pharm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S106 EP S106 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800308 ER PT J AU Mather, M Patel, T Espinoza, S AF Mather, M. Patel, T. Espinoza, S. TI Improving Transitions to Home in Older Veterans after Hospitalization. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Mather, M.; Patel, T.; Espinoza, S.] S Texas Vet Healthcare Syst, GRECC, San Antonio, TX USA. [Mather, M.; Patel, T.; Espinoza, S.] UT Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S57 EP S57 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800164 ER PT J AU Mills, WL Regev, T Kunik, ME Wilson, NL Moye, J McCullough, LB Naik, AD AF Mills, W. L. Regev, T. Kunik, M. E. Wilson, N. L. Moye, J. McCullough, L. B. Naik, A. D. TI A Screening Tool for Capacity to Live Safely and Independently in the Community. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Mills, W. L.; Kunik, M. E.; Wilson, N. L.; Naik, A. D.] Michael E DeBakey VA Med Ctr, Hlth Serv Res, Houston, TX USA. [Mills, W. L.; Kunik, M. E.; Wilson, N. L.; Naik, A. D.] Michael E DeBakey VA Med Ctr, Dev Ctr Excellence, Houston, TX USA. [Mills, W. L.; Kunik, M. E.; Wilson, N. L.; McCullough, L. B.; Naik, A. D.] Baylor Coll Med, Houston, TX 77030 USA. [Regev, T.] Harris Cty Hosp Dist, Houston, TX USA. [Moye, J.] VA Boston Healthcare Syst, Brockton, MA USA. [Moye, J.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S91 EP S92 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800265 ER PT J AU Mills, WL June, A Moye, J Mulligan, B Jahn, A King, K Gosian, J Herman, L Walder, A Naik, AD AF Mills, W. L. June, A. Moye, J. Mulligan, B. Jahn, A. King, K. Gosian, J. Herman, L. Walder, A. Naik, A. D. TI Intensity and Impact of Pain in Military Veterans Following Cancer Treatment. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Mills, W. L.; Herman, L.; Walder, A.; Naik, A. D.] Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Mills, W. L.; Herman, L.; Naik, A. D.] Baylor Coll Med, Houston, TX 77030 USA. [June, A.; Moye, J.; Mulligan, B.; Jahn, A.; King, K.; Gosian, J.] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S69 EP S69 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800200 ER PT J AU Morrison, LJ Carey, E Chittenden, E Block, S AF Morrison, L. J. Carey, E. Chittenden, E. Block, S. TI Hospice and Palliative Medicine Toolkit of Assessment Methods SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Morrison, L. J.] Baylor Coll Med, Houston, TX 77030 USA. [Morrison, L. J.] Methodist Hosp, Houston, TX 77030 USA. [Carey, E.] Mayo Clin, Rochester, MN USA. [Chittenden, E.; Block, S.] Harvard Univ, Sch Med, Boston, MA USA. [Chittenden, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Block, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S209 EP S209 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800607 ER PT J AU Paquin, AM Kostas, T Salow, M Rudolph, JL AF Paquin, A. M. Kostas, T. Salow, M. Rudolph, J. L. TI Discharge, Drugs, and Discrepancies: The Pharmacological Intervention in Late Life (PILL) Project. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Paquin, A. M.; Kostas, T.; Salow, M.; Rudolph, J. L.] VA Boston Healthcare Syst, GRECC, Boston, MA USA. [Paquin, A. M.; Salow, M.] VA Boston, Dept Pharm, Boston, MA USA. [Kostas, T.; Rudolph, J. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S171 EP S171 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800496 ER PT J AU Park, M Martin, J Fung, C Jouldjian, S Josephson, K Alessi, C AF Park, M. Martin, J. Fung, C. Jouldjian, S. Josephson, K. Alessi, C. TI Sedative-hypnotic Use Among Older Veterans With Insomnia And Unrecognized Sleep Apnea. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Park, M.] Western Univ Hlth Sci, Pomona, CA USA. [Martin, J.; Fung, C.; Jouldjian, S.; Josephson, K.; Alessi, C.] VA Greater Los Angeles, GRECC, Los Angeles, CA USA. [Martin, J.; Alessi, C.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S103 EP S104 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800300 ER PT J AU Ramaswamy, R Williams, A Kelley, AS Clark, EM AF Ramaswamy, R. Williams, A. Kelley, A. S. Clark, E. M. TI Fulfilling an ACGME Competency: Impact of a Novel Communication Skills Curriculum. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Ramaswamy, R.; Williams, A.; Kelley, A. S.; Clark, E. M.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Ramaswamy, R.; Williams, A.; Clark, E. M.] James J Peters VA Med Ctr, GRECC, Bronx, NY USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S40 EP S40 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800115 ER PT J AU Reuben, DB Ganz, DA Roth, C McCreath, H Ramirez, K Wenger, NS AF Reuben, D. B. Ganz, D. A. Roth, C. McCreath, H. Ramirez, K. Wenger, N. S. TI Team Care to Manage Chronic Illnesses in Older Persons. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 03-05, 2012 CL Seattle, WA SP Amer Geriatr Soc C1 [Reuben, D. B.; Ganz, D. A.; McCreath, H.; Ramirez, K.; Wenger, N. S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Roth, C.] RAND Corp, Santa Monica, CA USA. [Ganz, D. A.] Greater Los Angeles VAMC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2012 VL 60 SU 4 SI SI BP S109 EP S109 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921FZ UT WOS:000302464800317 ER PT J AU Di Salvo, DN Park, J Laing, FC AF Di Salvo, Donald N. Park, Joseph Laing, Faye C. TI Lithium Nephropathy Unique Sonographic Findings SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE lithium nephropathy; lithium toxicity; renal microcysts; renal sonography ID KIDNEY-DISEASE; THERAPY; FOCI AB This case series describes a unique sonographic appearance consisting of numerous microcysts and punctate echogenic foci seen on renal sonograms of 10 adult patients receiving chronic lithium therapy. Clinically, chronic renal insufficiency was present in 6 and nephrogenic diabetes insipidus in 2. Sonography showed numerous microcysts and punctate echogenic foci. Computed tomography in 5 patients confirmed microcysts and microcalcifications, which were fewer in number than on sonography. Magnetic resonance imaging in 2 patients confirmed microcysts in each case. Renal biopsy in 1 patient showed chronic interstitial nephritis, microcysts, and tubular dilatation. The diagnosis of lithium nephropathy should be considered when sonography shows these findings. C1 [Di Salvo, Donald N.] Dana Farber Canc Inst, Dept Imaging, Div Ultrasound Serv, Boston, MA 02215 USA. [Di Salvo, Donald N.; Park, Joseph] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Di Salvo, Donald N.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Laing, Faye C.] Georgetown Univ Hosp, Dept Radiol, Div Abdominal Imaging, Washington, DC 20007 USA. RP Di Salvo, DN (reprint author), Dana Farber Canc Inst, Dept Imaging, Div Ultrasound Serv, 450 Brookline Ave, Boston, MA 02215 USA. EM ddisalvo@partners.org NR 19 TC 7 Z9 8 U1 0 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2012 VL 31 IS 4 BP 637 EP 644 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 920YV UT WOS:000302446100015 PM 22441921 ER PT J AU Benacerraf, BR Groszmann, Y AF Benacerraf, Beryl R. Groszmann, Yvette TI Sonography Should Be the First Imaging Examination Done to Evaluate Patients With Suspected Endometriosis SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID GUIDED TRANSVAGINAL ULTRASONOGRAPHY; DEEP ENDOMETRIOSIS; DIAGNOSTIC-ACCURACY C1 [Benacerraf, Beryl R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Benacerraf, Beryl R.; Groszmann, Yvette] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Benacerraf, Beryl R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Benacerraf, Beryl R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Benacerraf, Beryl R.] Harvard Univ, Sch Med, Boston, MA USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, 1 Brookline Pl, Brookline, MA 02445 USA. NR 13 TC 14 Z9 14 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2012 VL 31 IS 4 BP 651 EP 653 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 920YV UT WOS:000302446100017 PM 22441923 ER PT J AU Buckley, JM Hughes, KS AF Buckley, Julliette M. Hughes, Kevin S. TI Aromatase inhibition to decrease background parenchymal enhancement: premedication before magnetic resonance imaging? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID BREAST-CANCER; THERAPY; WOMEN C1 [Buckley, Julliette M.; Hughes, Kevin S.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Buckley, JM (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. OI Hughes, Kevin/0000-0003-4084-6484 NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2012 VL 19 IS 4 BP 385 EP 386 DI 10.1097/gme.0b013e31824af478 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 916ZM UT WOS:000302141700004 PM 22453132 ER PT J AU Rogines-Velo, MP Heberle, AE Joffe, H AF Rogines-Velo, Maria Pia Heberle, Amy E. Joffe, Hadine TI Effect of medroxyprogesterone on depressive symptoms in depressed and nondepressed perimenopausal and postmenopausal women after discontinuation of transdermal estradiol therapy SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Medroxyprogesterone; Depression; Perimenopause; Menopause; Women; Estradiol ID HORMONE REPLACEMENT THERAPY; DOUBLE-BLIND; MENOPAUSAL TRANSITION; ESTROGEN REPLACEMENT; VASOMOTOR SYMPTOMS; MOOD; PROGESTERONE; TRIAL; SLEEP AB Objective: Concern about adverse effects of progestins on mood has influenced the use of medroxyprogesterone (MPA) and other progestins. In this brief report, we examined whether the administration of MPA leads to depressive symptoms in two groups of perimenopausal and postmenopausal women randomly assigned to treatment with estrogen: one currently experiencing clinical depression and another without depression. Methods: Open-label MPA 10 mg/day was administered for 14 days for endometrial protection after completion of double-blinded treatment with 17 beta-estradiol 0.1 mg/day for 8 to 12 weeks in 40- to 60-year-old perimenopausal and postmenopausal women enrolled in two separate randomized placebo-controlled trials for treatment of cognitive problems ("nondepressed group") or clinical depression ("depressed group"). Nonparametric tests were used to compare changes in depressive symptoms on the Beck Depression Inventory (BDI) within each group and between groups during MPA therapy. Results: Of the 24 nondepressed (median BDI at baseline, 5.5; interquartile range [IQR], 2.5-8.5) and 14 depressed (median BDI at baseline, 17; IQR, 15-21) women treated with MPA, the BDI scores did not change during MPA treatment in either group (median change, 0; IQR, =2 to 0.5 and median, 0; IQR, =0.5 to 1.5, P = 0.28 and P = 0.50, respectively). Changes in BDI scores during treatment with MPA did not differ between groups (P = 0.25). Conclusions: Among women receiving MPA for 2 weeks after discontinuation of estradiol, depressive symptoms did not emerge on MPA. These findings were consistent for both depressed and nondepressed women, suggesting that, even among women who are currently experiencing depression, brief treatment with MPA is unlikely to disrupt mood. C1 [Rogines-Velo, Maria Pia; Heberle, Amy E.; Joffe, Hadine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA 02114 USA. RP Joffe, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Womens Mental Hlth,Dept Psychiat, Simches Res Bldg,185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM hjoffe@partners.org OI Heberle, Amy/0000-0002-2935-828X FU NIH [K23 MH066978, R01 MH082922]; Pfizer/Society for the Advancement of Women's Health FX Financial support: This work was supported by NIH K23 MH066978 (H.J.), NIH R01 MH082922 (H.J.) and the Pfizer/Society for the Advancement of Women's Health Award (H.J.). Study medications were provided by Berlex/Bayer and Sanofi-Aventis. NR 31 TC 3 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD APR PY 2012 VL 19 IS 4 BP 471 EP 475 DI 10.1097/gme.0b013e3182333847 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 916ZM UT WOS:000302141700017 PM 22027945 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI BREAST CANCER Neoadjuvant bevacizumab treatment-signal or noise? SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID CHEMOTHERAPY AB Neoadjuvant bevacizumab, when added to standard chemotherapy for operable breast cancer, improved the rate of complete pathological response in two large, well-conducted trials. However, the modest incremental benefits, combined with uncertain long-term effects on disease recurrence, mean that this approach remains experimental until follow-up data are available. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM hburstein@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD APR PY 2012 VL 9 IS 4 BP 191 EP 192 DI 10.1038/nrclinonc.2012.34 PG 2 WC Oncology SC Oncology GA 916VD UT WOS:000302130400002 PM 22411347 ER PT J AU Joffe, S Miller, FG AF Joffe, Steven Miller, Franklin G. TI Equipoise: asking the right questions for clinical trial design SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; THERAPY; ETHICS; TAMOXIFEN; CHEMOTHERAPY; ONDANSETRON; LETROZOLE; WOMEN; RISK AB Randomized controlled trials (RCTs) are central to evidence-based clinical and health-policy decisions. However, RCTs highlight the tension between the therapeutic obligations of the physician and the scientific obligations of the investigator. Clinical equipoise, defined as honest professional disagreement among expert clinicians about the preferred treatment, is often cited as the solution to this RCT dilemma. Nevertheless, there are numerous practical and conceptual problems with the notion of equipoise. These problems include its mistaken imposition of therapeutic norms on the scientific enterprise of research, the difficulty of knowing when a state of equipoise exists, the susceptibility of expert judgment to bias and weak evidence, and its inability to support evidence necessary for health-policy decisions. An alternate approach to risk-benefit assessment that is congruent with the scientific purpose of RCTs can better guide ethical evaluation of these trials, as discussed in this Perspective. C1 [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 NR 36 TC 8 Z9 8 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD APR PY 2012 VL 9 IS 4 BP 230 EP 235 DI 10.1038/nrclinonc.2011.211 PG 6 WC Oncology SC Oncology GA 916VD UT WOS:000302130400010 PM 22231753 ER PT J AU Spasovski, G Busic, M Pipero, P Sarajlic, L Popovic, AS Dzhaleva, T Codreanu, I Ratkovic, MM Popescu, I Lausevic, M Avsec, D Raley, L Ekberg, H Ploeg, R Delmonico, F AF Spasovski, Goce Busic, Mirela Pipero, Pellumb Sarajlic, Lada Popovic, Andreja Subotic Dzhaleva, Theodora Codreanu, Igor Ratkovic, Marina Mugosa Popescu, Irinel Lausevic, Mirjana Avsec, Danica Raley, Lydia Ekberg, Henrik Ploeg, Rutger Delmonico, Francis TI Current status of transplantation and organ donation in the Balkans-could it be improved through the South-eastern European health Network (SEEHN) initiative? SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE Balkans; deceased donation; kidney transplantation; organ commercialism; SEE Health Network; transplant tourism ID RENAL-TRANSPLANTATION; TOURISM AB Organ donation and transplantation activity in the majority of Balkan countries (Albania, Bosnia and Herzegovina, Croatia, Macedonia, Moldova, Montenegro, Serbia, Romania and Bulgaria) are lagging far behind international averages. Inadequate financial resources, unclear regional data and lack of governmental infrastructure are some of the issues which should be recognized to draw attention and problem-solving decisions. The Regional Health Development Centre (RHDC) Croatia, being a technical body of the South-eastern European Health Network (SEEHN), was created in 2011 after Croatia's great success in the field over the last 10 years. The aim of the RHDC is to network the region and provide individualized country support to increase donation and transplantation activity in collaboration with professional societies (European Society of Organ Transplantation, European Transplant Coordinators Organization, The Transplantation Society and International Society of Organ Donation and Procurement). Such an improvement would in turn likely prevent transplant tourism. The regional data from 2010 show large discrepancies in donation and transplantation activities within geographically neighbouring countries. Thus, proposed actions to improve regional donation and transplantation rates include advancing living and deceased donation through regular public education, creating current and accurate waiting lists and increasing number of educated transplant nephrologists and hospital coordinators. In addition to the effort from the professionals, the governmental support with allocated funds per deceased donation, updated legislation and established national coordinating body is ultimately recognized as essential for the successful donation and transplantation programmes. By continuous RHDC communication and support asked from the health authorities and motivated professionals from the SEEHN initiative, an increased number of deceased as well as living donor kidney transplantations in the future should be more realistic. C1 [Spasovski, Goce] Univ Dept Nephrol, Skopje, Macedonia. [Busic, Mirela; Raley, Lydia] RHDC, Zagreb, Croatia. [Busic, Mirela; Raley, Lydia] Minist Hlth, Zagreb, Croatia. [Pipero, Pellumb] Minist Hlth, Tirana, Albania. [Sarajlic, Lada] Minist Hlth, Sarajevo, Bosnia & Herceg. [Popovic, Andreja Subotic] Minist Hlth & Social Welf, Banja Luka, Bosnia & Herceg. [Dzhaleva, Theodora] Minist Hlth, Sofia, Bulgaria. [Codreanu, Igor] Minist Hlth, Transplant Agcy, Kishinev, Moldova. [Ratkovic, Marina Mugosa] Univ Clin Ctr, Dept Nephrol, Podgorica, Montenegro. [Popescu, Irinel] Ctr Gen Surg & Liver Transplantat, Bucharest, Romania. [Lausevic, Mirjana] Univ Belgrade, Sch Med, Belgrade, Serbia. [Lausevic, Mirjana] Clin Ctr Serbia, Dept Nephrol, Belgrade, Serbia. [Avsec, Danica] Minist Hlth Slovenija Transplant, Ljubljana, Slovenia. [Ekberg, Henrik] Skane Univ Hosp, Dept Nephrol & Transplantat, Malmo, Sweden. [Ploeg, Rutger] Univ Oxford, Oxford, England. [Delmonico, Francis] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. RP Spasovski, G (reprint author), Univ Dept Nephrol, Skopje, Macedonia. EM gspas@sonet.com.mk NR 10 TC 11 Z9 11 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2012 VL 27 IS 4 BP 1319 EP 1323 DI 10.1093/ndt/gfs071 PG 5 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 919GM UT WOS:000302310700011 PM 22467749 ER PT J AU Lopes-Virella, MF Carter, RE Baker, NL Lachin, J Virella, G AF Lopes-Virella, Maria F. Carter, Rickey E. Baker, Nathaniel L. Lachin, John Virella, Gabriel CA DCCT EDIC Res Grp TI High levels of oxidized LDL in circulating immune complexes are associated with increased odds of developing abnormal albuminuria in Type 1 diabetes SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE albuminuria; diabetic nephropathy; immune complexes; modified lipoproteins ID LOW-DENSITY-LIPOPROTEIN; GLYCATION END-PRODUCTS; EURODIAB PROSPECTIVE COMPLICATIONS; RENAL-DISEASE; RISK-FACTORS; FOLLOW-UP; NEPHROPATHY; PROGRESSION; MELLITUS; PATHOGENESIS AB Background. Modified low-density lipoprotein (LDL) immune complexes (IC) have proinflammatory properties and play a role in albuminuria development. Methods. We measured oxidized LDL (oxLDL) and advanced glycation end-product (AGE)-LDL in IC isolated from sera of Type 1 diabetic subjects followed for 14-20 years and studied their association with abnormal albuminuria. Patients with albumin excretion rates (AER) < 40 mg/24 h at baseline and follow-up (n = 302) were deemed resistant to developing abnormal albuminuria. Patients with AER < 40 mg/24 h at baseline whose AER levels progressed to > 40 mg/24 h were considered prone to abnormal albuminuria (n = 185), those who progress to AER > 299 mg/24 h were considered as having macroalbuminuria (n = 57). The odds of developing abnormal albuminuria were estimated by logistic regression based on natural log-transformed levels of oxLDL and AGE-LDL in IC and stratified by baseline AER decile. Results. OxLDL and AGE-LDL were significantly higher in IC isolated from patients progressing to abnormal albuminuria. In unadjusted conditional logistic analysis, an increase of 1 SD in oxLDL and AGE-LDL levels in IC significantly increased the odds ratio (OR) for development of macroalbuminuria, respectively, by a factor of 2.5 and 1.8 (P < 0.001, P = 0.008). The increased odds of developing macroalbuminuria remained significant when adjusted for treatment group, diabetes duration, retinopathy, baseline hemoglobin A1c and LDL (OR = 2.5 and 1.8, respectively, P < 0.01). Conclusion. Higher levels of oxLDL and AGE-LDL in circulating IC were associated with increased odds to develop abnormal albuminuria. C1 [Lopes-Virella, Maria F.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.] Med Univ S Carolina, Lab Serv, Charleston, SC 29425 USA. [Lopes-Virella, Maria F.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Carter, Rickey E.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA. [Baker, Nathaniel L.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Lachin, John] George Washington Univ, Ctr Biostat, Washington, DC USA. [Virella, Gabriel] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. EM virellam@musc.edu OI Lachin, John/0000-0001-9838-2841 FU National Institutes of Health/NHLBI [PO1 HL 55782]; NIH/NIDDK [R01 DK081352]; Juvenile Diabetes Foundation [2006-49]; Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center; Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the NIH; National Center for Research Resources through the GCRC; Genentech Inc; NIDDK FX This work was supported by a Program Project funded by the National Institutes of Health/NHLBI (PO1 HL 55782), by an RO1 Grant funded by NIH/NIDDK (R01 DK081352) and by a Juvenile Diabetes Foundation Grant (2006-49). The work was also supported by the Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government.; The DCCT/EDIC was sponsored through research contracts from the Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the NIH. Additional support was provided by the National Center for Research Resources through the GCRC program and by Genentech Inc through a Cooperative Research and Development Agreement with the NIDDK. NR 46 TC 11 Z9 11 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 EI 1460-2385 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD APR PY 2012 VL 27 IS 4 BP 1416 EP 1423 DI 10.1093/ndt/gfr454 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 919GM UT WOS:000302310700023 PM 21856760 ER PT J AU Grossman, SA Ye, XB Peereboom, D Rosenfeld, MR Mikkelsen, T Supko, JG Desideri, S AF Grossman, Stuart A. Ye, Xiaobu Peereboom, David Rosenfeld, Myrna R. Mikkelsen, Tom Supko, Jeffrey G. Desideri, Serena CA Adult Brain Tumor Consortium TI Phase I study of terameprocol in patients with recurrent high-grade glioma SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; high grade glioma; phase I trial; terameprocol; transcription inhibitor ID METHYL NORDIHYDROGUAIARETIC ACID; TRANSCRIPTION INHIBITOR; ANTIVIRAL ACTIVITIES; ANTICANCER ACTIVITY; VAGINAL OINTMENT; CELL-DEATH; SURVIVIN; GROWTH; REPLICATION; DERIVATIVES AB Terameprocol is a global transcription inhibitor that affects cell division apoptosis, drug resistance, hypoxia responsive genes, and radiation resistance in hypoxia. A multicenter, dose-escalation study was conducted in heavily pretreated patients with recurrent, measurable, high-grade gliomas. Terameprocol was administered intravenously for 5 consecutive days each month and discontinued for toxicity or progression. Patients taking enzyme-inducing antiseizure drugs (EIASDs) were escalated independently. Thirty-five patients with a median Karnofsky performance status of 80, median age of 46 years, and median of 2 prior treatment regimens were accrued. Doses of 750, 1100, 1700, and 2200 mg/day were administered. Terameprocol was reformulated to avoid acidosis related to the excipient and was well tolerated at 1700 mg/day. Hypoxia and interstitial nephritis were noted at 2200 mg/day. Concurrent administration of EIASD did not significantly affect the serum pharmacokinetics of the terameprocol. Although no responses were seen, stable disease was noted in 9 (28%) of 32 evaluable patients, with 5 (13%) continuing treatment for >6 months (>= 6, 8, 10, 10, and >= 21 months). The overall median survival was 5.9 months. This phase I study defined the toxicity of terameprocol, determined that EIASDs do not affect its pharmacokinetics, and identified 1700 mg/day as the dose for future studies. Preclinical and human data suggest that this novel transcription inhibitor is worthy of further study. The long-term stability noted in some patients and the lack of associated myelosuppression suggest that terameprocol could be safely combined with radiation and temozolomide in newly diagnosed high-grade gliomas. C1 [Grossman, Stuart A.; Ye, Xiaobu; Desideri, Serena] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. [Peereboom, David] Cleveland Clin, Cleveland, OH 44106 USA. [Rosenfeld, Myrna R.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Supko, Jeffrey G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Grossman, SA (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Canc Res Bldg 2,Suite 1M-16,1550 Orleans St, Baltimore, MD 21231 USA. EM grossman@jhmi.edu OI Rosenfeld, Myrna/0000-0001-5095-2534 FU National Institutes of Health [CA-62475] FX This work was supported by the National Institutes of Health (CA-62475 to S.G.). NR 42 TC 13 Z9 13 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2012 VL 14 IS 4 BP 511 EP 517 DI 10.1093/neuonc/nor230 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 919OP UT WOS:000302338000015 PM 22323663 ER PT J AU Brun, R Michalek, W Surjanhata, BC Parkman, HP Semler, JR Kuo, B AF Brun, R. Michalek, W. Surjanhata, B. C. Parkman, H. P. Semler, J. R. Kuo, B. TI Comparative analysis of phase III migrating motor complexes in stomach and small bowel using wireless motility capsule and antroduodenal manometry SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE antroduodenal manometry; gastric contractility; GI motility; migrating motor complex; small bowel contractility; wireless motility capsule ID SLOW-TRANSIT CONSTIPATION; HUMAN GASTRIC-MOTILITY; SYSTEMIC-SCLEROSIS; HEALTHY; ABNORMALITIES; GASTROPARESIS; OBSTRUCTION; PATTERNS; DISEASE; COLON AB Background Assessment of phase III MMC is often not performed due to the invasive nature of antroduodenal manometry used to detect it. The aim of the study was to evaluate the ability of wireless motility capsule (WMC) to detect phase III MMC and correlate it with the simultaneous measurements by antroduodenal manometry (ADM). Methods Eighteen patients underwent simultaneous ADM and WMC. MMCs were identified first on ADM and then correlated with WMC events occurring simultaneously. Frequency of contractions per min, AUC, MI, and criteria for amplitude thresholds of contractions representing MCCs on WMC tracings were defined. Key Results In 18 patients, a total of 29 MMCs were recorded by ADM. WMC detected 86% of MMC events measured by ADM. Hundred percent (10/ 10) of MMCs in stomach were detected by WMC, whereas 79% (15/ 19) of MMCs were detected in SB. The sensitivity and specificity of WMC high amplitude contractions to represent phase III MMC were 90% and 71.8% in the stomach; 73.7% and 84.7% in SB, respectively, and negative predictive value was 99.9% in both regions. Conclusions & Inferences Wireless motility capsule was able to detect the phase III MMCs as the high amplitude contractions with good fidelity. WMC does not detect the propagation of MMC. Using the pressure thresholds, WMC can detect high amplitude contraction representing phase III MMC with favorable sensitivity/ specificity profile and 99.9% negative predictive value. This observation may have clinical significance, as the absence of high amplitude contractions recorded by WMC during fasting state suggests absence of MMCs. C1 [Brun, R.; Michalek, W.; Surjanhata, B. C.; Kuo, B.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Parkman, H. P.] Temple Univ, Sch Med, Dept Med, Gastroenterol Sect, Philadelphia, PA 19122 USA. [Semler, J. R.] SmartPill Corp, Buffalo, NY USA. RP Kuo, B (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, 55 Fruit St,GRJ 724, Boston, MA 02114 USA. EM bkuo@partners.org FU International Foundation for Functional Gastrointestinal Disorders (IFFGD) FX This work was supported by a grant from the International Foundation for Functional Gastrointestinal Disorders (IFFGD). NR 34 TC 6 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD APR PY 2012 VL 24 IS 4 DI 10.1111/j.1365-2982.2011.01862.x PG 8 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 908YZ UT WOS:000301530300009 PM 22292793 ER PT J AU Oaklander, AL AF Oaklander, Anne Louise TI Tarlov cysts SO NEUROSURGICAL FOCUS LA English DT Letter ID SACRAL MENINGEAL CYSTS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 2 U2 7 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD APR PY 2012 VL 32 IS 4 DI 10.3171/2012.1.FOCUS11374 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 918XN UT WOS:000302284900010 PM 22463119 ER PT J AU Noel, PH Wang, CP Bollinger, MJ Pugh, MJ Copeland, LA Tsevat, J Nelson, KM Dundon, MM Hazuda, HP AF Noel, Polly H. Wang, Chen-Pin Bollinger, Mary J. Pugh, Mary J. Copeland, Laurel A. Tsevat, Joel Nelson, Karin M. Dundon, Margaret M. Hazuda, Helen P. TI Intensity and Duration of Obesity-Related Counseling: Association With 5-Year BMI Trends Among Obese Primary Care Patients SO OBESITY LA English DT Article ID BODY-MASS INDEX; HEALTH-SERVICES RESEARCH; LIFE-STYLE INTERVENTION; WEIGHT-LOSS; LONGITUDINAL DATA; RANDOMIZED-TRIAL; NATIONAL TRENDS; POPULATION; MANAGEMENT; ADULTS AB We examined 5-year trends in BMI among obese primary care patients to determine whether obesity-related education such as nutrition counseling or a weight management program was associated with declines in BMI. Veterans with BMI = 30 kg/m(2) and = 1 primary care visits in fiscal year 2002 were identified from the Veterans Health Administration's (VHA) national databases. Outpatient visits from fiscal year 2002-2006 for nutrition counseling, exercise, or weight management were grouped into five categories varying in intensity and duration: (i) intenseand- sustained, (ii) intense-only, (iii) irregular, (iv) limited, and (v) no counseling. Generalized estimating equation assessed associations between obesity-related counseling and BMI trend (annual rate of BMI change fiscal year 2002-2006) among cohort members with complete race/ethnic data (N = 179,881). Multinomial logistic regression compared intensity and duration of counseling among patients whose net BMI increased or decreased by = 10% vs. remained stable. Compared with patients receiving " intense-and-sustained" counseling, the BMI trend of those receiving " intense-only" or " irregular" counseling was not significantly different, but patients receiving " no counseling" or " limited counseling" had significantly higher rates of decreasing BMI (-0.12 and -0.08 BMI per year; P < 0.01, respectively). This was especially true for veterans in their 50-60s, compared with the oldest veterans who were most likely to lose weight. In contrast, younger veterans (18-35 years) were least likely to lose weight; their BMI tended to increase regardless of counseling intensity and duration. Enhanced efforts are needed to detect and combat increasing weight trajectories among veterans who are already obese, especially among those aged 18-35 who are at greatest risk. C1 [Noel, Polly H.; Wang, Chen-Pin; Bollinger, Mary J.; Pugh, Mary J.; Copeland, Laurel A.; Hazuda, Helen P.] VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Noel, Polly H.; Wang, Chen-Pin; Pugh, Mary J.; Copeland, Laurel A.; Hazuda, Helen P.] UT Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Tsevat, Joel] Cincinnati VAMC, Cincinnati, OH USA. [Tsevat, Joel] Univ Cincinnati, Cincinnati, OH USA. [Nelson, Karin M.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA. [Dundon, Margaret M.] VA Western New York Healthcare Syst, Batavia, NY USA. RP Noel, PH (reprint author), VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX USA. EM noelp@uthscsa.edu OI Copeland, Laurel/0000-0002-9478-0209 FU Department of Veteran Affairs, Veterans Health Administration, Health Services Research and Development Service [IIR 05-121] FX The research reported here was supported by the Department of Veteran Affairs, Veterans Health Administration, Health Services Research and Development Service (project no. IIR 05-121). The authors thank Leila C. Kahwati, MD, MPH, Deputy Chief Consultant for Preventive Medicine, Office of Patient Care Services, Veterans Health Administration, for her review and suggestions. All of the authors except Dr Wang are employees of the Department of Veterans Affairs. The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs. NR 48 TC 6 Z9 6 U1 1 U2 6 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 2012 VL 20 IS 4 BP 773 EP 782 DI 10.1038/oby.2011.335 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 917AC UT WOS:000302143300010 PM 22134198 ER PT J AU Peraino, J Zhang, HP Hermanrud, CE Li, GY Sachs, DH Huang, CA Wang, ZR AF Peraino, Jaclyn Zhang, Huiping Hermanrud, Christina E. Li, Guoying Sachs, David H. Huang, Christene A. Wang, Zhirui TI Expression and purification of soluble porcine CTLA-4 in yeast Pichia pastoris SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Porcine CTLA-4; Pichia pastoris expression; Purification; Porcine CD80; Glycosylation ID T CELL IMMUNOTOXIN; BINDS; CD28; CD80 AB Co-stimulation blockade can be used to modulate the immune response for induction of organ transplantation tolerance, treatment of autoimmune disease as well as cancer treatment. Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4), also known as CD152, is an important co-stimulatory molecule which serves as a negative regulator for T cell proliferation and differentiation. CTLA-4/CD28-CD80/CD86 pathway is a critical co-stimulatory pathway for adaptive immune response. T cell activation through the T cell receptor and CD28 leads to increased expression of CTLA-4, an inhibitory receptor for CD80 and CD86. MGH MHC-defined miniature swine provide a unique large animal model useful for preclinical studies of transplantation tolerance and immune regulation. In this study, we have expressed the codon-optimized soluble porcine CTLA-4 in the yeast Pichia pastoris system. The secreted porcine CTLA-4 was captured using Ni-Sepharose 6 fast flow resin and further purified using strong anion exchange resin Poros 50HQ. Glycosylation analysis using PNGase F demonstrated the N-linked glycosylation on P. pastoris expressed soluble porcine CTLA-4. To improve the expression level and facilitate the downstream purification we mutated the two potential N-linked glycosylation sites with non-polarized alanines by site-directed mutagenesis. Removal of the two N-glycosylation sites significantly improved the production level from similar to 2 to similar to 8 mg/L. Biotinylated glycosylated and non-N-glycosylated soluble porcine CTLA-4 both bind to a porcine CD80-expressing B-cell lymphoma cell line (K-D = 13 nM) and competitively inhibit the binding of an anti-CD80 monoclonal antibody. The availability of soluble porcine CTLA-4, especially the non-N-glycosylated CTLA-4, will provide a very valuable tool for assessing co-stimulatory blockade treatment for translational studies in the clinically relevant porcine model. (C) 2012 Elsevier Inc. All rights reserved. C1 [Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA 02129 USA. DF HCC MGH Recombinant Prot Express & Purificat C, Boston, MA USA. RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-6113,13th St, Boston, MA 02129 USA. EM zhirui.wang@tbrc.mgh.harvard.edu FU National Institutes of Health [2P01A145897]; Dana Farber/Harvard Cancer Center FX The work was supported by National Institutes of Health (2P01A145897 to DHS) and Dana Farber/Harvard Cancer Center Core development grant. We thank Kazuhiko Yamada and David Leonard for intensive manuscript review. NR 16 TC 9 Z9 10 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2012 VL 82 IS 2 BP 270 EP 278 DI 10.1016/j.pep.2012.01.012 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 921PA UT WOS:000302488300003 PM 22326797 ER PT J AU King, JT Gordon, AJ Perkal, MF Crystal, S Rosenthal, RA Rodriguez-Barradas, MC Butt, AA Gibert, CL Rimland, D Simberkoff, MS Justice, AC AF King, Joseph T., Jr. Gordon, Adam J. Perkal, Melissa F. Crystal, Stephen Rosenthal, Ronnie A. Rodriguez-Barradas, Maria C. Butt, Adeel A. Gibert, Cynthia L. Rimland, David Simberkoff, Michael S. Justice, Amy C. TI Disparities in Rates of Spine Surgery for Degenerative Spine Disease Between HIV-Infected and Uninfected Veterans SO SPINE LA English DT Article DE disparities; HIV/AIDS; outcomes; spine; surgery ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL-PRACTICE GUIDELINE; AMERICAN PAIN SOCIETY; OF-THE-LITERATURE; LOW-BACK-PAIN; DISC DEGENERATION; MULTIPLE IMPUTATION; LUMBAR SPINE; LUNG-CANCER; ANTIRETROVIRAL THERAPY AB Study Design. Retrospective analysis of nationwide Veterans Health Administration clinical and administrative data. Objective. Examine the association between HIV infection and the rate of spine surgery for degenerative spine disease. Summary of Background Data. Combination antiretroviral therapy has prolonged survival in HIV-infected patients, increasing the prevalence of chronic conditions such as degenerative spine disease that may require spine surgery. Methods. We studied all HIV-infected patients under care in the Veterans Health Administration from 1996 to 2008 (n = 40,038) and uninfected comparator patients (n = 79,039) matched on age, sex, race, year, and geographic region. The primary outcome was spine surgery for degenerative spine disease, defined by International Classification of Diseases, Ninth Revision procedure and diagnosis codes. We used a multivariate Poisson regression to model spine surgery rates by HIV infection status, adjusting for factors that might affect suitability for surgery (demographics, year, comorbidities, body mass index, combination antiretroviral therapy, and laboratory values). Results. Two hundred twenty-eight HIV-infected and 784 uninfected patients underwent spine surgery for degenerative spine disease during 700,731 patient-years of follow-up (1.44 surgeries per 1000 patient-years). The most common procedures were spinal decompression (50%) and decompression and fusion (33%); the most common surgical sites were the lumbosacral (50%) and cervical (40%) spine. Adjusted rates of surgery were lower for HIV-infected patients (0.86 per 1000 patient-years of follow-up) than for uninfected patients (1.41 per 1000 patient-years; incidence rate ratio 0.61, 95% confidence interval: 0.51-0.74, P < 0.001). Among HIV-infected patients, there was a trend toward lower rates of spine surgery in patients with detectable viral load levels (incidence rate ratio 0.76, 95% confidence interval: 0.55-1.05, P = 0.099). Conclusion. In the Veterans Health Administration, HIV-infected patients experience significantly reduced rates of surgery for degenerative spine disease. Possible explanations include disease prevalence, emphasis on treatment of nonspine HIV-related symptoms, surgical referral patterns, impact of HIV on surgery risk-benefit ratio, patient preferences, and surgeon bias. C1 [King, Joseph T., Jr.] VA Connecticut Healthcare Syst, Neurosurg Sect, Dept Surg, West Haven, CT USA. [King, Joseph T., Jr.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Gordon, Adam J.; Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Gordon, Adam J.; Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Gordon, Adam J.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Perkal, Melissa F.; Rosenthal, Ronnie A.] VA Connecticut Healthcare Syst, Dept Surg, West Haven, CT USA. [Perkal, Melissa F.; Rosenthal, Ronnie A.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Crystal, Stephen] Rutgers State Univ, Ctr Pharmacotherapy Chron Dis Management & Outcom, New Brunswick, NJ 08903 USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Dept Med, Infect Dis Sect, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Gibert, Cynthia L.] VA Med Ctr, Dept Med, Div Infect Dis, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Rimland, David] Atlanta VA Med Ctr, Dept Med, Infect Dis Sect, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Simberkoff, Michael S.] VA New York Harbor Healthcare Syst, Dept Med, Infect Dis Sect, New York, NY USA. [Simberkoff, Michael S.] NYU, Sch Med, New York, NY USA. [Justice, Amy C.] VA Connecticut Healthcare Syst, Dept Med, Gen Internal Med Sect, West Haven, CT USA. [Justice, Amy C.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. RP King, JT (reprint author), VA Connecticut Healthcare Syst 112, Neurosurg Sect, 950 Campbell Ave, West Haven, CT 06516 USA. EM Joseph.KingJr@va.gov FU National Institutes of Health NIAAA [U10-AA13566]; National Institutes of Health NIA [R01-AG029154]; National Institutes of Health NHLBI [R01-HL095136, R01-HL090342, RCI-HL100347]; National Institutes of Health NIAID [U01-A1069918]; National Institutes of Health NIMH [P30-MH062294]; Veterans Health Administration Office of Research and Development [VA REA 08-266]; Office of Academic Affiliations FX National Institutes of Health: NIAAA (U10-AA13566), NIA (R01-AG029154), NHLBI (R01-HL095136; R01-HL090342; RCI-HL100347), NIAID (U01-A1069918), NIMH (P30-MH062294), and the Veterans Health Administration Office of Research and Development (VA REA 08-266) and Office of Academic Affiliations (Medical Informatics Fellowship) funds were received to support this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. NR 86 TC 2 Z9 2 U1 8 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 1 PY 2012 VL 37 IS 7 BP 612 EP 622 DI 10.1097/BRS.0b013e318228f32d PG 11 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 918QV UT WOS:000302266400019 PM 21697770 ER PT J AU Barbesino, G Goldfarb, M Parangi, S Yang, JY Ross, DS Daniels, GH AF Barbesino, Giuseppe Goldfarb, Melanie Parangi, Sareh Yang, Jingyun Ross, Douglas S. Daniels, Gilbert H. TI Thyroid Lobe Ablation with Radioactive Iodine as an Alternative to Completion Thyroidectomy After Hemithyroidectomy in Patients with Follicular Thyroid Carcinoma: Long-Term Follow-Up SO THYROID LA English DT Article ID WHOLE-BODY SCAN; SERUM THYROGLOBULIN; I-131 ABLATION; CANCER; RADIOIODINE; THERAPY; LOBECTOMY; REMNANT AB Background: Radioactive iodine lobe ablation (RAI-L-ABL) is a possible alternative to completion thyroidectomy (C-Tx) for follicular thyroid carcinoma (FTC), but no long-term outcome data are available after lobe ablation. We analyzed the long-term outcome of lobe ablation in a series of patients with FTC. Methods: This was a retrospective study of patients who were treated with lobe ablation between 1983 and 2008. Of 134 patients with FTC, 37 (27.6%) had lobe ablation with I-131 (30-32 mCi) (RAI-L-ABL), 68 (50.7%) had C-Tx, and 29 (21.6%) had initial total thyroidectomy (T-Tx). The main outcomes analyzed were I-131 uptake after lobe ablation, C-Tx or T-Tx, serum thyroglobulin (Tg), serum thyroid-stimulating hormone (TSH), long-term disease-specific mortality, and disease-free survival. Results: After lobe ablation, radioiodine uptake was significantly lower for the RAI-L-ABL group (0.6%) than for the C-Tx group (2.0%, p < 0.005) or T-Tx group (1.3%, p = 0.054). Subsequent remnant ablation was performed in 12 of 37 (32%) patients in the RAI-L-ABL group, in 58 of 68 (85.3%) patients in the C-Tx group, and in 25 of 29 (86.2%) patients in the T-Tx group (p < 0.01). With median follow-up of 95 months for the RAI-L-ABL group, 47 months for the C-Tx group, and 53 months for the T-Tx group, there was one death in the RAI-L-ABL group and one death in the T-Tx group. No other RAI-L-ABL patients had detectable disease, whereas patients in the C-Tx group and two patients in the T-Tx group had detectable disease (p = 0.18). Long-term stimulated or suppressed Tg of < 1 ng/mL were found in 87.5% of the RAI-L-ABL group (n = 28), 86.3% of the C-Tx group (n = 57), and 77.8% of the T-Tx group (n = 21). Tg was detectable in 40.6% of the RAI-L-ABL group compared to 13.8% of C-Tx and 28.6% of T-Tx groups (p < 0.05, between groups). Conclusions: RAI-L-ABL, C-Tx, and T-Tx are equally effective in achieving serum TSH concentrations of > 25 mIU/L and preparing patients for conventional I-131 treatment and whole body scanning with similar long-term outcomes. However, persistent measurable Tg (range 0.2-2.2 ng/mL) is more common after RAI-L-ABL. C1 [Barbesino, Giuseppe; Ross, Douglas S.; Daniels, Gilbert H.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. [Barbesino, Giuseppe; Ross, Douglas S.; Daniels, Gilbert H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Goldfarb, Melanie] Univ So Calif, Keck Sch Med, Dept Surg, Los Angeles, CA 90033 USA. [Parangi, Sareh] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Yang, Jingyun] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA. RP Barbesino, G (reprint author), Massachusetts Gen Hosp, Thyroid Unit, WACC 730S,15 Parkman St, Boston, MA 02114 USA. EM gbarbesino@partners.org FU NCI NIH HHS [R01 CA149738] NR 31 TC 11 Z9 13 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2012 VL 22 IS 4 BP 369 EP 376 DI 10.1089/thy.2011.0198 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 918AM UT WOS:000302221200006 PM 22385290 ER PT J AU Carty, SE Doherty, GM Inabnet, WB Pasieka, JL Randolph, GW Shaha, AR Terris, DJ Tufano, RP Tuttle, RM AF Carty, Sally E. Doherty, Gerard M. Inabnet, William B., III Pasieka, Janice L. Randolph, Gregory W. Shaha, Ashok R. Terris, David J. Tufano, Ralph P. Tuttle, R. Michael CA Surgical Affairs Comm Amer Thyroid TI American Thyroid Association Statement on the Essential Elements of Interdisciplinary Communication of Perioperative Information for Patients Undergoing Thyroid Cancer Surgery SO THYROID LA English DT Article ID OPERATIVE REPORTS; ACCURACY; TAUGHT AB Background: Thyroid cancer specialists require specific perioperative information to develop a management plan for patients with thyroid cancer, but there is not yet a model for effective interdisciplinary data communication. The American Thyroid Association Surgical Affairs Committee was asked to define a suggested essential perioperative dataset representing the critical information that should be readily available to participating members of the treatment team. Methods: To identify and agree upon a multidisciplinary set of critical perioperative findings requiring communication, we examined diverse best-practice documents relating to thyroidectomy and extracted common features felt to enhance precise, direct communication with nonsurgical caregivers. Results: Suggested essential datasets for the preoperative, intraoperative, and immediate postoperative findings and management of patients undergoing surgery for thyroid cancer were identified and are presented. For operative reporting, the essential features of both a dictated narrative format and a synoptic computer format are modeled in detail. The importance of interdisciplinary communication is discussed with regard to the extent of required resection, the final pathology findings, surgical complications, and other factors that may influence risk stratification, adjuvant treatment, and surveillance. Conclusions: Accurate communication of the important findings and sequelae of thyroidectomy for cancer is critical to individualized risk stratification as well as to the clinical issues of thyroid cancer care that are often jointly managed in the postoperative setting. True interdisciplinary care is essential to providing optimal care and surveillance. C1 [Carty, Sally E.] Univ Pittsburgh, Sch Med, Div Endocrine Surg, Pittsburgh, PA 15213 USA. [Doherty, Gerard M.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Inabnet, William B., III] Mt Sinai Med Ctr, Dept Surg, New York, NY 10029 USA. [Pasieka, Janice L.] Univ Calgary, Dept Surg, Calgary, AB, Canada. [Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Shaha, Ashok R.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Terris, David J.] Georgia Hlth Sci Univ, Dept Otolaryngol, Augusta, GA USA. [Tufano, Ralph P.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, Dept Endocrinol, New York, NY 10021 USA. RP Carty, SE (reprint author), Univ Pittsburgh, Sch Med, Div Endocrine Surg, 101 Kauffmann,3471 5th Ave, Pittsburgh, PA 15213 USA. EM cartyse@upmc.edu OI Doherty, Gerard/0000-0002-1685-9552 NR 12 TC 21 Z9 22 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2012 VL 22 IS 4 BP 395 EP 399 DI 10.1089/thy.2011.0423 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 918AM UT WOS:000302221200009 PM 22352873 ER PT J AU Hartwell, KJ Back, SE McRae-Clark, AL Shaftman, SR Brady, KT AF Hartwell, Karen J. Back, Sudie E. McRae-Clark, Aimee L. Shaftman, Stephanie R. Brady, Kathleen T. TI Motives for using: A comparison of prescription opioid, marijuana and cocaine dependent individuals SO ADDICTIVE BEHAVIORS LA English DT Article DE Opiates; Marijuana; Cocaine; Motives; IDTS ID ECOLOGICAL MOMENTARY ASSESSMENT; ALCOHOL-USE; COPING SKILLS; MOTIVATION; SITUATIONS; REASONS; USERS; DRUG; MEN AB Identification of the motives for drug use is critical to the development of effective interventions. Furthermore, consideration of the differences in motives for drug use across substance dependent populations may assist in tailoring interventions. To date, few studies have systematically compared motives for substance use across drug classes. The current study examined motives for drug use between non-treatment seeking individuals with current prescription opioid, marijuana, or cocaine dependence. Participants (N=227) completed the Inventory of Drug-Taking Situations (IDTS; Annis, Turner & Sklar,1997), which contains eight subscales assessing motives for drug use. The findings revealed that prescription opioid dependent individuals scored significantly higher than all other groups on the Physical Discomfort, Testing Personal Control and Conflict with Others subscales. Both the prescription opioid and cocaine dependent groups scored significantly higher than the marijuana group on the Urges or a Temptation to Use subscale. In contrast, marijuana dependent individuals scored highest on the Pleasant Emotions and Pleasant Times with Others subscales. The marked differences revealed in motives for drug use could be used in the development and implementation of specific treatment interventions for prescription opioid, marijuana and cocaine dependent individuals. Published by Elsevier Ltd. C1 [Hartwell, Karen J.] Med Univ S Carolina, Clin Neurosci Div, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Hartwell, Karen J.; Brady, Kathleen T.] Ralph H Johnson VAMC, Charleston, SC USA. [Shaftman, Stephanie R.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. RP Hartwell, KJ (reprint author), Med Univ S Carolina, Clin Neurosci Div, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA. EM hartwelk@musc.edu RI McRae-Clark, Aimee/I-3341-2013 OI McRae-Clark, Aimee/0000-0002-9774-318X FU NIH [K23 DA021228, R21 DA22424, P50 DA0165511] FX This work was supported in part by NIH grants K23 DA021228 (SEB), R21 DA22424 (ALM) and P50 DA0165511 (KTB). NR 34 TC 9 Z9 9 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2012 VL 37 IS 4 BP 373 EP 378 DI 10.1016/j.addbeh.2011.11.014 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 911BD UT WOS:000301691400003 PM 22284583 ER PT J AU Broyles, LM Rosenberger, E Hanusa, BH Kraemer, KL Gordon, AJ AF Broyles, Lauren M. Rosenberger, Emily Hanusa, Barbara H. Kraemer, Kevin L. Gordon, Adam J. TI Hospitalized Patients' Acceptability of Nurse-Delivered Screening, Brief Intervention, and Referral to Treatment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Patient Acceptance of Health Care; Alcohol Consumption; Inpatients; Nursing; Counseling ID BRIEF ALCOHOL INTERVENTION; PRIMARY HEALTH-CARE; DISORDERS IDENTIFICATION TEST; VETERANS-AFFAIRS; AUDIT-C; PHYSICIANS; ATTITUDES; ADVICE; IMPLEMENTATION; PARTICIPATE AB Background: Inpatient healthcare providers in the United States may soon be required to offer alcohol screening, brief intervention, and referral to treatment (SBIRT) for hospital accreditation, but little is known about inpatient acceptability for SBIRT, particularly when performed by nonphysician providers such as nurses. The purpose of this study was to assess patient acceptability for and comfort with nurse-delivered SBIRT care among hospitalized patients and to identify factors associated with SBIRT acceptability. Methods: We conducted a cross-sectional survey of 370 hospitalized medical-surgical patients at a large university-affiliated medical center, which is part of the U.S. Department of Veterans Affairs. Results: Patient acceptability for 8 of 10 individual nurse-delivered SBIRT tasks was >84%. Patients were more accepting of SBIRT tasks if they felt able to determine their alcohol risk, able to reduce alcohol-related health risks, and expressed some degree of concern about their own use of alcohol. Approximately 20% of patients reported some degree of personal discomfort with alcohol-related discussions. Patients who were less comfortable with these discussions had lower perceived ability to reduce alcohol-related health risk, were >60 years old, had a positive AUDIT-C screening, and were of nonblack race. Conclusions: Among hospitalized patients, patient acceptability for nurse-delivered SBIRT is high, and alcohol-related risk perceptions appear to be important factors associated with acceptability for SBIRT tasks. Providers can proceed with greater confidence in SBIRT-related discussions with most hospitalized patients but may need particular sensitivity and skill addressing alcohol with patient subgroups such as older patients and those with positive alcohol screenings. C1 [Broyles, Lauren M.; Hanusa, Barbara H.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Broyles, Lauren M.; Hanusa, Barbara H.; Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr VISN4, Pittsburgh, PA 15206 USA. [Broyles, Lauren M.; Kraemer, Kevin L.; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Broyles, Lauren M.; Kraemer, Kevin L.; Gordon, Adam J.] Univ Pittsburgh, Ctr Res Healthcare, Pittsburgh, PA USA. [Rosenberger, Emily] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Broyles, LM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA. EM Lauren.Broyles@va.gov FU American Nurses Foundation (ANF); Health Services Research & Development service of the U.S. Department of Veterans Affairs [CDA10-014] FX The authors thank the staff nurses, nursing leadership, and Veteran participants for their support and participation in the study. In addition, the authors thank John D. Harding, Jr., BA, and Caroline DeMeis, MPH, for their patient recruitment efforts. Funding for this study was provided by a 2009 American Nurses Foundation (ANF) grant; LMB is the 2009 Council for the Advancement of Nursing Science/ANF Scholar. LMB is currently supported by a Career Development Award (CDA) from the Health Services Research & Development service of the U.S. Department of Veterans Affairs. The material is the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Pittsburgh, PA. LMB is currently supported by a Career Development Award (CDA10-014) from the Health Services Research & Development service of the U.S. Department of Veterans Affairs. NR 34 TC 15 Z9 15 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2012 VL 36 IS 4 BP 725 EP 731 DI 10.1111/j.1530-0277.2011.01651.x PG 7 WC Substance Abuse SC Substance Abuse GA 916AN UT WOS:000302068900021 PM 22250713 ER PT J AU Pfab, F Kirchner, MT Huss-Marp, J Schuster, T Schalock, PC Fuqin, J Athanasiadis, GI Behrendt, H Ring, J Darsow, U Napadow, V AF Pfab, F. Kirchner, M. -T. Huss-Marp, J. Schuster, T. Schalock, P. C. Fuqin, J. Athanasiadis, G. I. Behrendt, H. Ring, J. Darsow, U. Napadow, V. TI Acupuncture compared with oral antihistamine for type I hypersensitivity itch and skin response in adults with atopic dermatitis - a patient- and examiner-blinded, randomized, placebo-controlled, crossover trial SO ALLERGY LA English DT Article DE acupuncture; allergen; atopic eczema; attention; cetirizine; itch ID HISTAMINE-INDUCED ITCH; HUMAN BRAIN; ELECTROACUPUNCTURE; ECZEMA; FMRI; MODULATION; MECHANISMS; PRURITUS; WHEAL; FLARE AB Background: Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and antihistamine itch therapy (cetirizine) on type I hypersensitivity itch and skin reaction in AD using a patient and examinerblinded, randomized, placebo-controlled, crossover trial. Methods: Allergen-induced itch was evaluated in 20 patients with AD after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture (VAp and VAa), cetirizine (10 mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC) and a no-intervention control (NI). Itch was induced on the forearm and temperature modulated over 20 min, using our validated model. Outcome parameters included itch intensity, wheal and flare size and the D2 attention test. Results: Mean itch intensity (SE: 0.31 each) was significantly lower following VAa (31.9) compared with all other groups (PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7; P < 0.05). There was no significant difference between VAp and VC (P > 0.1), although both therapies were significantly superior to their respective placebo interventions (P < 0.05). Flare size following VAp was significantly smaller (P = 0.034) than that following PAp. D2 attention test score was significantly lower following VC compared with all other groups (P < 0.001). Conclusions: Both VA and cetirizine significantly reduced type I hypersensitivity itch in patients with AD, compared with both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially because of counter-irritation and/ or distraction. Itch reduction following cetirizine coincided with reduced attention. C1 [Pfab, F.; Napadow, V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. [Pfab, F.; Huss-Marp, J.; Fuqin, J.; Athanasiadis, G. I.; Ring, J.; Darsow, U.] Tech Univ Munich, Dept Dermatol & Allergy, Munich, Germany. [Pfab, F.; Kirchner, M. -T.; Huss-Marp, J.; Fuqin, J.; Behrendt, H.; Darsow, U.] ZAUM Ctr Allergy & Environm, Div Environm Dermatol & Allergy, Helmholtz Zentrum Munchen TUM, Munich, Germany. [Pfab, F.] Tech Univ Muenchen, Dept Prevent & Sports Med, Klinikum Rechts Isar, Munich, Germany. [Schuster, T.] Tech Univ Munich, Inst Med Stat & Epidemiol, Munich, Germany. [Schalock, P. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02129 USA. [Behrendt, H.; Ring, J.] Christine Kuhne Ctr Allergy Res & Educ CK CARE, Munich, Germany. [Napadow, V.] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. RP Pfab, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, CNY 149-2301,13th St Charlestown, Boston, MA 02129 USA. EM pfab@nmr.mgh.harvard.edu OI Schalock, Peter/0000-0001-8953-4639 FU German Acupuncture Society (DAGfA); German Research Foundation [pf 690/2-1]; Christine Kuhne Center of Allergy and Education (CK-Care); National Center for Complementary and Alternative Medicine at the National Institutes of Health, USA [VN: R01-AT004714, P01-AT002048] FX This study was partly funded by a grant of the German Acupuncture Society (DAGfA), German Research Foundation (pf 690/2-1), the Christine Kuhne Center of Allergy and Education (CK-Care) and the National Center for Complementary and Alternative Medicine at the National Institutes of Health, USA (VN: R01-AT004714, P01-AT002048). NR 34 TC 25 Z9 28 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-4538 J9 ALLERGY JI Allergy PD APR PY 2012 VL 67 IS 4 BP 566 EP 573 DI 10.1111/j.1398-9995.2012.02789.x PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 908II UT WOS:000301483700015 PM 22313287 ER PT J AU Akinkuolie, AO Aleardi, M Ashaye, AO Gaziano, JM Djousse, L AF Akinkuolie, Akintunde O. Aleardi, Megan Ashaye, Ajibade O. Gaziano, J. Michael Djousse, Luc TI Height and Risk of Heart Failure in the Physicians' Health Study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; PULSE PRESSURE; SHORT STATURE; LUNG-FUNCTION; FOLLOW-UP; MORTALITY; FRAMINGHAM; POSITION; GROWTH AB Although previous studies have reported an association between height and cardiovascular disease, it is unclear whether height is associated with the risk of heart failure (HF). We hypothesized that height would be inversely associated with HF risk. We used prospective data from 22,042 male physicians (mean age 53.8 years) from the Physicians' Health Study. Height was self-reported at baseline. Incident HF was ascertained using follow-up questionnaires and validated through review of the medical records in a subsample. The Cox proportional hazard model was used to compute the hazard ratio (HR) and corresponding 95% confidence interval (CI). The mean height +/- SD was 1.78 +/- 0.07 m. A total of 1,444 HF cases occurred during a mean follow-up of 22.3 years. Compared to subjects in the lowest height category (1.40 to 1.73 m), the HR for HF was 0.86 (95% CI 0.74 to 0.99), 0.82 (95% CI 0.70 to 0.95), and 0.76 (95% CI 0.63 to 0.91) for the height categories of 1.74 to 1.78 m, 1.79 to 1.83 m, and 1.84 to 2.08 m, respectively, after adjustment for age, weight, hypertension, and diabetes mellitus (p for trend = 0.0023). The HR per SD increment in height was 0.92 (95% CI 0.86 to 0.98) in a fully adjusted model. The exclusion of those with prevalent atrial fibrillation, left ventricular hypertrophy, valvular heart disease, and a history of coronary artery bypass grafting yielded similar results (HR per SD 0.88, 95% CI 0.83 to 0.94). In conclusion, our data demonstrated an inverse association between height and incident HF in United States male physicians. Additional studies to elucidate the underlying biologic mechanisms are warranted. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:994-997) C1 [Akinkuolie, Akintunde O.; Gaziano, J. Michael; Djousse, Luc] Brigham & Womens Hosp, Boston, MA 02115 USA. [Akinkuolie, Akintunde O.; Gaziano, J. Michael; Djousse, Luc] Harvard Univ, Sch Med, Boston, MA USA. [Aleardi, Megan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ashaye, Ajibade O.] Univ Connecticut, Evidence Based Practice Ctr, Hartford Hosp, Hartford, CT 06112 USA. [Gaziano, J. Michael; Djousse, Luc] Vet Affairs Healthcare Syst, Boston, MA USA. RP Akinkuolie, AO (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM aoakinkuolie@partners.org RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Cancer Institute (Bethesda, Maryland) [CA-34944, CA-40360, CA-097193]; National Heart, Lung, and Blood Institute (Bethesda, Maryland) [HL-26490, HL-34595, K01 HL-70444] FX The Physicians' Health Study is supported by grants CA-34944, CA-40360 and CA-097193 from the National Cancer Institute (Bethesda, Maryland) and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute (Bethesda, Maryland). Dr. Djousse is the Principal Investigator supported by grant K01 HL-70444 from the National Heart, Lung, and Blood Institute (Bethesda, Maryland). NR 26 TC 4 Z9 5 U1 1 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 APR 1 PY 2012 VL 109 IS 7 BP 994 EP 997 DI 10.1016/j.amjcard.2011.11.032 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916NV UT WOS:000302111400011 PM 22221952 ER PT J AU Wasfy, MM Brady, TJ Abbara, S Nasir, K Ghoshhajra, BB Truong, QA Hoffmann, U Di Carli, MF Blankstein, R AF Wasfy, Meagan M. Brady, Thomas J. Abbara, Suhny Nasir, Khurram Ghoshhajra, Brian B. Truong, Quynh A. Hoffmann, Udo Di Carli, Marcelo F. Blankstein, Ron TI Comparison of the Diamond-Forrester Method and Duke Clinical Score to Predict Obstructive Coronary Artery Disease by Computed Tomographic Angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-MAGNETIC-RESONANCE; NORTH-AMERICAN-SOCIETY; DIAGNOSTIC-ACCURACY; NUCLEAR-CARDIOLOGY; PROGNOSTIC VALUE; INTERMEDIATE; CRITERIA; APPROPRIATENESS; INTERVENTIONS; PROBABILITY AB We sought to evaluate the ability of the Diamond and Forrester method (DFM) and the Duke Clinical Score (DCS) to predict obstructive coronary artery disease (CAD) on coronary computed tomographic angiography (CCTA) and the effect of these different risk scores on the appropriateness level using the 2010 Appropriate Use Criteria. Consecutive symptomatic patients who underwent CCTA for evaluation of CAD (n = 114) were classified as having a low, intermediate, or high pretest probability using the DFM and DCS. Using the Appropriate Use Criteria, the indications for CCTA were classified according to the pretest probability and previous testing. The CCTA results were classified as revealing obstructive (>= 70% stenosis), nonobstructive (<70%), or no CAD. When the patients' risk was classified using the DFM, 18% were low, 65% intermediate, and 17% high risk. When using the DCS, 53% of patients had a reclassification of their risk, most of whom changed from intermediate to either low or high risk (50% low, 19% intermediate, 35% high risk). The net reclassification improvement for the prediction of obstructive CAD was 51% (p = 0.01). Of the 37 patients who were reclassified as low risk, 36 (97%) lacked obstructive CAD. Appropriateness for CCTA was reclassified for 13% of patients when using the DCS instead of the DFM, and the number of appropriate examinations was significantly fewer (68% vs 55%, p <0.001). In conclusion, reclassification of risk using the DCS instead of the DFM resulted in improved prediction of obstructive CAD on CCTA, especially in low-risk patients. More patients were categorized as having a high pretest probability of CAD, resulting in reclassification of their examination indications as uncertain or inappropriate. These results identify the need for improved pretest risk scores for noninvasive tests such as CCTA and suggest that the method of risk assessment could have important implications for patient selection and quality assurance programs. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:998-1004) C1 [Wasfy, Meagan M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Brady, Thomas J.; Abbara, Suhny; Ghoshhajra, Brian B.; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Brady, Thomas J.; Abbara, Suhny; Ghoshhajra, Brian B.; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Nasir, Khurram] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Di Carli, Marcelo F.; Blankstein, Ron] Brigham & Womens Hosp, Dept Med, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Di Carli, Marcelo F.; Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. RP Wasfy, MM (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. FU National Institutes of Health (Baltimore, Maryland) [1T32 HL076136-02] FX Drs. Nasir, Ghoshhajra, Truong, and Blankstein received support from grant 1T32 HL076136-02 from the National Institutes of Health (Baltimore, Maryland). NR 19 TC 16 Z9 17 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2012 VL 109 IS 7 BP 998 EP 1004 DI 10.1016/j.amjcard.2011.11.028 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916NV UT WOS:000302111400012 PM 22236462 ER PT J AU Ramos-Casals, M Sanz, I Bosch, X Stone, JH Khamashta, MA AF Ramos-Casals, Manuel Sanz, Inaki Bosch, Xavier Stone, John H. Khamashta, Munther A. TI B-cell-depleting Therapy in Systemic Lupus Erythematosus SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Belimumab; Epratuzumab; Ocrelizumab; Rituximab; Systemic lupus erythematosus ID OFF-LABEL USE; AUTOIMMUNE-DISEASES; LONGITUDINAL ANALYSIS; DOUBLE-BLIND; RITUXIMAB; SLE; SAFETY; NEPHRITIS; BELIMUMAB; EFFICACY AB The emergence of a new class of agents (B-cell-depleting therapies) has opened a new era in the therapeutic approach to systemic lupus erythematosus, with belimumab being the first drug licensed for use in systemic lupus erythematosus in more than 50 years. Four agents deserve specific mention: rituximab, ocrelizumab, epratuzumab, and belimumab. Controlled trials have shown negative results for rituximab, promising results for epratuzumab, and positive results for belimumab. Despite these negative results, rituximab is the most-used agent in patients who do not respond or are intolerant to standard therapy and those with life-threatening presentations. B-cell-depleting agents should not be used in patients with mild disease and should be tailored according to individual patient characteristics, including ethnicity, organ involvement, and the immunological profile. Forthcoming studies of B-cell-directed strategies, particularly data from investigations of off-label rituximab use and postmarketing studies of belimumab, will provide new insights into the utility of these treatments in the routine management of patients with systemic lupus erythematosus. (C) 2012 Elsevier Inc. All rights reserved. The American Journal of Medicine (2012) 125, 327-336 C1 [Bosch, Xavier] Hosp Clin Barcelona, Dept Internal Med, ICMiD, E-08036 Barcelona, Spain. [Ramos-Casals, Manuel] Hosp Clin Barcelona, Dept Autoimmune Dis, IDIBAPS, Lab Autoimmune Dis Josep Font, E-08036 Barcelona, Spain. [Sanz, Inaki] Univ Rochester, Sch Med & Dent, Div Allergy Immunol & Rheumatol, Dept Med, Rochester, NY USA. [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Khamashta, Munther A.] Kings Coll London, St Thomas Hosp, Rayne Inst, Lupus Res Unit, London WC2R 2LS, England. RP Bosch, X (reprint author), Hosp Clin Barcelona, Dept Internal Med, ICMiD, Villarroel 170, E-08036 Barcelona, Spain. EM xavbosch@clinic.ub.es OI Ramos-Casals, Manuel/0000-0001-5709-6734 FU Genentech; Biogen-IDEC FX JHS has received research funding from Genentech and Biogen-IDEC and has served as a consultant for the development of B-cell depletion strategies in the treatment of antineutrophil cytoplasmic autoantibody-associated vasculitis. IS has served as consultant for MedImmune, GSK, Pfizer, BMS, Takeda Pharmaceuticals, and Biogen. The remaining authors declare no conflict of interest. NR 50 TC 36 Z9 36 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 2012 VL 125 IS 4 BP 327 EP 336 DI 10.1016/j.amjmed.2011.09.010 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 916RH UT WOS:000302120400013 PM 22444096 ER PT J AU Ain, DL Slovut, DP Kamath, R Jaff, MR AF Ain, David L. Slovut, David P. Kamath, Ravi Jaff, Michael R. TI The Association between Peripheral Artery and Lumbar Spine Disease: A Single-center Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Claudication; Peripheral artery disease; Spinal stenosis ID ANKLE-BRACHIAL INDEX; BACK-PAIN; LEG SYMPTOMS; ATHEROSCLEROSIS AB BACKGROUND: While intermittent claudication is the hallmark of symptomatic peripheral artery disease, most patients with peripheral artery disease have atypical symptoms. The presence of lumbosacral spine disease, a common cause of nonvascular lower extremity pain, may confound the diagnosis of peripheral artery disease. The goal of this study was to quantify the prevalence of severe lumbar spine degenerative disease in patients referred for lower extremity arterial studies. METHODS: All patients over age 18 years referred for segmental limb pressures and pulse volume recordings at rest and following treadmill exercise testing at a tertiary medical center accredited vascular diagnostic laboratory, who also underwent magnetic resonance imaging or computed tomography of the lumbar spine within 6 months of the arterial studies, were included in the analysis. Frequencies of peripheral artery disease and lumbar spine degenerative disease were determined, and medical records were reviewed for cardiovascular risk factors and prior vascular and spinal interventions. RESULTS: One hundred seven subjects (63 men) with a mean age of 70 years (range 35-88 years) were included in the analysis. Lumbar spine disease was present in 81 (75.7%) of the patients referred for vascular testing. The percentage of lumbar spine disease was equivalent in both patients with exercise-induced deterioration in arterial pressure and in those with a physiologic response to exercise. Compared with patients with a normal response to exercise, patients with exercise-induced peripheral artery disease had a lower resting ankle-brachial index (mean 0.79 vs 1.09, P <.001), abnormal pulse volume recordings, and were less likely to use opiate analgesics and more likely to have undergone lower extremity revascularization. CONCLUSIONS: Severe lumbar spine degenerative disease is widely prevalent in patients referred for lower extremity arterial studies. Our findings may help explain the high prevalence of atypical limb symptoms among peripheral artery disease patients. (C) 2012 Elsevier Inc. All rights reserved. The American Journal of Medicine (2012) 125, 411-415 C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. [Kamath, Ravi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ain, David L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Slovut, David P.] Montefiore Med Ctr, Dept Cardiol, Bronx, NY 10467 USA. [Slovut, David P.] Montefiore Med Ctr, Dept Endovasc & Vasc Surg, Bronx, NY 10467 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Vasc Ctr, 55 Fruit St,Gray Bigelow 800, Boston, MA 02114 USA. EM mjaff@partners.org NR 16 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 2012 VL 125 IS 4 BP 411 EP 415 DI 10.1016/j.amjmed.2011.09.008 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 916RH UT WOS:000302120400025 PM 22444105 ER PT J AU van Ryn, J Baruch, L Clemens, A AF van Ryn, Joanne Baruch, Lawrence Clemens, Andreas TI Interpretation of Point-of-care INR Results in Patients Treated with Dabigatran SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Coagulation assays; Dabigatran; Dabigatran etexilate; Direct thrombin inhibitor AB BACKGROUND: Point-of-care devices for measurement of the international normalized ratio (INR) are commonly used to monitor therapy and maintain therapeutic levels of anticoagulation in patients treated with vitamin K antagonists. Dabigatran, a new oral, reversible direct thrombin inhibitor approved for stroke prevention in patients with atrial fibrillation does not require routine coagulation monitoring. However, case reports have identified falsely elevated point-of-care INR levels in patients treated with dabigatran using one of these devices (Hemochron). This in vitro study was designed to verify this issue. METHODS: We compared INR levels in whole blood and plasma using a Hemochron Jr. Signature + point-of-care device (International Technidyne Corporation, Edison, NJ) with routine laboratory monitoring, using blood from healthy volunteers that was spiked with increasing concentrations of dabigatran. RESULTS: Prothrombin time and INR levels were increased about 2- to 4-fold with the point-of-care device compared with laboratory measures across the plasma dabigatran concentration range 50-1400 ng/mL. At plasma concentrations of dabigatran likely to be observed in patients, at a dose of 150 mg twice daily (60-275 ng/mL), whole blood point-of-care INR values increased from 1.7 to 4.0, versus 1.1 to 1.5 measured with the laboratory coagulometer. Similar differences in prothrombin time were observed in plasma samples. CONCLUSIONS: INR levels in patients taking dabigatran are substantially higher using a Hemochron Jr. point-of-care device compared with laboratory values. We discourage the use of these devices specifically, as well as the use of the INR in general, for measuring the anticoagulant effect of dabigatran. (C) 2012 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2012) 125, 417-420 C1 [van Ryn, Joanne] Boehringer Ingelheim Pharma GmbH & Co KG, Dept CardioMetabol Dis Res, D-88397 Biberach, Germany. [Baruch, Lawrence] James J Peters VA Med Ctr, Program Med, Bronx, NY USA. [Clemens, Andreas] Boehringer Ingelheim Pharma GmbH & Co KG, Global Clin Dev & Med Affairs, Ingelheim, Germany. RP van Ryn, J (reprint author), Boehringer Ingelheim Pharma GmbH & Co KG, Dept CardioMetabol Dis Res, Birkendorfer Str 65, D-88397 Biberach, Germany. EM joanne.vanryn@boehringer-ingelheim.com FU Boehringer Ingelheim FX Boehringer Ingelheim. NR 6 TC 46 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 2012 VL 125 IS 4 BP 417 EP 420 DI 10.1016/j.amjmed.2011.10.017 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 916RH UT WOS:000302120400028 PM 22306274 ER PT J AU Zile, MR Baicu, CF Stroud, RE Laer, AV Arroyo, J Mukherjee, R Jones, JA Spinale, FG AF Zile, Michael R. Baicu, Catalin F. Stroud, Robert E. An Van Laer Arroyo, Jazmine Mukherjee, Rupak Jones, Jeffrey A. Spinale, Francis G. TI Pressure overload-dependent membrane type 1-matrix metalloproteinase induction: relationship to LV remodeling and fibrosis SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hypertrophy; proteases; left ventricular ID CARDIAC-RESTRICTED OVEREXPRESSION; PRESERVED EJECTION FRACTION; FIBRILLAR COLLAGEN CONTENT; DIASTOLIC FUNCTION ROLE; MATRIX-METALLOPROTEINASE; MYOCARDIAL-INFARCTION; HEART-FAILURE; CYCLIC STRAIN; GROWTH-FACTOR; CANCER-CELLS AB Zile MR, Baicu CF, Stroud RE, Van Laer A, Arroyo J, Mukherjee R, Jones JA, Spinale FG. Pressure overload-dependent membrane type 1-matrix metalloproteinase induction: relationship to LV remodeling and fibrosis. Am J Physiol Heart Circ Physiol 302: H1429-H1437, 2012. First published January 27, 2012; doi: 10.1152/ajpheart.00580.2011.-Increased myocardial extracellular matrix collagen represents an important structural milestone during the development of left ventricular (LV) pressure overload (PO); however, the proteolytic pathways that contribute to this process are not fully understood. This study tested the hypothesis that membrane type 1-matrix metalloproteinase (MT1-MMP) is directly induced at the transcriptional level in vivo during PO and is related to changes in LV collagen content. PO was induced in vivo by transverse aortic constriction in transgenic mice containing the full length human MT1-MMP promoter region ligated to luciferase (MT1-MMP Prom mice). MT1-MMP promoter activation (luciferase expression), expression, and activity; collagen volume fraction (CVF); and left atrial dimension were measured at 1 (n = 8), 2 (n = 12), and 4 (n = 17) wk following PO. Non-PO mice (n = 10) served as controls. Luciferase expression increased by fivefold at 1 wk, fell at 2 wk, and increased again by ninefold at 4 wk of PO (P < 0.05). MT1-MMP expression and activity increased at 1 wk, fell at 2 wk, and increased again at 4 wk after PO. CVF increased at 1 wk, remained unchanged at 2 wk, and increased by threefold at 4 wk of PO (P < 0.05). There was a strong positive correlation between CVF and MT1-MMP activity (r = 0.80, P < 0.05). Left atrial dimension remained unchanged at 1 and 2 wk but increased by 25% at 4 wk of PO. When a mechanical load was applied in vitro to LV papillary muscles isolated from MT1-MMP Prom mice, increased load caused MT1-MMP promoter activation to increase by twofold and MT1-MMP expression to increase by fivefold (P < 0.05). These findings challenge the canonical belief that PO suppresses overall matrix proteolytic activity, but rather supports the concept that certain proteases, such as MT1-MMP, play a pivotal role in PO-induced matrix remodeling and fibrosis. C1 [Zile, Michael R.; Baicu, Catalin F.; An Van Laer] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Stroud, Robert E.; Arroyo, Jazmine; Mukherjee, Rupak; Jones, Jeffrey A.] Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Spinale, Francis G.] Univ S Carolina, Sch Med, Columbia, SC USA. [Spinale, Francis G.] Wm Jennings Bryan Dorn Dept Vet Affairs Med Ctr, Columbia, SC USA. RP Zile, MR (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Ashley River Towers,25 Courtenay Dr,Rm 7067, Charleston, SC 29425 USA. EM zilem@musc.edu FU National Heart, Lung, and Blood Institute [HL-057952, HL-059165, HL-095608]; Research Service of the Department of Veterans Affairs FX This work is supported by National Heart, Lung, and Blood Institute Grants HL-057952, HL-059165, and HL-095608 (to F. G. Spinale) and the Research Service of the Department of Veterans Affairs (to M. R. Zile and F. G. Spinale). NR 43 TC 27 Z9 27 U1 0 U2 3 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 APR PY 2012 VL 302 IS 7 BP H1429 EP H1437 DI 10.1152/ajpheart.00580.2011 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 919PR UT WOS:000302341000008 PM 22287584 ER PT J AU Funk, JA Schnellmann, RG AF Funk, Jason A. Schnellmann, Rick G. TI Persistent disruption of mitochondrial homeostasis after acute kidney injury SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE mitochondria; ischemia; rhabdomyolysis; proximal tubules ID ACUTE-RENAL-FAILURE; ISCHEMIA/REPERFUSION INJURY; PROXIMAL TUBULE; OXIDANT INJURY; CELL-DEATH; BIOGENESIS; RAT; DYSFUNCTION; FISSION; PATHOPHYSIOLOGY AB Funk JA, Schnellmann RG. Persistent disruption of mitochondrial homeostasis after acute kidney injury. Am J Physiol Renal Physiol 302: F853-F864, 2012. First published December 7, 2011; doi:10.1152/ajprenal.00035.2011.-While mitochondrial dysfunction is a pathological process that occurs after acute kidney injury (AKI), the state of mitochondrial homeostasis during the injury and recovery phases of AKI remains unclear. We examined markers of mitochondrial homeostasis in two nonlethal rodent AKI models. Myoglobinuric AKI was induced by glycerol injection into rats, and mice were subjected to ischemic AKI. Animals in both models had elevated serum creatinine, indicative of renal dysfunction, 24 h after injury which partially recovered over 144 h postinjury. Markers of proximal tubule function/injury, including neutrophil gelatinase-associated lipocalin and urine glucose, did not recover during this same period. The persistent pathological state was confirmed by sustained caspase 3 cleavage and evidence of tubule dilation and brush-border damage. Respiratory proteins NDUFB8, ATP synthase beta, cytochrome c oxidase subunit I (COX I), and COX IV were decreased in both injury models and did not recover by 144 h. Immunohistochemical analysis confirmed that COX IV protein was progressively lost in proximal tubules of the kidney cortex after ischemia-reperfusion (I/R). Expression of mitochondrial fission protein Drp1 was elevated after injury in both models, whereas the fusion protein Mfn2 was elevated after glycerol injury but decreased after I/R AKI. LC3-I/II expression revealed that autophagy increased in both injury models at the later time points. Markers of mitochondrial biogenesis, such as PGC-1 alpha and PRC, were elevated in both models. These findings reveal that there is persistent disruption of mitochondrial homeostasis and sustained tubular damage after AKI, even in the presence of mitochondrial recovery signals and improved glomerular filtration. C1 [Funk, Jason A.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health (NIH) [GM 084147, C06 RR-015455]; NIH/National Institute of Environmental Health Sciences [T32ES012878-05]; NIH/National Heart, Lung, and Blood Institute [T32HL007260-34]; Biomedical Laboratory of the Department of Veterans Affairs; South Carolina Clinical and Translational Research (SCTR) Institute; Medical University of South Carolina CTSA, NIH/NCRR [UL1RR029882] FX This study was supported by National Institutes of Health (NIH) Grant GM 084147, the NIH/National Institute of Environmental Health Sciences Training Program in Environmental Stress Signaling T32ES012878-05 and NIH/National Heart, Lung, and Blood Institute Training to Improve Cardiovascular Therapies T32HL007260-34, and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by NIH Grant C06 RR-015455. This publication was supported, in part, by the South Carolina Clinical and Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina CTSA, NIH/NCRR Grant UL1RR029882. NR 44 TC 52 Z9 55 U1 2 U2 4 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 APR PY 2012 VL 302 IS 7 BP F853 EP F864 DI 10.1152/ajprenal.00035.2011 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 919PC UT WOS:000302339500007 PM 22160772 ER PT J AU Lo, CS Liu, F Shi, YX Maachi, H Chenier, I Godin, N Filep, JG Ingelfinger, JR Zhang, SL Chan, JSD AF Lo, Chao-Sheng Liu, Fang Shi, Yixuan Maachi, Hasna Chenier, Isabelle Godin, Nicolas Filep, Janos G. Ingelfinger, Julie R. Zhang, Shao-Ling Chan, John S. D. TI Dual RAS blockade normalizes angiotensin-converting enzyme-2 expression and prevents hypertension and tubular apoptosis in Akita angiotensinogen-transgenic mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article ID GLOMERULOTUBULAR JUNCTION ABNORMALITIES; DIABETIC-NEPHROPATHY; GENE-EXPRESSION; KIDNEY-DISEASE; CARBOXYPEPTIDASE; OVEREXPRESSION; FIBROSIS; CATALASE; SYSTEM; ACE2 AB Lo CS, Liu F, Shi Y, Maachi H, Chenier I, Godin N, Filep JG, Ingelfinger JR, Zhang SL, Chan JSD. Dual RAS blockade normalizes angiotensin-converting enzyme-2 expression and prevents hypertension and tubular apoptosis in Akita angiotensinogen-transgenic mice. Am J Physiol Renal Physiol 302: F840-F852, 2012. First published December 28, 2011; doi:10.1152/ajprenal.00340.2011.-We investigated the effects of dual renin-angiotensin system (RAS) blockade on angiotensin-converting enzyme-2 (Ace2) expression, hypertension, and renal proximal tubular cell (RPTC) apoptosis in type 1 diabetic Akita angiotensinogen (Agt)-transgenic (Tg) mice that specifically overexpress Agt in their RPTCs. Adult (11 wk old) male Akita and Akita Agt-Tg mice were treated with two RAS blockers (ANG II receptor type 1 blocker losartan, 30 mg.kg(-1).day(-1)) and angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg.kg(-1).day(-1)) in drinking water. Same-age non-Akita littermates and Agt-Tg mice served as controls. Blood pressure, blood glucose, and albuminuria were monitored weekly. The animals were euthanized at age 16 wk. The left kidneys were processed for immunohistochemistry and apoptosis studies. Renal proximal tubules were isolated from the right kidneys to assess gene and protein expression. Urinary ANG II and ANG 1-7 were quantified by ELISA. RAS blockade normalized renal Ace2 expression and urinary ANG 1-7 levels (both of which were low in untreated Akita and Akita Agt-Tg), prevented hypertension, albuminuria, tubulointerstitial fibrosis and tubular apoptosis, and inhibited profibrotic and proapoptotic gene expression in RPTCs of Akita and Akita Agt-Tg mice compared with non-Akita controls. Our results demonstrate the effectiveness of RAS blockade in preventing intrarenal RAS activation, hypertension, and nephropathy progression in diabetes and support the important role of intrarenal Ace2 expression in modulating hypertension and renal injury in diabetes. C1 [Shi, Yixuan; Maachi, Hasna; Chenier, Isabelle; Godin, Nicolas; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, Ctr Rech, Ctr Hosp Univ Montreal CRCHUM, Hop Hotel Dieu, Montreal, PQ H2W 1T8, Canada. [Filep, Janos G.] Univ Montreal, Ctr Rech, Maisonneuve Rosemont Hosp, Montreal, PQ H2W 1T8, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Chan, JSD (reprint author), Univ Montreal, Ctr Rech, Ctr Hosp Univ Montreal CRCHUM, Hop Hotel Dieu, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU Kidney Foundation of Canada; Canadian Institutes of Health Research [MOP-84363, MOP-93650, MOP-106688, MOP-86450, MOP-12573]; National Institutes of Health [HL-48455]; Foundation of the Centre Hospitalier de L'Universite de Montreal (CHUM) FX This work was supported in part by grants from the Kidney Foundation of Canada, the Canadian Institutes of Health Research (MOP-84363, MOP-93650, and MOP-106688 to J. S. D. Chan, MOP-86450 to S.-L. Zhang, and MOP-12573 to J. G. Filetp), the National Institutes of Health (HL-48455 to J. R. Ingelfinger), and the Foundation of the Centre Hospitalier de L'Universite de Montreal (CHUM). Editorial assistance was provided by the Research Center of CHUM's Research Support Office and Ovid Da Silva. NR 47 TC 30 Z9 31 U1 0 U2 3 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 APR PY 2012 VL 302 IS 7 BP F840 EP F852 DI 10.1152/ajprenal.00340.2011 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 919PC UT WOS:000302339500006 PM 22205225 ER PT J AU Saigusa, T Reichert, R Guare, J Siroky, BJ Gooz, M Steele, S Fenton, RA Bell, PD Kolb, RJ AF Saigusa, Takamitsu Reichert, Ryan Guare, Jennifer Siroky, Brian J. Gooz, Monika Steele, Stacy Fenton, Robert A. Bell, P. Darwin Kolb, Robert J. TI Collecting duct cells that lack normal cilia have mislocalized vasopressin-2 receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporin 2; epithelial Na channel; hypertension; polycystic kidney disease ID POLYCYSTIC KIDNEY-DISEASE; EPITHELIAL NA+ CHANNEL; INTRAFLAGELLAR TRANSPORT; SUBCELLULAR-DISTRIBUTION; WATER REABSORPTION; V2 RECEPTOR; PROTEIN; EXPRESSION; GROWTH; GENE AB Saigusa T, Reichert R, Guare J, Siroky BJ, Gooz M, Steele S, Fenton RA, Bell PD, Kolb RJ. Collecting duct cells that lack normal cilia have mislocalized vasopressin-2 receptors. Am J Physiol Renal Physiol 302: F801-F808, 2012. First published December 28, 2011; doi:10.1152/ajprenal.00253.2011.-Polycystic kidney disease (PKD) is a ciliopathy characterized by renal cysts and hypertension. These changes are presumably due to altered fluid and electrolyte transport in the collecting duct (CD). This is the site where vasopressin (AVP) stimulates vasopressin-2 receptor (V2R)-mediated aquaporin-2 (AQP2) insertion into the apical membrane. Since cysts frequently occur in the CD, we studied V2R and AQP2 trafficking and function in CD cell lines with stunted and normal cilia [cilia (-), cilia (+)] derived from the orpk mouse (hypomorph of the Tg737/Ift88 gene). Interestingly, only cilia (-) cells grown on culture dishes formed domes after apical AVP treatment. This observation led to our hypothesis that V2R mislocalizes to the apical membrane in the absence of a full-length cilium. Immunofluorescence indicated that AQP2 localizes to cilia and in a subapical compartment in cilia (+) cells, but AQP2 levels were elevated in both apical and basolateral membranes in cilia (-) cells after apical AVP treatment. Western blot analysis revealed V2R and glycosylated AQP2 in biotinylated apical membranes of cilia (-) but not in cilia (+) cells. In addition, apical V2R was functional upon apical desmopressin (DDAVP) treatment by demonstrating increased cAMP, water transport, and benzamil-sensitive equivalent short-circuit current (I-sc) in cilia (-) cells but not in cilia (+) cells. Moreover, pretreatment with a PKA inhibitor abolished DDAVP stimulation of I-sc in cilia (-) cells. Thus we propose that structural or functional loss of cilia leads to abnormal trafficking of AQP2/V2R leading to enhanced salt and water absorption. Whether such apical localization contributes to enhanced fluid retention and hypertension in PKD remains to be determined. C1 [Saigusa, Takamitsu; Reichert, Ryan; Guare, Jennifer; Gooz, Monika; Steele, Stacy; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Kolb, Robert J.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Siroky, Brian J.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA. [Fenton, Robert A.] Aarhus Univ, Dept Biomed, Aarhus, Denmark. RP Bell, PD (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 173 Ashley Ave,CRI 211, Charleston, SC 29425 USA. EM bellpd@musc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [T32 DK007752, K01 DK075652, P30 DK074038, R01 DK32032]; Veterans Affairs Merit Grant; Dialysis Clinics, Inc. FX This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants T32 DK007752, K01 DK075652, P30 DK074038, and R01 DK32032, a Veterans Affairs Merit Grant, and Dialysis Clinics, Inc. NR 37 TC 16 Z9 16 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2012 VL 302 IS 7 BP F801 EP F808 DI 10.1152/ajprenal.00253.2011 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 919PC UT WOS:000302339500002 PM 22205228 ER PT J AU Linnman, C Zeidan, MA Furtak, SC Pitman, RK Quirk, GJ Milad, MR AF Linnman, Clas Zeidan, Mohamed A. Furtak, Sharon C. Pitman, Roger K. Quirk, Gregory J. Milad, Mohammed R. TI Resting Amygdala and Medial Prefrontal Metabolism Predicts Functional Activation of the Fear Extinction Circuit SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SOCIAL ANXIETY DISORDER; NETWORK CONNECTIVITY; CINGULATE CORTEX; BRAIN WORK; HUMANS; MEMORY; NEURONS; PTSD; PET AB Objective: Individual differences in a person's ability to control fear have been linked to activation in the dorsal anterior cingulate cortex, the ventromedial prefrontal cortex, and the amygdala. This study investigated whether functional variance in this network can be predicted by resting metabolism in these same regions. Method: The authors measured resting brain metabolism in healthy volunteers with positron emission tomography using [F-18]fluorodeoxyglucose. This was followed by a 2-day fear conditioning and extinction training paradigm using functional MRI to measure brain activation during fear extinction and recall. The authors used skin conductance response to index conditioned responding, and they used resting metabolism in the amygdala, the dorsal anterior cingulate cortex, and the ventromedial prefrontal cortex to predict responses during fear extinction and extinction recall. Results: During extinction training, resting amygdala metabolism positively predicted activation in the ventromeclial prefrontal cortex and negatively predicted activation in the dorsal anterior cingulate cortex. In contrast, during extinction recall, resting amygdala metabolism negatively predicted activation in the ventromedial prefrontal cortex and positively predicted activation in the dorsal anterior cingulate cortex. In addition, resting metabolism in the dorsal anterior cingulate cortex predicted fear expression (as measured by skin conductance response) during extinction recall. Conclusions: Resting brain metabolism predicted neuronal reactivity and skin conductance changes associated with the recall of the fear extinction memory. C1 [Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Milad, MR (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM milad@nmr.mgh.harvard.edu FU MicroTransponder, Inc.; NIH [K01 MH080346, R01 MH081975] FX Dr. Milad has received fees from MicroTransponder, Inc. The other authors report no financial relationships with commercial interests. Supported by NIH grants K01 MH080346 to Dr. Milad and R01 MH081975 to Drs. Quirk and Milad. NR 44 TC 44 Z9 45 U1 2 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2012 VL 169 IS 4 BP 415 EP 423 DI 10.1176/appi.ajp.2011.10121780 PG 9 WC Psychiatry SC Psychiatry GA 916PJ UT WOS:000302115400012 PM 22318762 ER PT J AU Huang, YJ Lynch, SV Wiener-Kronish, JP AF Huang, Yvonne J. Lynch, Susan V. Wiener-Kronish, Jeanine P. TI From Microbe to Microbiota: Considering Microbial Community Composition in Infections and Airway Diseases SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID CYSTIC-FIBROSIS; PSEUDOMONAS-AERUGINOSA; DIVERSITY; BACTERIA; CATALOG C1 [Huang, Yvonne J.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA. [Lynch, Susan V.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. [Wiener-Kronish, Jeanine P.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Huang, YJ (reprint author), Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [K23 HL105572] NR 16 TC 5 Z9 5 U1 0 U2 9 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2012 VL 185 IS 7 BP 691 EP 692 DI 10.1164/rccm.201111-2030ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 915QY UT WOS:000302043700001 PM 22467799 ER PT J AU Gadikota, HR Sim, JA Hosseini, A Gill, TJ Li, GA AF Gadikota, Hemanth R. Sim, Jae Ang Hosseini, Ali Gill, Thomas J. Li, Guoan TI The Relationship Between Femoral Tunnels Created by the Transtibial, Anteromedial Portal, and Outside-In Techniques and the Anterior Cruciate Ligament Footprint SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE ACL reconstruction; transtibial technique; anteromedial portal technique; outside-in technique ID ACL RECONSTRUCTION; PLACEMENT; KNEE; POSITION; TENDON AB Background: Tunnels created for reconstruction of a torn anterior cruciate ligament (ACL) are critical determinants of joint stability and clinical outcomes. There is limited objective evidence on the ability of transtibial (TT), anteromedial (AM) portal, and outside-in (OI) operative techniques in creating anatomic tunnels. Hypothesis: (1) Tibial tunnel-independent techniques can create tunnels more accurately at the anatomic ACL footprint center than the TT technique, and (2) femoral tunnel exit location of the OI and TT techniques on the lateral cortex will be significantly further away from the lateral epicondyle than the femoral tunnel exit location of the AM portal technique. Study Design: Controlled laboratory study. Methods: Eight cadaveric knee specimens with a mean age of 56 years were used in this study. A digitizing system was used to record points along the outlines of the ACL insertion area and apertures of tunnels created by the TT, AM portal, and OI techniques. The following parameters were measured from the digitized points: (1) amount of ACL, anteromedial bundle, and posterolateral bundle coverage by the tunnels; (2) relationship between the centers of the ACL and the tunnels; and (3) distance between the center of the femoral tunnel exit and the lateral epicondyle. All the recorded parameters were analyzed in 3-dimensional solid modeling software. Results: The percentage of ACL footprint coverage achieved by all 3 surgical techniques was not significantly different from one another. However, larger femoral posterolateral bundle coverage was observed in tunnels created by the AM portal and OI techniques than in the TT tunnel. In terms of anteromedial bundle coverage, no significant differences were observed between the 3 techniques. On average, 27.1% +/- 17.4% of the TT tunnel was outside the ACL footprint. This was significantly larger compared with 13.6% +/- 15.7% with the AM portal technique (P = .01) and 10.8% +/- 10.8% in the OI technique (P = .01). Centers of femoral tunnels created by the TT, AM portal, and OI techniques were located at a distance of 3.0 +/- 1.5 mm, 2.1 +/- 0.9 mm, and 1.5 +/- 1.2 mm, respectively, from the ACL footprint center. The femoral tunnel exit location of the AM portal technique on the lateral femoral cortex was closer to the lateral epicondyle than the femoral tunnel exit location of the OI and TT techniques. Conclusion: Findings of this study indicate that a larger posterolateral bundle coverage is achieved by the AM portal and OI techniques than by the TT technique. Centers of the tunnels created by the AM portal and OI techniques were closer to the native ACL footprint center than the center of the TT technique tunnel. The incidence of a posterior femoral tunnel exit relative to the lateral epicondyle is higher in the AM portal technique than in the OI and TT techniques. Clinical Relevance: For ACL reconstruction using soft tissue grafts, tibial tunnel-independent techniques can produce more anatomic tunnels than the TT technique. C1 [Gadikota, Hemanth R.; Sim, Jae Ang; Hosseini, Ali; Gill, Thomas J.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institutes of Health [R01AR055612] FX One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by the National Institutes of Health (R01AR055612). NR 27 TC 39 Z9 39 U1 0 U2 2 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 APR PY 2012 VL 40 IS 4 BP 882 EP 888 DI 10.1177/0363546511434276 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 918XO UT WOS:000302285100020 PM 22302206 ER PT J AU Bateman, BT Eikermann, M AF Bateman, Brian T. Eikermann, Matthias TI Obstructive Sleep Apnea Predicts Adverse Perioperative Outcome Evidence for an Association between Obstructive Sleep Apnea and Delirium SO ANESTHESIOLOGY LA English DT Editorial Material ID RISK; SURGERY C1 [Bateman, Brian T.; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA. [Eikermann, Matthias] Dusiburg Essen Univ, Univ Klinikum Essen, Klin Anaesthesiol & Intens Med, Essen, Germany. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA. EM meikermann@partners.org NR 13 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2012 VL 116 IS 4 BP 753 EP 755 DI 10.1097/ALN.0b013e31824b96e1 PG 3 WC Anesthesiology SC Anesthesiology GA 915BM UT WOS:000301997900003 PM 22337163 ER PT J AU Sackstein, R AF Sackstein, Robert TI Glycoengineering of HCELL, the Human Bone Marrow Homing Receptor: Sweetly Programming Cell Migration SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Multi-step paradigm; Selectin; Selectin ligand; E-selectin; L-selectin; Mesenchymal stem cell; Hematopoietic stem cell; Adoptive cell therapeutics; Step 2-bypass pathway; Glycosyltransferase-programmed stereosubstitution ID L-SELECTIN LIGAND; LEUKOCYTE ADHESION MOLECULE-1; NODE HIGH ENDOTHELIUM; HEMATOPOIETIC PROGENITOR CELLS; COLON-CARCINOMA CELLS; LYMPH-NODE; STEM-CELLS; DERMAL MICROVESSELS; ELECTRON-MICROSCOPE; MULTISTEP PARADIGM AB The successful clinical implementation of adoptive cell therapeutics, including bone marrow transplantation and other stem cell-based treatments, depends critically on the ability to deliver cells to sites where they are needed. E-selectin, an endothelial C-type lectin, binds sialofucosylated carbohydrate determinants on its pertinent ligands. This molecule is expressed in a constitutive manner on bone marrow and dermal microvascular endothelium, and inducibly on post-capillary venules at all sites of tissue injury. Engagement of E-selectin with relevant ligand(s) expressed on circulating cells mediates initial "tethering/rolling" endothelial adhesive interactions prerequisite for extravasation of blood-borne cells at any target tissue. Most mammalian cells express high levels of a transmembrane glycoprotein known as CD44. A specialized glycoform of CD44 called "Hematopoietic Cell E-/L-selectin Ligand" (HCELL) is a potent E-selectin ligand expressed on human cells. Under native conditions, HCELL expression is restricted to human hematopoietic stem/progenitor cells. We have developed a technology called "Glycosyltransferase-Programmed Stereosubstitution" (GPS) for custom-modifying CD44 glycans to create HCELL on the surface of living cells. GPS-based glycoengineering of HCELL endows cell migration to endothelial beds expressing E-selectin. Enforced HCELL expression targets human mesenchymal stem cell homing to marrow, licensing transendothelial migration without chemokine signaling via a VLA-4/VCAM-1-dependent "Step 2-bypass pathway." This review presents an historical framework of the homing receptor concept, and will describe the discovery of HCELL, its function as the bone marrow homing receptor, and how enforced expression of this molecule via chemical engineering of CD44 glycans could enable stem cell-based regenerative medicine and other adoptive cell therapeutics. C1 [Sackstein, Robert] Harvard Inst Med, Boston, MA 02115 USA. [Sackstein, Robert] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Sackstein, Robert] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sackstein, Robert] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. EM Rsackstein@rics.bwh.harvard.edu FU National Institutes of Health; National Heart Lung Blood Institute [PO1 HL107146, RO1 HL60528, RO1 HL73714]; National Cancer Institute [RO1 CA121335] FX I thank all my talented and devoted co-workers for their invaluable assistance in elucidating the structure and biology of HCELL. This study was supported by the National Institutes of Health, in particular, the National Heart Lung Blood Institute (PO1 HL107146, RO1 HL60528, RO1 HL73714) and the National Cancer Institute (RO1 CA121335). According to National Institutes of Health policies and procedures, the Brigham & Women's Hospital has assigned intellectual property rights regarding HCELL to the inventor (RS). NR 79 TC 17 Z9 18 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD APR PY 2012 VL 40 IS 4 BP 766 EP 776 DI 10.1007/s10439-011-0461-8 PG 11 WC Engineering, Biomedical SC Engineering GA 916JH UT WOS:000302097600003 PM 22068886 ER PT J AU Hartmann, AS Rief, W Hilbert, A AF Hartmann, Andrea Sabrina Rief, Winfried Hilbert, Anja TI Laboratory snack food intake, negative mood, and impulsivity in youth with ADHD symptoms and episodes of loss of control eating. Where is the missing link? SO APPETITE LA English DT Article DE Food intake; Trait impulsivity; Negative mood; Attention deficit hyperactivity disorder; Obesity; Loss of control eating ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; TEST MEAL INTAKE; BEHAVIORAL-INHIBITION; CLINICAL-SIGNIFICANCE; US CHILDREN; OBESITY; ADOLESCENTS; PREVALENCE; MODEL AB To compare laboratory food intake, negative mood and trait impulsivity and their association with attention deficit hyperactivity disorder (ADHD) and loss of control (LOC) eating in youth (middle childhood to early adolescence). Ninety 10-14 year old youths with symptoms of ADHD, symptoms of LOC eating, and control participants took part in a laboratory snack food meal after having rated trait impulsivity. Negative mood was self-reported pre and post snack food meal, while representativeness of eating behavior and liking of the food was assessed post laboratory snack food meal. The ADHD group consumed more snack food than the other groups. Food intake was not influenced by negative mood or trait impulsivity. All groups exhibited a decrease in negative mood from pre to post food intake that was not accounted for by level of hunger or liking of the food. The greater food intake of the ADHD group compared to the other groups may contribute to the development of overweight and therefore be in accordance with the high co-morbidity reported between ADHD and obesity in youth. The influence of impulsivity and negative mood on food intake could not be shown, which corroborates a recent review on the association of negative mood and bingeing in adults but needs further assessment, particularly in the younger age groups. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Hartmann, Andrea Sabrina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hartmann, Andrea Sabrina] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rief, Winfried] Univ Marburg, Marburg, Germany. [Hilbert, Anja] Univ Hosp Leipzig, Leipzig, Germany. RP Hartmann, AS (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA. EM ahartmann1@partners.org FU German Research Foundation [HI 1111/1-2, HI 1111/1-3] FX This research was supported by Grants HI 1111/1-2 and -3 from the German Research Foundation awarded to Anja Hilbert. NR 66 TC 10 Z9 10 U1 4 U2 28 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6663 J9 APPETITE JI Appetite PD APR PY 2012 VL 58 IS 2 BP 672 EP 678 DI 10.1016/j.appet.2012.01.006 PG 7 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA 913SX UT WOS:000301898800038 PM 22251461 ER PT J AU Lyman, S Oh, LS Reinhardt, KR Mandl, LA Katz, JN Levy, BA Marx, RG AF Lyman, Stephen Oh, Luke S. Reinhardt, Keith R. Mandl, Lisa A. Katz, Jeffrey N. Levy, Bruce A. Marx, Robert G. TI Surgical Decision Making for Arthroscopic Partial Meniscectomy in Patients Aged Over 40 Years SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID ORTHOPEDIC SURGEONS PERCEPTIONS; KNEE REPLACEMENT; RANDOMIZED-TRIAL; MENISCAL TEARS; OSTEOARTHRITIS; OUTCOMES; RESECTION AB Purpose: To identify clinical variables that affect a surgeon's decision to recommend arthroscopic partial meniscectomy (APM). Methods: Members of 2 orthopaedic specialty societies were invited to participate in an online survey by e-mail. The survey consisted of surgeon demographics and case scenarios to evaluate clinical decision making for APM. Posterior probabilities were calculated to determine the effect of clinical factors on the likelihood of recommending APM. Results: Of the respondents with valid e-mail addresses, 733 (19.3%) returned a completed survey, but only 533 (14.1%) met the eligibility criteria (treated or referred an APM candidate within the past year). Respondents were aged 46.7 +/- 9.4 and had performed a mean of 115 APMs in the previous year. Posterior probabilities for a combination of 6 clinical indicators identified 3 factors that most influenced a surgeon's decision to recommend APM: radiographic findings, McMurray test, and failure of nonoperative management. Conclusions: Significant variation exists among practicing orthopaedic surgeons with regard to decision making for APM. The 3 clinical factors that most influenced a surgeon's decision to recommend APM were normal radiographic findings, failed nonoperative treatment, and the presence of positive physical examination findings (i.e., positive McMurray test, joint line tenderness, and effusion). Level of Evidence: Level III, decision analysis. C1 [Lyman, Stephen; Reinhardt, Keith R.; Mandl, Lisa A.; Marx, Robert G.] Hosp Special Surg, New York, NY 10021 USA. [Oh, Luke S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Levy, Bruce A.] Mayo Clin, Coll Med, Rochester, MN USA. RP Lyman, S (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM LymanS@hss.edu OI Oh, Luke/0000-0002-6610-8204 NR 21 TC 7 Z9 7 U1 2 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD APR PY 2012 VL 28 IS 4 BP 492 EP U182 DI 10.1016/j.arthro.2011.09.004 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 916VM UT WOS:000302131300009 PM 22264828 ER PT J AU Abola, MTB Bhatt, DL Duval, S Cacoub, PP Baumgartner, I Keo, H Creager, MA Brennan, DM Steg, PG Hirsch, AT AF Abola, Maria Teresa B. Bhatt, Deepak L. Duval, Sue Cacoub, Patrice P. Baumgartner, Iris Keo, Hong Creager, Mark A. Brennan, Danielle M. Steg, Ph. Gabriel Hirsch, Alan T. CA REACH Investigators TI Fate of individuals with ischemic amputations in the REACH Registry: Three-year cardiovascular and limb-related outcomes SO ATHEROSCLEROSIS LA English DT Article DE Atherosclerosis; Peripheral artery disease; Amputation; Health outcomes; Amputation; Critical limb ischemia; Myocardial infarction ID PERIPHERAL ARTERIAL-DISEASE; LOWER-EXTREMITY AMPUTATION; DIABETES-MELLITUS; FOLLOW-UP; NONDIABETIC PATIENTS; MAJOR AMPUTATION; NATURAL-HISTORY; RISK-FACTORS; SURVIVAL; ATHEROTHROMBOSIS AB Objective: To evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes. Methods: The REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003-2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up. Results: PAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P < .001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P = .005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P <.001) and all-cause mortality (21.8% vs. 12.6%, P <.001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P <.001) were noted. Recent (= 1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level. Conclusions: Individuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of "minor" ischemic amputation may confer an identical systemic risk as "major" leg amputation. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Abola, Maria Teresa B.] Philippine Heart Ctr, Div Educ, Quezon City 1100, Philippines. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Creager, Mark A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Duval, Sue] Univ Minnesota, Sch Med, Div Cardiovasc, Lillehei Clin Res Unit, Minneapolis, MN 55455 USA. [Baumgartner, Iris] Univ Hosp Bern, Div Angiol, CH-3010 Bern, Switzerland. [Cacoub, Patrice P.] Grp Hosp Pitie Salpetriere, AP HP, Dept Internal Med, F-75634 Paris, France. [Cacoub, Patrice P.] Univ Paris 06, Paris, France. [Brennan, Danielle M.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Steg, Ph. Gabriel] INSERM, U698, Paris, France. [Steg, Ph. Gabriel] Univ Paris 07, Paris, France. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France. [Hirsch, Alan T.] Univ Minnesota, Sch Med, Vasc Med Program, Div Cardiovasc, Minneapolis, MN 55455 USA. [Keo, Hong] Kantonsspital Aarau AG, Div Angiol, CH-5001 Aarau, Switzerland. RP Abola, MTB (reprint author), Philippine Heart Ctr, Div Educ, Suite 409,4th Floor,Med Arts Bldg,East Ave, Quezon City 1100, Philippines. EM tesabola@mac.com FU AstraZeneca; Bayer; Boehringer-Ingelheim; Bristol-Myers Squibb; Daiichi-Sankyo; GSK; sanofi-aventis; Amarin; Eisai; Ethicon; Medtronic; Medicines Company; Schering Plough; Servier; Roche; Genzyme; Merck; Vasogen; Abbott Vascular; Waksman Foundation (Tokyo, Japan) FX Dr. Abola received honoraria from AstraZeneca, Bayer, Boehringer-Ingelheim, GSK, Otsuka, Servier, and sanofi-aventis, and research grants from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GSK and sanofi-aventis.; Dr Bhatt discloses the following relationships: Research grants - Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, sanofi-aventis, The Medicines Company.; Dr Cacoub has received research grants from sanofi-aventis, Schering Plough, Servier, and Roche; honoraria from sanofi-aventis, Schering Plough, Servier, Roche, AstraZeneca, and Bristol-Myers Squibb.; Dr Creager has received a research grant from Sanofi-Aventis and consulting fees from AstraZeneca, Genzyme, Merck, and Vasogen.; Dr. Hirsch has received research grants from Bristol-Myers Squibb, sanofi-aventis, and Abbott Vascular, and serves as a consultant to Roche, Cytokinetics, ev3, and Talecris.; The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The REACH Registry is endorsed by the World Heart Federation. A complete list of the REACH Registry Investigators appears in JAMA. 2006; 295: 180-9. The REACH Registry enforces a no ghostwriting policy. This manuscript was written and edited by the authors, who take full responsibility for its content. Dr. Abola wrote the first draft. We thank the Editorial Support Group for their assistance with coordinating revisions and providing editorial help in preparing this manuscript, including editing, checking content and language, formatting, referencing, and preparing tables and figures. NR 41 TC 15 Z9 15 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2012 VL 221 IS 2 BP 527 EP 535 DI 10.1016/j.atherosclerosis.2012.01.002 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 914TI UT WOS:000301974900037 PM 22321872 ER PT J AU Jacobson, CA Turki, AT McDonough, SM Steyenson, KE Kim, HT Kao, G Herrera, MI Reynolds, CG Alyea, EP Ho, VT Koreth, J Armand, P Chen, YB Ballen, K Soiffer, RJ Antin, JH Cutler, CS Ritz, J AF Jacobson, Caron A. Turki, Amin T. McDonough, Sean M. Steyenson, Kristen E. Kim, Haesook T. Kao, Grace Herrera, Maria I. Reynolds, Carol G. Alyea, Edwin P. Ho, Vincent T. Koreth, John Armand, Philippe Chen, Yi-Bin Ballen, Karen Soiffer, Robert J. Antin, Joseph H. Cutler, Corey S. Ritz, Jerome TI Immune Reconstitution after Double Umbilical Cord Blood Stem Cell Transplantation: Comparison with Unrelated Peripheral Blood Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Cord blood transplantation; Immune reconstitution ID VERSUS-HOST-DISEASE; T-CELLS; EXCESS BAFF; CHILDREN; ADULTS; HOMEOSTASIS; THYMOPOIESIS; MALIGNANCIES; ENGRAFTMENT; REPERTOIRE AB Double umbilical cord blood (DUCB) transplantation is an accepted transplantation strategy for patients without suitable human leukocyte antigen (HLA) matched donors. However, DUCB transplantation is associated with increased morbidity and mortality because of slow recovery of immunity and a high risk of infection. To define the differences in immune reconstitution between DUCB transplantation and HLA matched unrelated donor (MUD) transplantation, we performed a detailed, prospective analysis of immune reconstitution in 42 DUCB recipients and 102 filgrastim-mobilized unrelated peripheral blood stem cell recipients. Reconstitution of CD3 T cells was significantly delayed in the DUCB cohort compared with the MUD cohort for 1 to 6 months posttransplantation (P <.001), including naive (CD45RO-) and memory (CD45RO+) CD4 T cells, regulatory (CD4CD25) T cells, and CD8 T cells. In contrast, CD19 B cells recovered more rapidly in the DUCB cohort and numbers remained significantly greater from 3 to 24 months after transplantation (P =.001). CD56CD16 natural killer (NK) cells also recovered more rapidly in DUCB recipients and remained significantly greater from 1 to 24 months after transplantation. B cell activating factor (BAFF) levels were higher in the DUCB cohort at 1 month (P <.001), were similar in both cohorts at 3 and 6 months, and were lower in the DUCB cohort at 12 months (P =.002). BAFF/CD19 B cell ratios were lower in the DUCB cohort at 3 (P =.045), 6 (P =.02), and 12 months (P =.002) after transplantation. DUCB recipients had more infections within the first 100 days after transplantation (P <.001), and there was less chronic graft-versus-host disease (P <.001), but there were no differences in cumulative incidence of relapse, nonrelapse death, progression-free survival, or overall survival between the 2 groups. These results suggest that increased risk of infections is specifically associated with delayed reconstitution of all major T cell subsets, but the increased risk is limited to the first 3 months after DUCB transplantation. There is no increased risk of relapse, suggesting that graft-versus-leukemia activity is maintained. Early reconstitution of B cells and NK cells may, in part, account for these findings. Biol Blood Marrow Transplant 18: 565-574 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Jacobson, Caron A.; Turki, Amin T.; McDonough, Sean M.; Herrera, Maria I.; Reynolds, Carol G.; Alyea, Edwin P.; Ho, Vincent T.; Koreth, John; Armand, Philippe; Soiffer, Robert J.; Antin, Joseph H.; Cutler, Corey S.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. [Steyenson, Kristen E.; Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Kao, Grace] Dana Farber Canc Inst, Connell OReilly Cell Manipulat Core Facil, Boston, MA 02215 USA. [Chen, Yi-Bin; Ballen, Karen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM Jerome_Ritz@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NIH [AI29530, CA142106]; Ted and Eileen Pasquarello Research Fund; Jock and Bunny Adams Research and Education Endowment; Stem Cell Cyclists of the Pan Mass Challenge FX This research is supported by NIH Grants AI29530 and CA142106, the Ted and Eileen Pasquarello Research Fund, and the Jock and Bunny Adams Research and Education Endowment. Corey Cutler is supported by the Stem Cell Cyclists of the Pan Mass Challenge. NR 34 TC 59 Z9 60 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2012 VL 18 IS 4 BP 565 EP 574 DI 10.1016/j.bbmt.2011.08.018 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 913OM UT WOS:000301887300009 PM 21875503 ER PT J AU Blaser, BW Kim, HT Alyea, EP Ho, VT Cutler, C Armand, P Koreth, J Antin, JH Plutzky, J Soiffer, RJ AF Blaser, Bradley W. Kim, Haesook T. Alyea, Edwin P., III Ho, Vincent T. Cutler, Corey Armand, Philippe Koreth, John Antin, Joseph H. Plutzky, Jorge Soiffer, Robert J. TI Hyperlipidemia and Statin Use after Allogeneic Hematopoietic Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hyperlipidemia; Hypercholesterolemia; Hypertriglyceridemia; Statin; GVHD; Lipid ID PRIMARY BILIARY-CIRRHOSIS; VERSUS-HOST-DISEASE; REMITTING MULTIPLE-SCLEROSIS; BONE-MARROW-TRANSPLANTATION; COA REDUCTASE INHIBITION; LONG-TERM SURVIVORS; SIMVASTATIN TREATMENT; CARDIAC TRANSPLANTATION; CARDIOVASCULAR-DISEASE; HEART-TRANSPLANTATION AB An increased incidence of cardiovascular complications has been documented in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Despite this, little is known about the risk factors for hyperlipidemia or the role of lipid-lowering therapy early after transplantation. We performed a retrospective analysis of all patients who underwent allogeneic HSCT at the Dana-Farber Cancer Institute from 1998 to 2008 and who survived more than 100 days. The incidence of hypercholesterolemia and hypertriglyceridemia in the first 2 years after transplantation was 73.4% and 72.5%, respectively. In multivariable analysis, the development of acute graft-versus-host disease was independently associated with both hypercholesterolemia (odds ratio [OR] = 1.62) and hypertriglyceridemia (OR = 1.54) after transplantation. Statin use was instituted in 29% of patients and was associated with a significant net reduction in total cholesterol (65 mg/dL, P <.0001), triglyceride (118 mg/dL P <.0001), and LDL levels (59 mg/dL P <.0001) without any significant adverse effects. These data suggest that hyperlipidemia is common in the first 2 years after allogeneic transplantation when most patients remain under the care of the transplantation physician and lipid-lowering therapy may be underutilized. Given the cardiovascular risk associated with hyperlipidemia and the tolerability of statins, further prospective evaluation of lipid abnormalities and their treatment seems well warranted. Biol Blood Marrow Transplant 18: 575-583 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Kim, Haesook T.; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Blaser, Bradley W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Alyea, Edwin P., III; Ho, Vincent T.; Cutler, Corey; Armand, Philippe; Koreth, John; Antin, Joseph H.; Soiffer, Robert J.] Dana Farber Brigham & Womens Canc Ctr, Div Hematol Malignancies, Boston, MA USA. [Plutzky, Jorge] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Soiffer, RJ (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St,Dana 1B11, Boston, MA 02115 USA. EM robert_soiffer@dfci.harvard.edu FU Jock and Bunny Adams Research and Education Endowment; National Institutes of Health [CA142106] FX This work was supported by the Jock and Bunny Adams Research and Education Endowment and by the National Institutes of Health (Grant CA142106). NR 45 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2012 VL 18 IS 4 BP 575 EP 583 DI 10.1016/j.bbmt.2011.08.003 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 913OM UT WOS:000301887300010 PM 21839706 ER PT J AU Lim, TC Toh, WS Wang, LS Kurisawa, M Spector, M AF Lim, Teck Chuan Toh, Wei Seong Wang, Li-Shan Kurisawa, Motoichi Spector, Myron TI The effect of injectable gelatin-hydroxyphenylpropionic acid hydrogel matrices on the proliferation, migration, differentiation and oxidative stress resistance of adult neural stem cells SO BIOMATERIALS LA English DT Article DE Neural stem cell; Hydrogel; Oxidative stress resistance; Proliferation; Migration; Differentiation ID INJURED RAT-BRAIN; PROGENITOR CELLS; STROKE; TISSUE; REGENERATION; MODULUS; TRANSPLANTATION; REPLACEMENT; MECHANISMS; EXPRESSION AB Transplanted or endogenous neural stem cells often lack appropriate matrix in cavitary lesions in the central nervous system. In this study, gelatin-hydroxyphenylpropionic acid (Gtn-HPA), which could be enzymatically crosslinked with independent tuning of crosslinking degree and gelation rate, was explored as an injectable hydrogel for adult neural stem cells (aNSCs). The storage modulus of Gtn-HPA could be tuned (449-1717 Pa) to approximate adult brain tissue. Gtn-HPA was cytocompatible with aNSCs (yielding high viability > 93%) and promoted aNSC adhesion. Gtn-HPA demonstrated a cross-linking-based approach for preconditioning aNSCs and increased the resistance of aNSCs to oxidative stress, improving their viability from 8-15% to 84% when challenged with 500 mu M H2O2. In addition, Gtn-HPA was able to modulate proliferation and migration of aNSCs in relation to the crosslinking degree. Finally, Gtn-HPA exhibited bias for neuronal cells. In mixed differentiation conditions, Gtn-HPA increased the proportion of aNSCs expressing neuronal marker beta-tubulin III to a greater extent than that for astrocytic marker glial fibrillary acidic protein, indicating an enhancement in differentiation towards neuronal lineage. Between neuronal and astrocytic differentiation conditions, Gtn-HPA also selected for higher survival in the former. Overall, Gtn-HPA hydrogels are promising injectable matrices for supporting and influencing aNSCs in ways that may be beneficial for brain tissue regeneration after injuries. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Lim, Teck Chuan; Toh, Wei Seong; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Lim, Teck Chuan; Spector, Myron] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Toh, Wei Seong; Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Wang, Li-Shan; Kurisawa, Motoichi] Inst Bioengn & Nanotechnol, Singapore 138669, Singapore. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn Labs, Mail Stop 151 Res,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Wang, Li Shan/F-9460-2013; Toh, Wei Seong/K-7720-2013; KURISAWA, MOTOICHI/C-1325-2014 OI Toh, Wei Seong/0000-0001-9147-6423; KURISAWA, MOTOICHI/0000-0003-2413-6933 FU Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs; Agency for Science, Technology and Research, Singapore FX This work was supported by the Rehabilitation Research and Development Service of the U.S. Department of Veterans Affairs. M. Spector is a VA Research Career Scientist. T.C. Lim, W.S. Toh, L Wang and M. Kurisawa received support from the Agency for Science, Technology and Research, Singapore. The authors are grateful for the assistance of Daniel Macaya, Angela Juli Young, Marsha Doudna Guy and Chyan Ying Ke and for the aNSCs provided by UCSD. NR 48 TC 29 Z9 30 U1 3 U2 37 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD APR PY 2012 VL 33 IS 12 BP 3446 EP 3455 DI 10.1016/j.biomaterials.2012.01.037 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 913OC UT WOS:000301886300007 PM 22306021 ER PT J AU Couch, FJ Gaudet, MM Antoniou, AC Ramus, SJ Kuchenbaecker, KB Soucy, P Beesley, J Chen, XQ Wang, XS Kirchhoff, T McGuffog, L Barrowdale, D Lee, A Healey, S Sinilnikova, OM Andrulis, IL Ozcelik, H Mulligan, AM Thomassen, M Gerdes, AM Jensen, UB Skytte, AB Kruse, TA Caligo, MA von Wachenfeldt, A Barbany-Bustinza, G Loman, N Soller, M Ehrencrona, H Karlsson, P Nathanson, KL Rebbeck, TR Domchek, SM Jakubowska, A Lubinski, J Jaworska, K Durda, K Zlowocka, E Huzarski, T Byrski, T Gronwald, J Cybulski, C Gorski, B Osorio, A Duran, M Tejada, MI Benitez, J Hamann, U Hogervorst, FBL van Os, TA van Leeuwen, FE Meijers-Heijboer, HEJ Wijnen, J Blok, MJ Kets, M Hooning, MJ Oldenburg, RA Ausems, MGEM Peock, S Frost, D Ellis, SD Platte, R Fineberg, E Evans, DG Jacobs, C Eeles, RA Adlard, J Davidson, R Eccles, DM Cole, T Cook, J Paterson, J Brewer, C Douglas, F Hodgson, SV Morrison, PJ Walker, L Porteous, ME Kennedy, MJ Side, LE Bove, B Godwin, AK Stoppa-Lyonnet, D Fassy-Colcombet, M Castera, L Cornelis, F Mazoyer, S Leone, M Boutry-Kryza, N Bressac-de Paillerets, B Caron, O Pujol, P Coupier, I Delnatte, C Akloul, L Lynch, HT Snyder, CL Buys, SS Daly, MB Terry, M Chung, WK John, EM Miron, A Southey, MC Hopper, JL Goldgar, DE Singer, CF Rappaport, C Tea, MKM Fink-Retter, A Hansen, TVO Nielsen, FC Arason, A Vijai, J Shah, S Sarrel, K Robson, ME Piedmonte, M Phillips, K Basil, J Rubinstein, WS Boggess, J Wakeley, K Ewart-Toland, A Montagna, M Agata, S Imyanitov, EN Isaacs, C Janavicius, R Lazaro, C Blanco, I Feliubadalo, L Brunet, J Gayther, SA Pharoah, PPD Odunsi, KO Karlan, BY Walsh, CS Olah, E Teo, SH Ganz, PA Beattie, MS van Rensburg, EJ Dorfling, CM Diez, O Kwong, A Schmutzler, RK Wappenschmidt, B Engel, C Meindl, A Ditsch, N Arnold, N Heidemann, S Niederacher, D Preisler-Adams, S Gadzicki, D Varon-Mateeva, R Deissler, H Gehrig, A Sutter, C Kast, K Fiebig, B Heinritz, W Caldes, T de la Hoya, M Muranen, TA Nevanlinna, H Tischkowitz, M Spurdle, AB Neuhausen, SL Ding, YC Lindor, NM Fredericksen, Z Pankratz, VS Peterlongo, P Manoukian, S Peissel, B Zaffaroni, D Barile, M Bernard, L Viel, A Giannini, G Varesco, L Radice, P Greene, MH Mai, PL Easton, DF Chenevix-Trench, G Offit, K Simard, J AF Couch, Fergus J. Gaudet, Mia M. Antoniou, Antonis C. Ramus, Susan J. Kuchenbaecker, Karoline B. Soucy, Penny Beesley, Jonathan Chen, Xiaoqing Wang, Xianshu Kirchhoff, Tomas McGuffog, Lesley Barrowdale, Daniel Lee, Andrew Healey, Sue Sinilnikova, Olga M. Andrulis, Irene L. Ozcelik, Hilmi Mulligan, Anna Marie Thomassen, Mads Gerdes, Anne-Marie Jensen, Uffe Birk Skytte, Anne-Bine Kruse, Torben A. Caligo, Maria A. von Wachenfeldt, Anna Barbany-Bustinza, Gisela Loman, Niklas Soller, Maria Ehrencrona, Hans Karlsson, Per Nathanson, Katherine L. Rebbeck, Timothy R. Domchek, Susan M. Jakubowska, Ania Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Zlowocka, Elzbieta Huzarski, Tomasz Byrski, Tomasz Gronwald, Jacek Cybulski, Cezary Gorski, Bohdan Osorio, Ana Duran, Mercedes Isabel Tejada, Maria Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. van Os, Theo A. van Leeuwen, Flora E. Meijers-Heijboer, Hanne E. J. Wijnen, Juul Blok, Marinus J. Kets, Marleen Hooning, Maartje J. Oldenburg, Rogier A. Ausems, Margreet G. E. M. Peock, Susan Frost, Debra Ellis, Steve D. Platte, Radka Fineberg, Elena Evans, D. Gareth Jacobs, Chris Eeles, Rosalind A. Adlard, Julian Davidson, Rosemarie Eccles, Diana M. Cole, Trevor Cook, Jackie Paterson, Joan Brewer, Carole Douglas, Fiona Hodgson, Shirley V. Morrison, Patrick J. Walker, Lisa Porteous, Mary E. Kennedy, M. John Side, Lucy E. Bove, Betsy Godwin, Andrew K. Stoppa-Lyonnet, Dominique Fassy-Colcombet, Marion Castera, Laurent Cornelis, Francois Mazoyer, Sylvie Leone, Melanie Boutry-Kryza, Nadia Bressac-de Paillerets, Brigitte Caron, Olivier Pujol, Pascal Coupier, Isabelle Delnatte, Capucine Akloul, Linda Lynch, Henry T. Snyder, Carrie L. Buys, Saundra S. Daly, Mary B. Terry, MaryBeth Chung, Wendy K. John, Esther M. Miron, Alexander Southey, Melissa C. Hopper, John L. Goldgar, David E. Singer, Christian F. Rappaport, Christine Tea, Muy-Kheng M. Fink-Retter, Anneliese Hansen, Thomas V. O. Nielsen, Finn C. Arason, Adalgeir Vijai, Joseph Shah, Sohela Sarrel, Kara Robson, Mark E. Piedmonte, Marion Phillips, Kelly Basil, Jack Rubinstein, Wendy S. Boggess, John Wakeley, Katie Ewart-Toland, Amanda Montagna, Marco Agata, Simona Imyanitov, Evgeny N. Isaacs, Claudine Janavicius, Ramunas Lazaro, Conxi Blanco, Ignacio Feliubadalo, Lidia Brunet, Joan Gayther, Simon A. Pharoah, Paul P. D. Odunsi, Kunle O. Karlan, Beth Y. Walsh, Christine S. Olah, Edith Teo, Soo Hwang Ganz, Patricia A. Beattie, Mary S. van Rensburg, Elizabeth J. Dorfling, Cecelia M. Diez, Orland Kwong, Ava Schmutzler, Rita K. Wappenschmidt, Barbara Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Heidemann, Simone Niederacher, Dieter Preisler-Adams, Sabine Gadzicki, Dorothea Varon-Mateeva, Raymonda Deissler, Helmut Gehrig, Andrea Sutter, Christian Kast, Karin Fiebig, Britta Heinritz, Wolfram Caldes, Trinidad de la Hoya, Miguel Muranen, Taru A. Nevanlinna, Heli Tischkowitz, Marcd. Spurdle, Amanda B. Neuhausen, Susan L. Ding, Yuan Chun Lindor, Noralane M. Fredericksen, Zachary Pankratz, V. Shane Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Barile, Monica Bernard, Loris Viel, Alessandra Giannini, Giuseppe Varesco, Liliana Radice, Paolo Greene, Mark H. Mai, Phuong L. Easton, Douglas F. Chenevix-Trench, Georgia Offit, Kenneth Simard, Jacques CA OCGN SWE-BRCA HEBON EMBRACE GEMO Study Collaborators kConFab Investigators Consortium Investigators Modifiers TI Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; URIC-ACID NEPHROLITHIASIS; SUSCEPTIBILITY LOCI; TUMOR SUBTYPES; ALLELES; CONSORTIUM; RECEPTOR; DISEASE; GENE; 8Q24 AB Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 x 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 x 10(-3)). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR. C1 [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN 55905 USA. [Fredericksen, Zachary; Pankratz, V. Shane] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB2 1TN, England. [Pharoah, Paul P. D.] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England. [Paterson, Joan] Addenbrookes Hosp, E Anglian Reg Genet Serv, Dept Clin Genet, Cambridge, England. [Ramus, Susan J.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. [Karlan, Beth Y.; Walsh, Christine S.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Soucy, Penny; Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Soucy, Penny; Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Tischkowitz, Marcd.] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ H3A 2T5, Canada. [Tischkowitz, Marcd.] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ H3A 2T5, Canada. [Tischkowitz, Marcd.] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada. [Beesley, Jonathan; Chen, Xiaoqing; Healey, Sue; Spurdle, Amanda B.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet, Herston, Qld 4006, Australia. [Kirchhoff, Tomas; Vijai, Joseph; Shah, Sohela; Sarrel, Kara; Robson, Mark E.; Offit, Kenneth] Mem Sloane Kettering Canc Ctr, Clin Canc Genet Lab, New York, NY USA. [Terry, MaryBeth; Chung, Wendy K.] Columbia Univ, Dept Epidemiol, New York, NY USA. [Sinilnikova, Olga M.; Leone, Melanie; Boutry-Kryza, Nadia] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie] Univ Lyon 1, Ctr Rech Cancerol Lyon, CNRS, INSERM,UMR5286,U1052, F-69622 Villeurbanne, France. [Stoppa-Lyonnet, Dominique] Federat Natl Ctr Lutte Canc, GEMO Study Collaborators Canc Genet Network, Grp Genet & Canc, Lyon, France. [Andrulis, Irene L.] Univ Toronto, Canc Care Ontario, Mt Sinai Hosp, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna Marie] Univ Toronto, Canc Care Ontario, Mt Sinai Hosp, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna Marie] Univ Toronto, Canc Care Ontario, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Dept Lab Med, Toronto, ON M5B 1W8, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark. [Gerdes, Anne-Marie] Rigshosp, Dept Clin Genet, Copenhagen, Denmark. [Jensen, Uffe Birk] Skejby Hosp, Dept Clin Genet, Aarhus, Denmark. [Skytte, Anne-Bine] Vejle Hosp, Dept Clin Genet, Vejle, Denmark. [Caligo, Maria A.] Univ Hosp Pisa, Sect Genet Oncol, Pisa, Italy. [von Wachenfeldt, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Barbany-Bustinza, Gisela] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Loman, Niklas] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Soller, Maria] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. [Ehrencrona, Hans] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden. [Karlsson, Per] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. 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[Rubinstein, Wendy S.] Univ Chicago, Pritzker Sch Med, Dept Med, Chicago, IL 60637 USA. [Boggess, John] Univ N Carolina, Chapel Hill, NC USA. [Wakeley, Katie] S Shore Hosp, Dana Farber Brigham & Womens Canc Ctr, S Weymouth, MA USA. [Ewart-Toland, Amanda] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol, Columbus, OH 43210 USA. [Ewart-Toland, Amanda] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol & Med Genet, Columbus, OH 43210 USA. [Ewart-Toland, Amanda] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. [Montagna, Marco; Agata, Simona] Ist Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny N.] NN Petrov Inst Oncol, Oncol Mol Lab, St Petersburg, Russia. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Fisher Ctr Familial Canc Res, Washington, DC USA. [Janavicius, Ramunas] Vilnius Univ Hosp Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Vilnius, Lithuania. 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[Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany. [Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany. [Varon-Mateeva, Raymonda] Campus Virchov Klinikum, Inst Human Genet, Berlin, Germany. [Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Gehrig, Andrea] Univ Wurzburg, Inst Human Genet, Dept Med Genet, Ctr Familial Breast & Ovarian Canc, D-8700 Wurzburg, Germany. [Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Obstet & Gynaecol, D-01062 Dresden, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Muranen, Taru A.; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Muranen, Taru A.; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Biomedicum, Helsinki, Finland. [Neuhausen, Susan L.; Ding, Yuan Chun] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predicted Med, Barcelona, Spain. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predicted Med, Milan, Italy. [Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy. [Bernard, Loris] Ist Europeo Oncol, Dept Expt Oncol, Milan, Italy. [Bernard, Loris] Consortium Genom Technol Cogentech, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Unit Expt Oncol 1, Aviano, PN, Italy. [Giannini, Giuseppe] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. [Varesco, Liliana] Ist Nazl Ric Cancro IST, Dept Epidemiol Prevent & Special Funct, Unit Hereditary Canc, Genoa, Italy. [Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Couch, FJ (reprint author), Mayo Clin, Dept Lab Med & Pathol, Stabile 2-42,200 1st St SW, Rochester, MN 55905 USA. EM couch.fergus@mayo.edu RI Spurdle, Amanda/A-4978-2011; Feliubadalo, Lidia/G-4577-2016; , Ivan/D-6804-2012; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014; BYRSKI, Tomasz/I-2844-2014; Ehrencrona, Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; Kets, M./L-4429-2015; Gronwald, Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; Ditsch, Nina/F-6267-2014; Arnold, Norbert/E-3012-2010; Teo, Soo-hwang/H-2353-2014; montagna, marco/E-2225-2012; M Isabel, Tejada/E-2394-2012; Shah, Sohela/B-3137-2013; Giannini, Giuseppe/B-5672-2013; Kwong, Ava/D-8005-2013; Andrulis, Irene/E-7267-2013; Joseph, Vijai/J-9158-2013; Radice, Paolo/O-3119-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Blanco, Ignacio/D-2565-2013 OI Evans, Gareth/0000-0002-8482-5784; Spurdle, Amanda/0000-0003-1337-7897; Phillips, Kelly-Anne/0000-0002-0475-1771; Feliubadalo, Lidia/0000-0002-1736-0112; Kirchhoff, Tomas/0000-0002-9055-2364; Brunet, Joan/0000-0003-1945-3512; Nevanlinna, Heli/0000-0002-0916-2976; Jacobs, Chris/0000-0002-9557-9080; Muranen, Taru/0000-0002-5895-1808; Barrowdale, Daniel/0000-0003-1661-3939; TEJADA, Maria-Isabel/0000-0002-7334-1864; , Ivan/0000-0002-3108-058X; Eeles, Rosalind/0000-0002-3698-6241; Janavicius, Ramunas/0000-0002-3773-8485; Nathanson, Katherine/0000-0002-6740-0901; Ramus, Susan/0000-0003-0005-7798; Osorio, Ana/0000-0001-8124-3984; Ehrencrona, Hans/0000-0002-5589-3622; Gronwald, Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Rappaport-Fuerhauser, Christine/0000-0002-6820-0020; Arnold, Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; Giannini, Giuseppe/0000-0003-0299-4056; Kwong, Ava/0000-0002-6968-9489; Joseph, Vijai/0000-0002-7933-151X; Blanco, Ignacio/0000-0002-7414-7481 FU NIH [CA128978]; NCI [CA116201]; U.S. Department of Defence [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Komen Foundation for the Cure; Cancer Research UK (CR-UK) [C12292/A11174, C1287/A10118]; European Community [223175 (HEALTH-F2-2009-223175)]; Canadian Institutes of Health Research; Canadian Breast Cancer Research Alliance [019511]; Research Council of Lithuania [LIG-19/2010]; Cancer Association of South Africa (CANSA); National Cancer Institute, NIH [RFA-CA-06-503]; Breast Cancer Family Registry (BCFR); Neye Foundation; Fundacion Mutua Madrilena; Asociacion Espanola Contra el Cancer; Spanish Ministry of Science and Innovation [FIS PI08 1120]; Basque Foundation for Health Innovation and Research (BIOEF) [BIO07/CA/006]; Ministero della Salute; Ministero dell'Universita' e Ricerca [RBLAO3-BETH]; Fondazione Italiana per la Ricerca sul Cancro; Associazione Italiana per la Ricerca sulCancro [4017]; Fondazione IRCCS Istituto Nazionale Tumori; DKFZ; CR-UK [C1287/A10118, C1287/A11990]; NIHR; Royal Marsden NHS Foundation Trust; German Cancer Aid [109076]; Centre of Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association for International Cancer Research Grant [AICR-07-0454]; Association "Le cancer du sein, parlons-en!"; Familial Cancer Registry at Georgetown University (NIH/NCI) [P30-CA051008]; Cancer Genetics Network [HHSN261200744000C]; Swing Fore the Cure; Clinical Genetics Branch, DCEG; Community Oncology and Prevention Trials Program-COPTRG; Helsinki University Central Hospital; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; ZonMW [91109024]; Hungarian Research Grant [KTIA-OTKACK-80745]; Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute; Autonomous Government of Catalonia; Polish Foundation of Science; Postgraduate School of Molecular Medicine, Warsaw Medical University; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital; Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR); "Ministero della Salute" [RFPS 2006-5-341353, ACC2/R6.9]; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania; Cancer Foundation of Western Australia; NHMRC [145684, 288704, 454508]; FCCC; University of Kansas Cancer Center; Kansas Bioscience Authority Eminent Scholar Program; Jewish General Hospital; Starr Cancer Consortium; Norman and Carol Stone Cancer Research Initiative; Kate and Robert Niehaus Clinical Cancer Research Initiative; Lymphoma Foundation; Sabin Family Research Initiative; U.S. National Cancer Institute; Westat, Inc.; Russian Federation for Basic Research [10-04-92601, 10-04-92110, 11-04-00227]; Federal Agency for Science and Innovations [16.512.11.2237]; Cancer Care Ontario; U.S. National Cancer Institute, NIH under RFA [CA-06-503]; Ohio State University Comprehensive Cancer Center; Instituto Toscano Tumori grant; CARIF; University Malaya; Helen Diller Family Comprehensive Cancer Center at UCSF; Avon Foundation; Center for Translational and Policy Research in Personalized Medicine (TRANSPERS); NIH/NCI [P01 CA130818-02A1]; CRUK; American Cancer Society [SIOP-06-258-06-COUN]; [ISCIIIRETIC RD06/0020/1051]; [PI10/01422]; [PI10/31488]; [2009SGR290]; [U01CA69631]; [5U01CA113916]; [NO2-CP-11019-50]; [N02-CP-65504] FX This research was supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. This work was also supported by Cancer Research UK (CR-UK) grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175). Support was also provided by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511. A. C. Antoniou is a CR-UK Senior Cancer Research Fellow. D. F. Easton is CR-UK Principal Research Fellow. G. Chenevix-Trench6 is a NHMRC Senior Principal Research Fellow. BFBOCC was supported by the Research Council of Lithuania grant LIG-19/2010 to R. Janavicius. BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to E.J. van Rensburg. BCFR was supported by the National Cancer Institute, NIH under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center; U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). CBCS was supported by The Neye Foundation. CNIO was partially supported by Fundacion Mutua Madrilena, Asociacion Espanola Contra el Cancer, the Spanish Ministry of Science and Innovation (FIS PI08 1120), and the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006. CONSIT TEAM was supported by grants from Ministero della Salute (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro" to L. Varesco and P. Radice, and "Progetto Tumori Femminili" to P. Radice), Ministero dell'Universita' e Ricerca (RBLAO3-BETH to P. Radice), Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors" to P. Radice), Associazione Italiana per la Ricerca sulCancro (4017 to P. Pujol), and by funds from Italian citizens who allocated the 5 x 1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). The DKFZ study was supported by funds from the DKFZ. EMBRACE was supported by CR-UK Grants C1287/A10118 and C1287/A11990. D. G. Evans and Fiona Lalloo were supported by an NIHR grant to the Biomedical Research Centre, Manchester, UK. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust were supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. R. A. Eeles, Elizabeth Bancroft, and Lucia D'Mello were supported by CR-UK Grant C5047/A8385. GC-HBOC was supported by a grant of the German Cancer Aid (grant 109076) and by the Centre of Molecular Medicine Cologne (CMMC). The GEMO study was supported by the Ligue National Contre le Cancer; Association for International Cancer Research Grant (AICR-07-0454); and the Association "Le cancer du sein, parlons-en!" Award.; The Georgetown study was supported by the Familial Cancer Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure. GOG was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program-COPTRG) NCI programs. K. Phillips is the Cancer Council Victoria, Colebatch Clinical Research Fellow. HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HEBON study was supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, and the ZonMW grant 91109024. HUNBOCS was supported by the Hungarian Research Grant KTIA-OTKACK-80745. ICO was supported by Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; contract grant numbers ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488, and 2009SGR290. IHCC was supported by a Polish Foundation of Science award to K. Jaworska, a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University. ILUH was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. INHERIT was supported with J. Simard, Chairholder of the Canada Research Chair in Oncogenetics. IOVHBOCS was supported by Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), and "Ministero della Salute" ("Progetto Tumori Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9"). kConFab was supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by the NHMRC [145684, 288704, 454508]. A.-B. Skytte is supported by a NHMRC Senior Research Fellowship. A. K. Godwin was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A. K. Godwin is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor. The McGill study was supported by the Jewish General Hospital Weekend to End Breast Cancer. M. Thomassen holds a Fonds de la Recherche en Sante du Quebec clinician-scientist award. The MSKCC study was supported by the Starr Cancer Consortium, the Breast Cancer Research Foundation, the Norman and Carol Stone Cancer Research Initiative, the Kate and Robert Niehaus Clinical Cancer Research Initiative, the Lymphoma Foundation, and the Sabin Family Research Initiative. The NCI study was supported by the Intramural Research Program of the U.S. National Cancer Institute and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc. NNPIO was supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) and the Federal Agency for Science and Innovations (contract 16.512.11.2237). OCGN was supported by Cancer Care Ontario and the U.S. National Cancer Institute, NIH under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators.; OSU-CCG was supported by the Ohio State University Comprehensive Cancer Center. PBCS was supported by an Instituto Toscano Tumori grant to M. A. Caligo. SEABASS was supported by CARIF and University Malaya. The UCSF study was supported by the Helen Diller Family Comprehensive Cancer Center at UCSF, the Avon Foundation, and the Center for Translational and Policy Research in Personalized Medicine (TRANSPERS), NIH/NCI P01 CA130818-02A1. UKFOCR was supported by a project grant from CRUK to P. P. D. Pharoah. The UPENN study was supported Komen Foundation for the Cure to S. M. Domchek, the Breast Cancer Research Foundation to K. L. Nathanson, and NIH grants R01-CA083855 and R01-CA102776 to T. R. Rebbeck. WCRI was supported by the American Cancer Society Clinical Research Professorship # SIOP-06-258-06-COUN. NR 24 TC 24 Z9 24 U1 2 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2012 VL 21 IS 4 BP 645 EP 657 DI 10.1158/1055-9965.EPI-11-0888 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 918AG UT WOS:000302220600010 PM 22351618 ER PT J AU Tarique, AA Kalsy, A Arifuzzaman, M Rollins, SM Charles, RC Leung, DT Harris, JB LaRocque, RC Sheikh, A Bhuiyan, MS Saksena, R Clements, JD Calderwood, SB Qadri, F Kovac, P Ryan, ET AF Tarique, A. A. Kalsy, A. Arifuzzaman, M. Rollins, S. M. Charles, R. C. Leung, D. T. Harris, J. B. LaRocque, R. C. Sheikh, A. Bhuiyan, M. S. Saksena, R. Clements, J. D. Calderwood, S. B. Qadri, F. Kovac, P. Ryan, E. T. TI Transcutaneous Immunization with a Vibrio cholerae O1 Ogawa Synthetic Hexasaccharide Conjugate following Oral Whole-Cell Cholera Vaccination Boosts Vibriocidal Responses and Induces Protective Immunity in Mice SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HEAT-LABILE ENTEROTOXIN; INFECTION-DERIVED IMMUNITY; ADP-RIBOSYLATING EXOTOXINS; ESCHERICHIA-COLI; MUCOSAL ADJUVANTS; VECTOR STRAINS; SEROTYPE OGAWA; CVD 103-HGR; EL-TOR; TOXIN AB A shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide of Vibrio cholerae O1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) or Escherichia coli heat-labile toxin (LT) following oral priming with attenuated V. cholerae O1 vaccine strain O395-NT resulted in significant increases in serum anti-V. cholerae LPS IgG, IgM, and IgA (P < 0.01) responses as well as in anti-Ogawa (P < 0.01) and anti-Inaba (P < 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P < 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses against V. cholerae. C1 [Tarique, A. A.; Kalsy, A.; Arifuzzaman, M.; Rollins, S. M.; Charles, R. C.; Leung, D. T.; Harris, J. B.; LaRocque, R. C.; Calderwood, S. B.; Ryan, E. T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Tarique, A. A.; Arifuzzaman, M.; Sheikh, A.; Bhuiyan, M. S.; Qadri, F.] Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh. [Charles, R. C.; Leung, D. T.; LaRocque, R. C.; Calderwood, S. B.; Ryan, E. T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, J. B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Saksena, R.; Kovac, P.] NIDDK, LBC, NIH, Bethesda, MD USA. [Clements, J. D.] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA. [Calderwood, S. B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, E. T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM etryan@partners.org RI Tarique, Abdullah/M-2860-2013; Kovac, Pavol/B-8813-2008; OI Tarique, Abdullah/0000-0003-3782-345X; Kovac, Pavol/0000-0001-5044-3449; Rollins, Sean/0000-0002-3724-1989; leung, daniel/0000-0001-8401-0801 FU National Institutes of Health-NIDDK; International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b); National Institutes of Health; National Institute of Allergy & Infectious Diseases [U01 AI077883, U01 AI058935, R03 AI063079]; Fogarty International Center [D43 TW005572]; American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases [TW005572, K01 TW07409, TW07144, K08 AI089721]; Howard Hughes Medical Institute; Harvard Initiative for Global Health Postdoctoral Fellowship in Global Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health-NIDDK, the International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b) (F. Q., A. A. T.), grants from the National Institutes of Health, including the National Institute of Allergy & Infectious Diseases (U01 AI077883 [E. T. R.], U01 AI058935 [S. B. C., E. T. R.], and R03 AI063079 [F. Q.]), the Fogarty International Center Training Grant in Vaccine Development and Public Health (D43 TW005572 [A. A. T., M. A., A. S., M. S. B., F. Q., E. T. R.]), an American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases (TW005572 [D. T. L., R. C. L.]), and Career Development Awards (K01 TW07409 [J.B.H.], TW07144 [R. C. L.], and K08 AI089721 [R. C. C.]), a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute (R. C. L.), and a Harvard Initiative for Global Health Postdoctoral Fellowship in Global Infectious Diseases (D.T.L.). NR 49 TC 11 Z9 12 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD APR PY 2012 VL 19 IS 4 BP 594 EP 602 DI 10.1128/CVI.05689-11 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 917FA UT WOS:000302156700018 PM 22357651 ER PT J AU Hedrich, CM Rauen, T AF Hedrich, Christian M. Rauen, Thomas TI Epigenetic patterns in systemic sclerosis and their contribution to attenuated CD70 signaling cascades SO CLINICAL IMMUNOLOGY LA English DT Editorial Material DE CD70; TNFSF7; Systemic sclerosis; Methylation; Chromatin; T lymphocytes ID CD4+ T-CELLS; LUPUS-ERYTHEMATOSUS; DNA METHYLATION; EXPRESSION; DEMETHYLATION; DISEASE; SCLERODERMA; ACTIVATION; ARTHRITIS; RESPONSES C1 [Hedrich, Christian M.; Rauen, Thomas] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Rheumatol, Dept Med,Med Sch, Boston, MA 02215 USA. [Hedrich, Christian M.] Tech Univ Dresden, Div Pediat Rheumatol, Childrens Hosp Dresden, Univ Med Ctr Carl Gustav Carus, Dresden, Germany. [Rauen, Thomas] Rhein Westfal TH Aachen, Dept Nephrol & Clin Immunol, Aachen, Germany. RP Hedrich, CM (reprint author), Beth Israel Deaconess Med Ctr CLS 937, Div Rheumatol, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA. EM chedrich@bidmc.harvard.edu NR 24 TC 4 Z9 5 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2012 VL 143 IS 1 BP 1 EP 3 DI 10.1016/j.clim.2012.01.017 PG 3 WC Immunology SC Immunology GA 913WT UT WOS:000301908800001 PM 22386864 ER PT J AU Roane, BM Dolan, DC Bramoweth, AD Rosenthal, L Taylor, DJ AF Roane, Brandy M. Dolan, Diana C. Bramoweth, Adam D. Rosenthal, Leon Taylor, Daniel J. TI Altering Unhelpful Beliefs About Sleep with Behavioral and Cognitive Therapies SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Insomnia; DBAS; Unhelpful beliefs; Cognitive therapy; Behavior therapy; CBTi ID CLINICAL CASE SERIES; DYSFUNCTIONAL BELIEFS; INSOMNIA; METAANALYSIS; PHARMACOTHERAPY; ATTITUDES; CRITERIA; UPDATE; TRIAL AB Multi-component treatment of insomnia is widely practiced; although, the additive benefit of a cognitive therapy component to specifically target unhelpful beliefs about sleep has not been conclusively determined. A chart review study at a sleep medicine clinic of 45 insomnia patients evaluated scores on the Dysfunctional Beliefs and Attitudes Scale (DBAS-16) before, during, and after cognitive behavioral therapy for insomnia (CBTi). Treatment followed standard practice, which consisted of behavioral therapy approaches during the first half of treatment and cognitive therapy during the latter portion. DBAS-16 scores improved significantly after behavioral treatment, t(44) = 6.02, P < .001, d = .9, and improved significantly again after the cognitive component of treatment, t(19) = 7.11, P < .001, d = 1.59. A comparison of the change scores, however, demonstrated no significant difference in the effects of behavioral and cognitive therapies, t(19) = 5.1, P < .562, d = .17, which suggests that cognitive therapy did not produce a greater change compared to behavioral components. Analysis of the DBAS-16 individual items suggests that the two treatment components-behavioral and cognitive therapies-may affect unhelpful beliefs about sleep differently. These findings support the need for future research to explore the effectiveness of selecting insomnia treatment components based on individual presentation. C1 [Taylor, Daniel J.] Univ N Texas, Dept Psychol, Denton, TX 76203 USA. [Rosenthal, Leon] Sleep Med Associates Texas PA, Dallas, TX USA. [Bramoweth, Adam D.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Dolan, Diana C.] Wilford Hall USAF Med Ctr, Lackland AFB, TX USA. [Roane, Brandy M.] Brown Univ, Sleep Sci Res Lab, Providence, RI 02912 USA. [Roane, Brandy M.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA. RP Taylor, DJ (reprint author), Univ N Texas, Dept Psychol, 1155 Union Circle 311280, Denton, TX 76203 USA. EM Daniel.Taylor@unt.edu OI Bramoweth, Adam/0000-0002-3535-0292 NR 17 TC 2 Z9 2 U1 1 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2012 VL 36 IS 2 SI SI BP 129 EP 133 DI 10.1007/s10608-011-9417-4 PG 5 WC Psychology, Clinical SC Psychology GA 919GR UT WOS:000302311400003 ER PT J AU Haynes, PL Ancoli-Israel, S Walter, CM McQuaid, JR AF Haynes, Patricia L. Ancoli-Israel, Sonia Walter, Christina M. McQuaid, John R. TI Preliminary Evidence for a Relationship Between Sleep Disturbance and Global Attributional Style in Depression SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Sleep; Depression; Learned helplessness; Actigraphy ID COGNITIVE-BEHAVIORAL THERAPY; MAJOR DEPRESSION; HOPELESSNESS DEPRESSION; PSYCHIATRIC-DISORDERS; LEARNED HELPLESSNESS; WRIST ACTIVITY; INSOMNIA; SYMPTOMS; LIFE; QUESTIONNAIRE AB We hypothesized that a negative, stable, and global attributional style would mediate the relationship between sleep continuity and depression. Twenty-three currently depressed and 31 never-depressed participants completed the Attributional Styles Questionnaire and wore an actigraph during the course of 1 week. Linear and logistic regression techniques were used to calculate path coefficients to test the mediating relationship. Results indicated that a global attributional style mediated the relationship between poor sleep continuity (frequency of awakenings), delayed morning waketime, increased total time spent in bed, and depression. Reverse mediation analyses indicated that these relationships may be bidirectional. No effects were found for stable or internal attributions. These results suggest that global attributions may, in part, mediate the relationship between sleep disturbances and depression. They also provide data consistent with the hypothesis that disrupted sleep is associated with learned helplessness. Prospective studies are necessary to test the directionality of these relationships. C1 [Haynes, Patricia L.] Univ Arizona, Dept Psychiat, So Arizona VA Hlth Care Syst, Tucson, AZ 85724 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, San Diego, CA 92103 USA. [Walter, Christina M.] Arizona State Univ, So Arizona VA Hlth Care Syst, Univ Arizona, Tempe, AZ 85287 USA. [McQuaid, John R.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Haynes, PL (reprint author), Univ Arizona, Dept Psychiat, So Arizona VA Hlth Care Syst, 1501 N Campbell Ave,POB 245002, Tucson, AZ 85724 USA. EM thaynes@email.arizona.edu NR 46 TC 2 Z9 2 U1 5 U2 14 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2012 VL 36 IS 2 SI SI BP 140 EP 148 DI 10.1007/s10608-011-9416-5 PG 9 WC Psychology, Clinical SC Psychology GA 919GR UT WOS:000302311400005 ER PT J AU Yamada, K Scalea, J AF Yamada, Kazuhiko Scalea, Joseph TI Current progress in xenogeneic tolerance SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE mixed chimerism; pig-to-nonhuman primates; thymus transplantation; tolerance; xenotransplantation ID PLURIPOTENT STEM-CELLS; THYMIC LOBE TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; GENE-KNOCKOUT PIGS; LONG-TERM SURVIVAL; HUMAN T-CELLS; MINIATURE SWINE; XENOGRAFT REJECTION; NONHUMAN-PRIMATES; ALPHA-1,3-GALACTOSYLTRANSFERASE GENE AB Purpose of review The present review updates the current status of research regarding the immunologic responses of the recipient following xenotransplantation. Additionally, we present the recent progress with attempts to induce xenogeneic tolerance induction. Recent findings There continues to be great interest in xenotransplantation. Recently, descriptions of the mechanisms responsible for attempted T-cell xenogeneic tolerance in both large and small animal models have improved xenogeneic graft survivals. Additionally, the cellular signaling mechanisms, such as those involving CD39, CD44, and CD47, are proving to be highly important. Using the mixed chimerism approach to tolerance in xenogeneic model may be encouraging, especially given the recent clarification of the role for macrophage-induced phagocytosis of xenogeneic donor cells. Summary Induction of tolerance to xenogeneic antigens has been accomplished only in small animals; however, graft survivals in large animal models continue to improve. Further clarification of both the adaptive and innate immune responses to xenogeneic antigens is required for success to continue. C1 [Yamada, Kazuhiko] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Organ Transplantat Tolerance & Xenotransplantat L, Boston, MA 02129 USA. RP Yamada, K (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Organ Transplantat Tolerance & Xenotransplantat L, MGH E,Bldg 14909019,13th St, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NIAID NIH HHS [P01 AI045897, P01 AI045897-11A1] NR 70 TC 5 Z9 5 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD APR PY 2012 VL 17 IS 2 BP 168 EP 173 DI 10.1097/MOT.0b013e32835090f6 PG 6 WC Transplantation SC Transplantation GA 912LT UT WOS:000301800200007 PM 22262105 ER PT J AU Simon, MV Cole, AJ Chang, EC Buchbinder, BR Stufflebeam, SM Nozari, A Stemmer-Rachamimov, AO Eskandar, EN AF Simon, Mirela V. Cole, Andrew J. Chang, Eric C. Buchbinder, Bradley R. Stufflebeam, Steve M. Nozari, Ala Stemmer-Rachamimov, Anat O. Eskandar, Emad N. TI An intraoperative multimodal neurophysiologic approach to successful resection of precentral gyrus epileptogenic lesions SO EPILEPSIA LA English DT Article DE Electrocorticography; Motor mapping; Cortical dysplasia; Central sulcus ID FOCAL CORTICAL DYSPLASIA; MOTOR CORTEX; STIMULATION; MALFORMATIONS; ANESTHESIA; EPILEPSY; TUMORS AB Cortical dysplasias (CDs) are highly epileptogenic lesions with a good prognosis of seizure freedom, if totally resected. However, their accurate delineation and resection can be difficult, and depend on the extent of pathology and lesion location. Intraoperative neurophysiologic assessments are valuable in these situations. We present an illustrative case of intractable epilepsy where judicious use of intraoperative neurophysiologictechniques guided resection of precentral CD, under general anesthesia and in the absence of preoperative electrophysiologic mapping data. Ictal onset was accurately delineated using electrocorticography (ECoG). Phase reversal of the median somatosensory-evoked potentials (MSSEPs) localized the central sulcus (CS). Motor evoked potentials (MEPs) triggered by high-frequency monopolar anodal electrical cortical stimulation at the primary motor cortex (PMC) threshold delineated the PMC. Using this technique, PMC and the corticospinal tract (CST) were continuously monitored during resection. No changes in MEPs from the preresection baseline were seen; no residual abnormal activity was present in the postresection ECoG. The patient emerged from surgery without deficits and has been seizure free during a 10-month follow-up. Staged multimodal intraoperative neurophysiology can be used successfully under general anesthesia to guide resection of epileptogenic lesions within the precentral gyrus, as an add-on or, in certain situations, as a viable alternative to preoperative electrophysiologic mapping. C1 [Simon, Mirela V.; Cole, Andrew J.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Chang, Eric C.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, Boston, MA 02114 USA. [Buchbinder, Bradley R.; Stufflebeam, Steve M.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Nozari, Ala] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia, Sch Med, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02114 USA. RP Simon, MV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, WACC 739 G,55 Fruit St, Boston, MA 02114 USA. EM mvsimon@partners.org FU NINDS NIH HHS [R01 NS069696] NR 13 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD APR PY 2012 VL 53 IS 4 BP e75 EP e79 DI 10.1111/j.1528-1167.2011.03400.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 915ZG UT WOS:000302065600005 PM 22309192 ER PT J AU Gerits, A Ruff, CC Guipponi, O Wenderoth, N Driver, J Vanduffel, W AF Gerits, Annelies Ruff, Christian C. Guipponi, Olivier Wenderoth, Nicole Driver, Jon Vanduffel, Wim TI Response to comment on: Exp Brain Res. 2011 May 5th. Transcranial magnetic stimulation of macaque frontal eye fields decreases saccadic reaction time. Pierre Pouget PhD, Nicolas Wattiez MSc and Antoni Valero-Cabre MDPhD SO EXPERIMENTAL BRAIN RESEARCH LA English DT Editorial Material AB (not available). C1 [Gerits, Annelies; Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA USA. [Gerits, Annelies; Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gerits, Annelies; Guipponi, Olivier; Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neuro & Psychophysiol, Louvain, Belgium. [Wenderoth, Nicole] Katholieke Univ Leuven, Lab Movement Control & Neuroplast, Louvain, Belgium. [Ruff, Christian C.; Driver, Jon] UCL, Wellcome Trust Ctr Neuroimaging, London, England. [Ruff, Christian C.; Driver, Jon] UCL Inst Cognit Neurosci, London, England. [Ruff, Christian C.] Lab Social & Neural Syst Res SNS Lab, Zurich, Switzerland. RP Gerits, A (reprint author), Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA USA. EM annelies@nmr.mgh.harvard.edu RI Wenderoth, Nicole/D-7262-2015; OI Wenderoth, Nicole/0000-0002-3246-9386; Ruff, Christian/0000-0002-3964-2364 NR 3 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2012 VL 218 IS 1 BP 157 EP 158 DI 10.1007/s00221-012-3022-y PG 2 WC Neurosciences SC Neurosciences & Neurology GA 918KG UT WOS:000302247800016 PM 22311469 ER PT J AU Merfeld, DM AF Merfeld, Daniel M. TI Signal detection theory and vestibular thresholds: I. Basic theory and practical considerations (vol 210, pg 389, 2011) SO EXPERIMENTAL BRAIN RESEARCH LA English DT Correction C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Res Lab, Boston, MA 02114 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Res Lab, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2012 VL 218 IS 1 BP 159 EP 160 DI 10.1007/s00221-012-3024-9 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 918KG UT WOS:000302247800017 ER PT J AU Zimmer, SN Lemieux, ME Karia, BP Day, C Zhou, T Zhou, Q Kung, AL Suresh, U Chen, YD Kinney, MC Bishop, AJR Rebel, VI AF Zimmer, Stephanie N. Lemieux, Madeleine E. Karia, Bijal P. Day, Claudia Zhou, Ting Zhou, Qing Kung, Andrew L. Suresh, Uthra Chen, Yidong Kinney, Marsha C. Bishop, Alexander J. R. Rebel, Vivienne I. TI Mice heterozygous for CREB binding protein are hypersensitive to gamma-radiation and invariably develop myelodysplastic/myeloproliferative neoplasm SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID WORLD-HEALTH-ORGANIZATION; ROTHMUND-THOMSON SYNDROME; MYELODYSPLASTIC SYNDROME; DNA-DAMAGE; BIOLOGICAL NETWORKS; MYELOID NEOPLASMS; CBP; CELLS; P300; ACTIVATION AB Myelodysplastic syndrome is a complex family of preleukemic diseases in which hematopoietic stem cell defects lead to abnormal differentiation in one or more blood lineages. Disease progression is associated with increasing genomic instability and a large proportion of patients go on to develop acute myeloid leukemia. Primarily a disease of the elderly, it can also develop after chemotherapy. We have previously reported that CREB binding protein (Crebbp) heterozygous mice have an increased incidence of hematological malignancies, and others have shown that CREBBP is one of the genes altered by chromosomal translocations found in patients suffering from therapy-related myelodysplastic syndrome. This led us to investigate whether hematopoietic tumor development in Crebbp(+/-) mice is preceded by a myelodysplastic phase and whether we could uncover molecular mechanisms that might contribute to its development. We report here that Crebbp(+/-) mice invariably develop myelodysplastic/myeloproliferative neoplasm within 9 to 12 months of age. They are also hypersensitive to ionizing radiation and show a marked decrease in poly(ADP-ribose) polymerase-1 activity after irradiation. In addition, protein levels of XRCC1 and APEX1, key components of base excision repair machinery, are reduced in unirradiated Crebbp(+/-) cells or upon targeted knockdown of CREBBP levels. Our results provide validation of a novel myelodysplastic/myeloproliferative neoplasm mouse model and, more importantly, point to defective repair of DNA damage as a contributing factor to the pathogenesis of this currently incurable disease. (C) 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Zimmer, Stephanie N.; Karia, Bijal P.; Day, Claudia; Zhou, Ting; Zhou, Qing; Suresh, Uthra; Chen, Yidong; Bishop, Alexander J. R.; Rebel, Vivienne I.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Zimmer, Stephanie N.; Karia, Bijal P.; Zhou, Ting; Bishop, Alexander J. R.; Rebel, Vivienne I.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Lemieux, Madeleine E.; Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Lemieux, Madeleine E.; Kung, Andrew L.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Kinney, Marsha C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Rebel, VI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM rebel@uthscsa.edu OI Lemieux, Madeleine/0000-0001-6355-8691 FU Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonia, TX, USA; National Institutes of Health (NIH)/National Cancer Institute (Bethesda, MD, USA) [P30 CA054174-17]; NIH/National Center for Research Resources (Bethesda, MD, USA) [1UL1RR025767] FX This work was supported with funding from the Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonia, TX, USA (V.I.R.), National Institutes of Health (NIH)/National Cancer Institute (Bethesda, MD, USA; P30 CA054174-17 to Y.C. and the institutional flow cytometry core) and NIH/National Center for Research Resources (Bethesda, MD, USA; 1UL1RR025767 to Y.C.). NR 44 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 2012 VL 40 IS 4 BP 295 EP 306 DI 10.1016/j.exphem.2011.12.004 PG 12 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 917SG UT WOS:000302198300005 PM 22198154 ER PT J AU Desalermos, A Kourkoumpetis, TK Mylonakis, E AF Desalermos, Athanasios Kourkoumpetis, Themistoklis K. Mylonakis, Eleftherios TI Update on the epidemiology and management of cryptococcal meningitis SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Editorial Material DE amphotericin B; Cryptococcus gattii; Cryptococcus neoformans; fluconazole; flucytosine; fungal infection; HIV infection ID RECONSTITUTION INFLAMMATORY SYNDROME; ANTIRETROVIRAL THERAPY; LUMBAR PUNCTURES; VANCOUVER-ISLAND; NEOFORMANS; GATTII; PRESSURE; OUTBREAK; DISEASE; BURDEN AB Despite recent improvements in the diagnosis and treatment of cryptococcosis, cryptococcal meningitis is responsible for > 600,000 deaths/year worldwide. The aim of this work is to provide an update on the developments in its epidemiology and management. Understanding the pathogenesis of Cryptococcus has improved, and new insights for the virulence of the fungus and the host response have enabled scientists to design new ways to confront this infection. Additionally, invertebrate model hosts have greatly facilitated the research in this field. Importantly, the epidemiology of Cryptococcus gattii has continued to evolve, and the emergence of this highly virulent species in immunocompetent populations, especially in Northwestern America and British Columbia, warrants increased awareness because delayed diagnosis and inappropriate antifungal therapy is associated with high mortality. Diagnosis remains a challenge, but new techniques for early and inexpensive identification of the pathogen are under development. Management can vary, based on the patient population (HIV-seropositive, organ transplant recipients or non-transplant/non-HIV). In most patients, amphotericin B with flucytosine continues to be the most appropriate induction therapy. However, in organ transplant recipients the use of liposomal amphotericin B improves mortality compared with deoxycholate amphotericin B. Also, the combination of amphotericin B with fluconazole seems to be a reasonable alternative, while fluconazole with flucytosine is superior to fluconazole monotherapy. C1 [Desalermos, Athanasios; Kourkoumpetis, Themistoklis K.; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Div,Dept Med, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Div,Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIAID NIH HHS [AI070569] NR 26 TC 17 Z9 20 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD APR PY 2012 VL 13 IS 6 BP 783 EP 789 DI 10.1517/14656566.2012.658773 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 912YJ UT WOS:000301837600001 PM 22424297 ER PT J AU Iftimia, N Yoon, WJ Brugge, WR AF Iftimia, Nicusor Yoon, Won Jae Brugge, William R. TI Cystic lesions of the pancreas: more reliable differentiation with in situ high-resolution optical imaging? SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material DE confocal endomicroscopy; high-resolution optical imaging; optical coherence tomography; pancreatic cysts ID COHERENCE TOMOGRAPHY; EX-VIVO; DIAGNOSIS; NEOPLASMS; HISTOLOGY; BIOPSY C1 [Iftimia, Nicusor] Phys Sci Inc, Adv Microscopy & Image Guided Intervent Lab, Andover, MA 01810 USA. [Yoon, Won Jae; Brugge, William R.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02144 USA. RP Iftimia, N (reprint author), Phys Sci Inc, Adv Microscopy & Image Guided Intervent Lab, 20 New England Business Ctr, Andover, MA 01810 USA. EM iftimia@psicorp.corn NR 17 TC 1 Z9 2 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD APR PY 2012 VL 6 IS 2 BP 125 EP 127 DI 10.1586/EGH.11.96 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 915PR UT WOS:000302040400001 PM 22375515 ER PT J AU Wilson, KJ Mill, C Lambert, S Buchman, J Wilson, TR Hernandez-Gordillo, V Gallo, RM Ades, LMC Settleman, J Riese, DJ AF Wilson, Kristy J. Mill, Christopher Lambert, Sydney Buchman, Jennifer Wilson, Timothy R. Hernandez-Gordillo, Victor Gallo, Richard M. Ades, Laura M. C. Settleman, Jeffrey Riese, David J., II TI EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling SO GROWTH FACTORS LA English DT Article DE Amphiregulin; EGF; TGF alpha; EGF receptor; ligand specificity; autocrine and paracrine growth regulation ID EPIDERMAL-GROWTH-FACTOR; CBL-MEDIATED UBIQUITINYLATION; RECEPTOR TYROSINE KINASE; BREAST-CANCER CELLS; AMPHIREGULIN; DEGRADATION; ENDOCYTOSIS; ERBB4; PHOSPHORYLATION; NEUREGULIN2 AB Epidermal growth factor (EGF) family peptides are ligands for the EGF receptor (EGFR). Here, we elucidate functional differences among EGFR ligands and mechanisms underlying these distinctions. In 32D/EGFR myeloid and MCF10A breast cells, soluble amphiregulin (AR), transforming growth factor alpha (TGF alpha), neuregulin 2 beta, and epigen stimulate greater EGFR coupling to cell proliferation and DNA synthesis than do EGF, betacellulin, heparin-binding EGF-like growth factor, and epiregulin. EGF competitively antagonizes AR, indicating that its functional differences reflect dissimilar intrinsic activity at EGFR. EGF stimulates much greater phosphorylation of EGFR Tyr1045 than does AR. Moreover, the EGFR Y1045F mutation and z-cbl dominant-negative mutant of the c-cbl ubiquitin ligase potentiate the effect of EGF but not of AR. Both EGF and AR stimulate phosphorylation of EGFR Tyr992. However, the EGFR Y992F mutation and phospholipase C gamma inhibitor U73122 reduce the effect of AR much more than that of EGF. Expression of TGF alpha in 32D/EGFR cells causes greater EGFR coupling to cell proliferation than does expression of EGF. Moreover, expression of EGF in 32D/EGFR cells causes these cells to be largely refractory to stimulation with soluble EGF. Thus, EGFR ligands are functionally distinct in models of paracrine and autocrine signaling and EGFR coupling to biological responses may be specified by competition among functionally distinct EGFR ligands. C1 [Mill, Christopher; Riese, David J., II] Auburn Univ, Harrison Sch Pharm, Dept Pharmacal Sci, Auburn, AL 36849 USA. [Wilson, Kristy J.; Mill, Christopher; Lambert, Sydney; Buchman, Jennifer; Hernandez-Gordillo, Victor; Gallo, Richard M.; Ades, Laura M. C.; Riese, David J., II] Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA. [Wilson, Kristy J.; Mill, Christopher; Lambert, Sydney; Buchman, Jennifer; Hernandez-Gordillo, Victor; Gallo, Richard M.; Ades, Laura M. C.; Riese, David J., II] Purdue Univ, Ctr Canc Res, W Lafayette, IN 47907 USA. [Wilson, Kristy J.] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Wilson, Timothy R.; Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Wilson, Timothy R.; Settleman, Jeffrey] Genentech Inc, San Francisco, CA 94080 USA. RP Riese, DJ (reprint author), Auburn Univ, Harrison Sch Pharm, Dept Pharmacal Sci, 2316H Walker Bldg, Auburn, AL 36849 USA. EM driese@auburn.edu RI Wilson, Timothy/F-8210-2012 FU National Cancer Institute of the National Institutes of Health [R21CA080770, R01CA114209, R01CA115830, P30CA023168]; US Army Medical Research and Materiel Command [DAMD17-00-1-0416]; Indiana Elks Foundation; American Cancer Society [IRG-58-006]; National Institutes of Health; FIRST through Emory University [K12GM000680] FX We thank Allison Lange for minor contributions to the work described here. We acknowledge support from the National Cancer Institute of the National Institutes of Health (R21CA080770 and R01CA114209 to DJR; R01CA115830 to JS; P30CA023168 to the Purdue University Center for Cancer Research), the US Army Medical Research and Materiel Command Breast Cancer Research Program (DAMD17-00-1-0416 to DJR), the Indiana Elks Foundation (to DJR) and the American Cancer Society (IRG-58-006 to the Purdue University Center for Cancer Research). KJW was supported in part by a National Institutes of Health pre-doctoral training grant to the Purdue University interdisciplinary graduate program in Biochemistry and Molecular Biology and a FIRST post-doctoral fellowship (K12GM000680) through Emory University. NR 34 TC 42 Z9 43 U1 2 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PD APR PY 2012 VL 30 IS 2 BP 107 EP 116 DI 10.3109/08977194.2011.649918 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 915KV UT WOS:000302025100004 PM 22260327 ER PT J AU Sosa, MAG De Gasperi, R Elder, GA AF Sosa, Miguel A. Gama De Gasperi, Rita Elder, Gregory A. TI Modeling human neurodegenerative diseases in transgenic systems SO HUMAN GENETICS LA English DT Review ID ZINC-FINGER NUCLEASES; SITE-SPECIFIC RECOMBINATION; AMYLOID PRECURSOR PROTEIN; AMYOTROPHIC-LATERAL-SCLEROSIS; CAENORHABDITIS-ELEGANS MODEL; HUMAN ALPHA-SYNUCLEIN; EMBRYONIC STEM-CELLS; FRONTOTEMPORAL LOBAR DEGENERATION; INTRACYTOPLASMIC SPERM INJECTION; ASTROCYTE-SPECIFIC EXPRESSION AB Transgenic systems are widely used to study the cellular and molecular basis of human neurodegenerative diseases. A wide variety of model organisms have been utilized, including bacteria (Escherichia coli), plants (Arabidopsis thaliana), nematodes (Caenorhabditis elegans), arthropods (Drosophila melanogaster), fish (zebrafish, Danio rerio), rodents (mouse, Mus musculus and rat, Rattus norvegicus) as well as non-human primates (rhesus monkey, Macaca mulatta). These transgenic systems have enormous value for understanding the pathophysiological basis of these disorders and have, in some cases, been instrumental in the development of therapeutic approaches to treat these conditions. In this review, we discuss the most commonly used model organisms and the methodologies available for the preparation of transgenic organisms. Moreover, we provide selected examples of the use of these technologies for the preparation of transgenic animal models of neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) and discuss the application of these technologies to AD as an example of how transgenic modeling has affected the study of human neurodegenerative diseases. C1 [Sosa, Miguel A. Gama; De Gasperi, Rita] Vet Affairs Med Ctr, James J Peters Dept, Res & Dev Serv, Bronx, NY 10468 USA. [Sosa, Miguel A. Gama; De Gasperi, Rita; Elder, Gregory A.] NYU, Dept Psychiat, Mt Sinai Sch Med, New York, NY 10016 USA. [Sosa, Miguel A. Gama; De Gasperi, Rita; Elder, Gregory A.] NYU, Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. [Elder, Gregory A.] Vet Affairs Med Ctr, James J Peters Dept, Neurol Serv, Bronx, NY 10468 USA. [Elder, Gregory A.] NYU, Dept Neurol, Mt Sinai Sch Med, New York, NY 10016 USA. RP Sosa, MAG (reprint author), Vet Affairs Med Ctr, James J Peters Dept, Res & Dev Serv, 3F-20,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM miguel.gama-sosa@mssm.edu FU Alzheimer's Association [IIRG-07-57318]; Department of Veterans Affairs [1 I01 BX000342-01]; National Institute on Aging [P50 AG005138] FX Supported by the Alzheimer's Association (IIRG-07-57318), Department of Veterans Affairs (1 I01 BX000342-01) and the National Institute on Aging (P50 AG005138). NR 328 TC 45 Z9 46 U1 7 U2 65 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD APR PY 2012 VL 131 IS 4 BP 535 EP 563 DI 10.1007/s00439-011-1119-1 PG 29 WC Genetics & Heredity SC Genetics & Heredity GA 911NX UT WOS:000301725900002 ER PT J AU Zhao, Y Alonso, C Ballester, I Song, JH Chang, SY Guleng, B Arihiro, S Murray, PJ Xavier, R Kobayashi, KS Reinecker, HC AF Zhao, Yun Alonso, Carmen Ballester, Isabel Song, Joo Hye Chang, Sun Young Guleng, Bayasi Arihiro, Seiji Murray, Peter J. Xavier, Ramnik Kobayashi, Koichi S. Reinecker, Hans-Christian TI Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1 SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; NOD-like receptors; Src-kinase; tyrosine phosphorylation; innate immune regulation ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; TYROSINE KINASE; CARD15 MUTATIONS; EXCHANGE FACTOR; PROTEIN-KINASE; SRC; SUSCEPTIBILITY; INHIBITION; EXPRESSION AB Background: Genetic variants of nucleotide-binding oligomerization domain 2 (NOD2) lead to aberrant microbial recognition and can cause chronic inflammatory diseases in patients with Crohn's disease (CD). Methods: We utilized gene-specific siRNA mediated knockdown and expression of guanine nucleotide exchange factor H1 (GEF-H1) in wildtype, Rip2-, and Nod2-deficient macrophages, HCT-116 and HEK 293 cells to determine the role of GEF-H1 in NOD2 and Rip2-mediated NF kappa B- dependent induction of proinflammatory cytokine expression. Confocal microscopy was used to determine subcellular distribution of GEFH1, Rip2, and NOD2. Results: We identified GEF-H1 as an unexpected component of innate immune regulation during microbial pattern recognition by NOD2. Surprisingly, GEF-H1-mediated the activation of Rip2 during signaling by NOD2, but not in the presence of the 3020insC variant of NOD2 associated with CD. GEF-H1 functioned downstream of NOD2 as part of Rip2-containing signaling complexes and was responsible for phosphorylation of Rip2 by Src tyrosine kinase. Rip2 variants lacking the tyrosine target of GEF-H1-mediated phosphorylation were unable to mediate NF-kappa B activation in Rip2-deficient macrophages and failed to transduce NOD2 signaling. GEF-H1 is required downstream of NOD2 as part of Rip2-containing signaling complexes for the activation of innate immune responses. Conclusions: GEF-H1 connects tyrosine kinase function to NOD-like receptor signaling and is fundamental to the regulation of microbial recognition by ubiquitous innate immune mechanisms mediated by Rip2 kinase. C1 [Zhao, Yun; Alonso, Carmen; Ballester, Isabel; Song, Joo Hye; Chang, Sun Young; Guleng, Bayasi; Arihiro, Seiji; Xavier, Ramnik; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Zhao, Yun; Alonso, Carmen; Ballester, Isabel; Song, Joo Hye; Chang, Sun Young; Guleng, Bayasi; Arihiro, Seiji; Xavier, Ramnik; Reinecker, Hans-Christian] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Murray, Peter J.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA. [Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, 55 Fruit St,GRJ 711, Boston, MA 02114 USA. EM hans-christian_reinecker@hms.havard.edu RI Alonso-Cotoner, Carmen/N-7057-2014 OI Alonso-Cotoner, Carmen/0000-0002-3483-2919 FU National Institutes of Health [DK068181, DK033506, DK043351, DK074738]; Spanish Gastroenterological Association; American Gastroenterological Associations; Ministry of Science and Innovation of Spain FX Supported by grants DK068181 (to H.C.R.), DK033506 (to H.C.R.), DK043351 (to H.C.R., R.X.), and DK074738 (K.S.K.) from the National Institutes of Health. C.A. was supported by a postdoctoral fellowship from the Spanish Gastroenterological Association and the American Gastroenterological Associations (Jon Isenberg International Scholar Award). I.B. was supported by a postdoctoral fellowship from the Ministry of Science and Innovation of Spain. NR 43 TC 14 Z9 20 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD APR PY 2012 VL 18 IS 4 BP 603 EP 612 DI 10.1002/ibd.21851 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 910PV UT WOS:000301652700003 PM 21887730 ER PT J AU Volpicelli, G Elbarbary, M Blaivas, M Lichtenstein, DA Mathis, G Kirkpatrick, AW Melniker, L Gargani, L Noble, VE Via, G Dean, A Tsung, JW Soldati, G Copetti, R Bouhemad, B Reissig, A Agricola, E Rouby, JJ Arbelot, C Liteplo, A Sargsyan, A Silva, F Hoppmann, R Breitkreutz, R Seibel, A Neri, L Storti, E Petrovic, T AF Volpicelli, Giovanni Elbarbary, Mahmoud Blaivas, Michael Lichtenstein, Daniel A. Mathis, Gebhard Kirkpatrick, Andrew W. Melniker, Lawrence Gargani, Luna Noble, Vicki E. Via, Gabriele Dean, Anthony Tsung, James W. Soldati, Gino Copetti, Roberto Bouhemad, Belaid Reissig, Angelika Agricola, Eustachio Rouby, Jean-Jacques Arbelot, Charlotte Liteplo, Andrew Sargsyan, Ashot Silva, Fernando Hoppmann, Richard Breitkreutz, Raoul Seibel, Armin Neri, Luca Storti, Enrico Petrovic, Tomislav CA ILC-LUS ICC-LUS TI International evidence-based recommendations for point-of-care lung ultrasound SO INTENSIVE CARE MEDICINE LA English DT Article DE Lung ultrasound; Chest sonography; Emergency ultrasound; Critical ultrasound; Point-of-care ultrasound; Guideline; RAND; GRADE; Evidence-based medicine ID RESPIRATORY-DISTRESS-SYNDROME; ALVEOLAR-INTERSTITIAL SYNDROME; MALIGNANT PLEURAL EFFUSION; SONOGRAPHIC B-LINES; CHEST RADIOGRAPHY; TRAUMATIC PNEUMOTHORAX; THORACIC ULTRASOUND; BEDSIDE ULTRASOUND; PULMONARY-EDEMA; CRITICALLY-ILL AB The purpose of this study is to provide evidence-based and expert consensus recommendations for lung ultrasound with focus on emergency and critical care settings. A multidisciplinary panel of 28 experts from eight countries was involved. Literature was reviewed from January 1966 to June 2011. Consensus members searched multiple databases including Pubmed, Medline, OVID, Embase, and others. The process used to develop these evidence-based recommendations involved two phases: determining the level of quality of evidence and developing the recommendation. The quality of evidence is assessed by the grading of recommendation, assessment, development, and evaluation (GRADE) method. However, the GRADE system does not enforce a specific method on how the panel should reach decisions during the consensus process. Our methodology committee decided to utilize the RAND appropriateness method for panel judgment and decisions/consensus. Seventy-three proposed statements were examined and discussed in three conferences held in Bologna, Pisa, and Rome. Each conference included two rounds of face-to-face modified Delphi technique. Anonymous panel voting followed each round. The panel did not reach an agreement and therefore did not adopt any recommendations for six statements. Weak/conditional recommendations were made for 2 statements, and strong recommendations were made for the remaining 65 statements. The statements were then recategorized and grouped to their current format. Internal and external peer-review processes took place before submission of the recommendations. Updates will occur at least every 4 years or whenever significant major changes in evidence appear. This document reflects the overall results of the first consensus conference on "point-of-care" lung ultrasound. Statements were discussed and elaborated by experts who published the vast majority of papers on clinical use of lung ultrasound in the last 20 years. Recommendations were produced to guide implementation, development, and standardization of lung ultrasound in all relevant settings. C1 [Volpicelli, Giovanni] San Luigi Gonzaga Univ Hosp, Dept Emergency Med, I-10043 Turin, Italy. [Elbarbary, Mahmoud] King Saud Univ Hlth Sci, Natl & Gulf Ctr Evidence Based Hlth Practice, Riyadh, Saudi Arabia. [Blaivas, Michael] Northside Hosp Forsyth, Dept Emergency Med, Atlanta, GA USA. [Lichtenstein, Daniel A.] Hop Ambroise Pare, Serv Reanimat Med, Boulogne, France. [Kirkpatrick, Andrew W.] Foothills Med Ctr, Calgary, AB, Canada. [Melniker, Lawrence] Cornell Univ, Weill Med Coll, Dept Med, Clin Epidemiol Unit,Div Gen Internal Med, New York, NY 10021 USA. [Gargani, Luna] CNR, Inst Clin Physiol, Pisa, Italy. [Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Ultrasound, Boston, MA 02114 USA. [Via, Gabriele] IRCCS Fdn Policlin San Matteo, Dept Anesthesia & Intens Care Pavia 1, Pavia, Italy. [Dean, Anthony] Univ Penn, Med Ctr, Dept Emergency Med, Div Emergency Ultrasonog, Philadelphia, PA 19104 USA. [Tsung, James W.] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Tsung, James W.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Soldati, Gino] Valle Serchio Gen Hosp, Emergency Med Unit, Lucca, Italy. [Copetti, Roberto] Latisana Hosp, Dept Med, Udine, Italy. [Bouhemad, Belaid] Grp Hosp Paris St Joseph, Dept Anesthesia & Crit Care, Surg Intens Care Unit, Paris, France. [Reissig, Angelika] Univ Jena, Med Univ Clin 1, Dept Pneumol & Allergol, Jena, Germany. [Agricola, Eustachio] Ist Sci San Raffaele, IRCCS, Div Noninvas Cardiol, I-20132 Milan, Italy. [Rouby, Jean-Jacques; Arbelot, Charlotte] Univ Paris 06, Pitie Salpetriere Hosp, Dept Anesthesiol, Multidisciplinary Intens Care Unit, Paris 6, France. [Sargsyan, Ashot] Wyle NASA Lyndon B Johnson Space Ctr Bioastronaut, Houston, TX USA. [Silva, Fernando] UC Davis Med Ctr, Dept Emergency Med, Sacramento, CA USA. [Hoppmann, Richard] Univ S Carolina, Sch Med, Columbia, SC USA. [Breitkreutz, Raoul] Univ Hosp Saarland, Dept Anaesthesiol Intens Care & Pain Therapy, Homburg, Germany. [Breitkreutz, Raoul] Frankfurt Inst Emergency Med & Simulat Training F, Homburg, Germany. [Seibel, Armin] Diakonie Klinikum Jung Stilling, Siegen, Germany. [Neri, Luca] AREU EMS Publ Reg Co, Niguarda Ca Granda Hosp, Milan, Italy. [Storti, Enrico] Osped Niguarda Ca Granda, Intens Care Unit G Bozza, Milan, Italy. [Petrovic, Tomislav] Univ Hosp Avicenne, Bobigny, France. RP Volpicelli, G (reprint author), San Luigi Gonzaga Univ Hosp, Dept Emergency Med, I-10043 Turin, Italy. EM gio.volpicelli@tin.it; mahmoud_barbary@yahoo.com; mike@blaivas.org; dlicht@free.fr; gebhard.mathis@cable.vol.at; andrew.kirkpatrick@albertahealthservices.ca; lawrence.melniker@winfocus.org; gargani@ifc.cnr.it; vnoble@partners.org; gabriele.via@winfocus.org; anthony.dean@uphs.upenn.edu; jtsung@gmail.com; g.soldati@usl2.toscana.it; robcopet@tin.it; belaid_bouhemad@hotmail.com; Angelika.Reissig@med.uni-jena.de; agricola.eustachio@hsr.it; jjrouby@invivo.edu; charlotte.arbelot@psl.aphp.fr; aliteplo@partners.org; ashot.sargsyan@nasa.gov; fernando.silva@winfocus.org; Richard.hoppmann@uscmed.sc.edu; raoul.breitkreutz@gmail.com; arminseibel1@hotmail.com; luca.neri@winfocus.org; enrico.storti@winfocus.org; tomislav.petrovic@winfocus.org RI Gargani, Luna/C-6187-2015 OI Tsung, James/0000-0002-4718-8325; Gargani, Luna/0000-0002-0716-453X NR 80 TC 391 Z9 423 U1 5 U2 37 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2012 VL 38 IS 4 BP 577 EP 591 DI 10.1007/s00134-012-2513-4 PG 15 WC Critical Care Medicine SC General & Internal Medicine GA 912EQ UT WOS:000301777900005 PM 22392031 ER PT J AU Iovieno, N Tedeschini, E Levkovitz, Y Ameral, VE Papakostas, GI AF Iovieno, Nadia Tedeschini, Enrico Levkovitz, Yeciel Ameral, Victoria E. Papakostas, George I. TI Does the frequency of follow-up assessments affect clinical trial outcome? A meta-analysis and meta-regression of placebo-controlled randomized trials SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Antidepressants; assessments; clinical trials; major depressive disorder ID DIAGNOSTIC CRITERIA; MAJOR DEPRESSION; RATING-SCALE; DOUBLE-BLIND; RUN-IN; ANTIDEPRESSANT; DISORDERS; EFFICACY; DESIGN AB The number and temporal distribution of follow-up assessments during a clinical trial is a critical factor which may influence the outcome as well as the overall cost of a trial. Therefore, we aimed to examine whether the overall and differential frequency of study observations during the course of a clinical trial affects the risk ratio (RR) of responding to antidepressants vs. placebo, specifically in trials for major depressive disorder (MDD). Medline/Pubmed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for adults with MDD (1 January 1980-11 May 2010). A total of 142 manuscripts involving 256 drug-placebo comparison were pooled (n=38 860). We found that higher overall frequency (OF, frequency of assessments during the entire trial) and higher late frequency (LF, frequency of assessments after the first 3 wk of the trial), but not higher early frequency (EF, frequency of assessments during the first 3 wk of the trial), of follow-up visits predicted a significantly greater RR of responding to antidepressant vs. placebo (coefficient=0.213, p=0.014; coefficient=0.238, p=0.003; and coefficient=0.021, p=0.755, respectively, for OF, LF and EF). None of the measures of frequency examined (OF, EF, LF) significantly predicted the RR of discontinuing antidepressant vs. placebo. These findings suggest that increasing the number of follow-up visits, specifically after the third week rather than within the first 3 wk of the trial, may be an effective approach to improve the likelihood of success in placebo-controlled clinical trials for MDD. C1 [Tedeschini, Enrico] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Iovieno, Nadia; Tedeschini, Enrico; Levkovitz, Yeciel; Ameral, Victoria E.; Papakostas, George I.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tedeschini, Enrico] Univ Modena & Reggio Emilia, Modena, Italy. [Levkovitz, Yeciel] Tel Aviv Univ, Emot Cognit Res Ctr, Shalvata Mental Hlth Ctr, Tel Aviv, Israel. [Levkovitz, Yeciel] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. RP Tedeschini, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM etedeschini@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Bristol-Myers Squibb Company; Forest Pharmaceuticals; National Institute of Mental Health; PAMLAB LLC; Pfizer Inc.; Ridge Diagnostics FX Dr Papakostas has served as a consultant for Abbott Laboratories, AstraZeneca plc, Brainsway Ltd, Bristol-Myers Squibb Company, Cephalon Inc., Eli Lilly Co., GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc., Pierre Fabre Laboratories, Ridge Diagnostics (formerly known as Precision Human Biolaboratories), Shire Pharmaceuticals, and Wyeth Inc. He has received honoraria from Abbott Laboratories, Astra Zeneca plc, Bristol-Myers Squibb Company, Brainsway Ltd, Cephalon Inc., Eli Lilly Co., Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Ridge Diagnostics, Shire Pharmaceuticals, Titan Pharmaceuticals, and Wyeth Inc. Dr Papakostas has received research support from Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer Inc., and Ridge Diagnostics, and has served (not currently) on the speakers' bureaux for Bristol-Myers Squibb Co. and Pfizer Inc. NR 23 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD APR PY 2012 VL 15 IS 3 BP 289 EP 296 DI 10.1017/S1461145711000666 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915JQ UT WOS:000302020900001 PM 21557881 ER PT J AU Kradin, RL AF Kradin, Richard L. TI When ancestral heritage is a source of discomfort: culture, pre-object relatedness, and self-alienation SO JOURNAL OF ANALYTICAL PSYCHOLOGY LA English DT Article DE ancestral heritage; dominant culture; pre-object relatedness; self-alienation AB The ancestral claims on an individual can evoke mental conflict when they involve separating from an ethnic group whose beliefs and customs are devalued by the dominant culture. However, these claims are engraved on the psyche early in development by caretakers to the level of pre-object relatedness, where contents and affect tones are implicit and may be unavailable for later psychoanalytical interventions. In addition, as the anthropologist Clifford Geertz notes, one's culture of origin precedes the development of psyche and creates its own set of claims that must be renegotiated when one encounters a different domain of cultural symbols, a confrontation that can produce psychological dissonance and self-alienation. In this paper, three cases are examined in which mental conflicts were evoked by attempts at divesting ancestral claims in response to conscious efforts to assimilate into the dominant culture. These patients suffered from separation guilt and unstable self-esteem and reported dream imagery suggesting psychological imbalance. The requirement to carefully delineate the ancestral claims on psyche as well as those contents and affects that may not be accessible to therapeutic intervention is emphasized, and the importance of compromise and acceptance with respect to the psychological demands of the unconscious are considered. C1 [Kradin, Richard L.] Massachusetts Gen Hosp MGH, Boston, MA 02114 USA. [Kradin, Richard L.] MGH Ctr Psychoanalyt Studies, Boston, MA USA. [Kradin, Richard L.] Harvard Univ, Sch Med, Boston, MA USA. [Kradin, Richard L.] CG Jung Inst, Boston, MA USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp MGH, Boston, MA 02114 USA. EM rkradin@partners.com NR 18 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8774 J9 J ANAL PSYCHOL JI J. Anal. Psychol. PD APR PY 2012 VL 57 IS 2 BP 207 EP 222 DI 10.1111/j.1468-5922.2011.01962.x PG 16 WC Psychology, Psychoanalysis SC Psychology GA 914CD UT WOS:000301925400004 PM 22444356 ER PT J AU Sung, SC Porter, E Robinaugh, DJ Marks, EH Marques, LM Otto, MW Pollack, MH Simon, NM AF Sung, Sharon C. Porter, Eliora Robinaugh, Donald J. Marks, Elizabeth H. Marques, Luana M. Otto, Michael W. Pollack, Mark H. Simon, Naomi M. TI Mood regulation and quality of life in social anxiety disorder: An examination of generalized expectancies for negative mood regulation SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Social anxiety disorder; Social phobia; Emotion regulation; Generalized expectancies for mood regulation ID COGNITIVE-BEHAVIORAL THERAPY; EMOTION REGULATION; COLLEGE-STUDENTS; SATISFACTION QUESTIONNAIRE; PANIC DISORDER; PHOBIA; DYSREGULATION; DEPRESSION; DISTRESS; DIFFICULTIES AB The present study examined negative mood regulation expectancies, anxiety symptom severity, and quality of life in a sample of 167 patients with social anxiety disorder (SAD) and 165 healthy controls with no DSM-IV Axis I disorders. Participants completed the Generalized Expectancies for Negative Mood Regulation Scale (NMR), the Beck Anxiety Inventory, and the Quality of Life Enjoyment and Satisfaction Questionnaire. SAD symptom severity was assessed using the Liebowitz Social Anxiety Scale. Individuals with SAD scored significantly lower than controls on the NMR. Among SAD participants, NMR scores were negatively correlated with anxiety symptoms and SAD severity, and positively correlated with quality of life. NMR expectancies positively predicted quality of life even after controlling for demographic variables, comorbid diagnoses, anxiety symptoms, and SAD severity. Individuals with SAD may be less likely to engage in emotion regulating strategies due to negative beliefs regarding their effectiveness, thereby contributing to poorer quality of life. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Sung, Sharon C.; Porter, Eliora; Robinaugh, Donald J.; Marks, Elizabeth H.; Marques, Luana M.; Pollack, Mark H.; Simon, Naomi M.] Harvard Univ, Sch Med, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Otto, Michael W.] Boston Univ, Translat Res Program, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. RP Sung, SC (reprint author), Duke NUS Grad Med Sch Singapore, Off Clin Sci, 8 Coll Rd, Singapore 169857, Singapore. EM sharon.sung@duke-nus.edu.sg FU NIDA NIH HHS [DA017904, R01 DA017904]; NIMH NIH HHS [K23 MH096029] NR 52 TC 12 Z9 12 U1 4 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD APR PY 2012 VL 26 IS 3 BP 435 EP 441 DI 10.1016/j.janxdis.2012.01.004 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 913VZ UT WOS:000301906800008 PM 22343166 ER PT J AU Frias-Lopez, J Duran-Pinedo, A AF Frias-Lopez, Jorge Duran-Pinedo, Ana TI Effect of Periodontal Pathogens on the Metatranscriptome of a Healthy Multispecies Biofilm Model SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GENE SET ENRICHMENT; ORAL MICROBIAL COMMUNITIES; PHOSPHOENOLPYRUVATE PHOSPHOTRANSFERASE SYSTEM; PORPHYROMONAS-GINGIVALIS; STREPTOCOCCUS-MUTANS; BACTERIAL DIVERSITY; ESCHERICHIA-COLI; ACTINOMYCES-VISCOSUS; SUBGINGIVAL PLAQUE; UNITED-STATES AB Oral bacterial biofilms are highly complex microbial communities with up to 700 different bacterial taxa. We report here the use of metatranscriptomic analysis to study patterns of community gene expression in a multispecies biofilm model composed of species found in healthy oral biofilms ( Actinomyces naeslundii, Lactobacillus casei, Streptococcus mitis, Veillonella parvula, and Fusobacterium nucleatum) and the same biofilm plus the periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The presence of the periodontopathogens altered patterns in gene expression, and data indicate that transcription of protein-encoding genes and small noncoding RNAs is stimulated. In the healthy biofilm hypothetical proteins, transporters and transcriptional regulators were upregulated while chaperones and cell division proteins were downregulated. However, when the pathogens were present, chaperones were highly upregulated, probably due to increased levels of stress. We also observed a significant upregulation of ABC transport systems and putative transposases. Changes in Clusters of Orthologous Groups functional categories as well as gene set enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that in the absence of pathogens, only sets of proteins related to transport and secondary metabolism were upregulated, while in the presence of pathogens, proteins related to growth and division as well as a large portion of transcription factors were upregulated. Finally, we identified several small noncoding RNAs whose predicted targets were genes differentially expressed in the open reading frame libraries. These results show the importance of pathogens controlling gene expression of a healthy oral community and the usefulness of metatranscriptomic techniques to study gene expression profiles in complex microbial community models. C1 [Frias-Lopez, Jorge] Forsyth Inst, Cambridge, MA USA. [Duran-Pinedo, Ana] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Frias-Lopez, J (reprint author), Forsyth Inst, Cambridge, MA USA. EM jfrias@forsyth.org FU Colgate Palmolive Company FX This work was supported by a grant from the Colgate Palmolive Company. NR 83 TC 32 Z9 32 U1 0 U2 29 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2012 VL 194 IS 8 BP 2082 EP 2095 DI 10.1128/JB.06328-11 PG 14 WC Microbiology SC Microbiology GA 917MC UT WOS:000302180200026 PM 22328675 ER PT J AU Gros, DF Simms, LJ Antony, MM McCabe, RE AF Gros, Daniel F. Simms, Leonard J. Antony, Martin M. McCabe, Randi E. TI Development and Psychometric Evaluation of the Multidimensional Assessment of Social Anxiety (MASA) SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE social anxiety; social phobia; hybrid model; Multidimensional Assessment of Social Anxiety; MASA ID DIMENSIONAL CLASSIFICATION-SYSTEM; DSM-IV ANXIETY; SPECIAL SECTION; PARADIGM SHIFT; MOOD DISORDERS; FIT INDEXES; PHOBIA; PSYCHOPATHOLOGY; INVENTORY; SCALE AB Objective: Hybrid models of psychopathology propose to combine the current categorical diagnostic system with shared symptom dimensions common across various disorders. Recently, the first empirically derived hybrid model of social anxiety was developed, including both a specific factor for the diagnostic category of social anxiety and 5 nonspecific factors for related symptoms. The present investigation developed a self-report measure-the Multidimensional Assessment of Social Anxiety (MASA)-based on this model to further the research on hybrid models. Method: This investigation included three studies across large undergraduate (N = 411; 52.3% male; mean [M] age = 19.6) and clinical (N = 684; 61.4% female; M age = 35.8) samples, involving the administration of the MASA item pool and existing measures of related constructs. Results: Through a series of psychometric evaluations, the initial 466-item pool was reduced to a final 38-item measure that represented 6 distinct scales with adequate model fit, internal consistency, test-retest reliability, and convergent and discriminant validity. Conclusions: Together, these studies likely will lead to additional research and advances in the development of the hybrid models of the mood and anxiety disorders through the dissemination and administration of the MASA. (C) 2012 Wiley Periodicals, Inc. J. Clin. Psychol. 68: 432-447, 2012. C1 [Gros, Daniel F.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Simms, Leonard J.] SUNY Buffalo, Buffalo, NY 14260 USA. [Antony, Martin M.] Ryerson Univ, Toronto, ON, Canada. [McCabe, Randi E.] McMaster Univ, Anxiety Treatment & Res Ctr, Hamilton, ON L8S 4L8, Canada. RP Gros, DF (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu RI Antony, Martin/K-1991-2012 OI Antony, Martin/0000-0002-3508-377X NR 41 TC 13 Z9 13 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD APR PY 2012 VL 68 IS 4 BP 432 EP 447 DI 10.1002/jclp.21838 PG 16 WC Psychology, Clinical SC Psychology GA 916CD UT WOS:000302073400007 PM 24469929 ER PT J AU Purcell, P Jheon, A Vivero, MP Rahimi, H Joo, A Klein, OD AF Purcell, P. Jheon, A. Vivero, M. P. Rahimi, H. Joo, A. Klein, O. D. TI Spry1 and Spry2 Are Essential for Development of the Temporomandibular Joint SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE TMJ; condyle; disc; glenoid fossa; temporalis; pterygoid; bone ID CRANIOFACIAL DEVELOPMENT; CRE RECOMBINASE; EXPRESSION; DEFECTS; GROWTH; ROLES; SPROUTY2; CONDYLE; MOUSE; CELLS AB The temporomandibular joint (TMJ) is a specialized synovial joint essential for the function of the mammalian jaw. The main components of the TMJ are the mandibular condyle, the glenoid fossa of the temporal bone, and a fibrocartilagenous disc interposed between them. The genetic program for the development of the TMJ remains poorly understood. Here we show the crucial role of sprouty (Spry) genes in TMJ development. Sprouty genes encode intracellular inhibitors of receptor tyrosine kinase (RTK) signaling pathways, including those triggered by fibroblast growth factors (Fgfs). Using in situ hybridization, we show that Spry1 and Spry2 are highly expressed in muscles attached to the TMJ, including the lateral pterygoid and temporalis muscles. The combined inactivation of Spry1 and Spry2 results in overgrowth of these muscles, which disrupts normal development of the glenoid fossa. Remarkably, condyle and disc formation are not affected in these mutants, demonstrating that the glenoid fossa is not required for development of these structures. Our findings demonstrate the importance of regulated RTK signaling during TMJ development and suggest multiple skeletal origins for the fossa. Notably, our work provides the evidence that the TMJ condyle and disc develop independently of the mandibular fossa. C1 [Purcell, P.; Vivero, M. P.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Jheon, A.; Joo, A.; Klein, O. D.] UCSF, Dept Orofacial Sci, San Francisco, CA USA. [Jheon, A.; Joo, A.; Klein, O. D.] UCSF, Program Craniofacial & Mesenchymal Biol, San Francisco, CA USA. [Rahimi, H.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA USA. [Klein, O. D.] UCSF, Dept Pediat, San Francisco, CA USA. RP Purcell, P (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Plast & Oral Surg, Boston, MA 02115 USA. EM patricia.purcell@childrens.harvard.edu; ophir.klein@ucsf.edu FU NIDCR [K22DE-016309]; The Boston Plastic and Oral Surgery Foundation, Inc. [K99-DE022059]; National Institutes of Health through the NIH [1-DP2-OD007191] FX We are grateful to Drs. Matthew Warman, Cliff Tabin, Richard Maas, Bjorn Olsen, Pamela Tran, Bryan Macdonald, Philip Stashenko, and Saunders Ching for technical assistance, suggestions, and discussion. We thank Drs. Gail Martin, Albert Basson, and Wenhan Chang for providing mouse lines. This work was supported by NIDCR award K22DE-016309 to P.P., The Boston Plastic and Oral Surgery Foundation, Inc., a K99-DE022059 to A.H.J, and by the National Institutes of Health through the NIH Director's New Innovator Award Program, 1-DP2-OD007191, to O.D.K. The authors declare that there is no conflict of interest. NR 30 TC 14 Z9 16 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2012 VL 91 IS 4 BP 387 EP 393 DI 10.1177/0022034512438401 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 913JQ UT WOS:000301874200010 PM 22328578 ER PT J AU Estrada, CA Dolansky, MA Singh, MK Oliver, BJ Callaway-Lane, C Splaine, M Gilman, S Patrician, PA AF Estrada, Carlos A. Dolansky, Mary A. Singh, Mamta K. Oliver, Brant J. Callaway-Lane, Carol Splaine, Mark Gilman, Stuart Patrician, Patricia A. TI Mastering improvement science skills in the new era of quality and safety: the Veterans Affairs National Quality Scholars Program SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article DE clinical competence; curriculum; fellowships and scholarships; health personnel; education; interprofessional relations; program development; program evaluation; quality improvement; quality of health care; United States Department of Veterans Affairs ID IMPROVING PATIENT SAFETY; INTERNAL-MEDICINE; CONTROLLED-TRIAL; EDUCATION; HEALTH; CARE; COLLABORATION; TEAMWORK; PERFORMANCE; EXPERIENCE AB Rationale, aims and objectives Healthcare professionals need a new skill set to ensure the success of quality improvement in healthcare. The Department of Veterans Affairs (VA) initiated the VA National Quality Scholars fellowship in 1998; its mission is to improve the quality of care, ensure safety, accelerate healthcare re-design, and advance the improvement science by educating the next generation of leaders in quality and safety. We describe the critical need for leadership in quality and safety and interprofessional education, illustrate the curriculum, provide lessons learned by fellows, summarize key lessons learned from the implementation of an interprofessional education approach, and present most recent accomplishments. Methods Narrative review. Results As of 2011, 106 program alumni are embedded in the health care delivery system across the United States. Since 2009, when nurse fellows joined the program, of the first nine graduating interdisciplinary fellows, the tailored curriculum has resulted in five advanced academic degrees, 42 projects, 29 teaching activities, 44 presentations, 36 publications, six grants funded or submitted, and two awards. Conclusions The VA National Quality Scholars program continues to nurture and develop leaders for the new millennium focusing on interprofessional education. The nations' health care systems need strong interdisciplinary leaders in advanced quality improvement science who are dedicated to improving the overall quality of health and health care. C1 [Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Vet Affairs Natl Qual Scholars Program, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL 35294 USA. [Singh, Mamta K.] Case Western Reserve Univ, Louis Stokes Cleveland VA Med Ctr, Patient Based Programs, Cleveland, OH 44106 USA. [Dolansky, Mary A.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA. [Singh, Mamta K.] Case Western Reserve Univ, Ctr Excellence Primary Care Educ, Cleveland, OH 44106 USA. [Oliver, Brant J.] White River Junct Vet Affairs Med Ctr, Vet Affairs Natl Qual Scholars Program, White River Jct, VT USA. [Oliver, Brant J.] Dartmouth Med Sch, Colby Sawyer Coll, Hanover, NH USA. [Callaway-Lane, Carol] Vanderbilt Univ, Sch Nursing, Vet Affairs Natl Qual Scholars Jr Fac, Nashville, TN 37240 USA. [Callaway-Lane, Carol] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [Splaine, Mark] Dartmouth Med Sch, Ctr Leadership & Improvement, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Gilman, Stuart] VA Off Acad Affiliat, Washington, DC USA. [Patrician, Patricia A.] Univ Alabama Birmingham, Vet Affairs Natl Qual Scholars Program, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Patrician, Patricia A.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Vet Affairs Natl Qual Scholars Program, FOT 732,510 20th St S, Birmingham, AL 35294 USA. EM carlos.estrada@va.gov FU Veterans Affairs Office of Academic Affiliations, Washington, DC; QSEN initiative; Robert Wood Johnson Foundation FX The VAQS Program is supported by the Veterans Affairs Office of Academic Affiliations, Washington, DC.; Support for the Senior Nursing Fellows is currently provided by the QSEN initiative funded by the Robert Wood Johnson Foundation. NR 45 TC 4 Z9 4 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-1294 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD APR PY 2012 VL 18 IS 2 BP 508 EP 514 DI 10.1111/j.1365-2753.2011.01816.x PG 7 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA 902QQ UT WOS:000301053800041 PM 22304698 ER PT J AU Campbell, EG Donelan, K DesRoches, C Roman, A Bolcic-Jankovic, D AF Campbell, Eric G. Donelan, Karen DesRoches, Catherine Roman, Anthony Bolcic-Jankovic, Dragana TI The Patient-Doctor Relationship and Online Social Networks: Results of a National Survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Letter C1 [Campbell, Eric G.; Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [DesRoches, Catherine] Math Policy Res, Cambridge, MA USA. [Roman, Anthony; Bolcic-Jankovic, Dragana] Univ Massachusetts, Boston, MA 02125 USA. RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ecampbell@partners.org NR 1 TC 2 Z9 2 U1 7 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2012 VL 27 IS 4 BP 403 EP 403 DI 10.1007/s11606-012-1989-5 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 912YM UT WOS:000301837900006 PM 22311332 ER PT J AU Ahluwalia, SC Levin, JR Lorenz, KA Gordon, HS AF Ahluwalia, Sangeeta C. Levin, Jennifer R. Lorenz, Karl A. Gordon, Howard S. TI Missed Opportunities for Advance Care Planning Communication During Outpatient Clinic Visits SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE qualitative research; advance care planning; heart failure; physician-patient communication ID OF-LIFE CARE; DOCTOR-PATIENT COMMUNICATION; CHRONIC HEART-FAILURE; PALLIATIVE CARE; LUNG-CANCER; CONTROLLED-TRIAL; ILL PATIENTS; BAD-NEWS; END; SKILLS AB Early provider-patient communication about future care is critical for patients with heart failure (HF); however, advance care planning (ACP) discussions are often avoided or occur too late to usefully inform care over the course of the disease. To identify opportunities for physicians to engage in ACP discussions and to characterize physicians' responses to these opportunities. Qualitative study of audio-recorded outpatient clinic visits. Fifty-two patients a parts per thousand yenaEuro parts per thousand 65 years recently hospitalized for HF with one or more post-discharge follow-up outpatient visits, and their physicians (n = 44), at two Veterans Affairs Medical Centers. Using content analysis methods, we analyzed and coded transcripts of outpatient follow-up visits for 1) patient statements pertaining to their future health or their future physical, psychosocial and spiritual/existential care needs, and 2) subsequent physician responses to patient statements, using an iterative consensus-based coding process. In 13 of 71 consultations, patients expressed concerns, questions, and thoughts regarding their future care that gave providers opportunities to engage in an ACP discussion. The majority of these opportunities (84%) were missed by physicians. Instead, physicians responded by terminating the conversation, hedging their responses, denying the patient's expressed emotion, or inadequately acknowledging the sentiment underlying the patient's statement. Physicians often missed the opportunity to engage in ACP despite openers patients provided that could have prompted such discussions. Communication training efforts should focus on helping physicians identify patient openers and providing a toolbox to encourage appropriate physician responses; in order to successfully leverage opportunities to engage in ACP discussions. C1 [Ahluwalia, Sangeeta C.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA 90064 USA. [Levin, Jennifer R.; Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gordon, Howard S.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA. [Gordon, Howard S.] VA Ctr Management Complex Chron Care, Chicago, IL USA. [Gordon, Howard S.] Univ Illinois, Coll Med, Dept Med, Gen Internal Med Sect, Chicago, IL USA. [Gordon, Howard S.] Univ Illinois, Coll Med, Dept Med, Sect Hlth Promot Res, Chicago, IL USA. RP Ahluwalia, SC (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, 11301 Wilshire Blvd,111-G, Los Angeles, CA 90064 USA. EM sangeeta.ahluwalia@va.gov RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 FU United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service [ECV-02-254]; Office of Academic Affiliations' VA at the VA Greater Los Angeles HSR&D Center of Excellence FX This work was supported in part by #ECV-02-254 (PI: Gordon) from the United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service. The views expressed in the article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Dr. Ahluwalia is supported by an Office of Academic Affiliations' VA Associated health Postdoctoral Fellowship Program at the VA Greater Los Angeles HSR&D Center of Excellence. NR 58 TC 12 Z9 12 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2012 VL 27 IS 4 BP 445 EP 451 DI 10.1007/s11606-011-1917-0 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 912YM UT WOS:000301837900014 PM 22038469 ER PT J AU Baxi, SM Kohlwes, J AF Baxi, Sanjiv M. Kohlwes, Jeff TI ST-Segment Elevation and Minimally Reactive Pupils SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE neurology; cardiovascular; emergency medicine C1 [Baxi, Sanjiv M.; Kohlwes, Jeff] Univ Calif San Francisco, Dept Internal Med, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. RP Baxi, SM (reprint author), Univ Calif San Francisco, Dept Internal Med, San Francisco Vet Adm Med Ctr, VAMC 11,4150 Clement St, San Francisco, CA 94121 USA. EM sanjiv.baxi@ucsf.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2012 VL 27 IS 4 BP 478 EP 479 DI 10.1007/s11606-011-1847-x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 912YM UT WOS:000301837900019 PM 21935754 ER PT J AU Millington, T Koulmanda, M Ng, C Boskovic, S Nadazdin, OM Benichou, G Zheng, XX Strom, TB Madsen, JC AF Millington, Timothy Koulmanda, Maria Ng, Choo Boskovic, Svjetlan Nadazdin, Ognjenka M. Benichou, Gilles Zheng, Xin Xiao Strom, Terry B. Madsen, Joren C. TI Effects of an agonist interleukin-2/Fc fusion protein, a mutant antagonist interleukin-15/Fc fusion protein, and sirolimus on cardiac allograft survival in non-human primates SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE heart; transplantation; interleukin-15; primates; rejection ID REGULATORY T-CELLS; MEMORY; IL-15; LYMPHOCYTES; TOLERANCE; TRANSPLANTATION; IMMUNOTHERAPY; ACTIVATION; REJECTION; PHENOTYPE AB BACKGROUND: To tilt the immunologic balance toward tolerance and away from rejection, non-human primate recipients of cardiac allografts were treated with interleukin (IL)-2/Fc, mutant (m) antagonist type mIL-15/Fc, and sirolimus. METHODS: Heterotopic heart transplants were performed on 8 fully mismatched cynomolgus macaques. An untreated control recipient rejected its graft by post-operative Day 6. The remaining 7 animals received oral or intramuscular immunosuppression with sirolimus. A recipient treated with sirolimus alone rejected at the end of 28 days of immunosuppression. The remaining 6 monkeys also received IL-2/Fc and mIL-15/Fc intramuscularly until 28 days after transplant. One animal received a second 28-day course of fusion protein starting at Day 50. In these 6 animals, sirolimus was continued for 28 days (n = 4) or until protein levels were low (n = 2). RESULTS: In the 4 monkeys treated with a 28-day course of sirolimus and fusion proteins, mean graft survival was 51.5 days (range, 28-76 days). The animal receiving a second course of fusion protein rejected its graft on Day 177, despite detectable levels of the fusion proteins and sirolimus. The central memory, effector memory, and naive CD4(+) and CD8(+) T-cell populations in the peripheral blood did not change significantly during fusion protein administration. A 2.5-fold expansion in CD4(+) CD25(+) lymphocytes occurred in recipients treated with fusion proteins and sirolimus that was not observed in the recipient treated with sirolimus alone. CONCLUSIONS: Although IL-2/Fc, mIL-15/Fc, and sirolimus administered in this manner permitted modest prolongation of graft survival and expansion of CD4(+) CD25(+) T cells, tolerance was not achieved. J Heart Lung Transplant 2012;31:427-35 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Millington, Timothy; Ng, Choo; Boskovic, Svjetlan; Nadazdin, Ognjenka M.; Benichou, Gilles; Madsen, Joren C.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Koulmanda, Maria; Zheng, Xin Xiao; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA. [Madsen, Joren C.] Harvard Univ, Sch Med, Dept Surg, Div Cardiac Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Transplant Ctr, White 510C,55 Fruit St, Boston, MA 02114 USA. EM jcmadsen@partners.org FU National Institute of Allergy and Infectious Disease of the National Institutes of Health [U19AI066705]; International Society for Heart and Lung Transplantation (ISHLT) FX This work was partly supported by the National Institute of Allergy and Infectious Disease (U19AI066705) of the National Institutes of Health. T.M. is the recipient of an International Society for Heart and Lung Transplantation (ISHLT) Research Fellowship. NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2012 VL 31 IS 4 BP 427 EP 435 DI 10.1016/j.healun.2012.01.864 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 917WD UT WOS:000302208400011 PM 22366291 ER PT J AU Zhang, W O-Sullivan, I Unterman, TG Bu, S Mashek, DG Kahn, C AF Zhang, W. O-Sullivan, I. Unterman, T. G. Bu, S. Mashek, D. G. Kahn, C. TI REGULATION OF ADIPOSE TRIGLYCERIDE LIPASE (ATGL) AND GOS2 LIPID DROPLET PROTEINS BY FOXO TRANSCRIPTION FACTORS AND INSULIN IN THE LIVER SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Joint Annual Meeting of the Central-Society-for-Clinical-Research (CSCR) and Midwestern Section American Federation for Medical Research (MSAFMR) CY APR 26-27, 2012 CL Chicago, IL SP Cent Soc Clin Res (CSCR), Midwestern Sect Amer Federat Med Res (MSAFMR) C1 [Zhang, W.; O-Sullivan, I.; Unterman, T. G.] Univ Illinois, Chicago, IL USA. [Zhang, W.; O-Sullivan, I.; Unterman, T. G.] Jesse Brown VAMC, Chicago, IL USA. [Bu, S.; Mashek, D. G.] Univ Minnesota, St Paul, MN 55108 USA. [Kahn, C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 2012 VL 60 IS 4 BP 724 EP 724 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 914TS UT WOS:000301976100051 ER PT J AU Moolgavkar, SH Holford, TR Levy, DT Kong, CY Foy, M Clarke, L Jeon, J Hazelton, WD Meza, R Schultz, F McCarthy, W Boer, R Gorlova, O Gazelle, GS Kimmel, M McMahon, PM de Koning, HJ Feuer, EJ AF Moolgavkar, Suresh H. Holford, Theodore R. Levy, David T. Kong, Chung Yin Foy, Millenia Clarke, Lauren Jeon, Jihyoun Hazelton, William D. Meza, Rafael Schultz, Frank McCarthy, William Boer, Robert Gorlova, Olga Gazelle, G. Scott Kimmel, Marek McMahon, Pamela M. de Koning, Harry J. Feuer, Eric J. TI Impact of Reduced Tobacco Smoking on Lung Cancer Mortality in the United States During 1975-2000 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MULTISTAGE CARCINOGENESIS; COLORECTAL-CANCER; CIGARETTE-SMOKING; MODEL; AGE; DURATION; SMOKERS; COHORTS; HEALTH; TRENDS AB Background Considerable effort has been expended on tobacco control strategies in the United States since the mid-1950s. However, we have little quantitative information on how changes in smoking behaviors have impacted lung cancer mortality. We quantified the cumulative impact of changes in smoking behaviors that started in the mid-1950s on lung cancer mortality in the United States over the period 1975-2000. Methods A consortium of six groups of investigators used common inputs consisting of simulated cohort-wise smoking histories for the birth cohorts of 1890 through 1970 and independent models to estimate the number of US lung cancer deaths averted during 1975-2000 as a result of changes in smoking behavior that began in the mid-1950s. We also estimated the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking after the Surgeon General's first report on Smoking and Health in 1964. Results Approximately 795 851 US lung cancer deaths were averted during the period 1975-2000: 552 574 among men and 243 277 among women. In the year 2000 alone, approximately 70 218 lung cancer deaths were averted: 44 135 among men and 26 083 among women. However, these numbers are estimated to represent approximately 32% of lung cancer deaths that could have potentially been averted during the period 1975-2000, 38% of the lung cancer deaths that could have been averted in 1991-2000, and 44% of lung cancer deaths that could have been averted in 2000. Conclusions Our results reflect the cumulative impact of changes in smoking behavior since the 1950s. Despite a large impact of changing smoking behaviors on lung cancer deaths, lung cancer remains a major public health problem. Continued efforts at tobacco control are critical to further reduce the burden of this disease. J Natl Cancer Inst 2012; 104: 541-548 C1 [Moolgavkar, Suresh H.; Jeon, Jihyoun; Hazelton, William D.; Meza, Rafael] Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Seattle, WA 98109 USA. [Holford, Theodore R.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Levy, David T.] Univ Baltimore, Dept Econ, Baltimore, MD 21201 USA. [Levy, David T.] Pacific Inst Res & Evaluat, Calverton, MD USA. [Kong, Chung Yin; Gazelle, G. Scott; McMahon, Pamela M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kong, Chung Yin; Gazelle, G. Scott; McMahon, Pamela M.] Harvard Univ, Sch Med, Boston, MA USA. [Foy, Millenia] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX USA. [Gorlova, Olga] UT MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA. [Foy, Millenia; Kimmel, Marek] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Clarke, Lauren] Cornerstone Syst NW Inc, Lynden, WA USA. [Meza, Rafael] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Schultz, Frank; Boer, Robert; de Koning, Harry J.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [McCarthy, William] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [McCarthy, William] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Kimmel, Marek] Silesian Tech Univ, Syst Engn Grp, Gliwice, Poland. [Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Levy, David T.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Moolgavkar, SH (reprint author), Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, 1100 Fairview Ave N, Seattle, WA 98109 USA. EM smoolgav@fhcrc.org RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X FU National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET); National Cancer Institute at the National Institutes of Health [5U01CA097415-04, 2U01CA097432-04, 5U01CA097450-04, 5U01CA097416-04, 2U01CA097431-04, 1U01CA152956-01, 5R01CA097337-02, K25CA133141, R00CA126147]; American Cancer Society (ACS) [RSG 2008A060554] FX The research reported in this article was funded by the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET; http://cisnet.cancer.gov/). Specifically, this work was supported by grants from the National Cancer Institute at the National Institutes of Health (5U01CA097415-04 to SHM, 2U01CA097432-04 to TRH, 5U01CA097450-04 to DTL, 5U01CA097416-04 to RB and HJK, 2U01CA097431-04 to MK, 1U01CA152956-01 to PMM HJK, DTL, SHM, TRH). GSG acknowledges support from the National Cancer Institute at the National Institutes of Health (5R01CA097337-02) and the American Cancer Society (ACS RSG 2008A060554), PMM from the National Cancer Institute at the National Institutes of Health (R00CA126147), and CYK from the National Cancer Institute at the National Institutes of Health (K25CA133141). NR 29 TC 57 Z9 58 U1 0 U2 11 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 APR PY 2012 VL 104 IS 7 BP 541 EP 548 DI 10.1093/jnci/djs136 PG 8 WC Oncology SC Oncology GA 919AO UT WOS:000302293200009 PM 22423009 ER PT J AU Sanders, JL Fitzpatrick, AL Boudreau, RM Arnold, AM Aviv, A Kimura, M Fried, LF Harris, TB Newman, AB AF Sanders, Jason L. Fitzpatrick, Annette L. Boudreau, Robert M. Arnold, Alice M. Aviv, Abraham Kimura, Masayuki Fried, Linda F. Harris, Tamara B. Newman, Anne B. TI Leukocyte Telomere Length Is Associated With Noninvasively Measured Age-Related Disease: The Cardiovascular Health Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Leukocyte telomere length; Disease burden; Noninvasive measurements; Aging ID CAROTID ATHEROSCLEROSIS; OXIDATIVE STRESS; RISK-FACTORS; MORTALITY; ADULTS; DEMENTIA; DYNAMICS; PERFORMANCE; SENESCENCE; DEPRESSION AB Background. Most studies of leukocyte telomere length (LTL) focus on diagnosed disease in one system. A more encompassing depiction of health is disease burden, defined here as the sum of noninvasively measured markers of structure or function in different organ systems. We determined if (a) shorter LTL is associated with greater age-related disease burden and (b) shorter LTL is less strongly associated with disease in individual systems or diagnosed chronic conditions (cardiovascular disease, stroke, pulmonary disease, diabetes, kidney disease, arthritis, or depression). Methods. LTL was measured by Southern blots of terminal restriction fragment length. Age-related disease was measured noninvasively and included carotid intima-media thickness, lung vital capacity, white matter grade, cystatin-C, and fasting glucose; each graded 0 (best tertile), 1 (middle tertile), or 2 (worst tertile) and summed (0 to 10) to estimate disease burden. Of 419 participants randomly selected for LTL measurement, 236 had disease burden assessed (mean [SD] age 74.2 [4.9] years, 42.4% male, 86.8% white, and 13.2% black). Results. Mean (SD) LTL was 6,312 (615) bp, and disease score was 4.7 (2.1) points. An SD higher disease score (beta[SE] = -132 [47] bp, p < .01), age (beta[SE] = -107 [46], p = .02) or carotid thickness (beta[SE] = -95 [40] bp, p = .02) was associated with shorter LTL, but diagnosed conditions or number of conditions were not associated with LTL. Disease score attenuated the effect of age on LTL by 35%. Conclusion. LTL was associated with a characterization of age-related disease burden across multiple physiologic systems, which was comparable to, but independent of, its association with age. C1 [Sanders, Jason L.; Boudreau, Robert M.; Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Sanders, Jason L.] Univ Pittsburgh, Sch Med, Med Scientist Training Program, Pittsburgh, PA 15213 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Aviv, Abraham; Kimura, Masayuki] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, Newark, NJ 07103 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Sanders, JL (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Bellefield Profess Bldg,4th Floor,130 N Bellefiel, Pittsburgh, PA 15213 USA. EM sanders.jason@medstudent.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU Royalty Research Fund; University of Washington; Healthcare Foundation of New Jersey; National Institute on Aging [R01-AG-023629, 5-P30-AG-024827, AG-021593, AG-020132]; National Heart, Lung, and Blood Institute [R01-HL-80698-01, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-45133, N01-HC-75150, N01-HC-55222, U01 HL080295]; National Institute of Neurological Disorders and Stroke FX This research was supported by the Royalty Research Fund, the University of Washington, the Healthcare Foundation of New Jersey, the National Institute on Aging (grants R01-AG-023629 and 5-P30-AG-024827), and the National Heart, Lung, and Blood Institute (R01-HL-80698-01). The CHS is supported by the National Heart, Lung, and Blood Institute (contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-45133, N01-HC-75150, N01-HC-55222, and U01 HL080295), the National Institute on Aging (grants AG-021593 and AG-020132), and the National Institute of Neurological Disorders and Stroke. A full list of participating Cardiovascular Health Study investigators and institutions can be found at the study's website (http://www.chs-nhlbi.org). Role of sponsor(s): The investigators retained full independence in the conduct of this research. NR 45 TC 31 Z9 33 U1 4 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2012 VL 67 IS 4 BP 409 EP 416 DI 10.1093/gerona/glr173 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 914TE UT WOS:000301974500011 PM 21934123 ER PT J AU Hankey, GJ Patel, MR Stevens, SR Becker, RC Breithardt, G Carolei, A Diener, HC Donnan, GA Halperin, JL Mahaffey, KW Mas, JL Massaro, A Norrving, B Nessel, CC Paolini, JF Roine, RO Singer, DE Wong, L Califf, RM Fox, KAA Hacke, W AF Hankey, Graeme J. Patel, Manesh R. Stevens, Susanna R. Becker, Richard C. Breithardt, Gunter Carolei, Antonio Diener, Hans-Christoph Donnan, Geoffrey A. Halperin, Jonathan L. Mahaffey, Kenneth W. Mas, Jean-Louis Massaro, Ayrton Norrving, Bo Nessel, Christopher C. Paolini, John F. Roine, Risto O. Singer, Daniel E. Wong, Lawrence Califf, Robert M. Fox, Keith A. A. Hacke, Werner CA ROCKET AF Steering Comm TI Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF SO LANCET NEUROLOGY LA English DT Article ID CLINICAL-TRIALS; SECONDARY PREVENTION; THERAPY; EVENTS AB Background In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). Methods In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2-0-3.0). Patients and investigators were masked to treatment allocation. Between Dec 18,2006, and June 17,2009,14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. Findings 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2.79% rivaroxaban vs 2.96% warfarin; hazard ratio [HR] 0-94,95% CI 0.77-1.16) and those without (1.44% vs 1.88%; 0.77, 0.58-1-01; interaction p=0.23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13.31% rivaroxaban vs 13.87% warfarin; HR 0.96,95% CI 0.87-1-07) and those without (16.69% vs 15.19%; 1.10, 0.99-1.21; interaction p=0.08). Interpretation There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF. C1 [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Stroke Unit, Perth, WA, Australia. [Califf, Robert M.] Duke Univ, Med Ctr, Dept Med, Div Cardiol,Duke Translat Med, Durham, NC 27710 USA. [Stevens, Susanna R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Breithardt, Gunter] Hosp Univ Munster, Dept Cardiol & Angiol, Munster, Germany. [Carolei, Antonio] Univ Aquila, Dept Neurol, I-67100 Laquila, Italy. [Diener, Hans-Christoph] Univ Hosp Essen, Dept Neurol, Essen, Germany. [Donnan, Geoffrey A.] Univ Melbourne, Dept Neurol, Melbourne, Vic, Australia. [Halperin, Jonathan L.] Mt Sinai Sch Med, Cardiovasc Inst, New York, NY USA. [Mas, Jean-Louis] Paris Descartes Univ, Hop St Anne, Dept Neurol, Paris, France. [Massaro, Ayrton] Univ Sao Paulo, Inst Rehabil Lucy Montoro, Sao Paulo, Brazil. [Norrving, Bo] Lund Univ, Dept Clin Sci, Neurol Sect, Lund, Sweden. [Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Paolini, John F.] HealthCare Pharmaceut, Montville, NJ USA. [Roine, Risto O.] Turku Univ Hosp, Dept Neurol, FIN-20520 Turku, Finland. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wong, Lawrence] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Hacke, Werner] Univ Heidelberg, Dept Neurol, Heidelberg, Germany. RP Hankey, GJ (reprint author), Royal Perth Hosp, Dept Neurol, Stroke Unit, Perth, WA, Australia. EM gjhankey@cyllene.uwa.edu.au RI Wong, Ka Sing Lawrence/N-3434-2015; Urina, Miguel/H-2605-2016; bladin, chris/B-9136-2013; Walters, Darren/A-7069-2011; Zadionchenko, Vladimir/A-7445-2016; De Caterina, Raffaele/K-3857-2016; Sinkiewicz, Wladyslaw/G-5169-2014; Parsons, Mark/G-3750-2014; Hankey, Graeme /H-4968-2014; Mazurov, Vadim/J-9643-2014; Libis, Roman/O-9193-2015; Arkhipov, Mikhail/Q-2316-2015; OI Wong, Ka Sing Lawrence/0000-0002-2031-9866; Urina, Miguel/0000-0001-6003-4622; Zadionchenko, Vladimir/0000-0003-2377-5266; De Caterina, Raffaele/0000-0003-1637-574X; Hankey, Graeme /0000-0002-6044-7328; Mazurov, Vadim/0000-0002-0797-2051; Libis, Roman/0000-0003-0130-990X; Norrving, Bo/0000-0002-8024-5096; Donnan, Geoffrey/0000-0001-6324-3403; Prabhakaran, Dorairaj/0000-0002-3172-834X; Michel, GALINIER/0000-0003-1735-3390; Kaste, Markku/0000-0001-6557-6412; Macleod, Malcolm Robert/0000-0001-9187-9839 FU Johnson and Johnson Pharmaceutical Research and Development; Bayer HealthCare; Ortho McNeil Janssen; Bayer; Johnson and Johnson; AstraZeneca; GlaxoSmithKline; Boehringer Ingelheim; Lundbeck; Novartis; Janssen-Cilag Sanofi-Aventis; Syngis; Talecris; Bristol-Myers Squibb; Daiichi Sankyo; Eli Lilly; Merck; Momenta Pharmaceuticals; Portola; Pozen; Regado Biotechnologies; Sanofi-Aventis; Medicines Company; Ortho/McNeill; Pfizer; Polymedix; Allergan; Sanofi; Lilly FX Funding Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare.; GJH has received honoraria for serving on trial executive committees for Johnson and Johnson, Bayer, and Sanofi-Aventis; and on trial adjudication committees and an advisory board for Boehringer Ingelheim. MRP has received honoraria for serving on executive committees for Johnson and Johnson and Bayer, has received consulting fees from Ortho McNeil Janssen and Bayer HealthCare, and has served on an advisory board for Genzyme. RCB has received research support from Bayer and Johnson and Johnson. GB has received honoraria for serving on a steering committee for Johnson and Johnson and Bayer and has received fees for serving on advisory boards for Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. AC has received honoraria as a member of a steering committee for Johnson and Johnson and Bayer, and for participation in clinical trials, contributions to advisory boards, or oral presentations from Sanofi-Aventis, Bristol-Myers Squibb, Solvay, Abbott, and Pfizer. H-CD has received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from Abbott, Allergan, AstraZeneca, Bayer Vital, Bristol-Myers Squibb, Boehringer Ingelheim, CoAxia, D-Pharm, EV3, Fresenius, GlaxoSmithKline, Janssen Cilag, Knoll, MSD, Medtronic, MindFrame, Neurobiological Technologies, Novartis, Novo-Nordisk, Paion, Parke-Davis, Pfizer, Sanofi-Aventis, Sankyo, Schering-Plough, Servier, Solvay, Thrombogenics, Wyeth, and Yamaguchi; and H-CD's institution has received financial support for research projects from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Lundbeck, Novartis, Janssen-Cilag Sanofi-Aventis, Syngis, and Talecris. GAD has acted on an advisory board for Boehringer Ingelheim. JLH has received honoraria for serving on a steering committee for Johnson and Johnson and Bayer and fees for advisory activities for Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer. KWM has received grant support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson and Johnson, Merck, Momenta Pharmaceuticals, Novartis, Portola, Pozen, Regado Biotechnologies, Sanofi-Aventis, Schering-Plough (now Merck), and The Medicines Company; and consulting fees from AstraZeneca, Johnson and Johnson, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Ortho/McNeill, Pfizer, Polymedix, Sanofi-Aventis, and Schering-Plough (now Merck). J-LM has received honoraria for serving on a steering committee for Johnson and Johnson and Bayer and fees for serving on advisory boards for Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer. BN has received consultancy payments from Bayer, payment for lectures from Allergan and Bayer, and royalties for a book published by Karolinska University Press. BN's institution has received honoraria for consultancy from Syngis, Servier, Bayer, PhotoThera, and Boehringer Ingelheim. CCN is an employee of Johnson and Johnson Pharmaceutical Research and Development (Raritan, NJ, USA) and owns stock in Johnson and Johnson. JFP is a former employee of Bayer HealthCare. ROR has received honoraria as a member of a steering committee from Johnson and Johnson and Bayer and for participating in clinical trials, contributions to advisory boards, or oral presentations from Bayer, Boehringer Ingelheim, Servier, Lundbeck, and Schering.; DES has received honoraria for serving on advisory boards or payments for consulting, or both from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson and Johnson, Pfizer, and Sanofi. LW has received honoraria as a member of a steering committee for Johnson and Johnson and Bayer, and for participation in clinical trials, contributions to advisory boards, or oral presentations from Sanofi-Aventis, Bristol-Myers Squibb, Boehringer Ingelheim, and Pfizer. RMC has received consulting fees and research funding from Johnson and Johnson; all other industry interactions are listed at www.dcri.org. KAAF has received grants and honoraria from Bayer, Lilly, Boehringer Ingelheim, Sanofi-Aventis, and GlaxoSmithKline. WH has received honoraria for serving on an executive committee for Johnson and Johnson and Bayer and advisory board fees from Boehringer Ingelheim. SRS and AM declare that they have no conflicts of interest. NR 16 TC 126 Z9 137 U1 7 U2 47 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD APR PY 2012 VL 11 IS 4 BP 315 EP 322 DI 10.1016/S1474-4422(12)70042-X PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 915CD UT WOS:000301999600007 PM 22402056 ER PT J AU Kakarala, K Faquin, WC Cunningham, MJ AF Kakarala, Kiran Faquin, William C. Cunningham, Michael J. TI Radiofrequency volumetric tissue reduction of the inferior turbinate in a sheep model SO LARYNGOSCOPE LA English DT Article DE Sinonasal; general otolaryngology; allergy; Level of Evidence: 2c ID ACOUSTIC RHINOMETRY; ANIMAL-MODEL; NASAL CONGESTION; HYPERTROPHY; ABLATION; SURGERY; TURBINOPLASTY; MICRODEBRIDER; MONOPOLAR; SINUS AB Objectives/Hypothesis: To validate the sheep model for endoscopic nasal surgery, and to utilize this model to compare the immediate and early postoperative histopathologic effects of four electrosurgical turbinate reduction techniques. Study Design: Pilot comparative study of electrosurgical devices for inferior turbinate reduction using a sheep model. Methods: Three radiofrequency devices (one monopolar and two bipolar) were compared to monopolar electrosurgery in a sheep model of inferior turbinate reduction. Procedures were performed according to device manufacturer guidelines using standard endoscopic instruments. Normative acoustic rhinometry data were obtained for the sheep model. Histopathologic analysis of turbinate specimens was performed at postoperative day 0 and 21. Results: Turbinate reduction was performed on seven sheep, one procedure on each side, yielding 14 turbinate specimens. Acoustic rhinometry was validated in the sheep model and demonstrated increased nasal volumes following decongestion and turbinate reduction. Submucosal destruction of glands and venous sinusoids and replacement with fibrosis were demonstrated as a common mechanism of action for all four electrosurgical devices. Epithelial disruption was seen with all devices on postoperative day 0. Squamous metaplasia and normal respiratory epithelial regeneration were documented variably between devices at postoperative day 21. Conclusions: The sheep model is useful for study of both the anatomic and histopathologic effects of endonasal procedures. Standard endoscopic instruments and acoustic rhinometry can be used in this model with reproducible results. In this pilot animal study, radiofrequency devices for inferior turbinate reduction demonstrated greater preservation of normal nasal mucosal respiratory epithelium when compared to monopolar electrosurgery. C1 [Kakarala, Kiran] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cunningham, Michael J.] Childrens Hosp Boston, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. [Kakarala, Kiran; Cunningham, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Kakarala, K (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM kiran.kakarala@gmail.com OI Kakarala, Kiran/0000-0002-1003-8024 FU ArthroCare; Gyrus ACMI FX Funding for this project was provided by ArthroCare and Gyrus ACMI. The authors have no other funding, financial relationships, or conflicts of interest to disclose. NR 23 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2012 VL 122 IS 4 BP 724 EP 729 DI 10.1002/lary.23201 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 911KD UT WOS:000301714800004 PM 22302649 ER PT J AU Achkar, J Song, P Andrus, J Franco, R AF Achkar, Jihad Song, Phillip Andrus, Jennifer Franco, Ramon, Jr. TI Double-bend needle modification for transthyrohyoid vocal fold injection SO LARYNGOSCOPE LA English DT Article DE Transthyrohyoid; cricothyroid; transcutaneous ID THYROHYOID APPROACH; AUGMENTATION AB Our objective was to describe an injection needle modification for awake in-office vocal fold injections through a percutaneous transthyrohyoid approach. Two separate 45 degrees angle bends are created at the hub and 1 cm from the needle tip of a 25-gauge, 1.5-inch needle. After adequate endolaryngeal anesthesia, the needle is passed via the thyrohyoid membrane into the airway. The needle tip is at a 90 degrees angle to the syringe, providing access to the entire vocal fold surface, regardless of chin position or thyroid cartilage angulation. The bend at 1 cm also serves as a marker to measure the depth of the needle within the soft tissue. The double-bend needle modification allows for complete access to the entire length of the true vocal fold in one pass as well as a marker to measure depth of the needle in the tissue. Limitations may include bleeding from the injection site, insufficient needle length in patients with a long anterior-posterior dimension of the larynx, and potential difficulty passing a needle through a calcified thyrohyoid membrane. Laryngoscope, 2012 C1 [Achkar, Jihad; Song, Phillip; Franco, Ramon, Jr.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Laryngol, Boston, MA 02114 USA. [Achkar, Jihad; Song, Phillip; Franco, Ramon, Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Andrus, Jennifer] Billings Clin, Dept Otolaryngol Head & Neck Surg, Billings, MT USA. RP Franco, R (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. EM ramon_franco@meei.harvard.edu NR 9 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2012 VL 122 IS 4 BP 865 EP 867 DI 10.1002/lary.22181 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 911KD UT WOS:000301714800032 PM 22344556 ER PT J AU Fontana, RJ Litman, HJ Dienstag, JL Bonkovsky, HL Su, G Sterling, RK Lok, AS AF Fontana, Robert J. Litman, Heather J. Dienstag, Jules L. Bonkovsky, Herbert L. Su, Grace Sterling, Richard K. Lok, Anna S. CA HALT-C Trial Grp TI YKL-40 genetic polymorphisms and the risk of liver disease progression in patients with advanced fibrosis due to chronic hepatitis C SO LIVER INTERNATIONAL LA English DT Article DE cirrhosis; decompensation; genetic polymorphisms; hepatitis C; interferon; virological response ID CHITINASE PROTEIN FAMILY; SERUM FIBROSIS; MACROPHAGE DIFFERENTIATION; MARKERS; CHI3L1; CIRRHOSIS; CARTILAGE; PEGINTERFERON; VARIANTS AB Background/Aims: The aim of this study was to explore the association of a functional YKL-40 promoter polymorphism (rs4950928) with baseline disease stage, response to antiviral therapy and risk of liver disease progression in a group of patients with chronic hepatitis C (CHC). Methods: YKL-40 promoter polymorphisms were determined in 456 Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial patients with bridging fibrosis or cirrhosis entering a prerandomization lead-in peginterferon/ribavirin 24-week treatment phase and in 462 patients followed for a mean of 3.8 years after randomization to maintenance peginterferon or observation. Results: Mean patient age was 49.5 years, 70.4% were men and 71.2% were Caucasian. The 17% frequency of the YKL-40 minor allele (T) was similar to that reported in the general population. YKL-40 genotype was associated significantly with baseline serum YKL-40 levels but was not associated with the likelihood of a virological response following 24-48 weeks of peginterferon/ribavirin therapy. Serum YKL-40 levels remained significantly lower during follow-up in the randomized TT homozygotes compared with CT heterozygotes and CC homozygotes (P < 0.001). Despite this association, YKL-40 genotype was not associated with the risk of clinical or histological liver disease progression. Conclusions: A reduced frequency of the protective YKL-40 promoter polymorphism was not observed in the HALT-C Trial patient population. The absence of an association between YKL-40 promoter polymorphisms and baseline liver disease severity as well as with the risk of liver disease progression over time suggests that this polymorphism is not associated with disease progression in CHC patients with established fibrosis. C1 [Fontana, Robert J.; Su, Grace; Lok, Anna S.] Univ Michigan, Med Ctr, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Med Serv, Cambridge, MA 02138 USA. [Dienstag, Jules L.] Harvard Univ, Med Sch Boston, Dept Med, Cambridge, MA 02138 USA. [Bonkovsky, Herbert L.] Univ Connecticut Hlth Ctr CT, Dept Med, Storrs, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut Hlth Ctr CT, Dept Mol & Struct Biol, Storrs, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut Hlth Ctr CT, Liver Biliary Pancreat Ctr, Storrs, CT USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Med Ctr VA, Hepatol Sect, Richmond, VA 23284 USA. RP Fontana, RJ (reprint author), Univ Michigan, Med Ctr, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; General Clinical Research Center; Clinical and Translational Science Center from the National Center for Research Resources, National Institutes of Health; Hoffmann-La Roche, Inc.; National Institutes of Health; University of Massachusetts Medical Center, Worcester, MA [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, CT [M01RR-06192]; Massachusetts General Hospital, Boston, MA [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; Michigan Medical Center, Ann Arbor, MI [N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia Commonwealth University Health System, Richmond, VA [N01-DK-9-2322, M01RR-00065]; New England Research Institutes, Watertown, MA [N01-DK-9-2328]; Genentech; Vertex Pharmaceuticals; Clinuvel, Inc.; Novartis Pharmaceuticals; American Porphyria Foundation; Iron Disorders Institute; Merck; GlaxoSmithKline; Bayer; Pfize; Medtronic FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.; University of Massachusetts Medical Center, Worcester, MA: (Contract N01-DK-9-2326) Gyongyi Szabo, MD, Barbara F. Banner, MD, Maureen Cormier, RN, Donna Giansiracusa, RN; University of Connecticut Health Center, Farmington, CT: (Grant M01RR-06192) Gloria Borders, RN, Michelle Kelley, RN, ANP; Massachusetts General Hospital, Boston, MA: (Contract N01-DK-9-2319, Grant M01RR-01066; Grant 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center) Raymond T. Chung, MD, Andrea E. Reid, MD, Atul K. Bhan, MD, Wallis A. Molchen, Cara C. Gooch; Michigan Medical Center, Ann Arbor, MI: (Contract N01-DK-9-2323, Grant M01RR-00042, Grant 1 UL1 RR024986, Michigan Center for Clinical and Health Research) Joel K. Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, R. Tess Bonham, BS; Virginia Commonwealth University Health System, Richmond, VA: (Contract N01-DK-9-2322, Grant M01RR-00065) Mitchell L. Shiffman, MD, Melissa J. Contos, MD, A. Scott Mills, MD, Charlotte Hofmann, RN, Paula Smith, RN; New England Research Institutes, Watertown, MA: (Contract N01-DK-9-2328) Kristin K. Snow, MSc, ScD, Margaret C. Bell, MS, MPH, Teresa M. Curto, MSW, MPH; Financial relationships of the authors with Hoffmann-La Roche, Inc. (now Genentech), are as follows: R. J. Fontana was previously on the speaker's bureau; R. K. Sterling is a consultant and receives research support; A. S. Lok is a consultant and receives research support. Authors with no financial relationships related to this project are H. J. Litman, J. L. Dienstag, H. L. Bonkovsky, and G. L. Su.; J. L. Dienstag: Research support: Vertex Pharmaceuticals; Serves on Data Monitoring Committee: Schering-Plough Research Institute, Human Genome Sciences, and Medtronic; Ad hoc Hepatitis Advisory Board: Boehringer-Ingelheim; Antiviral Advisory Board: Gilead Sciences; Ad hoc Consultant (stock options): Achillion; Clinical Advisory Board (stock options): Nucleonics; Scientific Advisory Board (stock options): Metabasis.; H. L. Bonkovsky: Consultant: Boehringer-Ingelheim; Consultant/Advisory Board/Research support: Clinuvel, Inc.; Consultant/Advisory Board/Research support: Novartis Pharmaceuticals; Consultant/Speakers' Bureau: Lundbeck Pharmaceuticals; Research support: Vertex Pharmaceuticals. American Porphyria Foundation, Member of Scientific Advisory Board; Consultant; Receives research and educational support. Iron Disorders Institute, Chair, Scientific Advisory Board; Consultant.; R. K. Sterling: Consultant and Research support: Schering-Plough (now Merck); Research support: GlaxoSmithKline; Consultant: Vertex Pharmaceuticals; Consultant: Salix; Consultant and Research support: Bayer; Research support: Pfizer; Research support: Medtronic. NR 30 TC 8 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1478-3223 J9 LIVER INT JI Liver Int. PD APR PY 2012 VL 32 IS 4 BP 665 EP 674 DI 10.1111/j.1478-3231.2011.02686.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 904XY UT WOS:000301233800019 PM 22103814 ER PT J AU Aronis, KN Mantzoros, CS AF Aronis, Konstantinos N. Mantzoros, Christos S. TI A brief history of insulin resistance: from the first insulin radioimmunoassay to selectively targeting protein kinase C pathways SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID TYPE-2 DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; RECEPTOR SUBSTRATE-1; BETA-INHIBITOR; CLINICAL-TRIAL; PKC-LAMBDA; ESSENTIAL-HYPERTENSION; ENDOTHELIAL FUNCTION; ENDOMETRIAL CANCER; SKELETAL-MUSCLE C1 [Aronis, Konstantinos N.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02215 USA. RP Aronis, KN (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM karonis@bidmc.harvard.edu; cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 NR 74 TC 1 Z9 1 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2012 VL 61 IS 4 BP 445 EP 449 DI 10.1016/j.metabol.2012.01.001 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914YY UT WOS:000301991000001 PM 22304840 ER PT J AU Sajan, MP Nimal, S Mastorides, S Acevedo-Duncan, M Kahn, CR Fields, AP Braun, U Leitges, M Farese, RV AF Sajan, Mini P. Nimal, Sonali Mastorides, Stephen Acevedo-Duncan, Mildred Kahn, C. Ronald Fields, Alan P. Braun, Ursula Leitges, Michael Farese, Robert V. TI Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-i SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID LUNG-CANCER CELLS; NF-KAPPA-B; INSULIN-SENSITIVITY; TRANSFORMED GROWTH; PKC-LAMBDA; MUSCLE; ACTIVATION; LIVER; EXPRESSION; RESISTANCE AB Excessive activity of hepatic atypical protein kinase (aPKC) is proposed to play a critical role in mediating lipid and carbohydrate abnormalities in obesity, the metabolic syndrome, and type 2 diabetes mellitus. In previous studies of rodent models of obesity and type 2 diabetes mellitus, adenoviral-mediated expression of kinase-inactive aPKC rapidly reversed or markedly improved most if not all metabolic abnormalities. Here, we examined effects of 2 newly developed small-molecule PKC-i/lambda inhibitors. We used the mouse model of heterozygous muscle-specific knockout of PKC-lambda, in which partial deficiency of muscle PKC-lambda impairs glucose transport in muscle and thereby causes glucose intolerance and hyperinsulinemia, which, via hepatic aPKC activation, leads to abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. One inhibitor, 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)], binds to the substrate-binding site of PKC-lambda/i, but not other PKCs. The other inhibitor, aurothiomalate, binds to cysteine residues in the PB1-binding domains of aPKC-lambda/i/zeta and inhibits scaffolding. Treatment with either inhibitor for 7 days inhibited aPKC, but not Ala, in liver and concomitantly improved insulin signaling to Akt and aPKC in muscle and adipocytes. Moreover, both inhibitors diminished excessive expression of hepatic, aPKC-dependent lipogenic, proinflammatory, and gluconeogenic factors; and this was accompanied by reversal or marked improvements in hyperglycemia, hyperinsulinemia, abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. Our findings highlight the pathogenetic importance of insulin signaling to hepatic PKC-i in obesity, the metabolic syndrome, and type 2 diabetes mellitus and suggest that 1H-imidazole-4-carboxamide, 5-amino-1[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)] and aurothiomalate or similar agents that selectively inhibit hepatic aPKC may be useful treatments. Published by Elsevier Inc. C1 [Sajan, Mini P.; Mastorides, Stephen; Acevedo-Duncan, Mildred; Farese, Robert V.] James A Haley Vet Med Ctr, Med Serv, Tampa, FL 33612 USA. [Sajan, Mini P.; Mastorides, Stephen; Acevedo-Duncan, Mildred; Farese, Robert V.] James A Haley Vet Med Ctr, Res Serv, Tampa, FL 33612 USA. [Nimal, Sonali; Farese, Robert V.] Roskamp Inst, Sarasota, FL USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Res Fdn, Boston, MA USA. [Fields, Alan P.] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. [Braun, Ursula; Leitges, Michael] Biotechnol Ctr Oslo, Oslo, Norway. [Farese, Robert V.] Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA. RP Farese, RV (reprint author), James A Haley Vet Med Ctr, Med Serv, Tampa, FL 33612 USA. EM rfarese@health.usf.edu RI Farese, Robert/B-3605-2015 FU Department of Veterans Affairs; National Institutes of Health [DK38079, DK300136]; Deutsche Forschungsgemeinschaft [Sta314/2-1, KE246/7-2] FX Supported by funds from the Department of Veterans Affairs Merit Review Program and the National Institutes of Health Grants (DK38079 to RVF and DK300136 to CR Kahn), and the Deutsche Forschungsgemeinschaft Sta314/2-1 and KE246/7-2 (ML). NR 18 TC 16 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2012 VL 61 IS 4 BP 459 EP 469 DI 10.1016/j.metabol.2011.12.008 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914YY UT WOS:000301991000003 PM 22225955 ER PT J AU Aronis, KN Vamvini, MT Chamberland, JP Sweeney, LL Brennan, AM Magkos, F Mantzoros, CS AF Aronis, Konstantinos N. Vamvini, Maria T. Chamberland, John P. Sweeney, Laura L. Brennan, Aoife M. Magkos, Faidon Mantzoros, Christos S. TI Short-term walnut consumption increases circulating total adiponectin and apolipoprotein A concentrations, but does not affect markers of inflammation or vascular injury in obese humans with the metabolic syndrome: data from a double-blinded, randomized, placebo-controlled study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID MOLECULAR-WEIGHT ADIPONECTIN; CARDIOVASCULAR RISK-FACTORS; ENDOTHELIAL FUNCTION; NUTS; DISEASE; PLASMA; WOMEN; ATHEROSCLEROSIS; CANCER; EXPRESSION AB Long-term consumption of walnuts is associated with lower cardiovascular disease risk in epidemiological studies, possibly through improvements in lipid profile and endothelial function. It remains to be elucidated how soon after initiation of walnut consumption beneficial effects on lipid profile and biomarkers of inflammation or vascular injury can be observed. Fifteen obese subjects (9 men and 6 women; age, 58 +/- 2.5 years; body mass index, 36.6 +/- 1.7 kg/m(2)) with the metabolic syndrome participated as inpatients in a randomized, double-blinded, placebo-controlled crossover study involving short-term placebo or walnut-enriched diet (48 g/d for 4 days). Apolipoproteins and markers of inflammation and vascular injury were measured before and after consumption of the experimental diets. Consumption of walnuts was associated with a statistically significant increase in serum apolipoprotein A concentrations (P = .03), but did not affect circulating levels of fetuin A, resistin, C-reactive protein, serum amyloid A, soluble intercellular adhesion molecules 1 and 3, soluble vascular cell adhesion protein 1, interleukins 6 and 8, tumor necrosis factor alpha, E-selectin, P-selectin, and thrombomodulin. Four days of walnut consumption (48 g/d) leads to mild increases in apolipoprotein A concentrations, changes that may precede and lead to the beneficial effects of walnuts on lipid profile in obese subjects with the metabolic syndrome. (C) 2012 Elsevier Inc. All rights reserved. C1 [Aronis, Konstantinos N.; Vamvini, Maria T.; Chamberland, John P.; Sweeney, Laura L.; Brennan, Aoife M.; Magkos, Faidon; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. [Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Sect Endocrinol,Dept Internal Med, Boston, MA 02215 USA. [Magkos, Faidon] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Joslin & Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 FU National Center for Research Resources [M01-RR-01032-328840]; National Institute of Diabetes and Digestive and Kidney Diseases [DK081913]; California Walnut Commission FX Grant support: The project described was supported by grant M01-RR-01032-328840 to the Harvard Clinical and Translational Science Center from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases (grant DK081913) and the California Walnut Commission. NR 48 TC 15 Z9 15 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2012 VL 61 IS 4 BP 577 EP 582 DI 10.1016/j.metabol.2011.09.008 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 914YY UT WOS:000301991000018 PM 22075273 ER PT J AU Bowirrat, A Chen, TJH Oscar-Berman, M Madigan, M Chen, ALH Bailey, JA Braverman, ER Kerner, M Giordano, J Morse, S Downs, BW Waite, RL Fornari, F Armaly, Z Blum, K AF Bowirrat, Abdalla Chen, Thomas J. H. Oscar-Berman, Marlene Madigan, Margaret Chen, Amanda L. H. Bailey, John A. Braverman, Eric R. Kerner, Mallory Giordano, John Morse, Siobhan Downs, B. William Waite, Roger L. Fornari, Frank Armaly, Zaher Blum, Kenneth TI Neuropsychopharmacology and Neurogenetic Aspects of Executive Functioning: Should Reward Gene Polymorphisms Constitute a Diagnostic Tool to Identify Individuals at Risk for Impaired Judgment? SO MOLECULAR NEUROBIOLOGY LA English DT Article DE Executive functions; Dopamine; Prefrontal cortex; Genetics; Reward deficiency syndrome (RDS) ID DEFICIT HYPERACTIVITY DISORDER; WORKING-MEMORY PERFORMANCE; OBSESSIVE-COMPULSIVE DISORDER; NUCLEUS-ACCUMBENS NEURONS; RODENT PREFRONTAL CORTEX; LONG-TERM POTENTIATION; DOPAMINE D2 RECEPTORS; BASAL GANGLIA; DECISION-MAKING; ALZHEIMERS-DISEASE AB Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest that examination of multifactorial interactions of an individual's genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies, we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission. C1 [Bailey, John A.; Blum, Kenneth] Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA. [Bailey, John A.; Blum, Kenneth] Univ Florida, McKnight Brain Inst, Gainesville, FL 32610 USA. [Bowirrat, Abdalla; Armaly, Zaher] Nazareth English Hosp EMME, IL-16100 Nazareth, Israel. [Chen, Thomas J. H.] Chang Jung Christian Univ, Dept Occupat Safety & Hlth, Tainan, Taiwan. [Oscar-Berman, Marlene] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02130 USA. [Oscar-Berman, Marlene] Boston VA Healthcare Syst, Boston, MA 02130 USA. [Oscar-Berman, Marlene] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02130 USA. [Oscar-Berman, Marlene] Boston Univ, Dept Anat & Neurobiol, Sch Med, Boston, MA 02130 USA. [Madigan, Margaret; Downs, B. William; Waite, Roger L.; Blum, Kenneth] Lifegen Inc, Dept Nutrigenom & Personalized Med, San Diego, CA 92101 USA. [Chen, Amanda L. H.] Chang Jung Christian Univ, Tainan, Taiwan. [Braverman, Eric R.] Weill Cornell Coll Med, Dept Neurol Surg, New York, NY 10065 USA. [Braverman, Eric R.; Kerner, Mallory; Blum, Kenneth] PATH Fdn NY, New York, NY 10010 USA. [Giordano, John; Morse, Siobhan; Blum, Kenneth] G&G Holist Addict Treatment Ctr, N Miami Beach, FL USA. [Fornari, Frank; Blum, Kenneth] Dominion Diagnost LLC, N Kingstown, RI USA. RP Blum, K (reprint author), Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA. EM bowirrat@netvision.net.il; tjhchen@yahoo.com.tw; oscar@bu.edu; MARGBETTS@HOTMAIL.COM; ac8858@gmail.com; baileyjo@UFL.EDU; mallory.kerner@gmail.com; michg@hotmail.com; samorse10@aol.com; bill@lifegen.org; drw8@san.rr.com; ffornari@me.com; pathmedical@aol.com FU NIAAA [R01 AA07112, K05 AA 00219]; Medical Research Service of the US Department of Veterans Affairs FX Marlene Oscar Berman is the recipient of grants from NIAAA (R01 AA07112, K05 AA 00219) and from the Medical Research Service of the US Department of Veterans Affairs. NR 168 TC 6 Z9 6 U1 11 U2 16 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD APR PY 2012 VL 45 IS 2 BP 298 EP 313 DI 10.1007/s12035-012-8247-z PG 16 WC Neurosciences SC Neurosciences & Neurology GA 916JT UT WOS:000302099200008 PM 22371275 ER PT J AU Willour, VL Seifuddin, F Mahon, PB Jancic, D Pirooznia, M Steele, J Schweizer, B Goes, FS Mondimore, FM MacKinnon, DF Perlis, RH Lee, PH Huang, J Kelsoe, JR Shilling, PD Rietschel, M Nothen, M Cichon, S Gurling, H Purcell, S Smoller, JW Craddock, N DePaulo, JR Schulze, TG McMahon, FJ Zandi, PP Potash, JB AF Willour, V. L. Seifuddin, F. Mahon, P. B. Jancic, D. Pirooznia, M. Steele, J. Schweizer, B. Goes, F. S. Mondimore, F. M. MacKinnon, D. F. Perlis, R. H. Lee, P. H. Huang, J. Kelsoe, J. R. Shilling, P. D. Rietschel, M. Noethen, M. Cichon, S. Gurling, H. Purcell, S. Smoller, J. W. Craddock, N. DePaulo, J. R., Jr. Schulze, T. G. McMahon, F. J. Zandi, P. P. Potash, J. B. CA BiGS Consortium TI A genome-wide association study of attempted suicide SO MOLECULAR PSYCHIATRY LA English DT Article DE ACP1; LRRTM4; 2p25; Wnt; lithium ID PROTEIN-TYROSINE-PHOSPHATASE; BIPOLAR DISORDER; MAJOR DEPRESSION; GENE-EXPRESSION; EARLY-ONSET; GENOTYPE IMPUTATION; PREFRONTAL CORTEX; FAMILIAL PATHWAYS; BEHAVIOR; LINKAGE AB The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. Although attempted suicide linkage regions have been identified on 2p11-12 and 6q25-26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single-nucleotide polymorphism (SNP) genotypes of 1201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1497 BP subjects without a history of suicide attempts. In all, 2507 SNPs with evidence for association at P < 0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (P = 5.07 x 10(-8)). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 (acid phosphatase 1) gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. Molecular Psychiatry (2012) 17, 433-444; doi: 10.1038/mp.2011.4; published online 22 March 2011 C1 [Willour, V. L.; Seifuddin, F.; Mahon, P. B.; Jancic, D.; Pirooznia, M.; Schweizer, B.; Goes, F. S.; Mondimore, F. M.; MacKinnon, D. F.; DePaulo, J. R., Jr.; Zandi, P. P.; Potash, J. B.] Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Steele, J.; Schulze, T. G.; McMahon, F. J.] Natl Inst Mental Hlth Intramural Res Program, Genet Basis Mood & Anxiety Disorders Unit, NIH, US Dept HHS, Bethesda, MD USA. [Perlis, R. H.; Lee, P. H.; Huang, J.; Purcell, S.; Smoller, J. W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perlis, R. H.; Lee, P. H.; Huang, J.; Purcell, S.; Smoller, J. W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kelsoe, J. R.; Shilling, P. D.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Rietschel, M.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Rietschel, M.] Univ Bonn, Dept Psychiat, Bonn, Germany. [Noethen, M.; Cichon, S.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany. [Noethen, M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Cichon, S.] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Gurling, H.] UCL, Dept Mental Hlth Sci, London, England. [Craddock, N.] Cardiff Univ, Sch Med, Dept Psychol, Cardiff, Wales. [Schulze, T. G.] Univ Gottingen, Dept Psychiat & Psychotherapy, Sect Psychiat Genet, Gottingen, Germany. RP Willour, VL (reprint author), Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-132, Baltimore, MD 21287 USA. EM willour@jhmi.edu RI Smith, Erin/E-5933-2011; McInnis, Melvin/F-6963-2012; Schulze, Thomas/H-2157-2013; Gurling, Hugh/A-5029-2010; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Zhang, Peng/N-2920-2014; OI McInnis, Melvin/0000-0002-0375-6247; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Zhang, Peng/0000-0003-1182-1392; Nothen, Markus/0000-0002-8770-2464; McMahon, Francis/0000-0002-9469-305X FU Concordant Rater Systems; Proteus Biomedical; RIDVentures; National Institute of Mental Health [MH079240]; American Foundation for Suicide Prevention; Margaret Price Investigatorships; [R01 MH079799] FX The authors declare no conflict of interest. Dr Perlis has received consulting fees from Concordant Rater Systems, Proteus Biomedical, and RIDVentures, and royalties/patent fees from Concordant Rater Systems.; This work was supported by grants from the National Institute of Mental Health (MH079240 to VLW) and the American Foundation for Suicide Prevention (VLW). It was also supported in part by R01 MH079799 (JWS). Drs Willour and Potash were also supported by Margaret Price Investigatorships. DNA samples were prepared and distributed by Rutgers University under a contract from the NIMH. We are grateful to the many interviewers and diagnosticians who contributed to this project, and to the families who devoted their time and effort to the study. Genome-wide SNP genotyping of the NIMH samples was performed through the Genetic Association Information Network under the direction of The Bipolar Genome Study (BiGS) Consortium. The Principal Investigators and Co-Investigators were: University of California San Diego, La Jolla, CA: John R Kelsoe (PI), Tiffany A Greenwood, Thomas B Barrett, Caroline M Nievergelt, Rebecca McKinney, Paul D Shilling; Scripps Research Institute, La Jolla, CA: Nicholas Schork (PI), Erin N Smith, Cinnamon S Bloss; Indiana University, Bloomington, IN: John I Nurnberger, Jr (PI), Howard J Edenberg, Tatiana Foroud, Daniel M Koller; University of Chicago, Chicago, IL: Elliot Gershon (PI), Chunyu Liu, Judith A Badner; Rush University Medical Center, Chicago, IL: William A Scheftner; Howard University, Washington, DC: William B Lawson (PI), Evaristus A Nwulia, Maria Hipolito; University of Iowa, Iowa City, IA: William Coryell (PI); Washington University, St Louis, MO: John Rice (PI); University of California San Francisco, San Francisco, CA: William Byerley (PI); National Institute of Mental Health, Bethesda, MD: Francis McMahon (PI), Thomas G Schulze; University of Pennsylvania, Philadelphia, PA: Wade Berrettini (PI); Johns Hopkins University, Baltimore, MD: James B Potash (PI), Peter P Zandi, Pamela B Mahon; University of Michigan, Ann Arbor, MI: Melvin G McInnis (PI), Sebastian Zollner, Peng Zhang; The Translational Genomics Research Institute, Phoenix, AZ: David Craig (PI), Szabolics Szelinger. Data and biomaterials were collected in four projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1991 to 1998, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, U01 MH46282: John Nurnberger, Marvin Miller and Elizabeth Bowman; Washington University, St Louis, MO, U01 MH46280: Theodore Reich, Allison Goate and John Rice; Johns Hopkins University, Baltimore, MD U01 MH46274: J Raymond DePaulo, Jr, Sylvia Simpson and Colin Stine; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD: Elliot Gershon, Diane Kazuba and Elizabeth Maxwell. Data and biomaterials were collected as part of 10 projects that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative.; From 1999 to 2003, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, R01 MH59545: John Nurnberger, Marvin J Miller, Elizabeth S Bowman, N Leela Rau, P Ryan Moe, Nalini Samavedy, Rif El-Mallakh (at the University of Louisville), Husseini Manji (at the Wayne State University), Debra A Glitz (at the Wayne State University), Eric T Meyer, Carrie Smiley, Tatiana Foroud, Leah Flury, Danielle M Dick, Howard Edenberg; Washington University, St Louis, MO, R01 MH059534: John Rice, Theodore Reich, Allison Goate, Laura Bierut; Johns Hopkins University, Baltimore, MD, R01 MH59533: Melvin McInnis, J Raymond DePaulo, Jr, Dean F MacKinnon, Francis M Mondimore, James B Potash, Peter P Zandi, Dimitrios Avramopoulos and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553: Wade Berrettini; University of California at Irvine, CA, R01 MH60068: William Byerley and Mark Vawter; University of Iowa, IA, R01 MH059548: William Coryell and Raymond Crowe; University of Chicago, IL, R01 MH59535: Elliot Gershon, Judith Badner, Francis McMahon, Chunyu Liu, Alan Sanders, Maria Caserta, Steven Dinwiddie, Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567: John Kelsoe, Rebecca McKinney; Rush University, IL, R01 MH059556: William Scheftner, Howard M Kravitz, Diana Marta, Annette Vaughn-Brown and Laurie Bederow; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810-01: Francis J Mc Mahon, Layla Kassem, Sevilla Detera-Wadleigh, Lisa Austin and Dennis L Murphy. Data and biomaterials were collected as part of 11 projects (Study 40) that participated in the National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 2003 to 2007, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, R01 MH59545: John Nurnberger, Marvin J Miller, Elizabeth S Bowman, N Leela Rau, P Ryan Moe, Nalini Samavedy, Rif El-Mallakh (at the University of Louisville), Husseini Manji (at Johnson and Johnson), Debra A Glitz (at the Wayne State University), Eric T Meyer (at the Oxford University, UK), Carrie Smiley, Tatiana Foroud, Leah Flury, Danielle M Dick (at the Virginia Commonwealth University), Howard Edenberg; Washington University, St Louis, MO, R01 MH059534: John Rice, Theodore Reich, Allison Goate, Laura Bierut K02 DA21237; Johns Hopkins University, Baltimore, MD, R01 MH59533: Melvin McInnis, J Raymond DePaulo, Jr, Dean F MacKinnon, Francis M Mondimore, James B Potash, Peter P Zandi, Dimitrios Avramopoulos and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553: Wade Berrettini; University of California at San Francisco, CA, R01 MH60068: William Byerley and Sophia Vinogradov; University of Iowa, IA, R01 MH059548: William Coryell, and Raymond Crowe; University of Chicago, IL, R01 MH59535: Elliot Gershon, Judith Badner, Francis McMahon, Chunyu Liu, Alan Sanders, Maria Caserta, Steven Dinwiddie, Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567: John Kelsoe, Rebecca McKinney; Rush University, IL, R01 MH059556: William Scheftner, Howard M Kravitz, Diana Marta, Annette Vaughn-Brown, and Laurie Bederow; NIMH Intramural Research Program, Bethesda, MD, 1Z01MH002810-01: Francis J McMahon, Layla Kassem, Sevilla Detera-Wadleigh, Lisa Austin, Dennis L Murphy; Howard University: William B Lawson, Evarista Nwulia, and Maria Hipolito. NR 47 TC 43 Z9 43 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD APR PY 2012 VL 17 IS 4 BP 433 EP 444 DI 10.1038/mp.2011.4 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 917KL UT WOS:000302173900010 PM 21423239 ER PT J AU Chen, HH Feng, Y Zhang, M Chao, W Josephson, L Shaw, SY Sosnovik, DE AF Chen, Howard H. Feng, Yan Zhang, Ming Chao, Wei Josephson, Lee Shaw, Stanley Y. Sosnovik, David E. TI Protective effect of the apoptosis-sensing nanoparticle AnxCLIO-Cy5.5 SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Apoptosis; Magnetic nanoparticle; Cardioprotection; Iron oxide; Gene expression ID ACUTE MYOCARDIAL-INFARCTION; IRON-OXIDE NANOPARTICLES; ANNEXIN A5; CELL-DEATH; NONINVASIVE DETECTION; REPERFUSION INJURY; IN-VIVO; HEART; PHOSPHATIDYLSERINE; PARTICLES AB The diagnostic utility of the apoptosis-sensing nanoparticle (NP), AnxCLIO-Cy5.5, is well established. Here we sought to define the pathophysiological impact of the nanoparticle (NP) on apoptotic cells. Confocal microscopy showed that AnxCLIO-Cy5.5 remained bound to apoptotic cell membranes for 3 hours but by 7 hours had become completely internalized. AnxCLIO-Cy5.5 exposure did not impact energetics, metabolism or caspase-3 activity in apoptotic cells. Gene expression in cells exposed to AnxCLIO-Cy5.5 did not reveal upregulation of pro-inflammatory or cell-death pathways. Moreover, exposure to AnxCLIO-Cy5.5 decreased the frequency of membrane rupture of early apoptotic cells. Similarly, in mice exposed to 1 hour of ischemia -reperfusion, the injection of AnxCLIO-Cy5.5 at the onset of reperfusion reduced infarct size/area at risk by 16.2%. Our findings suggest that AnxCLIO-Cy5.5 may protect apoptotic cells by stabilizing their cell membranes and has the potential to become a theranostic agent, capable of both identifying and salvaging early apoptotic cells. C1 [Sosnovik, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,CNY, Charlestown, MA 02129 USA. [Chen, Howard H.; Josephson, Lee; Sosnovik, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Feng, Yan; Zhang, Ming; Chao, Wei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. [Shaw, Stanley Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA. RP Sosnovik, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,CNY, Charlestown, MA 02129 USA. EM sosnovik@nmr.mgh.harvard.edu FU [R01 HL093038] FX This study was funded in part by R01 HL093038 (DES). NR 27 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD APR PY 2012 VL 8 IS 3 BP 291 EP 298 DI 10.1016/j.nano.2011.06.012 PG 8 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 914KS UT WOS:000301949300004 PM 21704591 ER PT J AU Chiang, C Jacobsen, JC Ernst, C Hanscom, C Heilbut, A Blumenthal, I Mills, RE Kirby, A Lindgren, AM Rudiger, SR McLaughlan, CJ Bawden, CS Reid, SJ Faull, RLM Snell, RG Hall, IM Shen, YP Ohsumi, TK Borowsky, ML Daly, MJ Lee, C Morton, CC MacDonald, ME Gusella, JF Talkowski, ME AF Chiang, Colby Jacobsen, Jessie C. Ernst, Carl Hanscom, Carrie Heilbut, Adrian Blumenthal, Ian Mills, Ryan E. Kirby, Andrew Lindgren, Amelia M. Rudiger, Skye R. McLaughlan, Clive J. Bawden, C. Simon Reid, Suzanne J. Faull, Richard L. M. Snell, Russell G. Hall, Ira M. Shen, Yiping Ohsumi, Toshiro K. Borowsky, Mark L. Daly, Mark J. Lee, Charles Morton, Cynthia C. MacDonald, Marcy E. Gusella, James F. Talkowski, Michael E. TI Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration SO NATURE GENETICS LA English DT Article ID B DNA CONFORMATIONS; HUMAN GENOME; STRUCTURAL VARIATION; CANCER; MECHANISMS; DISEASE; CHROMOTHRIPSIS; MUTAGENESIS AB We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. C1 [Chiang, Colby; Jacobsen, Jessie C.; Ernst, Carl; Hanscom, Carrie; Heilbut, Adrian; Blumenthal, Ian; Kirby, Andrew; Shen, Yiping; Daly, Mark J.; MacDonald, Marcy E.; Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jacobsen, Jessie C.; Ernst, Carl; MacDonald, Marcy E.; Gusella, James F.; Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Jacobsen, Jessie C.; Ernst, Carl; MacDonald, Marcy E.; Gusella, James F.; Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Mills, Ryan E.; Lindgren, Amelia M.; Lee, Charles; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kirby, Andrew; Daly, Mark J.; Morton, Cynthia C.; MacDonald, Marcy E.; Gusella, James F.; Talkowski, Michael E.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Rudiger, Skye R.; McLaughlan, Clive J.; Bawden, C. Simon] S Australian Res & Dev Inst, Livestock & Farming Syst Div, Mol Biol Lab, Roseworthy, SA, Australia. [Rudiger, Skye R.; McLaughlan, Clive J.; Bawden, C. Simon] S Australian Res & Dev Inst, Livestock & Farming Syst Div, Reprod Technol Lab, Roseworthy, SA, Australia. [Reid, Suzanne J.; Faull, Richard L. M.; Snell, Russell G.] Univ Auckland, Ctr Brain Res, Fac Med & Hlth Sci, Auckland 1, New Zealand. [Reid, Suzanne J.; Snell, Russell G.] Univ Auckland, Fac Sci, Sch Biol Sci, Auckland 1, New Zealand. [Faull, Richard L. M.] Univ Auckland, Dept Anat Radiol, Fac Med & Hlth Sci, Auckland 1, New Zealand. [Hall, Ira M.] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. [Shen, Yiping] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA. [Ohsumi, Toshiro K.; Borowsky, Mark L.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Talkowski, ME (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM talkowski@chgr.mgh.harvard.edu RI perumal, murugiah/D-1565-2012; Mills, Ryan/A-1979-2011; Reid, Suzanne/H-7082-2012; Heilbut, Adrian/J-9427-2012; OI Mills, Ryan/0000-0003-3425-6998; Heilbut, Adrian/0000-0002-8169-7967; Reid, Suzanne/0000-0002-8068-6529; Chiang, Colby/0000-0002-4113-6065 FU US National Institutes of Health [GM061354, HD065286, MH087123, NS32765, NS16367]; Simons Foundation Autism Research Initiative; Autism Speaks; CHDI Foundation; Neurological Foundation of New Zealand; Canadian Institute for Health Research (CIHR) FX We thank all study participants, their families and the referring clinicians for their invaluable contributions. We thank T. Gillis, M.A. Anderson, W. Varney, J. Ruliera, T. Henderson, C. Zhang, L. Griffin, The Genomics Core of the Massachusetts General Hospital Center for Human Genetic Research, the Genome Sequencing Platform at the Broad Institute and the Partners Center for Personalized Genomic Medicine for technical assistance. We thank M. Sun for performing the multiplex ligation-dependent probe amplification (MLPA) experiments. We also thank the Partners Research Computing at Massachusetts General Hospital. This work was funded by grants from the US National Institutes of Health (GM061354, HD065286, MH087123, NS32765 and NS16367), the Simons Foundation Autism Research Initiative, Autism Speaks and the CHDI Foundation. J.C.J. was the recipient of the Philip Wrightson Fellowship of the Neurological Foundation of New Zealand, C.E. received a Bisby Fellowship from the Canadian Institute for Health Research (CIHR). NR 41 TC 95 Z9 95 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2012 VL 44 IS 4 BP 390 EP U195 DI 10.1038/ng.2202 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 916VF UT WOS:000302130600012 PM 22388000 ER PT J AU Stadtfeld, M Apostolou, E Ferrari, F Choi, J Walsh, RM Chen, TP Ooi, SSK Kim, SY Bestor, TH Shioda, T Park, PJ Hochedlinger, K AF Stadtfeld, Matthias Apostolou, Effie Ferrari, Francesco Choi, Jiho Walsh, Ryan M. Chen, Taiping Ooi, Steen S. K. Kim, Sang Yong Bestor, Timothy H. Shioda, Toshi Park, Peter J. Hochedlinger, Konrad TI Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells SO NATURE GENETICS LA English DT Article ID PLURIPOTENT STEM-CELLS; MOUSE; METHYLATION; DOMAIN; GENES; COMPLEMENTATION; ACTIVATION; SEQUENCES; GENOME; DNMT3A AB The generation of induced pluripotent stem cells (iPSCs) often results in aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster, compromising the ability to generate entirely iPSC-derived adult mice ('all-iPSC mice'). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration that interferes with binding of the de novo DNA methyltransferase Dnmt3a. This approach allowed us to generate all-iPSC mice from mature B cells, which have until now failed to support the development of exclusively iPSC-derived postnatal animals. Our data show that transcription factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that culture conditions during cellular reprogramming can strongly influence the epigenetic and biological properties of the resultant iPSCs. C1 [Stadtfeld, Matthias; Apostolou, Effie; Choi, Jiho; Walsh, Ryan M.; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Stadtfeld, Matthias; Apostolou, Effie; Choi, Jiho; Walsh, Ryan M.; Shioda, Toshi; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Stadtfeld, Matthias; Apostolou, Effie; Choi, Jiho; Walsh, Ryan M.; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Ferrari, Francesco; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA. [Chen, Taiping] Novartis Inst Biomed Res, Cambridge, MA USA. [Ooi, Steen S. K.] UCL, Inst Canc, London, England. [Ooi, Steen S. K.; Bestor, Timothy H.] Columbia Univ, Dept Genet & Dev, Coll Phys & Surg, New York, NY USA. [Kim, Sang Yong] Cold Spring Harbor Lab, Transgen Facil, Woodbury, NY USA. [Hochedlinger, Konrad] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Harvard Stem Cell Inst, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu RI Ferrari, Francesco/H-5007-2012; OI Ferrari, Francesco/0000-0002-9811-3753; Ooi, Steen/0000-0003-4198-9014; Kim, Sang Yong /0000-0001-7326-7505; Stadtfeld, Matthias/0000-0002-5852-9906 FU Howard Hughes Medical Institute (HHMI); Jane Coffin Childs; US National Institutes of Health [DP2OD003266, R01HD058013] FX We are grateful to B. Payer (Harvard University) for providing M. musculus x M. castaneus fibroblasts, D. Wesemann for advice on B-cell isolation and immunoglobulin rearrangements, A. Foudi for genomic DNA from B cells, H. Su for technical assistance and A. Riley for help with blastocyst injections. We thank past and present members of the Hochedlinger laboratory for suggestions. M.S. was supported by a postdoctoral fellowship from the Howard Hughes Medical Institute (HHMI), E.A. was supported by a Jane Coffin Childs postdoctoral fellowship, and support to K.H. was from the US National Institutes of Health (DP2OD003266 and R01HD058013). NR 34 TC 136 Z9 144 U1 9 U2 43 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD APR PY 2012 VL 44 IS 4 BP 398 EP U205 DI 10.1038/ng.1110 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 916VF UT WOS:000302130600013 PM 22387999 ER PT J AU Swanson, RA AF Swanson, Raymond A. TI One cell's poison is another cell's cure SO NATURE NEUROSCIENCE LA English DT Editorial Material ID CEREBRAL-ISCHEMIA; BCL-X; APOPTOSIS; MECHANISMS; DYNAMICS; BRAIN; DEATH AB A drug that promotes cell death in cancer cells prevents cell death in post-ischemic neurons. These contrasting effects stem from the distinct actions of the anti-apoptotic protein Bcl-x(L) and its cleavage product, Delta N-Bcl-x(L). C1 [Swanson, Raymond A.] Univ Calif San Francisco, Neurol & Rehabil Serv, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Swanson, RA (reprint author), Univ Calif San Francisco, Neurol & Rehabil Serv, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. EM raymond.swanson@ucsf.edu OI Swanson, Raymond/0000-0002-3664-5359 FU NINDS NIH HHS [R01 NS041421] NR 15 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2012 VL 15 IS 4 BP 505 EP 506 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 916PA UT WOS:000302114500005 PM 22449958 ER PT J AU Wu, LJ Wu, GX Sharif, MRA Baker, A Jia, YH Fahey, FH Luo, HBR Feener, EP Clapham, DE AF Wu, Long-Jun Wu, Gongxiong Sharif, M. Reza Akhavan Baker, Amanda Jia, Yonghui Fahey, Frederic H. Luo, Hongbo R. Feener, Edward P. Clapham, David E. TI The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke SO NATURE NEUROSCIENCE LA English DT Article ID NADPH OXIDASE; MICROGLIAL ACTIVATION; CEREBRAL-ISCHEMIA; INTRACELLULAR PH; ACID EXTRUSION; MECHANISMS; CELLS; MICE; CURRENTS; SLICES AB Phagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. The voltage-gated proton channel Hv1 enables NOX function by compensating cellular loss of electrons with protons. Accordingly, we investigated whether NOX-mediated brain damage in stroke can be inhibited by suppression of Hv1. We found that mouse and human brain microglia, but not neurons or astrocytes, expressed large Hv1-mediated currents. Hv1 was required for NOX-dependent ROS generation in brain microglia in situ and in vivo. Mice lacking Hv1 were protected from NOX-mediated neuronal death and brain damage 24 h after stroke. These results indicate that Hv1-dependent ROS production is responsible for a substantial fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke. C1 [Wu, Long-Jun; Clapham, David E.] Childrens Hosp Boston, Howard Hughes Med Inst, Dept Cardiol, Boston, MA 02115 USA. [Wu, Long-Jun; Clapham, David E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Wu, Gongxiong; Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA USA. [Sharif, M. Reza Akhavan] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Baker, Amanda; Fahey, Frederic H.] Childrens Hosp Boston, Dept Radiol, Boston, MA USA. [Jia, Yonghui; Luo, Hongbo R.] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA. [Jia, Yonghui; Luo, Hongbo R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Clapham, DE (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Dept Cardiol, Boston, MA 02115 USA. EM dclapham@enders.tch.harvard.edu RI Wu, Long-Jun /E-2684-2012; OI Wu, Long-Jun/0000-0001-8019-3380 FU US National Institutes of Health [R01 MH090293, R01 EY019029]; Harvard Medical School; American Heart Association [11SDG7340011] FX We thank L. Silberstein, W. Yang and M. Kurtev for technical assistance, S. Doctrow (Boston University) for kindly providing us with EUK-207, Y. Kirichok (University of California, San Francisco) for Hv1 antibody, and D. Chaudhuri for critical reading of the manuscript. This work was supported by the US National Institutes of Health (R01 MH090293 to D.E.C. and R01 EY019029 to E.P.F.). L.-J.W. is supported by a Lefler postdoctoral fellowship from Harvard Medical School and a Scientist Development Grant from the American Heart Association (11SDG7340011). NR 43 TC 89 Z9 90 U1 0 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2012 VL 15 IS 4 BP 565 EP 573 DI 10.1038/nn.3059 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 916PA UT WOS:000302114500016 PM 22388960 ER PT J AU Vanneman, M Dranoff, G AF Vanneman, Matthew Dranoff, Glenn TI Combining immunotherapy and targeted therapies in cancer treatment SO NATURE REVIEWS CANCER LA English DT Review ID NATURAL-KILLER-CELL; HEAT-SHOCK-PROTEIN; CHRONIC MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMOR; METASTATIC COLORECTAL-CANCER; ANTITUMOR IMMUNE-RESPONSE; MINIMAL RESIDUAL DISEASE; CD8(+) T-CELLS; MULTIPLE-MYELOMA; DENDRITIC CELLS AB During the past two decades, the paradigm for cancer treatment has evolved from relatively nonspecific cytotoxic agents to selective, mechanism-based therapeutics. Cancer chemotherapies were initially identified through screens for compounds that killed rapidly dividing cells. These drugs remain the backbone of current treatment, but they are limited by a narrow therapeutic index, significant toxicities and frequently acquired resistance. More recently, an improved understanding of cancer pathogenesis has given rise to new treatment options, including targeted agents and cancer immunotherapy. Targeted approaches aim to inhibit molecular pathways that are crucial for tumour growth and maintenance; whereas, immunotherapy endeavours to stimulate a host immune response that effectuates long-lived tumour destruction. Targeted therapies and cytotoxic agents also modulate immune responses, which raises the possibility that these treatment strategies might be effectively combined with immunotherapy to improve clinical outcomes. C1 [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM glenn_dranoff@dfci.harvard.edu FU US National Cancer Institute; Leukemia and Lymphoma Society; Melanoma Research Alliance; Alliance for Cancer Gene Therapy; Research Foundation for the Treatment of Ovarian Cancer; Novartis Inc. FX Glenn Dranoff is supported by grants from the US National Cancer Institute, the Leukemia and Lymphoma Society, the Melanoma Research Alliance, the Alliance for Cancer Gene Therapy, the Research Foundation for the Treatment of Ovarian Cancer, and Novartis Inc. NR 128 TC 406 Z9 415 U1 31 U2 202 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD APR PY 2012 VL 12 IS 4 BP 237 EP 251 DI 10.1038/nrc3237 PG 15 WC Oncology SC Oncology GA 916WW UT WOS:000302134900009 PM 22437869 ER PT J AU Rottiers, V Naar, AM AF Rottiers, Veerle Naeaer, Anders M. TI MicroRNAs in metabolism and metabolic disorders SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID SUBCUTANEOUS ADIPOSE-TISSUE; HEPATIC LIPID-METABOLISM; ELEMENT-BINDING PROTEIN; FATTY-ACID-METABOLISM; PANCREATIC BETA-CELLS; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; GLUCOSE-METABOLISM; IN-VIVO; CHOLESTEROL HOMEOSTASIS AB MicroRNAs (miRNAs) have recently emerged as key regulators of metabolism. For example, miR-33a and miR-33b have a crucial role in controlling cholesterol and lipid metabolism in concert with their host genes, the sterol-regulatory element-binding protein (SREBP) transcription factors. Other metabolic miRNAs, such as miR-103 and miR-107, regulate insulin and glucose homeostasis, whereas miRNAs such as miR-34a are emerging as key regulators of hepatic lipid homeostasis. The discovery of circulating miRNAs has highlighted their potential as both endocrine signalling molecules and disease markers. Dysregulation of miRNAs may contribute to metabolic abnormalities, suggesting that miRNAs may potentially serve as therapeutic targets for ameliorating cardiometabolic disorders. C1 [Rottiers, Veerle; Naeaer, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Rottiers, Veerle; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Naar, AM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM naar@helix.mgh.harvard.edu RI Xie, Huangming/B-2260-2012 FU US National Institutes of Health (NIH) [R21DK084459, R01DK094184] FX This work was supported by US National Institutes of Health (NIH) grants R21DK084459 and R01DK094184. The authors apologize for their inability to discuss and cite all relevant papers owing to space constraints. NR 148 TC 365 Z9 377 U1 3 U2 93 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD APR PY 2012 VL 13 IS 4 BP 239 EP 250 DI 10.1038/nrm3313 PG 12 WC Cell Biology SC Cell Biology GA 916PR UT WOS:000302116200011 PM 22436747 ER PT J AU Yenari, MA Han, HS AF Yenari, Midori A. Han, Hyung Soo TI Neuroprotective mechanisms of hypothermia in brain ischaemia SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID FOCAL CEREBRAL-ISCHEMIA; FACTOR-KAPPA-B; ASPHYXIAL CARDIAC-ARREST; TO-MODERATE HYPOTHERMIA; SIGNAL-REGULATED KINASE; WHOLE-BODY HYPOTHERMIA; NECROSIS-FACTOR-ALPHA; RNA-BINDING PROTEIN; MILD HYPOTHERMIA; THERAPEUTIC HYPOTHERMIA AB Cooling can reduce primary injury and prevent secondary injury to the brain after insults in certain clinical settings and in animal models of brain insult. The mechanisms that underlie the protective effects of cooling - also known as therapeutic hypothermia are slowly beginning to be understood. Hypothermia influences multiple aspects of brain physiology in the acute, subacute and chronic stages of ischaemia. It affects pathways leading to excitotoxicity, apoptosis, inflammation and free radical production, as well as blood flow, metabolism and blood-brain barrier integrity. Hypothermia may also influence neurogenesis, gliogenesis and angiogenesis after injury. It is likely that no single factor can explain the neuroprotection provided by hypothermia, but understanding its myriad effects may shed light on important neuroprotective mechanisms. C1 [Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Han, Hyung Soo] Kyungpook Natl Univ, Sch Med, Dept Physiol, Taegu 700422, South Korea. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. EM Yenari@alum.mit.edu FU US National Institutes of Health [NS40516]; Veteran's Merit Award; Ministry of Health & Welfare, Republic of Korea [A100870]; Industrial Strategic technology development program [10035197]; Ministry of Knowledge Economy (MKE) Korea FX This work was supported by grants from the US National Institutes of Health (NS40516 to M.Y.), the Veteran's Merit Award (M.Y.), the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A100870 to H.S.H.) and the Industrial Strategic technology development program (10035197 to H.S.H.), which is funded by the Ministry of Knowledge Economy (MKE), Korea. Grants to M.Y. were administered by the Northern California Institute for Research and Education, and supported by resources of the Veterans Affairs Medical Center, San Francisco, California. NR 126 TC 146 Z9 159 U1 2 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD APR PY 2012 VL 13 IS 4 BP 267 EP 278 DI 10.1038/nrn3174 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 914IH UT WOS:000301942500010 PM 22353781 ER PT J AU Ezzatizadeh, V Pinto, RM Sandi, C Sandi, M Al-Mahdawi, S Riele, HT Pook, MA AF Ezzatizadeh, Vahid Pinto, Ricardo Mouro Sandi, Chiranjeevi Sandi, Madhavi Al-Mahdawi, Sahar Riele, Hein Te Pook, Mark A. TI The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Friedreich ataxia; FRDA. frataxin; GAA trinucleotide repeat; Transgenic mouse model; Mismatch repair; MMR; Msh2; Msh3; Msh6; Pms2 ID BASE EXCISION-REPAIR; KNOCK-IN MICE; TRIPLET-REPEAT; TRINUCLEOTIDE EXPANSION; TRANSGENIC MICE; PARENTAL GENDER; FRDA GENE; DISEASE; CELLS; PROTEINS AB Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a dynamic GAA repeat expansion mutation within intron 1 of the FXN gene. Studies of mouse models for other trinucleotide repeat (TNR) disorders have revealed an important role of mismatch repair (MMR) proteins in TNR instability. To explore the potential role of MMR proteins on intergenerational GAA repeat instability in FRDA, we have analyzed the transmission of unstable GAA repeat expansions from FXN transgenic mice which have been crossed with mice that are deficient for Msh2, Msh3, Msh6 or Pms2. We find in all cases that absence of parental MMR protein not only maintains transmission of GM expansions and contractions, but also increases GAA repeat mutability (expansions and/or contractions) in the offspring. This indicates that Msh2, Msh3, Msh6 and Pms2 proteins are not the cause of intergenerational GAA expansions or contractions, but act in their canonical MMR capacity to protect against GAA repeat instability. We further identified differential modes of action for the four MMR proteins. Thus, Msh2 and Msh3 protect against GM repeat contractions, while Msh6 protects against both GAA repeat expansions and contractions, and Pms2 protects against GAA repeat expansions and also promotes contractions. Furthermore, we detected enhanced occupancy of Msh2 and Msh3 proteins downstream of the FXN expanded GAA repeat, suggesting a model in which Msh2/3 dimers are recruited to this region to repair mismatches that would otherwise produce intergenerational GAA contractions. These findings reveal substantial differences in the intergenerational dynamics of expanded GM repeat sequences compared with expanded CAG/CTG repeats, where Msh2 and Msh3 are thought to actively promote repeat expansions. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ezzatizadeh, Vahid; Sandi, Chiranjeevi; Sandi, Madhavi; Al-Mahdawi, Sahar; Pook, Mark A.] Brunel Univ, Div Biosci, Sch Hlth Sci & Social Care, Uxbridge UB8 3PH, Middx, England. [Pinto, Ricardo Mouro] Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Riele, Hein Te] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands. RP Pook, MA (reprint author), Brunel Univ, Div Biosci, Sch Hlth Sci & Social Care, Uxbridge UB8 3PH, Middx, England. EM Mark.Pook@brunel.ac.uk FU National Institutes of Health (NIH), USA; Muscular Dystrophy Association (MDA) USA; Ataxia UK; Friedreich's Ataxia Research Alliance (FARA); GoFAR; Wellcome Trust [089757]; European Union Seventh Framework Programme [242193/EFACTS] FX This work is dedicated to the memory of Steve Pash. We thank Sanjay Bidichandani (University of Oklahoma Health Sciences Centre) for initiating collaborative studies, and Michael Liskay (Oregon Health & Science University) and Darren Monckton (University of Glasgow) for providing the Pms2 knockout mice. This work was supported by the National Institutes of Health (NIH), USA; Muscular Dystrophy Association (MDA) USA; Ataxia UK; Friedreich's Ataxia Research Alliance (FARA); GoFAR; and the Wellcome Trust [089757]. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 242193/EFACTS. NR 38 TC 27 Z9 27 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD APR PY 2012 VL 46 IS 1 BP 165 EP 171 DI 10.1016/j.nbd.2012.01.002 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 913SQ UT WOS:000301898100018 PM 22289650 ER PT J AU Kennedy, DN Hodge, SM Gao, Y Frazier, JA Haselgrove, C AF Kennedy, David N. Hodge, Steven M. Gao, Yong Frazier, Jean A. Haselgrove, Christian TI The Internet Brain Volume Database: A Public Resource for Storage and Retrieval of Volumetric Data SO NEUROINFORMATICS LA English DT Article DE Brain; Volume; Quantitative neuroanatomy; Morphometry; Database; Website ID ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME; CEREBRAL-CORTEX; MRI; SCHIZOPHRENIA; METAANALYSIS; BIOMARKERS; COGNITION; SYSTEM; AUTISM AB Every month, numerous publications appear that include neuroanatomic volumetric observations. The current and past literature that includes volumetric measurements is vast, but variable with respect to specific species, structures, and subject characteristics (such as gender, age, pathology, etc.). In this report we introduce the Internet Brain Volume Database (IBVD), www.nitrc.org/projects/ibvd, a site devoted to facilitating access to and utilization of neuroanatomic volumetric observations as published in the literature. We review the design and functionality of the site. The IBVD is the first database dedicated to integrating, exposing and sharing brain volumetric observations across species and disease. It offers valuable functionality for quality assurance assessment of results as well as support for meta-analysis across large segments of the published literature that are obscured from traditional text-based search engines. C1 [Kennedy, David N.; Hodge, Steven M.; Frazier, Jean A.; Haselgrove, Christian] Univ Massachusetts, Div Neuroinformat, Sch Med, Worcester, MA 01605 USA. [Kennedy, David N.; Hodge, Steven M.; Frazier, Jean A.; Haselgrove, Christian] Univ Massachusetts, Child & Adolescent NeuroDev Initiat CANDI, Dept Psychiat, Sch Med, Worcester, MA 01605 USA. [Gao, Yong] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kennedy, DN (reprint author), Univ Massachusetts, Div Neuroinformat, Sch Med, 356 Plantat St,Biotech 1,Suite 100, Worcester, MA 01605 USA. EM David.Kennedy@umassmed.edu RI Kennedy, David/H-3627-2012 FU Human Brain Project [NS34189]; [MH083320]; [NS064354] FX This work was supported in part by grant NS34189 (PI Kennedy) as part of the Human Brain Project, MH083320 (Co PIs Kennedy and Frazier) and NS064354 (PI Gao). Thanks for tireless data entry efforts are owed to Julianne Steele, Aliya Dincer and Thomas Buckley. Marilyn Albert and Bruce Fischl provided access to individual data from their published work. Robert Williams provided group and individual mouse brain volumes from the Mouse Brain Library (MBL-http://www.mbl.org/). NR 34 TC 4 Z9 4 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD APR PY 2012 VL 10 IS 2 BP 129 EP 140 DI 10.1007/s12021-011-9130-1 PG 12 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 915VS UT WOS:000302056300003 PM 21931990 ER PT J AU Babu, MA Heary, RF Nahed, BV AF Babu, Maya A. Heary, Robert F. Nahed, Brian V. TI Device Innovation in Neurosurgery: Controversy, Learning, and Future Directions SO NEUROSURGERY LA English DT Review DE Device Innovation; Patents; Royalties; Conflicts of Interest ID ORTHOPEDIC SURGEONS; INDUSTRY; INSTRUMENTATION; STIMULATION; TECHNOLOGY; ETHICS; FUSION AB Innovation in medicine has led to advances directly benefitting patients. Yet recent legislation has created intense scrutiny of the relationship between surgeons and industry. Critics argue that surgeon-held patents and royalties incentivize surgeon loyalty, influencing decision making as to which devices are used intraoperatively. We explored the potential for inventor-related conflicts of interest. We searched patent records from the United States Patent and Trademark Office for every diplomate recognized by the American Board of Neurological Surgeons (4868 neurosurgeons). We also searched physician payment registries of the 5 largest device makers; of these, Medtronic, DePuy, and Zimmer were the only companies with available registries. A total of 147 neurosurgeons (3.0%) hold a total of 582 patents; the number of patents held per neurosurgeon ranges from 1 to 53. The fields in which patents are held include tumor (125), spine (98), vascular (54), trauma (27), stereotaxy/image guidance (88), pain (19), peripheral nerve (2), electrical stimulation (63), and pediatrics (9); surgical instruments (59), drug delivery (17), and other (21) account for the remainder. The total amount of royalties received by neurosurgeons in 2010 is expected to be $13 223 000 (minimum: $7K, maximum: $8.261M). Despite public and legislative perceptions of widespread conflicts of interest, there are relatively few neurosurgeons who hold patents and receive significant royalties. C1 [Babu, Maya A.] Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Neurol Surg, Rochester, MN 55905 USA. [Heary, Robert F.] Neurol Inst New Jersey, Dept Neurosurg, Newark, NJ USA. [Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Babu, MA (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM babu.maya@mayo.edu FU DePuy Spine; Biomet Spine FX Dr Heary receives support from DePuy Spine and Biomet Spine and receives royalties from DePuy Spine and Zimmer Spine. The other authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 56 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 2012 VL 70 IS 4 BP 789 EP 794 DI 10.1227/NEU.0b013e318237a68b PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 914FF UT WOS:000301934000022 PM 21946505 ER PT J AU Thurston, RC El Khoudary, SR Sutton-Tyrrell, K Crandall, CJ Gold, EB Sternfeld, B Joffe, H Selzer, F Matthews, KA AF Thurston, Rebecca C. El Khoudary, Samar R. Sutton-Tyrrell, Kim Crandall, Carolyn J. Gold, Ellen B. Sternfeld, Barbara Joffe, Hadine Selzer, Faith Matthews, Karen A. TI Vasomotor Symptoms and Lipid Profiles in Women Transitioning Through Menopause SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID DENSITY LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR RISK-FACTORS; CORONARY-HEART-DISEASE; POSTMENOPAUSAL WOMEN; HOT FLASHES; HORMONE-THERAPY; HEALTH; NATION; STANDARDIZATION; ESTRADIOL AB OBJECTIVE: To examine associations between vasomotor symptoms and lipids over 8 years, controlling for other cardiovascular risk factors, estradiol, and follicle-stimulating hormone. METHODS: Study of Women's Health Across the Nation participants (N = 3,201), aged 42-52 years at entry, completed interviews on frequency of hot flushes and night sweats (none, 1-5 days, 6 days or more, in the past 2 weeks) physical measures (blood pressure, height, weight), and blood draws (low-density lipoprotein [LDL], high-density lipoprotein [HDL], apolipoprotein A-1, apolipoprotein B, lipoprotein[a], triglycerides, serum estradiol, follicle-stimulating hormone) yearly for 8 years. Relations between symptoms and lipids were examined in linear mixed models adjusting for cardiovascular risk factors, medications, and hormones. RESULTS: Compared with no flushes, experiencing hot flushes was associated with significantly higher LDL (1-5 days: beta [standard error]=1.48 [0.47], P<.01; 6 days or more: beta [standard error]= 2.13 [0.62], P<.001), HDL (1-5 days: beta [standard error]=0.30 [0.18]; 6 days or more: beta [standard error]=0.77 [0.24], P<.01), apolipoprotein A-1 (1-5 days: beta [standard error]=0.92 [0.47], P<.10; 6 days or more: beta [standard error] beta 1.97 [0.62], P<.01), apolipoprotein B (1-5 days: beta [standard error]=1.41 [0.41], P<.001; 6 days or more: beta [standard error]=2.51 [0.54], P<.001), and triglycerides (1-5 days: percent change [95% confidence interval]=2.91 [1.41-4.43], P<.001; 6 days or more: percent change [95% confidence interval[=5.90 [3.86-7.97], P<.001) in multivariable models. Findings largely persisted adjusting for hormones. Estimated mean differences in lipid levels between hot flushes 6 days or more compared with no days ranged from less than 1 (for HDL) to 10 mg/dL (for triglycerides). Night sweats were similar. Associations were strongest for lean women. CONCLUSION: Vasomotor symptoms were associated with higher LDL, HDL, apolipoprotein A-1, apolipoprotein B, and triglycerides. Lipids should be considered in links between hot flushes and cardiovascular risk. (Obstet Gynecol 2012;119:753-61) DOI: 10.1097/AOG.0b013e31824a09ec C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Thurston, RC (reprint author), 3811 OHara St, Pittsburgh, PA 15213 USA. EM thurstonrc@upmc.edu OI El Khoudary Abushaban, Samar/0000-0003-2913-0821 FU NIH [AG029216]; Bayer Health Care Pharmaceuticals FX For full study acknowledgements, see the Appendix online at http://links.lww.com/AOG/A291. This work was also supported by NIH grant AG029216 (Dr. Thurston).; Dr. Joffe has received research support from Bayer Health Care Pharmaceuticals and has performed advisory or consulting work for Sanofi-Aventis/Sunovion, Pfizer, and Noven. The other authors did not report any potential conflicts of interest. NR 33 TC 22 Z9 22 U1 0 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 2012 VL 119 IS 4 BP 753 EP 761 DI 10.1097/AOG.0b013e31824a09ec PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 914SC UT WOS:000301971400010 PM 22433339 ER PT J AU Oaklander, AL Wilson, PR Moskovitz, PA Manning, DC Lubenow, T Levine, JD Harden, RN Galer, BS Cooper, MS Bruehl, S Broatch, J Berde, C Bennett, GJ AF Oaklander, Anne Louise Wilson, Peter R. Moskovitz, Peter A. Manning, Donald C. Lubenow, Timothy Levine, Jon D. Harden, R. Norman Galer, Bradley S. Cooper, Mark S. Bruehl, Stephen Broatch, James Berde, Charles Bennett, Gary J. TI Response to "A new definition of neuropathic pain'' SO PAIN LA English DT Letter ID SYNDROME TYPE-I; NERVE C1 [Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Wilson, Peter R.] Mayo Clin, Dept Anesthesiol, Rochester, MN USA. [Moskovitz, Peter A.] George Washington Univ, Dept Orthopaed Surg, Washington, DC USA. [Moskovitz, Peter A.] George Washington Univ, Dept Neurol Surg, Washington, DC USA. [Lubenow, Timothy] Rush Univ, Dept Anesthesiol, Med Ctr, Chicago, IL 60612 USA. [Levine, Jon D.] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. [Harden, R. Norman] Northwestern Univ, Rehabil Inst Chicago, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. [Galer, Bradley S.] Nuvo Res Inc, W Chester, PA USA. [Cooper, Mark S.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Bruehl, Stephen] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Broatch, James] RSDSA, Milford, CT USA. [Berde, Charles] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02114 USA. [Bennett, Gary J.] McGill Univ, Dept Anesthesiol, Montreal, PQ, Canada. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. EM aoaklander@partners.org FU NINDS NIH HHS [K24NS059892] NR 11 TC 3 Z9 3 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD APR PY 2012 VL 153 IS 4 BP 934 EP 935 DI 10.1016/j.pain.2012.01.012 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 913KS UT WOS:000301877300029 PM 22342073 ER PT J AU Horowitz, SH AF Horowitz, Steven H. TI Response to commentary: A new definition of neuropathic pain SO PAIN LA English DT Letter C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Horowitz, SH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM shhorowitz@partners.org NR 8 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD APR PY 2012 VL 153 IS 4 BP 935 EP 935 DI 10.1016/j.pain.2012.01.011 PG 1 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 913KS UT WOS:000301877300030 PM 22341564 ER PT J AU Grill, J Puget, S Andreiuolo, F Philippe, C MacConaill, L Kieran, MW AF Grill, Jacques Puget, Stephanie Andreiuolo, Felipe Philippe, Cathy MacConaill, Laura Kieran, Mark W. TI Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma SO PEDIATRIC BLOOD & CANCER LA English DT Article DE ATM; brainstem; PI3KCA; stereotactic biopsy; targeted therapy; TP53 ID BRAIN-STEM GLIOMAS; FUTURE STRATEGIES; CANCER; GENOME; EXPRESSION; CHILDREN; TUMORS; P53 AB Diffuse intrinsic pontine gliomas (DIPG) can not be cured with current treatment modalities. Targeted therapy in this disease would benefit from advanced technologies detecting relevant drugable mutations. Twenty patients with classic newly diagnosed DIPG underwent stereotactic biopsies and were analyzed for the presence of 983 different mutations in 115 oncogenes and tumor-suppressor genes using OncoMap, a mass spectrometric method of allele detection. Our results identified oncogenic mutations in TP53 (40%), PI3KCA (15%), and ATM/MPL (5%) while none were identified in a large number of other genes commonly mutated in malignant gliomas. The identification of oncogenic mutations in the PI3K pathway offers the potential of a therapeutic target at initial diagnosis in this devastating disease. Pediatr Blood Cancer 2012; 58: 489491. (c) 2011 Wiley Periodicals, Inc. C1 [Grill, Jacques; Andreiuolo, Felipe] Univ Paris 11, Gustave Roussy Canc Inst, Dept Pediat & Adolescent Oncol, Brain Tumor Program, Villejuif, France. [Puget, Stephanie] Univ Paris 05, Hop Necker Enfants Malades, Dept Neurosurg, Paris, France. [Andreiuolo, Felipe; Philippe, Cathy] Gustave Roussy Canc Inst, CNRS Vectorol & Anticancer Treatments 8203, Villejuif, France. [MacConaill, Laura] Brigham & Womens Hosp, Boston, MA 02115 USA. [MacConaill, Laura] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Kieran, Mark W.] Childrens Hosp, Boston, MA 02115 USA. RP Grill, J (reprint author), Univ Paris 11, Gustave Roussy Canc Inst, Dept Pediat & Adolescent Oncol, Brain Tumor Program, Villejuif, France. EM grill@igr.fr OI Kieran, Mark/0000-0003-2184-7692 FU Charity l'Etoile de Martin; French National Cancer Agency (INCa) FX JG and CP were supported by the Charity l'Etoile de Martin. FA was supported by a grant of the French National Cancer Agency (INCa). NR 22 TC 40 Z9 41 U1 0 U2 6 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2012 VL 58 IS 4 BP 489 EP 491 DI 10.1002/pbc.24060 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 895NK UT WOS:000300502800004 PM 22190243 ER PT J AU Denburg, AE Joffe, S Gupta, S Howard, SC Ribeiro, RC Antillon, FA Vasquez, R Sung, LL AF Denburg, Avram E. Joffe, Steven Gupta, Sumit Howard, Scott C. Ribeiro, Raul C. Antillon, Federico A. Vasquez, Roberto Sung, Lillian TI Pediatric oncology research in low income countries: Ethical concepts and challenges SO PEDIATRIC BLOOD & CANCER LA English DT Review DE ethics review; informed consent; low income countries; pediatric oncology; research ethics; standard of care; trial benefits ID ACUTE LYMPHOBLASTIC-LEUKEMIA; INTERNATIONAL RESEARCH; CLINICAL-RESEARCH; CHILDHOOD; INTERVENTIONS; ESTABLISHMENT; HELSINKI; OUTCOMES; TRIALS; CANCER AB Uneven strides in research and care have led to discrepancies in childhood cancer outcomes between high and low income countries (LICs). Collaborative research may help improve outcomes in LICs by generating knowledge for local scientific communities, augmenting knowledge translation, and fostering context-specific evaluation of treatment protocols. However, the risks of such research have received little attention. This paper investigates the relationship between pediatric oncology research in LICs and four core issues in the ethics literature: standard of care, trial benefits, ethics review, and informed consent. Our aims are to highlight the importance of this field and the need for further inquiry. Pediatr Blood Cancer 2012; 58: 492497. (c) 2011 Wiley Periodicals, Inc. C1 [Denburg, Avram E.; Gupta, Sumit; Sung, Lillian] Hosp Sick Children, Div Haematol Oncol, Dept Pediat Oncol, Toronto, ON M5G 1X8, Canada. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Dept Med, Boston, MA USA. [Howard, Scott C.; Ribeiro, Raul C.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Antillon, Federico A.] Unidad Nacl Oncol Pediat, Guatemala City, Guatemala. [Vasquez, Roberto] Benjamin Bloom Natl Childrens Hosp, San Salvador, El Salvador. RP Sung, LL (reprint author), Hosp Sick Children, Div Haematol Oncol, Dept Pediat Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM lillian.sung@sickkids.ca RI Howard, Scott/K-3401-2013; OI Howard, Scott/0000-0003-2244-1686; Gupta, Sumit/0000-0003-1334-3670; Denburg, Avram/0000-0003-0039-0742; Joffe, Steven/0000-0002-0667-7384 FU Canadian Institutes of Health Research [87719]; Greenwall Foundation FX Grant sponsor: Canadian Institutes of Health Research; Grant number: 87719; Grant sponsor: Greenwall Foundation. NR 45 TC 7 Z9 7 U1 1 U2 7 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2012 VL 58 IS 4 BP 492 EP 497 DI 10.1002/pbc.23419 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 895NK UT WOS:000300502800005 PM 22147674 ER PT J AU Rosenberg, AR Baker, KS Syrjala, K Wolfe, J AF Rosenberg, Abby R. Baker, K. Scott Syrjala, Karen Wolfe, Joanne TI Systematic review of psychosocial morbidities among bereaved parents of children with cancer SO PEDIATRIC BLOOD & CANCER LA English DT Review DE bereaved; cancer; outcomes; palliative care; parents; review ID SOCIAL SUPPORT; HEALTH-STATUS; FOLLOW-UP; DEATH; CARE; SYMPTOMS; IMPACT; GRIEF; LIFE; END AB The objective of this review was to comprehensively summarize existing studies utilizing validated instruments to measure psychosocial outcomes among bereaved parents of children with cancer. This population has increased risks of anxiety, depression, prolonged grief, and poor quality of life. Parental morbidity is associated with psychiatric co-morbidities, prior loss, economic hardship, duration, and intensity of child's cancer-therapy, perceptions of medical care, child's quality of life, preparedness for and location of the child's death. Rigorous, prospective research is needed to identify risk-groups, define outcomes, and design interventions which will improve parental outcomes after the death of a child due to cancer. Pediatr Blood Cancer 2012; 58: 503512. (c) 2011 Wiley Periodicals, Inc. C1 [Rosenberg, Abby R.; Baker, K. Scott] Seattle Childrens Hosp, Div Pediat Hematol Oncol, Seattle, WA 98105 USA. [Rosenberg, Abby R.; Baker, K. Scott; Syrjala, Karen] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Rosenberg, Abby R.; Baker, K. Scott; Syrjala, Karen] Univ Washington, Seattle, WA 98195 USA. [Wolfe, Joanne] Dana Farber Canc Inst, Boston, MD USA. [Wolfe, Joanne] Childrens Hosp, Boston, MD USA. [Wolfe, Joanne] Harvard Univ, Sch Med, Boston, MD USA. RP Rosenberg, AR (reprint author), Seattle Childrens Hosp, Div Hematol Oncol, M-S B-6553,POB 5371, Seattle, WA 98105 USA. EM abby.rosenberg@seattlechildrens.org FU Ruth L. Kirschstein National Research Service [T32CA009351] FX Grant sponsor: Ruth L. Kirschstein National Research Service Award; Grant number: T32CA009351. NR 48 TC 27 Z9 29 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2012 VL 58 IS 4 BP 503 EP 512 DI 10.1002/pbc.23386 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 895NK UT WOS:000300502800007 PM 22038675 ER PT J AU Shen, Y Nicoletti, P Floratos, A Pirmohamed, M Molokhia, M Geppetti, P Benemei, S Giomi, B Schena, D Vultaggio, A Stern, R Daly, MJ John, S Nelson, MR Pe'er, I AF Shen, Y. Nicoletti, P. Floratos, A. Pirmohamed, M. Molokhia, M. Geppetti, P. Benemei, S. Giomi, B. Schena, D. Vultaggio, A. Stern, R. Daly, M. J. John, S. Nelson, M. R. Pe'er, I. CA Int Serious Adverse Events TI Genome-wide association study of serious blistering skin rash caused by drugs SO PHARMACOGENOMICS JOURNAL LA English DT Article DE pharmacogenetics; GWAS; serious skin rash; Stevens-Johnson syndrome; SNP; drug adverse reactions ID STEVENS-JOHNSON-SYNDROME; TOXIC EPIDERMAL NECROLYSIS; CUTANEOUS ADVERSE-REACTIONS; GENETIC SUSCEPTIBILITY; NEUTROPHIL FUNCTION; SLC22 FAMILY; MARKER; TRANSPORTERS; ALLOPURINOL; POPULATION AB Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe, potentially life threatening adverse drug reactions characterized by skin blistering. Previous studies have identified drug-specific and population-specific genetic risk factors with large effects. In this study, we report the first genome-wide association study (GWAS) of SJS/TEN induced by a variety of drugs. Our aim was to identify common genetic risk factors with large effects on SJS/TEN risk. We conducted a genome-wide analysis of 96 retrospective cases and 198 controls with a panel of over one million single-nucleotide polymorphisms (SNPs). We further improved power with about 4000 additional controls from publicly available datasets. No genome-wide significant associations with SNPs or copy number variants were observed, although several genomic regions were suggested that may have a role in predisposing to drug-induced SJS/TEN. Our GWAS did not find common, highly penetrant genetic risk factors responsible for SJS/TEN events in the cases selected. The Pharmacogenomics Journal (2012) 12, 96-104; doi: 10.1038/tpj.2010.84; published online 11 January 2011 C1 [Shen, Y.] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. [Shen, Y.; Nicoletti, P.; Floratos, A.] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10027 USA. [Nicoletti, P.; Geppetti, P.; Benemei, S.; Giomi, B.] Univ Florence, Dept Clin Pharmacol, Florence, Italy. [Pirmohamed, M.] Univ Liverpool, MRC Ctr Drug Safety Sci, Dept Pharmacol, Liverpool L69 3BX, Merseyside, England. [Molokhia, M.] Univ London, London Sch Hyg & Trop Med, London, England. [Schena, D.] Univ Verona, Dept Dermatol, I-37100 Verona, Italy. [Vultaggio, A.] Univ Florence, Dept Internal Med, Immunoallergol Sect, Careggi Teaching Hosp, Florence, Italy. [Stern, R.] Harvard Univ, Dept Dermatol Beth Israel, Deaconess Med Ctr, Sch Med, Boston, MA USA. [Daly, M. J.] Broad Inst Harvard Univ & Massachusetts Inst Tech, Program Med & Populat Genet, Cambridge, MA USA. [Daly, M. J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [John, S.] Pfizer, New London, CT USA. [Nelson, M. R.; Pe'er, I.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Pe'er, I (reprint author), Columbia Univ, Dept Comp Sci, 1214 Amsterdam Ave,Mail Code 0401, New York, NY 10027 USA. EM matthew.r.nelson@gsk.com; itsik@cs.columbia.edu RI Benemei, Silvia/K-5552-2014; Pirmohamed, Munir/H-6004-2011 OI Benemei, Silvia/0000-0001-6316-430X; Pirmohamed, Munir/0000-0002-7534-7266 FU International Serious Adverse Events Consortium FX We thank Arthur L Holden (Serious Adverse Events Consortium) Brian Spear (Abbott), Joe Walker (Daiichi-Sankyo), Lon Cardon (GlaxoSmithKline), Vincent Mooser (GlaxoSmithKline), Nadine Cohen (Johnson & Johnson), Joanne Meyer (Novartis) Klaus Lindpaintner (Roche), Robert Dix (Sanofi-Aventis), Leonardo Sahelijo (Takeda), Michael Dunn (Wellcome Trust), and Michael E Burczynski (Wyeth) for their support. We also thank Bernd Jagla for his early contribution to the project. We also thank Julian Arbuckle and Clive Bowman for their contribution in recruiting the SJS-TEN cohort from study PGX40001, and all the clinicians who recruited cases and controls to the study, and all the patients who contributed DNA for the study. This work was funded by the International Serious Adverse Events Consortium. NR 45 TC 14 Z9 15 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD APR PY 2012 VL 12 IS 2 BP 96 EP 104 DI 10.1038/tpj.2010.84 PG 9 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 916WK UT WOS:000302133700002 PM 21221126 ER PT J AU Ravnskov, U McCully, KS Rosch, PJ AF Ravnskov, U. McCully, K. S. Rosch, P. J. TI The statin-low cholesterol-cancer conundrum SO QJM-AN INTERNATIONAL JOURNAL OF MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; COA REDUCTASE INHIBITORS; SERUM TOTAL CHOLESTEROL; CORONARY-HEART-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; PLASMA-CHOLESTEROL; CONTROLLED TRIAL; PROSTATE-CANCER; RISK; MORTALITY C1 [Ravnskov, U.] Independent Investigator, S-22350 Lund, Sweden. [McCully, K. S.] VA Boston Healthcare Syst, Pathol & Lab Med Serv, W Roxbury, MA USA. [McCully, K. S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Rosch, P. J.] New York Med Coll, Yonkers, NY USA. [Rosch, P. J.] Amer Inst Stress, Yonkers, NY USA. RP Ravnskov, U (reprint author), Magle Stora Kyrkogata 9, S-22350 Lund, Sweden. EM ravnskov@tele2.se NR 41 TC 17 Z9 17 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 EI 1460-2393 J9 QJM-INT J MED JI QJM-An Int. J. Med. PD APR PY 2012 VL 105 IS 4 BP 383 EP 388 DI 10.1093/qjmed/hcr243 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 915EG UT WOS:000302006200017 PM 22156736 ER PT J AU Porcel, JM Leung, CC Restrepo, MI Lee, P AF Porcel, Jose M. Leung, Chi Chiu Restrepo, Marcos I. Lee, Pyng TI Year in review 2011: Respiratory infections, tuberculosis, pleural diseases, bronchoscopic intervention and imaging SO RESPIROLOGY LA English DT Review DE endobronchial ultrasonography; pleural effusion; pneumonia; positron emission tomography; tuberculosis ID COMMUNITY-ACQUIRED PNEUMONIA; TRANSBRONCHIAL NEEDLE ASPIRATION; BRONCHOALVEOLAR LAVAGE FLUID; GAMMA RELEASE ASSAYS; INTERFERON-GAMMA; MYCOBACTERIUM-TUBERCULOSIS; ACTIVE TUBERCULOSIS; PARAPNEUMONIC EFFUSION; RESISTANT TUBERCULOSIS; PULMONARY SARCOIDOSIS C1 [Porcel, Jose M.] Arnau de Vilanova Univ Hosp, Dept Internal Med, Biomed Res Insitute Lleida, Pleural Dis Unit, Lleida 25198, Spain. [Leung, Chi Chiu] Tuberculosis & Chest Serv, Dept Hlth, Hong Kong, Hong Kong, Peoples R China. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, Audie L Murphy VA Hosp, VERDICT,S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Lee, Pyng] Natl Univ Singapore Hosp, Dept Med, Singapore 117548, Singapore. RP Porcel, JM (reprint author), Arnau de Vilanova Univ Hosp, Dept Internal Med, Biomed Res Insitute Lleida, Pleural Dis Unit, Avda Alcalde Rovira Roure 80, Lleida 25198, Spain. EM jporcelp@yahoo.es RI Restrepo, Marcos/H-4442-2014 FU Instituto de Salud Carlos III [FIS 09/00199]; NIH/NHLBI [K23HL096054] FX J.M.P. has received a research grant from the Instituto de Salud Carlos III (FIS 09/00199). M.I.R.'s time is partially covered by the NIH/NHLBI Grant K23HL096054. NR 82 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1323-7799 J9 RESPIROLOGY JI Respirology PD APR PY 2012 VL 17 IS 3 BP 573 EP 582 DI 10.1111/j.1440-1843.2012.02128.x PG 10 WC Respiratory System SC Respiratory System GA 915DO UT WOS:000302004300025 PM 22248294 ER PT J AU Cheng, YC Anderson, CD Bione, S Keene, K Maguire, JM Nalls, M Rasheed, A Zeginigg, M Attia, J Baker, R Barlera, S Biffi, A Bookman, E Brott, TG Brown, RD Chen, F Chen, WM Ciusani, E Cole, JW Cortellini, L Danesh, J Doheny, K Ferrucci, L Franzosi, MG Frossard, P Furie, KL Golledge, J Hankey, GJ Hernandez, D Holliday, EG Hsu, FC Jannes, J Kamal, A Khan, MS Kittner, SJ Koblar, SA Lewis, M Lincz, L Lisa, A Matarin, M Moscato, P Mychaleckyj, JC Parati, EA Parolo, S Pugh, E Rost, NS Schallert, M Schmidt, H Scott, RJ Sturm, JW Yadav, S Zaidi, M Boncoraglio, GB Levi, CR Meschia, JF Rosand, J Sale, M Saleheen, D Schmidt, R Sharma, P Worrall, B Mitchell, BD AF Cheng, Yu-Ching Anderson, Christopher D. Bione, Silvia Keene, Keith Maguire, Jane M. Nalls, Michael Rasheed, Asif Zeginigg, Marion Attia, John Baker, Ross Barlera, Simona Biffi, Alessandro Bookman, Ebony Brott, Thomas G. Brown, Robert D., Jr. Chen, Fang Chen, Wei-Min Ciusani, Emilio Cole, John W. Cortellini, Lynelle Danesh, John Doheny, Kimberly Ferrucci, Luigi Franzosi, Maria Grazia Frossard, Philippe Furie, Karen L. Golledge, Jonathan Hankey, Graeme J. Hernandez, Dena Holliday, Elizabeth G. Hsu, Fang-Chi Jannes, Jim Kamal, Ayeesha Khan, Muhammad Saleem Kittner, Steven J. Koblar, Simon A. Lewis, Martin Lincz, Lisa Lisa, Antonella Matarin, Mar Moscato, Pablo Mychaleckyj, Josyf C. Parati, Eugenio A. Parolo, Silvia Pugh, Elizabeth Rost, Natalia S. Schallert, Michael Schmidt, Helena Scott, Rodney J. Sturm, Jonathan W. Yadav, Sunaina Zaidi, Moazzam Boncoraglio, Giorgio B. Levi, Christopher Royce Meschia, James F. Rosand, Jonathan Sale, Michele Saleheen, Danish Schmidt, Reinhold Sharma, Pankaj Worrall, Bradford Mitchell, Braxton D. CA GARNET Collaborative Res Grp GENEVA Consortium Int Stroke Genetics Consortium TI Are Myocardial Infarction-Associated Single-Nucleotide Polymorphisms Associated With Ischemic Stroke? SO STROKE LA English DT Article DE cerebral infarct; genetics; ischemia ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; AMERICAN-HEART-ASSOCIATION; VITAMIN INTERVENTION; CEREBRAL INFARCTION; SEQUENCE VARIANTS; FAMILY-HISTORY; PREVENTION; CLASSIFICATION; SUBTYPES AB Methods-Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific beta s and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model. Results-Despite having power to detect odds ratio of 1.09-1.14 for overall IS and 1.20-1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons. Conclusions-Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events. (Stroke. 2012; 43:980-986.) C1 [Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Furie, Karen L.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Anderson, Christopher D.; Biffi, Alessandro; Cortellini, Lynelle; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Bione, Silvia; Lisa, Antonella; Parolo, Silvia] CNR, Inst Mol Genet, Pavia, Italy. [Keene, Keith; Schallert, Michael] Univ Virginia, Dept Med, Charlottesville, VA USA. [Keene, Keith; Chen, Fang; Chen, Wei-Min; Mychaleckyj, Josyf C.; Schallert, Michael] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Maguire, Jane M.; Attia, John; Holliday, Elizabeth G.; Lincz, Lisa; Scott, Rodney J.; Levi, Christopher Royce] Univ Newcastle, HMRI, Newcastle, NSW 2300, Australia. [Maguire, Jane M.] Univ Newcastle, Sch Nursing & Midwifery, Newcastle, NSW 2300, Australia. [Nalls, Michael; Hernandez, Dena] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Rasheed, Asif; Frossard, Philippe; Zaidi, Moazzam; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan. [Zeginigg, Marion; Schallert, Michael; Schmidt, Helena; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Zeginigg, Marion; Schallert, Michael; Schmidt, Helena; Schmidt, Reinhold] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Baker, Ross] Murdoch Univ, Ctr Thrombosis & Haemophilia, Perth, WA, Australia. [Baker, Ross] Royal Perth Hosp, Dept Haematol, Perth, WA, Australia. [Barlera, Simona; Franzosi, Maria Grazia] Ist Ric Farmacol Mario Negri, Milan, Italy. [Bookman, Ebony] NHGRI, NIH, Rockville, MD USA. [Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Chen, Wei-Min; Mychaleckyj, Josyf C.; Worrall, Bradford] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Ciusani, Emilio; Parati, Eugenio A.; Boncoraglio, Giorgio B.] Fdn IRCCS Ist Neurol Carlo Besta, Milan, Italy. [Cole, John W.; Kittner, Steven J.] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD USA. [Cole, John W.; Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Danesh, John; Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Doheny, Kimberly; Pugh, Elizabeth] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Golledge, Jonathan] James Cook Univ, Sch Med, Vasc Biol Unit, Townsville, Qld 4811, Australia. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia. [Hsu, Fang-Chi] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Hsu, Fang-Chi] Wake Forest Sch Med, Ctr Canc Genom, Winston Salem, NC USA. [Jannes, Jim; Koblar, Simon A.; Lewis, Martin] Univ Adelaide, Stroke Res Programme, Sch Med, Adelaide, SA, Australia. [Jannes, Jim; Koblar, Simon A.; Lewis, Martin] Univ Adelaide, Stroke Res Programme, Sch Mol Biomed Sci, Adelaide, SA, Australia. [Kamal, Ayeesha] Aga Khan Univ, Neurol Sect, Karachi, Pakistan. [Khan, Muhammad Saleem; Yadav, Sunaina; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England. [Matarin, Mar] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London, England. [Moscato, Pablo] Univ Newcastle, Ctr Bioinformat, Newcastle, NSW 2300, Australia. [Sturm, Jonathan W.] Univ Newcastle, Gosford Hosp, Dept Neurosci, Newcastle, NSW 2300, Australia. [Schallert, Michael] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Worrall, Bradford] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Saleheen, Danish] Univ Penn, Philadelphia, PA 19104 USA. RP Mitchell, BD (reprint author), Univ Maryland, Sch Med, Dept Med, 660 W Redwood St,Howard Hall,Room 492, Baltimore, MD 21201 USA. EM bmitchel@medicine.umaryland.edu RI MOSCATO, PABLO/G-7668-2013; golledge, jonathan/I-2371-2013; Attia, John/F-5376-2013; Hankey, Graeme /H-4968-2014; Lisa, Antonella/B-3117-2015; Boncoraglio, Giorgio/B-8647-2011; Matarin, Mar/F-1771-2016; OI Lewis, Martin/0000-0002-3332-3776; Attia, John/0000-0001-9800-1308; Hankey, Graeme /0000-0002-6044-7328; Lisa, Antonella/0000-0003-2458-5499; Matarin, Mar/0000-0002-4717-5735; Bione, Silvia/0000-0002-3924-4606; Parolo, Silvia/0000-0002-3671-5353; Anderson, Christopher/0000-0002-0053-2002; Koblar, Simon/0000-0002-8667-203X; Mitchell, Braxton/0000-0003-4920-4744 FU Australian National and Medical Health Research Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G 04S 1623]; University of Newcastle; Department of Health (United Kingdom); Henry Smith Charity; British Council (UKIERI); Italian Ministry of Health [RC 2007/LR6, RC 2008/LR6, RC 2009/LR8, RC 2010/LR8]; Cariplo Foundation [2010-0253]; University of Pavia; European Community [LSHM-CT-2007-037273]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; NIH-NINDS [K23NS064052, R01NS063925, P50NS051343]; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; Keane Stroke Genetics Research Fund; US National Institutes of Health; National Heart, Lung, and Blood Institute STAMPEED [R01 HL087676]; National Center for Research Resources; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research; National Institutes of Health Genes, Environment and Health Initiative (GEI), GENEVA consortium under GEI [U01 HG004436]; National Institutes of Health [HHSN268200782096C]; Office of Research and Development, Medical Research Service; Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs; National Institute of Neurological Disorders and Stroke (NINDS); NIH Office of Research on Women's Health [R01 NS45012, U01 NS069208-01]; Austrian Science Fund [P20545]; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000954-06, Z01 AG000015-50]; National Institute for Neurological Disorders and Stroke (United States) [R01 NS42733, R01 NS39987]; National Institute of Neurological Disorders And Stroke [21NS064908]; National Human Genome Research Institute (NHGRI) [U01 HG005160]; National Institutes of Health to the Johns Hopkins University; United States Public Health Service, National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Bethesda, MD [R01 NS34447] FX The ASGC was funded by grants from the Australian National and Medical Health Research Council (NHMRC Project Grant ID: 569257) and the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623). Support was also received from the University of Newcastle. E. G. H. was supported by an NHMRC Training (Postdoctoral) Fellowship. BRAINS was supported by a Department of Health (United Kingdom) senior fellowship to P. S. and also by a grant from the Henry Smith Charity and the British Council (UKIERI). The Besta Cerebrovascular Diseases Registry (CEDIR) was supported by the Italian Ministry of Health, years 2007-2010 (Annual Research Funding; Grant Numbers: RC 2007/LR6, RC 2008/LR6; RC 2009/LR8; RC 2010/LR8). This study was supported also by Cariplo Foundation (grant No. 2010-0253). S. P. was supported by a PhD fellowship of the University of Pavia (PhD program in Genetic and Biomolecular Sciences). The PROCARDIS study was supported by the European Community Sixth Framework Program (LSHM-CT-2007-037273). GASROS was supported by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N); NIH-NINDS grant Nos. K23NS064052 (N.S.R.), R01NS063925 (J.R.), and P50NS051343 (J.R and K. L. F.); the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; and the Keane Stroke Genetics Research Fund. The MIGen study was funded by the US National Institutes of Health and National Heart, Lung, and Blood Institute STAMPEED genomics research program (R01 HL087676) and a grant from the National Center for Research Resources. A. B., N.S.R., and C. D. A. were supported in part by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research. The GEOS study was supported by the National Institutes of Health Genes, Environment and Health Initiative (GEI) Grant U01 HG004436, as part of the GENEVA consortium under GEI. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University (contract No. HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI, Bruce S. Weir). Study recruitment and collection of datasets were supported by the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs and by grants from the National Institute of Neurological Disorders and Stroke (NINDS) and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). Genetic studies of the Austrian Stroke Prevention Study (GRAZ) are supported by the Austrian Science Fund (P20545). ISGS/SWISS: This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project No. Z01 AG000954-06. This work used samples and clinical data from the NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds), human subjects protocol Nos. 2003-081 and 2004-147. The inclusion of Baltimore Longitudinal Study of Aging samples was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project No. Z01 AG000015-50, human subjects protocol number 2003-078.; The ISGS study was funded by a grant from the National Institute for Neurological Disorders and Stroke (United States), grant No. R01 NS42733 (PI, J. Meschia). The SWISS study was funded by a grant from the National Institute for Neurological Disorders and Stroke (United States), grant No. R01 NS39987 (PI, J. Meschia). This study used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). The RACE study is supported by grants from the National Institute of Neurological Disorders And Stroke (Award No. 21NS064908) and educational awards to investigators at the Center for Noncommunicable Diseases, Pakistan. The GWAS component of the VISP study was supported by the National Human Genome Research Institute (NHGRI), Grant U01 HG005160 (PIs, Michele Sale and Bradford Worrall), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI, Bruce S. Weir). Study recruitment and collection of datasets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI, James Toole) from the United States Public Health Service, National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Bethesda, MD. NR 36 TC 17 Z9 17 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD APR PY 2012 VL 43 IS 4 BP 980 EP U143 DI 10.1161/STROKEAHA.111.632075 PG 26 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 916ST UT WOS:000302124200016 PM 22363065 ER PT J AU Economopoulos, KP Linos, D AF Economopoulos, Konstantinos P. Linos, Dimitrios TI General surgery residency and international medical graduates: A perspective from Greece SO SURGERY LA English DT Letter C1 [Economopoulos, Konstantinos P.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. Hygeia Hosp, Dept Surg, Athens, Greece. RP Economopoulos, KP (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM economopoulos@sni.gr OI Economopoulos, Konstantinos/0000-0003-4856-0405 NR 3 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2012 VL 151 IS 4 BP 633 EP 633 DI 10.1016/j.surg.2011.12.020 PG 1 WC Surgery SC Surgery GA 915AZ UT WOS:000301996600023 PM 22296987 ER PT J AU Ferrone, ML Raut, CP AF Ferrone, Marco L. Raut, Chandrajit P. TI Modern Surgical Therapy: Limb Salvage and the Role of Amputation for Extremity Soft-Tissue Sarcomas SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Extremity sarcoma; Limb salvage; Radiation therapy; Limb infusion/limb perfusion ID TUMOR-NECROSIS-FACTOR; EXTERNAL-BEAM RADIOTHERAPY; RANDOMIZED-TRIAL; FACTOR-ALPHA; POSTOPERATIVE RADIOTHERAPY; ADJUVANT CHEMOTHERAPY; ISOLATED PERFUSION; RADIATION-THERAPY; SPARING SURGERY; LOCAL-CONTROL AB Historically the surgical management of extremity soft-tissue sarcomas (ESTS) commonly involved amputation. Nowadays limb-sparing, function-preserving surgery is the standard of care for ESTS. Adjuvant therapies such as radiation therapy and chemotherapy are used selectively in an effort to minimize both local recurrence and distant spread. Less common modalities, such as isolated limb perfusion, isolated limb infusion, and hyperthermia are being evaluated to potentially expand the cohort of individuals who may be eligible for limb-sparing surgery and to improve outcomes. This article reviews the standard and evolving approaches to the management of ESTS. C1 [Raut, Chandrajit P.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol,Dept Surg,Sch Med, Boston, MA 02115 USA. [Ferrone, Marco L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol,Dept Orthoped,Sch Med, Boston, MA 02115 USA. RP Raut, CP (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol,Dept Surg,Sch Med, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org NR 39 TC 16 Z9 17 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1055-3207 EI 1558-5042 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD APR PY 2012 VL 21 IS 2 BP 201 EP + DI 10.1016/j.soc.2011.11.001 PG 14 WC Oncology; Surgery SC Oncology; Surgery GA 915NG UT WOS:000302033700004 PM 22365515 ER PT J AU DeLaney, TF AF DeLaney, Thomas F. TI Radiation Therapy: Neoadjuvant, Adjuvant, or Not at All SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Soft tissue sarcoma; Radiation therapy; Adjuvant; Neoadjuvant ID SOFT-TISSUE SARCOMA; LIMB-SPARING SURGERY; INTENSITY-MODULATED RADIOTHERAPY; PROSPECTIVE RANDOMIZED-TRIAL; ELECTRON-BEAM RADIOTHERAPY; LOCAL-CONTROL; POSTOPERATIVE RADIOTHERAPY; HIGH-GRADE; RETROPERITONEAL SARCOMA; PREOPERATIVE RADIATION AB Clinical trial data show that radiation enhances local tumor control of extremity sarcomas with acceptable morbidity when sophisticated radiation techniques are combined with limb-sparing resections performed by oncologic surgeons with sarcoma expertise. Similar controlled data is not available for retroperitoneal sarcomas but some studies suggest a benefit for radiotherapy. Radiation can be delivered by external beam or brachytherapy; it can be given pre-operatively, post-operatively, or intra-operatively. Indications for and advances in radiation therapy are discussed in this article. C1 [DeLaney, Thomas F.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Francis H Burr Proton Therapy Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. [DeLaney, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Francis H Burr Proton Therapy Ctr, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM tdelaney@partners.org NR 115 TC 11 Z9 11 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 1055-3207 EI 1558-5042 J9 SURG ONCOL CLIN N AM JI Surg. Oncol. Clin. N. Am. PD APR PY 2012 VL 21 IS 2 BP 215 EP + DI 10.1016/j.soc.2011.12.005 PG 28 WC Oncology; Surgery SC Oncology; Surgery GA 915NG UT WOS:000302033700005 PM 22365516 ER PT J AU Black-Schaffer, WS Crawford, JM AF Black-Schaffer, W. Stephen Crawford, James M. TI The Evolving Landscape for Pathology Subspecialty Fellowship Applications SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material C1 [Black-Schaffer, W. Stephen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Black-Schaffer, W. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Crawford, James M.] N Shore Long Isl Jewish Hlth Syst, Dept Pathol & Lab Med, Manhasset, NY USA. [Crawford, James M.] Hofstra Univ, Sch Med, Manhasset, NY USA. RP Black-Schaffer, WS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 2012 VL 137 IS 4 BP 513 EP 515 DI 10.1309/AJCPF0WTY3XEMILP PG 3 WC Pathology SC Pathology GA 912BJ UT WOS:000301768400001 PM 22431527 ER PT J AU Saslow, D Solomon, D Lawson, HW Killackey, M Kulasingam, SL Cain, J Garcia, FAR Moriarty, AT Waxman, AG Wilbur, DC Wentzensen, N Downs, LS Spitzer, M Moscicki, AB Franco, EL Stoler, MH Schiffman, M Castle, PE Myers, ER AF Saslow, Debbie Solomon, Diane Lawson, Herschel W. Killackey, Maureen Kulasingam, Shalini L. Cain, Joanna Garcia, Francisco A. R. Moriarty, Ann T. Waxman, Alan G. Wilbur, David C. Wentzensen, Nicolas Downs, Levi S., Jr. Spitzer, Mark Moscicki, Anna-Barbara Franco, Eduardo L. Stoler, Mark H. Schiffman, Mark Castle, Philip E. Myers, Evan R. TI American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; ATYPICAL SQUAMOUS-CELLS; INTRAEPITHELIAL NEOPLASIA GRADE-2; INTERNATIONAL INCIDENCE RATES; ADENOCARCINOMA IN-SITU; LIQUID-BASED CYTOLOGY; LONG-TERM RISK; WOMEN 30 YEARS; COST-EFFECTIVENESS AB An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HP V) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HP VI 6 and HPV18 infections. C1 [Saslow, Debbie] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30303 USA. [Solomon, Diane] NCI, Canc Prevent Div, NIH, Rockville, MD USA. [Lawson, Herschel W.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA. [Killackey, Maureen] Mem Sloan Kettering Canc Ctr, Dept Surg, Mem Sloan Kettering Canc Ctr Reg Network, Gynecol Serv, New York, NY 10021 USA. [Kulasingam, Shalini L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Cain, Joanna] Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA USA. [Garcia, Francisco A. R.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Ctr Excellence Womens Hlth, Tucson, AZ USA. [Moriarty, Ann T.] AmeriPath Indiana, Dept Esoter Testing, Indianapolis, IN USA. [Waxman, Alan G.] Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Downs, Levi S., Jr.] Univ Minnesota, Sch Med, Dept Obstet Gynecol & Womens Hlth, Div Gynecol Oncol,Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Spitzer, Mark] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Franco, Eduardo L.] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Franco, Eduardo L.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. [Stoler, Mark H.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA. [Schiffman, Mark] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Castle, Philip E.] Amer Soc Clin Pathol Inst, Washington, DC USA. [Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Saslow, D (reprint author), Amer Canc Soc, Canc Control Sci Dept, 250 Williams St NW,Suite 600, Atlanta, GA 30303 USA. EM debbie.saslow@cancer.org RI perumal, murugiah/D-1565-2012; Colgan, Terence/J-2339-2016; OI Franco, Eduardo/0000-0002-4409-8084 FU Merck and Company; Roche Pharmaceutical/Roche Molecular; Hologic; Third Wave Technologies; MTM Laboratories; Qiagen; Becton, Dickson and Company (BD); MediSpectra/LUMA; Roche; Gen-Probe, Inc; Abbott Laboratories; Roche Molecular Systems; Merck, Inc; GlaxoSmithKline (GSK), Inc.; Merck Research Laboratories; Ventana Medical Systems, Inc; BD Diagnostics; National Institute of Allergy and Infectious Diseases FX P. Castle receives payment for service on the Data Monitoring and Safety Board for Merck Sharp & Dohme and has received free or discounted human papillomavirus tests for research from Qiagen and Roche. C. Cohen serves as a speaker for Merck, Inc, and receives honoraria. M. Edelson's spouse is employed by and receives a salary from Merck and Company. F. Garcia is employed by the University of Arizona, which holds contracts for the performance of research with Roche Pharmaceutical/Roche Molecular; Hologic; Third Wave Technologies; MTM Laboratories; Qiagen; Becton, Dickson and Company (BD); and MediSpectra/LUMA. He also serves on the Speakers' Bureau for Qiagen and receives honoraria. J. Cuzick serves on advisory boards and as an ad hoc consultant for Qiagen; Roche; Gen-Probe, Inc; BD; and Abbott Laboratories, with research funds provided to his institution from Qiagen; Roche; Gen-Probe, Inc; BD; and Abbott Laboratories. P. Gravitt has acted as a member of the Women's Health Advisory Board for Qiagen Corporation and has received research funding from Roche Molecular Systems and Merck, Inc, within the last 5 years. E. Myers received research support for investigations for Gen-Probe, Inc, and from GlaxoSmithKline (GSK), Inc. He served as a speaker for and received honoraria from Gen-Probe, Inc, and has served as a consultant for and received honoraria from Gen-Probe, Inc; Merck and Company; and GSK. M Schiffman holds a research agreement to serve as a medical monitor in the National Cancer Institute (NCI) vaccine trial through GSK; he also receives research support from Qiagen for careHPV research in Nigeria. D. Solomon serves as a medical monitor for the NCI's Costa Rica HPV Vaccine Trial; the trial receives vaccine from GSK. M Stoler received fees for serving as a consultant to Merck Research Laboratories; Roche; Ventana Medical Systems, Inc; BD; Hologic; MTM Laboratories; and Gen-Probe, Inc. D. Mody conducted lectures and workshops for the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Cytopathology (ASC), for which she received honoraria and/or travel expenses. G. Birdsong 's employer receives funding for contracted research performed by him for BD Diagnostics. C. Wheeler is an employee of University of New Mexico, which is contracted by GSK for its vaccine trials and receives equipment/reagents from Roche Molecular Systems, Inc, for human papillomavirus genotyping. D. Wilbur serves on the scientific advisory board for Corista, LLC. T Darragh received ThinPrep supplies for research from Hologic. She also serves on an advisory board for OncoHealth Corporation and has received stock options as payment and serves on the advisory board of Arbor Vita Corporation. E. Mayeaux serves on the speakers' advisory board for both Merck, Inc, and PharmaDerm and receives honoraria from both companies for his service. M Spitzer serves as a speaker for both Merck, Inc, and Qiagen and receives honoraria. K. Ault received clinical research grants from the National Institute of Allergy and Infectious Diseases; Gen-Probe, Inc; Merck, Inc; and Roche and served as a site principal investigator for the research. All grants were provided to his employer, Emory University. E.; Franco received honorarium as a Study Steering Committee member for GSK; he also serves on the advisory boards of Merck, Inc; Roche; and Gen-Probe, Inc, from which he receives honoraria and has acted as an ad hoc consultant for Merck, Inc; Roche; Gen-Probe, Inc; and Qiagen, for which honoraria were paid to compensate for time away and work performed. M Gold received honorarium for serving as a speaker and consultant for Hologic. W. Huh serves as a consultant to Roche; Qiagen; Merck, Inc; and Inovio Pharmaceuticals, Inc, and receives honoraria from all 4 companies. A-B. Moscicki received honorarium for serving as a consultant to an advisory board for Merck, Inc. M Einstein has advised or participated in educational speaking activities, but does not receive an honorarium from any companies. His employer, Montefiore Medical Center, has received payment for his time spent on activities for Merck, Inc; GSK; Roche; Bristol-Myers Squibb; Hologic; Advaxis, Inc; Aura Biosciences, Inc; Inovio Pharmaceuticals, Inc; Photocure ASA; NeoDiagnostix, Inc; and PDS Biotechnology Corporation. Montefiore has received grant funding for research related to the costs of those Merck, GSK, Roche, Advaxis, and Hologic clinical trials for which Dr Einstein served as the Montefiore principal investigator. A. Moriarty received honorarium as a speaker for ASC. R. Guido has acted as the local principal investigator for a multicenter study (contracted research) for IKONOsys. A. Waxman receives honoraria and expenses for teaching related to the subject matter in this article from nonprofit professional organizations and governmental agencies and contractors. He is on the executive committee of the board of directors of the American Society for Colposcopy and Cervical Pathology; he lectures for them and codirects some of their courses and receives honoraria and expenses for these functions. He also lectures and directs courses for the American College/Congress of Obstetricians and Gynecologists on subjects related to this article and receives honoraria from them. Both organizations are nonprofit professional organizations. He has also received honoraria and expenses from the State of Alaska Department of Health and Social Services and several Alaska Native corporations (Southcentral Foundation, SouthEast Alaska Regional Health Corporation, Arctic Slope Regional Corporation, and Yukon-Kuskokwim Health Corporation) and the Breast Cancer Detection Center of Alaska for lecturing on material related to this article. He also received honoraria from the Center for Health Training, a contractor to Title X agencies for lecturing for the Texas Department of State Health Services. He also received a $200 honorarium from Quadrant HealthCom, Inc, for writing an article related to cervical cancer screening for the journal OBG Management. NR 159 TC 277 Z9 299 U1 3 U2 17 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 2012 VL 137 IS 4 BP 516 EP 542 DI 10.1309/AJCPTGD94EVRSJCG PG 27 WC Pathology SC Pathology GA 912BJ UT WOS:000301768400002 PM 22431528 ER PT J AU Slatore, CG Goy, ER O'Hearn, DJ Boudreau, EA O'Malley, JP Peters, D Ganzini, L AF Slatore, Christopher G. Goy, Elizabeth R. O'Hearn, Daniell J. Boudreau, Eilis A. O'Malley, Jean P. Peters, Dawn Ganzini, Linda TI Sleep Quality and Its Association With Delirium Among Veterans Enrolled in Hospice SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Sleep quality; delirium; hospice; Veterans ID ADVANCED CANCER-PATIENTS; OF-LIFE; WAKE DISTURBANCES; OLDER PERSONS; CAREGIVERS; DISTRESS; PEOPLE; END; DEPRESSION; MELATONIN AB Objectives: The objectives of this study were to describe sleep quality and evaluate the association of sleep quality with delirium onset among patients enrolled in hospice. Design: The study utilized secondary data from a prospective, observational, longitudinal study. Setting: Veterans enrolled in hospice were recruited from the Portland Veterans Affairs Medical Center, Portland, Oregon. Participants: The cohort consisted of 105 patients, of whom 73% had at least one sleep measurement. Measurements: Sleep quality was measured with the Pittsburgh Sleep Quality Index. Delirium was measured with the Confusion Assessment Method. Other important variables were recorded from the medical record and/or longitudinal interviews with patients and their caregivers. Cox regression was used to estimate hazard ratios (HRs) to measure the association between sleep quality and delirium onset. Results: Of the patients who could be assessed, 44% had poor average sleep quality and 58% reported at least one episode of poor sleep. Overall, sleep quality did not appear to worsen as patients neared death although an increasing number of patients were unable to report on sleep quality. Poor sleep quality was associated with an increased risk of developing delirium, with an HR of 2.37 (95% CI: 1.50-3.74), for every one point worsening in the sleep quality score on a 4-point scale. Conclusions: Poor sleep quality was common among Veteran patients enrolled in hospice. These findings may help guide decision making between clinicians, patients, and families regarding the likely impact of sleep disturbance and may help identify patients at higher risk of developing delirium. (Am J Geriatr Psychiatry 2012; 20:317-326) C1 [Slatore, Christopher G.; Goy, Elizabeth R.; Ganzini, Linda] Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR USA. [Slatore, Christopher G.; O'Hearn, Daniell J.; Boudreau, Eilis A.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. [Slatore, Christopher G.; O'Hearn, Daniell J.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Boudreau, Eilis A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Slatore, CG (reprint author), 3710SW,US Vet Hosp Rd,R&D 66, Portland, OR 97239 USA. EM christopher.slatore@va.gov OI Slatore, Christopher/0000-0003-0958-8122 FU Department of Veterans Affairs; VA HSRD; Portland VA Medical Center; Oregon Clinical and Translational Research Institute (OCTRI); National Center for Research Resources (NCRR) [UL1 RR024140 01] FX The study was funded by a Merit Review Award from the Clinical Sciences Research and Development Program, Department of Veterans Affairs (Dr. Ganzini). Drs. Slatore and Goy are recipients of VA HSRD Career Development Awards. Drs. Slatore, Goy, O'Hearn, Boudreau, and Ganzini are supported by resources from the Portland VA Medical Center. Dr. Dawn Peters and Jean O'Malley are supported by resources from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 01 from the National Center for Research Resources (NCRR). The Department of Veterans Affairs did not have a role in the conduct of the study, in the collection, management, analysis, or interpretation of data, or in the preparation of the manuscript. NR 36 TC 7 Z9 7 U1 1 U2 4 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 APR PY 2012 VL 20 IS 4 BP 317 EP 326 DI 10.1097/JGP.0b013e3182487680 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 912SA UT WOS:000301818800006 PM 22367162 ER PT J AU Spencer, RJ Ray, A Pirl, WF Prigerson, HG AF Spencer, Ryan J. Ray, Alaka Pirl, William F. Prigerson, Holly G. TI Clinical Correlates of Suicidal Thoughts in Patients With Advanced Cancer SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Cancer; depression; mental health; panic disorder; suicidal ideation; terminal illness ID QUALITY-OF-LIFE; TERMINALLY-ILL; PRIMARY-CARE; ANXIETY DISORDERS; HASTENED DEATH; RISK-FACTOR; FOLLOW-UP; IDEATION; DEPRESSION; END AB Objective: Cancer patients are at heightened risk of suicide. Clinical correlates of suicidal ideation in advanced cancer patients were examined to identify those at risk and to inform the development of interventions to reduce suicidal ideation in this vulnerable group. Methods: Coping with Cancer (CwC) is an NCI- and NIMH-funded multiinstitutional investigation examining psychosocial influences on the quality of life and care of advanced cancer patients. Baseline face-to-face interviews that assessed mental and physical functioning, coping, spirituality, and use of mental health services were conducted with 700 advanced cancer patients. Results: Compared with patients without suicidal ideation, the 8.9% of patients who reported suicidal thoughts were more likely to be white and report no affiliation with an organized religion (p < 0.05). Adjusted analyses revealed that cancer patients who met criteria for current panic disorder (adjusted odds ratio [95% confidence interval] 3.24 [1.01-10.4]) and posttraumatic stress disorder (3.97 [1.13-14.1]), who accessed mental health services (3.70 [2.07-6.67]), particularly psychotherapy (2.62 [1.20-5.71]), who were not feeling well physically, and who lacked a sense of self-efficacy, spirituality, and being supported were more likely than others to report thoughts of suicide (p < 0.05). Conclusions: Advanced cancer patients who report suicidal thoughts are more likely to meet criteria for posttraumatic stress disorder and panic disorder, feel unsupported, lack a religious affiliation, spirituality, and a sense of self:efficacy, and experience more physical distress. Palliative care interventions that promote a sense of self efficacy, spirituality, and support while minimizing physical distress may offer promise for reducing suicidal thoughts in this at-risk group. (Am J Geriatr Psychiatry 2012; 20:327-336) C1 [Prigerson, Holly G.] Harvard Univ, Brigham & Womens Hosp, Ctr Psychooncol & Palliat Care Res, Dana Farber Canc Inst,Sch Med,Dept Psychiat, Boston, MA 02115 USA. [Spencer, Ryan J.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Med, Boston, MA 02115 USA. [Ray, Alaka] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pirl, William F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Prigerson, HG (reprint author), Harvard Univ, Brigham & Womens Hosp, Ctr Psychooncol & Palliat Care Res, Dana Farber Canc Inst,Sch Med,Dept Psychiat, 268 Smith Bldg,44 Binney St, Boston, MA 02115 USA. EM Holly_Prigerson@fci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370, CA156732]; Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute FX This research was supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health and CA106370 and CA156732 from the National Cancer Institute; a pilot grant from the American Foundation for Suicide Prevention; and the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. NR 50 TC 13 Z9 14 U1 0 U2 9 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 APR PY 2012 VL 20 IS 4 BP 327 EP 336 DI 10.1097/JGP.0b013e318233171a PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 912SA UT WOS:000301818800007 PM 21989317 ER PT J AU Devanand, DP Mintzer, J Schultz, S Sultzer, D de la Pena, D Gupta, S Colon, S Schimming, C Pelton, GH Andrews, H Levin, B AF Devanand, D. P. Mintzer, Jacob Schultz, Susan Sultzer, David de la Pena, Danilo Gupta, Sanjay Colon, Sylvia Schimming, Corbett Pelton, Gregory H. Andrews, Howard Levin, Bruce TI The Antipsychotic Discontinuation in Alzheimer Disease Trial: Clinical Rationale and Study Design SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Agitation; Alzheimer disease; antipsychotic; discontinuation trial; psychosis; risperidone ID PLACEBO-CONTROLLED TRIALS; NURSING-HOME RESIDENTS; DOUBLE-BLIND; RANDOMIZED-TRIAL; ELDERLY-PATIENTS; NEUROPSYCHIATRIC INVENTORY; BEHAVIORAL DISTURBANCES; TARDIVE-DYSKINESIA; LEWY BODIES; DEMENTIA AB Objectives: Research studies on the effects of discontinuing antipsychotic medications in patients with dementia have not identified specific target symptoms or response to antipsychotics prior to discontinuation. The Antipsychotic Discontinuation in Alzheimer Disease (ADAD) trial addresses these issues in a randomized, double-blind, placebo-controlled, multicenter risperidone treatment and discontinuation trial. In Phase A, AD patients with psychosis or agitation receive open treatment with risperidone for 16 weeks. Responders are randomized, double-blind, to one of three arms in Phase B: 1) continuation risperidone for the next 32 weeks, 2) risperidone for the next 16 weeks followed by placebo for 16 weeks, or 3) placebo for the next 32 weeks. Methods: Several design features provide unique strengths to this trial: identification of target symptoms and systematic open Antipsychotic treatment with only responders randomized in the discontinuation trial, use of a single antipsychotic medication, two clinically relevant time-points for discontinuation to evaluate the impact of duration of treatment on relapse, exclusion of patients at increased risk of stroke, assessment of several affected symptom domains, and state-of-the-art approaches to assess relapse and handle dropout. Conclusions: This study will provide clinically relevant data on the likelihood and time to relapse, and predictors of relapse, in patients switched from risperidone to placebo after response to risperidone treatment. Given the warnings about antipsychotic use in patients with dementia, studies of this type are essential to determine the optimal duration of treatment that confers the greatest benefit to risk ratio and to improve evidence-based treatment strategies. (Am J Geriatr Psychiatry 2012; 20:362-373) C1 [Devanand, D. P.; Pelton, Gregory H.] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Div Geriatr Psychiat, New York, NY USA. [Devanand, D. P.; Pelton, Gregory H.; Andrews, Howard] Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY USA. [Devanand, D. P.; Pelton, Gregory H.; Andrews, Howard] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. [Devanand, D. P.; Pelton, Gregory H.; Andrews, Howard] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. [Levin, Bruce] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Mintzer, Jacob] Med Univ S Carolina, Dept Neurosci, Div Translat Res, Charleston, SC 29425 USA. [Mintzer, Jacob] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Schultz, Susan] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA USA. [Sultzer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Sultzer, David] VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. [de la Pena, Danilo] Res Ctr Clin Studies Inc, Norwalk, CT USA. [Gupta, Sanjay] Global Res & Consulting, Buffalo, NY USA. [Colon, Sylvia] VA Med Ctr, Dept Psychiat, Tuscaloosa, AL USA. [Schimming, Corbett] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Devanand, DP (reprint author), 1051 Riverside Dr,Unit 126, New York, NY 10032 USA. EM dpd3@columbia.edu FU NIH [R01 AG021488, R01 AG17761]; Department of Veterans Affairs; National Institutes of Health; Novartis; Eli Lilly; Elan; Esai; Danone; Genentech; Janssen; Avid; Pfizer; Baxter; Wyeth; Alzheimer Disease Cooperative Study; Forest Research Institute; Takeda Pharmaceuticals; GSK; Roche; Lundbeck; Toyoma Pharmaceuticals; Bristol Myers Squibb; Astra Zeneca; Myriad; Ono Pharmaceuticals; Memory Pharmaceuticals; Takeda; Forest FX This study was supported by NIH grants R01 AG021488, R01 AG17761 and the Department of Veterans Affairs. Risperidone tablets (0.25, 0.5, 1, or 2 mg) and matching placebo were donated by Janssen Pharmaceutical, which had no other role in this study.; Dr. Devanand has received grants from the National Institutes of Health, research support from Novartis and Eli Lilly, and has served as a consultant to GSK, Bristol Myers Squibb, and Sanofi-Aventis. Dr. Mintzer has received research support from Elan, Esai, Danone, Genentech, Janssen, Avid, Pfizer, Baxter, Wyeth, and Eli Lilly, has served as a consultant to Antigenics, and is majority owner of Bio Pharma Connex, a company whose mission is to bring biotechnology to Latin America. Dr. Schultz has received research support from Baxter Healthcare in cooperation with the Alzheimer Disease Cooperative Study. Dr. Sultzer has received research support from the National Institutes of Health, Eli Lilly, and Forest Research Institute, and has served as a consultant to Eli Lilly. Dr. de la Pena has received research support from Takeda Pharmaceuticals, GSK, Eli Lilly, Elan, Janssen, Wyeth, Roche, Lundbeck, Toyoma Pharmaceuticals, Pfizer, and Bristol Myers Squibb. Dr. Gupta has received research support from Eli Lilly, Pfizer, Astra Zeneca, GSK, Myriad, Ono Pharmaceuticals, Memory Pharmaceuticals, Takeda, and has served as a consultant to Eli Lilly, and has been on the Speaker's Bureau for Eli Lilly, Pfizer, Astra Zeneca, Merck, Forest, Novartis, and GSK. Dr. Pelton has received research support from GSK, Novartis, and Forest and has served as a consultant to Bristol Myers Squibb and Pfizer. NR 44 TC 7 Z9 7 U1 2 U2 7 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 APR PY 2012 VL 20 IS 4 BP 362 EP 373 DI 10.1097/JGP.0b013e3182110563 PG 12 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 912SA UT WOS:000301818800011 PM 21407047 ER PT J AU Weinberg, G Warren, L AF Weinberg, Guy Warren, Lisa TI Lipid Resuscitation: Listening to Our Patients and Learning from Our Models SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID BUPIVACAINE-INDUCED ASYSTOLE; PLEXUS BLOCK; EMULSION; INFUSION; INTOXICATION; EPINEPHRINE; ROPIVACAINE; TOXICITY; OVERDOSE; REVERSAL C1 [Weinberg, Guy] Univ Illinois, Jesse Brown VA Med Ctr, Dept Anesthesiol, Coll Med, Chicago, IL 60612 USA. [Warren, Lisa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Warren, Lisa] Harvard Univ, Sch Med, Boston, MA USA. RP Weinberg, G (reprint author), Univ Illinois, Jesse Brown VA Med Ctr, Dept Anesthesiol, Coll Med, 820 S Damen, Chicago, IL 60612 USA. EM guyw@uic.edu NR 17 TC 2 Z9 2 U1 1 U2 4 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 APR PY 2012 VL 114 IS 4 BP 710 EP 712 DI 10.1213/ANE.0b013e31824b7eed PG 3 WC Anesthesiology SC Anesthesiology GA 912UL UT WOS:000301826800003 PM 22434892 ER PT J AU Siller-Matula, JM Merhi, Y Tanguay, JF Duerschmied, D Wagner, DD McGinness, KE Pendergrast, PS Chung, JK Tian, XB Schaub, RG Jilma, B AF Siller-Matula, Jolanta M. Merhi, Yahye Tanguay, Jean-Francois Duerschmied, Daniel Wagner, Denisa D. McGinness, Kathleen E. Pendergrast, P. Shannon Chung, Jou-Ku Tian, Xianbin Schaub, Robert G. Jilma, Bernd TI ARC15105 Is a Potent Antagonist of Von Willebrand Factor Mediated Platelet Activation and Adhesion SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE adhesion molecules; antiplatelet drugs; arterial thrombosis; coagulation ID THROMBOTIC THROMBOCYTOPENIC PURPURA; MULTIPLE ELECTRODE AGGREGOMETRY; APTAMER ARC1779; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; HEALTHY-VOLUNTEERS; EX-VIVO; INHIBITION; TRIAL; BINDING AB Objective-We investigated the stability, pharmacokinetic, and pharmacodynamic profile of the 2nd generation anti-von Willeband factor aptamer ARC15105. Methods and Results-Platelet plug formation was measured by collagen/adenosine diphosphate-induced closure time with the platelet function analyzer-100 and platelet aggregation by multiple electrode aggregometry. Platelet adhesion was measured on denuded porcine aortas and in a flow chamber. Aptamer stability was assessed by incubation in nuclease rich human, monkey, and rat serum for up to 72 hours. Pharmacokinetic and pharmacodynamic profiles were tested in cynomolgus monkeys after IV and SC administration. The median IC100 and IC50 to prolong collagen/adenosine diphosphate-induced closure timewere 27 nmol/L and 12 nmol/L, respectively. ARC15105 (1.3 mu mol/L) completely inhibited ristocetin-induced platelet aggregation in whole blood (P < 0.001), but also diminished collagen, ADP, arachidonic acid, and thrombin receptor activating peptide-induced platelet aggregation to some extent (P < 0.05). ARC15105 (40 nmol/L) decreased platelet adhesion by > 90% on denuded porcine aortas (P < 0.001), which was comparable to the degree of inhibition obtained with abciximab. ARC15105 (100 nmol/L) also inhibited platelet adhesion to collagen under arterial shear in a flow chamber by > 90% (P < 0.001). The IV and SC terminal half-lives in cynomolgus monkeys were 67 and 65 hours, respectively, and the SC bioavailability was approximate to 98%. Allometric scaling estimates the human T-1/2 would be approximate to 217 hours. Pharmacodynamic analysis confirms that ARC15105 inhibits von Willeband factor activity > 90% in blood samples taken 300 hours after a 20 mg/kg IV or SC dose in monkeys. Conclusion-The potency, pharmacokinetic profile, and SC bioavailability of ARC15105 support its clinical investigation for chronic inhibition of von Willeband factor-mediated platelet activation. (Arterioscler Thromb Vasc Biol. 2012;32:902-909.) C1 [Jilma, Bernd] Med Univ Vienna, Dept Clin Pharmacol, A-1090 Vienna, Austria. [Siller-Matula, Jolanta M.] Med Univ Vienna, Dept Cardiol, A-1090 Vienna, Austria. Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Merhi, Yahye; Tanguay, Jean-Francois] Montreal Heart Inst, Lab Thrombosis & Hemostasis, Montreal, PQ, Canada. [Duerschmied, Daniel; Wagner, Denisa D.] Immune Dis Inst, Boston, MA USA. [Duerschmied, Daniel; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Duerschmied, Daniel] Univ Med Ctr Freiburg, Dept Cardiol & Angiol, Freiburg, Germany. [Wagner, Denisa D.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. [McGinness, Kathleen E.; Pendergrast, P. Shannon; Chung, Jou-Ku; Tian, Xianbin; Schaub, Robert G.] Archemix Corp, Cambridge, MA USA. RP Jilma, B (reprint author), Med Univ Vienna, Dept Clin Pharmacol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM bernd.jilma@meduniwien.ac.at RI Siller-Matula, Jolanta Maria/J-8992-2015 OI Siller-Matula, Jolanta Maria/0000-0001-6041-1635 FU National Heart, Lung and Blood Institute of the National Institutes of Health [R01 HL041002]; Archemix Corporation FX D.D. and D.D.W. were supported by National Heart, Lung and Blood Institute of the National Institutes of Health grant R01 HL041002.; The study was sponsored by the Archemix Corporation and Robert G. Schaub, Kathleen E. McGinness, P. Shannon Pendergrast, Jou-Ku Chung, and Xianbin Tian are employees of the company. Bernd Jilma was a consultant. Other authors declare no competing financial interests. NR 27 TC 17 Z9 17 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 APR PY 2012 VL 32 IS 4 BP 902 EP U100 DI 10.1161/ATVBAHA.111.237529 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 910VV UT WOS:000301672300014 PM 22282355 ER PT J AU Otzen, DE Blans, K Wang, HB Gilbert, GE Rasmussen, JT AF Otzen, Daniel E. Blans, Kristine Wang, Huabing Gilbert, Gary E. Rasmussen, Jan T. TI Lactadherin binds to phosphatidylserine-containing vesicles in a two-step mechanism sensitive to vesicle size and composition SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE Stopped-Flow kinetic; Phosphatidylserine; Association and dissociation rate constant; Mixed micelle ID MILK-FAT GLOBULE; ALPHA-SYNUCLEIN; FACTOR-VIII; L-SERINE; MEMBRANES; EXPOSURE; IDENTIFICATION; DETERGENTS; DOMAINS; PAS-6/7 AB Lactadherin binds to phosphatidylserine (PS) in a stereospecific and calcium independent manner that is promoted by vesicle curvature. Because membrane binding of lactadherin is supported by a PS content of as little as 0.5%, lactadherin is a useful marker for cell stress where limited PS is exposed, as well as for apoptosis where PS freely traverses the plasma membrane. To gain further insight into the membrane-binding mechanism, we have utilized intrinsic lactadherin fluorescence. Our results indicate that intrinsic fluorescence increases and is blue-shifted upon membrane binding. Stopped-flow kinetic experiments confirm the specificity for PS and that the C2 domain contains a PS recognition motif. The stopped-flow kinetic data are consistent with a two-step binding mechanism, in which initial binding is followed by a slower step that involves either a conformational change or an altered degree of membrane insertion. Binding is detected at concentrations down to 0.03% PS and the capacity of binding reaches saturation around 1% PS (midpoint 0.15% PS). Higher concentrations of PS (and also to some extent PE) increase the association kinetics and the affinity. Increasing vesicle curvature promotes association. Remarkably, replacement of vesicles with micelles destroys the specificity for PS lipids. We conclude that the vesicular environment provides optimal conditions for presentation and recognition of PS by lactadherin in a simple binding mechanism. This article is part of a Special Issue entitled: Protein Folding in Membranes. (C) 2011 Elsevier B.V. All rights reserved. C1 [Otzen, Daniel E.; Blans, Kristine; Wang, Huabing; Rasmussen, Jan T.] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus C, Denmark. [Otzen, Daniel E.; Wang, Huabing] Aarhus Univ, Interdisciplinary Nanosci Ctr iNANO, DK-8000 Aarhus C, Denmark. [Otzen, Daniel E.; Wang, Huabing] Aarhus Univ, Ctr Insoluble Prot Struct inSPIN, DK-8000 Aarhus C, Denmark. [Gilbert, Gary E.] Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Gilbert, Gary E.] Harvard Univ, Sch Med, Boston, MA USA. RP Otzen, DE (reprint author), Aarhus Univ, Dept Mol Biol & Genet, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark. EM dao@inano.au.dk; jatr@mb.au.dk OI Otzen, Daniel/0000-0002-2918-8989 FU Danish Research Foundation (inSPIN); Aarhus University; Danish Research Training Council; Novozymes A/S; Abbott Ltd FX D.E.O. is supported by the Danish Research Foundation (inSPIN). H.W. is supported by a pre-doctoral grant from Aarhus University, the Danish Research Training Council, Novozymes A/S and Abbott Ltd. We thank Valerie Novakovic for excellent technical assistance. NR 29 TC 10 Z9 11 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD APR PY 2012 VL 1818 IS 4 SI SI BP 1019 EP 1027 DI 10.1016/j.bbamem.2011.08.032 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 911YV UT WOS:000301761500012 PM 21920348 ER PT J AU Benmansour, S Weaver, RS Barton, AK Adeniji, OS Frazer, A AF Benmansour, Saloua Weaver, Rami S. Barton, Amanda K. Adeniji, Opeyemi S. Frazer, Alan TI Comparison of the Effects of Estradiol and Progesterone on Serotonergic Function SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Chronoamperometry; estradiol; FST; progesterone; serotonin transporter; SSRI ID ESTROGEN-RECEPTOR-BETA; PROTEIN-COUPLED RECEPTOR; FORCED-SWIMMING TEST; CENTRAL-NERVOUS-SYSTEM; RAT HIPPOCAMPAL-FORMATION; GROWTH-FACTOR RECEPTOR; ANXIETY-LIKE BEHAVIOR; BREAST-CANCER; REPLACEMENT THERAPY; DORSAL HIPPOCAMPUS AB Background: Ovarian hormones may contribute to the vulnerability to depression, as well as to the response to antidepressants (ADs). Previously, we reported that acute systemic treatment with estradiol or progesterone blocked the ability of the selective serotonin reuptake inhibitor, fluvoxamine, to inhibit serotonin transporter function in ovariectomized rats. In this study, behavioral consequences, as well as receptor mechanisms underlying these hormonal effects, were investigated. Methods: Using the forced swimming test, the acute effect of estradiol and/or progesterone on fluvoxamine's AD-like effects was investigated. Using in vivo chronoamperometry, the effect of local application of estradiol or progesterone into the hippocampus of ovariectomized rats on serotonin (5-HT) clearance, as well as on the ability of fluvoxamine to slow 5-HT clearance, were investigated. Results: The decreased immobility and increased swimming caused by fluvoxamine in the forced swimming test was blocked in rats treated with estradiol and/or progesterone. Local application of estradiol, but not progesterone, slowed 5-HT clearance and both hormones blocked the ability of fluvoxamine to slow 5-HT clearance. Use of hormone receptor agonists and antagonists, revealed that the effects of estradiol are mediated by activation of membrane, as well as nuclear estrogen receptors (ER). The AD-like effect of estradiol involved ER beta and G-protein coupled receptor 30, whereas its blockade of fluvoxamine's effects was ER alpha-mediated. The effects of progesterone occurred solely by activation of intracellular progesterone receptors. Conclusions: Targeting of ER beta or G-protein coupled receptor 30 might reveal a strategy to permit beneficial effects of estrogen without its deleterious effect on selective serotonin reuptake inhibitor efficacy. C1 [Benmansour, Saloua; Weaver, Rami S.; Barton, Amanda K.; Adeniji, Opeyemi S.; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Frazer, Alan] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Benmansour, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,MC 7764, San Antonio, TX 78229 USA. EM benmansour@uthscsa.edu FU National Alliance for Research on Schizophrenia and Depression; Department of Veterans Affairs; National Institute of Mental Health [MH090386]; Forest Research Institute; Eli Lilly and Company; Wyeth Pharmaceuticals; H. Lundbeck A/S FX This research was supported by funds from the National Alliance for Research on Schizophrenia and Depression to SB, the Department of Veterans Affairs, and the National Institute of Mental Health (MH090386) to AF.; Dr. Benmansour, Ms. Weaver, Ms. Barton, and Mr. Adeniji have no biomedical financial interests or potential conflicts of interest. Dr. Frazer has been on advisory boards for Cyberonics, Inc.; H. Lundbeck A/S; and Takeda Pharmaceuticals America, Inc., and he has consulted and/or received research support for preclinical studies from Forest Research Institute, Eli Lilly and Company, Wyeth Pharmaceuticals, and H. Lundbeck A/S. NR 81 TC 20 Z9 20 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2012 VL 71 IS 7 BP 633 EP 641 DI 10.1016/j.biopsych.2011.11.023 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 910RV UT WOS:000301659900012 PM 22225849 ER PT J AU Sandholm, J Kauppila, JH Pressey, C Tuomela, J Jukkola-Vuorinen, A Vaarala, M Johnson, MR Harris, KW Selander, KS AF Sandholm, Jouko Kauppila, Joonas H. Pressey, Christine Tuomela, Johanna Jukkola-Vuorinen, Arja Vaarala, Markku Johnson, Martin R. Harris, Kevin W. Selander, Katri S. TI Estrogen receptor-alpha and sex steroid hormones regulate Toll-like receptor-9 expression and invasive function in human breast cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Toll-like receptor 9; Invasion; Estradiol; Testosterone ID NF-KAPPA-B; SUBCELLULAR-LOCALIZATION; HELICOBACTER-PYLORI; MEDIATOR PRODUCTION; ANDROGEN RECEPTOR; CELLULAR INVASION; EPITHELIAL-CELLS; IN-VIVO; TLR9; TOLL-LIKE-RECEPTOR-9 AB Toll-like receptor 9 (TLR9) is a cellular DNA-receptor, which is widely expressed in cancer. Synthetic TLR9-ligands induce cancer cell invasion in vitro, but the role of TLR9 in cancer pathophysiology remains unclear. Increased TLR9 expression has been, however, detected in estrogen receptor negative (ER-) breast cancers. In this study, we investigated the effects of ER alpha expression and sex steroid hormones on TLR9 expression in human ER+ (MCF-7, T47-D) and ER- (MDA-MB-231) breast cancer cell lines in vitro. We also studied TLR9 mRNA expression in archival breast cancer specimens (n = 12) with qRT-PCR, using primer sets that detect only the TLR9A isoform or the isoforms A and B (TLR9A/B). The TLR9 mRNA expression was detected in 10/12 specimens with both primer sets, and in 1/12 with only the TLR9A or the TLR9A/B primer sets. The basal TLR9 mRNA expression levels were significantly lower in the ER+ cell lines as compared with the ER- MDA-MB-231 cells. The transfection of ER alpha cDNA into MDA-MB-231 cells also resulted in down-regulation of TLR9 expression. While sex steroids had no effect on TLR9 expression in MCF-7 cells, testosterone (10(-8) M) induced TLR9 expression in MDA-MB-231 and T47-D cells. Although bicalutamide blocked this testosterone effect in MDA-MB-231 cells, in T47-D cells bicalutamide increased TLR9 expression and only partially blocked the testosterone effects. Estradiol (10(-8) M) induced TLR9 expression in T47-D cells. The invasive effects of synthetic TLR9-ligands were augmented by testosterone in vitro. This effect was lost in TLR9 siRNA MDA-MB-231 cells and also decreased by over-expression of ER alpha, which also inhibited NF-kappa B activation by TLR9-ligands. In conclusion, expression of TLR9 isoforms A and B can be detected in clinical breast cancer specimens. The ER alpha and sex steroid hormones regulate TLR9 expression and invasive effects in the breast cancer cells. Also, the commonly used hormonal cancer therapy bicalutamide affects TLR9 expression. C1 [Selander, Katri S.] Univ Alabama, Div Hematol Oncol, Dept Med, Birmingham, AL 35294 USA. [Kauppila, Joonas H.] Univ Oulu, Dept Anat & Cell Biol, Oulu, Finland. [Kauppila, Joonas H.; Vaarala, Markku] Oulu Univ Hosp, Dept Surg, Oulu, Finland. [Jukkola-Vuorinen, Arja] Oulu Univ Hosp, Dept Radiotherapy & Oncol, Oulu, Finland. [Kauppila, Joonas H.; Vaarala, Markku] Oulu Univ Hosp, Dept Pathol, Oulu, Finland. [Johnson, Martin R.] Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. [Harris, Kevin W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Selander, KS (reprint author), Univ Alabama, Div Hematol Oncol, Dept Med, SHEL 14,1825 Univ Blvd, Birmingham, AL 35294 USA. EM Katri.Selander@ccc.uab.edu RI perumal, murugiah/D-1565-2012; Kauppila, Joonas/P-1363-2015; Vaarala, Markku/B-4116-2013 OI Kauppila, Joonas/0000-0001-6740-3726; Vaarala, Markku/0000-0003-4735-815X FU Northern Finnish Duodecim Foundation; Finnish Cultural Foundation; Cancer Foundation of Northern Ostrobotnia; Oulu University Scholarship Foundation; Elsa U. Pardee Foundation FX This study was financially supported by grants from the Northern Finnish Duodecim Foundation (A. J.-V.), Finnish Cultural Foundation, Lapland Funds (A. J.-V. and K. S. S.), Cancer Foundation of Northern Ostrobotnia, Oulu University Scholarship Foundation (J. H. K.), and Elsa U. Pardee Foundation (K. S. S.). NR 34 TC 14 Z9 16 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2012 VL 132 IS 2 BP 411 EP 419 DI 10.1007/s10549-011-1590-3 PG 9 WC Oncology SC Oncology GA 909ER UT WOS:000301545900005 PM 21607583 ER PT J AU Kwan, ML Chen, WY Kroenke, CH Weltzien, EK Beasley, JM Nechuta, SJ Poole, EM Lu, W Holmes, MD Quesenberry, CP Pierce, JP Shu, XO Caan, BJ AF Kwan, Marilyn L. Chen, Wendy Y. Kroenke, Candyce H. Weltzien, Erin K. Beasley, Jeannette M. Nechuta, Sarah J. Poole, Elizabeth M. Lu, Wei Holmes, Michelle D. Quesenberry, Charles P., Jr. Pierce, John P. Shu, Xiao Ou Caan, Bette J. TI Pre-diagnosis body mass index and survival after breast cancer in the After Breast Cancer Pooling Project SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Body mass index; Weight; Obesity; Breast cancer; Survival; Prognosis; Mortality ID POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; PROSPECTIVE COHORT; IMMUNE-RESPONSE; CLINICAL-TRIALS; UNITED-STATES; SEX-HORMONES; OBESITY; INFLAMMATION; METAANALYSIS AB Obese and underweight women who develop breast cancer may have poorer survival compared with normal-weight women. However, the optimal weight for best prognosis is still under study. We conducted a prospective investigation of pre-diagnosis body mass index (BMI) and mortality among 14,948 breast cancer patients in the After Breast Cancer Pooling Project. Breast cancer patients diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors were drawn from four prospective cohorts. Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of BMI categories (World Health Organization international classifications) with recurrence and mortality were estimated using delayed entry Cox proportional hazards models. Obese (30 to < 35 kg/m(2)), severely obese (35 to < 40 kg/m(2)), and morbidly obese (a parts per thousand yen40 kg/m(2)) were examined. After a mean follow-up of 7.8 years, 2,140 deaths and 2,065 recurrences were documented. Both underweight (HR = 1.59; 95% CI: 1.18, 2.13) and morbidly obese women (HR = 1.81; 95% CI: 1.42, 2.32) had the greatest risk of overall mortality compared with normal weight (18.5-24.9 kg/m(2)) women. Severe obesity (HR = 1.09; 95% CI: 0.88, 1.36) and obesity (HR = 1.11; 95% CI: 0.97, 1.27) were related to small non-significant increased risks. Overweight (25.0-29.9 kg/m(2)) was not associated with any excess risk compared with normal weight. Similar associations were found for breast cancer death and non-breast cancer death but not recurrence. Women who were underweight and morbidly obese before breast cancer diagnosis were at the greatest risk of all-cause mortality. Morbidly obese women were also at increased risk of death from breast cancer. These results suggest that degree of obesity confers differential risk on survival. C1 [Kwan, Marilyn L.; Kroenke, Candyce H.; Weltzien, Erin K.; Quesenberry, Charles P., Jr.; Caan, Bette J.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Chen, Wendy Y.; Poole, Elizabeth M.; Holmes, Michelle D.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Chen, Wendy Y.; Poole, Elizabeth M.; Holmes, Michelle D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beasley, Jeannette M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Nechuta, Sarah J.; Shu, Xiao Ou] Vanderbilt Univ, Div Epidemiol, Dept Med, Sch Med, Nashville, TN 37203 USA. [Lu, Wei] Shanghai Inst Prevent Med, Shanghai, Peoples R China. [Pierce, John P.] Univ Calif San Diego, Canc Prevent & Control Program, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. RP Kwan, ML (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Marilyn.L.Kwan@kp.org OI Beasley, Jeannette/0000-0002-9343-6895 FU National Cancer Institute [3R01CA118229-03S1, R01 CA118229, R01 CA129059, P01 CA87969]; Department of Defense [DAMD 17-02-1-0607]; Susan G. Komen Foundation [KG100988] FX This work was supported by the National Cancer Institute (3R01CA118229-03S1). Funding for each individual cohort participating in the After Breast Cancer Pooling Project is as follows: The SBCSS was supported by the Department of Defense (DAMD 17-02-1-0607) and the National Cancer Institute (R01 CA118229). The WHEL Study was supported by the Susan G. Komen Foundation (#KG100988). The LACE Study was supported by the National Cancer Institute (R01 CA129059). The NHS was supported by the National Cancer Institute (P01 CA87969). We thank Dr. Shannon M. Conroy at the University of Hawaii Cancer Center for her expertise on creating the cubic spline curves. NR 58 TC 43 Z9 43 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2012 VL 132 IS 2 BP 729 EP 739 DI 10.1007/s10549-011-1914-3 PG 11 WC Oncology SC Oncology GA 909ER UT WOS:000301545900037 PM 22187127 ER PT J AU Penrod, JD Pronovost, PJ Livote, EE Puntillo, KA Walker, AS Wallenstein, S Mercado, AF Swoboda, SM Ilaoa, D Thompson, DA Nelson, JE AF Penrod, Joan D. Pronovost, Peter J. Livote, Elayne E. Puntillo, Kathleen A. Walker, Amy S. Wallenstein, Sylvan Mercado, Alice F. Swoboda, Sandra M. Ilaoa, Debra Thompson, David A. Nelson, Judith E. TI Meeting standards of high-quality intensive care unit palliative care: Clinical performance and predictors SO CRITICAL CARE MEDICINE LA English DT Article DE critical care; intensive care units; palliative care; quality improvement; quality indicators, health care ID OF-LIFE CARE; FAMILY-MEMBERS; ADVANCE DIRECTIVES; DECISION-MAKING; ICU; COMMUNICATION; INDICATORS; STATEMENT; SYMPTOMS; MEDICINE AB Objectives: High-quality care for intensive care unit patients and families includes palliative care. To promote performance improvement, the Agency for Healthcare Research and Quality's National Quality Measures Clearinghouse identified nine evidence-based processes of intensive care unit palliative care (Care and Communication Bundle) that are measured through review of medical record documentation. We conducted this study to examine how frequently the Care and Communication Bundle processes were performed in diverse intensive care units and to understand patient factors that are associated with such performance. Design: Prospective, multisite, observational study of performance of key intensive care unit palliative care processes. Settings: A surgical intensive care unit and a medical intensive care unit in two different large academic health centers and a medical-surgical intensive care unit in a medium-sized community hospital. Patients: Consecutive adult patients with length of intensive care unit stay >= 5 days. Interventions: None. Measurements and Main Results: Between November 2007 and December 2009, we measured performance by specified day after intensive care unit admission on nine care process measures: identify medical decision-maker, advance directive and resuscitation preference, distribute family information leaflet, assess and manage pain, offer social work and spiritual support, and conduct interdisciplinary family meeting. Muttivariable regression analysis was used to determine predictors of performance of five care processes. We enrolled 518 (94.9%) patients and 336 (83.6%) family members. Performances on pain assessment and management measures were high. In contrast, interdisciplinary family meetings were documented for <20% of patients by intensive care unit day 5. Performance on other measures ranged from 8% to 43%, with substantial variation across and within sites. Chronic comorbidity burden and site were the most consistent predictors of care process performance. Conclusions: Across three intensive care units in this study, performance of key palliative care processes (other than pain assessment and management) was inconsistent and infrequent. Available resources and strategies should be utilized for performance improvement in this area of high importance to patients, families, and providers. (Crit Care Med 2012; 40:1105-1112) C1 [Walker, Amy S.; Mercado, Alice F.; Nelson, Judith E.] Mt Sinai Sch Med, Dept Med, Div Pulm Crit Care & Sleep Med, New York, NY USA. [Penrod, Joan D.; Livote, Elayne E.] James J Peters VA Med Ctr, Ctr Res Hlth Care Syst & Sites Care, Bronx, NY USA. [Penrod, Joan D.] Mt Sinai Sch Med, Hertzberg Palliat Care Inst, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Pronovost, Peter J.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Qual & Safety Res Grp, Baltimore, MD USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Bloomberg Sch Publ Hlth, Sch Nursing, Baltimore, MD 21218 USA. [Swoboda, Sandra M.; Thompson, David A.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Puntillo, Kathleen A.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Wallenstein, Sylvan] Mt Sinai Sch Med, Dept Community Med, New York, NY USA. [Ilaoa, Debra] Norman Reg Hlth Syst, Norman, OK USA. RP Nelson, JE (reprint author), Mt Sinai Sch Med, Dept Med, Div Pulm Crit Care & Sleep Med, New York, NY USA. EM judith.nelson@mssm.edu FU National Institute on Aging [R21 AG029955, AG024476, AG034234]; Department of Veterans Affairs, Health Services Research and Development Service [REA-08-260]; Providence Health and Science Center FX Supported, in part, by R21 AG029955 from the National Institute on Aging. During the period of this work, Dr. Nelson was supported by a K02 Independent Scientist Research Career Development Award AG024476, followed by a K07 Academic Career Leadership Award, AG034234, both from the National Institute on Aging. Additional support was provided by the Department of Veterans Affairs, Health Services Research and Development Service (grant REA-08-260). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.; Dr. Nelson consulted for the Voluntary Hospital Association, Inc. and Veterans Integrated Service Network 3 of the Department of Veterans Affairs. Dr. Puntillo consulted for Veterans Integrated Service Network 3 of the Department of Veterans Affairs and received honoraria/speaking fees from Providence Health and Science Center. The remaining authors have not disclosed any potential conflicts of interest NR 31 TC 22 Z9 22 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2012 VL 40 IS 4 BP 1105 EP 1112 DI 10.1097/CCM.0b013e3182374a50 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 912QC UT WOS:000301813700008 PM 22202706 ER PT J AU Kasotakis, G Schmidt, U Perry, D Grosse-Sundrup, M Benjamin, J Ryan, C Tully, S Hirschberg, R Waak, K Velmahos, G Bittner, EA Zafonte, R Cobb, JP Eikermann, M AF Kasotakis, George Schmidt, Ulrich Perry, Dana Grosse-Sundrup, Martina Benjamin, John Ryan, Cheryl Tully, Susan Hirschberg, Ronald Waak, Karen Velmahos, George Bittner, Edward A. Zafonte, Ross Cobb, J. Perren Eikermann, Matthias TI The surgical intensive care unit optimal mobility score predicts mortality and length of stay SO CRITICAL CARE MEDICINE LA English DT Article DE early mobilization; intensive care unit; mortality; outcomes; prediction; rehabilitation ID CRITICALLY-ILL PATIENTS; RESPIRATORY-DISTRESS-SYNDROME; EARLY MOBILIZATION; ACQUIRED WEAKNESS; EARLY AMBULATION; MUSCLE FORCE; BED REST; HYPERNATREMIA; SEVERITY; OUTCOMES AB Objectives: To test if the surgical intensive care unit optimal mobility score predicts mortality and intensive care unit and hospital length of stay. Design: Prospective single-center cohort study. Setting: Surgical intensive care unit of the Massachusetts General Hospital. Patients:One hundred thirteen consecutive patients admitted to the surgical intensive care unit. Investigations: We tested the hypotheses that the surgical intensive care unit optimal mobility score independent of comorbidity index, Acute Physiology and Chronic Health Evaluation II, creatinine, hypotension, hypernatremia, acidosis, hypoxia, and hypercarbia predicts hospital mortality, surgical intensive care unit and total hospital length of stay. Measurements and Main Results: Two nurses independently predicted the patients' mobilization capacity by using the surgical intensive care unit optimal mobility score the morning after admission, whereas a third nurse recorded the achieved mobilization levels of patients at the end of the day. A multidisciplinary expert team measured patients' grip strength and assessed their predicted mobilization capacity independently. Multivariate analysis revealed that the surgical intensive care unit optimal mobility score was the only independent predictor of mortality. Surgical intensive care unit optimal mobility score, hypotension, and hypernatremia (>144 mmol/L) independently predicted intensive care unit length of stay, whereas the surgical intensive care unit optimal mobility score and hypernatremia predicted total hospital length of stay. The Acute Physiology and Chronic Health Evaluation II score was not identified in the multivariate analysis. The surgical intensive care unit optimal mobility score was also a reliable and valid instrument in predicting achieved mobilization levels of patients. Conclusions: In surgical critically ill patients presenting without preexisting impairment of functional mobility, the surgical intensive care unit optimal mobility score is a reliable and valid tool to predict mortality and intensive care unit and hospital length of stay. (Crit Care Med 2012; 40:1122-1128) C1 [Schmidt, Ulrich; Grosse-Sundrup, Martina; Benjamin, John; Bittner, Edward A.; Cobb, J. Perren; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Kasotakis, George; Velmahos, George] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA USA. [Perry, Dana; Ryan, Cheryl; Tully, Susan] Massachusetts Gen Hosp, Dept Clin Nursing Serv, Boston, MA 02114 USA. [Hirschberg, Ronald; Zafonte, Ross] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Waak, Karen] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. RP Eikermann, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. EM meikermann@partners.org OI Kasotakis, George/0000-0002-7630-0742 NR 45 TC 37 Z9 38 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2012 VL 40 IS 4 BP 1122 EP 1128 DI 10.1097/CCM.0b013e3182376e6d PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 912QC UT WOS:000301813700010 PM 22067629 ER PT J AU Minei, JP Cuschieri, J Sperry, J Moore, EE West, MA Harbrecht, BG O'Keefe, GE Cohen, MJ Moldawer, LL Tompkins, RG Maier, RV AF Minei, Joseph P. Cuschieri, Joseph Sperry, Jason Moore, Ernest E. West, Michael A. Harbrecht, Brian G. O'Keefe, Grant E. Cohen, Mitchell J. Moldawer, Lyle L. Tompkins, Ronald G. Maier, Ronald V. CA Inflammation Host Response Injury TI The changing pattern and implications of multiple organ failure after blunt injury with hemorrhagic shock SO CRITICAL CARE MEDICINE LA English DT Article DE infection; mortality; multiple organ failure; injury; standards of care; trauma ID SCALE COLLABORATIVE PROJECT; ORIENTED RESEARCH CORE; STANDARD OPERATING PROCEDURES; ACUTE LUNG INJURY; CLINICAL CARE; HOST RESPONSE; TRAUMA PATIENT; SYSTEM FAILURE; TIDAL VOLUME; INFLAMMATION AB Objectives: To describe the incidence of postinjury multiple organ failure and its relationship to nosocomial infection and mortality in trauma centers using evidence-based standard operating procedures. Design: Prospective cohort study wherein standard operating procedures were developed and implemented to optimize postinjury care. Setting: Seven U.S. level I trauma centers. Patients: Severely injured patients (older than age 16 yrs) with a blunt mechanism, systolic hypotension (<90 mm Hg), and/or base deficit (>= 6 mEq/L), need for blood transfusion within the first 12 hrs, and an abbreviated injury score >= 2 excluding brain injury were eligible for inclusion. Measurements and Main Results: One thousand two patients were enrolled and 916 met inclusion criteria. Daily markers of organ dysfunction were prospectively recorded for all patients while receiving intensive care. Overall, 29% of patients had multiple organ failure develop. Development of multiple organ failure was early (median time, 2 days), short-lived, and predicted an increased incidence of nosocomial infection, whereas persistence of multiple organ failure predicted mortality. However, surprisingly, nosocomial infection did not increase subsequent multiple organ failure and there was no evidence of a "second-hit"-induced late-onset multiple organ failure. Conclusions: Multiple organ failure remains common after severe injury. Contrary to current paradigms, the onset is only early, and not bimodal, nor is it associated with a "second-hit"-induced late onset. Multiple organ failure is associated with subsequent nosocomial infection and increased mortality. Standard operating procedure-driven interventions may be associated with a decrease in late multiple organ failure and morbidity. (Crit Care Med 2012; 40:1129-1135) C1 [Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Minei, Joseph P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Minei, Joseph P.] Parkland Hlth & Hosp Syst, Dallas, TX USA. [Cuschieri, Joseph; O'Keefe, Grant E.; Maier, Ronald V.] Univ Washington, Sch Med, Seattle, WA USA. [Cuschieri, Joseph; O'Keefe, Grant E.; Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Sperry, Jason] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Sperry, Jason] Presbyterian Univ Hosp, Pittsburgh, PA 15213 USA. [Moore, Ernest E.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Moore, Ernest E.] Denver Hlth Med Ctr, Denver, CO USA. [West, Michael A.; Cohen, Mitchell J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [West, Michael A.; Cohen, Mitchell J.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Harbrecht, Brian G.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. [Moldawer, Lyle L.] Univ Florida, Coll Med, Gainesville, FL USA. [Moldawer, Lyle L.] Univ Florida, Shands Hosp, Gainesville, FL USA. RP Tompkins, RG (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM rtompkins@partners.org FU U.S. National Institutes of Health National Institute of General Medical Sciences [U54GM062119] FX Supported, in part, by the U.S. National Institutes of Health National Institute of General Medical Sciences Large-Scale Collaborative Project (U54GM062119). The funding source had no involvement in the study design, data collection and analysis, or manuscript preparation. NR 30 TC 49 Z9 50 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2012 VL 40 IS 4 BP 1129 EP 1135 DI 10.1097/CCM.0b013e3182376e9f PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 912QC UT WOS:000301813700011 PM 22020243 ER PT J AU Greer, DM Yang, JY Scripko, PD Sims, JR Cash, S Kilbride, R Wu, O Hafler, JP Schoenfeld, DA Furie, KL AF Greer, David M. Yang, Jingyun Scripko, Patricia D. Sims, John R. Cash, Sydney Kilbride, Ronan Wu, Ona Hafler, Jason P. Schoenfeld, David A. Furie, Karen L. TI Clinical examination for outcome prediction in nontraumatic coma SO CRITICAL CARE MEDICINE LA English DT Article DE cardiac arrest; coma; neurologic examination; outcome; prognosis ID CARDIAC-ARREST; CARDIOPULMONARY-RESUSCITATION; POSTANOXIC COMA; ISCHEMIC COMA; SURVIVORS; PROGNOSIS; CARE; CLASSIFICATION; HEMORRHAGE; PATIENT AB Objectives: Determine the utility of the neurologic examination in comatose patients from nontraumatic causes in the modern era. Design: Prospective observational study. Setting: Single academic medical center. Patients: Data from 500 patients in nontraumatic coma collected sequentially from 2000 to 2007 in the emergency department and neuroscience, medical, and cardiac intensive care units. Interventions: None. Measurements and Main Results: Clinical data were collected on days 0, 1, 3, and 7. Outcome was assessed at 6 months; good outcome was determined at two levels by modified Rankin Scale, <= 3 as independence and <= 4 as moderate but not severe disability. A classification and regression tree analysis was performed to determine prognostic variables, creating predictive algorithms of good vs. poor outcome for each day. Patients with coma attributable to subarachnoid hemorrhage (4/80; 5%) or global hypoxic-ischemic injury (20/202, 10%) were more likely to achieve good outcomes. The pupillary reflex was an important determinant, regardless of day or modified Rankin Scale cut point (mean odds ratio 12.51, range [6.01, 22.56] for modified Rankin Scale <= 3; mean odds ratio 19.26, range [5.38, 42.26] for modified Rankin Scale <= 4). A less robust effect was seen for oculocephalic reflexes (mean odds ratio 62.61, range [2.24, 177] for modified Rankin Scale <= 3; mean odds ratio 34.13, range [4.95, 89.93] for modified Rankin Scale <= 4). The motor response was selected as a predictor of outcome only on day 0 (odds ratio 2.35, 95% confidence interval 0.64-5.74 for modified Rankin Scale <= 3; odds ratio 2.1, 95% confidence interval 0.81-4.24 for modified Rankin Scale score <= 4). Age was not associated with outcome. Conclusions: The clinical neurologic examination remains central to determining prognosis in nontraumatic coma. Additional clinical and diagnostic variables may also aid in outcome prediction for specific disease states. (Crit Care Med 2012; 40:1150-1156) C1 [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Greer, David M.; Scripko, Patricia D.; Sims, John R.; Cash, Sydney; Kilbride, Ronan; Furie, Karen L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Yang, Jingyun] Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA. [Sims, John R.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Wu, Ona] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Hafler, Jason P.] Univ Cambridge, Juvenile Diabet Cambridge Inst Med Res, Addenbrookes Hosp, Cambridge CB2 1TN, England. [Schoenfeld, David A.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Greer, DM (reprint author), Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. EM david.greer@yale.edu FU National Institutes of Health FX Dr. Greer received departmental funding. Dr. Furie received grant support from the National Institutes of Health. The remaining authors have not disclosed any potential conflicts of interest. NR 41 TC 16 Z9 16 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2012 VL 40 IS 4 BP 1150 EP 1156 DI 10.1097/CCM.0b013e318237bafb PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 912QC UT WOS:000301813700014 PM 22020245 ER PT J AU Ryan, CM Fagan, SP Goverman, J Sheridan, RL AF Ryan, Colleen M. Fagan, Shawn P. Goverman, Jeremy Sheridan, Robert L. TI Grading inhalation injury by admission bronchoscopy SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE abbreviated injury score; bronchoscopy; burn injury; inhalation grade; inhalation injury; outcomes; smoke ID ACUTE LUNG INJURY; SMOKE-INHALATION; COMBINED BURN; SEVERITY; SHEEP C1 [Ryan, Colleen M.; Fagan, Shawn P.; Goverman, Jeremy; Sheridan, Robert L.] Harvard Univ, Massachusetts Gen Hosp, Sumner Redstone Burn Ctr,Med Sch, Shriners Hosp Children Boston,Surg Serv, Boston, MA 02115 USA. RP Ryan, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sumner Redstone Burn Ctr,Med Sch, Shriners Hosp Children Boston,Surg Serv, Boston, MA 02115 USA. NR 13 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2012 VL 40 IS 4 BP 1345 EP 1346 DI 10.1097/CCM.0b013e31823c8b2f PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 912QC UT WOS:000301813700047 PM 22425833 ER PT J AU Lee, SA Alston, TA AF Lee, Sarah A. Alston, Theodore A. TI A little hypothermia goes a long way SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE cytochrome P450; Leonor Michaelis; Maud Menten; resuscitation; Svante Arrhenius ID TEMPERATURE; ARREST C1 [Lee, Sarah A.; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. RP Lee, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. NR 11 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2012 VL 40 IS 4 BP 1369 EP 1370 DI 10.1097/CCM.0b013e31823b8b6a PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 912QC UT WOS:000301813700062 PM 22425848 ER PT J AU Thakkar, K Alsarraj, A Fong, E Holub, JL Gilger, MA El Serag, HB AF Thakkar, Kalpesh Alsarraj, Abeer Fong, Emily Holub, Jennifer L. Gilger, Mark A. El Serag, Hashem B. TI Prevalence of Colorectal Polyps in Pediatric Colonoscopy SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Colonic polyps; Hematochezia; Colonoscopy ID JUVENILE POLYPS; HYPERPLASTIC POLYPS; COLONIC POLYPS; RISK-FACTORS; LARGE-BOWEL; FOLLOW-UP; CHILDREN; CANCER; EXPERIENCE; MANAGEMENT AB The available data regarding the prevalence, types, and clinical determinants of colonic polyps in children is limited. We aimed to estimate the prevalence of colorectal polyps in a large cohort of children. We conducted a cross-sectional study to determine the presence, number, and location of colorectal polyps reported in all children (0-20 years) who underwent colonoscopy at 14 pediatric facilities between January 2000 and December 2007 recorded in Pediatric Endoscopy Database System Clinical Outcomes Research Initiative (PEDS-CORI). We compared procedures with and without polyps with respect to procedure indication, age, sex, and race. We also reviewed a sample of histopathologic reports from one participating center. We analyzed 13,115 colonoscopy procedures performed in 11,637 patients. Colorectal polyps were reported in 810 procedures (6.1%; 95% CI: 5.7-6.5%) performed in 705 patients, and in 12% of patients with lower GI bleeding. Children with colorectal polyps were significantly younger (8.9 years vs. 11.9 years; p < 0.0001), male (58.3% vs. 49.0%; p < 0.001), non-white race (27.5% vs. 21.9%; p < 0.001), and had lower GI bleeding (54.4% vs. 26.6%; p < 0.001) as compared to children without polyps. In a sample of 122 patients with polyps from a single center, the histological types were solitary juvenile in 91 (70.5%), multiple juvenile in 20 (15.5%), adenoma in 14 (10.9%) and hyperplastic polyps in four patients (3.1%). Colorectal polyps are detected in 6.1% overall and in 12.0% among those with lower gastrointestinal bleeding during pediatric colonoscopy. Approximately 26% are multiple juvenile or adenoma. C1 [Thakkar, Kalpesh; Gilger, Mark A.] Texas Childrens Hosp, Sect Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Alsarraj, Abeer; El Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Alsarraj, Abeer; El Serag, Hashem B.] Baylor Coll Med, Gastroenterol Sect, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. [Alsarraj, Abeer; El Serag, Hashem B.] Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. [Fong, Emily] Baylor Univ, Waco, TX 76798 USA. [Holub, Jennifer L.] Oregon Hlth & Sci Univ, Dept Gastroenterol, Portland, OR 97201 USA. RP Thakkar, K (reprint author), Texas Childrens Hosp, Sect Pediat Gastroenterol Hepatol & Nutr, 6621 Fannin St,CCC 1010, Houston, TX 77030 USA. EM kthakkar@bcm.tmc.edu FU NIDDK [U01DK57132]; AstraZeneca; Novartis; Bard International; Pentax USA; ProVation; Endosoft; GIVEN Imaging; Ethicon FX The study was supported with funding from NIDDK U01DK57132. In addition, the practice network (Clinical Outcomes Research Initiative) has received support from the following entities to support the infrastructure of the practice-based network: AstraZeneca, Novartis, Bard International, Pentax USA, ProVation, Endosoft, GIVEN Imaging, and Ethicon. The commercial entities had no involvement in this research. NR 28 TC 10 Z9 13 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 2012 VL 57 IS 4 BP 1050 EP 1055 DI 10.1007/s10620-011-1972-8 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 912XV UT WOS:000301835600033 PM 22147243 ER PT J AU Goetti, R Leschka, S Boschung, M Mayer, S Wyss, C Stolzmann, P Frauenfelder, T AF Goetti, Robert Leschka, Sebastian Boschung, Markus Mayer, Sabine Wyss, Christophe Stolzmann, Paul Frauenfelder, Thomas TI Radiation doses from phantom measurements at high-pitch dual-source computed tomography coronary angiography SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Radiation dose; High-pitch; Computed tomography; Coronary angiography; Anthropomorphic phantom ID CT ANGIOGRAPHY; CARDIAC CT; PROGRAM AB Objective: To compare radiation doses delivered at prospectively ECG-triggered sequential-(SEQ), retrospectively ECG-gated spiral-(RETRO) and prospectively ECG-triggered high-pitch spiral-(HP) computed tomography coronary angiography (CTCA) protocols, as well as catheter coronary angiography (CCA) using an anthropomorphic phantom. Materials and methods: An anthropomorphic Alderson phantom equipped with 50 thermoluminescent dosimeters (TLDs) was scanned using different CTCA protocols and an uncomplicated diagnostic CCA examination was simulated. Absorbed doses were experimentally determined and effective doses calculated using the dose-length product (DLP) for CTCA and the dose-area product (DAP) for CCA, as well as according to International Commission on Radiation Protection (ICRP) publications 60 and 103. Results: Effective organ doses were significantly lower for HP protocols (100 kV: 0.17 +/- 0.26 mSv; 120 kV: 0.26 +/- 0.39 mSv) compared to SEQ protocols (100 kV: 0.50 +/- 0.79 mSv; 120 kV: 0.90 +/- 1.41 mSv; each p < 0.05) and compared to RETRO protocols (100 kV: 1.59 +/- 2.12 mSv; 120 kV: 2.75 +/- 3.50 mSv; each p < 0.05). Effective organ doses at HP-CTCA tended to be lower than at CCA (0.37 +/- 0.40 mSv), however this was not statistically significant (p = 0.13). Effective doses calculated according to ICRP guidelines could be estimated using the DLP and a conversion coefficient of k = 0.034 mSv/[mGy cm] (ICRP103) or k = 0.028 mSv/[mGy cm] (ICRP60), respectively. HP-CTCA led to a dose reduction of 89% compared to RETRO-CTCA, regardless of the calculation method used. Conclusions: Radiation doses as determined by phantom measurements are significantly lower at HP-CTCA compared to SEQ-CTCA and RETRO-CTCA and comparable to uncomplicated diagnostic CCA. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Goetti, Robert; Stolzmann, Paul; Frauenfelder, Thomas] Univ Zurich Hosp, Dept Diagnost Radiol, CH-8091 Zurich, Switzerland. [Leschka, Sebastian] Kantonsspital, Inst Radiol, CH-9007 St Gallen, Switzerland. [Boschung, Markus; Mayer, Sabine] Paul Scherrer Inst, Div Radiat Safety & Secur, CH-5232 Villigen, Switzerland. [Wyss, Christophe] Univ Zurich Hosp, Div Cardiol, CH-8091 Zurich, Switzerland. [Stolzmann, Paul] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Stolzmann, Paul] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Goetti, R (reprint author), Univ Zurich Hosp, Dept Diagnost Radiol, Raemistr 100, CH-8091 Zurich, Switzerland. EM RobertPaul.Goetti@usz.ch RI Goetti, Robert/I-8961-2012; Frauenfelder, Thomas/O-1734-2016 OI Frauenfelder, Thomas/0000-0002-3295-6619 NR 22 TC 8 Z9 11 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD APR PY 2012 VL 81 IS 4 BP 773 EP 779 DI 10.1016/j.ejrad.2011.01.068 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 906UD UT WOS:000301372300071 PM 21310565 ER PT J AU del Carmen, MG Birrer, M Schorge, JO AF del Carmen, Marcela G. Birrer, Michael Schorge, John O. TI Carcinosarcoma of the ovary: A review of the literature SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Ovarian carcinosarcoma; Debulking surgery; Chemotherapy; Targeted therapy ID MIXED MULLERIAN TUMORS; GYNECOLOGIC-ONCOLOGY-GROUP; PLATINUM-BASED CHEMOTHERAPY; FEMALE GENITAL-TRACT; MESODERMAL TUMOR; PROGNOSTIC-FACTORS; IMMUNOHISTOCHEMICAL ANALYSIS; HISTOGENETIC CONSIDERATIONS; UTERINE; EXPRESSION AB Objective. Carcinosarcoma of the ovary is a rare tumor with a grim prognosis. This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with ovarian carcinosarcoma (OCS). Methods. MEDLINE was searched for all research articles published in English between January 1, 1981 and August 30, 2011 which reported on patients diagnosed with carcinosarcoma of the ovary. Given the rarity of this tumor, studies were not limited by design or number of reported patients. Results. Patients with OCS generally present with advanced stage disease, and symptoms similar to those of patients with epithelial ovarian cancer (EOC). Retrospective studies have shown that cytoreductive surgery improves outcomes in patients with OCS. Similarly, platinum-based chemotherapy appears to be active in the treatment of OCS. Conclusions. Ovarian carcinosarcomas are rare and aggressive tumors, associated with a poor prognosis. The mainstay of treatment remains cytoreductive surgical effort for metastatic disease followed by platinum-based chemotherapy. The role of targeted therapies may be promising in the treatment of OCS. (C) 2011 Elsevier Inc. All rights reserved. C1 [del Carmen, Marcela G.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Sch Med, Boston, MA 02114 USA. [del Carmen, Marcela G.; Birrer, Michael] Harvard Univ, Massachusetts Gen Hosp, Div Med Oncol, Sch Med, Boston, MA 02114 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Sch Med, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 64 TC 23 Z9 23 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2012 VL 125 IS 1 BP 271 EP 277 DI 10.1016/j.ygyno.2011.12.418 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 913LO UT WOS:000301879600048 PM 22155675 ER PT J AU Standiford, HC Chan, S Tripoli, M Weekes, E Forrest, GN AF Standiford, Harold C. Chan, Shannon Tripoli, Megan Weekes, Elizabeth Forrest, Graeme N. TI Antimicrobial Stewardship at a Large Tertiary Care Academic Medical Center: Cost Analysis Before, During, and After a 7-Year Program SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INFECTIOUS-DISEASES SOCIETY; AMERICA; IMPACT AB BACKGROUND. An antimicrobial stewardship program was fully implemented at the University of Maryland Medical Center in July 2001 (beginning of fiscal year [FY] 2002). Essential to the program was an antimicrobial monitoring team (AMT) consisting of an infectious diseases-trained clinical pharmacist and a part-time infectious diseases physician that provided real-time monitoring of antimicrobial orders and active intervention and education when necessary. The program continued for 7 years and was terminated in order to use the resources to increase infectious diseases consults throughout the medical center as an alternative mode of stewardship. DESIGN. A descriptive cost analysis before, during, and after the program. PATIENTS/SETTING. A large tertiary care teaching medical center. METHODS. Monitoring the utilization (dispensing) costs of the antimicrobial agents quarterly for each FY. RESULTS. The utilization costs decreased from $44,181 per 1,000 patient-days at baseline prior to the full implementation of the program (FY 2001) to $23,933 (a 45.8% decrease) by the end of the program (FY 2008). There was a reduction of approximately $3 million within the first 3 years, much of which was the result of a decrease in the use of antifungal agents in the cancer center. After the program was discontinued at the end of FY 2008, antimicrobial costs increased from $23,933 to $31,653 per 1,000 patient-days, a 32.3% increase within 2 years that is equivalent to a $ 2 million increase for the medical center, mostly in the antibacterial category. CONCLUSIONS. The antimicrobial stewardship program, using an antimicrobial monitoring team, was extremely cost effective over this 7-year period. Infect Control Hosp Epidemiol 2012; 33(4): 338-345 C1 [Standiford, Harold C.; Tripoli, Megan] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Standiford, Harold C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Chan, Shannon] Alfred I DuPont Hosp Children, Dept Pediat, Wilmington, DE USA. [Weekes, Elizabeth] Denver Hlth, Dept Pharm, Denver, CO USA. [Forrest, Graeme N.] Portland VA Med Ctr, Div Infect Dis, Portland, OR USA. RP Standiford, HC (reprint author), Univ Maryland, Med Ctr, 110 S Paca St,6th Floor, Baltimore, MD 21201 USA. EM hstandiford@umm.edu NR 10 TC 58 Z9 60 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD APR PY 2012 VL 33 IS 4 SI SI BP 338 EP 345 DI 10.1086/664909 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 911KW UT WOS:000301716700005 PM 22418628 ER PT J AU Jones, M Huttner, B Madaras-Kelly, K Nechodom, K Nielson, C Goetz, MB Neuhauser, MM Samore, MH Rubin, MA AF Jones, Makoto Huttner, Benedikt Madaras-Kelly, Karl Nechodom, Kevin Nielson, Christopher Goetz, Matthew Bidwell Neuhauser, Melinda M. Samore, Matthew H. Rubin, Michael A. TI Parenteral to Oral Conversion of Fluoroquinolones: Low-Hanging Fruit for Antimicrobial Stewardship Programs? SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; CRITICALLY-ILL PATIENTS; HOSPITALIZED-PATIENTS; INTRAABDOMINAL INFECTIONS; EARLY SWITCH; CIPROFLOXACIN; ANTIBIOTICS; THERAPY; INTERVENTION; TUBE AB OBJECTIVE. To estimate avoidable intravenous (IV) fluoroquinolone use in Veterans Affairs (VA) hospitals. DESIGN. A retrospective analysis of bar code medication administration (BCMA) data. SETTING. Acute care wards of 128 VA hospitals throughout the United States. METHODS. Data were analyzed for all medications administered on acute care wards between January 1, 2006, and December 31, 2010. Patient-days receiving therapy were expressed as fluoroquinolone-days (FD) and divided into intravenous (IV; all doses administered intravenously) and oral (PO; at least one dose administered per os) FD. We assumed IV fluoroquinolone use to be potentially avoidable on a given IV FD when there was at least 1 other medication administered via the enteral route. RESULTS. Over the entire study period, 884,740 IV and 830,572 PO FD were administered. Overall, avoidable IV fluoroquinolone use accounted for 46.8% of all FD and 90.9% of IV FD. Excluding the first 2 days of all IV fluoroquinolone courses and limiting the analysis to the non-ICU setting yielded more conservative estimates of avoidable IV use: 20.9% of all FD and 45.9% of IV FD. Avoidable IV use was more common for levofloxacin and more frequent in the ICU setting. There was a moderate correlation between avoidable IV FD and total systemic antibiotic use (r=0.32). CONCLUSIONS. Unnecessary IV fluoroquinolone use seems to be common in the VA system, but important variations exist between facilities. Antibiotic stewardship programs could focus on this patient safety issue as a "low-hanging fruit" to increase awareness of appropriate antibiotic use. Infect Control Hosp Epidemiol 2012; 33(4): 362-367 C1 [Jones, Makoto; Huttner, Benedikt; Nechodom, Kevin; Samore, Matthew H.; Rubin, Michael A.] Univ Utah, IDEAS Ctr, VA Salt Lake City Hlth Care Syst, Salt Lake City, UT 84148 USA. [Jones, Makoto; Huttner, Benedikt; Nechodom, Kevin; Samore, Matthew H.; Rubin, Michael A.] Univ Utah, Div Epidemiol, Salt Lake City, UT 84148 USA. [Madaras-Kelly, Karl] Idaho State Univ, Boise VA Med Ctr, Idaho Falls, ID USA. [Madaras-Kelly, Karl] Idaho State Univ, Coll Pharm, Idaho Falls, ID USA. [Nielson, Christopher] VA Sierra Nevada Hlth Care Syst, Reno, NV USA. [Nielson, Christopher] Univ Nevada, Sch Med, Reno, NV 89557 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, VA Greater LA Healthcare Syst, Los Angeles, CA 90095 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Neuhauser, Melinda M.] VA Pharm Benefits Management Serv, Hines, IL USA. RP Jones, M (reprint author), Univ Utah, IDEAS Ctr, VA Salt Lake City Hlth Care Syst, 500 Foothill Dr, Salt Lake City, UT 84148 USA. EM makoto.jones@va.gov RI Huttner, Benedikt/M-5616-2014; OI Huttner, Benedikt/0000-0002-1749-9464; Goetz, Matthew/0000-0003-4542-992X FU career development award [CDA 10-030-02]; Geneva University Hospitals FX Financial support. M.J. was supported by a career development award (CDA 10-030-02) and B. H. was supported by a fellowship grant from Geneva University Hospitals. NR 28 TC 14 Z9 15 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD APR PY 2012 VL 33 IS 4 SI SI BP 362 EP 367 DI 10.1086/664767 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 911KW UT WOS:000301716700008 PM 22418631 ER PT J AU DeBoyes, T Sherrod, Q El-Masry, M Williams, EA Chiu, MW AF DeBoyes, Telia Sherrod, Quyn El-Masry, Monica Williams, Eric A. Chiu, Melvin W. TI Circumscribed palmar hypokeratosis SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Letter ID PLANTAR HYPOKERATOSIS; MALFORMATION C1 [DeBoyes, Telia] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Ctr Hlth Sci 52 121, Los Angeles, CA 90095 USA. [El-Masry, Monica] Olive View UCLA Med Ctr, Dept Med, Sylmar, CA 91342 USA. [Williams, Eric A.] Kaiser Permanente Med Ctr, Dept Dermatol, Santa Rosa, CA USA. [Chiu, Melvin W.] W Los Angeles Vet Affairs Med Ctr, Dermatol Serv, Los Angeles, CA USA. RP DeBoyes, T (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Ctr Hlth Sci 52 121, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mchiu@mednet.ucla.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD APR PY 2012 VL 51 IS 4 BP 486 EP 488 DI 10.1111/j.1365-4632.2010.04547.x PG 3 WC Dermatology SC Dermatology GA 912GZ UT WOS:000301785100025 PM 21671909 ER PT J AU Melanson, SEF Snyder, ML Jarolim, P Flood, JG AF Melanson, Stacy E. F. Snyder, Marion L. Jarolim, Petr Flood, James G. TI A New Highly Specific Buprenorphine Immunoassay for Monitoring Buprenorphine Compliance and Abuse SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID MASS-SPECTROMETRY; URINE; ASSAY C1 [Melanson, Stacy E. F.; Snyder, Marion L.; Jarolim, Petr] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Flood, James G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Melanson, SEF (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. EM semelanson@partners.org NR 13 TC 8 Z9 8 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD APR PY 2012 VL 36 IS 3 BP 201 EP 206 DI 10.1093/jat/bks003 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 913NI UT WOS:000301884300008 PM 22417836 ER PT J AU Kirkpatrick, WR Najvar, LK Vallor, AC Wiederhold, NP Bocanegra, R Pfeiffer, J Perkins, K Kugler, AR Sweeney, TD Patterson, TF AF Kirkpatrick, William R. Najvar, Laura K. Vallor, Ana C. Wiederhold, Nathan P. Bocanegra, Rosie Pfeiffer, Juergen Perkins, Kimberly Kugler, Alan R. Sweeney, Theresa D. Patterson, Thomas F. TI Prophylactic efficacy of single dose pulmonary administration of amphotericin B inhalation powder in a guinea pig model of invasive pulmonary aspergillosis SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE ABIP; animal model; Aspergillus; prophylaxis ID GALACTOMANNAN ENZYME-IMMUNOASSAY; CELL TRANSPLANT RECIPIENTS; ANTIFUNGAL PROPHYLAXIS; FUNGAL-INFECTIONS; QUANTITATIVE PCR; FUMIGATUS BURDEN; MOLD INFECTIONS; LIPID COMPLEX; MURINE MODEL; DEOXYCHOLATE AB Amphotericin B inhalation powder (ABIP) is a novel dry-powder amphotericin B formulation that is directly delivered to the lung, resulting in elevated lung tissue drug concentrations of this polyene. We evaluated the prophylactic efficacy of single dose administration of ABIP in a guinea pig model of invasive pulmonary aspergillosis. Guinea pigs were immunosuppressed with cyclophosphamide and cortisone acetate and challenged with Aspergillus fumigatus conidia in an aerosol chamber. Guinea pigs received prophylaxis with a single inhaled dose of ABIP at 0.05, 0.5, 4 or 10 mg/kg administered 24 h prior to infection. Treatment with oral voriconazole at doses of 5 or 10 mg/kg twice daily beginning 24 h post-challenge served as the positive control. Improvements in survival were observed with ABIP prophylaxis. A single inhaled dose of 4 mg/kg ABIP and treatment with 5 mg/kg voriconazole both improved median and percentage survival compared with untreated controls. In addition, pulmonary fungal burden, as assessed by cfu, quantitative PCR and galactomannan, was also reduced in a dose-dependent fashion with ABIP prophylaxis as well as with both doses of voriconazole treatment. Single-dose prophylaxis with inhaled ABIP as prophylaxis demonstrated a significant survival advantage and reductions in pulmonary fungal burden in this model of invasive pulmonary aspergillosis. Optimization of the dose and dosing frequency of ABIP dose may help to further enhance the anti-Aspergillus activity of this novel amphotericin B formulation. C1 [Kirkpatrick, William R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Kirkpatrick, William R.; Najvar, Laura K.; Bocanegra, Rosie; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Vallor, Ana C.] Univ Incarnate Word, San Antonio, TX USA. [Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Pfeiffer, Juergen; Perkins, Kimberly; Kugler, Alan R.; Sweeney, Theresa D.] Nektar Therapeut, San Francisco, CA USA. [Kugler, Alan R.] Coastal Pharma Grp, Montara, CA USA. RP Kirkpatrick, WR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kirkpatrick@uthscsa.edu OI Wiederhold, Nathan/0000-0002-2225-5122 FU Nektar Therapeutics, San Francisco, CA, USA; Pfizer; Schering-Plough; Merck; Basilea; Astellas FX This work was supported by a grant from Nektar Therapeutics, San Francisco, CA, USA.; N. P. W. has received research support from Pfizer, Schering-Plough, Merck, Basilea and Astellas, and has served as a consultant for Merck and Viamet. T. F. P. has received research support from Basilea, Astellas, Merck, Pfizer and Schering-Plough, and has served as a consultant for Basilea, Astellas, Merck, Pfizer, Toyama and Viamet. J. P., K. P., A. R. K. and T. D. S. were employees of Nektar Therapeutics and held stock in the company at the time of these studies. All the remaining authors report no conflicts of interest. NR 36 TC 8 Z9 8 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD APR PY 2012 VL 67 IS 4 BP 970 EP 976 DI 10.1093/jac/dkr567 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 910YQ UT WOS:000301684900026 PM 22240402 ER PT J AU Terpstra, JL Chavez, LJ Ayala, GX AF Terpstra, Jennifer L. Chavez, Laura J. Ayala, Guadalupe X. TI An Intervention to Increase Caregiver Support for Asthma Management in Middle School-Aged Youth SO JOURNAL OF ASTHMA LA English DT Article DE adolescents; asthma control; caregiver; quality of life; self-efficacy; self-management ID QUALITY-OF-LIFE; PEDIATRIC ASTHMA; CHILDHOOD ASTHMA; SELF-EFFICACY; CHILDREN; PARENTS; IMPACT; ADOLESCENTS; STUDENTS; BARRIERS AB Objective. Asthma control requires adherence to a treatment regimen. Caregiver involvement is a key determinant of adolescent asthma control, but the involvement must recognize the youth's developmental stage and need for autonomy. This article describes the evaluation of a pilot asthma management intervention for middle school-aged youth and their adult network members, including caregivers, based on caregiver findings. Methods. Following approval from San Diego State University's Institutional Review Board and school district authorization, two middle schools were randomized into one of two conditions: 6-weekly group-based skills training for the adolescents followed by 6-weekly targeted newsletters for caregivers and others (Group 1) versus group-based skills training for adolescents only (Group 2). Outcome evaluation examined pre-post changes by study condition. Results. Caregivers in both groups reported improvements in quality of life (QOL) and access to asthma care resources among their adolescents. Caregiver self-efficacy increased significantly among Group 1 versus Group 2 caregivers, while Group 2 caregivers (those who did not receive newsletters) reported that their adolescents had more responsibility for their asthma care compared with Group 2 caregivers. Conclusions. The adolescent-only intervention resulted in improvements in caregivers' QOL and parenting behaviors that promoted the adolescent's access to asthma resources. When caregivers were directed with intervention materials, their self-efficacy increased. Those who did not receive materials reported that their adolescents had more responsibility for their asthma care. The latter finding may reflect an unintended consequence of an adolescent-only intervention as it may communicate to caregivers to assume less responsibility for their child's asthma care. C1 [Ayala, Guadalupe X.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92123 USA. [Ayala, Guadalupe X.] San Diego State Univ, Inst Behav & Community Hlth, San Diego, CA 92123 USA. [Chavez, Laura J.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Chavez, Laura J.] Vet Affairs Puget Sound Hlth Care Syst, NW Ctr Excellence Hlth Serv Res & Dev, Seattle, WA USA. [Terpstra, Jennifer L.] Ctr Excellence Intervent & Prevent Sci, Carlton, Vic, Australia. RP Ayala, GX (reprint author), San Diego State Univ, Grad Sch Publ Hlth, 9245 Sky Pk Court,Suite 220, San Diego, CA 92123 USA. EM ayala@mail.sdsu.edu FU American Lung Association [CG-939-N] FX In this study, the third author was funded by the American Lung Association through grant no. CG-939-N. NR 33 TC 5 Z9 5 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD APR PY 2012 VL 49 IS 3 BP 267 EP 274 DI 10.3109/02770903.2012.656866 PG 8 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 909AP UT WOS:000301534600008 PM 22316141 ER PT J AU Brown, WV Brook, R Hemphill, LC Moriarty, PM AF Brown, W. Virgil Brook, Robert Hemphill, Linda C. Moriarty, Patrick M. TI The use of lipopheresis in the practice of clinical lipidology SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Editorial Material ID DENSITY-LIPOPROTEIN APHERESIS; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; LDL-APHERESIS; CHOLESTEROL; DISEASE; SAFETY; RISK C1 [Brown, W. Virgil] Emory Univ, Sch Med, Atlanta, GA 30033 USA. [Brook, Robert] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hemphill, Linda C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Moriarty, Patrick M.] Univ Kansas, Med Ctr, Div Clin Pharmacol, Kansas City, KS 66103 USA. RP Brown, WV (reprint author), Emory Univ, Sch Med, 1670 Clairmont Rd, Atlanta, GA 30033 USA. EM editorjcl@yahoo.com NR 15 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 1933-2874 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD APR PY 2012 VL 6 IS 2 BP 98 EP 104 DI 10.1016/j.jacl.2011.12.003 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 910XU UT WOS:000301682700002 PM 22385541 ER PT J AU Yanamadala, V Walcott, BP Nahed, BV Coumans, JVCE AF Yanamadala, Vijay Walcott, Brian P. Nahed, Brian V. Coumans, Jean-Valery C. E. TI Delayed post-traumatic bilateral abducens nerve palsy with complete recovery SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Sixth nerve; Palsy; Trauma; Abducens; Extraocular ID HEAD TRAUMA; MECHANISM; INJURY AB Isolated bilateral abducens (sixth) nerve palsy is rare in the setting of trauma. To date, most cases have been reported in patients who sustain cranial fractures or have other acute intracranial pathologies, including acute hemorrhage. We describe the case of a 41-year-old man who presented with bilateral abducens nerve palsy in the setting of acute head trauma without evidence of cranial fractures or other acute intracranial pathology. Six months after the initial injury, he regained bilateral function of his abducens nerves with intact extraocular muscle movements. Full recovery is the natural history in the majority of traumatic abducens nerve palsies, and this is an important consideration when counseling patients with such injuries. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02115 USA. EM Walcott.Brian@mgh.harvard.edu NR 12 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD APR PY 2012 VL 19 IS 4 BP 585 EP 586 DI 10.1016/j.jocn.2011.09.007 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 912NA UT WOS:000301805700022 PM 22245273 ER PT J AU Meyer, DJ Messer, J Singh, T Thomas, PJ Woyczynski, WA Kaye, J Lerner, AJ AF Meyer, David J. Messer, Jason Singh, Tanya Thomas, Peter J. Woyczynski, Wojbor A. Kaye, Jeffrey Lerner, Alan J. TI Random local temporal structure of category fluency responses SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE Category Fluency Test; Semantic memory; Cognitive impairment; Alzheimer's disease; Statistical temporal structure; Weibull distribution; Inter response times ID VERBAL FLUENCY; MEMORY RETRIEVAL; WEIBULL DISTRIBUTION; RECOGNITION MEMORY; ALZHEIMERS-DISEASE; FREE-RECALL; DIFFUSION; MODELS; TIME; DYNAMICS AB The Category Fluency Test (CFT) provides a sensitive measurement of cognitive capabilities in humans related to retrieval from semantic memory. In particular, it is widely used to assess progress of cognitive impairment in patients with dementia. Previous research shows that, in the first approximation, the intensity of tested individuals' responses within a standard 60-s test period decays exponentially with time, with faster decay rates for more cognitively impaired patients. Such decay rate can then be viewed as a global (macro) diagnostic parameter of each test. In the present paper we focus on the statistical properties of the properly de-trended time intervals between consecutive responses (inter-call times) in the Category Fluency Test. In a sense, those properties reflect the local (micro) structure of the response generation process. We find that a good approximation for the distribution of the de-trended inter-call times is provided by the Weibull Distribution, a probability distribution that appears naturally in this context as a distribution of a minimum of independent random quantities and is the standard tool in industrial reliability theory. This insight leads us to a new interpretation of the concept of "navigating a semantic space" via patient responses. C1 [Woyczynski, Wojbor A.] Case Western Reserve Univ, Dept Stat, Cleveland, OH 44106 USA. [Woyczynski, Wojbor A.] Case Western Reserve Univ, Ctr Stochast & Chaot Proc Sci & Technol, Cleveland, OH 44106 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR 97239 USA. [Lerner, Alan J.] Case Western Reserve Univ, Case Med Ctr, Dept Neurol, Cleveland, OH 44106 USA. [Thomas, Peter J.] Oberlin Coll, Dept Neurosci, Oberlin, OH 44074 USA. [Thomas, Peter J.] Case Western Reserve Univ, Dept Math, Cleveland, OH 44106 USA. [Thomas, Peter J.] Case Western Reserve Univ, Dept Biol, Cleveland, OH 44106 USA. [Thomas, Peter J.] Case Western Reserve Univ, Dept Cognit Sci, Cleveland, OH 44106 USA. RP Woyczynski, WA (reprint author), Case Western Reserve Univ, Dept Stat, 11900 Euclid Ave, Cleveland, OH 44106 USA. EM waw@case.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU U.S. National Science Foundation [DUE-0634612]; National Science Foundation [DMS-0720142]; Oberlin College Libraries; National Institute on Aging [P30AG024978, P30AG08017, R01AG024059] FX This research has been supported by the U.S. National Science Foundation Grant "Interdisciplinary Training for Undergraduates in Biological and Mathematical Sciences" (DUE-0634612) administered by PJT; the first three authors were undergraduate students in biology and mathematics at Case while this work has been done. PJT was supported by the National Science Foundation's program in Mathematical Biology (DMS-0720142), and acknowledges research support from the Oberlin College Libraries. JK was supported by grants from the National Institute on Aging (P30AG024978, P30AG08017 and R01AG024059). NR 45 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD APR PY 2012 VL 32 IS 2 BP 213 EP 231 DI 10.1007/s10827-011-0349-5 PG 19 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 912YH UT WOS:000301837200002 PM 21739237 ER PT J AU Resick, PA Williams, LF Suvak, MK Monson, CM Gradus, JL AF Resick, Patricia A. Williams, Lauren F. Suvak, Michael K. Monson, Candice M. Gradus, Jairnie L. TI Long-Term Outcomes of Cognitive-Behavioral Treatments for Posttraumatic Stress Disorder Among Female Rape Survivors SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE cognitive processing therapy; prolonged exposure; posttraumatic stress disorder; long-term outcomes; randomized controlled trial ID 5-YEAR FOLLOW-UP; PROCESSING THERAPY; RANDOMIZED-TRIAL; PROLONGED EXPOSURE; ASSAULT VICTIMS; VETERANS; PTSD; COMPARABILITY; DEPRESSION; INVENTORY AB Objective: We conducted a long-term follow-up (LTFU) assessment of participants from a randomized controlled trial comparing cognitive processing therapy (CPT) with prolonged exposure (PE) for posttraumatic stress disorder (PTSD). Competing hypotheses for positive outcomes (i.e., additional therapy, medication) were examined. Method: Intention-to-treat (ITT) participants were assessed 5-10 years after participating in the study (M = 6.15, SD = 1.22). We attempted to locate the 171 original participants, women with PTSD who had experienced at least one rape. Of 144 participants located, 87.5% were reassessed (N = 126), which constituted 73.7% of the original ITT sample. Self-reported PTSD symptoms were the primary outcome. Clinician-rated PTSD symptoms, comorbid diagnoses, and self-reported depression were secondary outcomes. Results: Substantial decreases in symptoms due to treatment (as reported in Resick, Nishith, Weaver, Astin, & Feuer, 2002) were maintained throughout the LTFU period, as evidenced by little change over time from posttreatment through follow-up (effect sizes ranging from pr = .03 to .14). No significant differences emerged during the LTFU between the treatment conditions (Cohen's d = 0.06-0.29). The ITT examination of diagnostics indicated that 22.2% of CPT and 17.5% of PE participants met the diagnosis for PTSD according to the Clinician-Administered PTSD Scale (Blake et al., 1995) at the LTFU. Maintenance of improvements could not be attributed to further therapy or medications. Conclusions: CPT and PE resulted in lasting changes in PTSD and related symptoms over an extended period of time for female rape victims with extensive histories of trauma. C1 [Resick, Patricia A.] VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, Boston, MA 01230 USA. [Resick, Patricia A.; Gradus, Jairnie L.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Gradus, Jairnie L.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Williams, Lauren F.] New Mexico VA Healthcare Syst, Albuquerque, NM USA. [Monson, Candice M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. RP Resick, PA (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 01230 USA. EM patricia.resick@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU NIMH NIH HHS [R01 MH051509-06A1, 1 R01-MH51509, R01 MH051509] NR 43 TC 63 Z9 63 U1 4 U2 18 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2012 VL 80 IS 2 BP 201 EP 210 DI 10.1037/a0026602 PG 10 WC Psychology, Clinical SC Psychology GA 913MR UT WOS:000301882600004 PM 22182261 ER PT J AU Goreshi, R Okawa, J Rose, M Feng, R Lee, LA Hansens, CB Bangert, CA Connolly, MK Davis, MD Callen, JP Fett, NM Fakharzadeh, SS Clarke, JT Werth, VP AF Goreshi, Renato Okawa, Joyce Rose, Matt Feng, Rui Lee, Lela A. Hansens, Christopher B. Bangert, Carolyn A. Connolly, M. Kari Davis, Mark D. Callen, Jeff P. Fett, Nicole M. Fakharzadeh, Steven S. Clarke, Jennie T. Werth, Victoria P. TI Evaluation of Reliability, Validity, and Responsiveness of the CDASI and the CAT-BM SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CUTANEOUS ASSESSMENT-TOOL; JUVENILE DERMATOMYOSITIS; DISEASE; POLYMYOSITIS; VALIDATION; AGREEMENT; INDEX AB To properly evaluate therapies for cutaneous dermatomyositis (DM), it is essential to administer an outcome instrument that is reliable, valid, and responsive to clinical change, particularly when measuring disease activity. The purpose of this study was to compare two skin severity DM outcome measures, the Cutaneous Disease and Activity Severity Index (CDASI) and the Cutaneous Assessment Tool Binary Method (CAT-BM), with the Physician Global Assessment (PGA) as the "gold standard". Ten dermatologists evaluated 14 patients with DM using the CDASI, CAT-BM, and PGA scales. Inter- and intra-rater reliability, validity, responsiveness, and completion time were compared for each outcome instrument. Responsiveness was assessed from a different study population, where one physician evaluated 35 patients with 110 visits. The CDASI was found to have a higher inter- and intra-rater reliability. Regarding construct validity, both the CDASI and the CAT-BM were significant predictors of the PGA scales. The CDASI had the best responsiveness among the three outcome instruments examined. The CDASI had a statistically longer completion time than the CAT-BM by about 1.5 minutes. The small patient population may limit the external validity of the findings observed. The CDASI is a better clinical tool to assess skin severity in DM. C1 [Werth, Victoria P.] Univ Penn, Sch Med, Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Goreshi, Renato; Okawa, Joyce; Rose, Matt; Fett, Nicole M.; Fakharzadeh, Steven S.; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Feng, Rui] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lee, Lela A.] Univ Colorado, Denver, CO 80202 USA. [Hansens, Christopher B.] Univ Utah, Salt Lake City, UT USA. [Bangert, Carolyn A.] Univ Texas Houston, Houston, TX USA. [Connolly, M. Kari] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Davis, Mark D.] Mayo Clin, Rochester, MN USA. [Callen, Jeff P.] Univ Louisville, Louisville, KY 40292 USA. [Clarke, Jennie T.] Penn State Hershey, Hershey, PA USA. RP Werth, VP (reprint author), Univ Penn, Sch Med, Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Celgene Corporation; Department of Veterans Affairs Veterans Health Administration; Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health (NIH) [K24-AR 02207] FX This material is based on work supported by Celgene Corporation, the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and by the National Institutes of Health (NIH K24-AR 02207) (VPW). NR 24 TC 11 Z9 12 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2012 VL 132 IS 4 BP 1117 EP 1124 DI 10.1038/jid.2011.440 PG 8 WC Dermatology SC Dermatology GA 910XZ UT WOS:000301683200010 PM 22217740 ER PT J AU Celli, A Mackenzie, DS Zhai, YJ Tu, CL Bikle, DD Holleran, WM Uchida, Y Mauro, TM AF Celli, Anna Mackenzie, Donald S. Zhai, Yongjiao Tu, Chia-Ling Bikle, Daniel D. Holleran, Walter M. Uchida, Yoshikazu Mauro, Theodora M. TI SERCA2-Controlled Ca2+-Dependent Keratinocyte Adhesion and Differentiation Is Mediated via the Sphingolipid Pathway: A Therapeutic Target for Darier's Disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HAILEY-HAILEY-DISEASE; E-CADHERIN; RETICULUM CA2+; MOBILIZATION; CA2+-ATPASE; ACTIVATION; COMPONENTS; MUTATIONS; CATENIN; ATP2A2 AB Darier's disease (DD), caused by mutations in the endoplasmic reticulum (ER) Ca2+ ATPase ATP2A2 (SERCA2b), is a skin disease that exhibits impaired epidermal cell-to-cell adhesion and altered differentiation. Although previous studies have shown that keratinocyte Ca2+ sequestration and fluxes are controlled by sphingolipid signaling, the role of this signaling pathway in DD previously has not been investigated. We show here that sphingosine levels increase and sphingosine kinase (SPHK1) expression decreases after inactivating SERCA2b with the specific SERCA2 inhibitors thapsigargin (TG) or small interfering RNA to SERCA2b. Conversely, inhibiting sphingosine lyase rescues the defects in keratinocyte differentiation, E-cadherin localization, desmoplakin (DP) translocation, and ER Ca2+ sequestration seen in TG-treated keratinocytes. Here, we report early evidence that the keratinocyte sphingolipid and Ca2+ signaling pathways intersect in ATP2A2-controlled ER Ca2+ sequestration, E-cadherin and DP localization, and Ca2+-controlled differentiation, and thus may be important mediators in DD. C1 [Celli, Anna; Mackenzie, Donald S.; Zhai, Yongjiao; Mauro, Theodora M.] San Francisco Vet Adm Med Ctr, Dept Dermatol, San Francisco, CA USA. [Celli, Anna; Mackenzie, Donald S.; Zhai, Yongjiao; Holleran, Walter M.; Uchida, Yoshikazu; Mauro, Theodora M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Tu, Chia-Ling; Bikle, Daniel D.] San Francisco Vet Adm Med Ctr, Endocrine Unit, San Francisco, CA USA. RP Celli, A (reprint author), Dept Vet Affairs Med Ctr, Dermatol Res Unit, 4150 Clement St,Box 190, San Francisco, CA 94121 USA. EM celli.anna@gmail.com FU National Institutes of Health [AR051930]; San Francisco Veterans Administration Medical Service FX This work was supported by National Institutes of Health grants AR051930 and the San Francisco Veterans Administration Medical Service. NR 36 TC 11 Z9 11 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2012 VL 132 IS 4 BP 1188 EP 1195 DI 10.1038/jid.2011.447 PG 8 WC Dermatology SC Dermatology GA 910XZ UT WOS:000301683200018 PM 22277942 ER PT J AU Cohen, D Colvin, RB Daha, MR Drachenberg, CB Haas, M Nickeleit, V Salmon, JE Sis, B Zhao, MH Bruijn, JA Bajema, IM AF Cohen, Danielle Colvin, Robert B. Daha, Mohamed R. Drachenberg, Cinthia B. Haas, Mark Nickeleit, Volker Salmon, Jane E. Sis, Banu Zhao, Ming-Hui Bruijn, Jan A. Bajema, Ingeborg M. TI Pros and cons for C4d as a biomarker SO KIDNEY INTERNATIONAL LA English DT Review DE acute allograft rejection; chronic rejection; complement; transplantation; transplant pathology ID ANTIBODY-MEDIATED REJECTION; RENAL-ALLOGRAFT REJECTION; DONOR-SPECIFIC ANTIBODIES; KIDNEY-TRANSPLANT RECIPIENTS; COMPLEMENT ACTIVATION; HUMORAL REJECTION; GLOMERULAR C4D; PERITUBULAR CAPILLARIES; LUPUS NEPHRITIS; HLA ANTIBODIES AB The introduction of C4d in daily clinical practice in the late nineties aroused an ever-increasing interest in the role of antibody-mediated mechanisms in allograft rejection. As a marker of classical complement activation, C4d made it possible to visualize the direct link between anti-donor antibodies and tissue injury at sites of antibody binding in a graft. With the expanding use of C4d worldwide several limitations of C4d were identified. For instance, in ABO-incompatible transplantations C4d is present in the majority of grafts but this seems to point at 'graft accommodation' rather than antibody-mediated rejection. C4d is now increasingly recognized as a potential biomarker in other fields where antibodies can cause tissue damage, such as systemic autoimmune diseases and pregnancy. In all these fields, C4d holds promise to detect patients at risk for the consequences of antibody-mediated disease. Moreover, the emergence of new therapeutics that block complement activation makes C4d a marker with potential to identify patients who may possibly benefit from these drugs. This review provides an overview of the past, present, and future perspectives of C4d as a biomarker, focusing on its use in solid organ transplantation and discussing its possible new roles in autoimmunity and pregnancy. Kidney International (2012) 81, 628-639; doi:10.1038/ki.2011.497; published online 1 February 2012 C1 [Cohen, Danielle; Bruijn, Jan A.; Bajema, Ingeborg M.] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Daha, Mohamed R.] Leiden Univ, Med Ctr, Dept Immunol & Renal Dis, NL-2300 RC Leiden, Netherlands. [Drachenberg, Cinthia B.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Haas, Mark] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Nickeleit, Volker] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Salmon, Jane E.] Hosp Special Surg, Weill Cornell Med Coll, New York, NY 10021 USA. [Sis, Banu] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB T6G 2M7, Canada. [Zhao, Ming-Hui] Peking Univ, Hosp 1, Dept Med, Div Renal, Beijing 100871, Peoples R China. RP Cohen, D (reprint author), Leiden Univ, Med Ctr, Dept Pathol, L1 Q,POB 9600,P0-107, NL-2300 RC Leiden, Netherlands. EM d.cohen@lumc.nl FU NIAID NIH HHS [U19 AI102405]; NIAMS NIH HHS [R01 AR049772] NR 88 TC 64 Z9 67 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2012 VL 81 IS 7 BP 628 EP 639 DI 10.1038/ki.2011.497 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 913CB UT WOS:000301847900005 PM 22297669 ER PT J AU Fu, WX Wojtkiewicz, G Weissleder, R Benoist, C Mathis, D AF Fu, Wenxian Wojtkiewicz, Gregory Weissleder, Ralph Benoist, Christophe Mathis, Diane TI Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging SO NATURE IMMUNOLOGY LA English DT Article ID ALTERNATIVE PATHWAY; DENDRITIC CELLS; INFLAMMATION; ACTIVATION; MOUSE; MACROPHAGES; PROGRESSION; INHIBITOR; MONOCYTES; AUTOANTIBODIES AB All juvenile mice of the nonobese diabetic (NOD) strain develop insulitis, but there is considerable variation in their progression to diabetes. Here we used a strategy based on magnetic resonance imaging (MRI) of magnetic nanoparticles to noninvasively visualize local effects of pancreatic-islet inflammation to predict the onset of diabetes in NOD mice. MRI signals acquired during a narrow early time window allowed us to sort mice into groups that would progress to clinical disease or not and to estimate the time to diabetes development. We exploited this approach to identify previously unknown molecular and cellular elements correlated with disease protection, including the complement receptor of the immunoglobulin superfamily (CRIg), which marked a subset of macrophages associated with diabetes resistance. Administration of a fusion of CRIg and the Fc portion of immunoglobulin resulted in lower MRI signals and diabetes incidence. In addition to identifying regulators of disease progression, we show here that diabetes is set at an early age in NOD mice. C1 [Fu, Wenxian; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Wojtkiewicz, Gregory; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph; Benoist, Christophe; Mathis, Diane] Broad Inst MIT & Harvard, Cambridge, MA USA. [Mathis, Diane] Harvard Stem Cell Inst, Cambridge, MA USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. EM cbdm@hms.harvard.edu; cbdm@hms.harvard.edu FU US National Institutes of Health [P01 AI054904]; Joslin Diabetes Center [P30 DK036836]; Juvenile Diabetes Research Foundation Center on Immunological Tolerance at Harvard Medical School [4-2007-1057]; Massachusetts General Hospital [U24CA092782]; American Diabetes Association [7-07-BETA-14] FX We thank M. van Lookeren Campagne (Genentech) for discussions and for monoclonal antibody to CRIg and the CRIg-Fc fusion protein; G. Eisenbarth and L. Vu for measuring autoantibodies to insulin; U. Mahmood and A. Guimaraes for MRI protocol setup and discussions; C. Kaufman and J. Chan for assistance with MRI; J. Pagan, K. Hattori, P. Waterman and A. Sumski for assistance with mice; J. Hill, K. Leatherbee, M. Painter and S. Davis for microarray experimentation and analysis; J. Nishio for histology and diabetes monitoring; and I. LaVecchio and G. Buruzala for help with flow cytometry. Supported by the US National Institutes of Health (P01 AI054904 to D.M., C.B. and R.W.), the core facilities of the Joslin Diabetes Center (P30 DK036836), the Manipulated NOD Mouse Core of the Juvenile Diabetes Research Foundation Center on Immunological Tolerance at Harvard Medical School (4-2007-1057), the Mouse Imaging Resource at the Massachusetts General Hospital (U24CA092782) and the American Diabetes Association (7-07-BETA-14 to W.F.). NR 36 TC 40 Z9 41 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2012 VL 13 IS 4 BP 361 EP 368 DI 10.1038/ni.2233 PG 8 WC Immunology SC Immunology GA 913OH UT WOS:000301886800010 PM 22366893 ER PT J AU Engelman, A Cherepanov, P AF Engelman, Alan Cherepanov, Peter TI The structural biology of HIV-1: mechanistic and therapeutic insights SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; APOBEC3G CATALYTIC DOMAIN; HIGH-RESOLUTION STRUCTURES; SMALL-MOLECULE INHIBITION; REV RESPONSE ELEMENT; X-RAY STRUCTURES; REVERSE-TRANSCRIPTASE; CRYSTAL-STRUCTURE; DRUG-RESISTANCE; RESTRICTION FACTOR AB Three-dimensional molecular structures can provide detailed information on biological mechanisms and, for cases in which the molecular function affects human health, can significantly aid in the development of therapeutic interventions. For almost 25 years, key components of the lentivirus HIV-1, including the envelope glycoproteins, the capsid and the replication enzymes reverse transcriptase, integrase and protease, have been scrutinized to near atomic-scale resolution. Moreover, structural analyses of the interactions between viral and host cell components have yielded key insights into the mechanisms of viral entry, chromosomal integration, transcription and egress from cells. Here, we review recent advances in HIV-1 structural biology, focusing on the molecular mechanisms of viral replication and on the development of new therapeutics. C1 [Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Cherepanov, Peter] Canc Res UK London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM alan_engelman@dfci.harvard.edu; peter.cherepanov@cancer.org.uk RI Cherepanov, Peter/F-6859-2010 OI Cherepanov, Peter/0000-0002-0634-538X FU US National Institutes of Health [AI070042]; UK Medical Research Council [G1000917] FX The authors thank M. Yeager for sharing coordinates of the HIV-1 capsid model. This work was supported by grants AI070042 from the US National Institutes of Health (A. E.) and G1000917 from the UK Medical Research Council (P. C.). The opinions voiced herein in no way reflect those of these funding agencies. The authors apologize to colleagues whose work could not be cited or discussed owing to space limitations. NR 165 TC 85 Z9 89 U1 12 U2 94 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD APR PY 2012 VL 10 IS 4 BP 279 EP 290 DI 10.1038/nrmicro2747 PG 12 WC Microbiology SC Microbiology GA 912FU UT WOS:000301780900013 PM 22421880 ER PT J AU Butler, NJ Suhler, EB Rosenbaum, JT AF Butler, Nicholas J. Suhler, Eric B. Rosenbaum, James T. TI Interferon alpha 2b in the Treatment of Uveitic Cystoid Macular Edema SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE interferon alpha 2b; uveitis; cystoid; macular; edema ID ANTIINTERFERON ANTIBODIES; HEPATITIS-C; ALPHA; RETINOPATHY; PANUVEITIS; POSTERIOR AB Purpose: To determine the efficacy of interferon alpha 2b in the treatment of refractory, uveitic cystoid macular edema (CME). Methods: Retrospective chart review of 4 patients attending the uveitis clinic at the Casey Eye Institute, Oregon Health & Science University. Results: All 4 patients had uveitis and refractory CME, resistant to a variety of immunosuppressants. All patients, except one with severe scleral thinning, had tried and failed therapy with locally injected corticosteroids. Treatment with systemic interferon alpha 2b produced dramatic improvement in CME (central macular thickness: 563 to 267 mu m, p = .002) and visual acuity (logMAR: +0.81 to +0.45, p = .0004) in all 4 cases. All patients have been able to reduce the interferon dosage, but none has discontinued it completely. All patients had some mild adverse response that did not necessitate stopping therapy. Conclusions: Interferon alpha 2b is an effective option to treat refractory CME secondary to uveitis. C1 [Suhler, Eric B.; Rosenbaum, James T.] OHSU Casey Eye Inst, Portland, OR 97201 USA. [Butler, Nicholas J.] Wilmer Eye Inst, Baltimore, MD 21287 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Rosenbaum, JT (reprint author), OHSU Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97201 USA. EM rosenbaj@ohsu.edu FU Research to Prevent Blindness; Stan and Madelle Rosenfeld Family Trust; William and Mary Bauman Foundation; William C. Kuzell Foundation FX We are grateful for support from Research to Prevent Blindness, the Stan and Madelle Rosenfeld Family Trust, the William and Mary Bauman Foundation, and the William C. Kuzell Foundation. NR 21 TC 6 Z9 7 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR PY 2012 VL 20 IS 2 BP 86 EP 90 DI 10.3109/09273948.2011.645989 PG 5 WC Ophthalmology SC Ophthalmology GA 908FL UT WOS:000301476200004 PM 22409560 ER PT J AU Charkoudian, LD Ying, GS Pujari, SS Gangaputra, S Thorne, JE Foster, CS Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Kempen, JH AF Charkoudian, Leon D. Ying, Gui-shuang Pujari, Siddharth S. Gangaputra, Sapna Thorne, Jennifer E. Foster, C. Stephen Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Kempen, John H. TI High-dose Intravenous Corticosteroids for Ocular Inflammatory Diseases SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE corticosteroids; inflammation; intravenous; noninfectious; uveitis ID PULSE METHYLPREDNISOLONE THERAPY; UVEITIS; GLUCOCORTICOIDS; MECHANISMS; DISORDERS; DRUGS AB Purpose: To evaluate the effectiveness and risk of complications of high-dose intravenous pulsed corticosteroids for noninfectious ocular inflammatory diseases. Methods: Retrospective cohort study in which 104 eyes of 70 patients who received high-dose intravenous corticosteroids for treatment of active ocular inflammation were identified from five centers. The main outcome measures were control of inflammation and occurrence of ocular or systemic complications within 1 month after treatment. Results: Within <= 1 month of starting treatment, 57% of eyes achieved complete control of inflammation (95% confidence interval (CI): 33-83%), improving to 82% when near-complete control was included (95% CI: 61-96%). Most eyes (85%; 95% CI: 70-95%) gained clinically significant improvement in anterior chamber inflammation. One patient developed a colon perforation during treatment. No other major complications were recorded. Conclusions: Treatment of ocular inflammation with high-dose intravenous corticosteroids resulted in substantial clinical improvement for most cases within 1 month. Complications of therapy were infrequent. C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Charkoudian, Leon D.; Ying, Gui-shuang; Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Charkoudian, Leon D.] Emory Univ, Atlanta, GA 30322 USA. [Ying, Gui-shuang; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Pujari, Siddharth S.; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Pujari, Siddharth S.] LIONS NAB Eye Hosp, Miraj, Maharastra, India. [Gangaputra, Sapna; Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Gangaputra, Sapna] Univ Wisconsin, Sch Med, Fundus Photograph Reading Ctr, Madison, WI USA. [Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu FU National Eye Institute (Bethesda, MD) [EY014943]; Research to Prevent Blindness (New York, NY); Paul and Evanina Mackall Foundation (New York, NY); Research to Prevent Blindness; National Eye Institute; Unites States Veterans' Administration FX This study was supported primarily by the National Eye Institute (Bethesda, MD) Grant EY014943 (Dr. Kempen). Additional support was provided by Research to Prevent Blindness (New York, NY) and the Paul and Evanina Mackall Foundation (New York, NY). Dr. Kempen is a Research to Prevent Blindness James S. Adams Special Scholar Award recipient. Dr. Jabs and Dr. Rosenbaum were Research to Prevent Blindness Senior Scientific Investigator Award recipients during the conduct of the study. Dr. Thorne is a Research to Prevent Blindness Harrington Special Scholar Award recipient. Dr. Levy-Clarke was previously supported by and Dr. Nussenblatt continues to be supported by intramural funds of the National Eye Institute. Dr. Suhler also received support from the Unites States Veterans' Administration. None of the sponsors had any role in the design and conduct of the report; collection, management, analysis, and interpretation of the data; nor in the preparation, review, and approval of this paper. NR 25 TC 7 Z9 7 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR PY 2012 VL 20 IS 2 BP 91 EP 99 DI 10.3109/09273948.2011.646382 PG 9 WC Ophthalmology SC Ophthalmology GA 908FL UT WOS:000301476200005 PM 22409561 ER PT J AU Huynh, N Chang, HYP Borboli-Gerogiannis, S AF Huynh, Nancy Chang, Han-Ying Peggy Borboli-Gerogiannis, Sheila TI Ocular Involvement in Hospitalized Patients with Candidemia: Analysis at a Boston Tertiary Care Center SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Candida; chorioretinitis; endophthalmitis; eye; fungus ID FUNGAL-INFECTIONS AB Purpose: To study the prevalence, microbial profile, and risk factors for ocular involvement in patients with candidemia. Methods: The records of all inpatient consultations requested at the Brigham and Women's Hospital from October 2009 to June 2011 to evaluate for ocular involvement in patients with candidemia were retrospectively reviewed. Results: Forty-nine consults were requested to rule out ocular involvement in patients with candidemia. The mean patient age was 55 years. In decreasing frequency, the organisms isolated were Candida albicans (42%), Candida parapsilosis (23%), Candida glabrata (17%), Candida tropicalis (8%), Candida dublinensis (5%), Candida krusei (3%), and Candida lusitaniae (3%). All patients were on antifungal treatment at the time of their initial ophthalmologic examination. One patient had evidence of chorioretinitis, and 3 patients had nonspecific fundus findings. Common risk factors included presence of an intravenous catheter, malignancy, and abdominal surgery. Conclusions: Ocular involvement is rare among patients with systemic Candida infection. C1 [Huynh, Nancy; Chang, Han-Ying Peggy; Borboli-Gerogiannis, Sheila] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Borboli-Gerogiannis, S (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. EM sheila_borboli-gerogiannis@meei.harvard.edu NR 10 TC 9 Z9 9 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR PY 2012 VL 20 IS 2 BP 100 EP 103 DI 10.3109/09273948.2011.646383 PG 4 WC Ophthalmology SC Ophthalmology GA 908FL UT WOS:000301476200006 PM 22409562 ER PT J AU Ishii, S Cauley, JA Greendale, GA Danielson, ME Nili, NS Karlamangla, A AF Ishii, S. Cauley, J. A. Greendale, G. A. Danielson, M. E. Nili, N. Safaei Karlamangla, A. TI Ethnic differences in composite indices of femoral neck strength SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone size; Composite strength indices; Ethnic difference; Femoral neck strength; Hip geometry; Nativity ID BONE-MINERAL DENSITY; HIP FRACTURE RISK; NON-SPINE FRACTURES; OSTEOPOROTIC FRACTURES; PROXIMAL FEMUR; POSTMENOPAUSAL WOMEN; ELDERLY-WOMEN; WHITE WOMEN; PREDICTION; JAPANESE AB Bone mineral density does not explain race/ethnicity differences in hip fracture risk. In this study, we demonstrated that race/ethnicity differences in composite hip strength indices were consistent with documented race/ethnicity differences in hip fracture risk, suggesting that unlike bone density, the composite indices may represent ethnicity-independent measures of bone strength. African-American and Asian women have lower risks of hip fracture than Caucasian women, but such racial/ethnic variation in hip fracture risk cannot be explained by bone mineral density (BMD). The composite indices of femoral neck strength integrate femoral neck and body size with BMD and predict hip fracture risk in Caucasian women. We hypothesize that unlike race/ethnic differences in BMD, race/ethnic differences in the composite strength indices would be consistent with race/ethnic differences in hip fracture risk. We studied a community-based sample of Caucasian (n = 968), African-American (n = 512), Chinese (n = 221), and Japanese (n = 239) women, premenopausal or in early perimenopause, from the Study of Women's Health Across the Nation. Unadjusted indices were similar in Caucasian and African-American women but higher in Asian women. After adjusting for age, body mass index, and menopause status, all three minority groups had higher composite strength indices than Caucasian women. Foreign-born Japanese women had higher unadjusted and adjusted composite strength indices than US-born Japanese women, but such differences by nativity were not observed in Chinese women. We concluded that composite strength indices have the potential to explain racial/ethnic differences in hip fracture risk, suggesting that composite strength indices may represent ethnicity-independent measures of bone strength. This contention needs to be verified by further research on the fracture predictive ability of composite strength indices in multi-ethnic longitudinal cohorts. C1 [Ishii, S.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA 90073 USA. [Greendale, G. A.; Nili, N. Safaei; Karlamangla, A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Cauley, J. A.; Danielson, M. E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Ishii, S (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC, 11301 Wilshire Blvd,Bldg 220,Room 302, Los Angeles, CA 90073 USA. EM sishii@ucla.edu OI Cauley, Jane A/0000-0003-0752-4408 FU National Institutes of Health (NIH), DHHS, through National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; VA Advanced Geriatrics Fellowship; NIA [AG026463, AG028748] FX The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH) (grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). Dr. Ishii was supported by VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; and VA Advanced Geriatrics Fellowship. The Hip Strength Through the Menopausal Transition has grant support from the NIA (AG026463). The SWAN Hip Strength Sub-Study has grant support from the NIA (AG028748). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH, VA or the NIH. We thank the study staff at each of the following sites and all the women who participated in SWAN: Clinical centers: University of Michigan, Ann Arbor-MaryFran Sowers, PI; Massachusetts General Hospital, Boston, MA-Joel Finkelstein, PI 1999-present; Robert Neer, PI 1994-1999; Rush University, Rush University Medical Center, Chicago, IL-Howard Kravitz, PI 2009-present; Lynda Powell, PI 1994-2009; University of California, Davis/Kaiser-Ellen Gold, PI; University of California, Los Angeles-Gail Greendale, PI; Albert Einstein College of Medicine, Bronx, NY-Rachel Wildman, PI 2010; Nanette Santoro, PI 2004-2010; University of Medicine and Dentistry-New Jersey Medical School, Newark-Gerson Weiss, PI 1994-2004; and the University of Pittsburgh, Pittsburgh, PA-Karen Matthews, PI. NIH program office: National Institute on Aging, Bethesda, MD-Sherry Sherman 1994-present, Marcia Ory 19942001; National Institute of Nursing Research, Bethesda, MD-Program Officers. Central laboratory: University of Michigan, Ann ArborDaniel McConnell (Central Ligand Assay Satellite Services). Coordinating center: University of Pittsburgh, Pittsburgh, PA-Kim SuttonTyrrell, PI 2001-present; New England Research Institutes, Watertown, MA-Sonja McKinlay, PI 1995-2001. Steering committee: Susan Johnson, Current Chair; Chris Gallagher, Former Chair. NR 49 TC 22 Z9 22 U1 0 U2 4 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2012 VL 23 IS 4 BP 1381 EP 1390 DI 10.1007/s00198-011-1723-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 912IM UT WOS:000301790500020 PM 21927926 ER PT J AU Baniwal, SK Shah, PK Shi, Y Haduong, JH DeClerck, YA Gabet, Y Frenkel, B AF Baniwal, S. K. Shah, P. K. Shi, Y. Haduong, J. H. DeClerck, Y. A. Gabet, Y. Frenkel, B. TI Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Co-culture; Microarray; Osteoblast; Osteoclast; Runx2 ID PROSTATE-CANCER CELLS; TRANSCRIPTION FACTOR CBFA1; WIDE EXPRESSION ANALYSIS; BONE-MINERAL DENSITY; GROWTH-FACTOR-BETA; IN-VITRO; GENE-EXPRESSION; TARGET GENES; STROMAL CELLS; OSTEOPROTEGERIN LIGAND AB We profiled the global gene expression of a bone marrow-derived mesenchymal pluripotent cell line in response to Runx2 expression. Besides osteoblast differentiation, Runx2 promoted the osteoclastogenesis of co-cultured splenocytes. This was attributable to the upregulation of many novel osteoclastogenic genes and the downregulation of anti-osteoclastogenic genes. In addition to being a master regulator for osteoblast differentiation, Runx2 controls osteoblast-driven osteoclastogenesis. Previous studies profiling gene expression during osteoblast differentiation had limited focus on Runx2 or paid little attention to its role in mediating osteoblast-driven osteoclastogenesis. ST2/Rx2(dox), a bone marrow-derived mesenchymal pluripotent cell line that expresses Runx2 in response to Doxycycline (Dox), was used to profile Runx2-induced gene expression changes. Runx2-induced osteoblast differentiation was assessed based on alkaline phosphatase staining and expression of classical marker genes. Osteoclastogenic potential was evaluated by TRAP staining of osteoclasts that differentiated from primary murine splenocytes co-cultured with the ST2/Rx2(dox) cells. The BeadChip (TM) platform (Illumina) was used to interrogate genome-wide expression changes in ST2/Rx2(dox) cultures after treatment with Dox or vehicle for 24 or 48 h. Expression of selected genes was also measured by RT-qPCR. Dox-mediated Runx2 induction in ST2 cells stimulated their own differentiation along the osteoblast lineage and the differentiation of co-cultured splenocytes into osteoclasts. The latter was attributable to the stimulation of osteoclastogenic genes such as Sema7a, Ltc4s, Efnb1, Apcdd1, and Tnc as well as the inhibition of anti-osteoclastogenic genes such as Tnfrsf11b (OPG), Sema3a, Slco2b1, Ogn, Clec2d (Ocil), Il1rn, and Rspo2. Direct control of osteoblast differentiation and concomitant indirect control of osteoclast differentiation, both through the activity of Runx2 in pre-osteoblasts, constitute a novel mechanism of coordination with a potential crucial role in coupling bone formation and resorption. C1 [Baniwal, S. K.; Frenkel, B.] Univ So Calif, Keck Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90033 USA. [Baniwal, S. K.; DeClerck, Y. A.; Gabet, Y.; Frenkel, B.] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. [Haduong, J. H.; DeClerck, Y. A.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. [Baniwal, S. K.; Shi, Y.; Gabet, Y.; Frenkel, B.] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA. [Haduong, J. H.; DeClerck, Y. A.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. [Shah, P. K.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gabet, Y.] Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. RP Gabet, Y (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. EM yankel@post.tau.ac.il FU NIH [DK071122, DK071122S1, AR047052]; Arthritis Foundation Southern California Chapter FX We thank USC's Dr. Elizabeth Lowler (Children's Hospital Los Angeles) for the pSLIK system. This work was supported by NIH grants DK071122, DK071122S1, and AR047052 to BF, who holds the J. Harold and Edna L. LaBriola Chair in Genetic Orthopedic Research at USC. SKB was partially supported by a postdoctoral Innovative Chapter Research Award and YG was partially supported by a Meyer Young Investigator Fellowship, both from the Arthritis Foundation Southern California Chapter. NR 124 TC 15 Z9 16 U1 1 U2 11 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2012 VL 23 IS 4 BP 1399 EP 1413 DI 10.1007/s00198-011-1728-5 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 912IM UT WOS:000301790500022 PM 21881969 ER PT J AU Gong, L Thorn, CF Bertagnolli, MM Grosser, T Altman, RB Klein, TE AF Gong, Li Thorn, Caroline F. Bertagnolli, Monica M. Grosser, Tilo Altman, Russ B. Klein, Teri E. TI Celecoxib pathways: pharmacokinetics and pharmacodynamics SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE cardiovascular toxicity; colon cancer; COX-2; coxibs; celecoxib; CYP2C9; drug response; inflammation; nonsteroidal anti-inflammatory drugs; pathway; pharmacogenomics; selective COX-2 inhibitors ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYTOCHROME P4502C9 POLYMORPHISMS; CYCLOOXYGENASE-2 INHIBITOR CELECOXIB; SELECTIVE COX-2 INHIBITORS; ENDOPEROXIDE-H SYNTHASE-1; PROSTATE-CANCER CELLS; HUMAN COLON-CANCER; CARDIOVASCULAR RISK; MYOCARDIAL-INFARCTION; CARBONIC-ANHYDRASE C1 [Klein, Teri E.] Stanford Univ, Dept Genet, Med Ctr, Palo Alto, CA 94304 USA. [Altman, Russ B.] Stanford Univ, Dept Bioengn, Palo Alto, CA 94304 USA. [Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Div Surg Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Grosser, Tilo] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. RP Klein, TE (reprint author), Stanford Univ, Dept Genet, Med Ctr, 1501 Calif Ave, Palo Alto, CA 94304 USA. EM feedback@pharmgkb.org RI Grosser, Tilo/A-1057-2007 OI Grosser, Tilo/0000-0001-8569-8396 FU National Institutes of Health/National Institute of General Medical Sciences [U01GM61374] FX The authors thank Fen Liu for assistance with the graphics. PharmGKB is supported by the National Institutes of Health/National Institute of General Medical Sciences (U01GM61374). NR 96 TC 14 Z9 14 U1 4 U2 24 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 2012 VL 22 IS 4 BP 310 EP 318 DI 10.1097/FPC.0b013e32834f94cb PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 909BP UT WOS:000301537400010 PM 22336956 ER PT J AU Juliano, AFY Cunnane, MB AF Juliano, Amy Fan-Yee Cunnane, Mary Beth TI Benign Conditions of the Thyroid Gland SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID FLOW DOPPLER SONOGRAPHY; ACUTE SUPPURATIVE THYROIDITIS; MR-IMAGING FINDINGS; GRAVES-DISEASE; RIEDELS-THYROIDITIS; HASHIMOTOS-THYROIDITIS; SUBACUTE THYROIDITIS; BLOOD-FLOW; WEGENERS-GRANULOMATOSIS; TUBERCULOUS ABSCESS AB Infectious and autoimmune diseases account for the majority of benign conditions of the thyroid gland. They are usually diagnosed and followed by clinical examination and laboratory analyses, but when imaged, ultrasonography and computed tomography are the modalities of choice. In particular, fine needle aspiration under ultrasound guidance may be invaluable for diagnostic and therapeutic purposes. Semin Ultrasound CT MRI 33:130-137 (C) 2012 Elsevier Inc. All rights reserved. C1 [Juliano, Amy Fan-Yee; Cunnane, Mary Beth] Harvard Univ, Dept Radiol, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Juliano, AFY (reprint author), Harvard Univ, Dept Radiol, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM Amy_Juliano@MEEI.HARVARD.EDU NR 66 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD APR PY 2012 VL 33 IS 2 BP 130 EP 137 DI 10.1053/j.sult.2012.01.001 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 913OJ UT WOS:000301887000005 PM 22410361 ER PT J AU Grabowski, EF Curran, MA Van Cott, EM AF Grabowski, Eric F. Curran, Marjorie A. Van Cott, Elizabeth M. TI Assessment of a Cohort of Primarily Pediatric Patients with a Presumptive Diagnosis of Type 1 von Willebrand Disease with a Novel High Shear Rate, Non-citrated Blood Flow Device SO THROMBOSIS RESEARCH LA English DT Article DE von Willebrand disease (vWD); shear rate; blood flow; digital videomicroscopy; ristocetin cofactor activity; bleeding score ID PLATELET INTERACTION; BLEEDING SYMPTOMS; NATIVE BLOOD; ADHESION; ANALYZER; SUBENDOTHELIUM; QUANTITATION; AGGREGATION; MULTICENTER; ANTIBODY AB Background: A precise approach to the diagnosis of von Willebrand disease (vWD) remains elusive. One important reason is that vWD is a blood flow-related disorder: a vW Factor-platelet GPIb binding defect exists in this condition under the high shear-rate (> 1000 sec-1 inwhole blood; > 3000 sec-1 in PRP) conditions of physiologic blood flow which exist in the arterioles of mucous membranes, from which most bleeding in vWD occurs. Methods: We therefore studied 28 patients (mean 18.9 yrs) with vWD, diagnosed according to the 2007 NHLBI clinical guidelines, and 26 healthy controls (mean 17.5 yrs). Blood was collected into a plastic tube containing 4 U/ml FC dalteparin, 1.75 mu g/ml of the Tab (anti-CD41) monoclonal antibody directed against platelet GPIIb, and 1.0 mu g/ml of an ALEXA 555-conjugated rabbit anti-mouse second antibody. Within 30-90 min, the blood was then withdrawn at 667 and 1330 sec(-1) through a special flow chamber allowing for real-time epifluorescence digital videomicroscopy of platelets interacting with a microfibrillar collagen substrate. With MetaMorph software (Universal Imaging) we quantified the percent area (PA) covered by and total volume (TV) of adherent platelet aggregates within a 435 mu mx580 mu m field of view. Results: At 667 sec(-1) after 1 min PA and TV were similar for patients and controls, but at 1330 sec(-1) PA was 9.32 +/- 4.21 (mean +/- SD) for patients, a value lower (p<0.001) than the 12.8 +/- 3.39 for controls. TV was (1.43 +/- 0.91)x10(4) for patients, a value also lower (p<0.001) than the (2.22 +/- 0.77)x10(4) for controls. PA or TV was below the 2.5th percentile for controls in 10 patients (36%) and both PA and TV were below the 2.5th percentile in eight. Conclusions: The novel flow device found that PA and TV were significantly reduced under high shear stress in vWD patients compared to normal controls. However, there was some overlap between the vWD and the control group, suggesting that some vWD patients had normal platelet adhesion/aggregation under the conditions studied. Further study with a higher shear rate appears indicated. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Grabowski, Eric F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grabowski, EF (reprint author), Massachusetts Gen Hosp, Yawkey 8B,55 Fruit St, Boston, MA 02114 USA. EM Grabowski.Eric@MGH.Harvard.edu FU CSL Behring Foundation for Research and the Advancement of Patient Health; NHLBI [R01HL089332] FX This work was supported by an unrestricted grant from the CSL Behring Foundation for Research and the Advancement of Patient Health, and by NHLBI R01HL089332, "Tissue Factor, Flow, and Platelet Adhesion/Aggregation on Activated Endothelium." We thank Emily Bilouris and Amy Skaria for technical help with the blood flow studies and data collection, and Drs. Rachel P. Rosovsky and Annemarie E. Fogerty for help in recruiting adult patients. NR 29 TC 2 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD APR PY 2012 VL 129 IS 4 BP E18 EP E24 DI 10.1016/j.thromres.2011.12.016 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 909TI UT WOS:000301587400004 PM 22265674 ER PT J AU Kline, JA Marchick, MR Kabrhel, C Courtney, DM AF Kline, Jeffrey A. Marchick, Michael R. Kabrhel, Christopher Courtney, D. Mark TI Prospective Study of the Frequency and Outcomes of Patients with Suspected Pulmonary Embolism Administered Heparin Prior to Confirmatory Imaging SO THROMBOSIS RESEARCH LA English DT Article DE Pulmonary embolism; Empiric anticoagulation; Decision-making; Venous thromboembolism ID REDUCED MORTALITY; DIAGNOSIS; THROMBOEMBOLISM; PROBABILITY AB Objectives: The administration of empiric systemic anticoagulation (ESA) before confirmatory radiographic testing in patients with suspected pulmonary embolism (PE) may improve outcomes, but no data have been published regarding current practice. We describe the use of ESA in a large prospective cohort of emergency department (ED) patients and report the outcomes of those treated with ESA compared with patients not receiving ESA. Methods: 12-center, noninterventional study of ED patients who presented with symptoms concerning for PE. Clinical data including pretest probability and decision to start ESA were recorded at point of care by attending physicians. Patients were followed for adverse in-hospital outcomes and recurrence of venous thromboembolism. Results: ESA was initiated 342/7932 (4.3%) of enrolled patients, including 142/618 (23%) patients with high pretest probability. Patients receiving ESA had more abnormal vital signs and were more likely to have a history of venous thromboembolism than those who did not receive ESA. Overall, 481/7,932 (6.1%) had PE diagnosed, 72/481 (15.0%) with PE had ESA, and 72/342 (21%) of ESA patients had PE. Three patients (0.9%, 95%CI: 0.2-2.5%) who received ESA suffered hemorrhagic complications compared with 38 patients (0.5%, 95%CI: 0.4-0.7%) who did not receive ESA. Conclusions: In this multicenter sample, ED physicians administered ESA to a small, generally more acutely ill subset of patients with high pretest probability of PE, and very few had hemorrhagic complications. ESA was not associatedwith any clear difference in outcomes. More study is needed to clarify the risk versus benefit of ESA. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Kline, Jeffrey A.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28323 USA. [Marchick, Michael R.] Univ Florida, Gainesville, FL USA. [Kabrhel, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Courtney, D. Mark] Northwestern Univ, Chicago, IL 60611 USA. RP Kline, JA (reprint author), Carolinas Med Ctr, Dept Emergency Med, POB 32861, Charlotte, NC 28323 USA. EM Jkline@carolinas.org; marchick@ufl.edu; ckabrhel@partners.org; mcourtney@nmff.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU National Institutes for Health [R41HL074415, R42HL074415, K23HL077404, R01 HL074384]; Emergency Medicine Foundation FX Supported by Grants from the National Institutes for Health, R41HL074415 and R42HL074415, K23HL077404 and R01 HL074384, and a Medical Student Award from the Emergency Medicine Foundation. NR 11 TC 2 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD APR PY 2012 VL 129 IS 4 BP E25 EP E28 DI 10.1016/j.thromres.2012.01.005 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 909TI UT WOS:000301587400005 PM 22285109 ER PT J AU Baldessarini, RJ Undurraga, J Vazquez, GH Tondo, L Salvatore, P Ha, K Khalsa, HMK Lepri, B Ha, TH Chang, JS Tohen, M Vieta, E AF Baldessarini, R. J. Undurraga, J. Vazquez, G. H. Tondo, L. Salvatore, P. Ha, K. Khalsa, H. -M. K. Lepri, B. Ha, T. H. Chang, J. S. Tohen, M. Vieta, E. TI Predominant recurrence polarity among 928 adult international bipolar I disorder patients SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar I disorder; depression; mania; mixed-states; predominant-polarity; suicide ID MOOD DISORDERS; ILLNESS; RISKS; MANIA AB Objective: To test the hypothesis that patients with bipolar disorder (BPD) differ demographically and clinically within subgroups based on the predominant-polarity of major recurrences. Method: We tested factors for association with predominantly (>= 2 : 1) depressive vs. mania-like episodes with 928 DSM-IV type-I BPD subjects from five international sites. Results: Factors preliminarily associated with predominant-depression included: electroconvulsive treatment, longer latency-to-BPD diagnosis, first episode depressive or mixed, more suicide attempts, more Axis-II comorbidity, ever having mixed-states, ever married, and female sex. Predominant-mania was associated with: initial manic or psychotic episodes, more drug abuse, more education, and more family psychiatric history. Of the 47.3% of subjects without polarity-predominance, risks for all factors considered were intermediate. Expanding the definition of polarity-predominance to 51% added little, but shifting mixed-states to 'predominant-depression' increased risk of suicidal acts from 2.4- to 4.5-fold excess over predominant-mania-hypomania, and suicidal risk was associated continuously with increasing proportions of depressive or mixed episodes. Conclusion: Subtyping by predominant-polarity yielded predictive associations, including the polarity of first episodes and risk of suicide attempts. Such subtyping may contribute to improve planning of clinical care and to biological studies of BPD. C1 [Baldessarini, R. J.; Undurraga, J.; Vazquez, G. H.; Tondo, L.; Salvatore, P.; Ha, K.; Khalsa, H. -M. K.; Tohen, M.; Vieta, E.] Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. [Baldessarini, R. J.; Undurraga, J.; Tondo, L.; Salvatore, P.; Ha, K.; Khalsa, H. -M. K.; Tohen, M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Undurraga, J.; Vieta, E.] Univ Barcelona, Bipolar Disorders Program, Hosp Clin, IDIBAPS,CIBERSAM, Barcelona, Spain. [Vazquez, G. H.] Univ Palermo, Dept Clin Neurosci, Buenos Aires, DF, Argentina. [Tondo, L.; Lepri, B.] Lucio Bini Mood Disorder Ctr, Cagliari, Italy. [Salvatore, P.] Univ Parma, Dept Neurosci, Sect Psychiat, I-43100 Parma, Italy. [Chang, J. S.] Seoul Natl Univ, Bundang Hosp, Dept Psychiat, Bundang, Gyeonggi, South Korea. [Tohen, M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 312, 115 Mill St, Belmont, MA 02478 USA. EM rbaldessarini@mclean.harvard.edu RI Ha, Kyooseob/J-5698-2012; Vieta, Eduard/I-6330-2013; Undurraga, Juan/F-3438-2012 OI Vieta, Eduard/0000-0002-0548-0053; Undurraga, Juan/0000-0001-6958-2369 FU Bruce J. Anderson Foundation; McLean Private Donors Psychopharmacology Research Fund; University of Barcelona; Fundacion Espanola de Psiquiatria y Salud Mental; Lucio Bini Private Donors Mood Disorders Research Fund; Korean Ministry of Health [A-101905]; Pfizer; Otsuka; AstraZeneca; Eli Lilly Corporations; Almirall; Astra-Zeneca; Bristol-Myers-Squibb; Eli Lilly; Forest Research Institute; Geodon Richter; GlaxoSmith-Kline; Janssen-Cilag; Jazz; Lundbeck; Merck; Novartis; Sanofi; Servier; Schering-Plough; Takeda; United Biosource Corporations FX Supported in part by a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund (to RJB), by a Traveling Research Fellowship from the University of Barcelona and the Fundacion Espanola de Psiquiatria y Salud Mental (to JU), by the Lucio Bini Private Donors Mood Disorders Research Fund (to LT), and by research grant A-101905 from the Korean Ministry of Health (to KH).; Doctor K. Ha has received research support or honoraria from Pfizer, Otsuka, AstraZeneca, and Eli Lilly Corporations. Doctor Tohen is a former employee of Eli Lilly (to 2008) and has received honoraria or consulted for AstraZeneca, Bristol Myers Squibb, Glaxo Smith Kline, Eli Lilly, Johnson & Johnson, Sepracor, Otsuka, Merck, Sunovion, Forest, Lundbeck and Wyeth Corporations; his spouse is a current employee and minor stockholder at Eli Lilly. Doctor Vieta has been a consultant or grant recipient with the following companies: Almirall, Astra-Zeneca, Bristol-Myers-Squibb, Eli Lilly, Forest Research Institute, Geodon Richter, GlaxoSmith-Kline, Janssen-Cilag, Jazz, Lundbeck, Merck, Novartis, Otsuka, Pfizer, Sanofi, Servier, Schering-Plough, Takeda, and United Biosource Corporations. No other author or close family member has current financial relations that might represent a conflict of interest in the work presented. NR 30 TC 50 Z9 51 U1 3 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 2012 VL 125 IS 4 BP 293 EP 302 DI 10.1111/j.1600-0447.2011.01818.x PG 10 WC Psychiatry SC Psychiatry GA 905OB UT WOS:000301280800007 PM 22188017 ER PT J AU Magalhaes, PV Kapczinski, F Nierenberg, AA Deckersbach, T Weisinger, D Dodd, S Berk, M AF Magalhaes, P. V. Kapczinski, F. Nierenberg, A. A. Deckersbach, T. Weisinger, D. Dodd, S. Berk, M. TI Illness burden and medical comorbidity in the Systematic Treatment Enhancement Program for Bipolar Disorder SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar disorder; medical burden; staging; age at onset; comorbidity; outcome; treatment; mania; depression; course; diabetes; smoking; cardiovascular ID C-REACTIVE PROTEIN; STEP-BD; EARLY INTERVENTION; MAJOR DEPRESSION; WOMEN; RISK; ASSOCIATION; POPULATION; HEALTH; AGE AB Objective: Coexisting chronic medical conditions are common in bipolar disorder. Here, we report the prevalence and correlates of medical comorbidity in patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). We were particularly interested in associations between variables reflecting illness chronicity and burden with comorbid medical conditions. Method: We used intake data from the open-label component of the STEP-BD. History of medical comorbidity was obtained from the affective disorders evaluation, and its presence was the outcome of interest. The sample size in analyses varied from 3399 to 3534. We used multiple Poisson regression to obtain prevalence ratios. Results: The prevalence of any medical comorbidity in the sample was 58.8%. In addition to demographic variable, several clinical characteristics were associated with the frequency of medical comorbidity. Having more than 10 previous mood episodes, childhood onset, smoking, lifetime comorbidity with anxiety, and substance use disorders were independently associated with having a medical comorbidity in the final multivariate model. Conclusion: The results presented here reveal strong associations between variables related to illness chronicity and medical burden in bipolar disorder. This lends further support to recent multidimensional models incorporating medical morbidity as a core feature of bipolar disorder. C1 [Magalhaes, P. V.; Kapczinski, F.] Univ Fed Rio Grande do Sul, Natl Inst Translat Med, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Magalhaes, P. V.; Dodd, S.; Berk, M.] Deakin Univ, Barwon Hlth, Sch Med, Geelong, Vic 3217, Australia. [Nierenberg, A. A.; Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Weisinger, D.; Dodd, S.; Berk, M.] Univ Melbourne, Dept Psychiat, Geelong, Vic 3220, Australia. [Berk, M.] Orygen Youth Hlth Res Ctr, Melbourne, Vic, Australia. [Berk, M.] Mental Hlth Res Inst, Parkville, Vic, Australia. RP Berk, M (reprint author), Univ Melbourne, Barwon Hlth, Dept Clin & Biomed Sci, POB 281, Geelong, Vic 3220, Australia. EM mikebe@barwonhealth.org.au RI Kapczinski, Flavio/D-3175-2013; TM, Inct/J-8630-2013; Kapczinski, Flavio/J-5803-2014; Magalhaes, Pedro/A-8519-2008; OI Magalhaes, Pedro/0000-0002-5644-6357; Berk, Michael/0000-0002-5554-6946 FU National Institute for Translational Medicine, Brazil; National Institute of Mental Health; Astra-Zeneca; Eli Lilly; Janssen-Cilag; Servier; CNPq; CAPES; NARSAD; Stanley Medical Research Institute; Stanley Medical Research Foundation; MBF; NHMRC; Beyond Blue; Geelong Medical Research Foundation; Bristol Myers Squibb; Glaxo SmithKline; Glaxo SmithKline, Organon; Novartis; Mayne Pharma; Pamlab; Shire FX The Systematic Treatment Enhancement Program for Bipolar Disorder was funded by the National Institute of Mental Health, which had no role in drafting or analyzing and preparing this manuscript. The data set was obtained from the National Institutes of Mental Health by a request from Prof. Berk that was specifically approved by Barwon Health's Human Research Ethics Committee. STEP-BD was registered at clinicaltrials.gov with the identifier NCT00012558. Dr. Magalhaes is supported by the National Institute for Translational Medicine, Brazil.; Prof. Kapczinski has received grant/research support from Astra-Zeneca, Eli Lilly, the Janssen-Cilag, Servier, CNPq, CAPES, NARSAD, and the Stanley Medical Research Institute; has been a member of the speakers' boards for Astra-Zeneca, Eli Lilly, Janssen, and Servier; and has served as a consultant for Servier. Prof. Berk has received research support from Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma, Servier. He has been a speaker for Speakers: Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay, and Wyeth. He has been a consultant for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, and Servier.; As of September 2, 2009, Dr Nierenberg is a consultant for Appliance Computing (Mindsite), BrainCells, Brandeis University, PGx Health, Shire, Schering-Plough, Targacept, and Takeda; has received grant/research support from National Institute of Mental Health, Pamlab, Pfizer, and Shire; has received honoraria from Belvior Publishing, University of Texas Southwestern Dallas, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, IMEDEX, MJ Consulting, New York State, MBL Publishing, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, and the University of Pisa; is on the advisory boards of Appliance Computing, BrainCells, Eli Lilly, and Takeda; is a stock shareholder of Appliance Computing and BrainCells; and, through Massachusetts General Hospital, owns copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Rating Scale exclusively licensed to the MGH Clinical Trials Network and Institute. NR 40 TC 46 Z9 48 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 2012 VL 125 IS 4 BP 303 EP 308 DI 10.1111/j.1600-0447.2011.01794.x PG 6 WC Psychiatry SC Psychiatry GA 905OB UT WOS:000301280800008 PM 22098628 ER PT J AU Bech, P Fava, M Trivedi, MH Wisniewski, SR Rush, AJ AF Bech, P. Fava, M. Trivedi, M. H. Wisniewski, S. R. Rush, A. J. TI Outcomes on the pharmacopsychometric triangle in bupropion-SR vs. buspirone augmentation of citalopram in the STAR*D trial SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE citalopram; bupropion-SR; buspirone; HAM-D6; IDS-C6; pharmacopsychometric triangle ID MAJOR DEPRESSION; PLACEBO AB Objective: To compare within the framework of a novel pharmacopsychometric triangle, augmentation treatment with bupropion vs. buspirone in the acute therapy of major depression in the STAR*D study. The triangle provides a composite view in three domains of antidepressive activity, side effects, and quality of life. Method: Within the pharmacopsychometric triangle, the short six-item subscales of the Hamilton Depression Scale (HAM-D-17) and of the Inventory of Depressive Symptomatology (IDS-C-30), referred to as HAM-D-6 and IDS-C-6, were focussed on pure antidepressive effect. Side-effects (tolerable vs. intolerable) and quality of life were measured using patient-administered questionnaires. A modified intention to treat sample was used. Results: Within the pharmacopsychometric triangle, bupropion-SR (sustained release) was superior to buspirone when augmented to the current citalopram treatment. Thus, in the domain of pure antidepressive effect, bupropion-SR was superior (P = 0.05) on the HAM-D-6, IDS-C-6, and IDS-C-30, but not on the HAM-D-17. In the domain of side effects, the total scores on the Patient Rated Inventory of Side Effects (PRISE) were reduced significantly more by bupropion-SR than by buspirone (P = 0.03). In the domain of quality of life, the total scores on the Quality of Life Enjoyment and Satisfaction Questionnaire (QLES-Q) showed a trend (P = 0.10) from baseline to endpoint of a superiority for bupropion-SR compared with buspirone. Conclusion: In all domains of the pharmacopsychometric triangle, bupropion-SR was superior to buspirone as augmentation therapy in depressed outpatients not responding to citalopram. C1 [Bech, P.] Univ Copenhagen, Mental Hlth Ctr N Zealand, Psychiat Res Unit, DK-3400 Hillerod, Denmark. [Fava, M.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Trivedi, M. H.] Univ Texas Southwestern Med Sch, Dallas, TX USA. [Wisniewski, S. R.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Rush, A. J.] Duke NUS, Singapore, Singapore. RP Bech, P (reprint author), Univ Copenhagen, Mental Hlth Ctr N Zealand, Psychiat Res Unit, Dyrehavevej 48, DK-3400 Hillerod, Denmark. EM Per.bech@regionh.dk RI Trivedi, Madhukar/A-9029-2013; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; Brain-Cells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; Clinical Trials Solutions, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite(R) LLC; Roche; RTC Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Agency for Healthcare Research and Quality (AHRQ); Corcept Therapeutics, Inc.; Cyberonics, Inc.; Merck; National Alliance for Research in Schizophrenia and Depression; National Institute of Mental Health; National Institute on Drug Abuse; Novartis; Pharmacia Upjohn; Predix Pharmaceuticals (Epix); Targacept; Abbott Laboratories, Inc.; Abdi Ibrahim, Akzo (Organon Pharmaceuticals Inc.); Bristol-Myers Squibb Company; Evotec; Fabre Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals; Janssen Pharmaceutica Products, LP; Johnson Johnson PRD; Eli Lilly Company; Meade Johnson; Medtronic; Neuronetics; Otsuka Pharmaceuticals; Parke-Davis Pharmaceuticals, Inc.; Sepracor; SHIRE Development; VantagePoint; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Institutes of Health FX Research Support: Abbott Laboratories; Alkermes, Inc.; Aspect Medical Systems; AstraZeneca; BioResearch; Brain-Cells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; Clinical Trials Solutions, LLC; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer Inc.; Pharmavite (R) LLC; Roche; RTC Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo; Wyeth-Ayerst Laboratories.; Dr. Trivedi reports that he has received research support from the Agency for Healthcare Research and Quality (AHRQ), Corcept Therapeutics, Inc., Cyberonics, Inc., Merck, National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health, National Institute on Drug Abuse, Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals (Epix), Solvay Pharmaceuticals, Inc., and Targacept. He has received consulting and speaker fees from Abbott Laboratories, Inc., Abdi Ibrahim, Akzo (Organon Pharmaceuticals Inc.), AstraZeneca, Bristol-Myers Squibb Company, Cephalon, Inc., Evotec, Fabre Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica Products, LP, Johnson & Johnson PRD, Eli Lilly & Company, Meade Johnson, Medtronic, Neuronetics, Otsuka Pharmaceuticals, Parke-Davis Pharmaceuticals, Inc., Pfizer Inc., Sepracor, SHIRE Development, VantagePoint, and Wyeth-Ayerst Laboratories. Dr. Greer has received grant support from a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award and National Institutes of Health. NR 24 TC 14 Z9 15 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 2012 VL 125 IS 4 BP 342 EP 348 DI 10.1111/j.1600-0447.2011.01791.x PG 7 WC Psychiatry SC Psychiatry GA 905OB UT WOS:000301280800013 PM 22077211 ER PT J AU Ananthakrishnan, AN Guzman-Perez, R Gainer, V Cai, T Churchill, S Kohane, I Plenge, RM Murphy, S AF Ananthakrishnan, A. N. Guzman-Perez, R. Gainer, V. Cai, T. Churchill, S. Kohane, I. Plenge, R. M. Murphy, S. TI Predictors of severe outcomes associated with Clostridium difficile infection in patients with inflammatory bowel disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SEVERE ULCERATIVE-COLITIS; DIARRHEA; EPIDEMIOLOGY; BURDEN; STRATEGIES; GUIDELINES; VANCOMYCIN; DIAGNOSIS; UPDATE; ADULTS AB Background The increasing incidence of Clostridium difficile (C. difficile) infection (CDI) among patients with inflammatory bowel disease is well recognised. However, most studies have focused on demonstrating that CDI is associated with adverse outcomes in IBD patients. Few have attempted to identify predictors of severe outcomes associated with CDI among IBD patients. Aim To identify clinical and laboratory factors that predict severe outcomes associated with CDI in IBD patients. Methods From a multi-institution EMR database, we identified all hospitalised patients with at least one diagnosis code for C. difficile from among those with a diagnosis of Crohn's disease or ulcerative colitis. Our primary outcome was time to total colectomy or death with follow-up censored at 180 days after CDI. Cox proportional hazards models were used to identify predictors of the primary outcome from among demographic, disease-related, laboratory and medication variables. Results A total of 294 patients with CDI-IBD were included in our study. Of these, 58 patients (20%) met our primary outcome (45 deaths, 13 colectomy) at a median of 31 days. On multivariate analysis, serum albumin <3 g/dL (HR 5.75, 95% CI 1.34-24.56), haemoglobin below 9 g/dL (HR 5.29, 95% CI 1.58-17.69) and creatinine above 1.5 mg/dL (HR 1.98, 95% CI 1.04-3.79) were independent predictors of our primary outcome. Examining laboratory parameters as continuous variables or shortening our primary outcome to include events within 90 days yielded similar results. Conclusion Serum albumin below 3 g/dL, haemoglobin below 9 g/dL and serum creatinine above 1.5 mg/dL were independent predictors of severe outcomes in hospitalised IBD patients with Clostridium difficile infection. C1 [Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, Boston, MA 02114 USA. [Ananthakrishnan, A. N.; Kohane, I.] Harvard Univ, Sch Med, Boston, MA USA. [Guzman-Perez, R.; Gainer, V.; Murphy, S.] Partners Hlth Care Syst, Informat, Boston, MA USA. [Cai, T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Churchill, S.; Kohane, I.; Murphy, S.] I2b2 Natl Ctr Biomed Comp, Boston, MA USA. [Plenge, R. M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NIH/NLM [2U54LM008748]; American Gastroenterology Association; National Institutes of Health [R01-AR057108, R01-AR056768, U01-GM092691]; Burroughs Wellcome Fund FX Declaration of personal interests: None. Declaration of funding interests: The research was supported by NIH/NLM 2U54LM008748. Ananthakrishnan is also supported by a grant from the American Gastroenterology Association. Plenge was supported by grants from the National Institutes of Health (R01-AR057108, R01-AR056768 and U01-GM092691) and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. NR 36 TC 28 Z9 28 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD APR PY 2012 VL 35 IS 7 BP 789 EP 795 DI 10.1111/j.1365-2036.2012.05022.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 904VV UT WOS:000301227400004 PM 22360370 ER PT J AU Emmons, K AF Emmons, Karen TI Behavioral Medicine and the Health of Our Nation: Accelerating Our Impact SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Behavioral Medicine; Impact; Translation ID INSTITUTE-OF-MEDICINE; TOBACCO USE; CANCER PREVENTION; EXTERNAL VALIDITY; SOCIAL-CONTEXT; WORKING-CLASS; INTERVENTIONS; MASSACHUSETTS; DEPENDENCE; TRANSLATION AB A key goal of this paper is to illustrate the impact of behavioral medicine on the factors that influence population health. A second goal is to consider the delicate balance between relevance and excellence as we bring our science to bear on important social and public health problems. If we are to increase the translation of our evidence and accelerate our impact, we must increase our relevance while maintaining excellence in our scientific methods. What are the pressing questions facing those that we would like to use our work, and how we can increase our relevance to theirs? We must work on the marriage of relevance and excellence-use rigorous methodologies, but be flexible in our approach, using study designs and methods that will get rapid yet rigorous answers to the questions that are facing practice and policy settings. We have the tools and the knowledge to impact the health of our nation. C1 [Emmons, Karen] Harvard Univ, Sch Publ Hlth, Ctr Community Based Res, Boston, MA 02215 USA. [Emmons, Karen] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Emmons, K (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Community Based Res, 450 Brookline Ave,LW703, Boston, MA 02215 USA. EM karen_m_emmons@dfci.harvard.edu FU NCI NIH HHS [5R01CA106914, K05 CA124415, R01 CA106914, R01 CA126596, R01 CA123228, 5R01CA123228, U54CA156732, 5R01 CA126596, U54 CA156732] NR 47 TC 0 Z9 0 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 IS 2 BP 153 EP 161 DI 10.1007/s12160-011-9321-x PG 9 WC Psychology, Multidisciplinary SC Psychology GA 907ZT UT WOS:000301460500005 PM 22076696 ER PT J AU Kubzansky, LD Gilthorpe, MS Goodman, E AF Kubzansky, Laura D. Gilthorpe, Mark S. Goodman, Elizabeth TI A Prospective Study of Psychological Distress and Weight Status in Adolescents/Young Adults SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Obesity; Anxiety; Depression; Adolescence; Growth mixture model; Latent class ID DEPRESSIVE SYMPTOMS; DEVELOPMENTAL TRAJECTORIES; SOCIOECONOMIC-STATUS; OBESITY; ADOLESCENCE; ANXIETY; HEALTH; ASSOCIATION; OVERWEIGHT; DISORDERS AB The obesity-psychological distress relationship remains controversial. This study aims to assess whether adolescents' psychological distress was associated with body mass index (BMI) class membership determined by latent class analysis. Distress (anxiety, depression) and BMI were measured annually for 4 years in 1,528 adolescents. Growth mixture modeling derived latent BMI trajectory classes for models with 2-11 classes. The relationship of distress to class membership was examined in the best-fitting model using vector generalized linear regression. BMI trajectories were basically flat. The five-class model [normal weight (48.8%), overweight (36.7%), obese who become overweight (3.7%), obese (9.4%), and severely obese (1.3%)] was the preferred model (Bayesian information criterion = 22789.2, df = 31; rho = 0.84). Greater distress was associated with higher baseline BMI and, therefore, class membership. Psychological distress is associated with higher BMI class during adolescence. To determine whether distress "leads" to greater weight gain may require studies of younger populations. C1 [Goodman, Elizabeth] MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Goodman, Elizabeth] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kubzansky, Laura D.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilthorpe, Mark S.] Univ Leeds, Sch Med, Ctr Biostat & Epidemiol, Leeds LS2 9JT, W Yorkshire, England. RP Goodman, E (reprint author), MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, 100 Cambridge St,Suite 1570, Boston, MA 02114 USA. EM egoodman3@partners.org FU NICHD NIH HHS [R01 HD041527-12, HD041527, R01 HD041527] NR 37 TC 23 Z9 23 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2012 VL 43 IS 2 BP 219 EP 228 DI 10.1007/s12160-011-9323-8 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 907ZT UT WOS:000301460500012 PM 22090262 ER PT J AU Schmader, KE Levin, MJ Gnann, JW McNeil, SA Vesikari, T Betts, RF Keay, S Stek, JE Bundick, ND Su, SC Zhao, YL Li, XM Chan, ISF Annunziato, PW Parrino, J AF Schmader, Kenneth E. Levin, Myron J. Gnann, John W., Jr. McNeil, Shelly A. Vesikari, Timo Betts, Robert F. Keay, Susan Stek, Jon E. Bundick, Nickoya D. Su, Shu-Chih Zhao, Yanli Li, Xiaoming Chan, Ivan S. F. Annunziato, Paula W. Parrino, Janie TI Efficacy, Safety, and Tolerability of Herpes Zoster Vaccine in Persons Aged 50-59 Years SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID QUALITY-OF-LIFE; VARICELLA-ZOSTER; POSTHERPETIC NEURALGIA; IMMUNE-RESPONSES; OLDER-ADULTS; FUNCTIONAL STATUS; VIRUS; IMMUNOGENICITY; ZOSTAVAX; IMPACT AB Background. Herpes zoster (HZ) adversely affects individuals aged 50-59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50-59 years. Methods. This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50-59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for >= 1 year (mean, 1.3 years) postvaccination until accrual of >= 96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination. Results. The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1-80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups. Conclusions. In subjects aged 50-59 years, the ZV significantly reduced the incidence of HZ and was well tolerated. Clinical Trials Registration. NCT00534248. C1 [Schmader, Kenneth E.] Duke Univ, Durham, NC 27706 USA. [Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA. [Levin, Myron J.] Univ Colorado, Sch Med, Aurora, CO USA. [Gnann, John W., Jr.] Univ Alabama Birmingham, Birmingham, AL USA. [Gnann, John W., Jr.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [McNeil, Shelly A.] Dalhousie Univ, Halifax, NS, Canada. [Vesikari, Timo] Univ Tampere, FIN-33101 Tampere, Finland. [Betts, Robert F.] Univ Rochester, New York, NY USA. [Keay, Susan] Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA. [Stek, Jon E.; Bundick, Nickoya D.; Su, Shu-Chih; Zhao, Yanli; Li, Xiaoming; Chan, Ivan S. F.; Annunziato, Paula W.; Parrino, Janie] Merck Sharp, Whitehouse Stn, NJ USA. [Stek, Jon E.; Bundick, Nickoya D.; Su, Shu-Chih; Zhao, Yanli; Li, Xiaoming; Chan, Ivan S. F.; Annunziato, Paula W.; Parrino, Janie] Dohme Corp, Whitehouse Stn, NJ USA. RP Parrino, J (reprint author), Merck Sharp, POB 1000,UG3CD 28, N Wales, PA 19454 USA. EM janie_parrino@merck.com FU Merck; Sharp; Dohme Corp; Baltimore Research and Education Foundation FX This work was supported by Merck, Sharp, and Dohme Corp (sponsor). In conjunction with the external investigators, this study was designed, executed, and analyzed by the sponsor. Although the sponsor formally reviewed a penultimate draft, the opinions expressed are those of the authors and may not necessarily reflect those of the sponsor. All co-authors approved the final version of the manuscript.; R. F. B, J. W. G, S. A. M, T. V, and K. E. Ss received grant payment from Merck, Sharp, & Dohme Corp for this study. J. E. S, N. D. B, S. C. S, Y. Z, X. L, I. S. F. C, P. W. A, and J. P. are Merck, Sharp, and Dohme Corp employees and hold stock and/or stock options in the company. M. J. L. is a consultant for Merck and shares intellectual property rights on Zostavax. S. K. has received grant funds administered by the Baltimore Research and Education Foundation for this study. NR 29 TC 126 Z9 134 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2012 VL 54 IS 7 BP 922 EP 928 DI 10.1093/cid/cir970 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 905TB UT WOS:000301296200012 PM 22291101 ER PT J AU Justice, AC Freiberg, MS Tracy, R Kuller, L Tate, JP Goetz, MB Fiellin, DA Vanasse, GJ Butt, AA Rodriguez-Barradas, MC Gibert, C Oursler, KA Deeks, SG Bryant, K AF Justice, Amy C. Freiberg, Matthew S. Tracy, Russ Kuller, Lew Tate, Janet P. Goetz, Matthew Bidwell Fiellin, David A. Vanasse, Gary J. Butt, Adeel A. Rodriguez-Barradas, Maria C. Gibert, Cynthia Oursler, Kris Ann Deeks, Steven G. Bryant, Kendall CA VACS Project Team TI Does an Index Composed of Clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality Among Those Aging With HIV? SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTIRETROVIRAL THERAPY; COLLABORATIVE ANALYSIS; INFECTION; COHORT; FIBROSIS; COINFECTION; POPULATION; CLEARANCE; ANEMIA; MARKER AB Background. When added to age, CD4 count and human immunodeficiency virus type 1 (HIV-1) RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus (HCV), and estimated glomerular filtration rate improve prediction of mortality. Weighted and combined, these 7 routine clinical variables constitute the Veterans Aging Cohort Study (VACS) Index. Because nonroutine biomarkers of inflammation (interleukin 6 [IL-6]), coagulation (D-dimer), and monocyte activation (sCD14) also predict mortality, we test the association of these indices and biomarkers with each other and with mortality. Methods. Samples from 1302 HIV-infected veterans on antiretroviral therapy were analyzed. Indices were calculated closest to date of collection. We calculated Spearman correlations stratified by HIV-1 RNA and HCV status and measured association with mortality using C statistics and net reclassification improvement (NRI). Results. Of 1302 subjects, 915 had HIV-1 RNA < 500 copies/mL and 154 died. The VACS Index was more correlated with IL-6, D-dimer, and sCD14 than the Restricted Index (P < .001). It was also more predictive of mortality (C statistic, 0.76; 95% confidence interval [CI],.72-.80) than any biomarker (C statistic, 0.66-0.70) or the Restricted Index (C statistic, 0.71; 95% CI,.67-.75). Compared to the Restricted Index alone, NRI resulted from incremental addition of VACS Index components (10%), D-dimer (7%), and sCD14 (4%), but not from IL-6 (0%). Conclusions. Among HIV-infected individuals, independent of CD4, HIV-1 RNA, and age, hemoglobin and markers of liver and renal injury are associated with inflammation. Addition of D-dimer and sCD14, but not IL-6, improves the predictive accuracy of the VACS Index for mortality. C1 [Justice, Amy C.; Tate, Janet P.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Fiellin, David A.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Justice, Amy C.; Tate, Janet P.] Yale Univ, Gen Internal Med Sect, New Haven, CT USA. [Freiberg, Matthew S.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Freiberg, Matthew S.; Kuller, Lew] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Tracy, Russ] Univ Vermont, Coll Med, Burlington, VT 05405 USA. [Goetz, Matthew Bidwell] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Vanasse, Gary J.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA. [Gibert, Cynthia] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Sch Med, Washington, DC USA. [Oursler, Kris Ann] Baltimore Vet Affairs Hlth Care Syst, Baltimore, MD USA. [Oursler, Kris Ann] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bryant, Kendall] NIAAA, Bethesda, MD USA. RP Justice, AC (reprint author), VA CT Healthcare Syst 11ACSLG, Bldg 35A,Rm 2-212,950 Campbell Ave, West Haven, CT 06516 USA. EM amy.justice2@va.gov OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X FU National Institutes of Health; National Institute on Alcohol Abuse and Alcoholism [U10-AA13566]; National Heart, Lung, and Blood Institute [R01-HL095136, R01-HL090342, RCI-HL100347]; National Institute on Aging [R01-AG029154, K23 AG024896]; Training Program in Environmental Epidemiology [T32 ES07069] FX This work was supported by the National Institutes of Health: National Institute on Alcohol Abuse and Alcoholism (U10-AA13566), National Heart, Lung, and Blood Institute (R01-HL095136; R01-HL090342; RCI-HL100347), and National Institute on Aging (R01-AG029154; K23 AG024896). J. P. T. was supported by the Training Program in Environmental Epidemiology (T32 ES07069). NR 34 TC 98 Z9 98 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2012 VL 54 IS 7 BP 984 EP 994 DI 10.1093/cid/cir989 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 905TB UT WOS:000301296200023 PM 22337823 ER PT J AU Lawless, BM Greene, M Slover, J Kwon, YM Malchau, H AF Lawless, Bryan M. Greene, Meridith Slover, James Kwon, Young-Min Malchau, Henrik TI Does Age or Bilateral Disease Influence the Value of Hip Arthroplasty? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID HEALTH SURVEY QUESTIONNAIRE; COST-EFFECTIVENESS; KNEE ARTHROPLASTY; UNITED-STATES; REVISION HIP; REPLACEMENT; CARE; OSTEOARTHRITIS; SURGERY; INDIVIDUALS AB Measuring value in medicine is an increasingly important issue as healthcare spending continues to rise and cost containment becomes even more important. However, value assessments can be affected by patient factors and comorbidities. We therefore quantified the approximate value of total hip arthroplasty and determined if patient age and Charnley classification affected the EuroQol5D (EQ5D) after hip arthroplasty. Using charge data and an institutional joint registry, we evaluated 1442 patients after hip arthroplasty. Using the Charnley case-mix index to define bilateral disease and age of 65 years to distinguish between elderly and young patients, statistical comparisons were made among all groups. We obtained subspecialty physician charges and hospital charges. Patients with both unilateral and bilateral disease in both age groups had improved EQ5D scores after total hip arthroplasty, and the average change in scores was 0.27. There was no difference in the change in utility scores when patients older than 65 years of age were compared with patients younger than 65 years or when patients with unilateral disease were compared with those with bilateral disease. The average cost per quality-adjusted life-year (QALY) gained was $9773/QALY. Our data suggest the value of total hip arthroplasty compares favorably with other medical and surgical interventions for other patient groups. No adjustments for patient age or disease status of the contralateral limb are necessary when reporting the value of total hip arthroplasty. Level IV, economic and decision analyses study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Lawless, Bryan M.; Greene, Meridith; Slover, James; Kwon, Young-Min; Malchau, Henrik] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Slover, James] NYU, Hosp Joint Dis, New York, NY USA. RP Malchau, H (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM hmalchau@partners.org OI Malchau, Henrik/0000-0002-4291-2441 FU Smith and Nephew; Zimmer; DePuy; Biomet; MAKO FX One of the authors (HM) receives royalties from Smith and Nephew and is a paid consultant for Biomet and Smith and Nephew. The institution receives support from Zimmer, DePuy, Biomet, Smith and Nephew, and MAKO. NR 32 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2012 VL 470 IS 4 BP 1073 EP 1078 DI 10.1007/s11999-011-2118-1 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 907TY UT WOS:000301442800018 PM 22131126 ER PT J AU McCormick, F Nwachukwu, BU Provencher, MT AF McCormick, Frank Nwachukwu, Benedict U. Provencher, Matthew T. TI Stress Fractures in Runners SO CLINICS IN SPORTS MEDICINE LA English DT Article DE Stress fracture; Military training; Long-distance running; Runners ID EXERCISE-RELATED INJURIES; MILITARY RECRUITS; FEMORAL-NECK; RISK-FACTORS; YOUNG MEN; MENSTRUAL IRREGULARITY; SURGICAL-TREATMENT; CIGARETTE-SMOKING; RUNNING INJURIES; MANAGEMENT AB Stress fractures commonly plague runners; the repetitive, continuous, and or excessive forces placed on the bone lead to bony microdamage and progress to stress fractures. Stress fractures are classified as high or low risk; High-risk fractures draw special recognition because of their risk for nonunion and for the significant complications associated with fracture completion. Surgical fixation for a high-risk stress fracture is often indicated, where low-risk fractures can be treated conservatively. Proven measures to prevent stress fractures include cushioned running shoes, interval training, and calcium supplementation. C1 [Provencher, Matthew T.] USN, Dept Orthopaed Surg, San Diego Med Ctr, San Diego, CA 92134 USA. [McCormick, Frank] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Nwachukwu, Benedict U.] Harvard Univ, Sch Med, Holmes Soc, Boston, MA 02115 USA. RP Provencher, MT (reprint author), USN, Dept Orthopaed Surg, San Diego Med Ctr, 11800 Bob Wilson Dr, San Diego, CA 92134 USA. EM matthew.provencher@med.navy.mil NR 67 TC 12 Z9 12 U1 5 U2 50 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-5919 J9 CLIN SPORT MED JI Clin. Sports Med. PD APR PY 2012 VL 31 IS 2 BP 291 EP + DI 10.1016/j.csm.2011.09.012 PG 17 WC Sport Sciences SC Sport Sciences GA 909HG UT WOS:000301554000010 PM 22341018 ER PT J AU Blackford, T Holcomb, PJ Grainger, J Kuperberg, GR AF Blackford, Trevor Holcomb, Phillip J. Grainger, Jonathan Kuperberg, Gina R. TI A funny thing happened on the way to articulation: N400 attenuation despite behavioral interference in picture naming SO COGNITION LA English DT Article DE Semantic interference; Lexical selection; Response selection; Speech production; ERP; N400 ID EVENT-RELATED POTENTIALS; WORD INTERFERENCE; TIME-COURSE; BRAIN POTENTIALS; LEXICAL ACCESS; SEMANTIC INTERFERENCE; LANGUAGE PRODUCTION; SPEECH PRODUCTION; ELECTROPHYSIOLOGICAL EVIDENCE; NONAPHASIC SPEAKERS AB We measured Event-Related Potentials (ERPs) and naming times to picture targets preceded by masked words (stimulus onset asynchrony: 80 ms) that shared one of three different types of relationship with the names of the pictures: (1) Identity related, in which the prime was the name of the picture ("socks" - ), (2) Phonemic Onset related, in which the initial segment of the prime was the same as the name of the picture ("log" - ), and (3) Semantically related in which the prime was a co-category exemplar and associated with the name of the picture ("cake" - ). Each type of related picture target was contrasted with an Unrelated picture target, resulting in a 3 x 2 design that crossed Relationship Type between the word and the target picture (Identity, Phonemic Onset and Semantic) with Relatedness (Related and Unrelated). Modulation of the N400 component to related (versus unrelated) pictures was taken to reflect semantic processing at the interface between the picture's conceptual features and its lemma, while naming times reflected the end product of all stages of processing. Both attenuation of the N400 and shorter naming times were observed to pictures preceded by Identity related (versus Unrelated) words. No ERP effects within 600 ms, but shorter naming times, were observed to pictures preceded by Phonemic Onset related (versus Unrelated) words. An attenuated N400 (electrophysiological semantic priming) but longer naming times (behavioral semantic interference) were observed to pictures preceded by Semantically related (versus Unrelated) words. These dissociations between ERP modulation and naming times suggest that (a) phonemic onset priming occurred late, during encoding of the articulatory response, and (b) semantic behavioral interference was not driven by competition at the lemma level of representation, but rather occurred at a later stage of production. (C) 2011 Elsevier B.V. All rights reserved. C1 [Blackford, Trevor; Holcomb, Phillip J.; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Grainger, Jonathan] Univ Aix Marseille 1, LPC CNRS, F-13331 Marseille 3, France. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM kuperber@nmr.mgh.harvard.edu FU NICHD NIH HHS [R01 HD025889, R01 HD043251, R37 HD025889]; NIMH NIH HHS [R01 MH071635, R01 MH071635-04] NR 79 TC 29 Z9 29 U1 4 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD APR PY 2012 VL 123 IS 1 BP 84 EP 99 DI 10.1016/j.cognition.2011.12.007 PG 16 WC Psychology, Experimental SC Psychology GA 908EU UT WOS:000301474000006 PM 22245030 ER PT J AU Mechanick, JI Marchetti, AE Apovian, C Benchimol, AK Bisschop, PH Bolio-Galvis, A Hegazi, RA Jenkins, D Mendoza, E Sanz, ML Sheu, WHH Tatti, P Tsang, MW Hamdy, O AF Mechanick, Jeffrey I. Marchetti, Albert E. Apovian, Caroline Benchimol, Alexander Koglin Bisschop, Peter H. Bolio-Galvis, Alexis Hegazi, Refaat A. Jenkins, David Mendoza, Enrique Leon Sanz, Miguel Sheu, Wayne Huey-Herng Tatti, Patrizio Tsang, Man-Wo Hamdy, Osama TI Diabetes-Specific Nutrition Algorithm: A Transcultural Program to Optimize Diabetes and Prediabetes Care SO CURRENT DIABETES REPORTS LA English DT Article DE Diabetes; Diet; Glycemic control; Nutrition; Transcultural; Prediabetes ID CLINICAL-PRACTICE GUIDELINES; CARDIOVASCULAR-DISEASE RISK; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; AMERICAN-HEART-ASSOCIATION; CORONARY-ARTERY-DISEASE; LIFE-STYLE INTERVENTION; BODY-MASS INDEX; BLOOD-PRESSURE; MICROVASCULAR COMPLICATIONS AB Type 2 diabetes (T2D) and prediabetes have a major global impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. To mitigate this disease burden, interventions of proven effectiveness must be used. Evidence shows that nutrition therapy improves glycemic control and reduces the risks of diabetes and its complications. Accordingly, diabetes-specific nutrition therapy should be incorporated into comprehensive patient management programs. Evidence-based recommendations for healthy lifestyles that include healthy eating can be found in clinical practice guidelines (CPGs) from professional medical organizations. To enable broad implementation of these guidelines, recommendations must be reconstructed to account for cultural differences in lifestyle, food availability, and genetic factors. To begin, published CPGs and relevant medical literature were reviewed and evidence ratings applied according to established protocols for guidelines. From this information, an algorithm for the nutritional management of people with T2D and prediabetes was created. Subsequently, algorithm nodes were populated with transcultural attributes to guide decisions. The resultant transcultural diabetes-specific nutrition algorithm (tDNA) was simplified and optimized for global implementation and validation according to current standards for CPG development and cultural adaptation. Thus, the tDNA is a tool to facilitate the delivery of nutrition therapy to patients with T2D and prediabetes in a variety of cultures and geographic locations. It is anticipated that this novel approach can reduce the burden of diabetes, improve quality of life, and save lives. The specific Southeast Asian and Asian Indian tDNA versions can be found in companion articles in this issue of Current Diabetes Reports. C1 [Mechanick, Jeffrey I.] Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, New York, NY USA. [Marchetti, Albert E.] Univ Med & Dent New Jersey, Dept Prevent Med & Community Hlth, Newark, NJ 07103 USA. [Apovian, Caroline] Boston Univ, Sch Med, Nutr & Weight Management Ctr, Boston, MA 02118 USA. [Benchimol, Alexander Koglin] State Inst Diabet & Endocrinol Rio de Janeiro, Obes & Eating Disorders Grp, Rio De Janeiro, Brazil. [Bisschop, Peter H.] Univ Amsterdam, Acad Med Ctr, Div Endocrinol & Metab, NL-1105 AZ Amsterdam, Netherlands. [Bolio-Galvis, Alexis] La Salle Univ, Fac Mexicana Med, Mexico City, DF, Mexico. [Bolio-Galvis, Alexis] Hosp Angeles Pedregal, Dept Gen & Bariatr Surg & Clin Nutr, Mexico City, DF, Mexico. [Hegazi, Refaat A.] Abbott Nutr, Res & Dev, Columbus, OH USA. [Jenkins, David] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. [Mendoza, Enrique] Univ Panama, Sch Med, Panama City, Panama. [Leon Sanz, Miguel] Univ Complutense, Dept Med, Univ Hosp Doce Octubre, Serv Endocrinol & Nutr, E-28040 Madrid, Spain. [Sheu, Wayne Huey-Herng] Natl Yang Ming Med Univ, Sch Med, Taipei, Taiwan. [Sheu, Wayne Huey-Herng] Taichung Vet Gen Hosp, Div Endocrinol & Metab, Taichung, Taiwan. [Sheu, Wayne Huey-Herng] Chung Shan Med Univ, Coll Med, Taichung, Taiwan. [Tatti, Patrizio] ASL RMH, Dept Endocrinol & Diabetol, Rome, Italy. [Tsang, Man-Wo] Hosp Author, United Christian Hosp, Dept Med & Geriatr, Div Diabet & Endocrinol, Hong Kong, Hong Kong, Peoples R China. [Hamdy, Osama] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. RP Mechanick, JI (reprint author), Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, New York, NY USA. EM jeffreymechanick@gmail.com OI Apovian, Caroline/0000-0002-8029-1922 FU Abbott Nutrition; Amylin; Merck; Johnson Johnson; Arena; Sanofi-Aventis; Eli Lilly; Pfizer; Orexigen; MetaProteomics; Abbott; MSD; Novo Nordisk; Libbs; Torrent; Solae; Unilever; Haine Celestial; Orafti; Takeda; GlaxoSmithKline; Bristol-Myers Squibb; Abbott Nutrition International; GSK; Bayer FX Conflicts of interest: The development of this article was funded by Abbott Nutrition. The content was created and enriched solely by task force members through a process of ongoing literature searches, independent contributions and reviews, and group interactions for consensus. Other support may have been provided to task force members as indicated in the following statements. Caroline Apovian has received financial support from Amylin, Merck, Johnson & Johnson, Arena, and Sanofi-Aventis; and research funding from Eli Lilly, Pfizer, Orexigen, Amylin, and MetaProteomics. Alexander Koglin Benchimol has served as a board member for Abbott, MSD, and Novo Nordisk; served as a consultant for Abbott, MSD, and Novo Nordisk; served as a speaker and developed educational presentations for Abbott, MSD, Novo Nordisk, Libbs, Sanofi-Aventis, and Torrent; and received funding for travel and accommodations from Abbott, MSD, Novo Nordisk, Libbs, Sanofi-Aventis, and Torrent. Peter H. Bisschop has received financial support for consultancy and research from Abbott Nutrition; also received funding for travel from Abbott Nutrition. Alexis Bolio-Galvis has nothing to disclose. Osama Hamdy has served as a consultant for Abbott Nutrition and a speaker for Amylin/Eli Lilly. Refaat A. Hegazi is employed by Abbott Nutrition; the material presented in this article is based on the best-known clinical evidence and is not affected by this financial relationship. David Jenkins has served as a consultant for Solae, Unilever, and Haine Celestial; served as an advisory board member for Herbalife International, Nutritional Fundamentals for Health, Pacific Health Laboratories, Metagenics/MetaProteomics, Bayer Consumer Care, and Orafti; received research funding from Solae, Unilever, Haine Celestial and Orafti; and received honorarium from Unilever. Miguel Leon Sanz has nothing to disclose. Albert E. Marchetti has received financial support for research and the development of educational materials from Eli Lilly, Takeda, GlaxoSmithKline, Bristol-Myers Squibb, and Abbott Nutrition International. Jeffrey Mechanick has received financial support for the development of educational presentations from Abbott Nutrition. He has received financial support for consultancy and for writing and reviewing the manuscript from Abbott Nutrition. He has received fees for participation in review activities such as data monitoring boards, statistical analysis, and end point committees from Abbott Nutrition International. He has received funding for travel and accommodations from Abbott Nutrition. Enrique Mendoza has received financial support for consultancy from Abbott Nutrition; He has received funding for travel and accommodations from Abbott Nutrition. Wayne Huey-Herng Sheu has received financial support for consultancy from Abbott Nutrition, Pfizer, GSK and Bayer. Patrizio Tatti received financial support for participation in review activities for Abbott Nutrition. He has received funding for travel from Abbott Nutrition. Man-Wo Tsang has nothing to disclose. NR 115 TC 14 Z9 14 U1 0 U2 12 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD APR PY 2012 VL 12 IS 2 BP 180 EP 194 DI 10.1007/s11892-012-0253-z PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 909XI UT WOS:000301600000007 PM 22322477 ER PT J AU Brennig, S Rattmann, I Lachmann, N Schambach, A Williams, DA Moritz, T AF Brennig, Sebastian Rattmann, Ina Lachmann, Nico Schambach, Axel Williams, David A. Moritz, Thomas TI In vivo enrichment of cytidine deaminase gene-modified hematopoietic cells by prolonged cytosine-arabinoside application SO CYTOTHERAPY LA English DT Article DE cytidine deaminase; cytosine-arabinoside; hematotoxicity; in vivo selection ID DRUG-RESISTANCE GENES; STEM-CELLS; ARA-C; REPOPULATING CELLS; TRANSDUCED CELLS; PROGENITOR CELLS; THERAPY; SELECTION; CYTARABINE; MICE AB Background aims. Drug-resistance genes have been explored as powerful in vivo selection markers in hematopoietic cell gene therapy, and cytidine deaminase (CDD) represents a particularly attractive candidate given the virtual absence of non-hematopoietic side-effects after low/intermediate dose application of the associated drug cytosine-arabinoside (Ara-C). Methods. We investigated the in vivo selection potential of CDD overexpression and prolonged low/intermediate-dose Ara-C application in a murine model. Furthermore, non-transplanted mice were utilized to study Ara-C toxicity in different hematopoietic cell compartments. Results. Significant protection of myelo- and thrombopoiesis and up to 6-fold in vivo enrichment of CDD-transduced hematopoietic cells was observed. Enrichment was most robust early after Ara-C application and was correlated with dosage and duration of chemotherapy. Enrichment remained significant for several weeks, indicating selection at the level of a progenitor population. This notion was supported by Ara-C toxicity studies, demonstrating profound hematotoxicity and a marked delay in hematopoietic recovery, specifically in the progenitor/stem cell compartment after low/intermediate-dose Ara-C. Conclusions. These data support the concept of CDD/Ara-C as a clinically applicable in vivo selection system in hematopoietic gene therapy. The data also demonstrate marked differences in hematotoxicity between alternative Ara-C dosing schemes and suggest thorough in vivo toxicity studies to optimize further Ara-C dosing en route to safe and stable enrichment of gene-corrected hematopoiesis. C1 [Brennig, Sebastian; Rattmann, Ina; Lachmann, Nico; Moritz, Thomas] Hannover Med Sch, REBIRTH Cluster of Excellence, Res Grp Reprogramming, D-30625 Hannover, Germany. [Rattmann, Ina; Williams, David A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Rattmann, Ina; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rattmann, Ina; Williams, David A.; Moritz, Thomas] Cincinnati Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH USA. [Schambach, Axel] Hannover Med Sch, Inst Expt Hematol, D-30625 Hannover, Germany. [Schambach, Axel] Hannover Med Sch, Res Grp Hematopoiet Cell Therapy, REBIRTH Cluster of Excellence, D-30625 Hannover, Germany. RP Moritz, T (reprint author), Hannover Med Sch, REBIRTH Cluster of Excellence, Res Grp Reprogramming, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM moritz.thomas@mh-hannover.de OI Lachmann, Nico/0000-0002-4245-1497 FU Deutsche Forschungsgemeinschaft: Cluster of Excellence REBIRTH [Exc 62/1, SPP1230, MO 886/3-1, RA 1705/1-1] FX We thank Dr Sandra Zilz and the team of the central pharmacy of Hannover Medical School for preparing cytostatic drugs, and Doreen Luttge for technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft: Cluster of Excellence REBIRTH (Exc 62/1), SPP1230, grant MO 886/3-1 (T. M.) and grant RA 1705/1-1 (I.R.). NR 51 TC 8 Z9 8 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD APR PY 2012 VL 14 IS 4 BP 451 EP 460 DI 10.3109/14653249.2011.646043 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 909AH UT WOS:000301533700008 PM 22242831 ER PT J AU Gollub, MJ Gultekin, DH Akin, O Do, RK Fuqua, JL Gonen, M Kuk, D Weiser, M Saltz, L Schrag, D Goodman, K Paty, P Guillem, J Nash, GM Temple, L Shia, J Schwartz, LH AF Gollub, M. J. Gultekin, D. H. Akin, O. Do, R. K. Fuqua, J. L., III Gonen, M. Kuk, D. Weiser, M. Saltz, L. Schrag, D. Goodman, K. Paty, P. Guillem, J. Nash, G. M. Temple, L. Shia, J. Schwartz, L. H. TI Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer SO EUROPEAN RADIOLOGY LA English DT Article DE Rectal cancer; DCE-MRI; Neoadjuvant; Chemotherapy; Response ID CHEMORADIATION THERAPY; PREOPERATIVE CHEMORADIOTHERAPY; TUMOR MICROCIRCULATION; PREDICTING RESPONSE; RADIATION-THERAPY; SOLID TUMORS; CARCINOMA; ANGIOGENESIS; SURVIVAL AB To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K-trans, k(ep), v(e), AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P a parts per thousand currency signaEuro parts per thousand 0.05 was considered significant. Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K-trans (mean 0.5 min(-1) vs. 0.2 min(-1), P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. Dynamic contrast enhanced (DCE) MRI provides perfusion characteristics of tumours. These objective quantitative measures may be more helpful than subjective imaging alone Some parameters differed markedly between completely responding and incompletely responding rectal cancers. Thus DCE-MRI can potentially offer treatment-altering imaging biomarkers. C1 [Gollub, M. J.; Gultekin, D. H.; Akin, O.; Do, R. K.; Fuqua, J. L., III] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Gonen, M.; Kuk, D.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Weiser, M.; Paty, P.; Guillem, J.; Nash, G. M.; Temple, L.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA. [Saltz, L.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Goodman, K.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA. [Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shia, J.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Schwartz, L. H.] Columbia Univ, Med Ctr, Dept Radiol, New York Presbyterian Hosp, New York, NY 10032 USA. RP Gollub, MJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10065 USA. EM gollubm@mskcc.org RI Gonen, Mithat/E-4826-2012; OI Gultekin, David/0000-0002-1461-0980; Kuk, Deborah/0000-0003-1477-3170; Akin, Oguz/0000-0002-2041-6199; Shia, Jinru/0000-0002-4351-2511; Do, Richard/0000-0002-6554-0310; Saltz, Leonard/0000-0001-8353-4670 NR 32 TC 50 Z9 56 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD APR PY 2012 VL 22 IS 4 BP 821 EP 831 DI 10.1007/s00330-011-2321-1 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 908NK UT WOS:000301496900013 PM 22101743 ER PT J AU Hanasono, MM Lin, D Wax, MK Rosenthal, EL AF Hanasono, Matthew M. Lin, Derrick Wax, Mark K. Rosenthal, Eben L. TI Closure of laryngectomy defects in the age of chemoradiation therapy SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE salvage surgery; laryngectomy; wound complications; head and neck cancer; free flap ID SALVAGE TOTAL LARYNGECTOMY; FREE-FLAP RECONSTRUCTION; ORGAN PRESERVATION THERAPY; FREE JEJUNAL TRANSFER; FREE TISSUE TRANSFER; POSTLARYNGECTOMY PHARYNGOCUTANEOUS FISTULA; NEGATIVE-PRESSURE DRESSINGS; VESSEL-DEPLETED NECK; RADIAL FOREARM; MICROVASCULAR RECONSTRUCTION AB The use of chemoradiation therapy in laryngeal cancer has resulted in significant reconstructive challenges. Although reconstruction of salvage laryngectomy defects remains controversial, current literature supports aggressive management of these defects with vascularized tissue, even when there is sufficient pharyngeal tissue present for primary closure. Significant advancement in reconstructive techniques has permitted improved outcomes in patients with advanced disease who require total laryngopharyngectomy or total laryngoglossectomy. Use of enteric and fasciocutaneous flaps result in good patient outcomes. Finally, wound complication rates after salvage surgery approach 60% depending on comorbid conditions such as cardiac insufficiency, hypothyroidism, or extent of previous treatment. Neck dehiscence, great vessel exposure, fistula formation, or cervical skin necrosis results in complex wounds that can often be treated initially with negative pressure dressings followed by definitive reconstruction. The timing of repair and approach to the vessel-depleted neck also present challenges in this patient population. Currently, there is significant institutional bias in the management of the patient with postchemoradiation salvage laryngectomy. Future prospective multi-institutional studies are certainly needed to more clearly define optimal treatment of these difficult patients. (c) 2011 Wiley Periodicals, Inc. Head Neck, 2012 C1 [Rosenthal, Eben L.] Univ Alabama, Dept Surg, Div Otolaryngol Head & Neck Surg, Birmingham, AL 35294 USA. [Hanasono, Matthew M.] Univ Texas MD Anderson Canc Ctr Houston, Dept Plast Surg, Houston, TX USA. [Lin, Derrick] Massachusetts Eye & Ear Infirm, Dept Otol, Boston, MA 02114 USA. [Lin, Derrick] Massachusetts Eye & Ear Infirm, Dept Laryngol, Boston, MA 02114 USA. [Wax, Mark K.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Rosenthal, EL (reprint author), Univ Alabama, Dept Surg, Div Otolaryngol Head & Neck Surg, Birmingham, AL 35294 USA. EM eben.rosenthal@ccc.uab.edu FU NCI NIH HHS [R01 CA142637] NR 63 TC 16 Z9 16 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD APR PY 2012 VL 34 IS 4 BP 580 EP 588 DI 10.1002/hed.21712 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 901QB UT WOS:000300980800018 PM 21416549 ER PT J AU Kouri, EM Landrum, MB Lamont, EB Bozeman, S McNeil, BJ Keating, NL AF Kouri, Elena M. Landrum, Mary Beth Lamont, Elizabeth B. Bozeman, Sam McNeil, Barbara J. Keating, Nancy L. TI Location of Cancer Surgery for Older Veterans with Cancer SO HEALTH SERVICES RESEARCH LA English DT Article DE Veterans; cancer surgery; Medicare; health services ID MEDICARE DUAL BENEFICIARIES; ACUTE MYOCARDIAL-INFARCTION; AFFAIRS HEALTH-CARE; PRIVATE-SECTOR; RURAL VETERANS; ACCESS; VA; HOSPITALS; OUTCOMES; URBAN AB Objective. Many veterans undergo cancer surgery outside of the Veterans Health Administration (VHA). We assessed to what extent these patients obtained care in the VHA before surgery. Data Sources. VHA-Medicare data, VHA administrative data, and Veterans Affairs Central Cancer Registry data. Study Design. We identified patients aged >= 65 years in the VHA-Medicare cohort who underwent lung or colon cancer resection outside the VHA and assessed VHA visits in the year before surgery. Principal Findings. Over 60% of patients in the VHA-Medicare cohort who received lung or colon cancer surgeries outside the VHA did not receive any care in VHA before surgery. Conclusions. Veterans' receipt of major cancer surgery outside the VHA probably reflects usual private sector care among veterans who are infrequent VHA users. C1 [Kouri, Elena M.; Landrum, Mary Beth; Lamont, Elizabeth B.; McNeil, Barbara J.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Div Adult Oncol, Boston, MA 02114 USA. [Bozeman, Sam] ABT Associates Inc, Cambridge, MA 02138 USA. [McNeil, Barbara J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning FX This work was funded by the Department of Veterans Affairs through the Office of Policy and Planning. The authors would like to thank David Izrael, Jeffrey Souza, Stephanie Segers, Larry Hughes (VA-Austin Data Center), John Quinn (VA-Austin Data Center), and Elizabeth Axelrod for expert programming assistance, and Garrett Kirk for research and administrative assistance. This analysis would not have been possible without the invaluable feedback we received from the VA Oncology Program Evaluation Team, especially members with extensive clinical oncology experience within the VA system, including Dr. Albert Muhleman (Cincinnati VAMC), Dr. Nirmala Bhoopalam (Hines, ILVAMC), Dr. Paulette Mehta (Central AR VHA), Dr. Dawn Provenzale (VA HSR& D Researcher in Durham, NC), Dr. Michael Kelley (Chief of Oncology, VHA), Dr. Robert Kerns (National Program Director for Pain Management, VHA), and the chief VACCR registrar, Raye Anne Dorn (VHA -DC VAMC). A special acknowledgement goes to Marshall Amesquita and Barbara Stephens, Contracting Officer's Technical Representative, and the rest of our VA Oncology Program Evaluation Team: Stanlie Daniels (VHA), Heidi Martin (VHA), Diana Ordin (VHA), and Patricia Vandenberg (VHA OP&P). The views reflect those of the authors and not the Department of Veterans Affairs. NR 24 TC 5 Z9 5 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2012 VL 47 IS 2 BP 783 EP 793 DI 10.1111/j.1475-6773.2011.01327.x PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 904WJ UT WOS:000301229300014 PM 22092115 ER PT J AU Lee, LK Bateman, BT Wang, S Schumacher, HC Pile-Spellman, J Saposnik, G AF Lee, Leslie K. Bateman, Brian T. Wang, Shuang Schumacher, H. Christian Pile-Spellman, John Saposnik, Gustavo TI Trends in the hospitalization of ischemic stroke in the United States, 1998-2007 SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE acute; cerebral infarction; ischemic stroke; prevention; risk factors; stroke ID DRUG-THERAPY; RISK-FACTORS; POPULATION; PREVENTION; MORTALITY; CARE; REHABILITATION; HYPERTENSION; FATALITY AB Background The late 1990s/early 2000s was a time of change in both the prevention and acute care of ischemic stroke, with primary prevention driven by increased utilization of antihypertensive, antiplatelet, anticoagulation, and lipid-lowering agents. Aim To examine whether ischemic stroke hospitalization rates and outcomes in the United States have changed. Method We retrospectively identified 894 169 hospitalizations with a primary diagnosis of ischemic stroke from 1 January 1998 through to 31 December 2007 in the Nationwide Inpatient Sample, the largest all-payer healthcare database in the United States. Annual, national case estimates were combined with US Census data to derive age-adjusted and age-specific population hospitalization rates. Temporal trends were tested using linear regression. Results From 1998 through 2007, there were an estimated 4 382 336 ischemic stroke hospitalizations in the United States. Overall, the age-adjusted rate of ischemic stroke hospitalization decreased from 184 to 128 per 100 000 (P < 0.0001). Age-specific rates decreased among those 55+ years old (P < 0.0001), but increased among those 25-34 and 35-44 years old (P < 0.001 and P < 0.0001, respectively). Rates among those < 25 and 45-54 years old were unchanged. In-hospital mortality decreased from 7.0% (standard error 0.1) to 5.4% (standard error 0.1) (P < 0.0001). Case proportion at the highest quintile of hospitals by annual caseload increased from 54.0% (standard error 2.1) to 61.8% (standard error 2.0) (P < 0.0001). Mean adjusted hospitalization costs increased from $9273 (standard deviation 199) to $10 524 (standard deviation 77) (P < 0.0001). Conclusion In 1998 through to 2007, the overall rate of ischemic stroke hospitalization in the United States decreased. However, rates among young adults increased. In-hospital mortality rates decreased over the study period. C1 [Saposnik, Gustavo] Univ Toronto, St Michaels Hosp, Stroke Program, Stroke Res Unit, Toronto, ON M5C 1R6, Canada. [Saposnik, Gustavo] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON M5C 1R6, Canada. [Lee, Leslie K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Wang, Shuang] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA. [Schumacher, H. Christian] Albert Einstein Coll Med, Saul R Korey Dept Neurol, Div Vasc Neurol & Neurocrit Care, Bronx, NY 10467 USA. [Pile-Spellman, John] Columbia Univ, Div Intervent Neuroradiol, Dept Radiol, Med Ctr, New York, NY USA. RP Saposnik, G (reprint author), Univ Toronto, St Michaels Hosp, Stroke Program, Stroke Res Unit, 55 Queen St E,Suite 931, Toronto, ON M5C 1R6, Canada. EM saposnikg@smh.ca OI Saposnik, Gustavo/0000-0002-5950-9886 FU Doris Duke Charitable Foundation FX L. K. L. was supported by a Doris Duke Clinical Research Fellowship from the Doris Duke Charitable Foundation. L. K. L. performed the statistical analysis while affiliated with the Division of Interventional Neuroradiology, Department of Radiology, Columbia University Medical Center in New York, NY. NR 34 TC 10 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2012 VL 7 IS 3 BP 195 EP 201 DI 10.1111/j.1747-4949.2011.00700.x PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 905PS UT WOS:000301285300004 PM 22151527 ER PT J AU Schellinger, PD Bath, PMW Lees, KR Bornstein, NM Uriel, E Eisert, W Leys, D AF Schellinger, Peter D. Bath, Philip M. W. Lees, Kennedy R. Bornstein, Natan M. Uriel, Eitan Eisert, Wolfgang Leys, Didier CA European Stroke Org Outcomes Work TI Assessment of additional endpoints for trials in acute stroke - what, when, where, in who? SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE acute stroke therapy; clinical trial; ischaemic stroke; methodology; therapy; treatment ID MIDDLE CEREBRAL-ARTERY; MONTREAL COGNITIVE ASSESSMENT; 5 YEARS POSTSTROKE; INFARCTION; MULTICENTER; IMPAIRMENT; HEMICRANIECTOMY; DEPRESSION; DEMENTIA; OUTCOMES AB Functional outcome in acute stroke trials among others is usually measured on the modified Rankin Scale. However, new onset of depression, cognitive decline, and communication deficits alone or in combination affect more than 25% of patients. This report summarizes the findings and conclusions of a workshop by the European Stroke Organization held in February 2011 We propose that assessment of mood disorders, cognitive impairment/dementia, language or communication dysfunction, and quality of life should supplement outcome measures after acute stroke. C1 [Schellinger, Peter D.] Johannes Wesling Klinikum Minden, Dept Neurol, D-32429 Minden, Germany. [Bath, Philip M. W.] Univ Nottingham, Div Stroke Med, Nottingham NG7 2RD, England. [Lees, Kennedy R.] Univ Glasgow, Dept Cerebrovasc Med, Glasgow, Lanark, Scotland. [Bornstein, Natan M.; Uriel, Eitan] Massachusetts Gen Hosp, Dept Neurol, Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Bornstein, Natan M.; Uriel, Eitan] Harvard Univ, Sch Med, Boston, MA USA. [Eisert, Wolfgang] Med Univ MH, Dept Neurol, Hannover, Germany. [Leys, Didier] Univ Lille Nord France, Lille, France. RP Schellinger, PD (reprint author), Johannes Wesling Klinikum Minden, Dept Neurol, Hans Nolte Str 1, D-32429 Minden, Germany. EM Peter.Schellinger@muehlenkreiskliniken.de OI Bath, Philip/0000-0003-2734-5132; Kaste, Markku/0000-0001-6557-6412 NR 25 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2012 VL 7 IS 3 BP 227 EP 230 DI 10.1111/j.1747-4949.2012.00773.x PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 905PS UT WOS:000301285300010 PM 22405278 ER PT J AU Meng, R Yan, W Wang, XY Dornbos, D Liu, Y Ning, MM Buonanno, FS Ding, YC Ji, XM AF Meng, Ran Yan, Wu Wang, Xiaoying Dornbos, David, III Liu, Yu Ning, Mingming Buonanno, Ferdinando S. Ding, Yuchuan Ji, Xunming TI CVST, distinguished from nonthrombotic CVSS before treatment - a MUST SO INTERNATIONAL JOURNAL OF STROKE LA English DT Letter ID IDIOPATHIC INTRACRANIAL HYPERTENSION; VENOUS SINUS THROMBOSIS C1 [Meng, Ran; Yan, Wu; Ji, Xunming] Capital Med Univ, Cerebral Vasc Dis Res Inst, China Amer Joint Inst Neurosci, Xuanwu Hosp, Beijing, Peoples R China. [Meng, Ran; Liu, Yu] Capital Med Univ, Dept Neurol, Beijing Shijitan Hosp, Beijing, Peoples R China. [Meng, Ran; Wang, Xiaoying; Ning, Mingming; Buonanno, Ferdinando S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Dornbos, David, III; Ding, Yuchuan] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. RP Ji, XM (reprint author), Capital Med Univ, Cerebral Vasc Dis Res Inst, China Amer Joint Inst Neurosci, Xuanwu Hosp, Beijing, Peoples R China. EM Jixm@ccmu.edu.cn FU NINDS NIH HHS [R01 NS067139] NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD APR PY 2012 VL 7 IS 3 BP 274 EP 274 DI 10.1111/j.1747-4949.2012.00775.x PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 905PS UT WOS:000301285300017 PM 22405281 ER PT J AU O'Cleirigh, C Safren, SA Mayer, KH AF O'Cleirigh, Conall Safren, Steven A. Mayer, Kenneth H. TI The Pervasive Effects of Childhood Sexual Abuse: Challenges for Improving HIV Prevention and Treatment Interventions SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material ID PSYCHOSOCIAL HEALTH-PROBLEMS; TRANSMISSION RISK BEHAVIOR; DRUG-USE; MEN; INFECTION; HISTORY; ASSOCIATION; DEPRESSION; HIV/AIDS; PEOPLE C1 [O'Cleirigh, Conall; Safren, Steven A.; Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [O'Cleirigh, Conall; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [O'Cleirigh, Conall; Safren, Steven A.; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Sch, Boston, MA USA. RP O'Cleirigh, C (reprint author), Harvard Univ, Sch Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM cocleirigh@partners.org FU NIAID NIH HHS [5P30AI06354-08]; NIMH NIH HHS [K24 MH094214, R01 MH095624, 1 R01 MH095624-01, 1K24MH094214] NR 40 TC 12 Z9 12 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2012 VL 59 IS 4 BP 331 EP 334 DI 10.1097/QAI.0b013e31824aed80 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 907KL UT WOS:000301416100008 PM 22293545 ER PT J AU Mayer, KH Mimiaga, MJ Gelman, M Grasso, C AF Mayer, Kenneth H. Mimiaga, Matthew J. Gelman, Marcy Grasso, Chris TI Raltegravir, Tenofovir DF, and Emtricitabine for Postexposure Prophylaxis to Prevent the Sexual Transmission of HIV: Safety, Tolerability, and Adherence SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT Meeting of the International-AIDS-Society CY 2009 CL Capetown, SOUTH AFRICA SP Int AIDS Soc DE postexposure prophylaxis; raltegravir; tenofovir-emtricitabine; HIV prevention ID EXPERIENCED PATIENTS; COMBINATION THERAPY; DISOPROXIL FUMARATE; RANDOMIZED-TRIAL; INFECTION; VIRUS; EXPOSURE; EFFICACY; MACAQUES; CHEMOPROPHYLAXIS AB Antiretroviral drugs have been recommended for post-exposure prophylaxis (PEP) after high-risk sexual exposures for more than a decade. Three drug regimens could offer the highest levels of protection, particularly if the infectious source is taking medication, but drug intolerance has often led to suboptimal adherence. The current study evaluated a novel 3-drug PEP regimen, consisting of raltegravir, tenofovir DF, and emtricitabine. Of 100 participants enrolled in this study at a Boston community health center that has had a comprehensive PEP program for more than a decade, 85 were evaluable at 3 months and none became HIV infected. Fifty seven percent of those enrolled completed the regimen as prescribed, and 27% took their medicine daily, but sometimes missed the second daily dose of Raltegravir. The most common side effects reported included nausea or vomiting (27%), diarrhea (21%), headache (15%), fatigue (14%), abdominal symptoms (including pain, gas, or bloating) (16%), and myalgias or arthralgias (8%), all of which were mild and tended to be self-limited, not resulting in drug discontinuation. The side effects were significantly less common than those reported by historical controls, who used a 3-drug PEP regimen including zidovudine, lamivudine, and a ritonavir-boosted protease inhibitor. Raltegravir, tenofovir DF, and emtricitabine may be useful as a 3-drug regimen for PEP. C1 [Mayer, Kenneth H.; Mimiaga, Matthew J.; Gelman, Marcy; Grasso, Chris] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Mayer, KH (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM khmayer@gmail.com RI Ghartouchent, malek/B-9088-2012 NR 39 TC 38 Z9 38 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2012 VL 59 IS 4 BP 354 EP 359 DI 10.1097/QAI.0b013e31824a03b8 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 907KL UT WOS:000301416100012 PM 22267017 ER PT J AU Delaney, EM Walton, HM Trezza, GR Henley, KM Vielhauer, MJ Morgan, E Meyer, P Keane, TM AF Delaney, Eileen M. Walton, Heather M. Trezza, Glenn R. Henley, Karen M. Vielhauer, Melanie J. Morgan, Erin Meyer, Phil Keane, Terence M. TI Community Advisory Boards in HIV Research: Current Scientific Status and Future Directions SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID PARTICIPATORY RESEARCH; HEALTH; TRIALS C1 [Delaney, Eileen M.; Walton, Heather M.; Trezza, Glenn R.; Vielhauer, Melanie J.; Morgan, Erin; Keane, Terence M.] VA Boston Healthcare Syst, Boston, MA USA. [Walton, Heather M.] Harvard Univ, Sch Med, Boston, MA USA. [Trezza, Glenn R.; Henley, Karen M.; Vielhauer, Melanie J.; Morgan, Erin; Keane, Terence M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Meyer, Phil] Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. RP Delaney, EM (reprint author), VA Boston Healthcare Syst, Boston, MA USA. RI Ghartouchent, malek/B-9088-2012 NR 18 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2012 VL 59 IS 4 BP E78 EP E81 DI 10.1097/QAI.0b013e31824acdfb PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 907KL UT WOS:000301416100006 PM 22407304 ER PT J AU Que, CTB Hsing, LC Villet, R Bolduc, GR Estabrooks, Z Taguezem, GF Hooper, DC AF Que Chi Truong-Bolduc Hsing, Liao Chun Villet, Regis Bolduc, Gilles R. Estabrooks, Zoe Taguezem, G. Florent Hooper, David C. TI Reduced Aeration Affects the Expression of the NorB Efflux Pump of Staphylococcus aureus by Posttranslational Modification of MgrA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OXIDATION-SENSING MECHANISM; ANAEROBIC GENE-EXPRESSION; SYNDROME TOXIN 1; GLOBAL REGULATOR; SERINE-PROTEASE; CARBON-DIOXIDE; OXYGEN; ACID; MOXIFLOXACIN; VIRULENCE AB We previously showed that at acid pH, the transcription of norB, encoding the NorB efflux pump, increases due to a reduction in the phosphorylation level of MgrA, which in turn leads to a reduction in bacterial killing by moxifloxacin, a substrate of the NorB efflux pump. In this study, we demonstrated that reduced oxygen levels did not affect the transcript levels of mgrA but modified the dimerization of the MgrA protein, which remained mostly in its monomeric form. Under reduced aeration, we also observed a 21.7-fold increase in the norB transcript levels after 60 min of growth that contributed to a 4-fold increase in the MICs of moxifloxacin and sparfloxacin for Staphylococcus aureus RN6390. The relative proportions of MgrA in monomeric and dimeric forms were altered by treatment with H2O2, but incubation of purified MgrA with extracts of cells grown under reduced but not normal aeration prevented MgrA from being converted to its dimeric DNA-binding form. This modification was associated with cleavage of a fragment of the dimerization domain of MgrA without change in MgrA phosphorylation and an increase in transcript levels of genes encoding serine proteases in cells incubated at reduced aeration. Taken together, these data suggest that modification of MgrA by proteases underlies the reversal of its repression of norB and increased resistance to NorB substrates in response to reduced-aeration conditions, illustrating a third mechanism of posttranslational modification, in addition to oxidation and phosphorylation, that modulates the regulatory activities of MgrA. C1 [Que Chi Truong-Bolduc; Hsing, Liao Chun; Villet, Regis; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis & Med Serv, Boston, MA 02114 USA. [Que Chi Truong-Bolduc; Hsing, Liao Chun; Villet, Regis; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Bolduc, Gilles R.; Estabrooks, Zoe; Taguezem, G. Florent] Massasoit Community Coll, Brockton, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis & Med Serv, Boston, MA 02114 USA. EM dhooper@partners.org FU U.S. Public Health Service (from the National Institutes of Health) [R37-AI23988]; NSF-STEP (from the National Science Foundation) of Stonehill Undergraduate Research Experience (SURE), Easton, MA [NSF 06-502] FX This work was supported by the U.S. Public Health Service (grant R37-AI23988 from the National Institutes of Health to D.C.H.) and in part by the NSF-STEP Summer Research Program (grant NSF 06-502 from the National Science Foundation to G.R.B., Z.E., and G F.T.) of the Stonehill Undergraduate Research Experience (SURE), Easton, MA, for the period of June to August 2011. NR 30 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2012 VL 194 IS 7 BP 1823 EP 1834 DI 10.1128/JB.06503-11 PG 12 WC Microbiology SC Microbiology GA 906KT UT WOS:000301344700019 ER PT J AU Kandala, J Altman, RK Park, MY Singh, JP AF Kandala, Jagdesh Altman, Robert K. Park, Mi Young Singh, Jagmeet P. TI Clinical, Laboratory, and Pacing Predictors of CRT Response SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Cardiac resynchronization therapy; Congestive heart failure; Response predictors ID CARDIAC-RESYNCHRONIZATION THERAPY; LEFT-VENTRICULAR DYSFUNCTION; HEART-FAILURE PATIENTS; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ACUTE HEMODYNAMIC-RESPONSE; ICD ITALIAN REGISTRY; TISSUE DOPPLER; RESYNCHRONISATION THERAPY; ATRIOVENTRICULAR DELAY; INTERVENTRICULAR DELAY AB A decade of research has established the role of cardiac resynchronization therapy (CRT) in medically refractory, moderate to severe systolic heart failure (HF) with intraventricular conduction delay. CRT is an electrical therapy instituted to reestablish ventricular synchronization in order to improve cardiac function and favorably modulate the neurohormonal system. CRT confers a mortality benefit, improved HF hospitalizations, and functional outcome in this population, but not all patients consistently demonstrate a positive CRT response. The nonresponder rate varies from 20% to 40%, depending on the defined response criteria. Efforts to improve response to CRT have focused on a number of fronts. Methods to optimize the correction of electrical and mechanical dyssynchrony, which is the primary target of CRT, has been the focus of research, in addition to improving patient selection and optimizing post-implant care. However, a major issue in dealing with improving nonresponse rates has been finding an accurate and generally accepted definition of "response" itself. The availability of a standard consensus definition of CRT response would enable the estimation of nonresponder burden accurately and permit the development of strategies to improve CRT response. In this review, we define various aspects of "response" to CRT and outline variability in the definition criteria and the problems with its inconsistencies. We describe clinical, laboratory, and pacing predictors that influence CRT response and outcome and how to optimize response. C1 [Kandala, Jagdesh; Altman, Robert K.; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Cardiol Div, Boston, MA 02114 USA. [Park, Mi Young] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Echocardiog Div,Cardiol Div, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Cardiol Div, Boston, MA 02114 USA. EM jsingh@partners.org OI Altman, Robert/0000-0002-1612-3561 NR 141 TC 13 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD APR PY 2012 VL 5 IS 2 SI SI BP 196 EP 212 DI 10.1007/s12265-012-9352-0 PG 17 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 907WG UT WOS:000301449500010 PM 22362181 ER PT J AU Baker, MA Wilson, D Wallengren, K Sandgren, A Iartchouk, O Broodie, N Goonesekera, SD Sabeti, PC Murray, MB AF Baker, Meghan A. Wilson, Douglas Wallengren, Kristina Sandgren, Andreas Iartchouk, Oleg Broodie, Nisha Goonesekera, Sunali D. Sabeti, Pardis C. Murray, Megan B. TI Polymorphisms in the Gene That Encodes the Iron Transport Protein Ferroportin 1 Influence Susceptibility to Tuberculosis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; AFRICAN-AMERICANS; OVERLOAD; ASSOCIATION; MUTATION; DISEASE AB Background. We studied the association between iron intake and polymorphisms in the iron transporter gene SLC40A1 and the risk of tuberculosis. Methods. We compared iron intake, the frequency of SLC40A1 mutations, and interactions among these variables among 98 tuberculosis patients and 125 controls in Kwazulu-Natal, South Africa. Results. Four SLC40A1 single-nucleotide polymorphisms (SNPs) were associated with an increased risk of tuberculosis and 1 SNP with reduced risk. We also found a gene-environment interaction for 4 nonexonic SNPs and iron intake. Conclusions. This pilot study demonstrated an association between polymorphisms in SLC40A1 and tuberculosis and provided evidence of an interaction between dietary iron and SLC40A1. C1 [Baker, Meghan A.; Wallengren, Kristina; Sandgren, Andreas; Goonesekera, Sunali D.; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Baker, Meghan A.; Murray, Megan B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Wilson, Douglas] Univ KwaZulu Natal, Dept Med, Edendale Hosp, Pietermaritzburg, South Africa. [Wallengren, Kristina] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Iartchouk, Oleg] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA 02115 USA. [Broodie, Nisha] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, Ctr Syst Biol, Cambridge, MA 02138 USA. [Sabeti, Pardis C.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Murray, Megan B.] Brigham & Womens Hosp, Dept Med, Div Global Hlth Equ, Boston, MA 02115 USA. RP Murray, MB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 641 Huntington Ave, Boston, MA 02115 USA. EM mmurray@hsph.harvard.edu OI Broodie, Nisha/0000-0001-6911-328X FU Harvard Medical School; Harvard Initiative for Global Health; Massachusetts General Hospital, Department of Medicine FX This work was supported by the Milton Award from the Harvard Medical School (M. M.), an International Travel Award from the Harvard Initiative for Global Health (M. B.), and the Eleanor and Miles Shore 50th Anniversary Fellowship Program for Scholars in Medicine, Massachusetts General Hospital, Department of Medicine (M. B.). NR 15 TC 8 Z9 8 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2012 VL 205 IS 7 BP 1043 EP 1047 DI 10.1093/infdis/jis026 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 906OQ UT WOS:000301356200004 PM 22357659 ER PT J AU Cui, HL Grant, A Mukhamedova, N Pushkarsky, T Jennelle, L Dubrovsky, L Gaus, K Fitzgerald, ML Sviridov, D Bukrinsky, M AF Cui, Huanhuan L. Grant, Angela Mukhamedova, Nigora Pushkarsky, Tatiana Jennelle, Lucas Dubrovsky, Larisa Gaus, Katharina Fitzgerald, Michael L. Sviridov, Dmitri Bukrinsky, Michael TI HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux SO JOURNAL OF LIPID RESEARCH LA English DT Article DE cholesterol metabolism; cholesterol trafficking; ATP binding cassette transporter A1; human immunodeficiency virus ID IMMUNODEFICIENCY-VIRUS TYPE-1; CASSETTE TRANSPORTER A1; MEMBRANE MICRODOMAINS; IN-VIVO; BINDING; INCREASES; DOMAINS; ABCA1; TRAFFICKING; ASSOCIATION AB HIV infection, through the actions of viral accessory protein Nef, impairs activity of cholesterol transporter ABCA1, inhibiting cholesterol efflux from macrophages and elevating the risk of atherosclerosis. Nef also induces lipid raft formation. In this study, we demonstrate that these activities are tightly linked and affect macrophage function and HIV replication. Nef stimulated lipid raft formation in macrophage cell line RAW 264.7, and lipid rafts were also mobilized in HIV-1-infected human monocyte-derived macrophages. Nef-mediated transfer of cholesterol to lipid rafts competed with the ABCA1-dependent pathway of cholesterol efflux, and pharmacological inhibition of ABCA1 functionality or suppression of ABCA1 expression by RNAi increased Nef-dependent delivery of cholesterol to lipid rafts. Nef reduced cell-surface accessibility of ABCA1 and induced ABCA1 catabolism via the lysosomal pathway. Despite increasing the abundance of lipid rafts, expression of Nef impaired phagocytic functions of macrophages. The infectivity of the virus produced in natural target cells of HIV-1 negatively correlated with the level of ABCA1.(jlr) These findings demonstrate that Nef-dependent inhibition of ABCA1 is an essential component of the viral replication strategy and underscore the role of ABCA1 as an innate anti-HIV factor.-Cui, H. L., A. Grant, N. Mukhamedova, T. Pushkarsky, L. Jennelle, L. Dubrovsky, K. Gaus, M. L. Fitzgerald, D. Sviridov, and M. Bukrinsky. HIV-1 Nef mobilizes lipid rafts in macrophages through a pathway that competes with ABCA1-dependent cholesterol efflux. J. Lipid Res. 2012. 53: 696-708. C1 [Cui, Huanhuan L.; Mukhamedova, Nigora; Sviridov, Dmitri] Baker Heart & Diabet Inst, Melbourne, Vic, Australia. [Grant, Angela; Pushkarsky, Tatiana; Jennelle, Lucas; Dubrovsky, Larisa; Bukrinsky, Michael] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA. [Gaus, Katharina] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. [Fitzgerald, Michael L.] Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Sviridov, D (reprint author), Baker Heart & Diabet Inst, Melbourne, Vic, Australia. EM Dmitri.Sviridov@bakeridi.edu.au RI Bukrinsky, Jens/D-7151-2013; Sviridov, Dmitri/E-7943-2010 OI Bukrinsky, Jens/0000-0002-4993-6366; FU National Institutes of Health [HL-093818, HL-101274, AI-078743, 1P30AI-087714-01]; National Health and Medical Research Council of Australia [526615, 586607]; Victorian Government; District of Columbia Developmental Center for AIDS Research (DCD-CFAR) FX This work was supported by the National Institutes of Health Grants HL-093818, HL-101274, and AI-078743 (M. B. and D. S.); by National Health and Medical Research Council of Australia Grant 526615 (D. S. and M. B.); in part by the Victorian Government Operational Infrastructure Support (OIS) program; and in part by the District of Columbia Developmental Center for AIDS Research (DCD-CFAR), a National Institutes of Health-funded program (Grant 1P30AI-087714-01). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. D. S. is a fellow of the National Health and Medical Research Council of Australia (Grant 586607). NR 38 TC 29 Z9 29 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 2012 VL 53 IS 4 BP 696 EP 708 DI 10.1194/jlr.M023119 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 907PY UT WOS:000301431000008 PM 22262807 ER PT J AU Korrapati, MC Shaner, BE Schnellmann, RG AF Korrapati, Midhun C. Shaner, Brooke E. Schnellmann, Rick G. TI Recovery from Glycerol-Induced Acute Kidney Injury Is Accelerated by Suramin SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACUTE-RENAL-FAILURE; GELATINASE-ASSOCIATED LIPOCALIN; NF-KAPPA-B; HEME OXYGENASE-1; GENE-EXPRESSION; CELL-DEATH; RHABDOMYOLYSIS; ADHESION; MICE; MOLECULE-1 AB Acute kidney injury (AKI) is a common and potentially life-threatening complication after ischemia/reperfusion and exposure to nephrotoxic agents. In this study, we examined the efficacy and mechanism(s) of suramin in promoting recovery from glycerol-induced AKI, a model of rhabdomyolysis-induced AKI. After intramuscular glycerol injection (10 ml of 50% glycerol per kilogram) into male Sprague-Dawley rats, serum creatinine maximally increased at 24 to 72 h and then decreased at 120 h. Creatinine clearance (CrCl) decreased 75% at 24 to 72 h and increased at 120 h. Suramin (1 mg/kg i.v.) administered 24 h after glycerol accelerated recovery of renal function as demonstrated by increased CrCl, decreased renal kidney injury molecule-1, and improved histopathology 72 h after glycerol injection. Suramin treatment decreased interleukin-1 beta (IL-1 beta) mRNA, transforming growth factor-beta(1) (TGF-beta(1)), phospho-p65 of nuclear factor-kappa B (NF-kappa B), and cleaved caspase-3 at 48 h compared with glycerol alone. Suramin treatment also decreased glycerol-induced activation of intracellular adhesion molecule-1 (ICAM-1) and leukocyte infiltration at 72 h. Urinary/renal neutrophil gelatinase-associated lipocalin 2 (NGAL) levels, hemeoxygenase-1 expression, and renal cell proliferation were increased by suramin compared with glycerol alone at 72 h. Mechanistically, suramin decreases early glycerol-induced pro-inflammatory (IL-1 beta and NF-kappa B) and growth inhibitory (TGF-beta(1)) mediators, resulting in the prevention of late downstream inflammatory effects (ICAM-1 and leukocyte infiltration) and increasing compensatory nephrogenic repair. These results support the hypothesis that delayed administration of suramin is effective in abrogating apoptosis, attenuating inflammation, and enhancing nephrogenic repair after glycerol-induced AKI. C1 [Korrapati, Midhun C.; Shaner, Brooke E.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health National Institute of General Medical Sciences [GM084147]; Biomedical Laboratory Research and Development of Department of Veterans Affairs; National Institutes of Health National Center for Research Resources [C06-RR015455]; South Carolina Clinical & Translational Research Institute; Medical University of South Carolina, National Institutes of Health National Center for Research Resources [UL1-RR029882] FX This study was supported by National Institutes of Health National Institute of General Medical Sciences [Grant GM084147]; and the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by National Institutes of Health National Center for Research Resources [Grant C06-RR015455]. This publication (or project) was also supported by the South Carolina Clinical & Translational Research Institute, with an academic home at the Medical University of South Carolina, National Institutes of Health National Center for Research Resources [Grant UL1-RR029882]. NR 57 TC 19 Z9 22 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2012 VL 341 IS 1 BP 126 EP 136 DI 10.1124/jpet.111.190249 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 908YX UT WOS:000301530100013 PM 22228809 ER PT J AU Braunstein, I Goodman, NG Rosenbach, M Okawa, J Shah, A Krathen, M Kovarik, CL Prak, EL Werth, VP AF Braunstein, Inbal Goodman, Noah G. Rosenbach, Misha Okawa, Joyce Shah, Asha Krathen, Michael Kovarik, Carrie L. Prak, Eline Luning Werth, Victoria P. TI Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: Histologic and circulating leukocyte profile and potential risk of a systemic lupus flare SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE cutaneous lupus erythematosus; lenalidomide; lupus erythematosus; subacute cutaneous; lupus erythematosus; discoid; lupus erythematosus; tumid ID AICARDI-GOUTIERES-SYNDROME; SKIN-LESIONS; T-CELLS; IMMUNOHISTOCHEMICAL ANALYSIS; DISEASE-ACTIVITY; DENDRITIC CELLS; SEVERITY INDEX; EXPRESSION; LYMPHOCYTES; RECRUITMENT AB Background: Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment-refractory cutaneous lupus erythematosus (CLE). Objectives: We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment-refractory patients before and after treatment. Methods: Five subjects were treated with lenalidomide in an unblinded open-label study. Immunohistochemistry of skin was performed for T-cell markers, glycosaminoglycans, and CXCL10, an interferon-inducible chemokine, before and after treatment. Immunophenotyping and measurement of interferon-inducible genes from peripheral blood mononuclear cells was also performed before and after treatment. Results: Four subjects demonstrated clinical improvement of their skin, however one of these responders subsequently developed symptoms of systemic lupus erythematosus. Small changes in rare circulating leukocyte subsets, plasmacytoid dendritic cells, and regulatory T cells were observed with treatment and may correlate with clinical response. Treatment was associated with increased circulating HLA-DR expression and decreased markers of interferon-mediated pathways, regardless of clinical response. Limitations: Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets. Conclusions: Lenalidomide may have usefulness as therapy for severe, treatment-refractory CLE. However, our preliminary data suggest that lenalidomide may activate T cells and trigger systemic disease in some patients with CLE. We also saw a different histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment-refractory patients will improve our understanding of CLE. (J Am Acad Dermatol 2012;66:571-82.) C1 [Braunstein, Inbal; Rosenbach, Misha; Okawa, Joyce; Shah, Asha; Krathen, Michael; Kovarik, Carrie L.; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Goodman, Noah G.; Prak, Eline Luning] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Braunstein, Inbal; Okawa, Joyce; Shah, Asha; Krathen, Michael; Kovarik, Carrie L.; Werth, Victoria P.] Univ Penn, Dermatol Sect, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, PCAM Suite 1-330S,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Alliance for Lupus Research; Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; National Institutes of Health [K24-AR 02207] FX Supported in part by the Alliance for Lupus Research, a Merit Review Grant from the Department of Veterans Affairs Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and by the National Institutes of Health (K24-AR 02207) to Dr Werth. Celgene Corporation provided the drug free of charge. NR 38 TC 17 Z9 18 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 BP 571 EP 582 DI 10.1016/j.jaad.2011.01.015 PG 12 WC Dermatology SC Dermatology GA 907UP UT WOS:000301444600011 PM 21821308 ER PT J AU Nazarian, RM Due, B Deshpande, A Duncan, LM Misdraji, J AF Nazarian, Rosalynn M. Due, Brice Deshpande, Anita Duncan, Lyn M. Misdraji, Joseph TI An improved method of surgical pathology testing for onychomycosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE nail histology; onychomycosis; periodic acid-Schiff; pretreatment; section quality; sodium hydroxide ID NAIL CLIPPINGS; DIAGNOSING ONYCHOMYCOSIS; CHEMICAL MATRICECTOMY AB Background: Surgical pathology testing for onychomycosis using periodic acid-Schiff staining is the "gold standard." However, routine histopathological methods of processing nail clippings can be limited by poor section quality, higher costs, and delayed turnaround times for some specimens because of tissue hardness. Objective: We investigated the utility of sodium hydroxide (NaOH) pretreatment of nail specimens submitted for the histopathologic evaluation of onychomycosis. Methods: We report our validation of a sodium hydroxide (NaOH) pretreatment protocol during a 7-month study period from 2009-2010. Nail clippings (n = 45) were divided into NaOH-treated and routine processing halves and submitted in separate tissue blocks for parallel processing, embedding, sectioning, and staining for hematoxylin-eosin and periodic acid-Schiff. Histologic sections were scored for section quality and statistical analysis performed. Results: NaOH pretreatment yielded higher quality sections for both hematoxylin-eosin-stained (P < .001) and periodic acid Schiff-stained (P < .001) slides with reduced tissue folding and fragmentation, improved ease of cutting, and adherence of the tissue to glass slides. Limitations: Direct comparison of the proposed NaOH pretreatment protocol with other pretreatment techniques was not performed. Conclusion: NaOH pretreatment of nails submitted for a clinical suspicion of onychomycosis is a simple, rapid, and easily adopted method that leads to improved tissue section quality for optimal histopathologic evaluation and diagnosis. Improved tissue sections and adherence to glass slides can reduce the need for repeat sections, thereby reducing costs and preventing delays in turnaround time. (J Am Acad Dermatol 2012;66:655-60.) C1 [Nazarian, Rosalynn M.; Duncan, Lyn M.] Massachusetts Gen Hosp, Pathol Serv, Dermatopathol Unit, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nazarian, RM (reprint author), Massachusetts Gen Hosp, Pathol Serv, Dermatopathol Unit, James Homer Wright Pathol Labs, 55 Fruit St,WRN 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 21 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 BP 655 EP 660 DI 10.1016/j.jaad.2011.05.046 PG 6 WC Dermatology SC Dermatology GA 907UP UT WOS:000301444600022 PM 21816506 ER PT J AU Javorsky, E Kostecki, J Kimball, AB AF Javorsky, Emilia Kostecki, James Kimball, Alexa Boer TI The relative popularity of nonprocedural dermatology fellowships SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID WORKFORCE SHORTAGE C1 [Kimball, Alexa Boer] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Javorsky, Emilia] Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin CURTIS, Boston, MA 02114 USA. [Kostecki, James] Amer Acad Dermatol, Schaumburg, IL USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Dept Dermatol, 50 Staniford St,240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 5 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2012 VL 66 IS 4 BP 693 EP 694 DI 10.1016/j.jaad.2011.09.030 PG 3 WC Dermatology SC Dermatology GA 907UP UT WOS:000301444600032 PM 22421119 ER PT J AU Sorensen, MD Eisner, BH Stone, KL Kahn, AJ Lui, LY Sadetsky, N Stoller, ML AF Sorensen, Mathew D. Eisner, Brian H. Stone, Katie L. Kahn, Arnold J. Lui, Li-Yung Sadetsky, Natalia Stoller, Marshall L. TI Impact of Calcium Intake and Intestinal Calcium Absorption on Kidney Stones in Older Women: The Study of Osteoporotic Fractures SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Urological-Association CY MAY 14-19, 2011 CL Washington, DC SP Amer Urol Assoc DE intestinal absorption; calcium; kidney calculi; calcium, dietary; dietary supplements ID DIETARY CALCIUM; IDIOPATHIC HYPERCALCIURIA; AMBULATORY EVALUATION; VITAMIN-D; RISK; NEPHROLITHIASIS; AGE; DISABILITY; NUTRIENTS AB Purpose: Intestinal calcium absorption is thought to have a critical role in nephrolithiasis. However, to our knowledge no study has directly assessed this association. Therefore, we explored the relationship among intestinal fractional calcium absorption, calcium intake and nephrolithiasis. Materials and Methods: The Study of Osteoporotic Fractures is a prospective cohort of 9,704 postmenopausal women recruited from population based listings in 1986 and followed for more than 20 years. Secondary analyses were performed of 7,982 women who reported their history of nephrolithiasis, of which 5,452 (68%) underwent an oral radioactive calcium assay (45Ca). The impact of dietary and supplemental calcium on intestinal fractional calcium absorption was evaluated, and factors independently associated with nephrolithiasis were determined. Results: Fractional calcium absorption decreased with increased calcium intake, with no difference between dietary and supplemental calcium. Fractional calcium absorption was higher in women with a nephrolithiasis history among all calcium intake groups. Increased dietary calcium intake reduced the likelihood of nephrolithiasis by 45% to 54% (p = 0.03). Women with a history of nephrolithiasis were less likely to supplement calcium (p = 0.001). In adjusted analyses women who supplemented calcium were 21% to 38% less likely to have a nephrolithiasis history (p = 0.007) and there was a 24% increased risk of kidney stones for each 10% increase in fractional calcium absorption (p = 0.008). Conclusions: Fractional calcium absorption is higher in women with a history of nephrolithiasis. Higher intestinal fractional calcium absorption is associated with a greater risk of historical nephrolithiasis. Dietary and supplemental calcium decrease fractional calcium absorption, and may protect against nephrolithiasis. C1 [Sorensen, Mathew D.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. [Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Stone, Katie L.; Kahn, Arnold J.; Lui, Li-Yung] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Sadetsky, Natalia; Stoller, Marshall L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. RP Sorensen, MD (reprint author), Univ Washington, Sch Med, Dept Urol, 1959 NE Pacific St,Box 356510, Seattle, WA 98195 USA. EM mathews@uw.edu FU NIA NIH HHS [R01 AG027576-22, R01 AG027576, AG05394, R01 AG027574, R01 AG005407, 2 R01 AG027574-22A1, 2 R01 AG005394-22A1, R01 AG005394, AG05407]; NIAMS NIH HHS [R01 AR035584, R01 AR035583, AR35584, AR35583, R01 AR035582, AR35582] NR 27 TC 7 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2012 VL 187 IS 4 BP 1287 EP 1292 DI 10.1016/j.juro.2011.11.109 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 914AY UT WOS:000301922300049 PM 22341269 ER PT J AU Usami, Y Popov, S Weiss, ER Vriesema-Magnuson, C Calistri, A Gottlinger, HG AF Usami, Yoshiko Popov, Sergei Weiss, Eric R. Vriesema-Magnuson, Christie Calistri, Arianna Goettlinger, Heinrich G. TI Regulation of CHMP4/ESCRT-III Function in Human Immunodeficiency Virus Type 1 Budding by CC2D1A SO JOURNAL OF VIROLOGY LA English DT Article ID ESCRT-III COMPLEX; C2 DOMAIN PROTEIN; NF-KAPPA-B; STRUCTURAL BASIS; BINDING PARTNER; TERMINAL DOMAIN; HIV-1; PATHWAY; TSG101; ALIX AB The detachment of human immunodeficiency type 1 (HIV-1) virions depends on CHPM4 family members, which are late-acting components of the ESCRT pathway that mediate the cleavage of bud necks from the cytosolic side. We now show that in human cells, CHMP4 proteins are to a considerable extent bound to two high-molecular-weight proteins that we have identified as CC2D1A and CC2D1B. Both proteins bind to the core domain of CHMP4B, which has a strong propensity to polymerize and to inhibit HIV-1 budding. Further mapping showed that CC2D1A binds to an N-terminal hairpin within the CHMP4 core that has been implicated in polymerization. Consistent with a model in which CC2D1A and CC2D1B regulate CHMP4 polymerization, the overexpression of CC2D1A inhibited both the release of wild-type HIV-1 and the CHMP4-dependent rescue of an HIV-1 L domain mutant by exogenous ALIX. Furthermore, small interfering RNA against CC2D1A or CC2D1B increased HIV-1 budding under certain conditions. CC2D1A and CC2D1B possess four Drosophila melanogaster 14 (DM14) domains, and we demonstrate that these constitute novel CHMP4 binding modules. The DM14 domain that bound most avidly to CHMP4B was by itself sufficient to inhibit the function of ALIX in HIV-1 budding, indicating that the inhibition occurred through CHMP4 sequestration. However, N-terminal fragments of CC2D1A that did not interact with CHMP4B nevertheless retained a significant level of inhibitory activity. Thus, CC2D1A may also affect HIV-1 budding in a CHMP4-independent manner. C1 [Usami, Yoshiko; Popov, Sergei; Weiss, Eric R.; Vriesema-Magnuson, Christie; Goettlinger, Heinrich G.] Univ Massachusetts, Sch Med, Program Mol Med, Program Gene Funct & Express, Worcester, MA 01655 USA. [Calistri, Arianna; Goettlinger, Heinrich G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Gottlinger, HG (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, Program Gene Funct & Express, Worcester, MA 01655 USA. EM heinrich.gottlinger@umassmed.edu RI Ghartouchent, malek/B-9088-2012 FU National Institute of Allergy and Infectious Diseases [R37AI029873] FX This work was supported by grant R37AI029873 from the National Institute of Allergy and Infectious Diseases. NR 59 TC 13 Z9 13 U1 0 U2 3 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 APR PY 2012 VL 86 IS 7 BP 3746 EP 3756 DI 10.1128/JVI.06539-11 PG 11 WC Virology SC Virology GA 906TV UT WOS:000301371500032 PM 22258254 ER PT J AU Li, X Koh, Y Engelman, A AF Li, Xiang Koh, Yasuhiro Engelman, Alan TI Correlation of Recombinant Integrase Activity and Functional Preintegration Complex Formation during Acute Infection by Replication-Defective Integrase Mutant Human Immunodeficiency Virus SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; DNA-BINDING DOMAIN; STRUCTURE-BASED MUTAGENESIS; CARBOXYL-TERMINAL DOMAINS; AMINO-ACID-RESIDUES; FINGER-LIKE DOMAIN; TYPE-1 INTEGRASE; IN-VITRO; VIRAL-DNA; NUCLEAR IMPORT AB Previous studies characterized two types of replication-defective human immunodeficiency virus type 1 (HIV-1) integrase mutants: class I, which are specifically blocked at the integration step, and class II, which harbor additional virion production and/or reverse transcription defects. Class I mutant enzymes supported little if any metal ion-dependent 3 '-processing and DNA strand transfer activities in vitro, whereas class II enzymes displayed partial or full catalytic function in studies with simplified assay designs, suggesting that defective interaction(s) with heterologous integrase binding proteins might underlie the class II mutant viral phenotype. To address this hypothesis, class I and II mutant enzymes were interrogated under expanded sets of in vitro conditions. The majority failed to catalyze the concerted integration of two viral DNA ends into target DNA, highlighting defective integrase function as the root cause of most class II in addition to all class I mutant virus infection defects. One mutant protein, K264E, in contrast, could support the wild-type level of concerted integration activity. After accounting for its inherent reverse transcription defect, HIV-1(K264E) moreover formed preintegration complexes that supported the efficient integration of endogenous viral DNA in vitro and normal levels and sequences of 2-long terminal repeat-containing circle junctions during acute infection. K264E integrase furthermore efficiently interacted in vitro with two heterologous binding partners, LEDGF/p75 and reverse transcriptase. Our results underscore the physiological relevance of concerted integration assays for tests of integrase mutant function and suggest that the K264E mutation disrupts an interaction with an intranuclear integrase binding partner that is important for HIV-1 integration. C1 [Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu RI perumal, murugiah/D-1565-2012; Ghartouchent, malek/B-9088-2012 FU NIH [R37AI039394, P30AI060354]; Harvard University Center for AIDS Research (CFAR); NIAID; NCI; NIMH; NIDA; NICHD; NHLBI; NCCAM FX This work was funded by NIH grant R37AI039394 and the Harvard University Center for AIDS Research (CFAR), an NIH-funded program (P30AI060354) that is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, and NCCAM. NR 130 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2012 VL 86 IS 7 BP 3861 EP 3879 DI 10.1128/JVI.06386-11 PG 19 WC Virology SC Virology GA 906TV UT WOS:000301371500043 PM 22278243 ER PT J AU Kozora, E Filley, CM Zhang, L Brown, MS Miller, DE Arciniegas, DB Pelzman, JL West, SG AF Kozora, E. Filley, C. M. Zhang, L. Brown, M. S. Miller, D. E. Arciniegas, D. B. Pelzman, J. L. West, S. G. TI Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations SO LUPUS LA English DT Article DE autoantibodies; cognition; cytokines; lupus; neuroimaging ID CEREBROSPINAL-FLUID; COGNITIVE IMPAIRMENT; RHEUMATOID-ARTHRITIS; NEUROMETABOLIC ABNORMALITIES; ANTIPHOSPHOLIPID ANTIBODIES; ANTICARDIOLIPIN ANTIBODIES; ELEVATED LEVELS; INTERLEUKIN-6; CYTOKINES; INVOLVEMENT AB Objective: This study examined the relationship between immune, cognitive and neuroimaging assessments in subjects with systemic lupus erythematosus (SLE) without histories of overt neuropsychiatric (NP) disorders. Methods: In total, 84 subjects with nonNPSLE and 37 healthy controls completed neuropsychological testing from the American College of Rheumatology SLE battery. Serum autoantibody and cytokine measures, volumetric magnetic resonance imaging, and magnetic resonance spectroscopy data were collected on a subset of subjects. Results: NonNPSLE subjects had lower scores on measures of visual/complex attention, visuomotor speed and verbal memory compared with controls. No clinically significant differences between nonNPSLE patients and controls were found on serum measures of lupus anticoagulant, anticardiolipin antibodies, beta 2-glycoproteins, or pro-inflammatory cytokines (interleukin (IL)-1, IL-6, interferon alpha (IFN-alpha), and interferon gamma (IFN-gamma)). Higher scores on a global cognitive impairment index and a memory impairment index were correlated with lower IFN-alpha. Few associations between immune functions and neuroimaging parameters were found. Conclusions: Results indicated that nonNPSLE patients demonstrated cognitive impairment but not immune differences compared with controls. In these subjects, who were relatively young and with mild disease, no relationship between cognitive dysfunction, immune parameters, or previously documented neuroimaging abnormalities were noted. Immune measures acquired from cerebrospinal fluid instead of serum may yield stronger associations. Lupus (2012) 21, 402-411. C1 [Kozora, E.; Zhang, L.; Pelzman, J. L.] Natl Jewish Hlth, Denver, CO 80206 USA. [Filley, C. M.; Arciniegas, D. B.] Univ Colorado, Dept Neurol, Denver Sch Med, Denver, CO 80202 USA. [Kozora, E.; Filley, C. M.; Arciniegas, D. B.] Univ Colorado, Dept Psychiat, Denver Sch Med, Denver, CO 80202 USA. [Brown, M. S.; Miller, D. E.] Univ Colorado, Dept Radiol, Denver Sch Med, Denver, CO 80202 USA. [West, S. G.] Univ Colorado, Dept Rheumatol, Denver Sch Med, Denver, CO 80202 USA. [Filley, C. M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), Natl Jewish Hlth, 1400 Jackson St, Denver, CO 80206 USA. EM kozorae@njhealth.org FU National Institute of Musculoskeletal and Skin Diseases [RO1 AR049152-02] FX This work was supported by the National Institute of Musculoskeletal and Skin Diseases (Grant RO1 AR049152-02). NR 60 TC 16 Z9 18 U1 3 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PD APR PY 2012 VL 21 IS 4 BP 402 EP 411 DI 10.1177/0961203311429116 PG 10 WC Rheumatology SC Rheumatology GA 909RZ UT WOS:000301583400006 PM 22170761 ER PT J AU Ran, CZ Zhang, ZD Hooker, J Moore, A AF Ran, Chongzhao Zhang, Zhaoda Hooker, Jacob Moore, Anna TI In Vivo Photoactivation Without "Light": Use of Cherenkov Radiation to Overcome the Penetration Limit of Light SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Cherenkov radiation; Bioluminescence; Photoactivation; Caged luciferin ID CERENKOV LUMINESCENCE TOMOGRAPHY; POSITRON-EMITTING RADIOTRACERS; PHOTODYNAMIC THERAPY; CANCER; PHOTOSENSITIZERS; PORPHYRIN; CHEMISTRY; PET AB The poor tissue penetration of visible light has been a major barrier for optical imaging, photoactivatable conversions, and photodynamic therapy for in vivo targets with depths beyond 10 mm. In this report, as a proof-of-concept, we demonstrated that a positron emission tomography (PET) radiotracer, 2-deoxy-2-[F-18]fluoro-d-glucose ((18)FDG), could be used as an alternative light source for photoactivation. We utilized (18)FDG, which is a metabolic activity-based PET probe, as a source of light to photoactivate caged luciferin in a breast cancer animal model expressing luciferase. Bioluminescence produced from luciferin allowed for the real-time monitoring of Cherenkov radiation-promoted uncaging of the substrate. The proposed method may provide a very important option for in vivo photoactivation, in particular for activation of photosensitizers for photodynamic therapy and eventually for combining radioisotope therapy and photodynamic therapy. C1 [Ran, Chongzhao; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Mol Imaging Lab, Charlestown, MA 02129 USA. [Ran, Chongzhao; Zhang, Zhaoda; Hooker, Jacob; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,MIT,HMS Athinoula A Martinos Ctr Biom, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Mol Imaging Lab, Bldg 75, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu OI Hooker, Jacob/0000-0002-9394-7708 NR 25 TC 24 Z9 24 U1 3 U2 39 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD APR PY 2012 VL 14 IS 2 BP 156 EP 162 DI 10.1007/s11307-011-0489-z PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 909SG UT WOS:000301584100003 PM 21538154 ER PT J AU Tang, G Kawai, T Komatsuzawa, H Mintz, KP AF Tang, G. Kawai, T. Komatsuzawa, H. Mintz, K. P. TI Lipopolysaccharides mediate leukotoxin secretion in Aggregatibacter actinomycetemcomitans SO MOLECULAR ORAL MICROBIOLOGY LA English DT Article DE Lipopolysaccharides; Leukotoxin; Type I secretion system; TolC ID OUTER-MEMBRANE PROTEIN; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ESCHERICHIA-COLI; AUTOTRANSPORTER ADHESIN; SEROTYPE B; TOLC; IDENTIFICATION; VIRULENCE; EXPRESSION; PATHWAY AB We previously reported that lipopolysaccharide (LPS) -related sugars are associated with the glycosylation of the collagen adhesin EmaA, a virulence determinant of Aggregatibacter actinomycetemcomitans. In this study, the role of LPS in the secretion of other virulence factors was investigated. The secretion of the epithelial adhesin Aae, the immunoglobulin Fc receptor Omp34 and leukotoxin were examined in a mutant strain with inactivated TDP-4-keto-6-deoxy-d-glucose 3,5-epimerase (rmlC), which resulted in altered O-antigen polysaccharides (O-PS) of LPS. The secretion of Aae and Omp34 was not affected. However, the leukotoxin secretion, which is mediated by the TolC-dependent type I secretion system, was altered in the rmlC mutant. The amount of secreted leukotoxin in the bacterial growth medium was reduced nine-fold, with a concurrent four-fold increase of the membrane-bound toxin in the mutant compared with the wild-type strain. The altered leukotoxin secretion pattern was restored to the wild-type by complementation of the rmlC gene in trans. Examination of the ltxA mRNA levels indicated that the leukotoxin secretion was post-transcriptionally regulated in the modified O-PS containing strain. The mutant strain also showed increased resistance to vancomycin, an antibiotic dependent on TolC for internalization, indicating that TolC was affected. Overexpression of TolC in the rmlC mutant resulted in an increased TolC level in the outer membrane but did not restore the leukotoxin secretion profile to the wild-type phenotype. The data suggest that O-PS mediate leukotoxin secretion in A. actinomycetemcomitans. C1 [Tang, G.; Mintz, K. P.] Univ Vermont, Dept Microbiol & Mol Genet, Burlington, VT 05405 USA. [Kawai, T.] Forsyth Inst, Cambridge, MA USA. [Komatsuzawa, H.] Kagoshima Univ, Dept Oral Microbiol, Grad Sch Med & Dent Sci, Sakuragaoka, Kagoshima, Japan. RP Mintz, KP (reprint author), Univ Vermont, Dept Microbiol & Mol Genet, Room 118 Stafford Hall, Burlington, VT 05405 USA. EM Keith.Mintz@uvm.edu FU NIH-NIDCR [RO1-DE13824] FX We thank Edward Lally, University of Pennsylvania, for providing the anti-LtxA antibodies and Teresa Ruiz and Silvana Fabiola Parussini, for critical review of the manuscript. We also acknowledge Bin Deng for the mass spectrometric analysis (Vermont Genetics Network, P20 RR16462 from the INBRE program of the National Center for Research Resources). This research was supported by NIH-NIDCR grant RO1-DE13824 awarded to K.P.M. NR 50 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2041-1006 J9 MOL ORAL MICROBIOL JI Mol. Oral Microbiol. PD APR PY 2012 VL 27 IS 2 BP 70 EP 82 DI 10.1111/j.2041-1014.2011.00632.x PG 13 WC Dentistry, Oral Surgery & Medicine; Microbiology SC Dentistry, Oral Surgery & Medicine; Microbiology GA 904FA UT WOS:000301178300002 PM 22394466 ER PT J AU Paganoni, S Deng, J Jaffa, M Cudkowicz, ME Wills, AM AF Paganoni, Sabrina Deng, Jing Jaffa, Matthew Cudkowicz, Merit E. Wills, Anne-Marie TI What does body mass index measure in amyotrophic lateral sclerosis and why should we care? SO MUSCLE & NERVE LA English DT Letter C1 [Paganoni, Sabrina; Deng, Jing; Jaffa, Matthew; Cudkowicz, Merit E.; Wills, Anne-Marie] Harvard Univ, Neurol Clin Trials Unit, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. RP Paganoni, S (reprint author), Harvard Univ, Neurol Clin Trials Unit, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. FU NICHD NIH HHS [K12 HD001097] NR 2 TC 2 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD APR PY 2012 VL 45 IS 4 BP 612 EP 612 DI 10.1002/mus.22338 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 910QV UT WOS:000301657000023 PM 22431098 ER PT J AU Beyer, AS von Einem, B Schwanzar, D Keller, IE Hellrung, A Thal, DR Ingelsson, M Makarova, A Deng, MH Chhabra, ES Propper, C Bockers, TM Hyman, BT von Arnim, CAF AF Beyer, Anja-Silke von Einem, Bjoern Schwanzar, Daniel Keller, Ilona E. Hellrung, Anke Thal, Dietmar R. Ingelsson, Martin Makarova, Alexandra Deng, Meihua Chhabra, Ekta S. Proepper, Christian Boeckers, Tobias M. Hyman, Bradley T. von Arnim, Christine A. F. TI Engulfment adapter PTB domain containing 1 interacts with and affects processing of the amyloid-beta precursor protein SO NEUROBIOLOGY OF AGING LA English DT Article DE APP processing; GULP1; PTB domain; Abeta; sAPP secretion ID RECEPTOR-RELATED PROTEIN; ALZHEIMERS-DISEASE; APOPTOTIC CELLS; FE65; CED-6; GAMMA; CLEAVAGE; HOMOLOG; ELEGANS; BRAIN AB Previous studies identified engulfment adapter phosphotyrosine binding (PTB) domain containing 1 (GULP1) as an NPXY-motif interactor of low-density lipoprotein receptor-related protein 1 (LRP1) and suggested a potential relevance in Alzheimer's disease (AD). Since AD associated proteins amyloid-beta A4 precursor protein (APP) and LRP1 were shown to interact with the PTB domain of Fe65 and several other adapters via their intracellular NPXY-motifs, we examined a possible interaction of GULP1 PTB domain with the YENPTY-motif of APP. Here we demonstrate that GULP1 is present in human hippocampal and neocortical neurons. Confocal live cell imaging revealed that coexpressed and endogenous GULP1 colocalizes with APP in the Golgi and endoplasmic reticulum. Analysis of the interacting domains by co-immunoprecipitation of point and deletion mutants revealed that the interaction depends on the PTB domain of GULP1 and the YENPTY-motif of APP. Coexpression of GULP1 affected APP cell surface localization and suppressed generation of A beta 40/42 and sAPP alpha. Taken together, these data identify GULP1 as a novel neuronal APP interacting protein that alters trafficking and processing of APP. (C) 2012 Elsevier Inc. All rights reserved. C1 [Beyer, Anja-Silke; von Einem, Bjoern; Schwanzar, Daniel; Keller, Ilona E.; Hellrung, Anke; von Arnim, Christine A. F.] Univ Ulm, Clin Res Ctr, Dept Neurol, D-89081 Ulm, Germany. [Thal, Dietmar R.] Univ Ulm, Clin Res Ctr, Neuropathol Lab, Inst Pathol, D-89081 Ulm, Germany. [Ingelsson, Martin; Makarova, Alexandra; Deng, Meihua; Chhabra, Ekta S.; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. [Proepper, Christian; Boeckers, Tobias M.] Univ Ulm, Inst Anat, D-89081 Ulm, Germany. RP von Arnim, CAF (reprint author), Univ Ulm, Clin Res Ctr, Dept Neurol, Helmholtzstr 8-1, D-89081 Ulm, Germany. EM christine.arnim@uni-ulm.de FU Massachusetts Aging and Disability Resource Consortium (ADRC) [5P50AG005134, 5R01AG012406] FX The authors thank Angelika Ruck and Frank Dolp of the Institute for Lasertechnologies in Medicine and Metrology (ILM) in Ulm for supply and technical advice concerning confocal laser scanning microscopy (CLSM) measurements. This work was supported by Massachusetts Aging and Disability Resource Consortium (ADRC) grants 5P50AG005134 and 5R01AG012406. NR 36 TC 7 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2012 VL 33 IS 4 BP 732 EP 743 DI 10.1016/j.neurobiolaging.2010.06.006 PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 908RC UT WOS:000301506800010 PM 20674096 ER PT J AU Baker, LD Asthana, S Cholerton, BA Wilkinson, CW Plymate, SR Green, PS Merriam, GR Fishel, MA Watson, GS Cherrier, MM Kletke, ML Mehta, PD Craft, S AF Baker, Laura D. Asthana, Sanjay Cholerton, Brenna A. Wilkinson, Charles W. Plymate, Stephen R. Green, Pattie S. Merriam, George R. Fishel, Mark A. Watson, G. Stennis Cherrier, Monique M. Kletke, Monica L. Mehta, Pankaj D. Craft, Suzanne TI Cognitive response to estradiol in postmenopausal women is modified by high cortisol SO NEUROBIOLOGY OF AGING LA English DT Article DE Estrogen; Stress; Hypothalamic-pituitary-adrenal (HPA); Cognition; Executive function; Memory; A beta; Amyloid; IGF; Postmenopausal ID GROWTH-FACTOR-I; ESTROGEN REPLACEMENT THERAPY; MEDIAL PREFRONTAL CORTEX; CORTICOTROPIN-RELEASING-FACTOR; ACUTE PSYCHOSOCIAL STRESS; PITUITARY-ADRENAL AXIS; AMYLOID-BETA; WORKING-MEMORY; ALZHEIMERS-DISEASE; IMPROVES COGNITION AB Estradiol has potent favorable effects on brain function and behavior in animals while in human trials, the results are inconsistent. A number of potential mediating variables influencing response to estradiol have been proposed to account for this variability, 1 of which includes stress. We conducted a placebo-controlled study to examine joint and independent effects of estradiol and elevated levels of the stress hormone cortisol on cognition and biomarkers of aging and neurodegenerative disease. Thirty-nine healthy postmenopausal women (56-84 years) received 0.10 mg/dL of transdermal 17 beta-estradiol (E2) or placebo for 8 weeks. During the last 4 days of the trial, subjects also received 90 mg/day (30 mg 3 beta/day) of oral hydrocortisone (CORT) to induce stress-level elevations in cortisol, or a matched placebo. The 4 groups thus included placebo (placebo patch/placebo pill), CORT-alone (placebo patch/hydrocortisone), E2-alone (estradiol patch/placebo pill), and E2+CORT (estradiol patch/hydrocortisone). Eight weeks of E2 increased plasma estradiol by 167%, and 4 days of CORT increased plasma cortisol by 119%. Overall, E2 had favorable effects on verbal memory (p = 0.03), working memory (p = 0.02), and selective attention (p = 0.04), and the magnitude of these effects was attenuated for E2+CORT. E2-alone and E2+CORT had opposing effects on plasma levels of the amyloid-beta (A beta) biomarker (A beta 40/42 ratio, p < 0.05), with the more favorable response observed for E2-alone. CORT-induced increases in insulin-like growth factor-1 were blunted by E2 coadministration. Our findings indicate that cognitive and physiological responses to estradiol are adversely affected by elevated stress hormone levels of cortisol in healthy postmenopausal women. (C) 2012 Elsevier Inc. All rights reserved. C1 [Baker, Laura D.] VAPSHCS, GRECC S 182, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Baker, Laura D.; Cholerton, Brenna A.; Wilkinson, Charles W.; Watson, G. Stennis; Cherrier, Monique M.; Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Plymate, Stephen R.; Green, Pattie S.; Merriam, George R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Green, Pattie S.; Merriam, George R.; Kletke, Monica L.] VAPSHCS, Res & Dev, Seattle, WA 98108 USA. [Fishel, Mark A.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Mehta, Pankaj D.] New York State Inst Basic Res Dev Disabil, Dept Immunol, New York, NY USA. RP Baker, LD (reprint author), VAPSHCS, GRECC S 182, Geriatr Res Educ & Clin Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Ldbaker@uw.edu FU Office of Research and Development Medical Research Service; Geriatric Research, Education and Clinical Center of the Veterans Affairs Puget Sound Health Care System; National Alliance for Research on Schizophrenia and Depression (NARSAD) FX This work was supported by the Office of Research and Development Medical Research Service, the Geriatric Research, Education and Clinical Center of the Veterans Affairs Puget Sound Health Care System, and the National Alliance for Research on Schizophrenia and Depression (NARSAD). Berlex Laboratories provided the transdermal estradiol patches and matching placebo. We are grateful to the members of our laboratory who contributed many hours to this project including Karen Enstrom, R.N., Karen Hyde, R.N., Darla Chapman, R.N., Donna Davis, R.N., Jaime Tidwell, Dana Belongia, Tracia Clark, Amy Morgan, Michelle Keeling, and Margaret Pagoria. We also thank Elizabeth Colasurdo and Kathy Haugk for their assistance with the assays. NR 111 TC 3 Z9 3 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2012 VL 33 IS 4 AR 829.e9 DI 10.1016/j.neurobiolaging.2011.07.002 PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 908RC UT WOS:000301506800032 PM 21855173 ER PT J AU Palada, V Terzic, J Mazzulli, J Bwala, G Hagenah, J Peterlin, B Hung, AY Klein, C Krainc, D AF Palada, Vinko Terzic, Janos Mazzulli, Joseph Bwala, Grace Hagenah, Johann Peterlin, Borut Hung, Albert Y. Klein, Christine Krainc, Dimitri TI Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Parkinson's disease; Parkinsonism; Histamine; HNMT; Association studies in genetics ID ESSENTIAL TREMOR AB Histamine is a central neurotransmitter degraded by histamine-N-methyltransferase (HNMT). Several abnormalities in the histaminergic system were found in patients with Parkinson's disease (PD), thus we tested the possible association of a Thr105Ile functional polymorphism in HNMT with PD. A total of 913 patients with PD and 958 controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster City, California, USA). Lower frequency of HNMT Ile105 allele that is associated with decreased enzymatic activity was found in patients compared with controls (chi(2) = 11.65; p = 0.0006). We performed meta-analysis to confirm the association of Thr105Ile functional polymorphism with PD. Our results indicate that lower HNMT activity plays a role in the pathogenesis of PD. (C) 2012 Elsevier Inc. All rights reserved. C1 [Palada, Vinko; Krainc, Dimitri] Mediterranean Inst Life Sci, Split, Croatia. [Terzic, Janos] Univ Split, Sch Med, Split, Croatia. [Mazzulli, Joseph; Bwala, Grace; Hung, Albert Y.; Krainc, Dimitri] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mazzulli, Joseph; Bwala, Grace; Hung, Albert Y.; Krainc, Dimitri] Harvard Univ, Sch Med, Boston, MA USA. [Hagenah, Johann; Klein, Christine] Univ Lubeck, Sect Clin & Mol Neurogenet, Dept Neurol, Lubeck, Germany. [Peterlin, Borut] Univ Med Ctr, Div Med Genet, Ljubljana, Slovenia. RP Krainc, D (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM krainc@helix.mgh.harvard.edu RI peterlin, borut/C-6086-2011 OI peterlin, borut/0000-0001-7824-4978 FU National Parkinson Foundation; GENEPARK [EU-LSHB-CT-2006-037544]; Volkswagen Foundation; Hermann and Lilly Schilling Foundation; NGFN Plus (BMBF) [PNP-01GS08135-3] FX This study was sponsored by National Parkinson Foundation (DK), GENEPARK (EU-LSHB-CT-2006-037544) grant (DK), Volkswagen Foundation, Hermann and Lilly Schilling Foundation, and NGFN Plus PNP-01GS08135-3 (BMBF, CK). NR 10 TC 3 Z9 4 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2012 VL 33 IS 4 AR 836.e1 DI 10.1016/j.neurobiolaging.2011.06.015 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 908RC UT WOS:000301506800048 PM 21794955 ER PT J AU Shi, M Furay, AR Sossi, V Aasly, JO Armaly, J Wang, Y Wszolek, ZK Uitti, RJ Hasegawa, K Yokoyama, T Zabetian, CP Leverenz, JB Stoessl, AJ Zhang, J AF Shi, Min Furay, Amy R. Sossi, Vesna Aasly, Jan O. Armaly, Jeff Wang, Yu Wszolek, Zbigniew K. Uitti, Ryan J. Hasegawa, Kazuko Yokoyama, Teruo Zabetian, Cyrus P. Leverenz, James B. Stoessl, A. Jon Zhang, Jing TI DJ-1 and alpha SYN in LRRK2 CSF do not correlate with striatal dopaminergic function SO NEUROBIOLOGY OF AGING LA English DT Article DE Parkinson's disease; LRRK2; Gene mutation; Biomarker; DJ-1; alpha-synuclein ID PARKINSONS-DISEASE AB Previous studies demonstrated decreased levels of DJ-1 and alpha-synuclein (alpha SYN) in human cerebrospinal fluid (CSF) in patients with Parkinson's disease (PD), but neither marker correlated with PD severity, raising the possibility that they may be excellent progression markers during early or preclinical phases of PD. Individuals carrying the leucine-rich repeat kinase 2 (LRRK2) gene mutation are at increased risk for PD, and the phenotype of LRRK2 patients is almost identical to sporadic PD. To determine whether dopaminergic dysfunction in the basal ganglia, as determined by positron emission tomography (PET) scans, correlates with CSF levels of DJ-1 and alpha SYN during preclinical stages, Luminex assays were used to analyze CSF samples from asymptomatic LRRK2 mutation carriers, along with carriers who presented with a clinical diagnosis of PD. The data revealed no statistically significant relationship between PET scan evidence of loss of striatal dopaminergic function and the CSF biomarkers DJ-1 and alpha SYN, except for a weak correlation between DJ-1 and methylphenidate binding, suggesting that the use of these potential biomarkers on their own to screen LRRK2 gene mutation carriers for PD is not appropriate. (C) 2012 Elsevier Inc. All rights reserved. C1 [Shi, Min; Furay, Amy R.; Armaly, Jeff; Wang, Yu; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Sossi, Vesna] Univ British Columbia, Dept Phys & Astron, Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. [Aasly, Jan O.] St Olavs Hosp, Dept Neurol, Trondheim, Norway. [Wang, Yu] Huazhong Univ Sci & Technol, Dept Neurosurg, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China. [Wszolek, Zbigniew K.; Uitti, Ryan J.] Mayo Clin Florida, Dept Neurol, Jacksonville, FL USA. [Hasegawa, Kazuko; Yokoyama, Teruo] Sagamihara Natl Hosp, Dept Neurol, Natl Hosp Org, Sagamihara, Kanagawa, Japan. [Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. [Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Stoessl, A. Jon] Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Stoessl, A. Jon] Vancouver Coastal Hlth, Vancouver, BC, Canada. RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, HMC Box 359635,325 9th Ave, Seattle, WA 98104 USA. EM zhangj@uw.edu RI Shi, Min/G-6165-2012 OI Shi, Min/0000-0002-6901-2558 FU BLRD VA [I01 BX000531]; NIA NIH HHS [R01 AG033398, R01 AG033398-05, R01 AG025327]; NIEHS NIH HHS [R01 ES016873, R01 ES016873-03, R01 ES019277, R01 ES019277-01A1, R01 ES019277-02]; NINDS NIH HHS [P50 NS062684, P50 NS072187, R01 NS057567, R01 NS057567-05, R01 NS065070, R21 NS060252] NR 3 TC 4 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2012 VL 33 IS 4 AR 836.e5 DI 10.1016/j.neurobiolaging.2011.09.015 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 908RC UT WOS:000301506800049 PM 22019052 ER PT J AU Zhang, XY Zhou, DF Shen, YC Zhang, PY Zhang, WF Liang, J Chen, DC Xiu, MH Kosten, TA Kosten, TR AF Zhang, Xiang Yang Zhou, Dong Feng Shen, Yu Cun Zhang, Pei Yan Zhang, Wu Fang Liang, Jun Chen, Da Chun Xiu, Mei Hong Kosten, Therese A. Kosten, Thomas R. TI Effects of risperidone and haloperidol on superoxide dismutase and nitric oxide in schizophrenia SO NEUROPHARMACOLOGY LA English DT Article DE Schizophrenia; Free radical; Oxidative stress; Antipsychotic treatment ID ANTIOXIDANT DEFENSE SYSTEM; ACID-REACTIVE SUBSTANCES; POLYUNSATURATED FATTY-ACIDS; FREE-RADICAL PATHOLOGY; LIPID-PEROXIDATION; OXIDATIVE STRESS; RAT-BRAIN; ANTIPSYCHOTIC-DRUGS; THERAPEUTIC IMPLICATIONS; ATYPICAL ANTIPSYCHOTICS AB Oxidative stress may be involved in the pathophysiology of schizophrenia. No double-blind study has compared the effects of typical and atypical antipsychotics on both antioxidant enzyme activity and nitric oxide (NO) levels in schizophrenic patients. Seventy-eight inpatients with chronic schizophrenia were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design. Clinical efficacy was determined using the Positive and Negative Syndrome Scale. Blood superoxide dismutase (SOD) and plasma NO levels were measured in patients and 30 normal controls. Our results showed that following a 2-week washout period, levels of SOD and NO were significantly increased in patients with schizophrenia compared to normal controls. Both risperidone and haloperidol equivalently reduced the elevated blood SOD levels in schizophrenia, but neither medication reduced the elevated plasma NO levels in schizophrenia. Low blood SOD levels at baseline predicted greater symptom improvement during treatment, and greater change in SOD was correlated with greater symptom improvement. These results suggest that both typical and atypical antipsychotic drugs may at least partially normalize abnormal free radical metabolism in schizophrenia, and some free radical parameters at baseline may predict antipsychotic responses of schizophrenic patients. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Zhang, Xiang Yang; Zhou, Dong Feng; Shen, Yu Cun; Zhang, Wu Fang; Liang, Jun] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [Zhang, Xiang Yang; Zhang, Pei Yan; Chen, Da Chun; Xiu, Mei Hong] Beijing HuiLongGuan Hosp, Beijing, Peoples R China. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; zhoudf@bjmu.edu.cn; kosten@bcm.edu FU Stanley Medical Research Institute [03T-459, 05T-726]; Beijing Municipal Natural Science Foundation [7072035]; Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC),United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX This study was partially funded by the Stanley Medical Research Institute (03T-459 and 05T-726), the Beijing Municipal Natural Science Foundation (ID: 7072035), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. NR 58 TC 24 Z9 25 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD APR PY 2012 VL 62 IS 5-6 BP 1928 EP 1934 DI 10.1016/j.neuropharm.2011.12.014 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 908EX UT WOS:000301474300003 PM 22227558 ER PT J AU Roosli, C Linthicum, FH Cureoglu, S Merchant, SN AF Roosli, Christof Linthicum, Fred H., Jr. Cureoglu, Sebahattin Merchant, Saumil N. TI Dysfunction of the Cochlea Contributing to Hearing Loss in Acoustic Neuromas: An Underappreciated Entity SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Cochlear changes; Hair cell loss; Hearing loss; Temporal bone histopathology; Vestibular schwannoma ID EVOKED OTOACOUSTIC EMISSIONS; VESTIBULAR SCHWANNOMA; INNER-EAR; NEUROFIBROMATOSIS TYPE-2; PRESERVATION; NEURINOMA; SURGERY; HISTOPATHOLOGY; BEVACIZUMAB; RESPONSES AB Objective: Hearing loss is a common symptom in patients with cochleovestibular schwannoma. Clinical and histologic observations have suggested that the hearing loss may be caused by both retrocochlear and cochlear mechanisms. Our goal was to perform a detailed assessment of cochlear pathology in patients with vestibular schwannoma (VS). Study Design: Retrospective analysis of temporal bone histopathology. Setting: Multi-center study. Material: Temporal bones from 32 patients with unilateral, sporadic VS within the internal auditory canal. Main Outcome Measures: Sections through the cochleae on the VS side and opposite (control) ear were evaluated for loss of inner and outer hair cells, atrophy of the stria vascularis, loss of cochlear neurons, and presence of endolymphatic hydrops and precipitate within the endolymph or perilymph. Observed pathologies were correlated to nerve of origin, VS volume, and distance of VS from the cochlea. Hearing thresholds also were assessed. Results: VS caused significantly more inner and outer hair cell loss, cochlear neuronal loss, precipitate in endolymph and perilymph, and decreased pure tone average, when compared with the opposite ear. Tumor size, distance from the cochlea, and nerve of origin did not correlate with structural changes in the cochlea or the hearing threshold. Conclusion: There is significant degeneration of cochlear structures in ears with VS. Cochlear dysfunction may be an important contributor to the hearing loss caused by VS and can explain certain clinically observed phenomena in patients with VS. C1 [Roosli, Christof; Merchant, Saumil N.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Roosli, Christof] Univ Zurich Hosp, Clin Otorhinolaryngol Head & Neck Surg, CH-8091 Zurich, Switzerland. [Linthicum, Fred H., Jr.] House Ear Res Inst, Los Angeles, CA USA. [Cureoglu, Sebahattin] Univ Minnesota, Dept Otolaryngol, Minneapolis, MN USA. RP Roosli, C (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM christof_roosli@meei.harvard.edu FU National Institutes of Health (National Institute on Deafness and other Communcation Disorders) [U24 DC011943]; "Nachwuchsforderungskredit'' of the University of Zurich FX Supported by the National Institutes of Health (National Institute on Deafness and other Communcation Disorders) grant U24 DC011943, and the "Nachwuchsforderungskredit'' of the University of Zurich. NR 52 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD APR PY 2012 VL 33 IS 3 BP 473 EP 480 DI 10.1097/MAO.0b013e318248ee02 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 907SV UT WOS:000301439300035 PM 22377650 ER PT J AU De la Marche, W Steyaert, J Noens, I AF De la Marche, Wouter Steyaert, Jean Noens, Ilse TI Atypical sensory processing in adolescents with an autism spectrum disorder and their non-affected siblings SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism spectrum disorder; Adolescents; Siblings; Sensory profile; Intermediate phenotype ID PERVASIVE DEVELOPMENTAL DISORDERS; PSYCHIATRIC-DISORDERS; DIAGNOSTIC INTERVIEW; ASPERGER-SYNDROME; YOUNG-CHILDREN; ABNORMALITIES; DYSFUNCTION; SYMPTOMS; TODDLERS; BEHAVIOR AB Atypical sensory processing is common in autism spectrum disorders (ASD). Specific profiles have been proposed in different age groups, but no study has focused specifically on adolescents. Identifying traits of ASD that are shared by individuals with ASD and their non-affected family members can shed light on the genetic underpinnings of ASD. Eighty adolescents with ASD (64 boys, 16 girls), 56 non-affected adolescent siblings (21 boys, 35 girls) and 33 adolescent controls (18 boys, 15 girls) filled out the Adolescent/Adult Sensory Profile, a self-report questionnaire resulting in four sensory quadrants according to Dunn's model of sensory processing. Adolescents with ASD differed significantly from controls on the quadrants Sensation Seeking and Sensation Avoidance. On quadrant 2 (Sensation Seeking) siblings scored significantly lower than controls and significantly higher than ASD. These results confirm the presence of atypical sensory processing in adolescents with ASD. We argue that reduced Sensation Seeking might be a candidate for an intermediate phenotype. (c) 2011 Elsevier Ltd. All rights reserved. C1 [Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Grp, B-3000 Louvain, Belgium. [De la Marche, Wouter; Steyaert, Jean] UPC KU Leuven, Child & Adolescent Psychiat Dept, B-3000 Louvain, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, NL-6202 AZ Maastricht, Netherlands. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [De la Marche, Wouter; Steyaert, Jean; Noens, Ilse] Katholieke Univ Leuven, B-3000 Louvain, Belgium. RP Noens, I (reprint author), Katholieke Univ Leuven, Parenting & Special Educ Res Grp, Andreas Vesaliusstr 2, B-3000 Louvain, Belgium. EM ilse.noens@ped.kuleuven.be RI Steyaert, Jean/B-5326-2015 OI Steyaert, Jean/0000-0003-2512-4694 NR 48 TC 12 Z9 12 U1 3 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD APR-JUN PY 2012 VL 6 IS 2 BP 639 EP 645 DI 10.1016/j.rasd.2011.09.014 PG 7 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA 908DH UT WOS:000301470100007 ER PT J AU Al Natour, RH Huang, Q Sharma, AM Gold, JS AF Al Natour, Riad H. Huang, Qin Sharma, Ashish M. Gold, Jason S. TI Incidental Finding of Bulky Retroperitoneal Lymphadenopathy in a Patient with a Primary Occult Small Gastric Carcinoid Tumor SO AMERICAN SURGEON LA English DT Article C1 [Al Natour, Riad H.; Gold, Jason S.] VA Boston Healthcare Syst, Surg Serv, West Roxbury, MA USA. [Al Natour, Riad H.; Gold, Jason S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Huang, Qin] VA Boston Healthcare Syst, Pathol Serv, West Roxbury, MA USA. [Huang, Qin] Harvard Univ, Sch Med, Boston, MA USA. [Sharma, Ashish M.] VA Boston Healthcare Syst, Med Serv, West Roxbury, MA USA. [Sharma, Ashish M.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Gold, JS (reprint author), VA Boston Healthcare Syst 112, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM jgold4@partners.org RI Gold, Jason/O-5112-2014 OI Gold, Jason/0000-0002-2925-4755 NR 4 TC 0 Z9 0 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI CUMMING PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA SN 0003-1348 EI 1555-9823 J9 AM SURGEON JI Am. Surg. PD APR PY 2012 VL 78 IS 4 BP E224 EP E226 PG 3 WC Surgery SC Surgery GA V32LO UT WOS:000208952900015 PM 22472382 ER PT J AU Kwon, YM Mellon, SJ Monk, P Murray, DW Gill, HS AF Kwon, Y-M. Mellon, S. J. Monk, P. Murray, D. W. Gill, H. S. TI In vivo evaluation of edge-loading in metal-on-metal hip resurfacing patients with pseudotumours SO BONE & JOINT RESEARCH LA English DT Article DE Pseudotumours; Edge-loading; In vivo evaluation; Metal-on-metal; Hip resurfacing; Metal ions AB Objectives Pseudotumours (abnormal peri-prosthetic soft-tissue reactions) following metal-on-metal hip resurfacing arthroplasty (MoMHRA) have been associated with elevated metal ion levels, suggesting that excessive wear may occur due to edge-loading of these MoM implants. This study aimed to quantify in vivo edge-loading in MoMHRA patients with and without pseudotumours during functional activities. Methods The duration and magnitude of edge-loading in vivo was quantified during functional activities by combining the dynamic hip joint segment contact force calculated from the three-dimensional (3D) motion analysis system with the 3D reconstruction of orientation of the acetabular component and each patient's specific hip joint centre, based on CT scans. Results Edge-loading in the hips with pseudotumours occurred with a four-fold increase in duration and magnitude of force compared with the hips without pseudotumours (p = 0.02). Conclusions The study provides the first in vivo evidence to support that edge-loading is an important mechanism that leads to localised excessive wear (edge-wear), with subsequent elevation of metal ion levels in MoMHRA patients with pseudotumours. C1 [Kwon, Y-M.; Mellon, S. J.; Monk, P.; Murray, D. W.; Gill, H. S.] Univ Oxford, Nuffield Dept Rheumatol Orthopaed & Musculoskelet, Oxford OX3 7LD, England. RP Kwon, YM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Sch Med, 55 Fruit St,Suite 3B, Boston, MA 02114 USA. EM kwon.young-min@mgh.harvard.edu RI Mellon, Stephen/B-9744-2013 OI Mellon, Stephen/0000-0002-6375-6839 FU NIHR Biomedical Research Unit at the Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre FX This work was supported by institutional funding, the NIHR Biomedical Research Unit at the Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre. None of the authors have professional or financial affiliations that may be perceived to have biased the presentation. NR 42 TC 13 Z9 13 U1 0 U2 5 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 2046-3758 J9 BONE JOINT RES JI Bone Jt. Res. PD APR PY 2012 VL 1 IS 4 BP 42 EP 49 DI 10.1302/2046-3758.14.2000019 PG 8 WC Cell & Tissue Engineering; Orthopedics SC Cell Biology; Orthopedics GA V35GX UT WOS:000209139500001 PM 23610670 ER PT J AU Zhang, DF Cheriyan, T Martin, SD Schmid, TM Spector, M AF Zhang, Dafang Cheriyan, Thomas Martin, Scott D. Schmid, Thomas M. Spector, Myron TI Lubricin Distribution in the Menisci and Labra of Human Osteoarthritic Joints SO CARTILAGE LA English DT Article DE lubricin; fibrocartilage; meniscus; labrum AB Objective: Lubricin is the principal boundary lubricant on articular cartilage. We aimed to describe the distribution of lubricin in the other articulating structures in the human knee and hip-menisci and labra-and to relate this distribution to the degree of tissue degeneration. Methods: Eighteen menisci and 6 labra were obtained from patients with osteoarthritis undergoing total knee and total hip replacements, respectively. Macroscopically intact specimens were fixed in formalin and processed for H&E staining and immunohistochemical evaluation with an antilubricin monoclonal antibody. Results: Lubricin was found in all tissues as a discrete layer on the tissue surface, within the extracellular matrix, and intracellularly, indicating that it plays a role in the tribology of these tissues in human subjects, and can be synthesized by cells within the tissues. While none of the samples displayed macroscopic tears, approximately 40% of the surface of the menisci and 80% of the surface of the labra displayed microscopic fibrillations and slight fraying. There was no effect of the degenerative changes on the distribution of lubricin. Conclusions: Lubricin coats nearly the entirety of the surfaces of menisci and labra, including microfibrillations and tears, with possible implications towards the tribology of the tissues and healing of tissue damage. C1 [Zhang, Dafang; Cheriyan, Thomas; Martin, Scott D.; Spector, Myron] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, Dafang; Spector, Myron] Harvard Massachusetts Inst Technol MIT Div Hlth S, Cambridge, MA USA. [Zhang, Dafang; Cheriyan, Thomas; Spector, Myron] Vet Affairs VA Boston Healthcare Syst, Tissue Engn, Boston, MA USA. [Zhang, Dafang; Cheriyan, Thomas; Martin, Scott D.; Spector, Myron] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Schmid, Thomas M.] Rush Univ, Dept Biochem, Med Ctr, Chicago, IL 60612 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Mail Stop 151 Res,150 South Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu FU Department of Veterans Affairs FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by the Department of Veterans Affairs. The source of funding played no role in the study. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1947-6035 EI 1947-6043 J9 CARTILAGE JI Cartilage PD APR PY 2012 VL 3 IS 2 BP 165 EP 172 DI 10.1177/1947603511429699 PG 8 WC Orthopedics SC Orthopedics GA V36NF UT WOS:000209217800006 PM 26069629 ER PT J AU Wang, GC Chan, CH Gao, Y Lin, HK AF Wang, Guocan Chan, Chia-Hsin Gao, Yuan Lin, Hui-Kuan TI Novel roles of Skp2 E3 ligase in cellular senescence, cancer progression, and metastasis SO CHINESE JOURNAL OF CANCER LA English DT Review DE Skp2; p53; RhoA; cellular senescence; metastasis; cancer therapy AB S-phase kinase-associated protein 2 (Skp2) belongs to the F-box protein family. It is a component of the SCF E3 ubiquitin ligase complex. Skp2 has been shown to regulate cellular proliferation by targeting several cell cycle-regulated proteins for ubiquitination and degradation, including cyclin-dependent kinase inhibitor p27. Skp2 has also been demonstrated to display an oncogenic function since its overexpression has been observed in many human cancers. This review discusses the recent discoveries on the novel roles of Skp2 in regulating cellular senescence, cancer progression, and metastasis, as well as the therapeutic potential of targeting Skp2 for human cancer treatment. C1 [Wang, Guocan] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Wang, Guocan] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chan, Chia-Hsin; Gao, Yuan; Lin, Hui-Kuan] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. [Gao, Yuan; Lin, Hui-Kuan] Univ Texas Houston, Grad Sch Biomed Sci Houston, Houston, TX 77030 USA. RP Lin, HK (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. EM hklin@mdanderson.org FU MD Anderson Cancer Center Trust Scholar Award; NIH; CPRIT; DOD prostate cancer New Investigator Award; MD Anderson Cancer Center Breast SPORE Career Development Award FX We thank the members of Lin's laboratory, The University of Texas MD Anderson Cancer Center, for their valuable comments and suggestions. This work was supported by the MD Anderson Cancer Center Trust Scholar Award, NIH grants, CPRIT grant, and DOD prostate cancer New Investigator Award to H.K.L., as well as the MD Anderson Cancer Center Breast SPORE Career Development Award to C. H. C. NR 96 TC 22 Z9 27 U1 0 U2 9 PU SUN YAT SEN UNIV MED SCI WHO PI GUANGZHOU PA 651 DONGFENG RD E, GUANGZHOU, GUANGDONG 510060, PEOPLES R CHINA SN 1000-467X EI 1944-446X J9 CHIN J CANCER JI Chin. J. Cancer PD APR PY 2012 VL 31 IS 4 BP 169 EP 177 DI 10.5732/cjc.011.10319 PG 9 WC Oncology SC Oncology GA V33HB UT WOS:000209008800003 PM 22200179 ER PT J AU Sonpavde, G Sternberg, CN AF Sonpavde, Guru Sternberg, Cora N. TI Neoadjuvant Chemotherapy for Invasive Bladder Cancer SO CURRENT UROLOGY REPORTS LA English DT Article DE Bladder cancer; Neoadjuvant therapy; Surgery AB Neoadjuvant cisplatin- based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents. C1 [Sonpavde, Guru] Baylor Coll Med, Sect Med Oncol, Dept Med, Texas Oncol,Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Sternberg, Cora N.] San Camillo Hosp, I-00152 Rome, Italy. [Sternberg, Cora N.] Forlanini Hosp, I-00152 Rome, Italy. RP Sternberg, CN (reprint author), San Camillo Hosp, Padigl Flajani 1,Circonvallaz Gianicolense 87, I-00152 Rome, Italy. EM cstern@mclink.it RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU Cephalon; Celgene; Bristol-Myers Squibb; Pfizer; Bellicum Pharmaceuticals; Ascenta Therapeutics; Novartis; Cytogen; AstraZeneca; Imclone-Eli Lilly; Sanofi-Aventis; Cougar Biotech; Astellas FX Dr. Guru Sonpavde has served as board member for Novartis, Bristol-Myers Squibb, Pfizer, Dendreon, and Janssen; has received grants or research support or has grants pending from Cephalon, Celgene, Bristol-Myers Squibb, Pfizer, Bellicum Pharmaceuticals, Ascenta Therapeutics, Novartis, Cytogen, AstraZeneca, and Imclone-Eli Lilly; and has received honoraria from Wyeth/Pfizer, Novartis, Sanofi-Aventis, GlaxoSmithKline, Janssen Biotech, Dendreon, and Amgen. Dr. Cora Sternberg has received honoraria from Novartis, Pfizer, and GlaxoSmithKline; has received research support from Sanofi-Aventis, Cougar Biotech, and Astellas; and served on the advisory board or as a consultant for Bayer, Novartis, GlaxoSmithKline and Pfizer. NR 90 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2737 J9 CURR UROL REP JI Curr. Urol. Rep. PD APR PY 2012 VL 13 IS 2 BP 136 EP 146 DI 10.1007/s11934-012-0236-2 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA V32HX UT WOS:000208943400004 PM 22314880 ER PT J AU Yan, N Wheeler, LA Regalado-Magdos, AD Stiggelbout, B Lee-Kirsch, MA Lieberman, J AF Yan, Nan Wheeler, Lee Adam Regalado-Magdos, Ashton D. Stiggelbout, Bart Lee-Kirsch, Minh Ae Lieberman, Judy TI The Cytosolic Exonuclease TREX1 Digests HIV Reverse Transcripts to Avoid Triggering an Antiviral Interferon Response in T Cells and Macrophages SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 13th Annual International Meeting of the Institute of Human Virology CY OCT 30-NOV 03, 2011 CL Baltimore, MD C1 [Yan, Nan; Wheeler, Lee Adam; Regalado-Magdos, Ashton D.; Stiggelbout, Bart; Lee-Kirsch, Minh Ae; Lieberman, Judy] Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2012 VL 59 SU 1 MA 144 BP 60 EP 60 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V45YE UT WOS:000209851100053 ER PT J AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette TI Yin and Yang - the Gastric X/A-like Cell as Possible Dual Regulator of Food Intake SO JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE Desacyl ghrelin; Eating; Ghrelin; Nucleobindin; Obesity; Obestatin; Stomach ID DES-ACYL GHRELIN; HORMONE SECRETAGOGUE RECEPTOR; PROTEIN-COUPLED-RECEPTOR; AGOUTI-RELATED PROTEIN; HYPOTHALAMIC ARCUATE NUCLEUS; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA LEVELS; NEUROPEPTIDE-Y; BODY-WEIGHT; RAT STOMACH AB Ingestion of food affects secretion of hormones from enteroendocrine cells located in the gastrointestinal mucosa. These hormones are involved in the regulation of various gastrointestinal functions including the control of food intake. One cell in the stomach, the X/A-like has received much attention over the past years due to the production of ghrelin. Until now, ghrelin is the only known orexigenic hormone that is peripherally produced and centrally acting to stimulate food intake. Subsequently, additional peptide products of this cell have been described including desacyl ghrelin, obestatin and nesfatin-1. Desacyl ghrelin seems to be involved in the regulation of food intake as well and could play a counter-balancing role of ghrelin's orexigenic effect. In contrast, the initially proposed anorexigenic action of obestatin did not hold true and therefore the involvement of this peptide in the regulation of feeding is questionable. Lastly, the identification of nesfatin-1 in the same cell in different vesicles than ghrelin extended the function of this cell type to the inhibition of feeding. Therefore, this X/A-like cell could play a unique role by encompassing yin and yang properties to mediate not only hunger but also satiety. C1 [Stengel, Andreas] Univ Med Berlin, Charite, Dept Med, Div Psychosomat Med & Psychotherapy, Berlin, Germany. [Tache, Yvette] Univ Calif Los Angeles, Dept Med, Div Digest Dis, Ctr Neurobiol Stress,CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Stengel, A (reprint author), Obes Ctr Berlin, Div Psychosomat Med, Charitepl 1, D-10117 Berlin, Germany. EM andreas.stengel@charite.de FU Charite University; NIH [R01 DK-33061]; NIH Center Grant [DK-41301]; VA Research Career Scientist FX This work was supported by Charite University funding (A. S.) and NIH R01 DK-33061, NIH Center Grant DK-41301 (Animal Core) and VA Research Career Scientist (Y.T.). NR 165 TC 16 Z9 17 U1 0 U2 3 PU KOREAN SOC NEUROGASTERONTEROL & MOTILITY PI GANGNAM-GU PA RM 305, LOTTE GOLD ROSE VILL II, 31 SEOLLEUNG-RO 86-GIL, GANGNAM-GU, SEOUL 135-839, SOUTH KOREA SN 2093-0879 EI 2093-0887 J9 J NEUROGASTROENTEROL JI J. Neurogastroenterol. Motil. PD APR PY 2012 VL 18 IS 2 BP 138 EP 149 DI 10.5056/jnm.2012.18.2.138 PG 12 WC Gastroenterology & Hepatology; Clinical Neurology SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 225XR UT WOS:000324999000005 PM 22523723 ER PT J AU Conelea, CA Walther, MR Flessner, CA Woods, DW Franklin, ME Keuthen, NJ Piacentini, JC AF Conelea, Christine A. Walther, Michael R. Flessner, Christopher A. Woods, Douglas W. Franklin, Martin E. Keuthen, Nancy J. Piacentini, John C. TI The incremental validity of criteria B and C for diagnosis of Trichotillomania in children and adults SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Trichotillomania; Diagnosis; Hair pulling ID HAIR-PULLING DISORDER; PSYCHOMETRIC PROPERTIES; FUNCTIONAL IMPAIRMENT; EXPLORING DIFFERENCES; MILWAUKEE INVENTORY; SYMPTOM SEVERITY; PHENOMENOLOGY; IMPACT; STYLES; SCALE AB DSM-IV-TR diagnostic criteria for Trichotillomania (TTM) specify that hair pulling (criterion A) be associated with tension prior to pulling (criterion B) and relief, pleasure, or gratification while pulling (criterion C). However, research suggests that the phenomena described by criteria B and C may not apply to all who engage in repetitive hair pulling. The current study explored the incremental validity of criteria B and C in children and adults. Participants from the Child and Adolescent Trichotillomania Impact Project (CA-TIP; n=238) and the Trichotillomania Impact Project (TIP; n=1659) were grouped according to diagnostic criteria endorsed: (I) absence of criteria B and C, (2) presence of criterion B or C (but not both), and (3) criteria B and C. Groups did not differ on measures of TTM severity; automatic pulling; depression; age of onset; and social, interpersonal, and academic functioning. Differences included lower focused pulling scores in group 1, higher anxiety scores in group 3 children, and greater pulling severity in group 3 adults. The results obtained suggest that criteria B and C add little differential information to the overall clinical picture of TTM. Intervention and research should give equal attention to all who present with hair pulling causing marked distress/impairment (C) 2012 Elsevier Ltd All rights reserved. C1 [Conelea, Christine A.; Flessner, Christopher A.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA. [Walther, Michael R.; Woods, Douglas W.] Univ Wisconsin Milwaukee, Milwaukee, WI USA. [Franklin, Martin E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Piacentini, John C.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Conelea, CA (reprint author), Bradley Hasbro Childrens Res Ctr, Coro West 2nd Floor,1 Hoppin St, Providence, RI 02906 USA. EM Christine_Conelea@brown.edu RI Flessner, Christopher/K-1483-2015; OI Conelea, Christine/0000-0003-2791-9802 NR 30 TC 4 Z9 4 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD APR PY 2012 VL 1 IS 2 BP 98 EP 103 DI 10.1016/j.jocrd.2012.01.004 PG 6 WC Psychiatry SC Psychiatry GA 120BS UT WOS:000317145100005 ER PT J AU Snorrason, I Olafsson, RP Flessner, CA Keuthen, NJ Franklin, ME Woods, DW AF Snorrason, Ivar Olafsson, Ragnar P. Flessner, Christopher A. Keuthen, Nancy J. Franklin, Martin E. Woods, Douglas W. TI The Skin Picking Scale-Revised: Factor structure and psychometric properties SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Skin Picking Scale; Skin picking; Psychogenic excoriation; Validity; Reliability; Factor analysis ID CLINICAL CHARACTERISTICS; PSYCHOGENIC EXCORIATION; ECONOMIC-IMPACT; FIT INDEXES; SAMPLE; TRICHOTILLOMANIA; PHENOMENOLOGY; POPULATION; INHIBITION; DISORDER AB The Skin Picking Scale (SPS; Keuthen et al., 2001) is a 6-item self-report measure of skin picking disorder (SPD) severity. The current study reports on a psychometric evaluation of a revised eight-item version of the scale (the Skin Picking Scale-Revised; SPS-R). Participants were 652 responders to an Internet survey who met criteria for SPD. Exploratory and confirmatory factor analyses revealed two factors, one assessing impairment and the other symptom severity (4 items each). Both factors demonstrated high internal consistency and convergent/concurrent and discriminant validity. Potential advantages of the SPS-R compared to the original version include elimination of an ambiguous item, improved psychometric properties (e.g. clearer factor structure), and a more comprehensive assessment of the SPD symptom profile. (C) 2012 Elsevier Ltd All rights reserved. C1 [Snorrason, Ivar; Woods, Douglas W.] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53211 USA. [Olafsson, Ragnar P.] Univ Iceland, Sch Hlth Sci, Div Psychiat, Landspitali Univ Hosp,Iceland Fac Psychol, IS-101 Reykjavik, Iceland. [Flessner, Christopher A.] Kent State Univ, Dept Psychol, Kent, OH USA. [Keuthen, Nancy J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Franklin, Martin E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Snorrason, I (reprint author), Univ Wisconsin, Dept Psychol, 2441 East Hartford Ave, Milwaukee, WI 53211 USA. EM ivarsnorrason@gmail.com RI Flessner, Christopher/K-1483-2015 NR 30 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD APR PY 2012 VL 1 IS 2 BP 133 EP 137 DI 10.1016/j.jocrd.2012.03.001 PG 5 WC Psychiatry SC Psychiatry GA 120BS UT WOS:000317145100010 ER PT J AU Hsue, PY Scherzer, R Hunt, PW Schnell, A Bolger, AF Kalapus, SC Maka, K Martin, JN Ganz, P Deeks, SG AF Hsue, Priscilla Y. Scherzer, Rebecca Hunt, Peter W. Schnell, Amanda Bolger, Ann F. Kalapus, S. C. Maka, Kristinalisa Martin, Jeffrey N. Ganz, Peter Deeks, Steven G. TI Carotid Intima-Media Thickness Progression in HIV-Infected Adults Occurs Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE AIDS; carotid arteries; inflammation; atherosclerosis ID CARDIOVASCULAR RISK-FACTORS; ENDOTHELIAL SHEAR-STRESS; CORONARY-HEART-DISEASE; ANTIRETROVIRAL THERAPY; ATHEROSCLEROTIC LESIONS; MYOCARDIAL-INFARCTION; FLOW PATTERNS; IMMUNODEFICIENCY; ACTIVATION; PLAQUE AB Background-Shear stress gradients and inflammation have been causally associated with atherosclerosis development in carotid bifurcation regions. The mechanism underlying higher levels of carotid intima-media thickness observed among HIV-infected individuals remains unknown. Methods and Results-We measured carotid intima-media thickness progression and development of plaque in the common carotid, bifurcation region, and internal carotid artery in 300 HIV-infected persons and 47 controls. The median duration of follow-up was 2.4 years. When all segments were included, the rate of intima-media thickness progression was greater in HIV-infected subjects compared with controls after adjustment for traditional risk factors (0.055 vs. 0.024 mm/year, P=0.016). Rate of progression was also greater in the bifurcation region (0.067 vs. 0.025 mm/year, P=0.042) whereas differences were smaller in the common and internal regions. HIV-infected individuals had a greater incidence of plaque compared with controls in the internal (23% vs. 6.4%, P=0.0037) and bifurcation regions (34% vs. 17%, P=0.014). Among HIV-infected individuals, the rate of progression in the bifurcation region was more rapid compared with the common carotid, internal, or mean intima-media thickness; in contrast, progression rates among controls were similar at all sites. Baseline hsCRP was elevated in HIV-infected persons and was a predictor of progression in the bifurcation region. Conclusions-Atherosclerosis progresses preferentially in the carotid bifurcation region in HIV-infected individuals. hsCRP, a marker of inflammation, is elevated in HIV and is associated with progression in the bifurcation region. These data are consistent with a model in which the interplay between hemodynamic shear stresses and HIV-associated inflammation contribute to accelerated atherosclerosis. (J Am Heart Assoc. 2012; 1: jah3-e000422 doi: 10.1161/JAHA.111.000422.) C1 [Hsue, Priscilla Y.; Schnell, Amanda; Bolger, Ann F.; Maka, Kristinalisa; Ganz, Peter; Deeks, Steven G.] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Hunt, Peter W.; Martin, Jeffrey N.; Deeks, Steven G.] San Francisco Gen Hosp, Dept Med, Posit Hlth Program, San Francisco, CA 94110 USA. [Scherzer, Rebecca] San Francisco VA Med Ctr, San Francisco, CA USA. [Scherzer, Rebecca] Dept Med UCSF, San Francisco, CA USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Hsue, PY (reprint author), San Francisco Gen Hosp, Div Cardiol, Room 5G1,1001 Potrero Ave, San Francisco, CA 94110 USA. EM phsue@medsfgh.ucsf.edu FU Doris Duke Charitable Foundation; National Institutes of Health [K23 AI066885, K24AI069994, R01 HL095130, R01 AI052745, R01 CA119903, P30 AI27763, RO1 AI087145, MO1 RR000083]; UCSF CFAR [PO AI27763]; UCSF CTSI [UL1 RR024131]; amfAR [106710-40-RGRL]; Ragon Institute FX The work was supported by grants from the Doris Duke Charitable Foundation (Clinical Scientist Development Award to PYH), the National Institutes of Health (K23 AI066885, K24AI069994, R01 HL095130, R01 AI052745, R01 CA119903, P30 AI27763, RO1 AI087145, and MO1 RR000083), the UCSF CFAR (PO AI27763), the UCSF CTSI (UL1 RR024131), amfAR (106710-40-RGRL), and the Ragon Institute. NR 45 TC 31 Z9 31 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2012 VL 1 IS 2 AR UNSP jah3-e000422 DI 10.1161/JAHA.111.000422 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243QY UT WOS:000326333200003 ER PT J AU Musunuru, K Roden, DM Boineau, R Bristow, MR McCaffrey, TA Newton-Cheh, C Paltoo, DN Rosenberg, Y Wohlgemuth, JG Zineh, I Hasan, AAK AF Musunuru, Kiran Roden, Dan M. Boineau, Robin Bristow, Michael R. McCaffrey, Timothy A. Newton-Cheh, Christopher Paltoo, Dina N. Rosenberg, Yves Wohlgemuth, Jay G. Zineh, Issam Hasan, Ahmed A. K. TI Cardiovascular Pharmacogenomics: Current Status and Future Directions-Report of a National Heart, Lung, and Blood Institute Working Group SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE genetic polymorphisms; genetics; pharmacogenetics; pharmacogenetics anticoagulants; pharmacogenetics cholesterol ID ACUTE CORONARY SYNDROMES; GENOME-WIDE ASSOCIATION; TRP719ARG POLYMORPHISM; MYOCARDIAL-INFARCTION; CYP2C19 GENOTYPE; WARFARIN; CLOPIDOGREL; ANTICOAGULATION; EFFICACY; OUTCOMES C1 [Musunuru, Kiran] Brigham & Womens Hosp, Boston, MA 02115 USA. [Musunuru, Kiran] Harvard Univ, Cambridge, MA 02138 USA. [Roden, Dan M.] Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. [Boineau, Robin; Paltoo, Dina N.; Rosenberg, Yves; Hasan, Ahmed A. K.] NHLBI, Bethesda, MD 20892 USA. [Bristow, Michael R.] Univ Colorado, Cardiovasc Inst, Aurora, CO USA. [McCaffrey, Timothy A.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Wohlgemuth, Jay G.] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. [Zineh, Issam] US FDA, Silver Spring, MD USA. RP Musunuru, K (reprint author), Harvard Univ, 7 Divin Ave, Cambridge, MA 02138 USA. EM kiranmusunuru@gmail.com FU National Heart, Lung, and Blood Institute; Personalized Medicine Coalition; American College of Cardiology; American Medical Association; Cheney Cardiovascular Institute at George Washington University FX The Working Group meeting was underwritten by the National Heart, Lung, and Blood Institute at the National Institutes of Health, Bethesda, MD. The New Frontiers in Personalized Medicine: Cardiovascular Research and Clinical Care was supported and/or cosponsored by the National Heart, Lung, and Blood Institute; Personalized Medicine Coalition; American College of Cardiology; American Medical Association; and the Cheney Cardiovascular Institute at George Washington University. NR 37 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD APR PY 2012 VL 1 IS 2 AR UNSP e000554 DI 10.1161/JAHA.111.000554 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243QY UT WOS:000326333200009 PM 23130127 ER PT J AU Costanzi, C Bourdette, D Parisi, JE Woltjer, R Rodriguez, F Steensma, D Lucchinetti, CF AF Costanzi, Chiara Bourdette, Dennis Parisi, Joseph E. Woltjer, Randy Rodriguez, Fausto Steensma, David Lucchinetti, Claudia F. TI Crystal-storing histiocytosis: An unusual relapsing inflammatory CNS disorder SO MULTIPLE SCLEROSIS AND RELATED DISORDERS LA English DT Article DE Crystal storing histiocytosis; Plasma cell neoplasm; CNS demyelinating disease; Inflammatory CNS disorder; Acute leukoencephalopathy; T2-weight hypointensity AB The differential diagnosis of acute leukoencephalopathy often focuses on central nervous system idiopathic inflammatory demyelinating diseases (IIDDs) such as multiple sclerosis (MS). However, a spectrum of conditions mimic IIDDs, therefore it is critical to consider whether symptoms, signs, imaging and/or response to therapies are compatible with the diagnosis. We describe a 32-year-old previously healthy woman presenting with a 2 year history of steroid-responsive relapsing episodes lasting 2-10 days characterized by transient visual blurring, right-hemiparesis, and spells of aphasia. MRI demonstrated multifocal, relapsing, predominantly white matter enhancing brain lesions, a longitudinally extensive cord lesion, and abnormal visual evoked potentials. Notably, some lesions persistently enhanced whereas others demonstrated progressive T2W hypointensity. Brain biopsy revealed an atypical plasma cell infiltrate and crystal-storing histiocytosis, which by mass spectrometry confirmed the presence of macrophages containing intracellular kappa-light chain restricted crystals. Bone marrow was negative. The patient did well for several years on pulse dexamethasone, however subsequent scans demonstrated increasing enhancement. Repeat biopsy demonstrated a clonal plasma cell proliferation. She was treated with melphalan, and has remained stable. Although this patient initially met McDonald criteria, atypical imaging prompted further workup, and advanced proteomic technology helped secured an accurate diagnosis. Crystal-storing histiocytosis should be considered in the differential diagnosis of inflammatory CNS disorders. (C) 2012 Elsevier By. All rights reserved. C1 [Costanzi, Chiara; Lucchinetti, Claudia F.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN 55905 USA. [Bourdette, Dennis] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Portland, OR 97239 USA. [Parisi, Joseph E.] Mayo Clin, Coll Med, Lab Med Pathol, Rochester, MN 55901 USA. [Woltjer, Randy] Oregon Hlth & Sci Univ, Sch Med, Dept Pathol, Portland, OR 97203 USA. [Rodriguez, Fausto] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. [Steensma, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Lucchinetti, CF (reprint author), Mayo Clin, Coll Med, Dept Neurol, 200 First St SW, Rochester, MN 55905 USA. EM lucchinetti.claudia@mayo.edu OI Steensma, David/0000-0001-5130-9284 FU NCI NIH HHS [P30 CA006973] NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2211-0348 EI 2211-0356 J9 MULT SCLER RELAT DIS JI Mult. Scler. Relat. Disord. PD APR PY 2012 VL 1 IS 2 BP 95 EP 99 DI 10.1016/j.msard.2011.12.003 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA V37KY UT WOS:000209275900009 PM 25876937 ER PT J AU Huang, YY Sharma, SK Dai, TH Chung, H Yaroslavsky, A Garcia-Diaz, M Chang, JL Chiang, LY Hamblin, MR AF Huang, Ying-Ying Sharma, Sulbha K. Dai, Tianhong Chung, Hoon Yaroslavsky, Anastasia Garcia-Diaz, Maria Chang, Julie Chiang, Long Y. Hamblin, Michael R. TI Can nanotechnology potentiate photodynamic therapy? SO NANOTECHNOLOGY REVIEWS LA English DT Article DE dendrimer; fullerene; graphene; lipoplex; lipoprotein; liposome; magnetic nanoparticle; micelle; nanocell; nanoparticle; ORMOSIL; polymeric nanoparticle; porphysome; quantum dot; single-walled carbon nanotube; two-photon excitation; upconversion AB Photodynamic therapy (PDT) uses the combination of nontoxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one-photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, "can nanotechnology potentiate PDT?" C1 [Huang, Ying-Ying; Sharma, Sulbha K.; Dai, Tianhong; Chung, Hoon; Yaroslavsky, Anastasia; Garcia-Diaz, Maria; Chang, Julie; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Dai, Tianhong; Chung, Hoon; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Yaroslavsky, Anastasia] Boston Univ, Coll Engn, Boston, MA 02215 USA. [Garcia-Diaz, Maria] Univ Ramon Llull, Inst Quim Sarria, Barcelona 08017, Spain. [Chang, Julie] Harvard Univ, Dept Chem, Boston, MA 02115 USA. [Chiang, Long Y.] Univ Massachusetts, Dept Chem, Lowell, MA USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Geracitano, Laura/E-6926-2013; Garcia-Diaz, Maria/J-9202-2014 OI Garcia-Diaz, Maria/0000-0002-4794-5437 FU NIH [RO1 AI050875, 1R01CA137108]; US Air Force MFEL Program [FA9550-04-1-0079]; Bullock-Wellman Fellowship Award; Airlift Research Foundation Extremity Trauma Research [109421] FX Research conducted in the Hamblin Laboratory is supported by NIH (RO1 AI050875 to MRH) and US Air Force MFEL Program (FA9550-04-1-0079). T. D. was partially supported by a Bullock-Wellman Fellowship Award and an Airlift Research Foundation Extremity Trauma Research Grant (grant 109421). L.Y.C. was supported by NIH grant 1R01CA137108. NR 335 TC 35 Z9 35 U1 4 U2 62 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2191-9089 EI 2191-9097 J9 NANOTECHNOL REV JI Nanotechnol. Rev. PD APR PY 2012 VL 1 IS 2 BP 111 EP 146 DI 10.1515/ntrev-2011-0005 PG 36 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA V32WW UT WOS:000208982300001 PM 26361572 ER PT J AU Abbs, BR Liang, L Bitterman, JS Makris, N Seidman, LJ Goldstein, JM AF Abbs, Brandon R. Liang, Lichen Bitterman, Jason S. Makris, Nikos Seidman, Larry J. Goldstein, Jill M. TI SEX DIFFERENCES IN VERBAL MEMORY CIRCUITRY IN SCHIZOPHRENIA: STRUCTURAL, FUNCTIONAL, AND HORMONAL CONTRIBUTORS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Abbs, Brandon R.; Bitterman, Jason S.; Goldstein, Jill M.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Abbs, Brandon R.; Bitterman, Jason S.; Goldstein, Jill M.] Harvard Med Sch, Dept Med, Boston, MA USA. [Abbs, Brandon R.; Bitterman, Jason S.; Goldstein, Jill M.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [Abbs, Brandon R.; Liang, Lichen; Bitterman, Jason S.; Makris, Nikos; Seidman, Larry J.; Goldstein, Jill M.] MGH & MIT Athinoula Martinos Ctr Biomed Imaging, Boston, MA USA. [Liang, Lichen; Makris, Nikos] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Liang, Lichen; Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Publ Psychiat Div, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 41 BP S106 EP S106 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842101067 ER PT J AU del Re, EC Niznikiewicz, M Petryshen, T McCarley, RW AF del Re, Elisabetta C. Niznikiewicz, Margaret Petryshen, Tracy McCarley, Robert W. TI A CROSS SECTIONAL STUDY OF NOVEL P300 IN PRODROMES AND FIRST EPISODE SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [del Re, Elisabetta C.; Niznikiewicz, Margaret; McCarley, Robert W.] Harvard Med Sch, VABHS, Boston, MA USA. [Petryshen, Tracy] Harvard Med Sch, Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 134 BP S234 EP S234 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842101416 ER PT J AU DeLisi, LE Thermenos, HW Seidman, LJ Whitfielf-Gabrieli, S Juelich, R Jabbar, GA Salwen, KK Shenton, M Kubicki, M Gabrieli, JDE Manschreck, T Francis, A Keshavan, M AF DeLisi, Lynn E. Thermenos, Heidi W. Seidman, Larry J. Whitfielf-Gabrieli, Susan Juelich, Richard Jabbar, Gul A. Salwen, K. K. Shenton, Martha Kubicki, Marek Gabrieli, John D. E. Manschreck, Theo Francis, Alan Keshavan, Matcheri TI ALTERED LANGUAGE NETWORK ACTIVITY IN YOUNG PEOPLE AT GENETIC RISK FOR SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [DeLisi, Lynn E.; Thermenos, Heidi W.; Seidman, Larry J.; Juelich, Richard; Jabbar, Gul A.; Salwen, K. K.; Shenton, Martha; Kubicki, Marek; Keshavan, Matcheri] Harvard Med Sch, Boston, MA USA. [Thermenos, Heidi W.; Seidman, Larry J.; Keshavan, Matcheri] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Thermenos, Heidi W.; Seidman, Larry J.; Juelich, Richard; Salwen, K. K.; Manschreck, Theo; Francis, Alan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Whitfielf-Gabrieli, Susan; Gabrieli, John D. E.] MIT, McGovern Inst Brain Res, Boston, MA USA. [DeLisi, Lynn E.; Jabbar, Gul A.] VA Boston Healthcare Syst, Brockton, MA USA. [Shenton, Martha; Kubicki, Marek] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 108 BP S130 EP S130 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842101133 ER PT J AU Fisher, M Garrett, C Alexander, P Subramaniam, K Vinogradov, S AF Fisher, Melissa Garrett, Coleman Alexander, Phillip Subramaniam, Karuna Vinogradov, Sophia TI NEUROPLASTICITY-BASED COGNITIVE TRAINING IN SCHIZOPHRENIA: A FINAL REPORT ON THE EFFECTS 6-12 MONTHS LATER SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Fisher, Melissa; Garrett, Coleman; Alexander, Phillip; Subramaniam, Karuna; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Fisher, Melissa; Garrett, Coleman; Alexander, Phillip; Subramaniam, Karuna; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 163 BP S339 EP S339 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842102025 ER PT J AU Francis, AN Jabbar, GA Thermenos, HW Seidman, LJ Juelich, R Proal, A Kubicki, M Shenton, M Keshavan, M DeLisi, LE AF Francis, Alan N. Jabbar, Gul A. Thermenos, Heidi W. Seidman, Larry J. Juelich, Richard Proal, Ashley Kubicki, Marek Shenton, Martha Keshavan, Matcheri DeLisi, Lynn E. TI NEUROANATOMICAL ALTERATIONS IN REGIONS MEDIATING LANGUAGE IN YOUNG ADULTS AT HIGH RISK FOR INHERITANCE OF SCHIZOPHRENIA (GHR) SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Francis, Alan N.; Thermenos, Heidi W.; Seidman, Larry J.; Keshavan, Matcheri] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. [Thermenos, Heidi W.; Seidman, Larry J.; Juelich, Richard; Proal, Ashley; Kubicki, Marek; Shenton, Martha] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jabbar, Gul A.; Shenton, Martha; DeLisi, Lynn E.] Vet Affairs Med Ctr, Brockton, MA USA. [Francis, Alan N.; Thermenos, Heidi W.; Seidman, Larry J.; Kubicki, Marek; Shenton, Martha; Keshavan, Matcheri; DeLisi, Lynn E.] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 49 BP S203 EP S203 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842101331 ER PT J AU Goff, D AF Goff, Don TI DIFFICULTIES WITH TRANSLATIONAL RESEARCH SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Goff, Don] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 BP S60 EP S60 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842100218 ER PT J AU Goff, D AF Goff, Don TI POSSIBILITIES AND IMPOSSIBILITIES OF TMS FOR THE TREATMENT OF HALLUCINATIONS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Goff, Don] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 BP S22 EP S22 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842100075 ER PT J AU Pasternak, O Westin, CF Bouix, S Seidman, L Goldstein, J Woo, TU Petryshen, T Mesholam-Gately, R McCarley, R Shenton, M Kubicki, M AF Pasternak, Ofer Westin, Carl-Fredrik Bouix, Sylvain Seidman, Larry Goldstein, Jill Woo, Tsung-Ung Petryshen, Tracy Mesholam-Gately, Raquelle McCarley, Robert Shenton, Martha Kubicki, Marek TI FREE-WATER IMAGING REVEALS A GLOBAL INFLAMMATORY EFFECT AND LOCAL AXONAL DEGENERATION IN FIRST EPISODE SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Pasternak, Ofer; Bouix, Sylvain; Goldstein, Jill; Shenton, Martha; Kubicki, Marek] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. [Westin, Carl-Fredrik] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. [Goldstein, Jill] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Seidman, Larry; Goldstein, Jill; Mesholam-Gately, Raquelle; McCarley, Robert] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA USA. [Woo, Tsung-Ung] Harvard Med Sch, McLean Hosp, Dept Psychiat, Belmont, MA USA. [Seidman, Larry; Petryshen, Tracy] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Petryshen, Tracy] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Reseearch, Boston, MA USA. [Petryshen, Tracy] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [McCarley, Robert; Shenton, Martha] Vet Affairs Boston Healthcare Syst, Brockton Div, Dept Psychiat, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 14:45 BP S88 EP S89 PG 2 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842101022 ER PT J AU Rassovsky, Y Lee, J Nori, P Wu, AD Iacoboni, M Green, MF AF Rassovsky, Yuri Lee, Junghee Nori, Poorang Wu, Allan D. Iacoboni, Marco Green, Michael F. TI SPATIAL AND TEMPORAL PROPERTIES OF AFFECT PERCEPTION DEFICITS IN SCHIZOPHRENIA: A TMS STUDY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Rassovsky, Yuri; Lee, Junghee; Nori, Poorang; Wu, Allan D.; Iacoboni, Marco; Green, Michael F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Rassovsky, Yuri] Bar Ilan Univ, Ramat Gan, Israel. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 73 BP S306 EP S307 PG 2 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842101616 ER PT J AU Seidman, LJ AF Seidman, Larry J. TI IDENTIFYING NEUROCOGNITIVE IMPAIRMENTS PRIOR TO PSYCHOSIS: NEWMETA-ANALYSES OF NEUROCOGNITION IN THE PSYCHOSIS RISK SYNDROME AND IN YOUTH AT FAMILIAL RISK FOR SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Seidman, Larry J.] Harvard Med Sch, Massachusetts Mental Hlth Ctr, Div Publ Psychiat, Dept Psychiat,Beth Israel Deaconess Med Ctr, Boston, MA USA. [Seidman, Larry J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 14:45 BP S85 EP S85 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842101014 ER PT J AU Seidman, LJ AF Seidman, Larry J. TI NEUROPSYCHOLOGY OF THE PRODROME TO PSYCHOSIS IN THE NAPLS 2 CONSORTIUM: RELATIONSHIP TO FAMILY HISTORY AND CONVERSION TO PSYCHOSIS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Seidman, Larry J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 BP S35 EP S35 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842100128 ER PT J AU Sitnikova, T Gramfort, A Boyle, RW Cather, C Freudenreich, O Hamalainen, MS Rosen, BR Goff, DC AF Sitnikova, Tatiana Gramfort, Alexandre Boyle, Robert W. Cather, Corinne Freudenreich, Oliver Hamalainen, Matti S. Rosen, Bruce R. Goff, Donald C. TI PREFRONTAL CORTEX AND GOAL-DIRECTED BEHAVIOR IN SCHIZOPHRENIA: NEURAL MECHANISMS UNDERLYING INFLEXIBILITY SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Sitnikova, Tatiana; Cather, Corinne; Freudenreich, Oliver; Hamalainen, Matti S.; Rosen, Bruce R.; Goff, Donald C.] Harvard Med Sch, Boston, MA USA. [Sitnikova, Tatiana; Gramfort, Alexandre; Boyle, Robert W.; Cather, Corinne; Freudenreich, Oliver; Hamalainen, Matti S.; Rosen, Bruce R.; Goff, Donald C.] Massachusetts Gen Hosp, Charlestown, MA USA. [Boyle, Robert W.] Tufts Univ, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 35 BP S104 EP S104 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842101061 ER PT J AU Smith, MJ Horan, WP Karpouzian, T Abram, S Cobia, D Csernansky, JG AF Smith, Matthew J. Horan, William P. Karpouzian, Tatiana Abram, Samantha Cobia, Derin Csernansky, John G. TI EMPATHY DEFICITS ARE UNIQUELY ASSOCIATED WITH POOR FUNCTIONING IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 [Smith, Matthew J.; Karpouzian, Tatiana; Abram, Samantha; Cobia, Derin; Csernansky, John G.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Horan, William P.] Univ Calif Los Angeles, Los Angeles, CA USA. [Horan, William P.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 SU 1 MA 233 BP S365 EP S365 PG 1 WC Psychiatry SC Psychiatry GA V45US UT WOS:000209842102095 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Complications following gastrointestinal bleeding and their impact on outcome and death SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE complication of endoscopic procedure; esophago-gastro-duodenoscopy; gastrointestinal bleeding; gastrointestinal endoscopy; Markov chain modeling; outcome research; threshold analysis ID HEMORRHAGE; EPIDEMIOLOGY AB Background Bleeding from the upper gastrointestinal tract is one of the most common life-threatening morbidities encountered by gastroenterologists. A mathematical model has been developed to gain insights into how, after an initial event of upper gastrointestinal bleeding, complications can accumulate in individual patients and expose them to an increased risk of death. Methods The occurrence of complications and possible death after gastrointestinal bleeding are simulated using a Markov chain model. Results The accumulation of complications in an individual patient is influenced by the length of time a patient remains vulnerable to the probability of developing new complications. The model illustrates how the initial bleeding episode sets the stage for the occurrence of subsequent complications and how each subsequent complication increases in an exponential manner the risk for additional complications. Because of such a pattern, complications tend to cluster in a group of patients who run into an ever-increasing risk of multiple complications. Although the majority of patients go through their initial bleeding episode without ever experiencing any secondary complication, in a subset of patients the initial complication sets in motion a vicious cycle with frequently more than one consecutive complication after the initial gastrointestinal bleed. Conclusion The key to the successful management of a patient with gastrointestinal bleeding is to stop such a vicious cycle as early as possible, as each progression within the cycle renders the probability of additional complications more likely and its reversal more difficult. Eur J Gastroenterol Hepatol 24: 388-392 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3 GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 9 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD APR PY 2012 VL 24 IS 4 BP 388 EP 392 DI 10.1097/MEG.0b013e328350589e PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 905QY UT WOS:000301288700006 PM 22233622 ER PT J AU Spiro, A Oo, SA Marable, D Collins, JP AF Spiro, Anna Oo, Sarah Abernethy Marable, Danelle Collins, Jeffrey P. TI A Unique Model of the Community Health Worker The MGH Chelsea Community Health Improvement Team SO FAMILY & COMMUNITY HEALTH LA English DT Article DE community health worker; continuum of care; health disparities; patient navigation; vulnerable populations AB With current trends in legislation around the delivery of patient care, the role of a community health worker (CHW) is gaining growing and much deserved attention. However, a system needs to be built for any CHW program to be successful and sustainable. This article describes a unique approach to community health work at the Massachusetts General Hospital Chelsea HealthCare Center where a well-integrated CHW model provides support for everyone involved in patient care: patients, providers, the community at large, and the internal CHW staff. C1 [Spiro, Anna; Oo, Sarah Abernethy; Marable, Danelle] Massachusetts Gen Hosp, MGH Chelsea HealthCare Ctr, MGH Ctr Community Hlth Improvement, Chelsea, MA 02150 USA. [Collins, Jeffrey P.] Massachusetts Gen Hosp, MGH Chelsea HealthCare Ctr, Dept Urgent Care, Chelsea, MA 02150 USA. [Collins, Jeffrey P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Spiro, A (reprint author), Massachusetts Gen Hosp, MGH Chelsea HealthCare Ctr, MGH Ctr Community Hlth Improvement, 151 Everett Ave, Chelsea, MA 02150 USA. EM aspiro@partners.org NR 14 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-6379 J9 FAM COMMUNITY HEALTH JI Fam. Community Health PD APR-JUN PY 2012 VL 35 IS 2 BP 147 EP 160 DI 10.1097/FCH.0b013e3182465187 PG 14 WC Family Studies; Public, Environmental & Occupational Health SC Family Studies; Public, Environmental & Occupational Health GA 899DQ UT WOS:000300795700009 PM 22367262 ER PT J AU Farrell, JJ Zhang, L Zhou, H Chia, D Elashoff, D Akin, D Paster, BJ Joshipura, K Wong, DTW AF Farrell, James J. Zhang, Lei Zhou, Hui Chia, David Elashoff, David Akin, David Paster, Bruce J. Joshipura, Kaumudi Wong, David T. W. TI Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer SO GUT LA English DT Article ID HELICOBACTER-PYLORI INFECTION; FACTOR-KAPPA-B; AUTOIMMUNE PANCREATITIS; PERIODONTAL-DISEASE; PORPHYROMONAS-GINGIVALIS; ATHEROMATOUS PLAQUES; LUNG-CANCER; GRANULICATELLA-ADIACENS; ADENOCARCINOMA CELLS; CHLAMYDIA-PNEUMONIAE AB Objective The associations between oral diseases and increased risk of pancreatic cancer have been reported in several prospective cohort studies. In this study, we measured variations of salivary microbiota and evaluated their potential associations with pancreatic cancer and chronic pancreatitis. Methods This study was divided into three phases: (1) microbial profiling using the Human Oral Microbe Identification Microarray to investigate salivary microbiota variation between 10 resectable patients with pancreatic cancer and 10 matched healthy controls, (2) identification and verification of bacterial candidates by real-time quantitative PCR (qPCR) and (3) validation of bacterial candidates by qPCR on an independent cohort of 28 resectable pancreatic cancer, 28 matched healthy control and 27 chronic pancreatitis samples. Results Comprehensive comparison of the salivary microbiota between patients with pancreatic cancer and healthy control subjects revealed a significant variation of salivary microflora. Thirty-one bacterial species/clusters were increased in the saliva of patients with pancreatic cancer (n=10) in comparison to those of the healthy controls (n=10), whereas 25 bacterial species/clusters were decreased. Two out of six bacterial candidates (Neisseria elongata and Streptococcus mitis) were validated using the independent samples, showing significant variation (p<0.05, qPCR) between patients with pancreatic cancer and controls (n=56). Additionally, two bacteria (Granulicatella adiacens and S mitis) showed significant variation (p<0.05, qPCR) between chronic pancreatitis samples and controls (n=55). The combination of two bacterial biomarkers (N elongata and S mitis) yielded a receiver operating characteristic plot area under the curve value of 0.90 (95% CI 0.78 to 0.96, p<0.0001) with a 96.4% sensitivity and 82.1% specificity in distinguishing patients with pancreatic cancer from healthy subjects. Conclusions The authors observed associations between variations of patients' salivary microbiota with pancreatic cancer and chronic pancreatitis. This report also provides proof of salivary microbiota as an informative source for discovering non-invasive biomarkers of systemic diseases. C1 [Farrell, James J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med, Los Angeles, CA 90095 USA. [Zhang, Lei; Zhou, Hui; Akin, David; Wong, David T. W.] Univ Calif Los Angeles, Sch Dent, Dent Res Inst, Los Angeles, CA 90095 USA. [Chia, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Elashoff, David] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Paster, Bruce J.] Forsyth Inst, Dept Mol Genet, Boston, MA USA. [Joshipura, Kaumudi] Univ Puerto Rico, Sch Dent Med, San Juan, PR 00936 USA. [Wong, David T. W.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Wong, David T. W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg Otolaryngol, Los Angeles, CA 90095 USA. [Wong, David T. W.] Univ Calif Los Angeles, David Geffen Sch Med, Henry Samueli Sch Engn & Appl Sci, Los Angeles, CA 90095 USA. RP Farrell, JJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med, 200 Med Plaza,Suite 365A, Los Angeles, CA 90095 USA. EM jfarrell@mednet.ucla.edu OI Joshipura, Kaumudi/0000-0003-1964-7579 FU National Institute of Health [RO1DE017170, R21CA126733] FX Funding support was provided by the National Institute of Health (RO1DE017170 and R21CA126733). NR 69 TC 90 Z9 96 U1 3 U2 40 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2012 VL 61 IS 4 BP 582 EP 588 DI 10.1136/gutjnl-2011-300784 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 901HL UT WOS:000300955000016 PM 21994333 ER PT J AU Leoutsakos, JMS Muthen, BO Breitner, JC Lyketsos, CG AF Leoutsakos, Jeannie-Marie S. Muthen, Bengt O. Breitner, John C. S. Lyketsos, Constantine G. CA ADAPT Res Team TI Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE NSAIDs; Alzheimer; prevention; dementia; growth mixture models ID AMYLOID-BETA-PROTEIN; MIXTURE MODELING ANALYSIS; MICROGLIAL CELLS; DOUBLE-BLIND; NSAID USE; IMPAIRMENT; DEMENTIA; AD; TRAJECTORIES; PROGRESSION AB Objective: We examined the effects of non-steroidal anti-inflammatory drugs on cognitive decline as a function of phase of pre-clinical Alzheimer disease. Methods: Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer disease. We fit growth mixture models of Modified Mini-Mental State (3MS) Examination trajectories with data from 2388 participants in the Alzheimer's Disease Anti-inflammatory Prevention Trial and included class-specific effects of naproxen and celecoxib. Results: We identified three classes: "no decline", "slow decline", and "fast decline", and examined the effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (-2 log likelihood difference: 369.23; p < 0.001) but resulted in reversal of effects over time. Over 4 years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, whereas those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), whereas those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Conclusions: Our results appeared statistically robust but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then attenuated change in fast decliners. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Leoutsakos, Jeannie-Marie S.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Leoutsakos, Jeannie-Marie S.; Lyketsos, Constantine G.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Muthen, Bengt O.] Univ Calif Los Angeles, Los Angeles Grad Sch Educ & Informat Studies, Social Res Methodol Div, Los Angeles, CA USA. [Breitner, John C. S.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Breitner, John C. S.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Leoutsakos, JMS (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. EM jeannie-marie@jhu.edu FU AstraZeneca; Eisai; Forest Laboratories; Janssen; Lilly; Novartis; Pfizer; NIH [T32AG026778, U01-AG15477, P50-AG005146] FX Dr Lyketsos is a consultant to GlaxoSmithKline and receives lecture honoraria and support for continuing medical education activities from AstraZeneca, Eisai, Forest Laboratories, Janssen, Lilly, Novartis, and Pfizer.; This study was supported by NIH grants T32AG026778, U01-AG15477, and P50-AG005146. NR 61 TC 35 Z9 36 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD APR PY 2012 VL 27 IS 4 BP 364 EP 374 DI 10.1002/gps.2723 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 904WC UT WOS:000301228600004 PM 21560159 ER PT J AU Goetz, M Surman, CBH Mlynarova, E Krsek, P AF Goetz, Michal Surman, Craig Bruce Hackett Mlynarova, Eliska Krsek, Pavel TI Status Epilepticus Associated With the Administration of Long-Acting Methylphenidate in a 7-Year-Old Girl SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; FOCAL CORTICAL DYSPLASIA; EPILEPSY; CLASSIFICATION; CHILDREN C1 [Goetz, Michal] Charles Univ Prague, Fac Med 2, Dept Child & Adolescent Psychiat, Univ Hosp Motol, Prague, Czech Republic. [Surman, Craig Bruce Hackett] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA USA. [Mlynarova, Eliska] Univ Hosp Motol, Dept Radiol, Prague, Czech Republic. [Krsek, Pavel] Charles Univ Prague, Fac Med 2, Dept Child Neurol, Univ Hosp Motol, Prague, Czech Republic. RP Goetz, M (reprint author), Charles Univ Prague, Fac Med 2, Dept Child & Adolescent Psychiat, Univ Hosp Motol, Prague, Czech Republic. EM michal.goetz@lfmotol.cuni.cz NR 14 TC 1 Z9 1 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2012 VL 32 IS 2 BP 300 EP 302 DI 10.1097/JCP.0b013e3182499a16 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 903MQ UT WOS:000301121100033 PM 22388167 ER PT J AU Nguyen, KH Subramanian, SV Sorensen, G Tsang, K Wright, RJ AF Kim Hanh Nguyen Subramanian, S. V. Sorensen, Glorian Tsang, Kathy Wright, Rosalind J. TI Influence of experiences of racial discrimination and ethnic identity on prenatal smoking among urban black and Hispanic women SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID SELF-REPORTED DISCRIMINATION; HEALTH RESEARCH; SOCIAL SUPPORT; BLOOD-PRESSURE; MENTAL-HEALTH; UNITED-STATES; BIRTH-WEIGHT; SOCIOECONOMIC-STATUS; AFRICAN-AMERICANS; NEW-HAMPSHIRE AB Background Although the prevalence of prenatal smoking among minority women exceeds the projected 2010 national objective, data on the determinants of prenatal smoking among minorities remain sparse. Methods We examined associations between self-reported experiences of racial discrimination on prenatal smoking among urban black and Hispanic women aged 18-44 years (n=677). Our main independent variable was created from the Experiences of Discrimination (EOD) scale. Multivariable logistic regression models were estimated to examine the relationship between EOD (moderate EOD as the referent group) and smoking for the entire sample and then separately by race/ethnicity adjusted for sociodemographic variables. We also examined the role of ethnic identity (EI) as a buffer to racial discrimination (n=405). Results The prevalence of smoking was 18.1% versus 10% for black and Hispanic women, respectively (p=0.002). There were no significant differences in the level of EOD based on race. In multivariate regressions, compared to those reporting moderate EOD, women reporting high discrimination (OR 2.64, 95% CI 1.25 to 5.60) had higher odds of smoking. In stratified analyses, this relationship remained significant only in black women. Results suggest that foreign-born Hispanic women with higher EI were less likely to smoke compared to their low-EI counterparts (3.5 vs 10.1%; p=0.08). Conclusion These are the first data in pregnant minority women showing an association between discrimination and increased risk of smoking particularly among black women. Ethnic identity and nativity status were also associated with smoking risk. Smoking cessation programmes should consider such factors among childbearing minority women. C1 [Kim Hanh Nguyen] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Med, San Francisco, CA 94111 USA. [Subramanian, S. V.; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Hlth & Human Dev, Boston, MA 02115 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tsang, Kathy; Wright, Rosalind J.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. [Wright, Rosalind J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Nguyen, KH (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Med, 1450 3rd St, San Francisco, CA 94111 USA. EM nguyenk@cc.ucsf.edu FU National Institutes of Health [R01 ES10932, U01 HL072494, R01 HL080674, NHLBI 1 K25 HL081275, NCI 3R01CA129096] FX The Asthma Coalition on Community, Environment, and Social Stress (ACCESS) study was funded by National Institutes of Health grants R01 ES10932, U01 HL072494, and R01 HL080674. Dr. Subramanian is supported by the National Institutes of Health Career Development Award (NHLBI 1 K25 HL081275). Dr. Nguyen is supported by the National Institutes of Health Diversity Supplement Award (NCI 3R01CA129096). NR 48 TC 14 Z9 14 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD APR PY 2012 VL 66 IS 4 BP 315 EP 321 DI 10.1136/jech.2009.107516 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 902NL UT WOS:000301045100007 PM 20974840 ER PT J AU Xu, HZ Berendsen, T Kim, K Soto-Gutierrez, A Bertheium, F Yarmush, ML Hertl, M AF Xu, Hongzhi Berendsen, Tim Kim, Karen Soto-Gutierrez, Alejandro Bertheium, Francios Yarmush, Martin L. Hertl, Martin TI Excorporeal Normothermic Machine Perfusion Resuscitates Pig DCD Livers with Extended Warm Ischemia SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE donor after cardiac death (DCD); normothermic machine perfusion (NMP); warm ischemia; transplantation; ATP ID HEART-BEATING DONOR; CARDIAC DEATH; ORGAN-PRESERVATION; RAT-LIVER; EXTRACORPOREAL PERFUSION; REPERFUSION INJURY; TRANSPLANTATION; DONATION; VIABILITY; GRAFTS AB Background. The shortage in donor livers has led to increased use of allografts derived from donation after cardiac death (DCD). The compromised viability in these livers leads to inferior post-transplantation allograft function and survival compared with donation after brain death (DBD) donor grafts. In this study, we reconditioned DCD livers using an optimized normothermic machine perfusion system. Methods. Livers from 12 Yorkshire pigs (20-30 kg) were subjected to either 0 min (WI-0 group, n = 6) or 60 min (WI-60 group, n = 6) of warm ischemia and 2 h of cold storage in UW solution, followed by 4 h of oxygenated sanguineous normothermic machine perfusion. Liver viability and metabolic function were analyzed hourly. Results. Warm ischemic livers showed elevated transaminase levels and reduced ATP concentration. After the start of machine perfusion, transaminase levels stabilized and there was recovery of tissue ATP, coinciding with an increase in bile production. These parameters reached comparable levels to the control group after 1 h of machine perfusion. Histology and gross morphology confirmed recovery of the ischemic allografts. Conclusion. Our data demonstrate that metabolic and functional parameters of livers with extended warm ischemic time (60 min) can be significantly improved using normothermic machine perfusion. We hereby compound the existing body of evidence that machine perfusion is a viable solution for reconditioning marginal organs. Published by Elsevier Inc. C1 [Xu, Hongzhi; Berendsen, Tim; Soto-Gutierrez, Alejandro; Bertheium, Francios; Yarmush, Martin L.] Shriners Burn Hosp Children Boston, Ctr Engn Med, Boston, MA 02114 USA. [Xu, Hongzhi; Kim, Karen; Hertl, Martin] Harvard Univ, Sch Med, Dept Surg, Transplantat Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Xu, HZ (reprint author), Shriners Burn Hosp Children Boston, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM hongzhi2008@gmail.com FU New England Organ Bank; Michael-van Vloten Stichting Foundation FX The authors acknowledge funding for this work by the New England Organ Bank. BT was funded by the Michael-van Vloten Stichting Foundation. NR 22 TC 29 Z9 39 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD APR PY 2012 VL 173 IS 2 BP E83 EP E88 DI 10.1016/j.jss.2011.09.057 PG 6 WC Surgery SC Surgery GA 906IQ UT WOS:000301339100005 PM 22099594 ER PT J AU Wu, XQ Zhou, J Rogers, AM Janne, PA Benedettini, E Loda, M Hodi, FS AF Wu, Xinqi Zhou, Jun Rogers, Andrew M. Jaenne, Pasi A. Benedettini, Elisa Loda, Massimo Hodi, F. Stephen TI c-Met, epidermal growth factor receptor, and insulin-like growth factor-1 receptor are important for growth in uveal melanoma and independently contribute to migration and metastatic potential SO MELANOMA RESEARCH LA English DT Article DE c-Met; epidermal growth factor receptor; insulin-like growth factor-1R; tumor migration; uveal melanoma ID TYROSINE KINASE RECEPTOR; CELL-PROLIFERATION; CARCINOMA CELLS; VASCULOGENIC MIMICRY; MALIGNANT-MELANOMA; THERAPEUTIC TARGET; MEDIATED MIGRATION; LIVER COLONIZATION; CASPASE CLEAVAGE; CROSS-TALK AB Uveal melanoma (UM) has a high propensity to develop hepatic metastases. We sought to define the mechanisms required for preferential liver homing and to understand further the biologic behavior of this disease. The Met tyrosine kinase receptor and its ligand hepatocyte growth factor are expressed in hepatocytes. We therefore considered Met/hepatocyte growth factor signaling as a candidate migration/growth factor for UM cells. We further explored the relationship between c-Met and other growth factor receptors prevalent in the liver and their roles in UM metastatic potential. UM cell lines were evaluated for c-Met, epidermal growth factor receptor (EGFR), and insulin-like growth factor-1R (IGF-1R) expression by immunoblotting, and gene amplification by comparative genomic hybridization and fluorescence in-situ hybridization. High c-Met, phosphorylated c-Met, and EGFR expression were noted in two of nine cell lines, independent of IGF-1R levels. Knockdown of c-Met decreased proliferation of high c-Met-expressing UM cells but did not induce apoptosis. Selective inhibitors of EGFR and IGF-1R decreased proliferation and induced apoptosis in UM cells regardless of the expression levels of c-Met, EGFR, and IGF-1R. Although c-Met, EGFR, and IGF-1R play proliferative roles, EGFR and IGF-1R are also critical for UM cell survival. High c-Met/EGFR-expressing cell lines possessed the greatest migration potential. c-Met knockdown and selective inhibitors of c-Met, EGFR, and IGF-1R revealed independent contribution of these receptors to migration. UM can be categorized by levels of c-Met and EGFR expression which are associated with migratory/invasiveness responses to soluble factors present at high levels in the liver. This provides biologic relevance for UM clinical behavior with potential therapeutic implications. Melanoma Res 22:123-132 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Wu, Xinqi; Zhou, Jun; Rogers, Andrew M.; Jaenne, Pasi A.; Loda, Massimo; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Wu, Xinqi; Zhou, Jun; Rogers, Andrew M.; Jaenne, Pasi A.; Loda, Massimo; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Xinqi; Zhou, Jun; Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, Melanoma Dis Ctr, Boston, MA USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Benedettini, Elisa] Univ Milan, Div Pathol, Dept Med Surg & Dent, Milan, Italy. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu FU Dana-Farber Cancer Institute; Doctorate School of Molecular Medicine, University of Milan FX This work was supported in part by The Ron Gelb Melanoma Research Fund (F. S. H.) and Malcolm, Emily Mac Naught Fund for Melanoma Research (F. S. H.) at Dana-Farber Cancer Institute, and by a fellowship of the Doctorate School of Molecular Medicine, University of Milan (E. B.). Dr Hodi has received clinical trial support from Pfizer. NR 43 TC 20 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD APR PY 2012 VL 22 IS 2 BP 123 EP 132 DI 10.1097/CMR.0b013e3283507ffd PG 10 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 905RG UT WOS:000301289600003 PM 22343486 ER PT J AU Cajigas, I Srinivasan, L AF Cajigas, Iahn Srinivasan, Lakshminarayan TI A State-Space Analysis for Reconstruction of Goal-Directed Movements Using Neural Signals (vol 18, pg 2465, 2006) SO NEURAL COMPUTATION LA English DT Correction C1 [Cajigas, Iahn] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Charlestown, MA 02129 USA. [Cajigas, Iahn] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Cajigas, Iahn] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Srinivasan, Lakshminarayan] Univ Calif Los Angeles, David Geffen Sch Med, Neural Signal Proc Lab, Dept Radiol, Los Angeles, CA 90095 USA. RP Cajigas, I (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Charlestown, MA 02129 USA. NR 1 TC 1 Z9 1 U1 1 U2 1 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD APR PY 2012 VL 24 IS 4 BP 1106 EP 1107 PG 2 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 904UK UT WOS:000301223200010 ER PT J AU Jansen, M Mohapatra, G Betensky, RA Keohane, C Louis, DN AF Jansen, M. Mohapatra, G. Betensky, R. A. Keohane, C. Louis, D. N. TI Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE atypical; classification; genetics; meningioma; pathology ID NEGATIVE PROGNOSTIC MARKER; INTRACRANIAL MENINGIOMA; ANAPLASTIC MENINGIOMAS; CLASSIFICATION; HYBRIDIZATION; RECURRENCE; BENIGN; TUMORS AB Aims: Atypical (World Health Organization grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array comparative genomic hybridization to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumours show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: Eighty-six completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow-up was obtained. Utilizing a dual-colour interphase fluorescence in situ hybridization assay, 1q gain was assessed using Bacterial Artificial Chromosome probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas. C1 [Jansen, M.; Mohapatra, G.; Louis, D. N.] Massachusetts Gen Hosp, James Homer Wright Labs, Pathol Serv, Boston, MA 02114 USA. [Louis, D. N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mohapatra, G.; Louis, D. N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Betensky, R. A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Jansen, M.] Beaumont Hosp, Dept Neuropathol, Dublin 9, Ireland. [Keohane, C.] Cork Univ Hosp, Dept Neuropathol, Cork, Ireland. RP Louis, DN (reprint author), Massachusetts Gen Hosp, James Homer Wright Labs, Pathol Serv, WRN 225, Boston, MA 02114 USA. EM dlouis@partners.org FU NCI NIH HHS [R01 CA075971] NR 29 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD APR PY 2012 VL 38 IS 2 BP 213 EP 219 DI 10.1111/j.1365-2990.2011.01222.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 902PV UT WOS:000301051300008 PM 21988727 ER PT J AU Javitt, DC Buchanan, RW Keefe, RSE Kern, R McMahon, RP Green, MF Lieberman, J Goff, DC Csernansky, JG McEvoy, JP Jarskog, F Seidman, LJ Gold, JM Kimhy, D Nolan, KS Barch, DS Ball, MP Robinson, J Marder, SR AF Javitt, Daniel C. Buchanan, Robert W. Keefe, Richard S. E. Kern, Robert McMahon, Robert P. Green, Michael F. Lieberman, Jeffrey Goff, Donald C. Csernansky, John G. McEvoy, Joseph P. Jarskog, Fred Seidman, Larry J. Gold, James M. Kimhy, David Nolan, Karen S. Barch, Deanna S. Ball, M. Patricia Robinson, James Marder, Stephen R. TI Effect of the neuroprotective peptide davunetide (AL-108) on cognition and functional capacity in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2009 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol (ACNP) DE Schizophrenia; Cognition; Microtubule; Neurite ID TRANSGENIC MOUSE MODEL; RATING-SCALE; TAU-HYPERPHOSPHORYLATION; CORTICAL DEVELOPMENT; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; DISC1; NAP AB Background: Cognitive dysfunction is a key predictor of functional disability in schizophrenia. Davunetide (AL-108, NAP) is an intranasally administered peptide currently being developed for treatment of Alzheimer's disease and related disorders. This study investigates effects of davunetide on cognition in schizophrenia. Method: Sixty-three subjects with schizophrenia received davunetide at one of two different doses (5, 30 mg) or placebo for 12 weeks in a multicenter, double-blind, parallel-group randomized clinical trial. The MATRICS Consensus Cognitive Battery (MCCB) assessed cognitive effects. The UCSD Performance-based Skills Assessment (UPSA) and the Schizophrenia Cognition Rating Scale (SCoRS) assessed functional capacity. Subjects continued their current antipsychotic treatment during the trial. Results: There were no significant differences in MCCB change between davunetide and placebo over the three treatment arms (p=.45). Estimated effect-size (d) values were .34 and .21 favoring the 5 and 30 mg doses vs. placebo, respectively. For UPSA, there was a significant main effect of treatment across study arms (p=.048). Between-group effect size (d) values were .74 and .48, favoring the 5 and 30 mg doses, respectively. No significant effects were observed on the SCoRS or on symptom ratings. No significant side effects or adverse events were observed. Conclusion: Davunetide was well tolerated. Effects of davunetide on MCCB-rated cognition were not significant relative to placebo. In contrast, a significant beneficial effect was detected for the UPSA. Based upon effect-size considerations, sample sizes of at least 45-50 subjects/group would be required to obtain significant effects on both MCCB and UPSA, providing guidance for continued clinical development in schizophrenia. (C) 2011 Elsevier B.V. All rights reserved. C1 [Javitt, Daniel C.; Nolan, Karen S.; Robinson, James] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Buchanan, Robert W.; McMahon, Robert P.; Gold, James M.; Ball, M. Patricia] Maryland Psychiat Res Ctr, Catonsville, MD USA. [Keefe, Richard S. E.; McEvoy, Joseph P.] Duke Univ, Med Ctr, Durham, NC USA. [Kern, Robert; Green, Michael F.; Marder, Stephen R.] Univ Calif Los Angeles, Los Angeles, CA USA. [Lieberman, Jeffrey; Jarskog, Fred; Kimhy, David] Columbia Univ, Med Ctr, New York, NY USA. [Goff, Donald C.; Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Csernansky, John G.; Barch, Deanna S.] Washington Univ, St Louis, MO USA. RP Javitt, DC (reprint author), Nathan S Kline Inst Psychiat Res, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA. EM javitt@nki.rfmh.org RI McMahon, Robert/C-5462-2009; Barch, Deanna/G-8638-2013; OI Kimhy, David/0000-0001-7735-9378 FU NIMH NIH HHS [N01 MH041003]; PHS HHS [HHSN 27820044 1003C] NR 36 TC 53 Z9 53 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 IS 1-3 BP 25 EP 31 DI 10.1016/j.schres.2011.11.001 PG 7 WC Psychiatry SC Psychiatry GA 904LS UT WOS:000301198800005 PM 22169248 ER PT J AU Levitt, JJ Alvarado, JL Nestor, PG Rosow, L Pelavin, PE McCarley, RW Kubicki, M Shenton, ME AF Levitt, James J. Alvarado, Jorge L. Nestor, Paul G. Rosow, Laura Pelavin, Paula E. McCarley, Robert W. Kubicki, Marek Shenton, Martha E. TI Fractional anisotropy and radial diffusivity: Diffusion measures of white matter abnormalities in the anterior limb of the internal capsule in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Diffusion tensor imaging; Magnetic resonance imaging; Anterior limb of the internal capsule; Thalamus; Prefrontal cortex ID MEDIODORSAL THALAMIC NUCLEUS; FRONTAL-SUBCORTICAL CIRCUITS; POOR-OUTCOME SCHIZOPHRENIA; NEURON NUMBER; BASAL GANGLIA; PREFRONTAL CORTEX; CORPUS-CALLOSUM; CAUDATE-NUCLEUS; ECHO-PLANAR; VOLUME AB Introduction: Higher cognitive functioning is mediated by frontal-subcortical cognitive and limbic feedback sub-loops. The thalamo-cortical projection through the anterior limb of the internal capsule (ALIC) serves as the final step in these feedback sub-loops. We evaluated abnormalities in the ALIC fiber tract in schizophrenia using both structural MRI and diffusion tensor imaging (DTI). Methods: 20 chronic schizophrenia patients and 22 male, normal controls group matched for handedness, age, and parental SES, underwent structural and DTI brain imaging on a 1.5 Tesla GE system. We manually measured ALIC volume normalized for intracranial contents (ICC) using structural brain images and then registered these high resolution structural brain scan derived ALIC label maps to DTI space allowing for the measurement in the ALIC of diffusion indices including, fractional anisotropy (FA) mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Results: We found in the ALIC of chronic schizophrenia subjects, compared with normal controls, bilaterally lower FA and bilaterally higher RD, but no differences in AD, MD, or relative volume. Cognitive correlations in schizophrenia patients showed, in particular, that higher left ALIC FA correlated positively with better verbal and nonverbal declarative/episodic memory performance. Discussion: Using a novel approach to assess both diffusion and volume measures in the ALIC in schizophrenia, we found abnormalities in measures of diffusion, but not volume, supporting their importance as sensitive indices of abnormalities in white matter fiber bundles in schizophrenia. Our findings also support the role of ALIC white matter tract FA abnormalities in declarative/episodic memory in schizophrenia. (C) 2011 Elsevier B.V. All rights reserved. C1 [Levitt, James J.; Nestor, Paul G.; McCarley, Robert W.; Kubicki, Marek; Shenton, Martha E.] VA Boston Healthcare Syst, Brockton Div, Dept Psychiat, Clin Neurosci Div,Lab Neurosci, Brockton, MA 02301 USA. [Levitt, James J.; Nestor, Paul G.; McCarley, Robert W.; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alvarado, Jorge L.; Rosow, Laura; Pelavin, Paula E.; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Surg Planning Lab,MRI Div,Dept Radiol, Boston, MA 02115 USA. RP Levitt, JJ (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat 116A, 940 Belmont St, Brockton, MA 02301 USA. EM james_levitt@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Department of Veteran Affairs; Research Enhancement Award; VA Schizophrenia Center; National Institutes of Health [K05 MH 700047, R01 MH 50747, R01 MH 40799, RO3 MH068464-01] FX This work was supported in part by Department of Veteran Affairs Awards (Merits, JJL, MES, RWM; Research Enhancement Award Program, RWM, MES), by a VA Schizophrenia Center grant (RWM, MES), by a Middleton Award (RWM) from the Department of Veterans Affairs, by grants from the National Institutes of Health (K05 MH 700047 and R01 MH 50747 to MES, R01 MH 40799 to RWM, RO3 MH068464-01 to MK). NR 57 TC 30 Z9 31 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2012 VL 136 IS 1-3 BP 55 EP 62 DI 10.1016/j.schres.2011.09.009 PG 8 WC Psychiatry SC Psychiatry GA 904LS UT WOS:000301198800010 PM 22019073 ER PT J AU Chakraborty, N Menze, MA Elmoazzen, H Vu, HL Yarmush, ML Hand, SC Toner, M AF Chakraborty, Nilay Menze, Michael A. Elmoazzen, Heidi Vu, Halong Yarmush, Martin L. Hand, Steven C. Toner, Mehmet TI Trehalose transporter from African chironomid larvae improves desiccation tolerance of Chinese hamster ovary cells SO CRYOBIOLOGY LA English DT Article DE Trehalose; Desiccation tolerance; Lyopreservation; Anhydrobiosis ID MAMMALIAN-CELLS; INTRACELLULAR TREHALOSE; WATER-STRESS; ANHYDROBIOSIS; STABILIZATION; PRESERVATION; DEHYDRATION; EXPRESSION; PROTEINS AB Dry preservation has been explored as an energy-efficient alternative to cryopreservation, but the high sensitivity of mammalian cells to desiccation stress has been one of the major hurdles in storing cells in the desiccated state. An important strategy to reduce desiccation sensitivity involves use of the disaccharide trehalose. Trehalose is known to improve desiccation tolerance in mammalian cells when present on both sides of the cell membrane. Because trehalose is membrane impermeant the development of desiccation strategies involving this promising sugar is hindered. We explored the potential of using a high-capacity trehalose transporter (TRET1) from the African chironomid Polypedilum vanderplanki [21] to introduce trehalose into the cytoplasm of mammalian cells and thereby increase desiccation tolerance. When Chinese hamster ovary cells (CHO) were stably transfected with TRET1 (CHO-TRET1 cells) and incubated with 0.4 M trehalose for 4 h at 37 degrees C, a sevenfold increase in trehalose uptake was observed compared to the wild-type CHO cells. Following trehalose loading, desiccation tolerance was investigated by evaporative drying of cells at 14% relative humidity. After desiccation to 2.60 g of water per gram dry weight, a 170% increase in viability and a 400% increase in growth (after 7 days) was observed for CHO-TRET1 relative to control CHO cells. Our results demonstrate the beneficial effect of intracellular trehalose for imparting tolerance to partial desiccation. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chakraborty, Nilay; Elmoazzen, Heidi; Vu, Halong; Yarmush, Martin L.; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Chakraborty, Nilay; Elmoazzen, Heidi; Vu, Halong; Yarmush, Martin L.; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Menze, Michael A.] Eastern Illinois Univ, Dept Biol Sci, Charleston, IL 61920 USA. [Hand, Steven C.] Louisiana State Univ, Div Cellular Dev & Integrat Biol, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Chakraborty, Nilay; Elmoazzen, Heidi; Vu, Halong; Yarmush, Martin L.; Toner, Mehmet] Shriners Burn Hosp, Boston, MA 02114 USA. RP Chakraborty, N (reprint author), Harvard Univ, Sch Med, 51 Blossom St, Boston, MA 02114 USA. EM chakraborty.nilay@mgh.harvard.edu; mtoner@hms.harvard.edu RI Chakraborty, Nilay/C-3118-2009; OI Menze, Michael/0000-0003-1072-5462 FU National Institutes of Health [2 RO1 DK046270-14A1, 5 R01 GM086886] FX This work was supported by National Institutes of Health Grants 2 RO1 DK046270-14A1 and 5 R01 GM086886. NR 29 TC 9 Z9 9 U1 1 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD APR PY 2012 VL 64 IS 2 BP 91 EP 96 DI 10.1016/j.cryobiol.2011.11.007 PG 6 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 900CW UT WOS:000300865200003 PM 22155480 ER PT J AU Sonpavde, G Di Lorenzo, G Higano, CS Kantoff, PW Madan, R Shore, ND AF Sonpavde, Guru Di Lorenzo, Giuseppe Higano, Celestia S. Kantoff, Philip W. Madan, Ravi Shore, Neal D. TI The Role of Sipuleucel-T in Therapy for Castration-Resistant Prostate Cancer: A Critical Analysis of the Literature SO EUROPEAN UROLOGY LA English DT Article DE Immunotherapy; Prostate cancer; Sipuleucel-T; CTLA-4; PD-1; Prostvac VF Tricom; Ipilimumab ID COLONY-STIMULATING FACTOR; PHASE-I TRIAL; CELLULAR IMMUNOTHERAPY; RECEPTOR ACTIVATOR; ACID-PHOSPHATASE; DENDRITIC CELLS; WORKING GROUP; END-POINTS; ANTIGEN; SURVIVAL AB Context: Sipuleucel-T, an autologous antigen-presenting cell vaccine loaded with prostate acid phosphatase conjugated with granulocyte-macrophage colony-stimulating factor (GM-CSF), yielded a survival advantage in men with metastatic castration-resistant prostate cancer (mCRPC). Objective: Critically analyze the role of sipuleucel-T in therapy for mCRPC. Evidence acquisition: A systematic review of the literature was performed in June 2011 using Medline and an abstract search of major cancer conferences. The search strategy included the terms sipuleucel-T, APC-8015, castration-resistant, prostate cancer, and immunotherapy. Evidence synthesis: The era of targeted immunotherapy was initiated with the regulatory approval in 2010 of sipuleucel-T for asymptomatic and minimally symptomatic mCRPC. The median survival was prolonged by 4.1 mo (25.8 vs 21.7 mo; hazard ratio: 0.78; 95% confidence interval, 0.61-0.98; p = 0.03), coupled with an improvement in 3-yr survival (31.7% vs 23.0%). Outcomes were characterized by the lack of tumor regression or delay in progression. Further development is proceeding in earlier stages of prostate cancer and in the context of a host of emerging agents. Conclusions: The addition of sipuleucel-T, an immunotherapeutic agent, to the armamentarium represents a paradigm shift in therapy for mCRPC. The rational combination and proper sequencing of sipuleucel-T with other newly approved agents (abiraterone acetate, cabazitaxel) and emerging agents (MDV3100, TAK-700, ipilimumab) will be important to evaluate. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Sonpavde, Guru] Texas Oncol, Houston, TX USA. [Sonpavde, Guru] Vet Affairs Med Ctr, Houston, TX 77030 USA. [Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA. [Di Lorenzo, Giuseppe] Univ Naples Federico 2, Naples, Italy. [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA. [Madan, Ravi] NCI, Bethesda, MD 20892 USA. [Shore, Neal D.] Grand Strand Urol, Myrtle Beach, SC USA. RP Sonpavde, G (reprint author), 501 Med Ctr Blvd, Webster, TX 77598 USA. EM guru.sonpavde@usoncology.com FU Bellicum Pharmaceuticals; Dendreon; Medivation; Cougar Biotech; Dendreon Corporation FX I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Guru Sonpavde receives research support for his institution from Bellicum Pharmaceuticals and is on the speakers' bureau or advisory boards for Dendreon, Centocor Biotech, Amgen, Novartis, and Sanofi-Aventis. Giuseppe Di Lorenzo receives research support from, and is on the advisory board for, Dendreon. Celestia S. Higano receives research support for her institution from Dendreon, Medivation, and Cougar Biotech and is on the advisory board for Dendreon, Medivation, and Amgen. Philip W. Kantoff is a consultant to Dendreon, Bellicum Pharmaceuticals, and BN-IT. Neal D. Shore receives research support from, and is on the advisory board for, Dendreon.; Dendreon Corporation sponsored the trials that are discussed in this review. NR 51 TC 12 Z9 12 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD APR PY 2012 VL 61 IS 4 BP 639 EP 647 DI 10.1016/j.eururo.2011.10.027 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 899TB UT WOS:000300838000013 PM 22036643 ER PT J AU Sonpavde, G Di Lorenzo, G Higano, CS Kantoff, PW Madan, RA Shore, ND AF Sonpavde, Guru Di Lorenzo, Giuseppe Higano, Celestia S. Kantoff, Philip W. Madan, Ravi A. Shore, Neal D. TI Reply form Authors re: Bertrand Tombal. Continuous Improvement Versus Innovation: The Case for Sipuleucel-T. Eur Urol 2012;61:648-9 SO EUROPEAN UROLOGY LA English DT Editorial Material ID RESISTANT PROSTATE-CANCER; IMMUNOTHERAPY; TRIAL C1 [Sonpavde, Guru] Texas Oncol, Houston, TX USA. [Sonpavde, Guru] Vet Affairs Med Ctr, Houston, TX 77030 USA. [Sonpavde, Guru] Baylor Coll Med, Houston, TX 77030 USA. [Di Lorenzo, Giuseppe] Univ Naples Federico II, Naples, Italy. [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA. [Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA. [Madan, Ravi A.] NCI, Bethesda, MD 20892 USA. [Shore, Neal D.] Grand Strand Urol, Myrtle Beach, SC USA. RP Sonpavde, G (reprint author), 501 Med Ctr Blvd, Webster, TX 77598 USA. EM guru.sonpavde@usoncology.com NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD APR PY 2012 VL 61 IS 4 BP 650 EP 651 DI 10.1016/j.eururo.2011.12.007 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 899TB UT WOS:000300838000015 ER PT J AU Efstathiou, JA Spiegel, DY Shipley, WU Heney, NM Kaufman, DS Niemierko, A Coen, JJ Skowronski, RY Paly, JJ McGovern, FJ Zietman, AL AF Efstathiou, Jason A. Spiegel, Daphna Y. Shipley, William U. Heney, Niall M. Kaufman, Donald S. Niemierko, Andrzej Coen, John J. Skowronski, Rafi Y. Paly, Jonathan J. McGovern, Francis J. Zietman, Anthony L. TI Long-Term Outcomes of Selective Bladder Preservation by Combined-Modality Therapy for Invasive Bladder Cancer: The MGH Experience SO EUROPEAN UROLOGY LA English DT Article DE Bladder cancer; Chemotherapy; Combined-modality therapy; Cystectomy; Radiation therapy ID QUALITY-OF-LIFE; RADICAL CYSTECTOMY; ORGAN PRESERVATION; NEOADJUVANT CHEMOTHERAPY; TRANSURETHRAL SURGERY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; II TRIAL; RADIOTHERAPY; RTOG AB Background: Whether organ-conserving treatment by combined-modality therapy (CMT) achieves comparable long-term survival to radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) is largely unknown. Objective: Report long-term outcomes of patients with muscle-invasive BCa treated by CMT. Design, setting, and participants: We conducted an analysis of successive prospective protocols at the Massachusetts General Hospital (MGH) treating 348 patients with cT2-4a disease between 1986 and 2006. Median follow-up for surviving patients was 7.7 yr. Interventions: Patients underwent concurrent cisplatin-based chemotherapy and radiation therapy (RT) after maximal transurethral resection of bladder tumor (TURBT) plus neoadjuvant or adjuvant chemotherapy. Repeat biopsy was performed after 40 Gy, with initial tumor response guiding subsequent therapy. Those patients showing complete response (CR) received boost chemotherapy and RT. One hundred two patients (29%) underwent RC-60 for less than CR and 42 for recurrent invasive tumors. Measurements: Disease-specific survival (DSS) and overall survival (OS) were evaluated using the Kaplan-Meier method. Results and limitations: Seventy-two percent of patients (78% with stage T2) had CR to induction therapy. Five-, 10-, and 15-yr DSS rates were 64%, 59%, and 57% (T2 = 74%, 67%, and 63%; T3-4 = 53%, 49%, and 49%), respectively. Five-, 10-, and 15-yr OS rates were 52%, 35%, and 22% (T2: 61%, 43%, and 28%; T3-4 = 41%, 27%, and 16%), respectively. Among patients showing CR, 10-yr rates of noninvasive, invasive, pelvic, and distant recurrences were 29%, 16%, 11%, and 32%, respectively. Among patients undergoing visibly complete TURBT, only 22% required cystectomy (vs 42% with incomplete TURBT; log-rank p < 0.001). In multivariate analyses, clinical T-stage and CR were significantly associated with improved DSS and OS. Use of neoadjuvant chemotherapy did not improve outcomes. No patient required cystectomy for treatment-related toxicity. Conclusions: CMT achieves a CR and preserves the native bladder in > 70% of patients while offering long-term survival rates comparable to contemporary cystectomy series. These results support modern bladder-sparing therapy as a proven alternative for selected patients. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Efstathiou, Jason A.; Spiegel, Daphna Y.; Shipley, William U.; Niemierko, Andrzej; Coen, John J.; Skowronski, Rafi Y.; Paly, Jonathan J.; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Heney, Niall M.; McGovern, Francis J.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Kaufman, Donald S.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 32 TC 117 Z9 119 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD APR PY 2012 VL 61 IS 4 BP 705 EP 711 DI 10.1016/j.eururo.2011.11.010 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 899TB UT WOS:000300838000026 PM 22101114 ER PT J AU Efstathiou, JA Shipley, WU Zietman, AL AF Efstathiou, Jason A. Shipley, William U. Zietman, Anthony L. TI Reply from Authors re: Giuseppe Simone, Michele Gallucci. Multimodality Treatment Versus Radical Cystectomy: Bladder Sparing at Cost of Life? Eur Urol 2012;61:712-3 Bladder-Sparing Therapy: The Urologist Doth Protest Too Much, Methinks SO EUROPEAN UROLOGY LA English DT Editorial Material ID CANCER; TRIAL C1 [Efstathiou, Jason A.; Shipley, William U.; Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD APR PY 2012 VL 61 IS 4 BP 713 EP 714 DI 10.1016/j.eururo.2011.12.045 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 899TB UT WOS:000300838000028 ER PT J AU Bader, MJ Eisner, B Porpiglia, F Preminger, GM Tiselius, HG AF Bader, Markus J. Eisner, Brian Porpiglia, Francesco Preminger, Glen M. Tiselius, Hans-Goran TI Contemporary Management of Ureteral Stones SO EUROPEAN UROLOGY LA English DT Review DE Ureteral calculi; Medical expulsive therapy (MET); Lithotripsy; Ureterorenoscopy; Extracorporal shockwave lithotripsy (SWL); Antegrade percutaneous litholapaxie (PCNL); Laparoscopic stone treatment ID SHOCK-WAVE LITHOTRIPSY; HOLMIUM LASER LITHOTRIPSY; URINARY-TRACT CALCULI; PROSPECTIVE RANDOMIZED-TRIAL; YAG LITHOTRIPSY; MEDICAL THERAPY; IN-VITRO; URETEROSCOPIC LITHOTRIPSY; ENDOUROLOGICAL MANAGEMENT; RETROGRADE URETEROSCOPY AB Context: Ureteral calculi represent a common condition that urologists encounter in everyday practice. Several treatment options are available for calculi that do not pass spontaneously or are unlikely to do so. Objective: In this nonsystematic review, we summarize the existing data on contemporary management of ureteral stones focusing on medical expulsive therapy (MET) and different treatment modalities. Evidence acquisition: A PubMed search was performed. We reviewed the recent literature on the management of ureteral calculi. Articles were considered between 1997 and 2011. Older studies were included selectively if historically relevant. Evidence synthesis: For stones that do not pass spontaneously or with MET, shock wave lithotripsy (SWL) and ureteroscopy (URS) are the most common and efficient treatment modalities. Both techniques have obvious advantages and disadvantages as well as different patterns of complications. For select cases or patients, other modalities may be useful. Conclusions: Ureteral stones of up to 10 mm and eligible for observation may be offered MET. For most ureteral calculi that require treatment, advances in SWL and URS allow urologists to take a minimally invasive approach. Other more invasive treatments are reserved for select "nonstandard" cases. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Bader, Markus J.] Univ Munich, Dept Urol, Klinikum Grosshadern, D-81377 Munich, Germany. [Eisner, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol,Kidney Stone Ctr, Boston, MA USA. [Porpiglia, Francesco] Univ Turin, CDU Urol Dipartimento Sci Clin & Biol, Fac Med & Chirurg San Luigi Gonzaga, Turin, Italy. [Preminger, Glen M.] Duke Univ, Med Ctr, Dept Surg, Div Urol, Durham, NC 27710 USA. [Tiselius, Hans-Goran] Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. RP Bader, MJ (reprint author), Univ Munich, Dept Urol, Klinikum Grosshadern, Marchioninistr 15, D-81377 Munich, Germany. EM markus.bader@med.uni-muenchen.de RI Preminger, Glenn/B-3990-2011; OI Preminger, Glenn/0000-0003-4287-602X; PORPIGLIA, Francesco/0000-0002-0752-4857 NR 103 TC 51 Z9 60 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD APR PY 2012 VL 61 IS 4 BP 764 EP 772 DI 10.1016/j.eururo.2012.01.009 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 899TB UT WOS:000300838000041 PM 22266271 ER PT J AU Torriani, M Townsend, E Thomas, BJ Bredella, MA Ghomi, RH Tseng, BS AF Torriani, Martin Townsend, Elise Thomas, Bijoy J. Bredella, Miriam A. Ghomi, Reza H. Tseng, Brian S. TI Lower leg muscle involvement in Duchenne muscular dystrophy: an MR imaging and spectroscopy study SO SKELETAL RADIOLOGY LA English DT Article DE Duchenne muscular dystrophy; MR imaging; MR spectroscopy; Fatty atrophy; Muscle ID 6-MINUTE WALK TEST; QUANTIFICATION; TISSUE; SIZE; FAT AB To describe the involvement of lower leg muscles in boys with Duchenne muscular dystrophy (DMD) by using MR imaging (MRI) and spectroscopy (MRS) correlated to indices of functional status. Nine boys with DMD (mean age, 11 years) and eight healthy age- and BMI-matched boys (mean age, 13 years) prospectively underwent lower leg MRI, 1H-MRS of tibialis anterior (TA) and soleus (SOL) for lipid fraction measures, and 31P-MRS for pH and high-energy phosphate measures. DMD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk. DMD subjects had highest fatty infiltration scores in peroneal muscles, followed by medial gastrocnemius and soleus. Compared to controls, DMD boys showed higher intramuscular fat (P = 0.04), lipid fractions of TA and SOL (P = 0.02 and 0.003, respectively), pH of anterior compartment (P = 0.0003), and lower phosphocreatine/inorganic phosphorus ratio of posterior compartment (P = 0.02). The Vignos rating correlated with TA (r = 0.79, P = 0.01) and SOL (r = 0.71, P = 0.03) lipid fractions. The 6MWT correlated with fatty infiltration scores of SOL (r = -0.76, P = 0.046), medial (r = -0.80, P = 0.03) and lateral (r = -0.84, P = 0.02) gastrocnemius, intramuscular fat (r = -0.80, P = 0.03), and SOL lipid fraction (r = -0.89, P = 0.007). Time to walk 10 m correlated with anterior compartment pH (r = 0.78, P = 0.04). Lower leg muscles of boys with DMD show a distinct involvement pattern and increased adiposity that correlates with functional status. Lower leg MRI and 1H-MRS studies may help to noninvasively demonstrate the severity of muscle involvement. C1 [Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Torriani, Martin; Thomas, Bijoy J.; Bredella, Miriam A.; Ghomi, Reza H.] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Torriani, Martin; Thomas, Bijoy J.; Bredella, Miriam A.; Ghomi, Reza H.; Tseng, Brian S.] Harvard Univ, Sch Med, Boston, MA USA. [Townsend, Elise] MGH Inst Hlth Profess, Boston, MA USA. [Tseng, Brian S.] Massachusetts Gen Hosp, Pediat Neuromuscular Clin, Boston, MA 02114 USA. [Tseng, Brian S.] Novartis Inst Biomed Res, Cambridge, MA USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM mtorriani@hms.harvard.edu OI Hosseini Ghomi, Reza/0000-0003-4369-8237 FU Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University; Harvard University's academic health care centers FX We thank the boys and their families for their dedication and cooperation during this study. This work was conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). NR 24 TC 37 Z9 39 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD APR PY 2012 VL 41 IS 4 BP 437 EP 445 DI 10.1007/s00256-011-1240-1 PG 9 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 899YD UT WOS:000300851700009 PM 21800026 ER PT J AU Kaz, AM Luo, YX Dzieciatkowski, S Chak, A Willis, JE Upton, MP Leidner, RS Grady, WM AF Kaz, Andrew M. Luo, Yanxin Dzieciatkowski, Slavomir Chak, Amitabh Willis, Joseph E. Upton, Melissa P. Leidner, Rom S. Grady, William M. TI Aberrantly methylated PKP1 in the progression of Barrett's esophagus to esophageal adenocarcinoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; DNA METHYLATION; CANCER; PLAKOPHILIN-1; EXPRESSION; ADHESION; CADHERIN; DYSPLASIA; DESMOSOME; PROTEINS AB The aberrant DNA methylation of tumor suppressor genes occurs frequently in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) and likely affects the initiation and progression of BE to EAC. In the present study, we discovered PKP1 as a novel methylated gene in EAC and then investigated the role of loss of PKP1, a constituent of the desmosome complex found in stratified epithelial layers, on the behavior of Barrett's esophagus and esophageal adenocarcinoma cells. By using primary esophageal tissue samples we determined that PKP1 was rarely methylated in normal squamous esophagus (5/55; 9.1%) and BE (5/39; 12.8%) and more frequently methylated in Barrett's esophagus with high-grade dysplasia (HGD) or EAC (20/60; 33.3%; P < 0.05). Furthermore, PKP1 levels were decreased in BE and HGD/EAC cases compared to normal squamous esophagus cases. Knockdown of PKP1 in the BE cell lines CP-A and CP-D (both normally express PKP1) resulted in increased cell motility. Thus, PKP1 loss secondary to promoter methylation, as well as other mechanisms, may promote the progression of BE to EAC in a subset of patients via decreased desmosome assembly and increased cell motility. (c) 2011 Wiley Periodicals, Inc. C1 [Kaz, Andrew M.; Luo, Yanxin; Dzieciatkowski, Slavomir; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. [Luo, Yanxin] Sixth Affiliated Hosp, Dept Colorectal Surg, Guangzhou, Guangdong, Peoples R China. [Luo, Yanxin] Sun Yat Sen Univ, Gastrointestinal Inst, Guangzhou 510275, Guangdong, Peoples R China. [Chak, Amitabh; Leidner, Rom S.] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. [Willis, Joseph E.] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA. [Upton, Melissa P.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP Grady, WM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D4-100, Seattle, WA 98109 USA. EM akaz@fhcrc.org; wgrady@fhcrc.org FU NIH/NIDDK [5K08DK080630]; Takeda Pharmaceuticals North America; NIH [R21 5R21CA135692]; K24 Midcareer Award in Patient Oriented Research [DK002800]; Burroughs Wellcome Fund; NIH/NCI [U54CA143682, U01CA152756, U54CA163060] FX The authors thank Dr. James Wahl at the University of Nebraska Medical center for his generous gift of PKP1 antibody. This work was supported by NIH/NIDDK grant 5K08DK080630 (A. K.), an Investigator Initiated Research Award (Takeda Pharmaceuticals North America; W. M. G.), NIH R21 5R21CA135692 (A. C.), and a K24 Midcareer Award in Patient Oriented Research DK002800 (A. C.). Additional support was provided by Burroughs Wellcome Fund (W. M. G.), by NIH/NCI grant U54CA143682 (W. M. G.), U01CA152756 (W. M. G.), and U54CA163060 (W. M. G. and A.K.). NR 40 TC 9 Z9 9 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 2012 VL 51 IS 4 BP 384 EP 393 DI 10.1002/gcc.21923 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 889CL UT WOS:000300051000007 PM 22170739 ER PT J AU Chen, YI Ren, JQ Kaptchuk, TJ Kwong, KK AF Chen, Y. Iris Ren, Jia-Qian Kaptchuk, Ted J. Kwong, Kenneth K. TI Restoring cerebral dopamine homeostasis by electrical forepaw stimulation: An fMRI study SO SYNAPSE LA English DT Article DE fMRI; dopamine; Parkinson's disease; forepaw stimulation ID CROSS-SECTIONAL FMRI; PARKINSONS-DISEASE; FUNCTIONAL CONNECTIVITY; PHARMACOLOGICAL MRI; 6-OHDA LESION; RELEASE; RATS; MICRODIALYSIS; ACUPUNCTURE; MODULATION AB Deviation of dopamine homeostasis is known to be associated with disorders like drug addiction and Parkinson's disease. As dopamine function is tightly regulated within the basal ganglia circuitry, cortical perturbation would lead to modulation of dopaminergic activity in the striatum. We proposed and tested if somatosensory activity such as forepaw stimulation could modulate dopaminergic function. Specifically, we tested in rats if electrical forepaw stimulation (EFS) could attenuate dopamine release in the brain if dopamine is excessive, and boost dopamine release if dopamine is deficient. We had previously demonstrated that EFS effectively attenuated excessive DA concentration in the striatum. We now show in this manuscript with fMRI that EFS boosted DA release on two DA deficient conditions: (1) with quinpirole challenge, and (2) partial Parkinsonism model (PD). Quinpirole alone decreased dopamine release and thus the cerebral blood volume (CBV) that was restored by EFS. EFS also succeeded in increasing CBV in the basal-ganglia circuitry of the PD rats, but not in the controls. Context-dependent connectivity analysis showed increased connectivity during the basal state in the PD rats, compared with the controls. This enhanced yet abnormal connectivity of PD rats was reduced post-EFS. Our results suggest that EFS resets the deficient DA system by partially increasing DA release, in the meanwhile lessening the need for recruiting extra functional network in the basal ganglia circuitry. This study shows not only the capacity of peripheral stimulation to perturb neurotransmitter function, but also the potential of peripheral stimulation to restore neurotransmitter homeostasis. Synapse, 2012. (c) 2011 Wiley Periodicals, Inc. C1 [Chen, Y. Iris; Ren, Jia-Qian; Kwong, Kenneth K.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Chen, Y. Iris; Ren, Jia-Qian; Kaptchuk, Ted J.; Kwong, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA. [Kaptchuk, Ted J.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Chen, YI (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM iris@nmr.mgh.harvard.edu FU NIH, NCCAM [1R21AT004455-01A2, K24 AT004095] FX Contract grant sponsor: NIH, NCCAM; Contract grant numbers: 1R21AT004455-01A2 and K24 AT004095 NR 35 TC 3 Z9 3 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 2012 VL 66 IS 4 BP 331 EP 339 DI 10.1002/syn.21516 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 883FS UT WOS:000299620200006 PM 22170513 ER PT J AU Li, XB Alapati, V Jackson, C Xia, SG Bertisch, HC Branch, CA DeLisi, LE AF Li, Xiaobo Alapati, Venkatesh Jackson, Courtney Xia, Shugao Bertisch, Hilary C. Branch, Craig A. DeLisi, Lynn E. TI Structural abnormalities in language circuits in genetic high-risk subjects and schizophrenia patients SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Schizophrenia; Genetic high risk; Structural abnormality; Language circuits; Magnetic resonance imaging (MRI) ID ANTIPSYCHOTIC-NAIVE SCHIZOPHRENIA; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; GRAY-MATTER; CORTICAL SURFACE; SCHIZOAFFECTIVE DISORDER; VULNERABILITY INDICATOR; LIKELIHOOD ESTIMATION; COORDINATE SYSTEM AB Schizophrenia is a severe psychiatric disorder with a strong genetic predisposition. Structural and functional brain deficits throughout the cerebral cortex, particularly in the language-processing associated brain regions, are consistently reported. Recently, increasing evidence from magnetic resonance imaging (MRI) studies suggests that healthy relatives of schizophrenia patients also show structural brain abnormalities in cortical gray matter (GM) volume and thickness, suggesting that this may be associated with an unexpressed genetic liability for the disorder. Unfortunately, the findings are not consistent, which may be caused by different age ranges of the cohorts studied. In the present study, we examined the voxel-based whole brain cortical thickness, area, GM volume densities, and regional cortical thickness-related laterality indices in 14 bilateral regions of interest (ROIs) from known language-processing circuits in 20 schizophrenia patients, 21 young non-psychotic subjects with heightened genetic risk for schizophrenia at the peak ages for development of the disorder, and 48 matched controls. The results showed widespread significant reductions in cortical thickness, cortical GM volume density, and scattered decreases in cortical surface area in the schizophrenia patients compared with those in the high-risk subjects and normal controls. Moreover, the genetic high-risk subjects showed significantly increased regional cortical thickness in 7 of the 14 ROIs in the language-processing pathway when compared with controls. They also had increased GM volume density in scattered regions associated with language-processing when compared with the normal controls. Laterality analyses showed that the spatial distribution of abnormal cortical thickness in the schizophrenia patients, as well as in the high-risk subjects, contributes to a decrease of the normal left-greater-than-right anatomical asymmetry in the inferior orbital frontal area, and a increased left-greater-than-right pattern in the inferior parietal and occipital regions. Together with the existing findings in the literature, the results of the present study suggest that developmental disruption of the anatomical differentiation of the hemispheres provides a basis for understanding the language impairment and symptoms of psychosis, and that these may arise because of abnormal left-right hemispherical communications that interrupt the normal flow of information processing. The early structural deficits in language-processing circuits may precede the appearance of psychotic symptoms and may be an indicator of an increased risk of developing schizophrenia. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Li, Xiaobo; Alapati, Venkatesh; Xia, Shugao; Branch, Craig A.] Yeshiva Univ Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10461 USA. [Jackson, Courtney] Marist Coll, Dept Psychol, Poughkeepsie, NY USA. [Bertisch, Hilary C.] NYU, Sch Med, New York, NY USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. RP Li, XB (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Radiol, 1300 Morris Pk Ave,Gruss 204, Bronx, NY 10461 USA. EM xiaobo.li@einstein.yu.edu RI Xia, Shugao/F-6845-2013 OI Xia, Shugao/0000-0002-2960-3468 FU NIMH [R21 MH071720] FX This project was partially supported by a grant from NIMH, R21 MH071720. NR 58 TC 17 Z9 17 U1 2 U2 11 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 2012 VL 201 IS 3 BP 182 EP 189 DI 10.1016/j.pscychresns.2011.07.017 PG 8 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 964RG UT WOS:000305713800002 PM 22512952 ER PT J AU Turner, JA Chen, HJ Mathalon, DH Allen, EA Mayer, AR Abbott, CC Calhoun, VD Bustillo, J AF Turner, Jessica A. Chen, Hongji Mathalon, Daniel H. Allen, Elena A. Mayer, Andrew R. Abbott, Christopher C. Calhoun, Vince D. Bustillo, Juan TI Reliability of the amplitude of low-frequency fluctuations in resting state fMRI in chronic schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE ALFF; Schizophrenia; Stability ID NAIVE 1ST-EPISODE SCHIZOPHRENIA; FUNCTIONAL CONNECTIVITY; DEFICITS; MRI AB The resting state amplitude of low frequency fluctuations (ALFF) in functional magnetic resonance imaging has been shown to be reliable in healthy subjects, and to correlate with antipsychotic treatment response in antipsychotic-naive schizophrenia patients. We found moderate to high test-retest stability of ALFF in chronically treated schizophrenia patients assessed twice over a median interval of 2.5 months. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Turner, Jessica A.; Allen, Elena A.; Mayer, Andrew R.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87106 USA. [Turner, Jessica A.; Chen, Hongji; Abbott, Christopher C.; Calhoun, Vince D.; Bustillo, Juan] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA USA. [Mayer, Andrew R.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Turner, JA (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. EM jturner@mrn.org RI bustillo, juan/J-7067-2013; Turner, Jessica/H-7282-2015; OI Turner, Jessica/0000-0003-0076-8434; Mathalon, Daniel/0000-0001-6090-4974 FU NCATS NIH HHS [KL2 TR000089, UL1 TR000041]; NCRR NIH HHS [5P20RR021938, KL2 RR031976, KL2 RR031976-01, KL2 RR31976-1, P20 RR021938, P20 RR021938-01A2, P20 RR021938-02, P20 RR021938-03, P20 RR021938-04, P20 RR021938-05]; NIMH NIH HHS [L30 MH092098-01, R01 MH076989, R01 MH076989-01A1, R01 MH076989-02, R01 MH076989-03, R01 MH076989-04, R01 MH076989-05, R01 MH084898, R01 MH084898-01A1, R01 MH084898-02, R01 MH084898-03, R01 MH084898-04, R01MH084898-01A1] NR 17 TC 28 Z9 30 U1 2 U2 11 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 2012 VL 201 IS 3 BP 253 EP 255 DI 10.1016/j.pscychresns.2011.09.012 PG 3 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 964RG UT WOS:000305713800013 PM 22541511 ER PT J AU Ribeiro, RC Pinto, EM Zambetti, GP Rodriguez-Galindo, C AF Ribeiro, Raul C. Pinto, Emilia M. Zambetti, Gerard P. Rodriguez-Galindo, Carlos TI The International Pediatric Adrenocortical Tumor Registry initiative: Contributions to clinical, biological, and treatment advances in pediatric adrenocortical tumors SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE Rare disease; Adrenocortical tumor; Pediatric Adrenocortical Tumor Registry; TP53 mutation; Arg337His ID ADRENAL-CORTICAL CARCINOMA; LI-FRAUMENI-SYNDROME; BREAST-CANCER; FAMILIAL SYNDROME; P53 MUTATION; CHILDREN; CHILDHOOD; MANAGEMENT; NEOPLASMS; PREDISPOSITION AB Adrenocortical tumor (ACT), a rare tumor with a heterogeneous presentation, incompletely understood pathogenesis, and generally poor prognosis, occurs in 1-2 people per million and is even more uncommon in the pediatric population. Such rare cancers are a challenge to clinical practice. Exchange of experience, information, and data on rare cancers is lacking, and outcomes for these rare cancers could be improved through the establishment of an international registry. The establishment of the International Pediatric Adrenocortical Tumor Registry (IPACTR) in 1990 by the St. Jude Children's Research Hospital International Outreach Program offered a new opportunity to collect clinical and laboratory features, treatment practices, and outcome data for children with ACT, research this disease, and systematically investigate how to improve patient outcomes. These efforts will improve the availability of information for both patients and the medical community. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Ribeiro, Raul C.; Pinto, Emilia M.] St Jude Childrens Res Hosp, Int Outreach Program, Memphis, TN 38105 USA. [Ribeiro, Raul C.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Pinto, Emilia M.; Zambetti, Gerard P.] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. [Rodriguez-Galindo, Carlos] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. RP Pinto, EM (reprint author), St Jude Childrens Res Hosp, Int Outreach Program, MS 721,262 Danny Thomas Pl, Memphis, TN 38105 USA. EM emilia.pinto@stjude.org FU National Institutes of Health (U.S. Department of Health and Human Services) [CA-21765]; Center of Excellence; State of Tennessee; American Lebanese Syrian Associated Charities (ALSAC) FX This work was supported in part by Grant CA-21765 from the National Institutes of Health (U.S. Department of Health and Human Services), by a Center of Excellence grant from the State of Tennessee, and by the American Lebanese Syrian Associated Charities (ALSAC). NR 59 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 31 PY 2012 VL 351 IS 1 SI SI BP 37 EP 43 DI 10.1016/j.mce.2011.10.015 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 911ZE UT WOS:000301762400006 PM 22040600 ER PT J AU Camera, AA Tomaselli, V Fleming, J Jabbar, GA Trachtenberg, M Galvez-Buccollini, JA Proal, AC Rosenthal, RN DeLisi, LE AF Camera, Ariella A. Tomaselli, Veronica Fleming, Jerry Jabbar, Gul A. Trachtenberg, Melissa Galvez-Buccollini, Juan A. Proal, Ashley C. Rosenthal, Richard N. DeLisi, Lynn E. TI Correlates to the variable effects of cannabis in young adults: a preliminary study SO HARM REDUCTION JOURNAL LA English DT Article ID SOCIAL ANXIETY; INTERVIEW; SCHIZOTYPY; MARIJUANA; SUBSTANCE AB Background: Cannabis use can frequently have adverse affects in those that use it and these can be amplified by various characteristics of an individual, from demographic and environmental variations to familial predisposition for mental illnesses. Methods: The current study of 100 individuals, who were cannabis users during their adolescence and may still be users, was a survey of the self perceived effects of cannabis and their correlates. A reliable family member was also interviewed for determination of family history of various major mental illnesses and substance use. Results: As many as 40% of cannabis users had paranoid feelings (suspiciousness) when using cannabis, although the most frequent effect was feeling relaxed (46%). Having a familial background for mental illnesses such as depression or schizophrenia did not determine the effects of cannabis nor its pattern of use, although the number of subjects with such a history was small. An age at which an individual began using cannabis did have an effect on how heavily it was used and the heavier the cannabis use, the more likely the individual was also to have had psychotic symptoms after use. There were no sex differences in effects of cannabis. These results are tempered by the reliance on self-report for many of the variables ascertained. Conclusion: Cannabis can frequently have negative effects in its users, which can be amplified by certain demographic and/or psychosocial factors. Thus, users with a specific profile may be at a higher risk of unpleasant effects from cannabis use and caution should be noted when cannabis is administered to young people for medicinal purposes. C1 [Camera, Ariella A.; Fleming, Jerry; Galvez-Buccollini, Juan A.; DeLisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Tomaselli, Veronica; Rosenthal, Richard N.] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY 10027 USA. [Fleming, Jerry; Jabbar, Gul A.; Galvez-Buccollini, Juan A.; Proal, Ashley C.; DeLisi, Lynn E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tomaselli, Veronica; Trachtenberg, Melissa] NYU, Langone Sch Med, New York, NY 10016 USA. RP Camera, AA (reprint author), VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM AAC167@gmail.com; veronica_tomaselli@yahoo.com; Jerry.Fleming@va.gov; Mtracht1@alumni.binghamton.edu; Lynn.DeLisi@VA.gov NR 18 TC 0 Z9 0 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7517 J9 HARM REDUCT J JI Harm Reduct. J. PD MAR 30 PY 2012 VL 9 AR 15 DI 10.1186/1477-7517-9-15 PG 7 WC Substance Abuse SC Substance Abuse GA 026LY UT WOS:000310281400001 PM 22462481 ER PT J AU Li, JZ Brumme, CJ Lederman, MM Brumme, ZL Wang, HY Spritzler, J Carrington, M Medvik, K Walker, BD Schooley, RT Kuritzkes, DR AF Li, Jonathan Z. Brumme, Chanson J. Lederman, Michael M. Brumme, Zabrina L. Wang, Hongying Spritzler, John Carrington, Mary Medvik, Kathleen Walker, Bruce D. Schooley, Robert T. Kuritzkes, Daniel R. CA AIDS Clin Trials Grp A5197 Study TI Characteristics and Outcomes of Initial Virologic Suppressors during Analytic Treatment Interruption in a Therapeutic HIV-1 gag Vaccine Trial SO PLOS ONE LA English DT Article ID REVERSE-TRANSCRIPTASE INHIBITOR; IMMUNODEFICIENCY-VIRUS TYPE-1; PLACEBO-CONTROLLED TRIAL; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; PROTEASE INHIBITOR; HIV-1-INFECTED PERSONS; VIRAL LOAD; INFECTION AB Background: In the placebo-controlled trial ACTG A5197, a trend favoring viral suppression was seen in the HIV-1-infected subjects who received a recombinant Ad5 HIV-1 gag vaccine. Objective: To identify individuals with initial viral suppression (plasma HIV-1 RNA set point <3.0 log(10) copies/ml) during the analytic treatment interruption (ATI) and evaluate the durability and correlates of virologic control and characteristics of HIV sequence evolution. Methods: HIV-1 gag and pol RNA were amplified and sequenced from plasma obtained during the ATI. Immune responses were measured by flow cytometric analysis and intracellular cytokine expression assays. Characteristics of those with and without initial viral suppression were compared using the Wilcoxon rank sum and Fisher's exact tests. Results: Eleven out of 104 participants (10.6%) were classified as initial virologic suppressors, nine of whom had received the vaccine. Initial virologic suppressors had significantly less CD4+ cell decline by ATI week 16 as compared to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04). However, of the ten initial virologic suppressors with a pVL at ATI week 49, only three maintained pVL <3.0 log10 copies/ml. HIV-1 Gag-specific CD4+ interferon-c responses were not associated with initial virologic suppression and no evidence of vaccine-driven HIV sequence evolution was detected. Participants with initial virologic suppression were found to have a lower percentage of CD4+ CTLA-4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag-reactive CD4+ TNF-alpha+ cells expressing either CTLA-4 or PD-1. Conclusions: Among individuals participating in a rAd5 therapeutic HIV-1 gag vaccine trial, initial viral suppression was found in a subset of patients, but this response was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T cells and virologic outcome warrants further study in trials of other therapeutic vaccines in development. C1 [Li, Jonathan Z.; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Li, Jonathan Z.; Walker, Bruce D.; Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA. [Brumme, Chanson J.; Brumme, Zabrina L.; Carrington, Mary; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Brumme, Chanson J.; Brumme, Zabrina L.; Carrington, Mary; Walker, Bruce D.] Harvard Univ, Cambridge, MA 02138 USA. [Lederman, Michael M.; Medvik, Kathleen] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA. [Brumme, Zabrina L.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Wang, Hongying; Spritzler, John] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Carrington, Mary] NCI Frederick, SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Schooley, Robert T.] Univ Calif San Diego, Div Infect Dis, La Jolla, CA 92093 USA. RP Li, JZ (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. EM Jli22@partners.org OI Brumme, Chanson/0000-0003-2722-5288 FU National Institutes of Health (NIH) [T32 AI07387, U01 AI068636, U01 AI068634, P30 AI60354, K24 RR016482]; Clinical Investigator Training Program Fellowship: Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center; Pfizer Inc.; Merck Co.; New Investigator Award from the Canadian Institutes of Health Research (CIHR); National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Merck FX This work was supported in part by National Institutes of Health (NIH) grants T32 AI07387 (to Dr. Li), U01 AI068636 (AIDS Clinical Trials Group), U01 AI068634 (ACTG Statistical and Data Management Center), P30 AI60354 (Harvard University Center for AIDS Research), K24 RR016482 (to Dr. Kuritzkes), and subcontracts from U01 AI068636 to the Harvard Virology Support Laboratory and the Case Immunology Support Laboratory. The Harvard Virologic Support Laboratory is affiliated with Harvard Medical School and the Case Immunology Support Laboratory is affiliated with Case Western Reserve University. Dr. Li is the recipient of a Clinical Investigator Training Program Fellowship: Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc. and Merck & Co. Dr. Brumme is supported by a New Investigator Award from the Canadian Institutes of Health Research (CIHR). This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The authors have the following competing interests: Drs. Kuritzkes, Lederman, and Schooley are consultants to Merck; Dr. Kuritzkes has received research support from Merck. Mary Carrington is an employee of SAIC-Frederick, Inc. Dr. Li is the recipient of a Clinical Investigator Training Program Fellowship: Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc. and Merck & Co. The authors appreciate Dr. Michael Robertson's (Merck Research Laboratories) input in the design of the study and review of the manuscript. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 34 TC 4 Z9 5 U1 0 U2 3 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 30 PY 2012 VL 7 IS 3 AR e34134 DI 10.1371/journal.pone.0034134 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UC UT WOS:000305339100121 PM 22479542 ER PT J AU Sahara, M Sata, M Morita, T Hirata, Y Nagai, R AF Sahara, Makoto Sata, Masataka Morita, Toshihiro Hirata, Yasunobu Nagai, Ryozo TI Nicorandil Attenuates Monocrotaline-Induced Vascular Endothelial Damage and Pulmonary Arterial Hypertension SO PLOS ONE LA English DT Article ID K-ATP CHANNELS; CELL-PROLIFERATION; POTASSIUM CHANNELS; CARDIAC PROTECTION; ACTIVATION; INHIBITION; SURVIVAL; INJURY; RATS AB Background: An antianginal K-ATP channel opener nicorandil has various beneficial effects on cardiovascular systems; however, its effects on pulmonary vasculature under pulmonary arterial hypertension (PAH) have not yet been elucidated. Therefore, we attempted to determine whether nicorandil can attenuate monocrotaline (MCT)-induced PAH in rats. Materials and Methods: Sprague-Dawley rats injected intraperitoneally with 60 mg/kg MCT were randomized to receive either vehicle; nicorandil (5.0 mg.kg(-1).day(-1)) alone; or nicorandil as well as either a K-ATP channel blocker glibenclamide or a nitric oxide synthase (NOS) inhibitor N-infinity-nitro-L-arginine methyl ester (L-NAME), from immediately or 21 days after MCT injection. Four or five weeks later, right ventricular systolic pressure (RVSP) was measured, and lung tissue was harvested. Also, we evaluated the nicorandil-induced anti-apoptotic effects and activation status of several molecules in cell survival signaling pathway in vitro using human umbilical vein endothelial cells (HUVECs). Results: Four weeks after MCT injection, RVSP was significantly increased in the vehicle-treated group (51.0 +/- 4.7 mm Hg), whereas it was attenuated by nicorandil treatment (33.2 +/- 3.9 mm Hg; P<0.01). Nicorandil protected pulmonary endothelium from the MCT-induced thromboemboli formation and induction of apoptosis, accompanied with both upregulation of endothelial NOS (eNOS) expression and downregulation of cleaved caspase-3 expression. Late treatment with nicorandil for the established PAH was also effective in suppressing the additional progression of PAH. These beneficial effects of nicorandil were blocked similarly by glibenclamide and L-NAME. Next, HUVECs were incubated in serum-free medium and then exhibited apoptotic morphology, while these changes were significantly attenuated by nicorandil administration. Nicorandil activated the phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) pathways in HUVECs, accompanied with the upregulation of both eNOS and Bcl-2 expression. Conclusions: Nicorandil attenuated MCT-induced vascular endothelial damage and PAH through production of eNOS and anti-apoptotic factors, suggesting that nicorandil might have a promising therapeutic potential for PAH. C1 [Sahara, Makoto; Morita, Toshihiro; Hirata, Yasunobu; Nagai, Ryozo] Univ Tokyo, Dept Cardiovasc Med, Grad Sch Med, Tokyo, Japan. [Sata, Masataka] Univ Tokushima, Grad Sch, Dept Cardiovasc Med, Inst Hlth Biosci, Tokushima 770, Japan. [Sahara, Makoto] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol,Cardiovasc Res Ctr, Boston, MA USA. RP Sahara, M (reprint author), Univ Tokyo, Dept Cardiovasc Med, Grad Sch Med, Tokyo, Japan. EM saharam-tky@umin.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan [17390227]; Japan Society for the Promotion of Science FX This study was supported in part by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan to M. Sata (#17390227; http://kaken.nii.ac.jp/) and by a research fellowship from the Japan Society for the Promotion of Science to M. Sahara. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 16 Z9 16 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 30 PY 2012 VL 7 IS 3 AR e33367 DI 10.1371/journal.pone.0033367 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 959UC UT WOS:000305339100045 PM 22479390 ER PT J AU AhnAllen, CG Liverant, GI Gregor, KL Kamholz, BW Levitt, JJ Gulliver, SB Pizzagalli, DA Koneru, VK Kaplan, GB AF AhnAllen, Christopher G. Liverant, Gabrielle I. Gregor, Kristin L. Kamholz, Barbara W. Levitt, James J. Gulliver, Suzy Bird Pizzagalli, Diego A. Koneru, Vamsi K. Kaplan, Gary B. TI The relationship between reward-based learning and nicotine dependence in smokers with schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE Cigarette smoking; Anhedonia; Reward responsiveness ID SMOKING-CESSATION; MENTAL-ILLNESS; REINFORCEMENT; DEPRESSION; ANHEDONIA; TOBACCO; SENSITIVITY; IMPAIRMENT; WITHDRAWAL; SYMPTOMS AB Cigarette smoking rates remain remarkably high in schizophrenia relative to smoking in other psychiatric groups. Impairments in the reward system may be related to elevated rates of nicotine dependence and lower cessation rates in this psychiatric group. Smokers with schizophrenia and schizoaffective disorder (SWS; n = 15; M-age = 54.87, S.D. = 6.51, 100% male) and a non-psychiatric control group of smokers (NCL; n = 16; M-age = 50.38, S.D. = 11.52; 93.8% male) were administered a computerized signal detection task to measure reward-based learning. Performance on the signal detection task was assessed by response bias, discriminability, reaction time, and hit rate. Clinician-assessed and self-reported measures of smoking and psychiatric symptoms were completed. SWS exhibited similar patterns of reward-based learning compared to control smokers. However, decreased reward-based learning was associated with increased levels of nicotine dependence in SWS, but not among control smokers. Nicotine withdrawal and urge to smoke were correlated with anhedonia within the SWS group. Among SWS, reduced reward responsiveness and increased anhedonia were associated with and may contribute to greater co-occurring nicotine dependence. These findings emphasize the importance of targeting reward system functioning in smoking cessation treatment for individuals with schizophrenia. Published by Elsevier Ireland Ltd. C1 [AhnAllen, Christopher G.] VA Boston Healthcare Syst, Inpatient Mental Hlth Serv, Brockton, MA 02301 USA. [AhnAllen, Christopher G.; Gregor, Kristin L.; Levitt, James J.; Pizzagalli, Diego A.; Koneru, Vamsi K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Liverant, Gabrielle I.; Kamholz, Barbara W.; Kaplan, Gary B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gulliver, Suzy Bird] Waco Med Ctr, VISN Ctr Excellence Res Returning War Vet 17, Waco, TX 76711 USA. [Gulliver, Suzy Bird] Texas A&M Univ, Coll Med, Hlth Sci Ctr, College Stn, TX 77843 USA. [Pizzagalli, Diego A.] McLean Hosp, Neuroimaging Ctr, Belmont, MA 02478 USA. RP AhnAllen, CG (reprint author), VA Boston Healthcare Syst, Inpatient Mental Hlth Serv, Ward 23B,940 Belmont St, Brockton, MA 02301 USA. EM cga111777@yahoo.com FU VA Center Grant; NIMH [R01 MH68376, R21 MH078979]; VA Merit Award; VA Career Development Award; Advanced Neuro Technology (ANT); AstraZeneca FX This study was supported by a VA Center Grant (Co-PIs: Kaplan, Gulliver). During this project, Dr. Pizzagalli was partially supported by NIMH grants (R01 MH68376, R21 MH078979), Dr. Levitt was partially supported by a VA Merit Award, and Dr. Liverant was partially supported by a VA Career Development Award. The authors wish to acknowledge Casey Pabian and Virginia Davis CNS for their assistance in recruiting participants for this study. The authors also acknowledge the administrative support of Marie Fairbanks. All participants who volunteered for this research study are thanked for their important contributions to the study.; Dr. Pizzagalli is the inventor of the software program used in this study. In the past three years, Dr. Pizzagalli received research support and consulting fees from Advanced Neuro Technology (ANT) and honoraria and consulting fees from AstraZeneca for studies unrelated to the current project. All other authors declare no conflicts of interest. NR 46 TC 18 Z9 18 U1 4 U2 11 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 30 PY 2012 VL 196 IS 1 BP 9 EP 14 DI 10.1016/j.psychres.2011.09.011 PG 6 WC Psychiatry SC Psychiatry GA 955SL UT WOS:000305041100002 PM 22342123 ER PT J AU Storch, EA Lewin, AB Larson, MJ Geffken, GR Murphy, TK Geller, DA AF Storch, Eric A. Lewin, Adam B. Larson, Michael J. Geffken, Gary R. Murphy, Tanya K. Geller, Daniel A. TI Depression in youth with obsessive-compulsive disorder: Clinical phenomenology and correlates SO PSYCHIATRY RESEARCH LA English DT Article DE Obsessive-compulsive disorder; Children; Depression; Treatment; Assessment; Impairment ID MULTIDIMENSIONAL ANXIETY SCALE; COGNITIVE-BEHAVIORAL THERAPY; COMORBID MAJOR DEPRESSION; TEST-RETEST RELIABILITY; INTERVIEW SCHEDULE; DSM-IV; INTERRATER RELIABILITY; FUNCTIONAL IMPAIRMENT; FAMILY ACCOMMODATION; GENDER-DIFFERENCES AB This study examined differences in clinical presentation and functional impairment in youth with obsessive-compulsive disorder (OCD) with or without comorbid depressive disorders and sought to determine the predictors of youth-reported depressive symptoms. One-hundred and sixty youth were reliably diagnosed with OCD and comorbid disorders using the Anxiety Disorders Interview Schedule for DSM-IV: Parent version (Silverman and Albano, 1996) and confirmed by an experienced clinician. Sixteen percent (n = 25) had a comorbid diagnosis of a current depressive disorder (DD). Significantly more females than males had a DD. Those with a DD showed increased OCD symptom severity, OCD-related functional impairment, and family accommodation relative to those without a comorbid DD. Depressive symptoms were significantly positively correlated with years of age, degree of OCD symptom severity, measures of OCD-related functional impairment, and non-OCD anxiety symptoms. Hierarchical regression analyses showed that age, gender, functional impairment, and non-OCD anxiety were significant predictors of depressive symptoms, even when OCD symptom severity was controlled. Notably, functional impairment was a partial mediator of the relationship between OCD symptom severity and depression levels, suggesting depression levels are the product of both degree of symptoms and amount of day-to-day impairment. Results are discussed in terms of implications for assessment and treatment. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Storch, Eric A.; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. [Storch, Eric A.; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Psychiat & Behav Neurosci, Tampa, FL 33620 USA. [Storch, Eric A.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. [Larson, Michael J.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Geffken, Gary R.] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. [Geller, Daniel A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Storch, EA (reprint author), Univ S Florida, Dept Pediat, Rothman Ctr Neuropsychiat, 880 6th St S,Box 7523, St Petersburg, FL 33701 USA. EM estorch@health.usf.edu RI Storch, Eric/I-4935-2012; Lewin, Adam/A-9832-2013; Larson, Michael/C-8543-2012; Murphy, Tanya/J-7079-2013 OI Larson, Michael/0000-0002-8199-8065; NR 50 TC 18 Z9 18 U1 2 U2 11 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 30 PY 2012 VL 196 IS 1 BP 83 EP 89 DI 10.1016/j.psychres.2011.10.013 PG 7 WC Psychiatry SC Psychiatry GA 955SL UT WOS:000305041100015 PM 22370151 ER PT J AU Liu, KH McCormack, M Sheen, J AF Liu, Kun-hsiang McCormack, Matthew Sheen, Jen TI Targeted parallel sequencing of large genetically-defined genomic regions for identifying mutations in Arabidopsis SO PLANT METHODS LA English DT Article DE Next generation sequencing; EMS; PCR-amplified genomic library; Nitrate signalling; Positional cloning ID MAP-BASED CLONING; THALIANA; IDENTIFICATION; NITROGEN; GALAXY; TRANSFORMATION; DNA AB Large-scale genetic screens in Arabidopsis are a powerful approach for molecular dissection of complex signaling networks. However, map-based cloning can be time-consuming or even hampered due to low chromosomal recombination. Current strategies using next generation sequencing for molecular identification of mutations require whole genome sequencing and advanced computational devises and skills, which are not readily accessible or affordable to every laboratory. We have developed a streamlined method using parallel massive sequencing for mutant identification in which only targeted regions are sequenced. This targeted parallel sequencing (TPSeq) method is more cost-effective, straightforward enough to be easily done without specialized bioinformatics expertise, and reliable for identifying multiple mutations simultaneously. Here, we demonstrate its use by identifying three novel nitrate-signaling mutants in Arabidopsis. C1 [Liu, Kun-hsiang; McCormack, Matthew; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Liu, Kun-hsiang; McCormack, Matthew; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Liu, Kun-hsiang; McCormack, Matthew; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Liu, KH (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM Khliu@molbio.mgh.harvard.edu; McCormack@molbio.mgh.harvard.edu FU NIH [NIH R01GM060493] FX We thank the ABRC for providing Arabidopsis mutant seeds, and Jenifer Bush, Yajie Niu, Lei Li, Qi Hall and Matthew Ramon for critically reading the manuscript. Funding was provided by the NIH grant (NIH R01GM060493) to J.S. NR 32 TC 5 Z9 5 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1746-4811 J9 PLANT METHODS JI Plant Methods PD MAR 30 PY 2012 VL 8 AR 12 DI 10.1186/1746-4811-8-12 PG 12 WC Biochemical Research Methods; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 942PA UT WOS:000304056400001 PM 22462410 ER PT J AU Boninger, ML Cowan, RE AF Boninger, Michael L. Cowan, Rachel E. TI Why do we need improved mobility technology? SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Editorial Material C1 [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Cowan, Rachel E.] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA. [Cowan, Rachel E.] Lois Pope Life Ctr, Miami, FL 33136 USA. RP Boninger, ML (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. EM boninger@upmc.edu OI Boninger, Michael/0000-0001-6966-919X FU NIA NIH HHS [P30 AG024827] NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD MAR 30 PY 2012 VL 9 AR 16 DI 10.1186/1743-0003-9-16 PG 2 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 940AM UT WOS:000303862400001 PM 22463101 ER PT J AU Boninger, ML Cowan, RE Fregly, BJ AF Boninger, Michael L. Cowan, Rachel E. Fregly, Benjamin J. TI Structures promoting research, training, and technology transfer in mobility: lessons learned from a visit to European centers SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Article AB The purpose of this paper is to describe the education, research, technology transfer, and cooperative models that appear to have the greatest likelihood of successfully tackling the issue of technology to improve mobility. Ideally better models in each of these areas will lead to an increased number of researchers who are more productive. There will be increased international collaboration that will allow for better research with small and/or disadvantaged populations, and the research completed will lead to changes in clinical care that positively impact individuals with impair mobility. C1 [Boninger, Michael L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Cowan, Rachel E.] Univ Miami, Miller Sch Med, Dept Neurol Surg, Miami Project Cure Paralysis, Miami, FL 33136 USA. [Fregly, Benjamin J.] Univ Florida, Dept Mech & Aerosp Engn, Gainesville, FL 32611 USA. RP Boninger, ML (reprint author), Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, 3741 5th Ave,Suite 201, Pittsburgh, PA 15260 USA. EM boninger@upmc.edu RI Fregly, Benjamin/O-6860-2016; OI Fregly, Benjamin/0000-0003-1166-4358; Boninger, Michael/0000-0001-6966-919X FU NIA NIH HHS [P30 AG024827] NR 3 TC 0 Z9 0 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD MAR 30 PY 2012 VL 9 AR 19 DI 10.1186/1743-0003-9-19 PG 5 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 940AM UT WOS:000303862400004 PM 22463495 ER PT J AU Reinkensmeyer, DJ Boninger, ML AF Reinkensmeyer, David J. Boninger, Michael L. TI Technologies and combination therapies for enhancing movement training for people with a disability SO JOURNAL OF NEUROENGINEERING AND REHABILITATION LA English DT Editorial Material ID SPINAL-CORD-INJURY; ROBOTIC-ASSISTED REHABILITATION; ANKLE-FOOT ORTHOSIS; UPPER-LIMB; VIRTUAL-REALITY; MOTOR RECOVERY; CHRONIC STROKE; GAIT; RATS; WALKING AB There has been a dramatic increase over the last decade in research on technologies for enhancing movement training and exercise for people with a disability. This paper reviews some of the recent developments in this area, using examples from a National Science Foundation initiated study of mobility research projects in Europe to illustrate important themes and key directions for future research. This paper also reviews several recent studies aimed at combining movement training with plasticity or regeneration therapies, again drawing in part from European research examples. Such combination therapies will likely involve complex interactions with motor training that must be understood in order to achieve the goal of eliminating severe motor impairment. C1 [Reinkensmeyer, David J.] Univ Calif Irvine, Dept Mech & Aerosp Engn, Irvine, CA 92697 USA. [Reinkensmeyer, David J.] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA. [Reinkensmeyer, David J.] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA. [Boninger, Michael L.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Boninger, Michael L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. RP Reinkensmeyer, DJ (reprint author), Univ Calif Irvine, Dept Mech & Aerosp Engn, 4200 Engn Gateway, Irvine, CA 92697 USA. EM dreinken@uci.edu OI Boninger, Michael/0000-0001-6966-919X NR 68 TC 17 Z9 18 U1 1 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-0003 J9 J NEUROENG REHABIL JI J. NeuroEng. Rehabil. PD MAR 30 PY 2012 VL 9 AR 17 DI 10.1186/1743-0003-9-17 PG 10 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA 940AM UT WOS:000303862400002 PM 22463132 ER PT J AU Havens, CG Shobnam, N Guarino, E Centore, RC Zou, L Kearsey, SE Walter, JC AF Havens, Courtney G. Shobnam, Nadia Guarino, Estrella Centore, Richard C. Zou, Lee Kearsey, Stephen E. Walter, Johannes C. TI Direct Role for Proliferating Cell Nuclear Antigen in Substrate Recognition by the E3 Ubiquitin Ligase CRL4(Cdt2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT KINASE INHIBITOR; XENOPUS EGG EXTRACTS; DNA-POLYMERASE ALPHA; S-PHASE; STRUCTURAL BASIS; CDT1 PROTEOLYSIS; FISSION YEAST; HISTONE H3; PIP BOX; CHROMATIN ASSOCIATION AB The E3 ubiquitin ligase Cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) is emerging as an important cell cycle regulator that targets numerous proteins for destruction in S phase and after DNA damage, including Cdt1, p21, and Set8. CRL4(Cdt2) substrates contain a "PIP degron," which consists of a canonical proliferating cell nuclear antigen (PCNA) interaction motif (PIP box) and an adjacent basic amino acid. Substrates use their PIP box to form a binary complex with PCNA on chromatin and the basic residue to recruit CRL4(Cdt2) for substrate ubiquitylation. Using Xenopus egg extracts, we identify an acidic residue in PCNA that is essential to support destruction of all CRL4(Cdt2) substrates. This PCNA residue, which adjoins the basic amino acid of the bound PIP degron, is dispensable for substrate binding to PCNA but essential for CRL4(Cdt2) recruitment to chromatin. Our data show that the interaction of CRL4(Cdt2) with substrates requires molecular determinants not only in the substrate degron but also on PCNA. The results illustrate a potentially general mechanism by which E3 ligases can couple ubiquitylation to the formation of protein-protein interactions. C1 [Havens, Courtney G.; Shobnam, Nadia; Walter, Johannes C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Guarino, Estrella; Kearsey, Stephen E.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Centore, Richard C.; Zou, Lee] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Walter, JC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave,Bldg C2-226A, Boston, MA 02115 USA. EM johannes_walter@hms.harvard.edu FU National Institutes of Health [GM80676, GM082014, GM089150]; Cancer Research UK [C814/A9035] FX This work was supported, in whole or in part, by National Institutes of Health Grants GM80676 (to J. C. W.), GM082014 (to C. G. H.), and GM089150 (to R. C. C.). This work was also supported by Cancer Research UK Grant C814/A9035 (to S. E. K.). NR 65 TC 18 Z9 19 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 30 PY 2012 VL 287 IS 14 BP 11410 EP 11421 DI 10.1074/jbc.M111.337683 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925RY UT WOS:000302780100070 PM 22303007 ER PT J AU Krause, DS Scadden, DT AF Krause, Daniela S. Scadden, David T. TI Deconstructing the Complexity of a Microenvironmental Niche SO CELL LA English DT Editorial Material ID PROTEIN; THYMUS AB Cells acquire their fate in vivo in the context of a complex microenvironmental "niche" comprised of heterologous cell types, signaling molecules, extracellular matrix, biophysical forces, and metabolic substrates. Now Calderon and Boehm report the "refunctionalization" of a defective thymic epithelial niche, offering insights into how signaling molecules may be hierarchically organized to direct differentiation outcomes. C1 [Krause, Daniela S.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med & Canc Ctr, Boston, MA 02114 USA. [Krause, Daniela S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Krause, Daniela S.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Krause, Daniela S.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med & Canc Ctr, Boston, MA 02114 USA. EM dscadden@mgh.harvard.edu FU NCI NIH HHS [K08 CA138916]; NHLBI NIH HHS [R01 HL044851, U01 HL100402] NR 6 TC 11 Z9 11 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 30 PY 2012 VL 149 IS 1 BP 16 EP 17 DI 10.1016/j.cell.2012.03.005 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 918FT UT WOS:000302235400004 PM 22464318 ER PT J AU Rankin, EB Wu, C Khatri, R Wilson, TLS Andersen, R Araldi, E Rankin, AL Yuan, J Kuo, CJ Schipani, E Giaccia, AJ AF Rankin, Erinn B. Wu, Colleen Khatri, Richa Wilson, Tremika L. S. Andersen, Rebecca Araldi, Elisa Rankin, Andrew L. Yuan, Jenny Kuo, Calvin J. Schipani, Emestina Giaccia, Amato J. TI The HIF Signaling Pathway in Osteoblasts Directly Modulates Erythropoiesis through the Production of EPO SO CELL LA English DT Article ID HYPOXIA-INDUCIBLE-FACTOR; HEMATOPOIETIC STEM-CELLS; TUMOR-SUPPRESSOR; MICE; NICHE; HIF-1-ALPHA; ANEMIA; DIFFERENTIATION; PROGENITORS; DEFICIENCY AB Osteoblasts are an important component of the hematopoietic microenvironment in bone. However, the mechanisms by which osteoblasts control hematopoiesis remain unknown. We show that augmented HIF signaling in osteoprogenitors results in HSC niche expansion associated with selective expansion of the erythroid lineage. Increased red blood cell production occurred in an EPO-dependent manner with increased EPO expression in bone and suppressed EPO expression in the kidney. In contrast, inactivation of HIF in osteoprogenitors reduced EPO expression in bone. Importantly, augmented HIF activity in osteoprogenitors protected mice from stress-induced anemia. Pharmacologic or genetic inhibition of prolyl hydroxylases1/2/3 in osteoprogenitors elevated EPO expression in bone and increased hematocrit. These data reveal an unexpected role for osteoblasts in the production of EPO and modulation of erythropoiesis. Furthermore, these studies demonstrate a molecular role for osteoblastic PHD/VHL/HIF signaling that can be targeted to elevate both HSCs and erythroid progenitors in the local hematopoietic microenvironment. C1 [Rankin, Erinn B.; Wu, Colleen; Andersen, Rebecca; Giaccia, Amato J.] Stanford Univ, Div Radiat & Canc Biol, Dept Radiat Oncol, Ctr Clin Sci Res, Stanford, CA 94303 USA. [Yuan, Jenny; Kuo, Calvin J.] Stanford Univ, Div Hematol, Stanford, CA 94303 USA. [Khatri, Richa; Wilson, Tremika L. S.; Araldi, Elisa; Schipani, Emestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Rankin, Andrew L.] Pfizer, Inflammat & Immunol, Cambridge, MA 02140 USA. RP Giaccia, AJ (reprint author), Stanford Univ, Div Radiat & Canc Biol, Dept Radiat Oncol, Ctr Clin Sci Res, Stanford, CA 94303 USA. EM giaccia@stanford.edu FU NIH [CA67166, CA088480, AR048191-06]; Sydney Frank Foundation; NIH National Research Service from the National Cancer Institute [T32 CA09151]; Canadian Institutes of Health Research FX This work was supported by NIH grants CA67166 and CA088480 and the Sydney Frank Foundation (A.J.G.) and NIH AR048191-06 (A.J.G. and E.S.). E.B.R. is supported by the NIH National Research Service Award T32 CA09151 from the National Cancer Institute. C.W. is supported by a Canadian Institutes of Health Research Fellowship. The authors would like to thank all of the investigators that generated and made the floxed/transgenic mice available for these studies: Dr. Volker Haase (Vhlh floxed), Dr. Randall Johnson (Hif-1 floxed), Drs. Brian Keith and Celeste Simon (Hif-2 floxed), Dr. Guo-Hua Fong (Phd1,2,3 floxed), and Dr. Andrew McMahon (Osterix-Cre). NR 43 TC 81 Z9 90 U1 3 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 30 PY 2012 VL 149 IS 1 BP 63 EP 74 DI 10.1016/j.cell.2012.01.051 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 918FT UT WOS:000302235400010 PM 22464323 ER PT J AU Powell, AE Wang, Y Li, YN Poulin, EJ Means, AL Washington, MK Higginbotham, JN Juchheim, A Prasad, N Levy, SE Guo, Y Shyr, Y Aronow, BJ Haigis, KM Franklin, JL Coffey, RJ AF Powell, Anne E. Wang, Yang Li, Yina Poulin, Emily J. Means, Anna L. Washington, Mary K. Higginbotham, James N. Juchheim, Alwin Prasad, Nripesh Levy, Shawn E. Guo, Yan Shyr, Yu Aronow, Bruce J. Haigis, Kevin M. Franklin, Jeffrey L. Coffey, Robert J. TI The Pan-ErbB Negative Regulator Lrig1 Is an Intestinal Stem Cell Marker that Functions as a Tumor Suppressor SO CELL LA English DT Article ID IMMUNOHISTOCHEMICAL ANALYSIS; OXIDATIVE STRESS; EXPRESSION MARKS; CANCER; RECEPTOR; GENE; PROLIFERATION; GROWTH; CRYPTS; POPULATION AB Lineage mapping has identified both proliferative and quiescent intestinal stem cells, but the molecular circuitry controlling stem cell quiescence is incompletely understood. By lineage mapping, we show Lrig1, a pan-ErbB inhibitor, marks predominately noncycling, long-lived stem cells that are located at the crypt base and that, upon injury, proliferate and divide to replenish damaged crypts. Transcriptome profiling of Lrig1(+) colonic stem cells differs markedly from the profiling of highly proliferative, Lgr5(+) colonic stem cells; genes upregulated in the Lrig1(+) population include those involved in cell cycle repression and response to oxidative damage. Loss of Apc in Lrig1(+) cells leads to intestinal adenomas, and genetic ablation of Lrig1 results in heightened ErbB1-3 expression and duodenal adenomas. These results shed light on the relationship between proliferative and quiescent intestinal stem cells and support a model in which intestinal stem cell quiescence is maintained by calibrated ErbB signaling with loss of a negative regulator predisposing to neoplasia. C1 [Powell, Anne E.; Wang, Yang; Li, Yina; Poulin, Emily J.; Higginbotham, James N.; Franklin, Jeffrey L.; Coffey, Robert J.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Powell, Anne E.; Wang, Yang; Li, Yina; Poulin, Emily J.; Higginbotham, James N.; Franklin, Jeffrey L.; Coffey, Robert J.] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. [Means, Anna L.] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN 37232 USA. [Washington, Mary K.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Guo, Yan; Shyr, Yu] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN 37232 USA. [Coffey, Robert J.] Vanderbilt Univ, Med Ctr, Epithelial Biol Ctr, Nashville, TN 37232 USA. [Juchheim, Alwin; Haigis, Kevin M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Pathol Unit, Charlestown, MA 02129 USA. [Juchheim, Alwin; Haigis, Kevin M.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. [Prasad, Nripesh; Levy, Shawn E.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA. [Aronow, Bruce J.] Cincinnati Childrens Hosp, Med Ctr, Dept Biomed Informat, Cincinnati, OH 45229 USA. [Aronow, Bruce J.] Cincinnati Childrens Hosp, Med Ctr, Dept Dev Biol, Cincinnati, OH 45229 USA. [Coffey, Robert J.] Dept Vet Affairs Med Ctr, Nashville, TN 37232 USA. RP Coffey, RJ (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. EM robert.coffey@vanderbilt.edu RI Aronow, Bruce/F-8438-2012; Wang, Yang/O-2300-2013; OI Wang, Yang/0000-0003-2801-8416; Prasad, Nripesh/0000-0003-4074-2538 FU National Cancer Institute [CA151566, CA46413]; MMHCC [U01CA084239]; Gastrointestinal Specialized Program of Research Excellence [P50CA095103, T32GM008554, T32CA119925]; Vanderbilt's Clinical and Translational Science Award; Transgenic Mouse/ES Cell, Cell Imaging, and Flow Cytometry Shared Resources; Coffey Memorial Gastrointestinal Cancer Fund FX A.E.P., Y.W., Y.L., K.M.H., J.L.F. and R.J.C. designed, executed and analyzed data. E.J.P., J.N.H., and A.J. provided technical assistance. S.E.L. conducted the RNA-Seq. A.L.M., M.K.W., N.P., Y.G., Y.S., and B.J.A. provided expert analysis. A.E.P. and R.J.C. assembled the manuscript. We thank Frank Revetta and Catherine Meador for technical assistance and Robert Whitehead for guidance. This work was supported by the National Cancer Institute CA151566 to R.J.C. and K.M.H., and CA46413, MMHCC U01CA084239, and Gastrointestinal Specialized Program of Research Excellence P50CA095103 to R.J.C., T32GM008554 to E.J.P. and T32CA119925 to A.E.P. The authors acknowledge the support of Vanderbilt's Clinical and Translational Science Award and Transgenic Mouse/ES Cell, Cell Imaging, and Flow Cytometry Shared Resources. We thank the Peter Powell and Mary Catherine Mundell Coffey Memorial Gastrointestinal Cancer Fund for its generous support. NR 49 TC 228 Z9 230 U1 3 U2 37 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 30 PY 2012 VL 149 IS 1 BP 146 EP 158 DI 10.1016/j.cell.2012.02.042 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 918FT UT WOS:000302235400017 PM 22464327 ER PT J AU Farago, AF Snyder, EL Jacks, T AF Farago, Anna F. Snyder, Eric L. Jacks, Tyler TI SnapShot: Lung Cancer Models SO CELL LA English DT Editorial Material ID RAPAMYCIN COMBINATION THERAPY; SOMATIC MUTATIONS; MOUSE; ADENOCARCINOMA; CELL C1 [Farago, Anna F.; Snyder, Eric L.; Jacks, Tyler] MIT, Cambridge, MA 02139 USA. [Farago, Anna F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farago, Anna F.] Dana Farber Partners Canc Care, Boston, MA 02215 USA. [Snyder, Eric L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Farago, AF (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 10 TC 17 Z9 18 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 30 PY 2012 VL 149 IS 1 BP 246 EP + AR 246.e1 DI 10.1016/j.cell.2012.03.015 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 918FT UT WOS:000302235400025 PM 22464334 ER PT J AU Lee, EK Kim, W Tominaga, K Martindale, JL Yang, XL Subaran, SS Carlson, OD Mercken, EM Kulkarni, RN Akamatsu, W Okano, H Perrone-Bizzozero, NI de Cabo, R Egan, JM Gorospe, M AF Lee, Eun Kyung Kim, Wook Tominaga, Kumiko Martindale, Jennifer L. Yang, Xiaoling Subaran, Sarah S. Carlson, Olga D. Mercken, Evi M. Kulkarni, Rohit N. Akamatsu, Wado Okano, Hideyuki Perrone-Bizzozero, Nora I. de Cabo, Rafael Egan, Josephine M. Gorospe, Myriam TI RNA-Binding Protein HuD Controls Insulin Translation SO MOLECULAR CELL LA English DT Article ID MESSENGER-RNA; BETA-CELL; POSTTRANSCRIPTIONAL REGULATION; GLUCOSE; ELEMENT; BIOSYNTHESIS; INCREASE; RECEPTOR; REGION; ELAV AB Although expression of the mammalian RNA-binding protein HuD was considered to be restricted to neurons, we report that HuD is present in pancreatic (3 cells, where its levels are controlled by the insulin receptor pathway. We found that HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR) of preproinsulin (Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production. Following treatment with glucose, HuD rapidly dissociated from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice displayed higher insulin levels in pancreatic islets, while HuD-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify HuD as a pivotal regulator of insulin translation in pancreatic beta cells. C1 [Lee, Eun Kyung; Tominaga, Kumiko; Martindale, Jennifer L.; Yang, Xiaoling; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Kim, Wook; Subaran, Sarah S.; Carlson, Olga D.; Egan, Josephine M.] NIA, Clin Invest Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Mercken, Evi M.; de Cabo, Rafael] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Lee, Eun Kyung] Catholic Univ Korea, Dept Biochem, Coll Med, Seoul 137701, South Korea. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Islet Cell Biol & Regenerat Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Akamatsu, Wado; Okano, Hideyuki] Keio Univ, Dept Physiol, Grad Sch Med, Shinjuku Ku, Tokyo 1608582, Japan. [Perrone-Bizzozero, Nora I.] Univ New Mexico, Dept Neurosci, Sch Med, Albuquerque, NM 87131 USA. RP Gorospe, M (reprint author), NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov RI Akamatsu, Wado/L-1214-2013; Hidokano, Hideyuki/J-5973-2013; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU National Institute on Aging-Intramural Research Program, National Institutes of Health (NIH); NIH [RO1 DK 67536, 68721]; Japanese Ministry of Education, Science, Sports, Culture and Technology; Korean Ministry of Education, Science and Technology [5-2011-A0154-00046] FX We thank H.J. Okano, M. Igarashi, R. Selimyan, D. Nines, and D. Boyer for assistance and H. Huang for reagents. This work was supported in part by the National Institute on Aging-Intramural Research Program, National Institutes of Health (NIH). R.N.K. is supported by NIH grants RO1 DK 67536 and 68721. H.O. and W.A. are funded by the Japanese Ministry of Education, Science, Sports, Culture and Technology. E.K.L. is funded by the Korean Ministry of Education, Science and Technology (5-2011-A0154-00046). NR 22 TC 35 Z9 35 U1 2 U2 11 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 30 PY 2012 VL 45 IS 6 BP 826 EP 835 DI 10.1016/j.molcel.2012.01.016 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 920ES UT WOS:000302386100014 PM 22387028 ER PT J AU Zhou, XH Johnson, LL AF Zhou, Xiao-Hua Johnson, Laura Lee TI Preface SO STATISTICS IN MEDICINE LA English DT Article C1 [Zhou, Xiao-Hua] Univ Washington, Dept Biostat, VA Puget Sound Hlth Care Syst, HSB, Seattle, WA 98195 USA. [Johnson, Laura Lee] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, VA Puget Sound Hlth Care Syst, HSB, 1705 Pacific St NE,F600, Seattle, WA 98195 USA. EM azhou@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 30 PY 2012 VL 31 IS 7 SI SI BP 601 EP 601 DI 10.1002/sim.4442 PG 1 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 903MY UT WOS:000301121900001 PM 22392624 ER PT J AU Zhou, XH Li, SL Tian, F Cai, BJ Xie, YM Pei, Y Kang, S Fan, M Li, JP AF Zhou, X. H. Li, S. L. Tian, F. Cai, B. J. Xie, Y. M. Pei, Y. Kang, S. Fan, M. Li, J. P. TI Building a disease risk model of osteoporosis based on traditional Chinese medicine symptoms and western medicine risk factors SO STATISTICS IN MEDICINE LA English DT Article DE GPLM; SVM-RFE; random forest; association rule learning; TCM symptoms ID PARTIAL LINEAR-MODELS; FRACTURE; WOMEN AB In the Traditional Chinese Medicine (TCM) cross-sectional survey conducted by our team, we were interested in determining the risk factors of osteoporosis. To analyze this TCM study, we had to deal with three statistical problems: (1) a very large number of potential risk factors, (2) interactions among potential risk factors, and (3) nonlinear effects of some continuous-scale risk factors. To address these analytic issues, we used two data mining methods, support vector machine recursive feature elimination and random forest; to deal with the curse of high-dimensional risk factors, we applied another data mining technique of association rule learning to discover the potential associations among risk factors. Finally, we employed the generalized partial linear model (GPLM) to determine nonlinear effects of an important continuous-scale risk factor. The final GPLM model shows that TCM symptoms play an important role in assessing the risk of osteoporosis. The GPLM also reveals a nonlinear effect of the important risk factor, menopause years, which might be missed by the generalized linear model. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Tian, F.; Xie, Y. M.; Li, J. P.] China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing 100700, Peoples R China. [Zhou, X. H.; Li, S. L.; Cai, B. J.; Pei, Y.; Fan, M.] Renmin Univ China, Sch Stat, Beijing 100872, Peoples R China. [Zhou, X. H.] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Zhou, X. H.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Kang, S.] Beijing Univ Chinese Med, Dongzhimen Hosp, Beijing 100700, Peoples R China. RP Xie, YM (reprint author), China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing 100700, Peoples R China. EM zhinanb2010@yahoo.com.cn FU National Science Foundation of China (NSFC) [30728019, 30873339] FX Dr. Xiao-Hua Zhou, PhD, is presently a Core Investigator and Biostatistics Unit Director at the Northwest HSR&D Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA. Part of this work was supported by the two National Science Foundation of China grants (NSFC No. 30728019 to Dr. Zhou and NSFC No. 30873339 to Dr. Xie). This paper presents the findings and conclusions of the authors. It does not necessarily represent those of VA HSR&D Service. NR 23 TC 6 Z9 7 U1 3 U2 26 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 30 PY 2012 VL 31 IS 7 SI SI BP 643 EP 652 DI 10.1002/sim.4382 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 903MY UT WOS:000301121900007 PM 22354891 ER PT J AU Nahrendorf, M McCarthy, JR Libby, P AF Nahrendorf, Matthias McCarthy, Jason R. Libby, Peter TI Over a Hump for Imaging Atherosclerosis Nanobodies Visualize Vascular Cell Adhesion Molecule-1 in Inflamed Plaque SO CIRCULATION RESEARCH LA English DT Editorial Material DE adhesion molecule; atherosclerosis; imaging ID CORONARY ATHEROSCLEROSIS; VCAM-1; INFLAMMATION; EXPRESSION; DIET C1 [Nahrendorf, Matthias; McCarthy, Jason R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias; McCarthy, Jason R.] Harvard Univ, Sch Med, Boston, MA USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU NHLBI NIH HHS [R01HL096576, R01HL095629]; PHS HHS [HHSN268201000044C] NR 15 TC 5 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 30 PY 2012 VL 110 IS 7 BP 902 EP 903 DI 10.1161/CIRCRESAHA.112.267260 PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 917ZZ UT WOS:000302219900003 PM 22461358 ER PT J AU Wedeen, VJ Rosene, DL Wang, RP Dai, GP Mortazavi, F Hagmann, P Kaas, JH Tseng, WYI AF Wedeen, Van J. Rosene, Douglas L. Wang, Ruopeng Dai, Guangping Mortazavi, Farzad Hagmann, Patric Kaas, Jon H. Tseng, Wen-Yih I. TI The Geometric Structure of the Brain Fiber Pathways SO SCIENCE LA English DT Article ID NERVOUS-SYSTEM; TRACTOGRAPHY; ARCHITECTURE; CORTEX; MRI AB The structure of the brain as a product of morphogenesis is difficult to reconcile with the observed complexity of cerebral connectivity. We therefore analyzed relationships of adjacency and crossing between cerebral fiber pathways in four nonhuman primate species and in humans by using diffusion magnetic resonance imaging. The cerebral fiber pathways formed a rectilinear three-dimensional grid continuous with the three principal axes of development. Cortico-cortical pathways formed parallel sheets of interwoven paths in the longitudinal and medio-lateral axes, in which major pathways were local condensations. Cross-species homology was strong and showed emergence of complex gyral connectivity by continuous elaboration of this grid structure. This architecture naturally supports functional spatio-temporal coherence, developmental path-finding, and incremental rewiring with correlated adaptation of structure and function in cerebral plasticity and evolution. C1 [Wedeen, Van J.; Wang, Ruopeng; Dai, Guangping] Harvard Univ, Sch Med, Massachusetts Gen Hosp MGH, Dept Radiol, Charlestown, MA 02129 USA. [Wedeen, Van J.; Wang, Ruopeng; Dai, Guangping] MGH Massachussetts Inst Technol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Rosene, Douglas L.; Mortazavi, Farzad] Boston Univ, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Hagmann, Patric] Univ Lausanne, Univ Hosp Ctr, Dept Radiol, CH-1011 Lausanne, Switzerland. [Kaas, Jon H.] Vanderbilt Univ, Coll Arts & Sci, Dept Psychol, Nashville, TN 37240 USA. [Tseng, Wen-Yih I.] Natl Taiwan Univ, Coll Med, Dept Radiol, Ctr Optoelect Biomed, Taipei 100, Taiwan. RP Wedeen, VJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp MGH, Dept Radiol, Bldg 129,13th St,2nd Floor, Charlestown, MA 02129 USA. EM van@nmr.mgh.harvard.edu RI Rosene, Douglas/G-1973-2015; OI /0000-0002-1911-5428; Rosene, Douglas/0000-0001-8719-1441; Tseng, Wen-Yih Isaac/0000-0002-2314-6868 FU Human Connectome Project [U01 MH093765]; [NSF PHY-0855161]; [NIH R01-MH652456]; [P41 RR-023953]; [P41 RR-14075] FX The authors thank L. C. Abbate, J. W. Belliveau, D. A. Feinberg, B. R. Rosen, S. A. Wedeen, and M. W. Weiner for reviewing this manuscript; J. D. Schmahmann, B. I. Shraiman, R. Turner, H. E. Stanley, and T. J. Brady for their comments; K. Mansfield of the New England Primate Center and L. Worthylake of the Oregon National Primate Research Center for primate specimens; C. Devitt for myelin stains; and M. P. Frosch for human specimens. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Science Foundation, the National Institute Of Mental Health, or the National Institutes of Health. This work is directly supported by grants NSF PHY-0855161, NIH R01-MH652456, P41 RR-023953, P41 RR-14075, and The Human Connectome Project U01 MH093765. V.J.W. designed the methods of MRI acquisition, reconstruction, and analysis; acquired and analyzed the data; discovered the grid structure; and wrote the paper. W.-Y.I.T. collaborated in the development of theoretical, imaging, and anatomic ideas and methods. G.D. implemented MRI acquisition techniques, including hardware and pulse sequences; optimized protocols; and acquired ex vivo MRI. R.W. implemented analysis algorithms and created their user interface. J.H.K. and D.L.R. obtained and prepared specimens, participated in analyses, and contributed to this manuscript. F.M. optimized and obtained immunofluorescent microscopy. P.H. provided in vivo human studies. All authors discussed the results and commented on the manuscript. No author has a major competing interest to declare. All human studies were obtained after signed informed consent, with review and approval by the Institutional Review Board. Tissue specimens were studied as discarded materials, with review and approval by the Institutional Subcommittee on Animal Care. Human tissue specimens were studied as deidentified discarded materials, with review and approval by the Institutional Review Board. NR 36 TC 160 Z9 165 U1 7 U2 79 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAR 30 PY 2012 VL 335 IS 6076 BP 1628 EP 1634 DI 10.1126/science.1215280 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 915YD UT WOS:000302062600046 PM 22461612 ER PT J AU Chen, CH Gutierrez, ED Thompson, W Panizzon, MS Jernigan, TL Eyler, LT Fennema-Notestine, C Jak, AJ Neale, MC Franz, CE Lyons, MJ Grant, MD Fischl, B Seidman, LJ Tsuang, MT Kremen, WS Dale, AM AF Chen, Chi-Hua Gutierrez, E. D. Thompson, Wes Panizzon, Matthew S. Jernigan, Terry L. Eyler, Lisa T. Fennema-Notestine, Christine Jak, Amy J. Neale, Michael C. Franz, Carol E. Lyons, Michael J. Grant, Michael D. Fischl, Bruce Seidman, Larry J. Tsuang, Ming T. Kremen, William S. Dale, Anders M. TI Hierarchical Genetic Organization of Human Cortical Surface Area SO SCIENCE LA English DT Article ID HUMAN BRAIN; NEOCORTEX; RECONSTRUCTION; TRANSCRIPTOME; SEGMENTATION; EXPRESSION; HINDBRAIN; EVOLUTION; BEHAVIOR; CORTEX AB Surface area of the cerebral cortex is a highly heritable trait, yet little is known about genetic influences on regional cortical differentiation in humans. Using a data-driven, fuzzy clustering technique with magnetic resonance imaging data from 406 twins, we parceled cortical surface area into genetic subdivisions, creating a human brain atlas based solely on genetically informative data. Boundaries of the genetic divisions corresponded largely to meaningful structural and functional regions; however, the divisions represented previously undescribed phenotypes different from conventional (non-genetically based) parcellation systems. The genetic organization of cortical area was hierarchical, modular, and predominantly bilaterally symmetric across hemispheres. We also found that the results were consistent with human-specific regions being subdivisions of previously described, genetically based lobar regionalization patterns. C1 [Chen, Chi-Hua; Thompson, Wes; Panizzon, Matthew S.; Jernigan, Terry L.; Eyler, Lisa T.; Fennema-Notestine, Christine; Jak, Amy J.; Franz, Carol E.; Tsuang, Ming T.; Kremen, William S.; Dale, Anders M.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Gutierrez, E. D.; Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. [Eyler, Lisa T.] Vet Adm VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Fennema-Notestine, Christine; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Jak, Amy J.; Tsuang, Ming T.; Kremen, William S.] VA Ctr Excellence Stress & Mental Hlth, San Diego, CA 92093 USA. [Neale, Michael C.; Tsuang, Ming T.; Kremen, William S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23219 USA. [Neale, Michael C.; Tsuang, Ming T.; Kremen, William S.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23219 USA. [Franz, Carol E.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Lyons, Michael J.; Grant, Michael D.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Kremen, WS (reprint author), Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. EM wkremen@ucsd.edu OI Lyons, Michael/0000-0001-6516-9219; Fennema-Notestine, Christine/0000-0002-6527-6361 FU National Institute on Aging [AG022381, AG018386, AG018384, AG022982, AG031224]; National Institute of Drug Abuse [DA029475]; National Institute of Neurological Disorders and Stroke [NS056883]; National Center for Research Resources [P41-RR14075, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [EB006758]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [NS052585-01, 1R21NS072652-01, 1R01NS070963]; National Institutes of Health [T32DC000041]; Ellison Medical Foundation; VA San Diego Center of Excellence for Stress and Mental Health; Office of Research and Development, U.S. Department of Veterans Affairs FX This work was funded by the National Institute on Aging (AG022381, AG018386, AG018384, AG022982, and AG031224), National Institute of Drug Abuse (DA029475), National Institute of Neurological Disorders and Stroke (NS056883), National Center for Research Resources (P41-RR14075, BIRN002, and U24 RR021382), National Institute for Biomedical Imaging and Bioengineering (EB006758), National Center for Alternative Medicine (RC1 AT005728-01), National Institute for Neurological Disorders and Stroke (NS052585-01, 1R21NS072652-01, and 1R01NS070963), National Institutes of Health (T32DC000041), and the Ellison Medical Foundation. This material is also partly the result of work supported with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program, Office of Research and Development, U.S. Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. A.M.D. is a founder and holds equity in CorTechs Laboratories and also serves on its Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. NR 24 TC 105 Z9 107 U1 1 U2 23 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAR 30 PY 2012 VL 335 IS 6076 BP 1634 EP 1636 DI 10.1126/science.1215330 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 915YD UT WOS:000302062600047 PM 22461613 ER PT J AU Zhou, XH Chen, B Xie, YM Tian, F Liu, H Liang, X AF Zhou, X. H. Chen, B. Xie, Y. M. Tian, F. Liu, H. Liang, X. TI Variable selection using the optimal ROC curve: An application to a traditional Chinese medicine study on osteoporosis disease SO STATISTICS IN MEDICINE LA English DT Article DE AUC; classification; ROC; variable selection ID ORACLE PROPERTIES; REGRESSION; CLASSIFICATION; MANAGEMENT; LASSO AB In biomedical studies, there are multiple sources of information available of which only a small number of them are associated with the diseases. It is of importance to select and combine these factors that are associated with the disease in order to predict the disease status of a new subject. The receiving operating characteristic (ROC) technique has been widely used in disease classification, and the classification accuracy can be measured with area under the ROC curve (AUC). In this article, we combine recent variable selection methods with AUC methods to optimize diagnostic accuracy of multiple risk factors. We first describe one new and some recent AUC-based methods for effectively combining multiple risk factors for disease classification. We then apply them to analyze the data from a new clinical study, investigating whether a combination of traditional Chinese medicine symptoms and standard Western medicine risk factors can increase discriminative accuracy in diagnosing osteoporosis (OP). Based on the results, we conclude that we can make a better diagnosis of primary OP by combining traditional Chinese medicine symptoms with Western medicine risk factors. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Xie, Y. M.; Tian, F.; Liu, H.] China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing 100700, Peoples R China. [Zhou, X. H.; Liang, X.] Renmin Univ, Sch Stat, Beijing 100872, Peoples R China. [Zhou, X. H.] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. [Zhou, X. H.; Chen, B.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Xie, YM (reprint author), China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing 100700, Peoples R China. EM zhinanb2005@yahoo.com.cn; tianfengzzz@126.com FU National Science Foundation of China (NSFC) [30728019, 30873339] FX Dr Xiao-Hua Zhou, PhD, is presently a Core Investigator and Biostatistics Unit Director at the Northwest HSR&D Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA. Part of this work was supported by the two National Science Foundation of China grants (NSFC No. 30728019 and NSFC No. 30873339). This paper presents the findings and conclusions of the authors. It does not necessarily represent those of VA HSR&D Service. NR 30 TC 5 Z9 5 U1 3 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD MAR 30 PY 2012 VL 31 IS 7 SI SI BP 628 EP 635 DI 10.1002/sim.3980 PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 903MY UT WOS:000301121900005 PM 21290404 ER PT J AU Kelleher, CM Forcione, DG Gee, MS Mino-Kenudson, M AF Kelleher, Cassandra M. Forcione, David G. Gee, Michael S. Mino-Kenudson, Mari TI Case 10-2012: A 16-Year-Old Boy with Epigastric Pain and a Mediastinal Mass Esophageal duplication cyst with chronic inflammation, necrosis, and calcification. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BRONCHOGENIC CYSTS; LYMPHANGIOMA; MYELOMENINGOCELE; DIAGNOSIS; RESECTION; ADULT; FNA; EUS C1 [Kelleher, Cassandra M.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Forcione, David G.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Gee, Michael S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kelleher, Cassandra M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Forcione, David G.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gee, Michael S.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kelleher, CM (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. NR 27 TC 0 Z9 0 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 29 PY 2012 VL 366 IS 13 BP 1241 EP 1249 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 915DW UT WOS:000302005100014 PM 22455419 ER PT J AU Kitami, T Logan, DJ Negri, J Hasaka, T Tolliday, NJ Carpenter, AE Spiegelman, BM Mootha, VK AF Kitami, Toshimori Logan, David J. Negri, Joseph Hasaka, Thomas Tolliday, Nicola J. Carpenter, Anne E. Spiegelman, Bruce M. Mootha, Vamsi K. TI A Chemical Screen Probing the Relationship between Mitochondrial Content and Cell Size SO PLOS ONE LA English DT Article ID OXIDATIVE-PHOSPHORYLATION; SKELETAL-MUSCLE; GENE-EXPRESSION; RECEPTOR-ALPHA; ERR-ALPHA; BIOGENESIS; KINASE; COACTIVATOR; PGC-1-ALPHA; INHIBITORS AB The cellular content of mitochondria changes dynamically during development and in response to external stimuli, but the underlying mechanisms remain obscure. To systematically identify molecular probes and pathways that control mitochondrial abundance, we developed a high-throughput imaging assay that tracks both the per cell mitochondrial content and the cell size in confluent human umbilical vein endothelial cells. We screened 28,786 small molecules and observed that hundreds of small molecules are capable of increasing or decreasing the cellular content of mitochondria in a manner proportionate to cell size, revealing stereotyped control of these parameters. However, only a handful of compounds dissociate this relationship. We focus on one such compound, BRD6897, and demonstrate through secondary assays that it increases the cellular content of mitochondria as evidenced by fluorescence microscopy, mitochondrial protein content, and respiration, even after rigorous correction for cell size, cell volume, or total protein content. BRD6897 increases uncoupled respiration 1.6-fold in two different, non-dividing cell types. Based on electron microscopy, BRD6897 does not alter the percent of cytoplasmic area occupied by mitochondria, but instead, induces a striking increase in the electron density of existing mitochondria. The mechanism is independent of known transcriptional programs and is likely to be related to a blockade in the turnover of mitochondrial proteins. At present the molecular target of BRD6897 remains to be elucidated, but if identified, could reveal an important additional mechanism that governs mitochondrial biogenesis and turnover. C1 [Kitami, Toshimori; Logan, David J.; Negri, Joseph; Hasaka, Thomas; Tolliday, Nicola J.; Carpenter, Anne E.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA. [Kitami, Toshimori; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Kitami, Toshimori; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. RP Kitami, T (reprint author), Broad Inst, Cambridge, MA USA. EM vamsi@hms.harvard.edu RI Carpenter, Anne/C-4982-2008 OI Carpenter, Anne/0000-0003-1555-8261 FU National Institutes of Health (NIH) [R24DK080261]; Richard and Susan Smith Family Foundation; Nestle Research Center [R01GM089652] FX This work was funded by a grant from the National Institutes of Health (NIH) (R24DK080261) to Dr. Spiegelman and Dr. Mootha, Richard and Susan Smith Family Foundation and Nestle Research Center award to Dr. Mootha, and a grant from NIH (R01GM089652) to Dr. Carpenter. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 16 Z9 16 U1 0 U2 10 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 29 PY 2012 VL 7 IS 3 AR e33755 DI 10.1371/journal.pone.0033755 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 948SR UT WOS:000304523400032 PM 22479437 ER PT J AU Simonis, N Rual, JF Lemmens, I Boxus, M Hirozane-Kishikawa, T Gatot, JS Dricot, A Hao, T Vertommen, D Legros, S Daakour, S Klitgord, N Martin, M Willaert, JF Dequiedt, F Navratil, V Cusick, ME Burny, A Van Lint, C Hill, DE Tavernier, J Kettmann, R Vidal, M Twizere, JC AF Simonis, Nicolas Rual, Jean-Francois Lemmens, Irma Boxus, Mathieu Hirozane-Kishikawa, Tomoko Gatot, Jean-Stephane Dricot, Amelie Hao, Tong Vertommen, Didier Legros, Sebastien Daakour, Sarah Klitgord, Niels Martin, Maud Willaert, Jean-Francois Dequiedt, Franck Navratil, Vincent Cusick, Michael E. Burny, Arsene Van Lint, Carine Hill, David E. Tavernier, Jan Kettmann, Richard Vidal, Marc Twizere, Jean-Claude TI Host-pathogen interactome mapping for HTLV-1 and -2 retroviruses SO RETROVIROLOGY LA English DT Article DE HTLV; Interactome; Retrovirus; ORFeome; Tax; HBZ ID T-CELL LEUKEMIA; VIRUS TYPE-1 TAX; ANAPHASE-PROMOTING COMPLEX; PROTEIN-INTERACTION NETWORK; TRANSCRIPTION FACTORS; INTERACTION DATABASE; NUCLEOTIDE-SEQUENCE; GENE-EXPRESSION; FANCONI-ANEMIA; RNA-BINDING AB Background: Human T-cell leukemia virus type 1 (HTLV-1) and type 2 both target T lymphocytes, yet induce radically different phenotypic outcomes. HTLV-1 is a causative agent of Adult T-cell leukemia (ATL), whereas HTLV-2, highly similar to HTLV-1, causes no known overt disease. HTLV gene products are engaged in a dynamic struggle of activating and antagonistic interactions with host cells. Investigations focused on one or a few genes have identified several human factors interacting with HTLV viral proteins. Most of the available interaction data concern the highly investigated HTLV-1 Tax protein. Identifying shared and distinct host-pathogen protein interaction profiles for these two viruses would enlighten how they exploit distinctive or common strategies to subvert cellular pathways toward disease progression. Results: We employ a scalable methodology for the systematic mapping and comparison of pathogen-host protein interactions that includes stringent yeast two-hybrid screening and systematic retest, as well as two independent validations through an additional protein interaction detection method and a functional transactivation assay. The final data set contained 166 interactions between 10 viral proteins and 122 human proteins. Among the 166 interactions identified, 87 and 79 involved HTLV-1 and HTLV-2 -encoded proteins, respectively. Targets for HTLV-1 and HTLV-2 proteins implicate a diverse set of cellular processes including the ubiquitin-proteasome system, the apoptosis, different cancer pathways and the Notch signaling pathway. Conclusions: This study constitutes a first pass, with homogeneous data, at comparative analysis of host targets for HTLV-1 and -2 retroviruses, complements currently existing data for formulation of systems biology models of retroviral induced diseases and presents new insights on biological pathways involved in retroviral infection. C1 [Simonis, Nicolas; Rual, Jean-Francois; Hirozane-Kishikawa, Tomoko; Dricot, Amelie; Hao, Tong; Klitgord, Niels; Cusick, Michael E.; Hill, David E.; Vidal, Marc; Twizere, Jean-Claude] Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA. [Simonis, Nicolas; Rual, Jean-Francois; Hirozane-Kishikawa, Tomoko; Dricot, Amelie; Hao, Tong; Klitgord, Niels; Cusick, Michael E.; Hill, David E.; Vidal, Marc; Twizere, Jean-Claude] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Simonis, Nicolas; Rual, Jean-Francois; Hirozane-Kishikawa, Tomoko; Dricot, Amelie; Hao, Tong; Klitgord, Niels; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Simonis, Nicolas] Univ Libre Brussels, Lab Bioinformat Genomes & Reseaux BiGRe, B-1050 Brussels, Belgium. [Boxus, Mathieu; Legros, Sebastien; Daakour, Sarah; Martin, Maud; Willaert, Jean-Francois; Dequiedt, Franck; Burny, Arsene; Kettmann, Richard; Twizere, Jean-Claude] Univ Liege, Prot Signaling & Interact GIGA Res Ctr, B-4000 Liege, Belgium. [Boxus, Mathieu; Legros, Sebastien; Daakour, Sarah; Martin, Maud; Willaert, Jean-Francois; Dequiedt, Franck; Burny, Arsene; Kettmann, Richard; Twizere, Jean-Claude] Univ Liege, Dept Chem Gembloux ABT, B-4000 Liege, Belgium. [Lemmens, Irma; Tavernier, Jan] Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium. [Gatot, Jean-Stephane; Van Lint, Carine] Univ Libre Brussels, Lab Mol Virol, Inst Biol & Med Mol, B-6041 Gosselies, Belgium. [Vertommen, Didier] Catholic Univ Louvain, Hormones & Metab Unit, B-1200 Brussels, Belgium. [Vertommen, Didier] de Duve Inst, B-1200 Brussels, Belgium. [Navratil, Vincent] Univ Lyon, INRA, UMR754, Ecole Natl Vet Lyon, F-69007 Lyon, France. [Navratil, Vincent] INSERM, U851, F-69007 Lyon, France. RP Vidal, M (reprint author), Dana Farber Canc Inst, CCSB, 450 Brookline Ave, Boston, MA 02215 USA. EM marc_vidal@dfci.harvard.edu; jean-claude.twizere@ulg.ac.be RI navratil, vincent/C-4193-2008; Hill, David/B-6617-2011; OI Rual, Jean-Francois/0000-0003-4465-8819; Vertommen, Didier/0000-0001-7648-8282 FU Belspo (Belgian Federal Government); Deutsche Jose Carreras Leukamie-Stiftung; US National Human Genome Research Institute [2R01HG001715, 5P50HG004233]; US National Cancer Institute [5U54CA112952]; Ellison Foundation; DFCI Institute; FRS-FNRS [7.4.594.07, 7.4.545.08]; Interuniversity Attraction Poles Program-Belgian Science Policy (IUAP-BELSPO) [PVI/28] FX We thank Jean-Francois Dewulf and Aurelie Devresse for excellent technical support and Dr. Marlene Oeffinger for proofreading and useful comments. We also thank the AIDS Research and Reference Reagent Program (Division of AIDS, NIAID, NIH, USA), Dr. F. Bex (Universite Libre de Bruxelles, Belgium) and Dr. R. Mahieux (INSERM-U758 Virologie Humaine, France) for providing key reagents. J.-C.T., R.K., F.D., M.B., M.M., S.L., S.D. are members of the "Fonds de la Recherche Scientifique" (FRS-FNRS, French Community of Belgium). N.S. is supported by a return grant from Belspo (Belgian Federal Government). I. L. is a postdoctoral fellow with the Fonds Wetenschappelijk Onderzoek-Vlaanderen. J.-F.R. is supported by the Deutsche Jose Carreras Leukamie-Stiftung. M. V. is a "Chercheur Qualifie Honoraire" of the "Fonds de la Recherche Scientifique". This work was supported by US National Human Genome Research Institute grants 2R01HG001715 (to M. V. and D. E. H.) and 5P50HG004233 (to M. V.), US National Cancer Institute grant 5U54CA112952 (to J. Nevins, subcontract to M. V.), the Ellison Foundation (to M. V.), DFCI Institute Sponsored Research funds (to M. V.), FRS-FNRS grants 7.4.594.07 and 7.4.545.08 (to R.K. and J.-C.T.) and Interuniversity Attraction Poles Program-Belgian Science Policy (IUAP-BELSPO PVI/28 to F.D. and J.T.). NR 92 TC 43 Z9 44 U1 1 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAR 29 PY 2012 VL 9 AR 26 DI 10.1186/1742-4690-9-26 PG 20 WC Virology SC Virology GA 942QA UT WOS:000304060200001 PM 22458338 ER PT J AU Waldron, L Simpson, P Parmigiani, G Huttenhower, C AF Waldron, Levi Simpson, Peter Parmigiani, Giovanni Huttenhower, Curtis TI Report on emerging technologies for translational bioinformatics: a symposium on gene expression profiling for archival tissues SO BMC CANCER LA English DT Article AB Background: With over 20 million formalin-fixed, paraffin-embedded (FFPE) tissue samples archived each year in the United States alone, archival tissues remain a vast and under-utilized resource in the genomic study of cancer. Technologies have recently been introduced for whole-transcriptome amplification and microarray analysis of degraded mRNA fragments from FFPE samples, and studies of these platforms have only recently begun to enter the published literature. Results: The Emerging Technologies for Translational Bioinformatics symposium on gene expression profiling for archival tissues featured presentations of two large-scale FFPE expression profiling studies (each involving over 1,000 samples), overviews of several smaller studies, and representatives from three leading companies in the field (Illumina, Affymetrix, and NuGEN). The meeting highlighted challenges in the analysis of expression data from archival tissues and strategies being developed to overcome them. In particular, speakers reported higher rates of clinical sample failure (from 10% to 70%) than are typical for fresh-frozen tissues, as well as more frequent probe failure for individual samples. The symposium program is available at http://www.hsph.harvard.edu/ffpe. Conclusions: Multiple solutions now exist for whole-genome expression profiling of FFPE tissues, including both microarray- and sequencing-based platforms. Several studies have reported their successful application, but substantial challenges and risks still exist. Symposium speakers presented novel methodology for analysis of FFPE expression data and suggestions for improving data recovery and quality assessment in pre-analytical stages. Research presentations emphasized the need for careful study design, including the use of pilot studies, replication, and randomization of samples among batches, as well as careful attention to data quality control. Regardless of any limitations in quantitave transcriptomics for FFPE tissues, they are often the only biospecimens available for large patient populations with long-term history and clinical follow-up. Current challenges can be expected to remain as RNA sequencing matures, and they will thus motivate ongoing research efforts into noise reduction and identification of robust, translationally relevant biological signals in expression data from FFPE tissues. C1 [Waldron, Levi; Parmigiani, Giovanni; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Waldron, Levi; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Simpson, Peter] Univ Queensland, UQ Ctr Clin Res, Brisbane, Qld 4029, Australia. RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM chuttenh@hsph.harvard.edu RI Simpson, Peter/F-1225-2010; OI Simpson, Peter/0000-0002-4816-8289; Waldron, Levi/0000-0003-2725-0694; Huttenhower, Curtis/0000-0002-1110-0096 FU National Science Foundation [NSF DBI-1053486]; National Cancer Institute [1RC4CA156551-01]; National Breast Cancer Foundation, Australia; Illumina; NuGEN; Affymetrix; HSPH FX This work was supported by the National Science Foundation grant NSF DBI-1053486 (to CH) and by the National Cancer Institute 1RC4CA156551-01 (to GP). PTS is a recipient of a fellowship from the National Breast Cancer Foundation, Australia. The Symposium was sponsored by Illumina, NuGEN, Affymetrix, and the HSPH Program in Quantitative Genomics (PQG), and co-hosted by DFCI Biostatistics & Computational Biology, the HSPH Department of Biostatistics and the Biostatistics and Computational Biology Program of the Dana Farber Harvard Comprehensive Cancer Center. NR 3 TC 11 Z9 11 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 29 PY 2012 VL 12 AR 124 DI 10.1186/1471-2407-12-124 PG 4 WC Oncology SC Oncology GA 934NP UT WOS:000303451300002 PM 22458912 ER PT J AU Garnett, MJ Edelman, EJ Heidorn, SJ Greenman, CD Dastur, A Lau, KW Greninger, P Thompson, IR Luo, X Soares, J Liu, QS Iorio, F Surdez, D Chen, L Milano, RJ Bignell, GR Tam, AT Davies, H Stevenson, JA Barthorpe, S Lutz, SR Kogera, F Lawrence, K McLaren-Douglas, A Mitropoulos, X Mironenko, T Thi, H Richardson, L Zhou, WJ Jewitt, F Zhang, TH O'Brien, P Boisvert, JL Price, S Hur, W Yang, WJ Deng, XM Butler, A Choi, HG Chang, J Baselga, J Stamenkovic, I Engelman, JA Sharma, SV Delattre, O Saez-Rodriguez, J Gray, NS Settleman, J Futreal, PA Haber, DA Stratton, MR Ramaswamy, S McDermott, U Benes, CH AF Garnett, Mathew J. Edelman, Elena J. Heidorn, Sonja J. Greenman, Chris D. Dastur, Anahita Lau, King Wai Greninger, Patricia Thompson, I. Richard Luo, Xi Soares, Jorge Liu, Qingsong Iorio, Francesco Surdez, Didier Chen, Li Milano, Randy J. Bignell, Graham R. Tam, Ah T. Davies, Helen Stevenson, Jesse A. Barthorpe, Syd Lutz, Stephen R. Kogera, Fiona Lawrence, Karl McLaren-Douglas, Anne Mitropoulos, Xeni Mironenko, Tatiana Thi, Helen Richardson, Laura Zhou, Wenjun Jewitt, Frances Zhang, Tinghu O'Brien, Patrick Boisvert, Jessica L. Price, Stacey Hur, Wooyoung Yang, Wanjuan Deng, Xianming Butler, Adam Choi, Hwan Geun Chang, JaeWon Baselga, Jose Stamenkovic, Ivan Engelman, Jeffrey A. Sharma, Sreenath V. Delattre, Olivier Saez-Rodriguez, Julio Gray, Nathanael S. Settleman, Jeffrey Futreal, P. Andrew Haber, Daniel A. Stratton, Michael R. Ramaswamy, Sridhar McDermott, Ultan Benes, Cyril H. TI Systematic identification of genomic markers of drug sensitivity in cancer cells SO NATURE LA English DT Article ID MESENCHYMAL PROGENITOR CELLS; KINASE INHIBITOR; IN-VIVO; POLY(ADP-RIBOSE) POLYMERASE; EWINGS-SARCOMA; LUNG-CANCER; P53 PATHWAY; GROWTH; EXPRESSION; MELANOMA AB Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines-which represent much of the tissue-type and genetic diversity of human cancers-with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies. C1 [Garnett, Mathew J.; Heidorn, Sonja J.; Greenman, Chris D.; Lau, King Wai; Thompson, I. Richard; Soares, Jorge; Iorio, Francesco; Bignell, Graham R.; Davies, Helen; Barthorpe, Syd; Kogera, Fiona; Lawrence, Karl; McLaren-Douglas, Anne; Mironenko, Tatiana; Richardson, Laura; Jewitt, Frances; O'Brien, Patrick; Price, Stacey; Yang, Wanjuan; Butler, Adam; Futreal, P. Andrew; Stratton, Michael R.; McDermott, Ultan] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. [Edelman, Elena J.; Dastur, Anahita; Greninger, Patricia; Luo, Xi; Chen, Li; Milano, Randy J.; Stevenson, Jesse A.; Lutz, Stephen R.; Mitropoulos, Xeni; Thi, Helen; Boisvert, Jessica L.; Baselga, Jose; Engelman, Jeffrey A.; Sharma, Sreenath V.; Settleman, Jeffrey; Haber, Daniel A.; Ramaswamy, Sridhar; Benes, Cyril H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Liu, Qingsong; Zhou, Wenjun; Zhang, Tinghu; Hur, Wooyoung; Deng, Xianming; Choi, Hwan Geun; Chang, JaeWon; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, Qingsong; Zhou, Wenjun; Zhang, Tinghu; Hur, Wooyoung; Deng, Xianming; Choi, Hwan Geun; Chang, JaeWon; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Iorio, Francesco; Saez-Rodriguez, Julio] EMBL EBI, Cambridge CB10 1SD, England. [Surdez, Didier; Delattre, Olivier] Inst Curie, Lab Genet & Biol Canc, F-75248 Paris 05, France. [Stamenkovic, Ivan] CHU Vaudois, Inst Pathol, Div Expt Pathol, CH-1005 Lausanne, Switzerland. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP McDermott, U (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. EM um1@sanger.ac.uk; cbenes@partners.org RI Thompson, Ian/J-9900-2016; OI Iorio, Francesco/0000-0001-7063-8913; McDermott, Ultan/0000-0001-9032-4700; liu, qing song/0000-0002-7829-2547; Saez-Rodriguez, Julio/0000-0002-8552-8976 FU Wellcome Trust [086357]; National Institutes of Health [P41GM079575-02, 1U54HG006097-01]; Howard Hughes Medical Institute; Cancer Research UK Clinician Scientist Fellowship FX We thank P. Lo Grasso of the Scripps Research Institute for providing the inhibitor JNK9L. This work was supported by a grant from the Wellcome Trust (086357; M. R. S., P. A. F., J.S., D. A. H.) and by grants from the National Institutes of Health (P41GM079575-02 to N.S.G. and 1U54HG006097-01 to N.S.G. and D. A. H.). S. R. is supported by a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute. U. M. is supported by a Cancer Research UK Clinician Scientist Fellowship. NR 37 TC 705 Z9 714 U1 25 U2 215 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 29 PY 2012 VL 483 IS 7391 BP 570 EP U87 DI 10.1038/nature11005 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 915EF UT WOS:000302006100033 PM 22460902 ER PT J AU Onder, TT Kara, N Cherry, A Sinha, AU Zhu, N Bernt, KM Cahan, P Mancarci, BO Unternaehrer, J Gupta, PB Lander, ES Armstrong, SA Daley, GQ AF Onder, Tamer T. Kara, Nergis Cherry, Anne Sinha, Amit U. Zhu, Nan Bernt, Kathrin M. Cahan, Patrick Mancarci, B. Ogan Unternaehrer, Juli Gupta, Piyush B. Lander, Eric S. Armstrong, Scott A. Daley, George Q. TI Chromatin-modifying enzymes as modulators of reprogramming SO NATURE LA English DT Article ID PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; HISTONE METHYLATION; SEQUENCES; LEUKEMIA; GENOME; DOT1L; PRC2 AB Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling(1). Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells before and after reprogramming(2,3), the role of specific chromatin-modifying enzymes in reprogramming remains to be determined. To address how chromatin-modifying proteins influence reprogramming, we used short hairpin RNAs (shRNAs) to target genes in DNA and histone methylation pathways, and identified positive and negative modulators of iPSC generation. Whereas inhibition of the core components of the polycomb repressive complex 1 and 2, including the histone 3 lysine 27 methyltransferase EZH2, reduced reprogramming efficiency, suppression of SUV39H1, YY1 and DOT1L enhanced reprogramming. Specifically, inhibition of the H3K79 histone methyltransferase DOT1L by shRNA or a small molecule accelerated reprogramming, significantly increased the yield of iPSC colonies, and substituted for KLF4 and c-Myc (also known as MYC). Inhibition of DOT1L early in the reprogramming process is associated with a marked increase in two alternative factors, NANOG and LIN28, which play essential functional roles in the enhancement of reprogramming. Genome-wide analysis of H3K79me2 distribution revealed that fibroblast-specific genes associated with the epithelial to mesenchymal transition lose H3K79me2 in the initial phases of reprogramming. DOT1L inhibition facilitates the loss of this mark from genes that are fated to be repressed in the pluripotent state. These findings implicate specific chromatin-modifying enzymes as barriers to or facilitators of reprogramming, and demonstrate how modulation of chromatinmodifying enzymes can be exploited to more efficiently generate iPSCs with fewer exogenous transcription factors. C1 [Onder, Tamer T.; Cherry, Anne; Cahan, Patrick; Unternaehrer, Juli; Daley, George Q.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. [Onder, Tamer T.; Cherry, Anne; Cahan, Patrick; Unternaehrer, Juli; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Onder, Tamer T.; Cherry, Anne; Cahan, Patrick; Unternaehrer, Juli; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Onder, Tamer T.; Cherry, Anne; Zhu, Nan; Bernt, Kathrin M.; Cahan, Patrick; Unternaehrer, Juli; Armstrong, Scott A.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Onder, Tamer T.; Cherry, Anne; Cahan, Patrick; Unternaehrer, Juli; Daley, George Q.] Childrens Hosp Boston, Stem Cell Program, Boston, MA 02115 USA. [Kara, Nergis] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Sinha, Amit U.; Zhu, Nan; Bernt, Kathrin M.; Armstrong, Scott A.; Daley, George Q.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Sinha, Amit U.; Zhu, Nan; Bernt, Kathrin M.; Armstrong, Scott A.] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. [Mancarci, B. Ogan] Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey. [Gupta, Piyush B.; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Gupta, Piyush B.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lander, Eric S.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Daley, GQ (reprint author), Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. EM George.Daley@childrens.harvard.edu RI Cherry, Anne/E-7333-2011; Onder, Tamer /H-3330-2013; Bernt, Kathrin/L-1826-2016; OI Onder, Tamer /0000-0002-2372-9158; Bernt, Kathrin/0000-0002-5400-0482; Cahan, Patrick/0000-0003-3652-2540 FU US National Institutes of Health (NIH) [CA140575]; CHB Stem Cell Program FX We thank G. Hu and S. J. Elledge for providing the MSCV-PM vector, K. Ng and M. W. Lensch for teratoma injections and assessment and S. Loewer for discussions. We also thank E. Olhava and Epizyme Inc. for synthesizing and providing the DOT1L inhibitor, EPZ004777. G. Q. D. is an investigator of the Howard Hughes Medical Institute. Research was funded by grants from the US National Institutes of Health (NIH) to S. A. A. (CA140575) and G. Q. D., and the CHB Stem Cell Program. NR 29 TC 273 Z9 279 U1 16 U2 99 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 29 PY 2012 VL 483 IS 7391 BP 598 EP U119 DI 10.1038/nature10953 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 915EF UT WOS:000302006100039 PM 22388813 ER PT J AU Barretina, J Caponigro, G Stransky, N Venkatesan, K Margolin, AA Kim, S Wilson, CJ Lehar, J Kryukov, GV Sonkin, D Reddy, A Liu, MW Murray, L Berger, MF Monahan, JE Morais, P Meltzer, J Korejwa, A Jane-Valbuena, J Mapa, FA Thibault, J Bric-Furlong, E Raman, P Shipway, A Engels, IH Cheng, J Yu, GYK Yu, JJ Aspesi, P de Silva, M Jagtap, K Jones, MD Wang, L Hatton, C Palescandolo, E Gupta, S Mahan, S Sougnez, C Onofrio, RC Liefeld, T MacConaill, L Winckler, W Reich, M Li, NX Mesirov, JP Gabriel, SB Getz, G Ardlie, K Chan, V Myer, VE Weber, BL Porter, J Warmuth, M Finan, P Harris, JL Meyerson, M Golub, TR Morrissey, MP Sellers, WR Schlegel, R Garraway, LA AF Barretina, Jordi Caponigro, Giordano Stransky, Nicolas Venkatesan, Kavitha Margolin, Adam A. Kim, Sungjoon Wilson, Christopher J. Lehar, Joseph Kryukov, Gregory V. Sonkin, Dmitriy Reddy, Anupama Liu, Manway Murray, Lauren Berger, Michael F. Monahan, John E. Morais, Paula Meltzer, Jodi Korejwa, Adam Jane-Valbuena, Judit Mapa, Felipa A. Thibault, Joseph Bric-Furlong, Eva Raman, Pichai Shipway, Aaron Engels, Ingo H. Cheng, Jill Yu, Guoying K. Yu, Jianjun Aspesi, Peter, Jr. de Silva, Melanie Jagtap, Kalpana Jones, Michael D. Wang, Li Hatton, Charles Palescandolo, Emanuele Gupta, Supriya Mahan, Scott Sougnez, Carrie Onofrio, Robert C. Liefeld, Ted MacConaill, Laura Winckler, Wendy Reich, Michael Li, Nanxin Mesirov, Jill P. Gabriel, Stacey B. Getz, Gad Ardlie, Kristin Chan, Vivien Myer, Vic E. Weber, Barbara L. Porter, Jeff Warmuth, Markus Finan, Peter Harris, Jennifer L. Meyerson, Matthew Golub, Todd R. Morrissey, Michael P. Sellers, William R. Schlegel, Robert Garraway, Levi A. TI The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity SO NATURE LA English DT Article ID MALIGNANT-MELANOMA; INHIBITOR; KINASE; RECEPTOR; ANTAGONIST; EXPRESSION AB The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available(1). Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens(2). C1 [Barretina, Jordi; Stransky, Nicolas; Margolin, Adam A.; Kryukov, Gregory V.; Murray, Lauren; Berger, Michael F.; Morais, Paula; Korejwa, Adam; Jane-Valbuena, Judit; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C.; Liefeld, Ted; Winckler, Wendy; Reich, Michael; Mesirov, Jill P.; Gabriel, Stacey B.; Getz, Gad; Ardlie, Kristin; Meyerson, Matthew; Golub, Todd R.; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Barretina, Jordi; Jane-Valbuena, Judit; Meyerson, Matthew; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Barretina, Jordi; Hatton, Charles; Palescandolo, Emanuele; MacConaill, Laura; Meyerson, Matthew; Golub, Todd R.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Caponigro, Giordano; Venkatesan, Kavitha; Wilson, Christopher J.; Lehar, Joseph; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Monahan, John E.; Meltzer, Jodi; Mapa, Felipa A.; Bric-Furlong, Eva; Raman, Pichai; Aspesi, Peter, Jr.; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D.; Wang, Li; Myer, Vic E.; Weber, Barbara L.; Porter, Jeff; Warmuth, Markus; Finan, Peter; Morrissey, Michael P.; Sellers, William R.; Schlegel, Robert] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Kim, Sungjoon; Thibault, Joseph; Shipway, Aaron; Engels, Ingo H.; Li, Nanxin; Harris, Jennifer L.] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. [Cheng, Jill; Yu, Guoying K.; Yu, Jianjun; Chan, Vivien] Novartis Inst Biomed Res, Emeryville, CA 94608 USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Garraway, LA (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM robert.schlegel@novartis.com; Levi_Garraway@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Kryukov, Gregory/A-9592-2008; Morrissey, Michael/C-6792-2013; OI Kryukov, Gregory/0000-0002-6131-9483; Sonkin, Dmitriy/0000-0002-1649-0652; Monahan, John/0000-0002-3125-8704 FU Novartis Institutes for Biomedical Research; National Cancer Institute; Starr Cancer Consortium; NIH FX We thank the staff of the Biological Samples Platform, the Genetic Analysis Platform and the Sequencing Platform at the Broad Institute. We thank S. Banerji, J. Che, C. M. Johannessen, A. Su and N. Wagle for advice and discussion. We are grateful for the technical assistance and support of G. Bonamy, R. Brusch III, E. Gelfand, K. Gravelin, T. Huynh, S. Kehoe, K. Matthews, J. Nedzel, L. Niu, R. Pinchback, D. Roby, J. Slind, T. R. Smith, L. Tan, V. Trinh, C. Vickers, G. Yang, Y. Yao and X. Zhang. The Cancer Cell Line Encyclopedia project was enabled by a grant from the Novartis Institutes for Biomedical Research. Additional funding support was provided by the National Cancer Institute (M. M., L. A. G.), the Starr Cancer Consortium (M. F. B., L. A. G.), and the NIH Director's New Innovator Award (L.A.G.). NR 26 TC 1422 Z9 1438 U1 28 U2 240 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 29 PY 2012 VL 483 IS 7391 BP 603 EP 607 DI 10.1038/nature11003 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 915EF UT WOS:000302006100040 PM 22460905 ER PT J AU Chen, Z Cheng, K Walton, Z Wang, YC Ebi, H Shimamura, T Liu, Y Tupper, T Ouyang, J Li, J Gao, P Woo, MS Xu, CX Yanagita, M Altabef, A Wang, SM Lee, C Nakada, Y Pena, CG Sun, YP Franchetti, Y Yao, C Saur, A Cameron, MD Nishino, M Hayes, DN Wilkerson, MD Roberts, PJ Lee, CB Bardeesy, N Butaney, M Chirieac, LR Costa, DB Jackman, D Sharpless, NE Castrillon, DH Demetri, GD Janne, PA Pandolfi, PP Cantley, LC Kung, AL Engelman, JA Wong, KK AF Chen, Zhao Cheng, Katherine Walton, Zandra Wang, Yuchuan Ebi, Hiromichi Shimamura, Takeshi Liu, Yan Tupper, Tanya Ouyang, Jing Li, Jie Gao, Peng Woo, Michele S. Xu, Chunxiao Yanagita, Masahiko Altabef, Abigail Wang, Shumei Lee, Charles Nakada, Yuji Pena, Christopher G. Sun, Yanping Franchetti, Yoko Yao, Catherine Saur, Amy Cameron, Michael D. Nishino, Mizuki Hayes, D. Neil Wilkerson, Matthew D. Roberts, Patrick J. Lee, Carrie B. Bardeesy, Nabeel Butaney, Mohit Chirieac, Lucian R. Costa, Daniel B. Jackman, David Sharpless, Norman E. Castrillon, Diego H. Demetri, George D. Jaenne, Pasi A. Pandolfi, Pier Paolo Cantley, Lewis C. Kung, Andrew L. Engelman, Jeffrey A. Wong, Kwok-Kin TI A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response SO NATURE LA English DT Article ID STANDARDIZED UPTAKE VALUE; VOLUME MEASUREMENT; MOUSE MODELS; SURVIVAL; METAANALYSIS; GEFITINIB; DOCETAXEL; ADENOCARCINOMA; ARRY-142886; ACTIVATION AB Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers(1-4). Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy(1,3). The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors(5-) (9), has not been fully explored. Here we use genetically engineeredmousemodels to conduct a ` co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244)(10) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors(6,9,11,12), markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies. C1 [Chen, Zhao; Ebi, Hiromichi; Liu, Yan; Xu, Chunxiao; Jaenne, Pasi A.; Engelman, Jeffrey A.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Chen, Zhao; Cheng, Katherine; Walton, Zandra; Liu, Yan; Ouyang, Jing; Gao, Peng; Woo, Michele S.; Xu, Chunxiao; Yanagita, Masahiko; Altabef, Abigail; Yao, Catherine; Butaney, Mohit; Jackman, David; Jaenne, Pasi A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Zhao; Cheng, Katherine; Walton, Zandra; Liu, Yan; Gao, Peng; Xu, Chunxiao; Demetri, George D.; Wong, Kwok-Kin] Dana Farber Canc Inst, Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA 02115 USA. [Wang, Yuchuan; Tupper, Tanya; Sun, Yanping; Saur, Amy; Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. [Wang, Yuchuan; Sun, Yanping; Nishino, Mizuki] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Wang, Yuchuan; Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Ebi, Hiromichi; Bardeesy, Nabeel; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Dept Med Oncol, Boston, MA 02114 USA. [Shimamura, Takeshi] Loyola Univ Chicago, Stritch Sch Med, Inst Oncol, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. [Li, Jie] Iowa State Univ, Dept Stat & Stat Lab, Ctr Survey Stat & Methodol, Ames, IA 50010 USA. [Wang, Shumei; Lee, Charles; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nakada, Yuji; Pena, Christopher G.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Nakada, Yuji; Pena, Christopher G.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Franchetti, Yoko] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst,Dept Biostat, Boston, MA 02115 USA. [Cameron, Michael D.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA. [Hayes, D. Neil; Wilkerson, Matthew D.; Roberts, Patrick J.; Lee, Carrie B.; Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Costa, Daniel B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. [Jaenne, Pasi A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Genet Program,Dept Med & Pathol, Boston, MA 02115 USA. [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kung, Andrew L.] Childrens Hosp, Boston, MA 02115 USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. EM andrew_kung@dfci.harvard.edu; jengelman@partners.org; kwong1@partners.org RI Cantley, Lewis/D-1800-2014; OI wong, kwok kin/0000-0001-6323-235X; Cantley, Lewis/0000-0002-1298-7653; Hayes, D. Neil/0000-0001-6203-7771; Costa, Daniel/0000-0002-0689-395X; Wang, Yuchuan/0000-0001-5111-6562; Ebi, Hiromichi/0000-0003-3155-7576; Kung, Andrew/0000-0002-9091-488X FU National Institutes of Health [CA122794, CA140594, CA137181, CA137008, CA147940, CA137008-01, 1U01CA141576, Lung SPORE P50CA090578]; United against Lung Cancer Foundation; American Lung Association; Susan Spooner Research Fund FX This work is supported by the National Institutes of Health (CA122794, CA140594, CA137181, CA137008, CA147940, CA137008-01, 1U01CA141576, Lung SPORE P50CA090578), United against Lung Cancer Foundation, American Lung Association and Susan Spooner Research Fund. NR 30 TC 194 Z9 200 U1 4 U2 42 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 29 PY 2012 VL 483 IS 7391 BP 613 EP 617 DI 10.1038/nature10937 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 915EF UT WOS:000302006100042 PM 22425996 ER PT J AU Ludwig, H Durie, BGM McCarthy, P Palumbo, A Miguel, JS Barlogie, B Morgan, G Sonneveld, P Spencer, A Andersen, KC Facon, T Stewart, KA Einsele, H Mateos, MV Wijermans, P Waage, A Beksac, M Richardson, PG Hulin, C Niesvizky, R Lokhorst, H Landgren, O Bergsagel, PL Orlowski, R Hinke, A Cavo, M Attal, M AF Ludwig, Heinz Durie, Brian G. M. McCarthy, Philip Palumbo, Antonio San Miguel, Jesus Barlogie, Bart Morgan, Gareth Sonneveld, Pieter Spencer, Andrew Andersen, Kenneth C. Facon, Thierry Stewart, Keith A. Einsele, Hermann Mateos, Maria-Victoria Wijermans, Pierre Waage, Anders Beksac, Meral Richardson, Paul G. Hulin, Cyrille Niesvizky, Ruben Lokhorst, Henk Landgren, Ola Bergsagel, P. Leif Orlowski, Robert Hinke, Axel Cavo, Michele Attal, Michel CA Int Myeloma Working Grp TI IMWG consensus on maintenance therapy in multiple myeloma SO BLOOD LA English DT Review ID PREDNISONE PLUS THALIDOMIDE; RANDOMIZED CONTROLLED-TRIAL; STEM-CELL TRANSPLANTATION; ELDERLY-PATIENTS; INDUCTION THERAPY; IMPROVES SURVIVAL; ORAL MELPHALAN; DEXAMETHASONE; INTERFERON; LENALIDOMIDE AB Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study after conventional melphalan, prednisone, and lenalidomide induction therapy showed a significant risk reduction for PFS and an increase in OS in one of the transplant trials. Maintenance therapy with single-agent bortezomib or in combination with thalidomide or prednisone has been studied. One trial revealed a significantly increased OS with a bortezomib-based induction and bortezomib maintenance therapy compared with conventional induction and thalidomide maintenance treatment. Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established. (Blood. 2012; 119(13):3003-3015) C1 [Ludwig, Heinz] Wilhelminenspital Stadt Wien, Ctr Oncol & Hematol, Dept Med 1, A-1160 Vienna, Austria. [Durie, Brian G. M.] Int Myeloma Fdn, SW Oncol Grp, Los Angeles, CA USA. [Durie, Brian G. M.] Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. [McCarthy, Philip] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Palumbo, Antonio] Univ Turin, Div Hematol, Azienda Osped Univ S Giovanni Battista, Myeloma Unit, Turin, Italy. [San Miguel, Jesus; Mateos, Maria-Victoria] Univ Hosp Salamanca, Salamanca, Spain. [Barlogie, Bart] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Sonneveld, Pieter] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Morgan, Gareth] Royal Marsden Hosp, Haematooncol Unit, London SW3 6JJ, England. [Spencer, Andrew] Alfred Hosp, Clin Haematol Bone Marrow Transplant Dept, Melbourne, Vic, Australia. [Andersen, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Facon, Thierry] Hosp Claude Huriez, Dept Hematol, Lille, France. [Stewart, Keith A.; Bergsagel, P. Leif] Mayo Clin, Div Hematol Oncol, Scottsdale, AZ USA. [Einsele, Hermann] Univ Hosp, Dept Internal Med 2, Wurzburg, Germany. [Wijermans, Pierre] Haga Hosp, The Hague, Netherlands. [Waage, Anders] Norwegian Univ Sci & Technol, St Olavs Hosp, Dept Hematol, N-7034 Trondheim, Norway. [Beksac, Meral] Ankara Univ, Sch Med, Dept Microbiol & Clin Microbiol, Ibn I Sina Hosp, TR-06100 Ankara, Turkey. [Hulin, Cyrille] Univ Hosp, Dept Hematol, Nancy, France. [Niesvizky, Ruben] Weill Cornell Med Coll, New York, NY USA. [Lokhorst, Henk] Univ Med Ctr, Utrecht, Netherlands. [Landgren, Ola] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Orlowski, Robert] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Hinke, Axel] WISP Res Inst, Langenfeld, Germany. [Cavo, Michele] S Orsolas Univ Hosp, Bologna Sch Med, Seragnoli Inst Haematol, Bologna, Italy. [Attal, Michel] Hosp Purpan, Serv Hematol, Toulouse, France. RP Ludwig, H (reprint author), Wilhelminenspital Stadt Wien, Ctr Oncol & Hematol, Dept Med 1, Montleartstr 37, A-1160 Vienna, Austria. EM heinz.ludwig@wienkav.at RI Beksac, Meral/D-6411-2013; Waage, Anders/D-7705-2013; FACON, THIERRY/M-9736-2014; OI FACON, THIERRY/0000-0001-7705-8460; SAN MIGUEL, JESUS/0000-0002-9183-4857; CAVO, MICHELE/0000-0003-4514-3227 FU International Myeloma Foundation; Austrian Forum against Cancer; Celgene; Novartis; NCI; Millennium; Johnson Johnson; Centocor; Onyx; Icon; Janssen-Cilag; Mundipharma FX The experts' meetings on maintenance therapy were supported by the International Myeloma Foundation. This study was supported in part by the Austrian Forum against Cancer.; K.C.A. received honoraria from ONYX, Millennium, Celgene, Novartis, BMS, and Merck and was the cofounder for Acetylon. B.B. received honoraria from Celgene, IMF, MMRF, Millennium, and Genzyme and research funding from Celgene, Novartis, NCI, Millennium, Johnson & Johnson, Centocor, Onyx, and Icon. M.B. received honoraria from Celgene and Janssen-Cilag. P.L.B. received honoraria from Celgene. M.C. received honoraria from Celgene and Janssen-Cilag. B.G.M.D. received honoraria from Celgene and Millennium. H.E. received honoraria from Celgene and Janssen-Cilag. T.F. received honoraria from Celgene, Merck, Onyx, BMS, and Janssen-Cilag. H. Lokhorst received honoraria from Celgene. H. Ludwig received honoraria from Celgene, Janssen-Cilag, and Mundipharma and research funding from Celgene, Janssen-Cilag, and Mundipharma. M.-V.M. received honoraria from Janssen-Cilag, Celgene, and Millennium. P.M. received honoraria from Celgene and Onyx. R.N. received honoraria from Celgene and Millennium and research funding from Celgene, Onyx, and Millennium. A.P. received honoraria from Celgene, Janssen-Cilag, Merck, and AMGEN. P.G.R. received honoraria from Celgene, Millennium, and Johnson & Johnson. J.S.M. received honoraria from Celgene, Millennium, and Janssen-Cilag. K.A.S. received honoraria from Celgene, Millennium, and ONYX and research funding from Millenium. A.W. received honoraria from Janssen-Cilag, Celgene, and Mundipharma. The remaining authors declare no competing financial interests. NR 48 TC 83 Z9 90 U1 0 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 29 PY 2012 VL 119 IS 13 BP 3003 EP 3015 DI 10.1182/blood-2011-11-374249 PG 13 WC Hematology SC Hematology GA 916ZH UT WOS:000302141200013 PM 22271445 ER PT J AU Chen, BB Glasser, JR Coon, TA Zou, CB Miller, HL Fenton, M McDyer, JF Boyiadzis, M Mallampalli, RK AF Chen, Bill B. Glasser, Jennifer R. Coon, Tiffany A. Zou, Chunbin Miller, Hannah L. Fenton, Moon McDyer, John F. Boyiadzis, Michael Mallampalli, Rama K. TI F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation SO BLOOD LA English DT Article ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; DEPENDENT KINASE 4; D1 DEGRADATION; HEMATOPOIETIC-CELLS; BCR-ABL; EXPRESSION; GENE; CALMODULIN; CANCER; IDENTIFICATION AB Hematologic maligancies exhibit a growth advantage by up-regulation of components within the molecular apparatus involved in cell-cycle progression. The SCF (Skip-Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell-cycle proteins. By screening several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G(0) phase arrest and apoptosis in leukemic and B-lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels, whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate, which is typical of other F-box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F-box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G(0) phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an antiproliferative effect of SCFFBXL2 in lymphoproliferative malignancies. (Blood. 2012;119(13):3132-3141) C1 [Chen, Bill B.; Glasser, Jennifer R.; Coon, Tiffany A.; Zou, Chunbin; Miller, Hannah L.; Fenton, Moon; McDyer, John F.; Boyiadzis, Michael; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Chen, Bill B.; Glasser, Jennifer R.; Coon, Tiffany A.; Zou, Chunbin; Miller, Hannah L.; Fenton, Moon; McDyer, John F.; Boyiadzis, Michael; Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Glasser, Jennifer R.; Coon, Tiffany A.; Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, UPMC Montefiore, NW Dept Med 628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; US Department of Veterans Affairs; National Institutes of Health [HL096376, HL097376, HL098174] FX This material is based on work supported, in part, by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. This work was supported by a Merit Review Award from the US Department of Veterans Affairs and National Institutes of Health R01 grants HL096376, HL097376, and HL098174 (to R.K.M.). The contents presented do not represent the views of the Department of Veterans Affairs or the United States Government. NR 54 TC 34 Z9 37 U1 0 U2 6 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 29 PY 2012 VL 119 IS 13 BP 3132 EP 3141 DI 10.1182/blood-2011-06-358911 PG 10 WC Hematology SC Hematology GA 916ZH UT WOS:000302141200029 PM 22323446 ER PT J AU Biernacki, MA Tai, YT Zhang, GL Alonso, A Zhang, WD Prabhala, R Zhang, L Munshi, N Neuberg, D Soiffer, RJ Ritz, J Alyea, EP Brusic, V Anderson, KC Wu, CJ AF Biernacki, Melinda A. Tai, Yu-tzu Zhang, Guang Lan Alonso, Anselmo Zhang, Wandi Prabhala, Rao Zhang, Li Munshi, Nikhil Neuberg, Donna Soiffer, Robert J. Ritz, Jerome Alyea, Edwin P. Brusic, Vladimir Anderson, Kenneth C. Wu, Catherine J. TI Novel myeloma-associated antigens revealed in the context of syngeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; MULTIPLE-MYELOMA; T-CELLS; PROTEIN MICROARRAYS; TUMOR-IMMUNITY; B-CELL; ALLOGENEIC TRANSPLANTATION AB Targets of curative donor-derived graft-versus-myeloma (GVM) responses after allogeneic hematopoietic stem cell transplantation (HSCT) remain poorly defined, partly because immunity against minor histocompatibility Ags (mHAgs) complicates the elucidation of multiple myeloma (MM)-specific targets. We hypothesized that syngeneic HSCT would facilitate the identification of GVM-associated Ags because donor immune responses in this setting should exclusively target unique tumor Ags in the absence of donor-host genetic disparities. Therefore, in the present study, we investigated the development of tumor immunity in an HLA-A0201(+) MM patient who achieved durable remission after myeloablative syngeneic HSCT. Using high-density protein microarrays to screen post-HSCT plasma, we identified 6 Ags that elicited high-titer (1:5000-1:10 000) Abs that correlated with clinical tumor regression. Two Ags (DAPK2 and PIM1) had enriched expression in primary MM tissues. Both elicited Ab responses in other MM patients after chemotherapy or HSCT (11 and 6 of 32 patients for DAPK2 and PIM1, respectively). The index patient also developed specific CD8(+) T-cell responses to HLA-A2-restricted peptides derived from DAPK2 and PIM1. Peptide-specific T cells recognized HLA-A2(+) MM-derived cell lines and primary MM tumor cells. Coordinated T- and B-cell immunity develops against MM-associated Ags after syngeneic HSCT. DAPK1 and PIM1 are promising target Ags for MM-directed immunotherapy. (Blood. 2012;119(13):3142-3150) C1 [Biernacki, Melinda A.; Zhang, Guang Lan; Alonso, Anselmo; Zhang, Wandi; Zhang, Li; Ritz, Jerome; Brusic, Vladimir; Wu, Catherine J.] Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Tai, Yu-tzu; Prabhala, Rao; Zhang, Li; Munshi, Nikhil; Soiffer, Robert J.; Ritz, Jerome; Alyea, Edwin P.; Anderson, Kenneth C.; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Biernacki, Melinda A.] Univ Connecticut, Sch Med, Farmington, CT USA. [Tai, Yu-tzu; Prabhala, Rao; Munshi, Nikhil; Soiffer, Robert J.; Ritz, Jerome; Alyea, Edwin P.; Anderson, Kenneth C.; Wu, Catherine J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Munshi, Nikhil] Vet Adm Boston Healthcare Syst, W Roxbury, MA USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Rm 416B,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwu@partners.org OI Ritz, Jerome/0000-0001-5526-4669 FU Multiple Myeloma Research Foundation; Pasquarello Tissue Bank; Miles and Eleanor Shore Award; National Cancer Institute [5R21CA115043-2]; Howard Hughes Medical Institute; Damon-Runyon Cancer Research Foundation [CI-38-07] FX This work was supported by the Multiple Myeloma Research Foundation and the Pasquarello Tissue Bank. C.J.W. also received a Miles and Eleanor Shore Award, a grant from the National Cancer Institute (5R21CA115043-2), the Early Career Physician-Scientist Award of the Howard Hughes Medical Institute, and a clinical investigator award supported by the Damon-Runyon Cancer Research Foundation (CI-38-07). NR 48 TC 5 Z9 5 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 29 PY 2012 VL 119 IS 13 BP 3142 EP 3150 DI 10.1182/blood-2011-11-388926 PG 9 WC Hematology SC Hematology GA 916ZH UT WOS:000302141200030 PM 22267603 ER PT J AU Hoch, DB Watson, AJ Linton, DA Bello, HE Senelly, M Milik, MT Baim, MA Jethwani, K Fricchione, GL Benson, H Kvedar, JC AF Hoch, Daniel B. Watson, Alice J. Linton, Deborah A. Bello, Heather E. Senelly, Marco Milik, Mariola T. Baim, Margaret A. Jethwani, Kamal Fricchione, Gregory L. Benson, Herbert Kvedar, Joseph C. TI The Feasibility and Impact of Delivering a Mind-Body Intervention in a Virtual World SO PLOS ONE LA English DT Article ID RELAXATION RESPONSE; BEHAVIORAL TREATMENT; INTERNET; MEDITATION; PROGRAM; DISEASE; STRESS; TRIAL AB Introduction: Mind-body medical approaches may ameliorate chronic disease. Stress reduction is particularly helpful, but face-to-face delivery systems cannot reach all those who might benefit. An online, 3-dimensional virtual world may be able to support the rich interpersonal interactions required of this approach. In this pilot study, we explore the feasibility of translating a face-to-face stress reduction program into an online virtual setting and estimate the effect size of the intervention. Methods and Findings: Domain experts in virtual world technology joined with mind body practitioners to translate an existing 8 week relaxation response-based resiliency program into an 8-week virtual world-based program in Second Life (TM) (SL). Twenty-four healthy volunteers with at least one month's experience in SL completed the program. Each subject filled out the Perceived Stress Scale (PSS) and the Symptom Checklist 90-Revised (SCL-90-R) before and after taking part. Participants took part in one of 3 groups of about 10 subjects. The participants found the program to be helpful and enjoyable. Many reported that the virtual environment was an excellent substitute for the preferred face-to-face approach. On quantitative measures, there was a general trend toward decreased perceived stress, (15.7 to 15.0), symptoms of depression, (57.6 to 57.0) and anxiety (56.8 to 54.8). There was a significant decrease of 2.8 points on the SCL-90-R Global Severity Index (p < 0.05). Conclusions: This pilot project showed that it is feasible to deliver a typical mind-body medical intervention through a virtual environment and that it is well received. Moreover, the small reduction in psychological distress suggests further research is warranted. Based on the data collected for this project, a randomized trial with less than 50 subjects would be appropriately powered if perceived stress is the primary outcome. C1 [Hoch, Daniel B.; Milik, Mariola T.; Baim, Margaret A.; Fricchione, Gregory L.; Benson, Herbert] Benson Henry Inst Mind Body Med, Boston, MA USA. [Jethwani, Kamal; Kvedar, Joseph C.] Partners Healthcare, Ctr Connected Hlth, Boston, MA USA. [Hoch, Daniel B.; Watson, Alice J.; Jethwani, Kamal; Fricchione, Gregory L.; Kvedar, Joseph C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoch, Daniel B.; Baim, Margaret A.; Jethwani, Kamal; Fricchione, Gregory L.; Benson, Herbert; Kvedar, Joseph C.] Harvard Univ, Sch Med, Boston, MA USA. [Bello, Heather E.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Linton, Deborah A.] Hlth 20, San Francisco, CA USA. [Senelly, Marco] OneVis Solut Inc, Austin, TX USA. RP Hoch, DB (reprint author), Benson Henry Inst Mind Body Med, Boston, MA USA. EM dhoch@partners.org OI Hoch, Daniel/0000-0002-4294-024X FU Partners Healthcare Information Systems Research Council FX This research was supported by a grant from the Partners Healthcare Information Systems Research Council. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 9 Z9 9 U1 1 U2 9 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 28 PY 2012 VL 7 IS 3 AR e33843 DI 10.1371/journal.pone.0033843 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 948FM UT WOS:000304489000039 PM 22470483 ER PT J AU Krakower, DS Mimiaga, MJ Rosenberger, JG Novak, DS Mitty, JA White, JM Mayer, KH AF Krakower, Douglas S. Mimiaga, Matthew J. Rosenberger, Joshua G. Novak, David S. Mitty, Jennifer A. White, Jaclyn M. Mayer, Kenneth H. TI Limited Awareness and Low Immediate Uptake of Pre-Exposure Prophylaxis among Men Who Have Sex with Men Using an Internet Social Networking Site SO PLOS ONE LA English DT Article ID RISK BEHAVIOR; CAGE QUESTIONNAIRE; UNITED-STATES; PARTNER NOTIFICATION; HIV RISK; STUDY-II; INFECTION; ONLINE; GAY; PREVENTION AB Background: In 2010, the iPrEx trial demonstrated that oral antiretroviral pre-exposure prophylaxis (PrEP) reduced the risk of HIV acquisition among high-risk men who have sex with men (MSM). The impact of iPrEx on PrEP knowledge and actual use among at-risk MSM is unknown. Online surveys were conducted to assess PrEP awareness, interest and experience among at-risk MSM before and after iPrEx, and to determine demographic and behavioral factors associated with these measures. Methods and Findings: Cross-sectional, national, internet-based surveys were administered to U. S. based members of the most popular American MSM social networking site 2 months before (n=398) and 1 month after (n=4 558) publication of iPrEx results. Comparisons were made between these samples with regards to PrEP knowledge, interest, and experience. Data were collected on demographics, sexual risk, and experience with post-exposure prophylaxis (PEP). Regression analyses were performed to identify factors associated with PrEP awareness, interest, and experience post-iPrEx. Most participants were white, educated, and indicated high-risk sexual behaviors. Awareness of PrEP was limited pre-and post-iPrEx (13% vs. 19%), whereas interest levels after being provided with a description of PrEP remained high (76% vs. 79%). PrEP use remained uncommon (0.7% vs. 0.9%). PrEP use was associated with PEP awareness (OR 7.46; CI 1.52-36.6) and PEP experience (OR 34.2; CI 13.3-88.4). PrEP interest was associated with older age (OR 1.01; CI 1.00-1.02), unprotected anal intercourse with >= 1 male partner in the prior 3 months (OR 1.40; CI 1.10-1.77), and perceiving oneself at increased risk for HIV acquisition (OR 1.20; CI 1.13-1.27). Conclusions: Among MSM engaged in online networking, awareness of PrEP was limited 1 month after the iPrEx data were released. Utilization was low, although some MSM who reported high-risk behaviors were interested in using PrEP. Studies are needed to understand barriers to PrEP utilization by at-risk MSM. C1 [Krakower, Douglas S.; Mimiaga, Matthew J.; Mitty, Jennifer A.; Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Krakower, Douglas S.; Mitty, Jennifer A.; Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosenberger, Joshua G.] George Mason Univ, Dept Global & Community Hlth, Fairfax, VA 22030 USA. [Novak, David S.] Online Buddies Inc, OLB Res Inst, Cambridge, MA USA. [Mimiaga, Matthew J.; Mitty, Jennifer A.; White, Jaclyn M.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. RP Krakower, DS (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM dkrakowe@bidmc.harvard.edu FU Gilead Sciences; Harvard T32 post-doctoral HIV Clinical Research Fellowship [NIAID AI 007433]; National Institute of Mental Health (NIMH) [1R21MH095535-01]; OLB Research Institute; Harvard Center for AIDS Research [NIAID 5P30AI06354-08] FX This study was funded with project support from Gilead Sciences. Douglas Krakower received support from the Harvard T32 post-doctoral HIV Clinical Research Fellowship (NIAID AI 007433). Jennifer Mitty, Matthew Mimiaga, and Jackie White received support from the National Institute of Mental Health (NIMH 1R21MH095535-01). Joshua Rosenberger received support from The OLB Research Institute, Online Buddies Incorporated. Ken Mayer received support from the Harvard Center for AIDS Research (NIAID 5P30AI06354-08). NR 44 TC 82 Z9 82 U1 1 U2 19 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 28 PY 2012 VL 7 IS 3 AR e33119 DI 10.1371/journal.pone.0033119 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 948FM UT WOS:000304489000015 PM 22470438 ER PT J AU Kwee, LC Liu, YT Haynes, C Gibson, JR Stone, A Schichman, SA Kamel, F Nelson, LM Topol, B Van Den Eeden, SK Tanner, CM Cudkowicz, ME Grasso, DL Lawson, R Muralidhar, S Oddone, EZ Schmidt, S Hauser, MA AF Kwee, Lydia Coulter Liu, Yutao Haynes, Carol Gibson, Jason R. Stone, Annjanette Schichman, Steven A. Kamel, Freya Nelson, Lorene M. Topol, Barbara Van Den Eeden, Stephen K. Tanner, Caroline M. Cudkowicz, Merit E. Grasso, Daniela L. Lawson, Robert Muralidhar, Sumitra Oddone, Eugene Z. Schmidt, Silke Hauser, Michael A. TI A High-Density Genome-Wide Association Screen of Sporadic ALS in US Veterans SO PLOS ONE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; GULF-WAR VETERANS; HEXANUCLEOTIDE REPEAT; RISK; GENE; POPULATION; SUSCEPTIBILITY; EXPOSURE; SURVIVAL; DIAGNOSIS AB Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U. S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U. S. veterans. We tested,1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4x10(-4)) and rs6985069 near ELP3 (p = 4.8x10(-4)). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder. C1 [Kwee, Lydia Coulter; Liu, Yutao; Gibson, Jason R.; Oddone, Eugene Z.; Schmidt, Silke; Hauser, Michael A.] Durham Vet Affairs Med Ctr, Epidemiol Res & Informat Ctr, Durham, NC 27705 USA. [Kwee, Lydia Coulter; Liu, Yutao; Haynes, Carol; Gibson, Jason R.; Schmidt, Silke; Hauser, Michael A.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. [Kwee, Lydia Coulter; Liu, Yutao; Haynes, Carol; Gibson, Jason R.; Oddone, Eugene Z.; Schmidt, Silke; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Stone, Annjanette; Schichman, Steven A.] Cent Arkansas Vet Healthcare Syst, Pathol & Lab Med Serv, Little Rock, AR USA. [Stone, Annjanette; Schichman, Steven A.] Cent Arkansas Vet Healthcare Syst, Res Serv, Little Rock, AR USA. [Schichman, Steven A.] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. [Kamel, Freya] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Nelson, Lorene M.; Topol, Barbara] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA. [Van Den Eeden, Stephen K.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA USA. [Cudkowicz, Merit E.; Grasso, Daniela L.; Lawson, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trial Unit, Boston, MA USA. [Muralidhar, Sumitra] Dept Vet Affairs, Off Res & Dev, Washington, DC USA. RP Kwee, LC (reprint author), Durham Vet Affairs Med Ctr, Epidemiol Res & Informat Ctr, Durham, NC 27705 USA. EM mike.hauser@duke.edu OI Kamel, Freya/0000-0001-5052-6615 FU Office of Research and Development, Cooperative Studies Program, Department of Veterans Affairs [CSP] [500B, 500A, 478]; National Institute of Environmental Health Sciences/National Institutes of Health [R01 ES 013244]; ALS Association [ALSA 1230]; National Institutes of Health; National Institute of Environmental Health Sciences [Z01-ES049005, R01-ES08150]; National Institute of Neurological Disorders and Stroke/National Institutes of Health [R01 NS 031964]; ALS Therapy Alliance; Wellcome Trust [076113, 085475] FX The authors gratefully acknowledge support for this work from the Office of Research and Development, Cooperative Studies Program, Department of Veterans Affairs [CSP #500B]. The GENEVA study was supported by National Institute of Environmental Health Sciences/National Institutes of Health [R01 ES 013244] and the ALS Association [ALSA 1230]. The National Registry of Veterans with ALS and its DNA bank were supported by the Office of Research and Development, Cooperative Studies Program, Department of Veterans Affairs [CSP #500A, CSP #478]. The study was supported in part by the intramural research program of the National Institutes of Health, by National Institute of Environmental Health Sciences [Z01-ES049005]. The GEM study was supported by the National Institute of Environmental Health Sciences [R01-ES08150] and the National Institute of Neurological Disorders and Stroke/National Institutes of Health [R01 NS 031964]. The NEALS consortium was supported by the ALS Association and the ALS Therapy Alliance. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113 and 085475. This study was overseen by an Executive Committee appointed by the Veterns Affairs (VA): Mary Brophy, MD, MPH; MAH, PhD; Donald Humphries, PhD; LCK, PhD; EZO, MD, MHSc; SAS, MD, PhD; SS, PhD. The VA Cooperative Studies Program provided policies and requirements for conducting the research, contributed to study design, and provided administrative review of the paper but did not alter the contents. All other funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 19 Z9 19 U1 0 U2 4 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 28 PY 2012 VL 7 IS 3 AR e32768 DI 10.1371/journal.pone.0032768 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 948FM UT WOS:000304489000008 PM 22470424 ER PT J AU Volz, MS Mendonca, M Pinheiro, FS Cui, HS Santana, M Fregni, F AF Volz, Magdalena S. Mendonca, Mariana Pinheiro, Fernando S. Cui, Huashun Santana, Marcus Fregni, Felipe TI Dissociation of Motor Task-Induced Cortical Excitability and Pain Perception Changes in Healthy Volunteers SO PLOS ONE LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; ADULT SQUIRREL-MONKEYS; SILENT PERIOD; INTRACORTICAL INHIBITION; CORTEX STIMULATION; MOVEMENT REPRESENTATIONS; THALAMIC PAIN; PLASTICITY; MUSCLE; HAND AB Background: There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks. Methodology/Principal Findings: Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements. Conclusions/Significance: Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training. C1 [Volz, Magdalena S.; Mendonca, Mariana; Pinheiro, Fernando S.; Cui, Huashun; Santana, Marcus; Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Lab Neuromodulat,Spaulding Rehabil Hosp, Boston, MA 02115 USA. [Volz, Magdalena S.; Mendonca, Mariana; Pinheiro, Fernando S.; Cui, Huashun; Santana, Marcus; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Volz, Magdalena S.] Charite, Charite Ctr Neurol Neurosurg & Psychiat, Campus Charite Mitte, D-13353 Berlin, Germany. RP Volz, MS (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Lab Neuromodulat,Spaulding Rehabil Hosp, Boston, MA 02115 USA. EM fregni.felipe@mgh.harvard.edu FU German Academic Exchange Service (DAAD); National Institutes of Heatlh [R21 DK081773-03] FX Volz MS was funded by a grant scholarship from the German Academic Exchange Service (DAAD). This work was partially supported by a National Institutes of Heatlh grant (R21 DK081773-03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. NR 65 TC 7 Z9 7 U1 1 U2 4 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 28 PY 2012 VL 7 IS 3 AR e34273 DI 10.1371/journal.pone.0034273 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 948FM UT WOS:000304489000087 PM 22470548 ER PT J AU Lee, MS Hang, JQ Zhang, FY Dai, HL Su, L Christiani, DC AF Lee, Mi-Sun Hang, Jing-qing Zhang, Feng-ying Dai, He-lian Su, Li Christiani, David C. TI In-home solid fuel use and cardiovascular disease: a cross-sectional analysis of the Shanghai Putuo study SO ENVIRONMENTAL HEALTH LA English DT Article DE Household fuels; Cardiovascular disease; Indoor air pollution; Chinese ID INDOOR AIR-POLLUTION; PARTICULATE MATTER; HOSPITAL ADMISSIONS; PLATELET ACTIVATION; BIOMASS SMOKE; HEART-DISEASE; LUNG-CANCER; RISK-FACTOR; CHINA; EXPOSURE AB Background: Although recent research evidence suggests an association between household air pollution from solid fuel use, such as coal or biomass, and cardiovascular events such as hypertension, little epidemiologic data are available concerning such exposure effects on cardiovascular endpoints other than hypertension. We explored the association between in-home solid fuel use and self-reported diagnoses of cardiovascular endpoints, such as hypertension, coronary heart disease (CHD), stroke, and diabetes. Methods: We analyzed 14,068 Chinese adults, aged 18 years and older. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using logistic regression models for the risk of each outcome after adjusting for potential confounders. Results: The use of solid fuel in home was significantly associated with an increased risk for hypertension (OR 1.70, 95% CI 1.40 to 2.07), CHD (OR 2.58, 95% CI 1.53 to 4.32), and diabetes (OR 2.48, 95% CI 1.59 to 3.86), after adjusting for potential confounders. Compared with individuals in the lowest tertile of the duration of solid fuel exposure, those in the highest tertile of the duration of solid fuel exposure had an increased odds of hypertension (OR 1.73, 95% CI 1.45 to 2.06), stroke (OR 1.87, 95% CI 1.03 to 3.38), and diabetes (OR 3.18, 95% CI 2.11 to 4.78). Conclusions: Our data suggest that in-home solid fuel exposure maybe associated with increased risk for hypertension, CHD, stroke, and diabetes in the Chinese adult population. Further large-scale longitudinal studies are warranted to confirm these findings. C1 [Lee, Mi-Sun; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Hang, Jing-qing; Zhang, Feng-ying; Dai, He-lian] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institute of Environmental Health Sciences (NIEHS) [ES000002]; Centers for Disease Control [RO1OH0421]; Shanghai Putuo District People's Hospital FX This study was funded by National Institute of Environmental Health Sciences (NIEHS grant ES000002), Centers for Disease Control (RO1OH0421), and Shanghai Putuo District People's Hospital. The authors gratefully acknowledge the contribution of all participants and the research team in Shanghai, and the research assistance of Ms. Marcia Chertok. NR 27 TC 30 Z9 31 U1 3 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD MAR 28 PY 2012 VL 11 AR 18 DI 10.1186/1476-069X-11-18 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 940JR UT WOS:000303886300001 PM 22455369 ER PT J AU Hayakawa, K Seo, JH Pham, LDD Miyamoto, N Som, AT Guo, SZ Kim, KW Lo, EH Arai, K AF Hayakawa, Kazuhide Seo, Ji Hae Pham, Loc-Duyen D. Miyamoto, Nobukazu Som, Angel T. Guo, Shuzhen Kim, Kyu-Won Lo, Eng H. Arai, Ken TI Cerebral endothelial derived vascular endothelial growth factor promotes the migration but not the proliferation of oligodendrocyte precursor cells in vitro SO NEUROSCIENCE LETTERS LA English DT Article DE Oligodendrocyte precursor cell; Vascular endothelial growth factor; Migration; Proliferation; Cerebral endothelial cell; Neurovascular unit; Oligovascular niche; White matter ID HYPOXIA-INDUCED HYPERPERMEABILITY; BRAIN; EXPRESSION; STROKE; VEGF; NEUROGENESIS; ANGIOGENESIS; RAT; NEURONS; NICHE AB In gray matter, cerebral endothelium is known to provide trophic support for neighboring cells such as neurons. However, signaling from cerebral endothelium to white matter cells remains to be elucidated. Here, we show that vascular endothelial growth factor (VEGF-A) secreted from cerebral endothelial cells promotes the migration but not the proliferation of oligodendrocyte precursor cells (OPCs). Cultured OPCs were obtained from newborn rat cortex, and treatment with conditioned culture media of cerebral endothelial cells increased the OPC proliferation and migration. Importantly, co-treatment with anti-neutralizing antibody for Flk-1 (VEGF-receptor2) inhibited OPC movement but did not affect OPC propagation. Western blot and flow cytometry analyses confirmed that our cultured cerebral endothelial cells produced VEGF-A and our cultured OPCs expressed Flk-1. Taken together, our current data suggest that cerebral endothelium is supportive for oligodendrocyte lineage cells and VEGF-A may participate in the endothelium-OPC cell-cell signaling. This phenomenon may be important for white matter homeostasis. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Hayakawa, Kazuhide; Seo, Ji Hae; Pham, Loc-Duyen D.; Miyamoto, Nobukazu; Som, Angel T.; Guo, Shuzhen; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. [Hayakawa, Kazuhide; Seo, Ji Hae; Pham, Loc-Duyen D.; Miyamoto, Nobukazu; Som, Angel T.; Guo, Shuzhen; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Hayakawa, Kazuhide; Seo, Ji Hae; Pham, Loc-Duyen D.; Miyamoto, Nobukazu; Som, Angel T.; Guo, Shuzhen; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm & Res, Neurovasc Coordinat Res Ctr, Inst Pharmaceut Sci, Seoul 51742, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul 151742, South Korea. RP Arai, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, MGH E 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU Deane Foundation; MGH ECOR; American Heart Association; National Institutes of Health; Research Abroad from the Japan Society for the Promotion of Science; National Research Foundation of Korea; World Class University; Global Research Laboratory FX Supported in part by the Deane Foundation, MGH ECOR Fund for Medical Discovery, American Heart Association, National Institutes of Health, Research Abroad from the Japan Society for the Promotion of Science, National Research Foundation of Korea, the World Class University Program, and the Global Research Laboratory Program. NR 27 TC 16 Z9 17 U1 0 U2 3 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 28 PY 2012 VL 513 IS 1 BP 42 EP 46 DI 10.1016/j.neulet.2012.02.004 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 921YA UT WOS:000302512800009 PM 22342913 ER PT J AU Temereanca, S Hamalainen, MS Kuperberg, GR Stufflebeam, SM Halgren, E Brown, EN AF Temereanca, Simona Haemaelaeinen, Matti S. Kuperberg, Gina R. Stufflebeam, Steve M. Halgren, Eric Brown, Emery N. TI Eye Movements Modulate the Spatiotemporal Dynamics of Word Processing SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LATERAL GENICULATE-NUCLEUS; EVENT-RELATED POTENTIALS; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; SACCADIC SUPPRESSION; VISUAL-PERCEPTION; COORDINATE SYSTEM; STRIATE CORTEX; MEG; RESPONSES AB Active reading requires coordination between frequent eye movements (saccades) and short fixations in text. Yet, the impact of saccades on word processing remains unknown, as neuroimaging studies typically employ constant eye fixation. Here we investigate eye-movement effects on word recognition processes in healthy human subjects using anatomically constrained magnetoencephalography, psychophysical measurements, and saccade detection in real time. Word recognition was slower and brain responses were reduced to words presented early versus late after saccades, suggesting an overall transient impairment of word processing after eye movements. Response reductions occurred early in visual cortices and later in language regions, where they colocalized with repetition priming effects. Qualitatively similar effects occurred when words appeared early versus late after background movement that mimicked saccades, suggesting that retinal motion contributes to postsaccadic inhibition. Further, differences in postsaccadic and background-movement effects suggest that central mechanisms also contribute to postsaccadic modulation. Together, these results suggest a complex interplay between visual and central saccadic mechanisms during reading. C1 [Temereanca, Simona; Haemaelaeinen, Matti S.; Kuperberg, Gina R.; Stufflebeam, Steve M.] Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Sch Med, Charlestown, MA 02129 USA. [Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Massachusetts Inst Technol Div Hlth Sci &, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Temereanca, S (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM temerean@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013 FU NIH [HD050627, EB006385, DP1 OD003646, EB009048, MH071635]; National Center for Research Resources [P41 RR14075]; Massachusetts General Hospital FX This work was supported by NIH Grants HD050627 (S. T.), EB006385 (E.N.B. and M. S. H.), DP1 OD003646 (E.N.B.), EB009048 (M. S. H.), MH071635 (G. R. K.), National Center for Research Resources Grant P41 RR14075 (M. S. H.), and a Claflin Distinguished Scholars Award from Massachusetts General Hospital (S.T.). NR 45 TC 3 Z9 3 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 28 PY 2012 VL 32 IS 13 BP 4482 EP 4494 DI 10.1523/JNEUROSCI.5571-11.2012 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 917GA UT WOS:000302159400013 PM 22457496 ER PT J AU Nguyen, PL Je, YJ Choueiri, TK AF Nguyen, Paul L. Je, Youjin Choueiri, Toni K. TI Androgen Deprivation Therapy for Prostate Cancer and Cardiovascular Death Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID SERUM TESTOSTERONE; HORMONE AGONIST; CESSATION C1 [Nguyen, Paul L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Je, Youjin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM pnguyen@lroc.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 28 PY 2012 VL 307 IS 12 BP 1252 EP 1253 DI 10.1001/jama.2012.353 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 914UP UT WOS:000301978400012 ER PT J AU Karaca-Mandic, P Jena, AB Joyce, GF Goldman, DP AF Karaca-Mandic, Pinar Jena, Anupam B. Joyce, Geoffrey F. Goldman, Dana P. TI Out-of-Pocket Medication Costs and Use of Medications and Health Care Services Among Children With Asthma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID UNITED-STATES; INHALED CORTICOSTEROIDS; PHARMACY BENEFITS; INSURANCE; DRUGS; THERAPY; CAPS AB Context Health plans have implemented policies to restrain prescription medication spending by shifting costs toward patients. It is unknown how these policies have affected children with chronic illness. Objective To analyze the association of medication cost sharing with medication and hospital services utilization among children with asthma, the most prevalent chronic disease of childhood. Design, Setting, and Patients Retrospective study of insurance claims for 8834 US children with asthma who initiated asthma control therapy between 1997 and 2007. Using variation in out-of-pocket costs for a fixed "basket" of asthma medications across 37 employers, we estimated multivariate models of asthma medication use, asthma-related hospitalization, and emergency department (ED) visits with respect to out-of-pocket costs and child and family characteristics. Main Outcome Measures Asthma medication use, asthma-related hospitalizations, and ED visits during 1-year follow-up. Results The mean annual out-of-pocket asthma medication cost was $154 (95% CI, $152-$156) among children aged 5 to 18 years and $151 (95% CI, $148-$153) among those younger than 5 years. Among 5913 children aged 5 to 18 years, filled asthma prescriptions covered a mean of 40.9% of days (95% CI, 40.2%-41.5%). During 1-year follow-up, 121 children (2.1%) had an asthma-related hospitalization and 220 (3.7%) had an ED visit. Among 2921 children younger than 5 years, mean medication use was 46.2% of days (95% CI, 45.2%-47.1%); 136 children (4.7%) had an asthma-related hospitalization and 231 (7.9%) had an ED visit. An increase in out-of-pocket medication costs from the 25th to the 75th percentile was associated with a reduction in adjusted medication use among children aged 5 to 18 years (41.7% [95% CI, 40.7%-42.7%] vs 40.3% [95% CI, 39.4%-41.3%] of days; P=.02) but no change among younger children. Adjusted rates of asthma-related hospitalization were higher for children aged 5 to 18 years in the top quartile of out-of-pocket costs (2.4 [95% CI, 1.9-2.8] hospitalizations per 100 children vs 1.7 [95% CI, 1.3-2.1] per 100 in bottom quartile; P=.004) but not for younger children. Annual adjusted rates of ED use did not vary across out-of-pocket quartiles for either age group. Conclusion Greater cost sharing for asthma medications was associated with a slight reduction in medication use and higher rates of asthma hospitalization among children aged 5 years or older. JAMA. 2012;307(12):1284-1291 www.jama.com C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wang Ambulatory Care Ctr,Dept Med, Boston, MA 02114 USA. [Karaca-Mandic, Pinar] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. [Joyce, Geoffrey F.; Goldman, Dana P.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wang Ambulatory Care Ctr,Dept Med, 15 Parkman St, Boston, MA 02114 USA. EM jena.anupam@mgh.harvard.edu FU National Institute of Child Health and Human Development [1R03HD058203-01A1]; National Institute on Aging [7R01AG02514]; Roybal Center for Health Policy Simulation [5P30AG024968] FX Support was provided by the National Institute of Child Health and Human Development (grant 1R03HD058203-01A1), the National Institute on Aging (grant 7R01AG02514), and the Roybal Center for Health Policy Simulation (grant 5P30AG024968). NR 32 TC 40 Z9 40 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 28 PY 2012 VL 307 IS 12 BP 1284 EP 1291 DI 10.1001/jama.2012.340 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 914UP UT WOS:000301978400024 PM 22453569 ER PT J AU Boekholdt, SM Arsenault, BJ Mora, S Pedersen, TR LaRosa, JC Nestel, PJ Simes, RJ Durrington, P Hitman, GA Welch, KMA DeMicco, DA Zwinderman, AH Clearfield, MB Downs, JR Tonkin, AM Colhoun, HM Gotto, AM Ridker, PM Kastelein, JJP AF Boekholdt, S. Matthijs Arsenault, Benoit J. Mora, Samia Pedersen, Terje R. LaRosa, John C. Nestel, Paul J. Simes, R. John Durrington, Paul Hitman, Graham A. Welch, K. M. A. DeMicco, David A. Zwinderman, Aeilko H. Clearfield, Michael B. Downs, John R. Tonkin, Andrew M. Colhoun, Helen M. Gotto, Antonio M., Jr. Ridker, Paul M. Kastelein, John J. P. TI Association of LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins A Meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; HIGH-DOSE ATORVASTATIN; MYOCARDIAL-INFARCTION; PRIMARY PREVENTION; LIPID PARAMETERS; CONTROLLED-TRIAL; A-I; WOMEN; MEN AB Context The associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented. Objective To evaluate the relative strength of the associations of LDL-C, non-HDL-C, and apoB with cardiovascular risk among patients treated with statin therapy. Design Meta-analysis of individual patient data from randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Data Sources Relevant trials were identified by a literature search updated through December 31, 2011. Investigators were contacted and individual patient data were requested and obtained for 62154 patients enrolled in 8 trials published between 1994 and 2008. Data Extraction Hazard ratios (HRs) and corresponding 95% CIs for risk of major cardiovascular events adjusted for established risk factors by 1-SD increase in LDL-C, non-HDL-C, and apoB. Results Among 38 153 patients allocated to statin therapy, 158 fatal myocardial infarctions, 1678 nonfatal myocardial infarctions, 615 fatal events from other coronary artery disease, 2806 hospitalizations for unstable angina, and 1029 fatal or nonfatal strokes occurred during follow-up. The adjusted HRs for major cardiovascular events per 1-SD increase were 1.13 (95% CI, 1.10-1.17) for LDL-C, 1.16 (95% CI, 1.12-1.19) for non-HDL-C, and 1.14 (95% CI, 1.11-1.18) for apoB. These HRs were significantly higher for non-HDL-C than LDL-C (P=.002) and apoB (P=.02). There was no significant difference between apoB and LDL-C (P=.21). Conclusion Among statin-treated patients, on-treatment levels of LDL-C, non-HDL-C, and apoB were each associated with risk of future major cardiovascular events, but the strength of this association was greater for non-HDL-C than for LDL-C and apoB. JAMA. 2012;307(12):1302-1309 www.jama.com C1 [Arsenault, Benoit J.; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Zwinderman, Aeilko H.] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol & Biostat, NL-1105 AZ Amsterdam, Netherlands. [Mora, Samia; Ridker, Paul M.] Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Pedersen, Terje R.] Oslo Univ Hosp, Ctr Prevent Med, Ulleval, Norway. [Pedersen, Terje R.] Univ Oslo, N-0316 Oslo, Norway. [LaRosa, John C.] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. [Nestel, Paul J.] Baker Heart & Diabet Res Inst, Melbourne, Vic, Australia. [Simes, R. John] Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW 2006, Australia. [Durrington, Paul] Univ Manchester, Sch Biomed, Manchester, Lancs, England. [Hitman, Graham A.] Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Diabet & Metab Med, London, England. [Welch, K. M. A.] Rosalind Franklin Univ Med & Sci, N Chicago, IL USA. [DeMicco, David A.] Global Pharmaceut Pfizer, New York, NY USA. [Clearfield, Michael B.] Touro Univ, Mare Isl, CA USA. [Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Downs, John R.] S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. [Colhoun, Helen M.] Univ Dundee, Med Res Inst, Dundee, Scotland. [Tonkin, Andrew M.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Gotto, Antonio M., Jr.] Weill Cornell Med Coll, New York, NY USA. RP Kastelein, JJP (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM j.j.kastelein@amc.uva.nl RI Boekholdt, Matthijs/G-7562-2014; Simes, Robert/P-1497-2014; OI Colhoun, Helen/0000-0002-8345-3288 FU Merck Sharpe Dohme; AstraZeneca; Pfizer; Quest Diagnostics; Amgen; CSL; Boehringer-Ingelheim; EU Innovative Medicines Initiative from Roche; EU Innovative Medicines Initiative from Pfizer; EU Innovative Medicines Initiative from Eli Lilly; EU Innovative Medicines Initiative from Boehringer-Ingelheim; EU Innovative Medicines Initiative from sanofi-aventis; EU Innovative Medicines Initiative from AstraZeneca; Novartis; Eli Lilly; Kowa FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest Drs Boekholdt and Arsenault report receipt of consultancy fees from Pfizer. Dr Mora reports receipt of research grant support through her institution from Merck Sharpe & Dohme and AstraZeneca; consultancy fees from Pfizer and Quest Diagnostics; and lecture honoraria from AstraZeneca and Abbott. Dr LaRosa reports receipt of consultancy fees from Pfizer and Amgen, and travel expenses from Pfizer. Dr Pedersen reports receipt of research grant support and lecture fees from Pfizer. Dr Nestel reports serving as a board member for AstraZeneca and Merck Sharpe & Dohme; receipt of consultancy fees from AstraZeneca; lecture honoraria from Merck Sharpe & Dohme; and travel expenses from AstraZeneca and Merck Sharpe & Dohme. Dr DeMicco reports being a full-time employee of Pfizer. Dr Tonkin reports receipt of consultancy fees from Amgen, AstraZeneca, CSL, and Boehringer-Ingelheim; and lecture honoraria from AstraZeneca, CSL, Merck Sharpe & Dohme, and Boehringer-Ingelheim. Dr Colhoun reports receipt of research grant support through the EU Innovative Medicines Initiative from Roche, Pfizer, Eli Lilly, Boehringer-Ingelheim, sanofi-aventis, and AstraZeneca; consultancy fees from Pfizer, sanofi-aventis, Novartis, and Eli Lilly; stocks from Roche; and lecture honoraria and travel expenses from Pfizer. Dr Gotto reports serving on the board of directors for Aegerion Pharmaceuticals and Arisaph Pharmaceuticals; being a member of advisory boards for DuPont and Vatera Capital; and receiving consultancy fees from AstraZeneca, Kowa, and Merck Sharpe & Dohme. Dr Ridker reports receipt of research grant funding from Novartis and AstraZeneca; serving as a consultant to ISIS, Vascular Biogenics, Merck Sharpe & Dohme, Abbott, and Boerringer-Ingelheim; and being listed as a coinventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes that have been licensed to AstraZeneca and Siemens. Dr Kastelein reports receipt of lecture honoraria from Merck Sharpe & Dohme, Roche, Novartis, ISIS, Genzyme, Pfizer, Kowa, and AstraZeneca. Drs Downs, Hitman, Durrington, Simes, Welch, Clearfield, and Zwinderman reported no conflicts of interest. NR 31 TC 256 Z9 265 U1 2 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 28 PY 2012 VL 307 IS 12 BP 1302 EP 1309 DI 10.1001/jama.2012.366 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 914UP UT WOS:000301978400026 PM 22453571 ER PT J AU Thakral, PP Moo, LR Slotnick, SD AF Thakral, Preston P. Moo, Lauren R. Slotnick, Scott D. TI A neural mechanism for aesthetic experience SO NEUROREPORT LA English DT Article DE art; functional magnetic resonance imaging; motion; MT; prefrontal cortex ID IMPLIED MOTION; PAINTINGS; CORTEX; PERCEPTION; ACTIVATION; BEAUTY AB Aesthetic experience associated with viewing art has been hypothesized to depend on both low-level sensory processing and high-level conceptual processing. To test these hypotheses, we used functional MRI to evaluate the magnitude of activity in sensory motion processing region MT+ and in the prefrontal cortex while participants viewed van Gogh paintings that evoked a range of motion experience. In support of the sensory hypothesis of aesthetic experience and the conceptual hypothesis of aesthetic experience, MT+ activity was correlated to the degree of motion experience (but not the experience of pleasantness) and activity in the right anterior prefrontal cortex was associated with the experience of pleasantness (but not motion experience). These findings provide a neural mechanism for aesthetic experience that depends on sensory processing and conceptual processing. The techniques employed in the current study will serve as a framework for future studies to investigate the neural basis of aesthetic experience associated with other visual and nonvisual art forms such as sculpture, architecture, or music. NeuroReport 23:310-313 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Thakral, Preston P.; Slotnick, Scott D.] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Moo, Lauren R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Thakral, PP (reprint author), Boston Coll, Dept Psychol, McGuinn Hall, Chestnut Hill, MA 02467 USA. EM thakralp@bc.edu NR 20 TC 13 Z9 14 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 28 PY 2012 VL 23 IS 5 BP 310 EP 313 DI 10.1097/WNR.0b013e328351759f PG 4 WC Neurosciences SC Neurosciences & Neurology GA 905RE UT WOS:000301289300009 PM 22357395 ER PT J AU Schonkeren, D Swings, G Roberts, D Claas, F de Heer, E Scherjon, S AF Schonkeren, Dorrith Swings, Godelieve Roberts, Drucilla Claas, Frans de Heer, Emile Scherjon, Sicco TI Pregnancy Close to the Edge: An Immunosuppressive Infiltrate in the Chorionic Plate of Placentas from Uncomplicated Egg Cell Donation SO PLOS ONE LA English DT Article ID REGULATORY T-CELLS; DECIDUAL MACROPHAGES; REACTION PATTERNS; PREECLAMPSIA; DONOR; HLA; REPRODUCIBILITY; EXPRESSION; PHENOTYPE; NOSOLOGY AB In pregnancies achieved after egg donation (ED) tolerance towards a completely allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still unknown. A distinct lesion not described previously in the literature, was repeatedly found in the chorionic plate in a substantial portion of placentas from ED pregnancies, but never in placentas from normal term pregnancies. The aim of this study was to assess its origin and its cellular composition. The relation between the lesion, the clinical and histological parameters were assessed. In addition we investigated the relation with the number of HLA-mismatches and KIR genotype of mother and child. In ten out of twenty-six (38.5%) placentas from ED pregnancies an inflammatory lesion was present in the chorionic plate. A significantly lower incidence of pre-eclampsia was found in the group with the lesion; 0% versus 45.5%. A significant relation was found between this lesion and the presence of intervillositis, chronic deciduitis, presence of plasma cells and fibrin deposition in the decidua. Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the majority of cells present in the lesion are of maternal origin. The expression of the macrophage marker CD14+ and of the type 2 macrophage (M2) marker CD163+ was significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was significantly higher in cases with a lesion compared to the group without the lesion. In conclusion, a striking relationship was observed between the presence of a not previously described inflammatory lesion in the chorionic plate and the absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly maternal cells with a higher expression of the macrophage marker CD14+ and the M2 marker CD163+. These findings suggest a protective immune mechanism which might contribute to the prevention of severe clinical complications like pre-eclampsia. C1 [Schonkeren, Dorrith; Swings, Godelieve; Scherjon, Sicco] Leiden Univ, Dept Obstet, Med Ctr, Leiden, Netherlands. [Roberts, Drucilla] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Claas, Frans] Leiden Univ, Dept Immunohematol & Blood Transfus, Med Ctr, Leiden, Netherlands. [de Heer, Emile] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands. RP Schonkeren, D (reprint author), Leiden Univ, Dept Obstet, Med Ctr, Leiden, Netherlands. EM C.M.C.Schonkeren@lumc.nl NR 26 TC 12 Z9 13 U1 1 U2 4 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 27 PY 2012 VL 7 IS 3 AR e32347 DI 10.1371/journal.pone.0032347 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 940MY UT WOS:000303894900007 PM 22479322 ER PT J AU Arokiaraj, M Guerrero, LJ Levine, R Palacios, I AF Arokiaraj, Mark Guerrero, Luis J. Levine, Robert Palacios, Igor TI A NOVEL CARDIAC RESYNCHRONISATION THERAPY MODEL TO AUGMENT VENTICULAR CONTRACTION USING POLYMER BASED ACTUATORS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Pondicherry Inst Med Sci, Pondicherry, India. 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 27 PY 2012 VL 59 IS 13 SU S BP E974 EP E974 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701085 ER PT J AU Aronis, KN Chamberland, JP Mantzoros, CS AF Aronis, Konstantinos N. Chamberland, John P. Mantzoros, Christos S. TI GLP-1 PROMOTES ANGIOGENESIS IN A DOSE-DEPENDENT MANNER, THROUGH THE PI3K/AKT, PKC AND NITRIC OXIDE PATHWAYS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. RI Aronis, Konstantinos/F-3586-2012; Aronis, Konstantinos/J-6582-2014 OI Aronis, Konstantinos/0000-0001-7189-8434; 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 27 PY 2012 VL 59 IS 13 SU S BP E902 EP E902 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701015 ER PT J AU Baron, S Agnihotri, A Eisenhauer, A Roberts, D McCabe, J Zheng, H Nagurney, J Lyn, E Yeh, R AF Baron, Suzanne Agnihotri, Arvind Eisenhauer, Andrew Roberts, David McCabe, James Zheng, Hui Nagurney, John Lyn, Everett Yeh, Robert TI UNDERSTANDING THE PATTERNS AND EFFECTS OF EMERGENCY MEDICAL SERVICE UTILIZATION IN ACUTE CORONARY SYNDROME PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 27 PY 2012 VL 59 IS 13 SU S BP E382 EP E382 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700383 ER PT J AU Beaudoin, J Dal-Bianco, J Aikawa, E Bischoff, J Guerrero, L Sullivan, S Wylie-Sears, J Aaron, J Levine, RA AF Beaudoin, Jonathan Dal-Bianco, Jacob Aikawa, Elena Bischoff, Joyce Guerrero, Luis Sullivan, Suzanne Wylie-Sears, Jill Aaron, Jacob Levine, Robert A. TI MITRAL LEAFLET CHANGES FOLLOWING MYOCARDIAL INFARCTION: EVIDENCE FOR MALADAPTIVE REMODELING FAVORING ISCHEMIC MITRAL REGURGITATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 3 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 27 PY 2012 VL 59 IS 13 SU S BP E2136 EP E2136 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702347 ER PT J AU Bhatia, R Carne, D Picard, M Weiner, R AF Bhatia, Rajan Carne, Dana Picard, Michael Weiner, Rory TI COMPARISON OF THE 2007 AND 2011 APPROPRIATE USE CRITERIA FOR TRANSTHORACIC ECHOCARDIOGRAPHY IN VARIOUS CLINICAL SETTINGS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Bhatia, Rajan; Carne, Dana; Picard, Michael; Weiner, Rory] Massachusetts Gen Hosp, Bostons, MA 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 27 PY 2012 VL 59 IS 13 SU S BP E1809 EP E1809 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702020 ER PT J AU Bose, A Kandala, J Upadhyay, G Ahmado, I Altman, R Riedl, L Mulligan, LJ Singh, J AF Bose, Abhishek Kandala, Jagdesh Upadhyay, Gaurav Ahmado, Imad Altman, Robert Riedl, Lindsay Mulligan, Lawrence J. Singh, Jagmeet TI ANGIOGRAPHIC AND NUCLEAR IMAGING PREDICTORS OF RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY (CRT) IN ISCHEMIC CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Bose, Abhishek; Kandala, Jagdesh; Upadhyay, Gaurav; Ahmado, Imad; Altman, Robert; Riedl, Lindsay; Mulligan, Lawrence J.; Singh, Jagmeet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2012 VL 59 IS 13 SU S BP E636 EP E636 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700638 ER PT J AU Bui, AH Cannon, C Steg, P Storey, R Husted, S Ren, F James, S Michelson, E Horrow, J Wallentin, L Scirica, B AF Bui, An Hong Cannon, Christopher Steg, Philippe Storey, Robert Husted, Steen Ren, Fang James, Stefan Michelson, Eric Horrow, Jay Wallentin, Lars Scirica, Benjamin TI RELATIONSHIP BETWEEN NONSUSTAINED VENTRICULAR TACHYCARDIA AND VASCULAR DEATH IN PATIENTS WITH ACUTE CORONARY SYNDROME IN THE PLATO (PLATELET INHIBITION AND PATIENT OUTCOMES) TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 TIMI Study Grp, Boston, MA 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 27 PY 2012 VL 59 IS 13 SU S BP E629 EP E629 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700631 ER PT J AU Daniels, KM Lecker, S Zavin, A Allsup, K Joseph, J Arena, R Schulze, PC Cao, PR Santhanam, M Forman, D AF Daniels, Karla M. Lecker, Stewart Zavin, Alexandra Allsup, Kelly Joseph, Jacob Arena, Ross Schulze, P. Christian Cao, Peirang Santhanam, Mahalakshmi Forman, Daniel TI GENE EXPRESSION OF THE UBIQUITIN-PROTEASOME PATHWAY IS REFLECTED BY VENTILATORY EXPIRED GAS ANALYSIS INDICES AT PEAK EXERCISE IN HEART FAILURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Daniels, Karla M.; Lecker, Stewart; Zavin, Alexandra; Allsup, Kelly; Joseph, Jacob; Arena, Ross; Schulze, P. Christian; Cao, Peirang; Santhanam, Mahalakshmi; Forman, Daniel] VA Boston Healthcare Syst, Boston, MA USA. RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 NR 0 TC 0 Z9 0 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 27 PY 2012 VL 59 IS 13 SU S BP E999 EP E999 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701110 ER PT J AU Daniels, KM Lecker, S Zavin, A Allsup, K Joseph, J Arena, R Schulze, PC Lazzari, A Cao, P Santhanam, M Forman, D AF Daniels, Karla M. Lecker, Stewart Zavin, Alexandra Allsup, Kelly Joseph, Jacob Arena, Ross Schulze, P. Christian Lazzari, Antonio Cao, Peirang Santhanam, Mahalakshmi Forman, Daniel TI PGC-1 alpha AND IGFBP-5 EXPRESSION IN SKELETAL MUSCLE OF HF PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Daniels, Karla M.; Lecker, Stewart; Zavin, Alexandra; Allsup, Kelly; Joseph, Jacob; Arena, Ross; Schulze, P. Christian; Lazzari, Antonio; Cao, Peirang; Santhanam, Mahalakshmi; Forman, Daniel] VA Boston Healthcare Syst, Boston, MA USA. RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 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 27 PY 2012 VL 59 IS 13 SU S BP E966 EP E966 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701077 ER PT J AU Desai, NR Shrank, WH Antman, E Avorn, J Glynn, R Levin, R Choudhry, N AF Desai, Nihar R. Shrank, William H. Antman, Elliott Avorn, Jerry Glynn, Robert Levin, Raisa Choudhry, Niteesh TI THE RELATIVE BENEFIT OF FULL PRESCRIPTION COVERAGE VERSUS USUAL PRESCRIPTION COVERAGE IN PATIENTS UNDERGOING PCI: AN ANALYSIS FROM THE MI FREEE TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 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 27 PY 2012 VL 59 IS 13 SU S BP E511 EP E511 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700512 ER PT J AU Dhakal, BP Murphy, R Baggish, A Pappagianopoulos, PP Hough, SS Semigran, M Lewis, G AF Dhakal, Bishnu Prasad Murphy, Ryan Baggish, Aaron Pappagianopoulos, Paul P. Hough, Stacyann S. Semigran, Marc Lewis, Gregory TI IMPAIRED SYSTEMIC OXYGEN EXTRACTION IN HEART FAILURE WITH PRESERVED EJECTION FRACTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Dhakal, Bishnu Prasad; Murphy, Ryan; Baggish, Aaron; Pappagianopoulos, Paul P.; Hough, Stacyann S.; Semigran, Marc; Lewis, Gregory] 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 27 PY 2012 VL 59 IS 13 SU S BP E933 EP E933 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701044 ER PT J AU Elmariah, S Budoff, M Delaney, JAC Nasir, K Hamirani, Y Kronmal, R Fuster, V Halperin, J O'Brien, K AF Elmariah, Sammy Budoff, Matthew Delaney, Joseph A. C. Nasir, Khurram Hamirani, Yasmin Kronmal, Richard Fuster, Valentin Halperin, Jonathan O'Brien, Kevin TI RISK FACTORS FOR PROGRESSION OF MITRAL ANNULUS CALCIFICATION: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Elmariah, Sammy; Budoff, Matthew; Delaney, Joseph A. C.; Nasir, Khurram; Hamirani, Yasmin; Kronmal, Richard; Fuster, Valentin; Halperin, Jonathan; O'Brien, Kevin] 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 27 PY 2012 VL 59 IS 13 SU S BP E2005 EP E2005 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702216 ER PT J AU Engel, LC Sidhu, M Lee, A Abbara, S Kalra, M Brady, TJ Hoffmann, U Ghoshhajra, B AF Engel, Leif-Christopher Sidhu, Manavjot Lee, Ashley Abbara, Suhny Kalra, Manudeep Brady, Thomas J. Hoffmann, Udo Ghoshhajra, Brian TI RADIATION DOSE REDUCTION IN PEDIATRIC CARDIAC COMPUTED TOMOGRAPHY: EXPERIENCE FROM A TERTIARY MEDICAL CENTER SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2012 VL 59 IS 13 SU S BP E1356 EP E1356 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701467 ER PT J AU Flynn, A Afilalo, J Agnihotri, A Castrillo, C Shahian, D Picard, M AF Flynn, Aidan Afilalo, Jonathan Agnihotri, Arvind Castrillo, Cristina Shahian, David Picard, Michael TI THE SEVERITY OF AORTIC SCLEROSIS IS ASSOCIATED WITH MORTALITY AND MAJOR MORBIDITY AFTER CORONARY ARTERY BYPASS SURGERY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Flynn, Aidan; Afilalo, Jonathan; Agnihotri, Arvind; Castrillo, Cristina; Shahian, David; Picard, Michael] 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 27 PY 2012 VL 59 IS 13 SU S BP E1920 EP E1920 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702131 ER PT J AU Ge, Y Cheng, S Larson, M Ghorbani, A Martin, R Klein, R O'Donnell, C Ramachandran, V Shaw, S Wang, T Cohen, K AF Ge, Yin Cheng, Susan Larson, Martin Ghorbani, Anahita Martin, Roderick Klein, Rachael O'Donnell, Christopher Ramachandran, Vasan Shaw, Stanley Wang, Thomas Cohen, Kenneth TI RELATION OF DISTINCT CD31 CELL POPULATIONS WITH CARDIOVASCULAR RISK SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol 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 27 PY 2012 VL 59 IS 13 SU S BP E1646 EP E1646 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701757 ER PT J AU Gilstrap, LG Fernandez-Golarz, C Malhotra, R Pineda, E Peltier-Saxe, D Wood, M AF Gilstrap, Lauren Gray Fernandez-Golarz, Carina Malhotra, Rajeev Pineda, Eliana Peltier-Saxe, Donna Wood, Malissa TI COMMUNITY-BASED, PRIMARY PREVENTION PROGRAMS IMPROVE PSYCHOLOGICAL AND CARDIOVASCULAR HEALTH SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) 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 27 PY 2012 VL 59 IS 13 SU S BP E1752 EP E1752 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701863 ER PT J AU Giri, JS Yeh, R Kennedy, K Calfon, M Drachman, D White, C Rosenfield, K AF Giri, Jay S. Yeh, Robert Kennedy, Kevin Calfon, Marcella Drachman, Douglas White, Christopher Rosenfield, Kenneth TI COMPARATIVE EFFECTIVENESS OF COMMONLY USED DEVICES FOR CAROTID ARTERY STENTING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Giri, Jay S.; Yeh, Robert; Kennedy, Kevin; Calfon, Marcella; Drachman, Douglas; White, Christopher; Rosenfield, Kenneth] 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 27 PY 2012 VL 59 IS 13 SU S BP E252 EP E252 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700253 ER PT J AU Giri, JS Yeh, R Kennedy, K Weinberg, M Garasic, J White, C Rosenfield, K AF Giri, Jay S. Yeh, Robert Kennedy, Kevin Weinberg, Mitchell Garasic, Joseph White, Christopher Rosenfield, Kenneth TI UNPROTECTED CAROTID ARTERY STENTING IN MODERN PRACTICE: INSIGHTS FROM THE NCDRR SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Giri, Jay S.; Yeh, Robert; Kennedy, Kevin; Weinberg, Mitchell; Garasic, Joseph; White, Christopher; Rosenfield, Kenneth] 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 27 PY 2012 VL 59 IS 13 SU S BP E253 EP E253 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700254 ER PT J AU Hage, FG Lusa, L Dondi, M Giubbini, R Iskandrian, AE AF Hage, Fadi G. Lusa, Lara Dondi, Maurizio Giubbini, Raffaele Iskandrian, Ami E. TI COMPARISON OF EXERCISE MYOCARDIAL PERFUSION IMAGING AND EXERCISE ELECTROCARDIOGRAM IN DETECTING ISCHEMIA IN ASYMPTOMATIC PATIENTS WITH TYPE 2 DIABETES MELLITUS: RESULT OF A PROSPECTIVE MULTICENTER STUDY IN DEVELOPING NATIONS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Univ Alabama, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, 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 27 PY 2012 VL 59 IS 13 SU S BP E1163 EP E1163 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701274 ER PT J AU Hage, FG Wackers, FJT Bansal, S Chyun, DA Young, LH Inzucchi, S Iskandrian, AE AF Hage, Fadi G. Wackers, Frans J. Th Bansal, Shanti Chyun, Deborah A. Young, Lawrence H. Inzucchi, Silvio Iskandrian, Ami E. TI THE HEART RATE RESPONSE TO ADENOSINE AS A PREDICTOR OF ADVERSE CARDIAC OUTCOMES IN THE DETECTION OF ISCHEMIA IN ASYMPTOMATIC DIABETICS STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Univ Alabama, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, 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 27 PY 2012 VL 59 IS 13 SU S BP E1162 EP E1162 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701273 ER PT J AU Heist, EK Toluie, K Mazer, S Lee, K AF Heist, Edwin Kevin Toluie, Kamran Mazer, Sean Lee, Kwangdeok TI FACTORS AFFECTING RADIATION EXPOSURE DURING CRT IMPLANTATION: RESULTS OF THE LAND-IT REGISTRY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Heist, Edwin Kevin; Toluie, Kamran; Mazer, Sean; Lee, Kwangdeok] Massachusetts Gen Hosp, Boston, MA 02114 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 27 PY 2012 VL 59 IS 13 SU S BP E706 EP E706 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700708 ER PT J AU Hou, JB Xing, L Jia, HB Han, ZG Yang, S Meng, LB Kato, K Yonetsu, T Kim, SJ Lee, H Zhang, SS Bo, Y Jang, IK AF Hou, Jingbo Xing, Lei Jia, Haibo Han, Zhigang Yang, Shuang Meng, Lingbo Kato, Koji Yonetsu, Tiashi Kim, Soo Joong Lee, Hang Zhang, Shaosong Bo, Yu Jang, Ik-Kyung TI CORONARY PLAQUE CHARACTERISTICS IN PATIENTS WITH DIABETES MELLITUS WHO PRESENTED WITH ACUTE CORONARY SYNDROME: OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Harbin Med Coll, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 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 27 PY 2012 VL 59 IS 13 SU S BP E355 EP E355 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700356 ER PT J AU Jansen, K Mani, N Mehrotra, P Tan, T Rincon, L Picard, M Hung, J AF Jansen, Katrijn Mani, Navin Mehrotra, Praveen Tan, Timothy Rincon, Luis Picard, Michael Hung, Judy TI LEFT ATRIAL VOLUMES: SHOULD WE RESET THE REFERENCE STANDARD? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Jansen, Katrijn; Mani, Navin; Mehrotra, Praveen; Tan, Timothy; Rincon, Luis; Picard, Michael; Hung, Judy] 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 27 PY 2012 VL 59 IS 13 SU S BP E1264 EP E1264 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701375 ER PT J AU Joseph, J Zavin, A Lecker, SH Daniels, K Allsup, K Arena, R Schulze, PC Forman, DE AF Joseph, Jacob Zavin, Alexandra Lecker, Stewart H. Daniels, Karla Allsup, Kelly Arena, Ross Schulze, P. Christian Forman, Daniel E. TI CORRELATIONS BETWEEN RECOVERY KINETICS AND SKELETAL MUSCLE GENE EXPRESSION IN SYSTOLIC HEART FAILURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 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 27 PY 2012 VL 59 IS 13 SU S BP E937 EP E937 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701048 ER PT J AU Kandala, J Upadhyay, G Wu, S Drachman, D Singh, J AF Kandala, Jagdesh Upadhyay, Gaurav Wu, Sean Drachman, Douglas Singh, Jagmeet TI STEM CELL THERAPY IN CHRONIC ISCHEMIC CARDIOMYOPATHY: A META-ANALYSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Kandala, Jagdesh; Upadhyay, Gaurav; Wu, Sean; Drachman, Douglas; Singh, Jagmeet] 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 27 PY 2012 VL 59 IS 13 SU S BP E983 EP E983 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701094 ER PT J AU Kato, K Yonetsu, T Xing, L Kim, SJ McNulty, I Lee, H Yeh, R Sakhuja, R Uemura, S Zhang, SS Yu, B Mizuno, K Jang, IK AF Kato, Koji Yonetsu, Taishi Xing, Lei Kim, Soo Joong McNulty, Iris Lee, Hang Yeh, Robert Sakhuja, Rahul Uemura, Shiro Zhang, Shaosong Yu, Bo Mizuno, Kyoichi Jang, Ik-Kyung TI OPTICAL COHERENCE TOMOGRAPHY FINDINGS IMMEDIATELY POST-STENT IMPLANTATION AND THEIR CLINICAL SIGNIFICANCE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Kato, Koji; Yonetsu, Taishi; Xing, Lei; Kim, Soo Joong; McNulty, Iris; Lee, Hang; Yeh, Robert; Sakhuja, Rahul; Uemura, Shiro; Zhang, Shaosong; Yu, Bo; Mizuno, Kyoichi; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 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 27 PY 2012 VL 59 IS 13 SU S BP E1440 EP E1440 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701551 ER PT J AU Kato, K Yonetsu, T Kim, SJ Xing, L Lee, H McNulty, I Yeh, R Sakhuja, R Zhang, SS Uemura, S Yu, B Mizuno, K Jang, IK AF Kato, Koji Yonetsu, Taishi Kim, Soo-Joong Xing, Lei Lee, Hang McNulty, Iris Yeh, Robert Sakhuja, Rahul Zhang, Shaosong Uemura, Shiro Yu, Bo Mizuno, Kyoichi Jang, Ik-Kyung TI CORONARY PLAQUE CHARACTERISTICS IN DIABETIC PATIENTS: A 3 VESSEL OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Kato, Koji; Yonetsu, Taishi; Kim, Soo-Joong; Xing, Lei; Lee, Hang; McNulty, Iris; Yeh, Robert; Sakhuja, Rahul; Zhang, Shaosong; Uemura, Shiro; Yu, Bo; Mizuno, Kyoichi; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 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 27 PY 2012 VL 59 IS 13 SU S BP E1434 EP E1434 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701545 ER PT J AU Kato, K Yonetsu, T Kim, SJ Xing, L McNulty, I Yeh, R Sakhuja, R Lee, H Zhang, SS Uemura, S Yu, B Mizuno, K Jang, IK AF Kato, Koji Yonetsu, Taishi Kim, Soo-Joong Xing, Lei McNulty, Iris Yeh, Robert Sakhuja, Rahul Lee, Hang Zhang, Shaosong Uemura, Shiro Yu, Bo Mizuno, Kyoichi Jang, Ik-Kyung TI NON-CULPRIT PLAQUES IN PATIENTS WITH ACUTE CORONARY SYNDROME (ACS) HAVE MORE VULNERABLE FEATURES COMPARED TO THOSE WITH NON-ACS: A 3 VESSEL OCT STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Kato, Koji; Yonetsu, Taishi; Kim, Soo-Joong; Xing, Lei; McNulty, Iris; Yeh, Robert; Sakhuja, Rahul; Lee, Hang; Zhang, Shaosong; Uemura, Shiro; Yu, Bo; Mizuno, Kyoichi; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2012 VL 59 IS 13 SU S BP E407 EP E407 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700408 ER PT J AU Kim, SJ Lee, H Kato, K Yonetsu, T Xing, L Zhang, SS Jang, IK AF Kim, Soo-Joong Lee, Hang Kato, Koji Yonetsu, Taishi Xing, Lei Zhang, Shaosong Jang, Ik-Kyung TI IN VIVO REPRODUCIBILITY OF MEASUREMENTS FOR FIBROUS CAP THICKNESS AND LIPID ARC IN LIPID PLAQUES BY OPTICAL COHERENCE TOMOGRAPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Kyung Hee Univ Hosp, Seoul, South Korea. 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 27 PY 2012 VL 59 IS 13 SU S BP E1438 EP E1438 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701549 ER PT J AU Kohli, P Wallentin, L Reyes, E Horrow, J Husted, S Storey, R James, S Cannon, C AF Kohli, Payal Wallentin, Lars Reyes, Eric Horrow, Jay Husted, Steen Storey, Robert James, Stefan Cannon, Christopher TI REDUCTION IN FIRST AND RECURRENT CARDIOVASCULAR AND ISCHEMIC EVENTS WITH TICAGRELOR COMPARED WITH CLOPIDOGREL IN THE PLATO STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2012 VL 59 IS 13 SU S BP E504 EP E504 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700505 ER PT J AU Kohli, P Morrow, D Murphy, S Cannon, C Ridker, P Braunwald, E Sabatine, M AF Kohli, Payal Morrow, David Murphy, Sabina Cannon, Christopher Ridker, Paul Braunwald, Eugene Sabatine, Marc TI PROGNOSTIC VALUE OF SERIAL C-REACTIVE PROTEIN LEVELS AFTER AN ACUTE CORONARY SYNDROME: AN ANALYSIS FROM PROVE-IT TIMI 22 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Kohli, Payal; Morrow, David; Murphy, Sabina; Cannon, Christopher; Ridker, Paul; Braunwald, Eugene; Sabatine, Marc] Brigham & Womens Hosp, TIMI Study Grp, 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 27 PY 2012 VL 59 IS 13 SU S BP E399 EP E399 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700400 ER PT J AU Kohli, P Udell, J Murphy, S Antman, E Braunwald, E Wiviott, S AF Kohli, Payal Udell, Jacob Murphy, Sabina Antman, Elliott Braunwald, Eugene Wiviott, Stephen TI DISCHARGE ASPIRIN DOSE AND CLINICAL OUTCOMES IN PATIENTS WITH ACS: AN ANALYSIS FROM THE TRITON-TIMI 38 STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 TIMI Study Grp, 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 27 PY 2012 VL 59 IS 13 SU S BP E342 EP E342 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700343 ER PT J AU Kumbhani, DJ Steg, P Cannon, C Eagle, K Smith, S Crowley, K Goto, S Ohman, E Bakris, G Perlstein, T Kinlay, S Bhatt, D AF Kumbhani, Dharam J. Steg, Philippe Cannon, Christopher Eagle, Kim Smith, Sidney Crowley, Kevin Goto, Shinya Ohman, Erik Bakris, George Perlstein, Todd Kinlay, Scott Bhatt, Deepak TI RESISTANT HYPERTENSION: A FREQUENT AND OMINOUS FINDING AMONG HYPERTENSIVE PATIENTS WITH ATHEROTHROMBOSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, W Roxbury, 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 27 PY 2012 VL 59 IS 13 SU S BP E1733 EP E1733 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701844 ER PT J AU Le, DTE Nugent, M Zhao, Y Bragadeesh, T Alkayed, N Kaul, S AF Le, Dai-Trang Elizabeth Nugent, Matthew Zhao, Yan Bragadeesh, Thanjavur Alkayed, Nabil Kaul, Sanjiv TI MECHANISM OF MYOGENIC RESPONSE IN CORONARY AUTOREGULATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 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 27 PY 2012 VL 59 IS 13 SU S BP E426 EP E426 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700427 ER PT J AU Lloyd, SG Liu, J AF Lloyd, Steven G. Liu, Jian TI HIGH-FAT, LOW-CARBOHYDRATE DIET RESULTS IN INCREASED MYOCARDIAL OXIDATIVE STRESS AND IMPAIRED MITOCHONDRIAL FUNCTION IN OBESE RATS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL 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 27 PY 2012 VL 59 IS 13 SU S BP E446 EP E446 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700447 ER PT J AU Lloyd, SG Wang, PP Tate, JM Douglas, SL AF Lloyd, Steven G. Wang, Peipei Tate, Joshua M. Douglas, Samuel L. TI IMPACT OF HIGH-FAT, LOW-CARBOHYDRATE DIET ON INSULIN SENSITIVITY AND TCA CYCLE SUBSTRATE ENTRY DURING ISCHEMIA-REPERFUSION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 7 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 27 PY 2012 VL 59 IS 13 SU S BP E438 EP E438 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700439 ER PT J AU Lumish, H Sidhu, M Engel, LC Uthamalingam, S Brady, TJ Hoffmann, U Ghoshhajra, B AF Lumish, Heidi Sidhu, Manavjot Engel, Leif-Christopher Uthamalingam, Shanmugam Brady, Thomas J. Hoffmann, Udo Ghoshhajra, Brian TI ADHERENCE TO THE 2010 AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION APPROPRIATE USE CRITERIA FOR CARDIAC COMPUTED TOMOGRAPHY IS INDEPENDENT OF PROVIDER TYPE IN AN ACADEMIC TERTIARY REFERRAL CENTER SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) 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 27 PY 2012 VL 59 IS 13 SU S BP E1862 EP E1862 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702073 ER PT J AU Mehrotra, P Jansen, K Tan, T Flynn, A Picard, M Hung, J AF Mehrotra, Praveen Jansen, Katrijn Tan, Timothy Flynn, Aidan Picard, Michael Hung, Judy TI LOW STROKE VOLUME IN PATIENTS WITH SEVERE AORTIC STENOSIS IS ASSOCIATED WITH ADVERSE LEFT VENTRICULAR REMODELING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Mehrotra, Praveen; Jansen, Katrijn; Tan, Timothy; Flynn, Aidan; Picard, Michael; Hung, Judy] Massachusetts Gen Hosp, Boston, MA 02114 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 27 PY 2012 VL 59 IS 13 SU S BP E1254 EP E1254 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701365 ER PT J AU Mukete, BN Sidhu, G Rosendorff, C AF Mukete, Bertrand N. Sidhu, Gurpreet Rosendorff, Clive TI EFFECTS OF LOW-DOSE THIAZIDE DIURETICS ON GLUCOSE TOLERANCE AND SERUM POTASSIUM A META-ANALYSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Mt Sinai Sch Med, New York, NY USA. James J Peters VAMC, Bronx, NY 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 27 PY 2012 VL 59 IS 13 SU S BP E1720 EP E1720 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701831 ER PT J AU Murphy, RM Weiner, RB Hough, SS Pappagianopoulos, PP Systrom, DM Hutter, AM Baggish, AL Lewis, GD AF Murphy, Ryan M. Weiner, Rory B. Hough, Stacyann S. Pappagianopoulos, Paul P. Systrom, David M. Hutter, Adolph M. Baggish, Aaron L. Lewis, Gregory D. TI DETERMINANTS OF VE/VCO2 SLOPE IN NORMAL INDIVIDUALS - VENTILATORY EFFICIENCY IS MODIFIABLE WITH ENDURANCE TRAINING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Murphy, Ryan M.; Weiner, Rory B.; Hough, Stacyann S.; Pappagianopoulos, Paul P.; Systrom, David M.; Hutter, Adolph M.; Baggish, Aaron L.; Lewis, Gregory D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 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 27 PY 2012 VL 59 IS 13 SU S BP E1943 EP E1943 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702154 ER PT J AU Neilan, TG Coelho, O Danik, S Verdini, DJ Michifumi, T Shah, R Tedrow, U Stevenson, W Jerosch-Herold, M Ghoshhajra, B Kwong, R AF Neilan, Tomas G. Coelho-Filho, Otavio Danik, Stephan Verdini, Daniel J. Michifumi, Tokuda Shah, Ravi Tedrow, Usha Stevenson, William Jerosch-Herold, Michael Ghoshhajra, Brian Kwong, Raymond TI THE IMPACT OF MYOCARDIAL SCAR BY CARDIAC MAGNETIC RESONANCE IN PATIENTS WITH NON-ISCHEMIC DILATED CARDIOMYOPATHY REFERRED FOR AN IMPLANTABLE CARDIOVERTER DEFIBRILLATOR FOR PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusettes Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2012 VL 59 IS 13 SU S BP E866 EP E866 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700869 ER PT J AU Nunes, MP Handschumacher, M Barbosa, M Levine, R Esteves, W Carvalho, V Rincon, L Tan, T Zeng, X Hung, J AF Nunes, Maria Pereira Handschumacher, Mark Barbosa, Marcia Levine, Robert Esteves, William Carvalho, Vinicius Rincon, Luis Tan, Timothy Zeng, Xin Hung, Judy TI THE ROLE OF LEFT ATRIAL SHAPE IN PREDICTING EMBOLIC EVENTS IN MITRAL STENOSIS: INSIGHTS FROM 3D ECHOCARDIOGRAPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. Univ Fed Minas Gerais, Sch Med, Belo Horizonte, MG, Brazil. 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 27 PY 2012 VL 59 IS 13 SU S BP E1969 EP E1969 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702180 ER PT J AU Nunes, MP Hung, J Barbosa, MM Esteves, WA Carvalho, VT Lodi-Junqueira, L Neto, C Levine, R AF Nunes, Maria Pereira Hung, Judy Barbosa, Marcia M. Esteves, William A. Carvalho, Vinicius T. Lodi-Junqueira, Lucas Neto, Cirilo Levine, Robert TI IMPACT OF ATRIOVENTRICULAR COMPLIANCE ON CLINICAL OUTCOME IN MITRAL STENOSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Nunes, Maria Pereira; Hung, Judy; Barbosa, Marcia M.; Esteves, William A.; Carvalho, Vinicius T.; Lodi-Junqueira, Lucas; Neto, Cirilo; Levine, Robert] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, 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 27 PY 2012 VL 59 IS 13 SU S BP E1967 EP E1967 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702178 ER PT J AU O'Malley, RG Bonaca, M Sabatine, M Scirica, B Jarolim, P Conrad, M Murphy, S Braunwald, E Morrow, D AF O'Malley, Ryan G. Bonaca, Marc Sabatine, Marc Scirica, Benjamin Jarolim, Petr Conrad, Michael Murphy, Sabina Braunwald, Eugene Morrow, David TI PROGNOSTIC PERFORMANCE OF A SINGLE-MOLECULE HIGH-SENSITIVITY CARDIAC TROPONIN ASSAY AFTER NON-ST ELEVATION ACUTE CORONARY SYNDROME: ANALYSIS FROM MERLIN-TIMI 36 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Brigham & Womens Hosp, Boston, MA 02115 USA. TIMI Study Grp, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2012 VL 59 IS 13 SU S BP E402 EP E402 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700403 ER PT J AU Schopfer, DW Regan, M Whooley, M AF Schopfer, David W. Regan, Mathilda Whooley, Mary TI GROWTH-DIFFERENTIATION FACTOR-15 PREDICTS CARDIOVASCULAR OUTCOMES IN PATIENTS WITH STABLE ISCHEMIC HEART DISEASE (THE HEART AND SOUL STUDY) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 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 27 PY 2012 VL 59 IS 13 SU S BP E1475 EP E1475 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701586 ER PT J AU Scirica, B Morrow, D Antman, E Bonaca, M Murphy, S Braunwald, E Wiviott, S AF Scirica, Benjamin Morrow, David Antman, Elliott Bonaca, Marc Murphy, Sabina Braunwald, Eugene Wiviott, Stephen TI TIMING AND CLINICAL SETTING OF CARDIOVASCULAR DEATH OR MYOCARDIAL INFARCTION FOLLOWING PCI FOR ACS - OBSERVATIONS FROM THE TRITON-TIMI 38 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2012 VL 59 IS 13 SU S BP E340 EP E340 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700341 ER PT J AU Seifarth, H Schlett, C Nakano, M Otsuka, F Gary, L Maurovich-Horvat, P Virmani, R Hoffmann, U AF Seifarth, Harald Schlett, Christopher Nakano, Masataka Otsuka, Fumiyuki Gary, Liew Maurovich-Horvat, Pal Virmani, Renu Hoffmann, Udo TI MORPHOLOGY AND COMPOSITION OF ADVANCED CORONARY PLAQUES IN HISTOLOGY PREDICT THE DELINEATION OF THE OF NAPKIN RING SIGN IN CORONARY CT ANGIOGRAPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) 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 27 PY 2012 VL 59 IS 13 SU S BP E1219 EP E1219 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701330 ER PT J AU Shah, R Gaggin, H Bhardwaj, A Januzzi, J AF Shah, Ravi Gaggin, Hanna Bhardwaj, Anju Januzzi, James TI MID-REGIONAL PRO-ATRIAL NATRIURETIC PEPTIDE AND MID-REGIONAL PRO-ADRENOMEDULLIN ARE VALUABLE FOR THE EVALUATION OF PATIENTS WITH ACUTE DYSPNEA: RESULTS FROM THE PRO-BNP INVESTIGATION OF DYSPNEA IN THE EMERGENCY DEPARTMENT (PRIDE) STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Shah, Ravi; Gaggin, Hanna; Bhardwaj, Anju; Januzzi, James] 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 27 PY 2012 VL 59 IS 13 SU S BP E948 EP E948 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701059 ER PT J AU Subramanian, S Marincheva-Savcheva, G Medina, H Maurovich-Horvat, P Abdelbaky, A Vijayakumar, J Mogg, R Shankar, S Rudd, J Fayad, Z Brady, T Hoffmann, U Tawakol, A AF Subramanian, Sharath Marincheva-Savcheva, Gergana Medina, Hector Maurovich-Horvat, Pal Abdelbaky, Amr Vijayakumar, Jayanthi Mogg, Robin Shankar, Sudha Rudd, James Fayad, Zahi Brady, Tom Hoffmann, Udo Tawakol, Ahmed TI INFLAMMATION IS INCREASED IN NON-CALCIFIED/MIXED LEFT MAIN CORONARY PLAQUES AND IS MODIFIABLE BY STATINS: A MULTI-CENTER PET-CT STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC)/Conference on ACC-i2 with TCT CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Subramanian, Sharath; Marincheva-Savcheva, Gergana; Medina, Hector; Maurovich-Horvat, Pal; Abdelbaky, Amr; Vijayakumar, Jayanthi; Mogg, Robin; Shankar, Sudha; Rudd, James; Fayad, Zahi; Brady, Tom; Hoffmann, Udo; Tawakol, Ahmed] 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 27 PY 2012 VL 59 IS 13 SU S BP E1218 EP E1218 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701329 ER PT J AU Syed, Z Ali, M Scirica, B Morrow, D Stultz, C Guttag, J AF Syed, Zeeshan Ali, Moiz Scirica, Benjamin Morrow, David Stultz, Collin Guttag, John TI ASSOCIATION OF ELECTROCARDIOGRAPHIC MARKERS WITH HEART FAILURE FOLLOWING NON-STELEVATION ACUTE CORONARY SYNDROME: RESULTS FROM THE MERLIN-TIMI 36 TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Univ Michigan, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, TIMI Study Grp, 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 27 PY 2012 VL 59 IS 13 SU S BP E419 EP E419 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700420 ER PT J AU Tian, JW Hou, JB Xing, L Jia, HB Zhang, SS Yu, B Jang, IK AF Tian, JinWei Hou, Jingbo Xing, Lei Jia, Haibo Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI DOES NEOVASCULARIZATION PREDICT RESPONSE TO STATIN THERAPY? OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Harbin Med Coll, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NR 0 TC 0 Z9 0 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 27 PY 2012 VL 59 IS 13 SU S BP E1537 EP E1537 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701648 ER PT J AU Tian, JW Hou, JB Xing, L Jia, HB Zhang, SS Yu, B Jang, IK AF Tian, JinWei Hou, Jingbo Xing, Lei Jia, Haibo Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI SIGNIFICANCE OF INTRAPLAQUE NEOVASCULARIZATION FOR VULNERABILITY: OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Harbin Med Coll, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 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 27 PY 2012 VL 59 IS 13 SU S BP E1439 EP E1439 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701550 ER PT J AU Tian, JW Hu, SN Jia, HB Hou, JB Zhang, SS Yu, B Jang, IK AF Tian, JinWei Hu, Sining Jia, Haibo Hou, Jingbo Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI CORRELATION OF VASA VASORUM AND PLAQUE PROGRESSION AND RESPONSE TO ATORVASTATIN THERAPY AN A RABBIT MODEL OF ATHEROSCLEROSIS: IN VIVO INTRAVASCULAR ULTRASOUND AND CONTRAST-ENHANCED ULTRASOUND IMAGING STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Harbin Med Coll, Affiliated Hosp 2, Haerbin, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 2 Z9 2 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 27 PY 2012 VL 59 IS 13 SU S BP E1072 EP E1072 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701183 ER PT J AU Tikkanen, AU Opotowsky, A Landzberg, M Bhatt, A Rhodes, J AF Tikkanen, Ana Ubeda Opotowsky, Alexander Landzberg, Michael Bhatt, Ami Rhodes, Jonathan TI PHYSICAL ACTIVITY AND IMPROVED EXERCISE CAPACITY IN ADULTS WITH CONGENITAL HEART DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Childrens Hosp Boston, Boston, MA USA. Massachusettes Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 7 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 27 PY 2012 VL 59 IS 13 SU S BP E846 EP E846 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700849 ER PT J AU Tsai, T Patel, U Chang, TI Kennedy, KF Masoudi, F Matheny, M Kosiborod, M Messenger, J Rumsfeld, J Spertus, J AF Tsai, Thomas Patel, Uptal Chang, Tara I. Kennedy, Kevin F. Masoudi, Frederick Matheny, Michael Kosiborod, Mikhail Messenger, John Rumsfeld, John Spertus, John TI CONTEMPORARY INCIDENCE AND PREDICTORS OF ACUTE KIDNEY INJURY IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTIONS: INSIGHTS FROM THE NCDR CATH-PCI REGISTRY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 U Colorado Denver, Denver VA Med Ctr, Denver, CO USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 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 27 PY 2012 VL 59 IS 13 SU S BP E337 EP E337 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700338 ER PT J AU Upadhyay, GA Kandala, J Bose, A Altman, R Parks, K Singh, J AF Upadhyay, Gaurav A. Kandala, Jagdesh Bose, Abhishek Altman, Robert Parks, Kimberly Singh, Jagmeet TI PRIOR VALVE SURGERY DOES NOT ALTER OUTCOMES IN PATIENTS TREATED WITH CARDIAC RESYNCHRONIZATION THERAPY (CRT) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Upadhyay, Gaurav A.; Kandala, Jagdesh; Bose, Abhishek; Altman, Robert; Parks, Kimberly; Singh, Jagmeet] Harvard Univ, Massachusetts Gen Hosp, 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 27 PY 2012 VL 59 IS 13 SU S BP E2044 EP E2044 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702255 ER PT J AU Weiner, RB Hutter, A Lewis, G Wang, FC Berkstresser, B Wang, T Picard, M Baggish, A AF Weiner, Rory B. Hutter, Adolph Lewis, Gregory Wang, Francis Berkstresser, Brant Wang, Thomas Picard, Michael Baggish, Aaron TI THE IMPACT OF EXERCISE TRAINING ON LEFT VENTRICULAR TORSION IS SPORT-SPECIFIC: A NEW TWIST ON THE MORGANROTH HYPOTHESIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ Hlth Serv, Cambridge, 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 27 PY 2012 VL 59 IS 13 SU S BP E1928 EP E1928 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702139 ER PT J AU Weiner, RB Hutter, A Lewis, G Wang, FC Berkstresser, B Wang, TM Picard, M Baggish, A AF Weiner, Rory B. Hutter, Adolph Lewis, Gregory Wang, Francis Berkstresser, Brant Wang, Thomas Picard, Michael Baggish, Aaron TI SPORT-SPECIFIC LEFT VENTRICULAR RESPONSE TO ACUTE PRESSURE CHALLENGE: FUNCTIONAL IMPLICATIONS OF THE ATHLETE'S HEART SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ Hlth Serv, Cambridge, 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 27 PY 2012 VL 59 IS 13 SU S BP E1932 EP E1932 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326702143 ER PT J AU Xing, L Tian, JW Hou, JB Jia, HB Kato, K Yonetsu, T Kim, SJ Huai, Y Ren, XF Huang, XT Zhang, SS Yu, B Jang, IK AF Xing, Lei Tian, Jinwei Hou, Jingbo Jia, Haibo Kato, Koji Yonetsu, Taishi Kim, Soo-Joong Huai, Yu Ren, Xuefeng Huang, Xingtao Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI MICROVESSELS IN FIBROUS PLAQUE: AN OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harbin Med Coll, Affiliated Hosp 2, Harbin, Peoples R China. 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 27 PY 2012 VL 59 IS 13 SU S BP E1432 EP E1432 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701543 ER PT J AU Xing, L Hou, JB Jia, HB Han, ZG Kim, SJ Kato, K Yonetsu, T Zhang, SS Yu, B Jang, IK AF Xing, Lei Hou, Jingbo Jia, Haibo Han, Zhigang Kim, Soo-Joong Kato, Koji Yonetsu, Taishi Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI HE NATURAL HISTORY OF LIPID PLAQUES: LONGITUDINAL OBSERVATION AT BASELINE, 6 MONTHS, AND 12 MONTHS USING OPTICAL COHERENCE TOMOGRAPHY AND INTRAVASCULAR ULTRASOUND SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harbin Med Coll, Affiliated Hosp 2, Harbin, Peoples R China. 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 27 PY 2012 VL 59 IS 13 SU S BP E384 EP E384 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326700385 ER PT J AU Yonetsu, T Kim, JS Kato, K Kim, SJ Xing, L Yeh, R Sakhuja, R McNulty, I Lee, H Aguirre, A Zhang, SS Uemura, S Yu, B Kakuta, T Jang, IK AF Yonetsu, Taishi Kim, Jung-Sun Kato, Koji Kim, Soo-Joong Xing, Lei Yeh, Robert Sakhuja, Rahul McNulty, Iris Lee, Hang Aguirre, Aaron Zhang, Shaosong Uemura, Shiro Yu, Bo Kakuta, Tsunekazu Jang, Ik-Kyung TI INCIDENCE, TIME COURSE, AND CHARACTERISTICS OF NEOATHEROSCLEROSIS: COMPARISON BETWEEN BARE-METAL STENTS AND DRUG ELUTING STENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Yonetsu, Taishi; Kim, Jung-Sun; Kato, Koji; Kim, Soo-Joong; Xing, Lei; Yeh, Robert; Sakhuja, Rahul; McNulty, Iris; Lee, Hang; Aguirre, Aaron; Zhang, Shaosong; Uemura, Shiro; Yu, Bo; Kakuta, Tsunekazu; Jang, Ik-Kyung] Massachusetts Gen Hosp, Caridiol Div, 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 27 PY 2012 VL 59 IS 13 SU S BP E1505 EP E1505 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701616 ER PT J AU Yonetsu, T Kato, K Kim, SJ Xing, L Yeh, R Sakhuja, R McMulty, I Lee, H Zhang, SS Uemura, S Yu, B Jang, IK AF Yonetsu, Taishi Kato, Koji Kim, Soo-Joong Xing, Lei Yeh, Robert Sakhuja, Rahul McMulty, Iris Lee, Hang Zhang, Shaosong Uemura, Shiro Yu, Bo Jang, Ik-Kyung TI CORONARY PLAQUE CHARACTERISTICS IN PATIENTS WITH METABOLIC SYNDROME: COMPARISON TO THOSE WITH DIABETES AND WITH NORMAL GLYCEMIA: AN OPTICAL COHERENCE TOMOGRAPHY STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Yonetsu, Taishi; Kato, Koji; Kim, Soo-Joong; Xing, Lei; Yeh, Robert; Sakhuja, Rahul; McMulty, Iris; Lee, Hang; Zhang, Shaosong; Uemura, Shiro; Yu, Bo; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 27 PY 2012 VL 59 IS 13 SU S BP E1433 EP E1433 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701544 ER PT J AU Zavin, A Daniels, K Allsup, K Arena, R Lecker, S Joseph, J Schulze, PC Forman, D AF Zavin, Alexandra Daniels, Karla Allsup, Kelly Arena, Ross Lecker, Stewart Joseph, Jacob Schulze, P. Christian Forman, Daniel TI THE SIX MINUTE WALK DISTANCE AS AN INDICATOR OF FRAILTY AND FUNCTIONAL INCAPACITY IN ELDERLY HEART FAILURE PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 61st Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC) CY MAR 24-27, 2012 CL Chicago, IL SP Amer Coll Cardiol (ACC) C1 [Zavin, Alexandra; Daniels, Karla; Allsup, Kelly; Arena, Ross; Lecker, Stewart; Joseph, Jacob; Schulze, P. Christian; Forman, Daniel] VA Boston Healthcare Syst, Jamaica Plain, MA USA. RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 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 27 PY 2012 VL 59 IS 13 SU S BP E934 EP E934 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 919LB UT WOS:000302326701045 ER PT J AU Yang, Y Al-Mozaini, M Buzon, MJ Beamon, J Ferrando-Martinez, S Ruiz-Mateos, E Rosenberg, ES Pereyra, F Yu, XG Lichterfeld, M AF Yang, Yue Al-Mozaini, Maha Buzon, Maria J. Beamon, Jill Ferrando-Martinez, Sara Ruiz-Mateos, Ezequiel Rosenberg, Eric S. Pereyra, Florencia Yu, Xu G. Lichterfeld, Mathias TI CD4 T-cell regeneration in HIV-1 elite controllers SO AIDS LA English DT Article DE elite controllers; HIV-1; naive T cells; thymic function ID INFECTION; INDIVIDUALS; HOMEOSTASIS; THERAPY; DISEASE; THYMUS; VIRUS; NAIVE AB Background: Elite controllers spontaneously control HIV-1 replication, which in many cases is associated with preservation of normal CD4 T-cell counts. However, a subset of elite controllers has progressive CD4 T-cell losses despite undetectable viral loads, for reasons that remain undefined. Here, we assessed mechanisms of CD4 T-cell homeostasis in elite controllers with progressive vs. nonprogressive HIV-1 disease courses. Methods: Flow cytometry assays were used to determine the proliferation, activation and apoptosis levels of naive T cells in elite controllers with high or low CD4 T-cell counts and reference cohorts of HIV-1-negative and HAART-treated persons. Thymic output was measured by single-joint T-cell receptor excision circle (sjTREC)/beta T-cell receptor excision circle (beta TREC) ratios, and the frequency of circulating recent thymic emigrants was flow cytometrically determined by surface expression of protein tyrosine kinase 7. Results: Proportions of naive T cells in elite controllers were severely reduced and closely resemble those of HIV-1 patients with progressive disease. Despite reductions in naive T cells, most elite controllers were able to maintain normal total CD4 T-cell counts by preservation of uncompromised thymic function in conjunction with extrathymic processes that led to elevated levels of circulating recent thymic emigrants. In contrast, elite controllers with low CD4 T-cell counts had reduced thymic output that mirrored thymic dysfunction during untreated progressive HIV-1 infection. Conclusion: These results indicate that both thymic and extrathymic mechanisms contribute to CD4 T-cell maintenance in elite controllers and support the idea that CD4 T-cell homeostasis and control of viral replication are distinct but frequently coinciding processes. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Yang, Yue; Al-Mozaini, Maha; Buzon, Maria J.; Beamon, Jill; Rosenberg, Eric S.; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Yang, Yue; Al-Mozaini, Maha; Buzon, Maria J.; Pereyra, Florencia; Yu, Xu G.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Al-Mozaini, Maha] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Ferrando-Martinez, Sara] Gregorio Maranon Hosp, Lab Mol Immunobiol, Madrid, Spain. [Ferrando-Martinez, Sara; Ruiz-Mateos, Ezequiel] Virgen del Roci Univ Hosp, Inst Biomed Seville IBiS, Lab Immunovirol, Seville, Spain. RP Lichterfeld, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM mlichterfeld@partners.org RI Ruiz-Mateos, Ezequiel/F-2937-2015; IBIS, INMUNOVIROLOGI/O-9246-2015; Buzon, Maria J/G-8286-2015 OI Ruiz-Mateos, Ezequiel/0000-0001-6747-7813; Buzon, Maria J/0000-0003-4427-9413 FU Doris Duke Clinical Scientist Development Award [2009034]; NIH [AI078799, AI089339, AI093203]; Dubai Harvard Foundation for Medical Research; European Molecular Biology Organization (EMBO); Bill and Melinda Gates Foundation; Mark and Lisa Swartz Foundation; International HIV Controller Study; Fondo de Investigaciones Sanitaria [CD10/00382, CP08/00172]; Redes Tematicas de Investigacion Cooperativa en Salud (RETICS) [RD06/0006/0021, RD06/0006/0035] FX M.L. and X.G.Y. are recipients of the Doris Duke Clinical Scientist Development Award (Grant number 2009034). X.G.Y. is supported by NIH grants AI078799 and AI089339 and M. L. is supported by NIH grant AI093203. M. A. M. is supported by a fellowship award from the Dubai Harvard Foundation for Medical Research. M.J.B. is supported by a fellowship award from the European Molecular Biology Organization (EMBO). Patient recruitment was supported by the Bill and Melinda Gates Foundation, the Mark and Lisa Swartz Foundation and the International HIV Controller Study. S. F. M. and E. R. M. are supported by Fondo de Investigaciones Sanitaria (CD10/00382 and CP08/00172) and by Redes Tematicas de Investigacion Cooperativa en Salud (RETICS, Red de SIDA RD06/0006/0021 and RD06/0006/0035). NR 19 TC 18 Z9 18 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 27 PY 2012 VL 26 IS 6 BP 701 EP 706 DI 10.1097/QAD.0b013e3283519b22 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 914UA UT WOS:000301976900005 PM 22301416 ER PT J AU Zhang, X Giovannucci, EL Wu, K Smith-Warner, SA Fuchs, CS Pollak, M Willett, WC Ma, J AF Zhang, X. Giovannucci, E. L. Wu, K. Smith-Warner, S. A. Fuchs, C. S. Pollak, M. Willett, W. C. Ma, J. TI Magnesium intake, plasma C-peptide, and colorectal cancer incidence in US women: a 28-year follow-up study SO BRITISH JOURNAL OF CANCER LA English DT Article DE magnesium; calcium; insulin resistance; plasma C-peptide; colorectal cancer; incidence ID FOOD FREQUENCY QUESTIONNAIRE; DIETARY MAGNESIUM; COLON-CANCER; RISK; CALCIUM; INSULIN; REPRODUCIBILITY; METAANALYSIS; ASSOCIATION; MECHANISMS AB BACKGROUND: Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive. METHOD: We tested magnesium-colorectal cancer hypothesis in the Nurses' Health Study, in which 85 924 women free of cancer in 1980 were followed until June 2008. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95% confidence intervals). RESULTS: In the age-adjusted model, magnesium intake was significantly inversely associated with colorectal cancer risk; the RRs from lowest to highest decile of total magnesium intake were 1.0 (ref), 0.93, 0.81, 0.72, 0.74, 0.77, 0.72, 0.75, 0.80, and 0.67 (P-trend <0.001). However, in the MV model adjusted for known dietary and non-dietary risk factors for colorectal cancer, the association was significantly attenuated; the MV RRs were 1.0 (ref), 0.96, 0.85, 0.78, 0.82, 0.86, 0.84, 0.91, 1.02, and 0.93 (P-trend = 0.77). Similarly, magnesium intakes were significantly inversely associated with concentrations of plasma C-peptide in age-adjusted model (P-trend = 0.002) but not in multivariate-adjusted model (P-trend = 0.61). Results did not differ by subsite or modified by calcium intakes or body mass index. CONCLUSION: These prospective results do not support an independent association of magnesium intake with either colorectal cancer risk or plasma C-peptide levels in women. C1 [Zhang, X.; Giovannucci, E. L.; Fuchs, C. S.; Willett, W. C.; Ma, J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Zhang, X.; Giovannucci, E. L.; Pollak, M.; Willett, W. C.; Ma, J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Giovannucci, E. L.; Wu, K.; Smith-Warner, S. A.; Willett, W. C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, E. L.; Smith-Warner, S. A.; Willett, W. C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pollak, M.] McGill Univ, Dept Oncol, Montreal, PQ H3T 1E2, Canada. [Pollak, M.] Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada. RP Zhang, X (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. EM xuehong.zhang@channing.harvard.edu RI Pollak, Michael/G-9094-2011; Zhang, Xuehong/E-6219-2012 OI Pollak, Michael/0000-0003-3047-0604; FU NIH [CA87969]; National Cancer Institute of Canada [019894] FX We thank the participants and staff of the Nurses' Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This work was supported by a NIH Grant CA87969 and the National Cancer Institute of Canada Grant (#019894). NR 40 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 27 PY 2012 VL 106 IS 7 BP 1335 EP 1341 DI 10.1038/bjc.2012.76 PG 7 WC Oncology SC Oncology GA 916VG UT WOS:000302130700013 PM 22415230 ER PT J AU Shahian, DM O'Brien, SM Sheng, S Grover, FL Mayer, JE Jacobs, JP Weiss, JM DeLong, ER Peterson, ED Weintraub, WS Grau-Sepulveda, MV Klein, LW Shaw, RE Garratt, KN Moussa, ID Shewan, CM Dangas, GD Edwards, FH AF Shahian, David M. O'Brien, Sean M. Sheng, Shubin Grover, Frederick L. Mayer, John E. Jacobs, Jeffrey P. Weiss, Jocelyn M. DeLong, Elizabeth R. Peterson, Eric D. Weintraub, William S. Grau-Sepulveda, Maria V. Klein, Lloyd W. Shaw, Richard E. Garratt, Kirk N. Moussa, Issam D. Shewan, Cynthia M. Dangas, George D. Edwards, Fred H. TI Predictors of Long-Term Survival After Coronary Artery Bypass Grafting Surgery Results From the Society of Thoracic Surgeons Adult Cardiac Surgery Database (The ASCERT Study) SO CIRCULATION LA English DT Article DE CABG; long-term outcomes; registries; risk factors; survival analysis ID BODY-MASS INDEX; CLINICAL REGISTRY DATA; MEDICARE CLAIMS DATA; ADMINISTRATIVE DATABASES; INDIRECT IDENTIFIERS; QUALITY MEASUREMENT; CABG SURGERY; RISK-FACTORS; MORTALITY; OUTCOMES AB Background-Most survival prediction models for coronary artery bypass grafting surgery are limited to in-hospital or 30-day end points. We estimate a long-term survival model using data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database and Centers for Medicare and Medicaid Services. Methods and Results-The final study cohort included 348 341 isolated coronary artery bypass grafting patients aged >= 65 years, discharged between January 1, 2002, and December 31, 2007, from 917 Society of Thoracic Surgeons-participating hospitals, randomly divided into training (n = 174 506) and validation (n = 173 835) samples. Through linkage with Centers for Medicare and Medicaid Services claims data, we ascertained vital status from date of surgery through December 31, 2008 (1- to 6-year follow-up). Because the proportional hazards assumption was violated, we fit 4 Cox regression models conditional on being alive at the beginning of the following intervals: 0 to 30 days, 31 to 180 days, 181 days to 2 years, and >2 years. Kaplan-Meier-estimated mortality was 3.2% at 30 days, 6.4% at 180 days, 8.1% at 1 year, and 23.3% at 3 years of follow-up. Harrell's C statistic for predicting overall survival time was 0.732. Some risk factors (eg, emergency status, shock, reoperation) were strong predictors of short-term outcome but, for early survivors, became nonsignificant within 2 years. The adverse impact of some other risk factors (eg, dialysis-dependent renal failure, insulin-dependent diabetes mellitus) continued to increase. Conclusions-Using clinical registry data and longitudinal claims data, we developed a long-term survival prediction model for isolated coronary artery bypass grafting. This provides valuable information for shared decision making, comparative effectiveness research, quality improvement, and provider profiling. (Circulation. 2012;125:1491-1500.) C1 [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [O'Brien, Sean M.; Sheng, Shubin; DeLong, Elizabeth R.; Peterson, Eric D.; Grau-Sepulveda, Maria V.] Duke Clin Res Inst, Durham, NC USA. [Grover, Frederick L.] Univ Colorado, Sch Med, Denver, CO USA. [Mayer, John E.] Childrens Hosp Boston, Boston, MA USA. [Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA. [Weiss, Jocelyn M.] Amer Coll Cardiol, Washington, DC USA. [Weintraub, William S.] Christiana Care Ctr Outcome Res, Newark, DE USA. [Klein, Lloyd W.] Gottlieb Mem Hosp, Melrose Pk, IL USA. [Shaw, Richard E.] Calif Pacific Med Ctr, San Francisco, CA USA. [Garratt, Kirk N.] Lenox Hill Heart & Vasc Inst New York, New York, NY USA. [Moussa, Issam D.] Mayo Clin, Jacksonville, FL 32224 USA. [Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA. [Dangas, George D.] Columbia Univ, Med Ctr, New York, NY USA. [Edwards, Fred H.] Univ Florida Shands Jacksonville, Jacksonville, FL USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org RI O'Brien, Sean/H-6268-2013 FU National Heart, Lung, and Blood Institute [RC2HL101489] FX The ASCERT study is supported by award RC2HL101489 from the National Heart, Lung, and Blood Institute. This award has been issued under the American Recovery and Reinvestment Act of 2009 for a 2-year period. The funders played no role in the design, interpretation, or decision to publish the analysis presented herein. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. NR 39 TC 78 Z9 81 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 27 PY 2012 VL 125 IS 12 BP 1491 EP U113 DI 10.1161/CIRCULATIONAHA.111.066902 PG 35 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 916TA UT WOS:000302124900016 PM 22361330 ER PT J AU Weintraub, WS Grau-Sepulveda, MV Weiss, JM DeLong, ER Peterson, ED O'Brien, SM Kolm, P Klein, LW Shaw, RE Mckay, C Ritzenthaler, LL Popma, JJ Messenger, JC Shahian, DM Grover, FL Mayer, JE Garratt, KN Moussa, ID Edwards, FH Dangas, GD AF Weintraub, William S. Grau-Sepulveda, Maria V. Weiss, Jocelyn M. DeLong, Elizabeth R. Peterson, Eric D. O'Brien, Sean M. Kolm, Paul Klein, Lloyd W. Shaw, Richard E. Mckay, Charles Ritzenthaler, Laura L. Popma, Jeffrey J. Messenger, John C. Shahian, David M. Grover, Frederick L. Mayer, John E. Garratt, Kirk N. Moussa, Issam D. Edwards, Fred H. Dangas, George D. TI Prediction of Long-Term Mortality After Percutaneous Coronary Intervention in Older Adults Results From the National Cardiovascular Data Registry SO CIRCULATION LA English DT Article DE coronary artery disease; mortality; percutaneous coronary intervention; registries; revascularization ID IN-HOSPITAL MORTALITY; AMERICAN-COLLEGE; RISK SCORE; CLINICAL-OUTCOMES; MODELS; COMPLICATIONS AB Background-The purpose of this study was to develop a long-term model to predict mortality after percutaneous coronary intervention in both patients with ST-segment elevation myocardial infarction and those with more stable coronary disease. Methods and Results-The American College of Cardiology Foundation CathPCI Registry data were linked to the Centers for Medicare and Medicaid Services 100% denominator file by probabilistic matching. Preprocedure demographic and clinical variables from the CathPCI Registry were used to predict the probability of death over 3 years as recorded in the Centers for Medicare and Medicaid Services database. Between 2004 and 2007, 343 466 patients (66%) of 518 195 patients aged >= 65 years undergoing first percutaneous coronary intervention in the CathPCI Registry were successfully linked to Centers for Medicare and Medicaid Services data. This study population was randomly divided into 60% derivation and 40% validation cohorts. Median follow-up was 15 months, with mortality of 3.0% at 30 days and 8.7%, 13.4%, and 18.7% at 1, 2, and 3 years, respectively. Twenty-four characteristics related to demographics, clinical comorbidity, prior history of disease, and indices of disease severity and acuity were identified as being associated with mortality. The C indices in the validation cohorts for patients with and without ST-segment elevation myocardial infarction were 0.79 and 0.78. The model calibrated well across a wide range of predicted probabilities. Conclusions-On the basis of the large and nationally representative CathPCI Registry, we have developed a model that has excellent discrimination, calibration, and validation to predict survival up to 3 years after percutaneous coronary intervention. (Circulation. 2012;125:1501-1510.) C1 [Weintraub, William S.; Kolm, Paul] Christiana Care Ctr Outcome Res, Newark, DE USA. [Grau-Sepulveda, Maria V.; DeLong, Elizabeth R.; Peterson, Eric D.; O'Brien, Sean M.] Duke Clin Res Inst, Durham, NC USA. [Weiss, Jocelyn M.; Ritzenthaler, Laura L.] Amer Coll Cardiol, Washington, DC USA. [Klein, Lloyd W.] Advocate Illinois Mason Med Ctr, Chicago, IL USA. [Shaw, Richard E.] Calif Pacific Med Ctr, San Francisco, CA USA. [Mckay, Charles] Harbor Univ Calif Angeles, Med Ctr, Torrance, CA USA. [Popma, Jeffrey J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Messenger, John C.; Grover, Frederick L.] Univ Colorado, Sch Med, Denver, CO USA. [Shahian, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mayer, John E.] Childrens Hosp Boston, Boston, MA USA. [Garratt, Kirk N.] Lenox Hill Heart & Vasc Inst New York, New York, NY USA. [Moussa, Issam D.] Mayo Clin, Jacksonville, FL 32224 USA. [Edwards, Fred H.] Univ Florida Shands Jacksonville, Jacksonville, FL USA. [Dangas, George D.] Mt Sinai Med Ctr, New York, NY 10029 USA. RP Weintraub, WS (reprint author), Christiana Care Hlth Syst, 4755 Ogletown Stanton Rd,Suite 2E99, Newark, DE 19718 USA. EM wweintraub@christianacare.org RI O'Brien, Sean/H-6268-2013 FU National Heart, Lung, and Blood Institute [RC2HL101489] FX The ASCERT Study is supported by award RC2HL101489 from the National Heart, Lung, and Blood Institute. This award has been issued under the American Recovery and Reinvestment Act of 2009 for a 2-year period. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. NR 27 TC 43 Z9 43 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 27 PY 2012 VL 125 IS 12 BP 1501 EP U126 DI 10.1161/CIRCULATIONAHA.111.066969 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 916TA UT WOS:000302124900017 PM 22361329 ER PT J AU Parikh, VN Jin, RC Rabello, S Gulbahce, N White, K Hale, A Cottrill, KA Shaik, RS Waxman, AB Zhang, YY Maron, BA Hartner, JC Fujiwara, Y Orkin, SH Haley, KJ Barabasi, AL Loscalzo, J Chan, SY AF Parikh, Victoria N. Jin, Richard C. Rabello, Sabrina Gulbahce, Natali White, Kevin Hale, Andrew Cottrill, Katherine A. Shaik, Rahamthulla S. Waxman, Aaron B. Zhang, Ying-Yi Maron, Bradley A. Hartner, Jochen C. Fujiwara, Yuko Orkin, Stuart H. Haley, Kathleen J. Barabasi, Albert-Laszlo Loscalzo, Joseph Chan, Stephen Y. TI MicroRNA-21 Integrates Pathogenic Signaling to Control Pulmonary Hypertension Results of a Network Bioinformatics Approach SO CIRCULATION LA English DT Article DE microRNA; molecular biology; network biology; pulmonary heart disease; vasculature ID GROWTH-FACTOR-BETA; SMOOTH-MUSCLE-CELLS; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; FACTOR-KAPPA-B; MORPHOGENETIC PROTEIN-RECEPTOR; NITRIC-OXIDE SYNTHASE; HETEROZYGOUS BMPR2-MUTANT MICE; MALIGNANT HUMAN CHOLANGIOCYTES; INTESTINAL-PEPTIDE GENE; ARTERIAL-HYPERTENSION AB Background-Pulmonary hypertension (PH) is driven by diverse pathogenic etiologies. Owing to their pleiotropic actions, microRNA molecules are potential candidates for coordinated regulation of these disease stimuli. Methods and Results-Using a network biology approach, we identify microRNA associated with multiple pathogenic pathways central to PH. Specifically, microRNA-21 (miR-21) is predicted as a PH-modifying microRNA, regulating targets integral to bone morphogenetic protein (BMP) and Rho/Rho-kinase signaling as well as functional pathways associated with hypoxia, inflammation, and genetic haploinsufficiency of BMP receptor type 2. To validate these predictions, we have found that hypoxia and BMP receptor type 2 signaling independently upregulate miR-21 in cultured pulmonary arterial endothelial cells. In a reciprocal feedback loop, miR-21 downregulates BMP receptor type 2 expression. Furthermore, miR-21 directly represses RhoB expression and Rho-kinase activity, inducing molecular changes consistent with decreased angiogenesis and vasodilation. In vivo, miR-21 is upregulated in pulmonary tissue from several rodent models of PH and in humans with PH. On induction of disease in miR-21-null mice, RhoB expression and Rho-kinase activity are increased, accompanied by exaggerated manifestations of PH. Conclusions-A network-based bioinformatic approach coupled with confirmatory in vivo data delineates a central regulatory role for miR-21 in PH. Furthermore, this study highlights the unique utility of network biology for identifying disease-modifying microRNA in PH. (Circulation. 2012;125:1520-1532.) C1 [Parikh, Victoria N.; Jin, Richard C.; White, Kevin; Hale, Andrew; Cottrill, Katherine A.; Zhang, Ying-Yi; Maron, Bradley A.; Loscalzo, Joseph; Chan, Stephen Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Shaik, Rahamthulla S.; Waxman, Aaron B.; Haley, Kathleen J.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. [Rabello, Sabrina; Gulbahce, Natali; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Hartner, Jochen C.] Tacon Artemis GmbH, Cologne, Germany. [Rabello, Sabrina; Gulbahce, Natali; Barabasi, Albert-Laszlo] Childrens Hosp Boston, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA USA. [Gulbahce, Natali] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. [Rabello, Sabrina; Gulbahce, Natali; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Chan, SY (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, New Res Bldg,Room 630N,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM sychan@partners.org FU Sarnoff Cardiovascular Research Foundation; American Heart Association [0825906D]; National Institutes of Health [R37HL061795, U54HL070819, PO1HL48743, P50HL107192, U01HL108630]; Lerner Fund; Harris Fund; Watkins Fund; Gilead Research Scholars Fund; Pulmonary Hypertension Association; National Institutes of Health-Center of Excellence in Genomic Sciences FX This work was supported by the Sarnoff Cardiovascular Research Foundation (Dr Parikh); American Heart Association grant 0825906D, National Institutes of Health grant KO8, Lerner, Harris, and Watkins Funds, Gilead Research Scholars Fund, and Pulmonary Hypertension Association (Dr Chan); National Institutes of Health grants R37HL061795, U54HL070819, PO1HL48743, P50HL107192, and U01HL108630 (Dr Loscalzo); and National Institutes of Health-Center of Excellence in Genomic Sciences (Drs Rabello, Gulbahce, and Barabasi). NR 269 TC 104 Z9 110 U1 4 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 27 PY 2012 VL 125 IS 12 BP 1520 EP U216 DI 10.1161/CIRCULATIONAHA.111.060269 PG 79 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 916TA UT WOS:000302124900019 PM 22371328 ER PT J AU Xing, DQ Li, P Gong, KZ Yang, ZQ Yu, H Hage, FG Oparil, S Chen, YF AF Xing, Dongqi Li, Peng Gong, Kaizheng Yang, Zhengqin Yu, Hao Hage, Fadi G. Oparil, Suzanne Chen, Yiu-Fai TI Endothelial Cells Overexpressing Interleukin-8 Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury SO CIRCULATION LA English DT Article DE restenosis; endothelial cells; inflammation; receptors; interleukin-8; tissue therapy ID RAT CAROTID-ARTERY; PROGENITOR CELLS; BALLOON INJURY; ESTROGEN; REENDOTHELIALIZATION; DYSFUNCTION; MICE; INFILTRATION; NEUTROPHILS; DISEASE AB Background-Interleukin-8 (IL8) receptors IL8RA and IL8RB on neutrophil membranes bind to IL8 and direct neutrophil recruitment to sites of inflammation, including acutely injured arteries. This study tested whether administration of IL8RA- and/or IL8RB-transduced rat aortic endothelial cells (ECs) accelerates adhesion of ECs to the injured surface, thus suppressing inflammation and neointima formation in balloon-injured rat carotid arteries. We tested the hypothesis that targeted delivery of ECs by overexpressing IL8RA and IL8RB receptors prevents inflammatory responses and promotes structural recovery of arteries after endoluminal injury. Methods and Results-Young adult male rats received balloon injury of the right carotid artery and were transfused intravenously with ECs (total, 1.5 x 10(6) cells at 1, 3, and 5 hours after injury) transduced with adenoviral vectors carrying IL8RA, IL8RB, and IL8RA/RB (dual transduction) genes, AdNull (empty vector), or vehicle (no EC transfusion). ECs overexpressing IL8Rs inhibited proinflammatory mediators expression significantly (by 60% to 85%) and reduced infiltration of neutrophils and monocytes/macrophages into injured arteries at 1 day after injury, as well as stimulating a 2-fold increase in reendothelialization at 14 days after injury. IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC treatment reduced neointima formation dramatically (by 80%, 74%, and 95%) at 28 days after injury. Conclusions-ECs with overexpression of IL8RA and/or IL8RB mimic the behavior of neutrophils that target and adhere to injured tissues, preventing inflammation and neointima formation. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the prevention and treatment of cardiovascular disease. (Circulation. 2012;125:1533-1541.) C1 [Xing, Dongqi; Li, Peng; Yang, Zhengqin; Yu, Hao; Hage, Fadi G.; Oparil, Suzanne; Chen, Yiu-Fai] Univ Alabama, Dept Med, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, Birmingham, AL 35294 USA. [Gong, Kaizheng] Yangzhou Univ, Sch Clin Med 2, Dept Cardiol, Yangzhou, Peoples R China. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Chen, YF (reprint author), Univ Alabama, Dept Med, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, 1008 Zeigler Res Bldg,703 19th St S, Birmingham, AL 35294 USA. EM yfchen@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU National Heart, Lung, and Blood Institute [HL080017, HL044195, HL07457]; American Heart Association [10POST3180007, 09BGIA2250367] FX This work was supported in part by National Heart, Lung, and Blood Institute grants HL080017 (to Dr Chen), HL044195 (to Dr Chen), and HL07457 (to Dr Oparil) and by American Heart Association grants 10POST3180007 (to Dr Gong) and 09BGIA2250367 (to Dr Xing). NR 33 TC 12 Z9 14 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 27 PY 2012 VL 125 IS 12 BP 1533 EP U232 DI 10.1161/CIRCULATIONAHA.111.078436 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 916TA UT WOS:000302124900020 PM 22361324 ER PT J AU Thadhani, R Hemphill, L Kisner, T Hagmann, H Noack, S Benzing, T Bossung, V Mallmann, P Kribs, A Cornely, OA Schaarschmidt, W Jank, A Stepan, H Kreyssig, C Lindner, TH Rigby, AC Khedkar, S Karumanchi, SA AF Thadhani, Ravi Hemphill, Linda Kisner, Tuelay Hagmann, Henning Noack, Stefanie Benzing, Thomas Bossung, Verena Mallmann, Peter Kribs, Angela Cornely, Oliver A. Schaarschmidt, Wiebke Jank, Alexander Stepan, Holger Kreyssig, Claudia Lindner, Tom H. Rigby, Alan C. Khedkar, Santosh Karumanchi, S. Ananth TI Response to Letters Regarding Article, "Pilot Study of Extracorporeal Removal of Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia" SO CIRCULATION LA English DT Letter C1 [Thadhani, Ravi; Hemphill, Linda] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Nephrol, Boston, MA 02114 USA. [Kisner, Tuelay; Hagmann, Henning; Noack, Stefanie; Benzing, Thomas] Univ Cologne, Div Renal, D-50931 Cologne, Germany. [Kisner, Tuelay; Hagmann, Henning; Noack, Stefanie; Benzing, Thomas] Univ Cologne, Dept Med, D-50931 Cologne, Germany. [Kisner, Tuelay; Hagmann, Henning; Noack, Stefanie; Benzing, Thomas] Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany. [Bossung, Verena; Mallmann, Peter] Univ Cologne, Dept Obstet & Ginecol, D-50931 Cologne, Germany. [Kribs, Angela] Univ Cologne, Dept Neonatol, D-50931 Cologne, Germany. [Cornely, Oliver A.] Univ Cologne, ZKS Koln, Dept Internal Med, D-50931 Cologne, Germany. [Cornely, Oliver A.] Univ Cologne, ZKS Koln, Clin Trials Ctr, D-50931 Cologne, Germany. [Schaarschmidt, Wiebke; Jank, Alexander; Stepan, Holger] Univ Hosp Leipzig, Dept Obstet, Leipzig, Germany. [Kreyssig, Claudia; Lindner, Tom H.] Univ Hosp Leipzig, Dept Internal Med Neurol & Dermatol, Div Nephrol, Leipzig, Germany. [Rigby, Alan C.; Khedkar, Santosh] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Nephrol, Boston, MA 02114 USA. NR 5 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 27 PY 2012 VL 125 IS 12 BP E523 EP E524 DI 10.1161/CIRCULATIONAHA.111.078378 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 916TA UT WOS:000302124900011 ER PT J AU Devaraj, NK Thurber, GM Keliher, EJ Marinelli, B Weissleder, R AF Devaraj, Neal K. Thurber, Greg M. Keliher, Edmund J. Marinelli, Brett Weissleder, Ralph TI Reactive polymer enables efficient in vivo bioorthogonal chemistry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE in vivo chemistry; pharmacokinetics; PET imaging; intravital microscopy; pretargeting ID TRANS-CYCLOOCTENE LIGATION; FREE CLICK CHEMISTRY; COPPER-FREE; LIVING CELLS; A33 ANTIGEN; CYCLOADDITION; AZIDES; MICE AB There has been intense interest in the development of selective bioorthogonal reactions or "click" chemistry that can proceed in live animals. Until now however, most reactions still require vast surpluses of reactants because of steep temporal and spatial concentration gradients. Using computational modeling and design of pharmacokinetically optimized reactants, we have developed a predictable method for efficient in vivo click reactions. Specifically, we show that polymer modified tetrazines (PMT) are a key enabler for in vivo bioorthogonal chemistry based on the very fast and catalyst-free [4 + 2] tetrazine/ trans-cyclooctene cycloaddition. Using fluorescent PMT for cellular resolution and F-18 labeled PMT for whole animal imaging, we show that cancer cell epitopes can be easily reacted in vivo. This generic strategy should help guide the design of future chemistries and find widespread use for different in vivo bioorthogonal applications, particularly in the biomedical sciences. C1 [Devaraj, Neal K.; Thurber, Greg M.; Keliher, Edmund J.; Marinelli, Brett; Weissleder, Ralph] Harvard Univ, Sch Med, Ctr Syst Biol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Ctr Syst Biol, Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu RI Devaraj, Neal/B-4712-2014; OI Thurber, Greg/0000-0001-7570-2080 FU National Institutes of Health (NIH) [P50CA86355, R01EB010011, K01EB010078, T32CA079443] FX The authors gratefully acknowledge S.A. Hilderbrand, J.B. Haun, and R. Mazitschek for many helpful discussions and suggestions. This work was funded in part by National Institutes of Health (NIH) grants P50CA86355, R01EB010011, K01EB010078, and T32CA079443. NR 29 TC 80 Z9 80 U1 8 U2 85 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 27 PY 2012 VL 109 IS 13 BP 4762 EP 4767 DI 10.1073/pnas.1113466109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 917HT UT WOS:000302164200019 PM 22411831 ER PT J AU Ludwig, B Rotem, A Schmid, J Weir, GC Colton, CK Brendel, MD Neufeld, T Block, NL Yavriyants, K Steffen, A Ludwig, S Chavakis, T Reichel, A Azarov, D Zimermann, B Maimon, S Balyura, M Rozenshtein, T Shabtay, N Vardi, P Bloch, K de Vos, P Schally, AV Bornstein, SR Barkai, U AF Ludwig, Barbara Rotem, Avi Schmid, Janine Weir, Gordon C. Colton, Clark K. Brendel, Mathias D. Neufeld, Tova Block, Norman L. Yavriyants, Karina Steffen, Anja Ludwig, Stefan Chavakis, Triantafyllos Reichel, Andreas Azarov, Dimitri Zimermann, Baruch Maimon, Shiri Balyura, Mariya Rozenshtein, Tania Shabtay, Noa Vardi, Pnina Bloch, Konstantin de Vos, Paul Schally, Andrew V. Bornstein, Stefan R. Barkai, Uriel TI Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE treatment of diabetes; immune isolation; beta cells ID BLOOD-FLOW; INSULIN-SECRETION; IMMUNOISOLATION DEVICE; EDMONTON PROTOCOL; CONSUMPTION RATE; NUDE-MICE; TRANSPLANTATION; CELLS; SURVIVAL; RAT AB Islet transplantation is a feasible therapeutic alternative for metabolically labile patients with type 1 diabetes. The primary therapeutic target is stable glycemic control and prevention of complications associated with diabetes by reconstitution of endogenous insulin secretion. However, critical shortage of donor organs, gradual loss in graft function over time, and chronic need for immunosuppression limit the indication for islet transplantation to a small group of patients. Here we present a promising approach to address these limitations by utilization of a macrochamber specially engineered for islet transplantation. The s.c. implantable device allows for controlled and adequate oxygen supply and provides immunological protection of donor islets against the host immune system. The minimally invasive implantable chamber normalized blood glucose in streptozotocin-induced diabetic rodents for up to 3 mo. Sufficient graft function depended on oxygen supply. Pretreatment with the growth hormone-releasing hormone (GHRH) agonist, JI-36, significantly enhanced graft function by improving glucose tolerance and increasing beta-cell insulin reserve in rats thereby allowing for a reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Consequently, this system opens up a fundamental strategy for therapy of diabetes and may provide a promising avenue for future approaches to xenotransplantation. C1 [Block, Norman L.; Schally, Andrew V.] Univ Miami, Miller Sch Med, Dept Pathol, Div Endocrinol & Hematol Oncol, Miami, FL 33136 USA. [Block, Norman L.; Schally, Andrew V.] Univ Miami, Miller Sch Med, Dept Med, Div Endocrinol & Hematol Oncol, Miami, FL 33136 USA. [Ludwig, Barbara; Schmid, Janine; Brendel, Mathias D.; Steffen, Anja; Chavakis, Triantafyllos; Reichel, Andreas; Balyura, Mariya; Bornstein, Stefan R.] Univ Hosp Carl Gustav Carus, Dept Med 3, D-01307 Dresden, Germany. [Rotem, Avi; Neufeld, Tova; Yavriyants, Karina; Azarov, Dimitri; Zimermann, Baruch; Maimon, Shiri; Balyura, Mariya; Rozenshtein, Tania; Shabtay, Noa] Beta O2 Technol, IL-49511 Kiryat Arie, Petach Tikva, Israel. [Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Trasnplantat & Cell Biol, Boston, MA 02215 USA. [Colton, Clark K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Block, Norman L.] Vet Adm Med Ctr, Miami, FL 33125 USA. [Ludwig, Stefan] Univ Hosp Carl Gustav Carus, Dept Visceral Thorax & Vasc Surg, D-01307 Dresden, Germany. [Vardi, Pnina] Clalit Hlth Serv, Lin Med Ctr, Dept Diabet, IL-35152 Haifa, Israel. [Bloch, Konstantin] Tel Aviv Univ, Sackler Fac Med, Felsenstein Med Res Ctr, Diabet & Obes Res Lab, IL-49100 Petah Tiqwa, Israel. [de Vos, Paul] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Sect Immunoendocrinol, NL-9700 RB Groningen, Netherlands. RP Schally, AV (reprint author), Univ Miami, Miller Sch Med, Dept Pathol, Div Endocrinol & Hematol Oncol, Miami, FL 33136 USA. EM andrew.schally@va.gov RI de Vos, Paul/A-3170-2013; OI Schally, Andrew/0000-0003-1273-6747 FU Deutsche Forschungsgemeinschaft [SFB 655, KFO 252, BR 1179]; Dresden Tumor Centre of Excellence, Center for Regenerative Therapies Dresden (CRTD); Paul Langerhans Institute Dresden; German Center for Diabetes Research (DZD); Medical Research Service of the Veterans Affairs Department; University of Miami Miller School of Medicine; Division of Hematology/Oncology; Department of Pathology; Department of Medicine; Austin Weeks Family Endowment for Urologic Research FX We thank Silke Zeugner for her assistance with immunohistochemistry and Martina Talke for help in preparation of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft Grants SFB 655 "From Cells to Tissues" (to S.R.B.), KFO 252 (to B.L., T.C., and S.R.B.), and BR 1179 (to M.D.B. and B.L.); Dresden Tumor Centre of Excellence, Center for Regenerative Therapies Dresden (CRTD); Paul Langerhans Institute Dresden; and the German Center for Diabetes Research (DZD). Studies in Miami were supported by the Medical Research Service of the Veterans Affairs Department and University of Miami Miller School of Medicine, Division of Hematology/Oncology, Departments of Pathology and Medicine (all to A.V.S.) and the Austin Weeks Family Endowment for Urologic Research (to N.L.B.). NR 60 TC 60 Z9 61 U1 3 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 27 PY 2012 VL 109 IS 13 BP 5022 EP 5027 DI 10.1073/pnas.1201868109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 917HT UT WOS:000302164200063 PM 22393012 ER PT J AU Menon, S Yecies, JL Zhang, HH Howell, JJ Nicholatos, J Harputlugil, E Bronson, RT Kwiatkowski, DJ Manning, BD AF Menon, Suchithra Yecies, Jessica L. Zhang, Hui H. Howell, Jessica J. Nicholatos, Justin Harputlugil, Eylul Bronson, Roderick T. Kwiatkowski, David J. Manning, Brendan D. TI Chronic Activation of mTOR Complex 1 Is Sufficient to Cause Hepatocellular Carcinoma in Mice SO SCIENCE SIGNALING LA English DT Article ID HEPATITIS-C VIRUS; TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR GENE; NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; AUTOPHAGY-DEFICIENT MICE; FATTY LIVER-DISEASE; MAMMALIAN TARGET; NONALCOHOLIC STEATOHEPATITIS; MOUSE MODEL AB The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a nutrient-sensitive protein kinase that is aberrantly activated in many human cancers. Whether dysregulation of mTORC1 signaling in normal tissues increases the risk for cancer, however, is unknown. We focused on hepatocellular carcinoma, which has been linked to environmental factors that affect mTORC1 activity, including diet. Ablation of the gene encoding TSC1 (tuberous sclerosis complex 1), which as part of the TSC1-TSC2 complex is an upstream inhibitor of mTORC1, results in constitutively increased mTORC1 signaling, an effect on this pathway similar to that of obesity. We found that mice with liver-specific knockout of Tsc1 developed sporadic hepatocellular carcinoma with heterogeneous histological and biochemical features. The spontaneous development of hepatocellular carcinoma in this mouse model was preceded by a series of pathological changes that accompany the primary etiologies of this cancer in humans, including liver damage, inflammation, necrosis, and regeneration. Chronic mTORC1 signaling led to unresolved endoplasmic reticulum stress and defects in autophagy, factors that contributed to hepatocyte damage and hepatocellular carcinoma development. Therefore, we conclude that increased activation of mTORC1 can promote carcinogenesis and may thus represent a key molecular link between cancer risk and environmental factors, such as diet. C1 [Menon, Suchithra; Yecies, Jessica L.; Zhang, Hui H.; Howell, Jessica J.; Nicholatos, Justin; Harputlugil, Eylul; Manning, Brendan D.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Bronson, Roderick T.] Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. [Kwiatkowski, David J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Translat Med Div, Boston, MA 02115 USA. RP Manning, BD (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM bmanning@hsph.harvard.edu FU American Diabetes Association [1-10-BS-115]; Department of Defense [W81XWH-10-1-0861]; NIH [CA120964, CA122617] FX We are indebted to J. Kim for advice on statistical analyses. We thank G. Hotamisligil, L. Yang, R. Chung, R. X. Shao, and M. Zbinden for helpful discussions and critical comments regarding this study and S. Fu for assistance with electron microscopy. Funding: This work was supported in part by research grants from the American Diabetes Association (1-10-BS-115 to B.D.M.), Department of Defense Tuberous Sclerosis Complex Research Program (W81XWH-10-1-0861 to B.D.M.), and the NIH (CA120964 to D.J.K. and B.D.M.; CA122617 to B.D.M.). Author contributions: S.M., H.H.Z., and B.D.M. conceived and designed the experiments; S.M., J.L.Y., J.J.H., and E.H. performed the experiments; J.N. was responsible for animal breeding and genotyping; R.T.B. is an expert rodent pathologist who examined all histological slides; D.J.K. provided the mice and intellectual contributions to the experimental design; and S.M. and B.D.M. analyzed the data and wrote the manuscript. Competing interests: The authors declare that they have no competing interests. NR 100 TC 58 Z9 59 U1 1 U2 15 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 27 PY 2012 VL 5 IS 217 AR ra24 DI 10.1126/scisignal.2002739 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 916VL UT WOS:000302131200004 PM 22457330 ER PT J AU Lakkireddy, D Reddy, YM Di Biase, L Vanga, SR Santangeli, P Swarup, V Pimentel, R Mansour, MC D'Avila, A Sanchez, JE Burkhardt, JD Chalhoub, F Mohanty, P Coffey, J Shaik, N Monir, G Reddy, VY Ruskin, J Natale, A AF Lakkireddy, Dhanunjaya Reddy, Yeruva Madhu Di Biase, Luigi Vanga, Subba Reddy Santangeli, Pasquale Swarup, Vijay Pimentel, Rhea Mansour, Moussa C. D'Avila, Andre Sanchez, Javier E. Burkhardt, J. David Chalhoub, Fadi Mohanty, Prasant Coffey, James Shaik, Naushad Monir, George Reddy, Vivek Y. Ruskin, Jeremy Natale, Andrea TI Feasibility and Safety of Dabigatran Versus Warfarin for Periprocedural Anticoagulation in Patients Undergoing Radiofrequency Ablation for Atrial Fibrillation Results From a Multicenter Prospective Registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE anticoagulation; atrial fibrillation ablation; dabigatran; matched case-control study; periprocedural complications ID INTERNATIONAL NORMALIZED RATIO; VEIN ANTRUM ISOLATION; CATHETER ABLATION; THROMBIN INHIBITOR; COMPLICATIONS; MANAGEMENT; ASSOCIATION; PREDICTORS; ETEXILATE AB Objectives The purpose of this study was to evaluate the feasibility and safety of periprocedural dabigatran during atrial fibrillation (AF) ablation. Background AF ablation requires optimal periprocedural anticoagulation for minimizing bleeding and thromboembolic complications. The safety and efficacy of dabigatran as a periprocedural anticoagulant for AF ablation are unknown. Methods We performed a multicenter, observational study from a prospective registry including all consecutive patients undergoing AF ablation in 8 high-volume centers in the United States. All patients receiving dabigatran therapy who underwent AF ablation on periprocedural dabigatran, with the dose held on the morning of the procedure, were matched by age, sex, and type of AF with an equal number of patients undergoing AF ablation with uninterrupted warfarin therapy over the same period. Results A total of 290 patients, including 145 taking periprocedural dabigatran and an equal number of matched patients taking uninterrupted periprocedural warfarin, were included in the study. The mean age was 60 years with 79% being male and 57% having paroxysmal AF. Both groups had a similar CHADS(2) score, left atrial size, and left ventricular ejection fraction. Three thromboembolic complications (2.1%) occurred in the dabigatran group compared with none in the warfarin group (p = 0.25). The dabigatran group had a significantly higher major bleeding rate (6% vs. 1%; p = 0.019), total bleeding rate (14% vs. 6%; p = 0.031), and composite of bleeding and thromboembolic complications (16% vs. 6%; p = 0.009) compared with the warfarin group. Dabigatran use was confirmed as an independent predictor of bleeding or thromboembolic complications (odds ratio: 2.76, 95% confidence interval: 1.22 to 6.25; p = 0.01) on multivariate regression analysis. Conclusions In patients undergoing AF ablation, periprocedural dabigatran use significantly increases the risk of bleeding or thromboembolic complications compared with uninterrupted warfarin therapy. (J Am Coll Cardiol 2012; 59: 1168-74) (C) 2012 by the American College of Cardiology Foundation C1 [Lakkireddy, Dhanunjaya; Reddy, Yeruva Madhu; Vanga, Subba Reddy; Pimentel, Rhea] Univ Kansas Hosp & Med Ctr, Div Cardiovasc Dis, Cardiovasc Res Inst, Kansas City, KS USA. [Di Biase, Luigi; Santangeli, Pasquale; Sanchez, Javier E.; Burkhardt, J. David; Mohanty, Prasant; Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Di Biase, Luigi] Univ Foggia, Dept Cardiol, Foggia, Italy. [Di Biase, Luigi; Natale, Andrea] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Swarup, Vijay] Arizona Heart Rhythm Ctr, Phoenix, AZ USA. [Mansour, Moussa C.; Chalhoub, Fadi; Ruskin, Jeremy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [D'Avila, Andre; Coffey, James; Reddy, Vivek Y.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Shaik, Naushad] Cent Florida Cardiovasc Heart Inst, Kissimmee, FL USA. [Monir, George] Florida S Hosp, Orlando, FL USA. [Natale, Andrea] Calif Pacific Med Ctr, San Francisco, CA USA. RP Lakkireddy, D (reprint author), KU Cardiovasc Res Inst, 3901 Rainbow Blvd,MS 4023, Kansas City, KS 66160 USA. EM dlakkireddy@mac.md RI d'Avila, Andre/F-8009-2010; OI d'Avila, Andre/0000-0001-8769-1411; Di Biase, Luigi/0000-0001-6508-4047 FU Biosense Webster; St. Jude Medical; MC10; VOyage Medical; Medtronic FX Dr. Lakkireddy receives modest speaker's honorarium from Boehringer Ingelheim, Sanofi, St. Jude Medical, Biotronik, and Estech. Dr. Di Biase is a consultant for Hansen Medical and Biosense Webster. Dr. Monir is on the advisory board of Medtronic; and has received honorarium from Biosense Webster. Dr. Mansour has received research grants from Biosense Webster, St. Jude Medical, MC10, and VOyage Medical; and is a consultant for Biosense Webster and St. Jude Medical. Dr. Reddy has received speaker's honorarium (modest) from Boehringer Ingelheim. Dr. Ruskin is a consultant for Arrhythmia Education Inc., Astellas/Cardiome, Sanofi-Aventis, Third Rock Ventures, Atricure, Bristol-Myers Squibb, and GE Healthcare; honoraria from Med-IQ; is on the scientific steering committee for Pfizer and CryoCath; has equity in Portola; has received fellowship support from St. Jude Medical, Medtronic, and Biosense Webster; is on the clinical oversight committee for CardioFocus; and is on the scientific advisory board for CardioInsight. Dr. Natale is a consultant and/or receives speaker honoraria from Biosense Webster, Medtronic, Biotronik, Boston Scientific, and Life Watch. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 30 TC 147 Z9 154 U1 0 U2 13 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 27 PY 2012 VL 59 IS 13 BP 1168 EP 1174 DI 10.1016/j.jacc.2011.12.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 914LB UT WOS:000301950300007 PM 22305113 ER PT J AU Berkowitz, SA Johansen, KL AF Berkowitz, Seth A. Johansen, Kirsten L. TI Does Motivational Interviewing Improve Outcomes? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; MANAGEMENT; ADHERENCE; SUPPORT C1 [Berkowitz, Seth A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Berkowitz, SA (reprint author), Univ Calif San Francisco, Dept Med, 1545 Divisidero St,Box 0320, San Francisco, CA 94143 USA. EM Seth.Berkowitz@ucsf.edu OI Berkowitz, Seth/0000-0003-1030-4297 NR 10 TC 4 Z9 4 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 26 PY 2012 VL 172 IS 6 BP 463 EP 464 DI 10.1001/archinternmed.2012.155 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 914MI UT WOS:000301953800001 PM 22371877 ER PT J AU Yazdanpanah, Y Walensky, RP Rozenbaum, W Yeni, P Paltiel, AD AF Yazdanpanah, Yazdan Walensky, Rochelle P. Rozenbaum, Willy Yeni, Patrick Paltiel, A. David TI What Is a Modest Public Health Impact? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID HIV-INFECTION C1 [Yazdanpanah, Yazdan] Hop Bichat Claude Bernard, Serv Malad Infectieuses & Trop, F-75877 Paris, France. [Yazdanpanah, Yazdan] Univ Paris Diderot, ATIP Avenir, INSERM, U738, Paris, France. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Rozenbaum, Willy] Conseil Natl Sida, Paris, France. [Yeni, Patrick] Grp Expert Prise Charge Med Personnes VIH, Paris, France. [Paltiel, A. David] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Yazdanpanah, Y (reprint author), Hop Bichat Claude Bernard, Serv Malad Infectieuses & Trop, 46 Rue Henri Huchard, F-75877 Paris, France. EM yazdan.yazdanpanah@bch.aphp.fr OI Walensky, Rochelle P./0000-0002-8795-379X; Rozenbaum, Willy/0000-0003-1975-3566 NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 26 PY 2012 VL 172 IS 6 BP 521 EP 522 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 914MI UT WOS:000301953800018 PM 22450944 ER PT J AU Agasti, SS Liong, M Tassa, C Chung, HJ Shaw, SY Lee, H Weissleder, R AF Agasti, Sarit S. Liong, Monty Tassa, Carlos Chung, Hyun Jung Shaw, Stanley Y. Lee, Hakho Weissleder, Ralph TI Bioorthogonal nanoparticle labeling and detection of biomarkers through supramolecular host-guest interaction SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 11th International Biorelated Polymer Symposium / 243rd National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc C1 [Agasti, Sarit S.; Liong, Monty; Tassa, Carlos; Chung, Hyun Jung; Shaw, Stanley Y.; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM Agasti.Sarit@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 3 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 25 PY 2012 VL 243 MA 468-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219AH UT WOS:000324475103908 ER PT J AU Ams, MR Bhayana, B Grabnic, T AF Ams, Mark R. Bhayana, Brijesh Grabnic, Timothy TI Effect of diazocine bridgehead modification on the folding of the Wilcox molecular torsion balance SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 243rd National Spring Meeting of the American-Chemical-Society CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc C1 [Ams, Mark R.; Grabnic, Timothy] Allegheny Coll, Meadville, PA 16335 USA. [Bhayana, Brijesh] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 16335 USA. EM mams@allegheny.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2012 VL 243 MA 499-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219JX UT WOS:000324503202697 ER PT J AU Arevalo, E Chiara, DC Yamodo, IH Cohen, JB Miller, KW AF Arevalo, Enrique Chiara, David C. Yamodo, Innocent H. Cohen, Jonathan B. Miller, Keith W. TI Photolabeling anesthetic sites on different conformations of ion channels SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 11th International Biorelated Polymer Symposium / 243rd National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc C1 [Arevalo, Enrique; Yamodo, Innocent H.; Miller, Keith W.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. [Arevalo, Enrique; Yamodo, Innocent H.; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Chiara, David C.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM k_miller@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 25 PY 2012 VL 243 MA 57-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219AH UT WOS:000324475104254 ER PT J AU Chung, HJ Reiner, T Budin, G Min, C Liong, M Issadore, D Lee, H Weissleder, R AF Chung, Hyun Jung Reiner, Thomas Budin, Ghyslain Min, Changwook Liong, Monty Issadore, David Lee, Hakho Weissleder, Ralph TI Bioorthogonal nanosensors for magnetic and optical detection of infectious pathogens SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 11th International Biorelated Polymer Symposium / 243rd National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc C1 [Chung, Hyun Jung; Reiner, Thomas; Budin, Ghyslain; Min, Changwook; Liong, Monty; Issadore, David; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM chung.hyunjung@mgh.harvard.edu RI Issadore, David/L-8451-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 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 25 PY 2012 VL 243 MA 521-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219AH UT WOS:000324475101053 ER PT J AU Grabnic, T Ams, MR Bhayana, B AF Grabnic, Timothy Ams, Mark R. Bhayana, Brijesh TI Molecular torsion balances for probing the distance dependency of CH-pi interactions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 243rd National Spring Meeting of the American-Chemical-Society CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc C1 [Grabnic, Timothy; Ams, Mark R.] Allegheny Coll, Meadville, PA 16335 USA. [Bhayana, Brijesh] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM grabnit@allegheny.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 25 PY 2012 VL 243 MA 144-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219JX UT WOS:000324503202367 ER PT J AU Liong, M Lee, H Weissleder, R AF Liong, Monty Lee, Hakho Weissleder, Ralph TI Multiplexed labeling and signal amplification in diagnostic magnetic resonance SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 11th International Biorelated Polymer Symposium / 243rd National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc C1 [Liong, Monty; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM liong.monty@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2012 VL 243 MA 179-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219AH UT WOS:000324475103633 ER PT J AU Peterson, RT AF Peterson, Randall T. TI Automated, in vivo screening for behavior-modifying compounds SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 243rd National Spring Meeting of the American-Chemical-Society CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc C1 [Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Broad Inst, Charlestown, MA 02129 USA. EM peterson@cvrc.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2012 VL 243 MA 4-LIFE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219JX UT WOS:000324503201640 ER PT J AU Sheridan, S AF Sheridan, Steven TI Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 11th International Biorelated Polymer Symposium / 243rd National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc C1 [Sheridan, Steven] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet, Boston, MA 02114 USA. EM sdsheridan2002@yahoo.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 25 PY 2012 VL 243 MA 25-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219AH UT WOS:000324475100566 ER PT J AU Shur, O Blenner, M Banta, S AF Shur, Oren Blenner, Mark Banta, Scott TI Development of a calcium-responsive beta roll peptide as a purification tag for non-chormatographic recombinant protein purification SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 11th International Biorelated Polymer Symposium / 243rd National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc C1 [Shur, Oren; Banta, Scott] Columbia Univ, Dept Chem Engn, New York, NY 10027 USA. [Blenner, Mark] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Blenner, Mark] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM ocs2004@columbia.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 25 PY 2012 VL 243 MA 196-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219AH UT WOS:000324475100731 ER PT J AU Szostak, JW AF Szostak, Jack W. TI Role of the environment in the reproduction of primitive cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 243rd National Spring Meeting of the American-Chemical-Society CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2012 VL 243 MA 258-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219JX UT WOS:000324503203500 ER PT J AU Vasdev, N AF Vasdev, Neil TI Multi-step reactions with fluorine-18 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 11th International Biorelated Polymer Symposium / 243rd National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc C1 [Vasdev, Neil] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vasdev, Neil] Harvard Univ, Sch Med, Boston, MA 02114 USA. EM vasdev.neil@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 25 PY 2012 VL 243 MA 45-FLUO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219AH UT WOS:000324475105367 ER PT J AU Wilson, AA Sadovski, O Hicks, J Vasdev, N AF Wilson, Alan A. Sadovski, Oleg Hicks, Justin Vasdev, Neil TI Mostly harmless: A study of [F-18]-fluoride substitution reaction conditions with a base sensitive substrate SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 11th International Biorelated Polymer Symposium / 243rd National Spring Meeting of the American-Chemical-Society (ACS) CY MAR 25-29, 2012 CL San Diego, CA SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc C1 [Wilson, Alan A.; Sadovski, Oleg; Hicks, Justin; Vasdev, Neil] Ctr Addict & Mental Hlth, Dept Mol Imaging, Toronto, ON M5T 1R8, Canada. [Vasdev, Neil] Massachusetts Gen Hosp, Dept Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM alan.wilson@camhpet.ca NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2012 VL 243 MA 44-FLUO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 219AH UT WOS:000324475105366 ER PT J AU Moseman, EA Iannacone, M Bosurgi, L Tonti, E Chevrier, N Tumanov, A Fu, YX Hacohen, N von Andrian, UH AF Moseman, E. Ashley Iannacone, Matteo Bosurgi, Lidia Tonti, Elena Chevrier, Nicolas Tumanov, Alexei Fu, Yang-Xin Hacohen, Nir von Andrian, Ulrich H. TI B Cell Maintenance of Subcapsular Sinus Macrophages Protects against a Fatal Viral Infection Independent of Adaptive Immunity SO IMMUNITY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; SIMULIUM-VITTATUM DIPTERA; BETA LT-BETA; LYMPH-NODES; DEFICIENT MICE; T-CELLS; ANTIVIRAL PROTECTION; ANTIBODY-RESPONSES; RNA VIRUSES; LYMPHOTOXIN AB Neutralizing antibodies have been thought to be required for protection against acutely cytopathic viruses, such as the neurotropic vesicular stomatitis virus (VSV). Utilizing mice that possess B cells but lack antibodies, we show here that survival upon subcutaneous (s.c.) VSV challenge was independent of neutralizing antibody production or cell-mediated adaptive immunity. However, B cells were absolutely required to provide lymphotoxin (LT) alpha 1 beta 2, which maintained a protective subcapsular sinus (SCS) macrophage phenotype within virus draining lymph nodes (LNs). Macrophages within the SCS of B cell-deficient LNs, or of mice that lack LT alpha 1 beta 2 selectively in B cells, displayed an aberrant phenotype, failed to replicate VSV, and therefore did not produce type I interferons, which were required to prevent fatal VSV invasion of intranodal nerves. Thus, although B cells are essential for survival during VSV infection, their contribution involves the provision of innate differentiation and maintenance signals to macrophages, rather than adaptive immune mechanisms. C1 [Moseman, E. Ashley; Iannacone, Matteo; Bosurgi, Lidia; Tonti, Elena; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & lmmunobiol, Immune Dis Inst, Boston, MA 02115 USA. [Moseman, E. Ashley; Iannacone, Matteo; Bosurgi, Lidia; Tonti, Elena; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & lmmunobiol, Div Immunol, Boston, MA 02115 USA. [Iannacone, Matteo; Tonti, Elena] Ist Sci San Raffaele, Div Immunol Infect Dis & Transplantat, I-20132 Milan, Italy. [Bosurgi, Lidia] Univ Vita Salute San Raffaele, Milan, Italy. [Chevrier, Nicolas; Hacohen, Nir] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Chevrier, Nicolas; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Tumanov, Alexei] Trudeau Inst, Saranac Lake, NY 12983 USA. [Fu, Yang-Xin] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Iannacone, M (reprint author), Harvard Univ, Sch Med, Dept Microbiol & lmmunobiol, Immune Dis Inst, Boston, MA 02115 USA. EM matteo.iannacone@hsr.it; uva@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008; OI fu, yang-xin/0000-0001-8441-6617 FU National Institutes of Health (NIH) [AI069259, AI072252, AI078897, 5T32-HL07623-20]; Giovanni Armenise-Harvard Foundation FX We thank G. Cheng and M. Flynn for technical support; M. Perdue for secretarial assistance; K. Rajewsky for providing DHLMP2A mice; L. Martinez-Pomares for CR-Fc; S. Whelan for VSV and VSVeGFP; N. van Rooijen for clodronate liposomes; J. Browning for LT beta R-Ig; L.G. Guidotti for helpful advice; and the members of the U.H.v.A. laboratory for helpful discussion. This work was supported by the National Institutes of Health (NIH) grants AI069259, AI072252, and AI078897 (to U.H.v.A.), the Giovanni Armenise-Harvard Foundation (to M.I.), and a NIH T32 Training Grant in Hematology 5T32-HL07623-20 (to E.A.M.). NR 56 TC 61 Z9 62 U1 4 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR 23 PY 2012 VL 36 IS 3 BP 415 EP 426 DI 10.1016/j.immuni.2012.01.013 PG 12 WC Immunology SC Immunology GA 915ST UT WOS:000302048400013 PM 22386268 ER PT J AU Liu, QS Kirubakaran, S Hur, W Niepel, M Westover, K Thoreen, CC Wang, JH Ni, J Patricelli, MP Vogel, K Riddle, S Waller, DL Traynor, R Sanda, T Zhao, Z Kang, SA Zhao, J Look, AT Sorger, PK Sabatini, DM Gray, NS AF Liu, Qingsong Kirubakaran, Sivapriya Hur, Wooyoung Niepel, Mario Westover, Kenneth Thoreen, Carson C. Wang, Jinhua Ni, Jing Patricelli, Matthew P. Vogel, Kurt Riddle, Steve Waller, David L. Traynor, Ryan Sanda, Takaomi Zhao, Zheng Kang, Seong A. Zhao, Jean Look, A. Thomas Sorger, Peter K. Sabatini, David M. Gray, Nathanael S. TI Kinome-wide Selectivity Profiling of ATP-competitive Mammalian Target of Rapamycin (mTOR) Inhibitors and Characterization of Their Binding Kinetics SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTITUMOR-ACTIVITY; CANCER; DISCOVERY; ACTIVATION; SIMULATION; MUTATIONS; PROTEINS; KINASES; COMPLEX; POTENT AB An intensive recent effort to develop ATP-competitive mTOR inhibitors has resulted in several potent and selective molecules such as Torin1, PP242, KU63794, and WYE354. These inhibitors are being widely used as pharmacological probes of mTOR-dependent biology. To determine the potency and specificity of these agents, we have undertaken a systematic kinome-wide effort to profile their selectivity and potency using chemical proteomics and assays for enzymatic activity, protein binding, and disruption of cellular signaling. Enzymatic and cellular assays revealed that all four compounds are potent inhibitors of mTORC1 and mTORC2, with Torin1 exhibiting similar to 20-fold greater potency for inhibition of Thr-389 phosphorylation on S6 kinases (EC50 = 2 nM) relative to other inhibitors. In vitro biochemical profiling at 10 mu M revealed binding of PP242 to numerous kinases, although WYE354 and KU63794 bound only to p38 kinases and PI3K isoforms and Torin1 to ataxia telangiectasia mutated, ATM and Rad3-related protein, and DNA-PK. Analysis of these protein targets in cellular assays did not reveal any off-target activities for Torin1, WYE354, and KU63794 at concentrations below 1 mu M but did show that PP242 efficiently inhibited the RET receptor (EC50, 42 nM) and JAK1/2/3 kinases (EC50, 780 nM). In addition, Torin1 displayed unusually slow kinetics for inhibition of the mTORC1/2 complex, a property likely to contribute to the pharmacology of this inhibitor. Our results demonstrated that, with the exception of PP242, available ATP-competitive compounds are highly selective mTOR inhibitors when applied to cells at concentrations below 1 mu M and that the compounds may represent a starting point for medicinal chemistry efforts aimed at developing inhibitors of other PI3K kinase-related kinases. C1 [Liu, Qingsong; Kirubakaran, Sivapriya; Hur, Wooyoung; Thoreen, Carson C.; Wang, Jinhua; Ni, Jing; Waller, David L.; Zhao, Jean; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dept Canc Biol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Niepel, Mario; Sorger, Peter K.] Harvard Univ, Sch Med, Ctr Cell Decis Proc, Boston, MA 02115 USA. [Niepel, Mario; Sorger, Peter K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Westover, Kenneth] Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Vogel, Kurt; Riddle, Steve] Invitrogen Corp, Madison, WI 53719 USA. [Patricelli, Matthew P.] ActivX Biosci Inc, La Jolla, CA 92037 USA. [Traynor, Ryan] Univ Dundee, Coll Life Sci, Dundee Div Signal Transduct Therapy, Natl Ctr Prot Kinase Profiling, Dundee DD1 5EH, Scotland. [Sanda, Takaomi; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Zhao, Zheng] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China. [Kang, Seong A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Kang, Seong A.; Sabatini, David M.] MIT, Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA. [Sabatini, David M.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dept Canc Biol,Dana Farber Canc Inst, 250 Longwood Ave, Boston, MA 02115 USA. EM Nathanael_Gray@dfci.harvard.edu RI Niepel, Mario/G-5443-2011; OI Niepel, Mario/0000-0003-1415-6295; liu, qing song/0000-0002-7829-2547 FU National Institutes of Health [HG006097, RO1 AI47389, CA103866]; William Lawrence and Blanche Hughes Fund; Children's Leukemia Research Association; Japan Society for the Promotion of Science FX This work was supported, in whole or in part, by National Institutes of Health Grant HG006097 (to Q. L., M.N., and P.K.S.).; Supported by National Institutes of Health Grants RO1 AI47389 and CA103866.; Supported by grants from the William Lawrence and Blanche Hughes Fund, the Children's Leukemia Research Association, and the Japan Society for the Promotion of Science. NR 32 TC 47 Z9 50 U1 2 U2 22 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 23 PY 2012 VL 287 IS 13 BP 9742 EP 9752 DI 10.1074/jbc.M111.304485 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917IN UT WOS:000302167200008 PM 22223645 ER PT J AU Rajabi, H Ahmad, R Jin, CN Kosugi, M Alam, M Joshi, MD Kufe, D AF Rajabi, Hasan Ahmad, Rehan Jin, Caining Kosugi, Michio Alam, Maroof Joshi, Maya Datt Kufe, Donald TI MUC1-C Oncoprotein Induces TCF7L2 Transcription Factor Activation and Promotes Cyclin D1 Expression in Human Breast Cancer Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; BETA-CATENIN; KINASE-ACTIVITY; WNT; PROTEIN; DOMAIN; GENE; BINDING; TARGET; OVEREXPRESSION AB MUC1 is a heterodimeric glycoprotein that is overexpressed in breast cancers. The present studies demonstrate that the oncogenic MUC1 C-terminal subunit (MUC1-C) associates with the TCF7L2 transcription factor. The MUC1-C cytoplasmic domain (MUC1-CD) binds directly to the TCF7L2 C-terminal region. MUC1-C blocks the interaction between TCF7L2 and the C-terminal-binding protein (CtBP), a suppressor of TCF7L2-mediated transcription. TCF7L2 and MUC1-C form a complex on the cyclin D1 gene promoter and MUC1-C promotes TCF7L2-mediated transcription by the recruitment of beta-catenin and p300. Silencing MUC1-C in human breast cancer cells down-regulated activation of the cyclin D1 promoter and decreased cyclin D1 expression. In addition, a MUC1-C inhibitor blocked the interaction with TCF7L2 and suppressed cyclin D1 levels. These findings indicate that the MUC1-C oncoprotein contributes to TCF7L2 activation and thereby promotes cyclin D1 expression in breast cancer cells. C1 [Rajabi, Hasan; Ahmad, Rehan; Jin, Caining; Kosugi, Michio; Alam, Maroof; Joshi, Maya Datt; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 830, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU National Institutes of Health [CA97098, CA42802, CA100707]; NCI FX This work was supported, in whole or in part, by National Institutes of Health Grants CA97098, CA42802, and CA100707 awarded by the NCI. NR 45 TC 35 Z9 37 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 23 PY 2012 VL 287 IS 13 BP 10703 EP 10713 DI 10.1074/jbc.M111.323311 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917IN UT WOS:000302167200095 PM 22318732 ER PT J AU Payne, JD Tucker, MA Ellenbogen, JM Wamsley, EJ Walker, MP Schacter, DL Stickgold, R AF Payne, Jessica D. Tucker, Matthew A. Ellenbogen, Jeffrey M. Wamsley, Erin J. Walker, Matthew P. Schacter, Daniel L. Stickgold, Robert TI Memory for Semantically Related and Unrelated Declarative Information: The Benefit of Sleep, the Cost of Wake SO PLOS ONE LA English DT Article ID PROCEDURAL MEMORY; CONSOLIDATION; SPINDLES; SYSTEMS AB Numerous studies have examined sleep's influence on a range of hippocampus-dependent declarative memory tasks, from text learning to spatial navigation. In this study, we examined the impact of sleep, wake, and time-of-day influences on the processing of declarative information with strong semantic links (semantically related word pairs) and information requiring the formation of novel associations (unrelated word pairs). Participants encoded a set of related or unrelated word pairs at either 9am or 9pm, and were then tested after an interval of 30 min, 12 hr, or 24 hr. The time of day at which subjects were trained had no effect on training performance or initial memory of either word pair type. At 12 hr retest, memory overall was superior following a night of sleep compared to a day of wakefulness. However, this performance difference was a result of a pronounced deterioration in memory for unrelated word pairs across wake; there was no sleep-wake difference for related word pairs. At 24 hr retest, with all subjects having received both a full night of sleep and a full day of wakefulness, we found that memory was superior when sleep occurred shortly after learning rather than following a full day of wakefulness. Lastly, we present evidence that the rate of deterioration across wakefulness was significantly diminished when a night of sleep preceded the wake period compared to when no sleep preceded wake, suggesting that sleep served to stabilize the memories against the deleterious effects of subsequent wakefulness. Overall, our results demonstrate that 1) the impact of 12 hr of waking interference on memory retention is strongly determined by word-pair type, 2) sleep is most beneficial to memory 24 hr later if it occurs shortly after learning, and 3) sleep does in fact stabilize declarative memories, diminishing the negative impact of subsequent wakefulness. C1 [Payne, Jessica D.] Univ Notre Dame, Dept Psychol, Indiana, PA USA. [Payne, Jessica D.; Tucker, Matthew A.; Wamsley, Erin J.; Stickgold, Robert] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Payne, Jessica D.; Tucker, Matthew A.; Wamsley, Erin J.; Stickgold, Robert] Ctr Sleep & Cognit, Boston, MA USA. [Ellenbogen, Jeffrey M.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Ellenbogen, Jeffrey M.] Harvard Med Sch, Div Sleep Med, Boston, MA USA. [Walker, Matthew P.] Univ Calif, Dept Psychol, Berkeley, CA USA. [Payne, Jessica D.; Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Payne, JD (reprint author), Univ Notre Dame, Dept Psychol, Indiana, PA USA. EM jpayne7@nd.edu OI Schacter, Daniel/0000-0002-2460-6061 FU National Institutes of Health [R01-MH48832] FX National Institutes of Health R01-MH48832. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. NR 33 TC 26 Z9 26 U1 6 U2 29 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 22 PY 2012 VL 7 IS 3 AR e33079 DI 10.1371/journal.pone.0033079 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 940QX UT WOS:000303909200018 PM 22457736 ER PT J AU Dimopoulos, MA Richardson, PG Brandenburg, N Yu, ZA Weber, DM Niesvizky, R Morgan, GJ AF Dimopoulos, Meletios A. Richardson, Paul G. Brandenburg, Nancy Yu, Zhinuan Weber, Donna M. Niesvizky, Ruben Morgan, Gareth J. TI A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide SO BLOOD LA English DT Article ID PLUS DEXAMETHASONE; ACUTE-LEUKEMIA; NEOPLASMS; TRANSPLANTATION; CHEMOTHERAPY; CANCERS; SAFETY AB In a retrospective pooled analysis of 11 clinical trials of lenalidomide-based therapy for relapsed/refractory multiple myeloma (MM; N = 3846), the overall incidence rate (IR, events per 100 patient-years) of second primary malignancies (SPMs) was 3.62. IR of invasive (hematologic and solid tumor) SPMs was 2.08, consistent with the background incidence of developing cancer. In a separate analysis of pooled data from pivotal phase 3 trials of relapsed or refractory MM (N = 703), the overall IR of SPMs was 3.98 (95% confidence interval [CI], 2.51-6.31) with lenalidomide/dexamethasone and 1.38 (95% CI, 0.44-4.27) with placebo/dexamethasone; IRs of nonmelanoma skin cancers were 2.40 (95% CI, 1.33-4.33) and 0.91 (95% CI, 0.23-3.66), respectively; IRs of invasive SPMs were 1.71 (95% CI, 0.86-3.43) and 0.91 (95% CI, 0.23-3.66), respectively. The risk of SPMs must be taken into account before initiating lenalidomide treatment. In the context of the observed survival benefit in relapsed or refractory MM patients, the benefit/risk profile of lenalidomide/dexamethasone remains positive. (Blood. 2012; 119(12): 2764-2767) C1 [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. [Brandenburg, Nancy; Yu, Zhinuan] Celgene Corp, Summit, NJ USA. [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weber, Donna M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Niesvizky, Ruben] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Morgan, Gareth J.] Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. RP Dimopoulos, MA (reprint author), Univ Athens, Sch Med, Dept Clin Therapeut, Alexandra Hosp, 80 Vas Sofias, Athens 11528, Greece. EM mdimop@med.uoa.gr FU Celgene Corporation FX All studies included in these analyses were sponsored by Celgene Corporation. Databases were provided by and analyzed by Celgene Corporation. NR 24 TC 75 Z9 78 U1 0 U2 5 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 22 PY 2012 VL 119 IS 12 BP 2764 EP 2767 DI 10.1182/blood-2011-08-373514 PG 4 WC Hematology SC Hematology GA 916RU UT WOS:000302121700013 PM 22323483 ER PT J AU Koivunen, P Lee, S Duncan, CG Lopez, G Lu, G Ramkissoon, S Losman, JA Joensuu, P Bergmann, U Gross, S Travins, J Weiss, S Looper, R Ligon, KL Verhaak, RGW Yan, H Kaelin, WG AF Koivunen, Peppi Lee, Sungwoo Duncan, Christopher G. Lopez, Giselle Lu, Gang Ramkissoon, Shakti Losman, Julie A. Joensuu, Paivi Bergmann, Ulrich Gross, Stefan Travins, Jeremy Weiss, Samuel Looper, Ryan Ligon, Keith L. Verhaak, Roel G. W. Yan, Hai Kaelin, William G., Jr. TI Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation SO NATURE LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR; OXYGEN SENSING PATHWAY; ONCOMETABOLITE 2-HYDROXYGLUTARATE; L-2-HYDROXYGLUTARIC ACIDURIA; PROLYL 4-HYDROXYLASES; ACTIVE-SITE; HYDROXYLASES; MUTATIONS; TUMORS; CELLS AB The identification of succinate dehydrogenase (SDH), fumarate hydratase (FH) and isocitrate dehydrogenase (IDH) mutations in human cancers has rekindled the idea that altered cellular metabolism can transform cells. Inactivating SDH and FH mutations cause the accumulation of succinate and fumarate, respectively, which can inhibit 2-oxoglutarate (2-OG)-dependent enzymes, including the EGLN prolyl 4-hydroxylases that mark the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation(1). Inappropriate HIF activation is suspected of contributing to the pathogenesis of SDH-defective and FH-defective tumours but can suppress tumour growth in some other contexts. IDH1 and IDH2, which catalyse the interconversion of isocitrate and 2-OG, are frequently mutated in human brain tumours and leukaemias. The resulting mutants have the neomorphic ability to convert 2-OG to the (R)-enantiomer of 2-hydroxyglutarate ((R)-2HG)(2,3). Here we show that (R)-2HG, but not (S)-2HG, stimulates EGLN activity, leading to diminished HIF levels, which enhances the proliferation and soft agar growth of human astrocytes. These findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumours promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy. C1 [Lee, Sungwoo; Lu, Gang; Ramkissoon, Shakti; Losman, Julie A.; Ligon, Keith L.; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lee, Sungwoo; Lu, Gang; Ramkissoon, Shakti; Losman, Julie A.; Ligon, Keith L.; Kaelin, William G., Jr.] Brigham & Womens Hosp, Boston, MA 02215 USA. [Koivunen, Peppi] Univ Oulu, Oulu Ctr Cell Matrix Res, Dept Med Biochem & Mol Biol, Bioctr Oulu, FIN-90014 Oulu, Finland. [Duncan, Christopher G.; Lopez, Giselle; Yan, Hai] Pediat Brain Tumor Fdn Inst, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. [Duncan, Christopher G.; Lopez, Giselle; Yan, Hai] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Ramkissoon, Shakti; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ramkissoon, Shakti; Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Joensuu, Paivi] Univ Oulu, Dept Chem, FIN-90014 Oulu, Finland. [Bergmann, Ulrich] Univ Oulu, Dept Biochem, Mass Spectrometry Core Facil, Bioctr Oulu, FIN-90014 Oulu, Finland. [Gross, Stefan; Travins, Jeremy] Agios Pharmaceut, Cambridge, MA 02139 USA. [Weiss, Samuel] Univ Calgary, Fac Med, Dept Cell Biol, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Weiss, Samuel] Univ Calgary, Fac Med, Dept Anat, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada. [Looper, Ryan] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. [Ligon, Keith L.] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA. [Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM william_kaelin@dfci.harvard.edu RI Waha, Andreas/J-2950-2014; OI Lopez, Giselle/0000-0001-5435-6668; Looper, Ryan/0000-0003-1626-1363 FU National Institutes of Health; HHMI; Doris Duke Foundation; Academy of Finland [120156, 140765, 218129]; S. Juselius Foundation FX We thank R. P. Hausinger and J. D. Rabinowitz for helpful suggestions and critical reading of the manuscript, C. Schofield and Y. Zhang for reagents, S. Chen and Y. Shi for JMJD2D assays, K. Koski for modelling and T. Aatsinki and E. Lehtimaki for technical assistance. W. G. K. is a Doris Duke Distinguished Clinical Scholar and a Howard Hughes Medical Institute (HHMI) Investigator. Supported by the National Institutes of Health (W. G. K.), HHMI (W. G. K.), Doris Duke Foundation (W. G. K.), Academy of Finland Grants 120156, 140765 and 218129 (P. K.) and S. Juselius Foundation (P.K.). NR 41 TC 250 Z9 254 U1 8 U2 60 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 22 PY 2012 VL 483 IS 7390 BP 485 EP U144 DI 10.1038/nature10898 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912CC UT WOS:000301771200047 PM 22343896 ER PT J AU Steinman, MA Landefeld, CS Baron, RB AF Steinman, Michael A. Landefeld, C. Seth Baron, Robert B. TI Industry Support of CME - Are We at the Tipping Point? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Steinman, Michael A.; Landefeld, C. Seth] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Steinman, Michael A.; Landefeld, C. Seth; Baron, Robert B.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Steinman, Michael A.; Landefeld, C. Seth] San Francisco VA Med Ctr, San Francisco, CA USA. [Baron, Robert B.] Univ Calif San Francisco, Off Associate Dean Grad & Continuing Med Educ, San Francisco, CA 94143 USA. RP Steinman, MA (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. NR 5 TC 14 Z9 16 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 22 PY 2012 VL 366 IS 12 BP 1069 EP 1071 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 912BO UT WOS:000301769700003 PM 22435367 ER PT J AU Patel, JP Gonen, M Figueroa, ME Fernandez, H Sun, ZX Racevskis, J Van Vlierberghe, P Dolgalev, I Thomas, S Aminova, O Huberman, K Cheng, J Viale, A Socci, ND Heguy, A Cherry, A Vance, G Higgins, RR Ketterling, RP Gallagher, RE Litzow, M van den Brink, MRM Lazarus, HM Rowe, JM Luger, S Ferrando, A Paietta, E Tallman, MS Melnick, A Abdel-Wahab, O Levine, RL AF Patel, Jay P. Goenen, Mithat Figueroa, Maria E. Fernandez, Hugo Sun, Zhuoxin Racevskis, Janis Van Vlierberghe, Pieter Dolgalev, Igor Thomas, Sabrena Aminova, Olga Huberman, Kety Cheng, Janice Viale, Agnes Socci, Nicholas D. Heguy, Adriana Cherry, Athena Vance, Gail Higgins, Rodney R. Ketterling, Rhett P. Gallagher, Robert E. Litzow, Mark van den Brink, Marcel R. M. Lazarus, Hillard M. Rowe, Jacob M. Luger, Selina Ferrando, Adolfo Paietta, Elisabeth Tallman, Martin S. Melnick, Ari Abdel-Wahab, Omar Levine, Ross L. TI Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NORMAL CYTOGENETICS; YOUNGER ADULTS; OLDER PATIENTS; MUTATIONS; TET2; IDENTIFY; DNMT3A; AML AB BACKGROUND Acute myeloid leukemia (AML) is a heterogeneous disease with respect to presentation and clinical outcome. The prognostic value of recently identified somatic mutations has not been systematically evaluated in a phase 3 trial of treatment for AML. METHODS We performed a mutational analysis of 18 genes in 398 patients younger than 60 years of age who had AML and who were randomly assigned to receive induction therapy with high-dose or standard-dose daunorubicin. We validated our prognostic findings in an independent set of 104 patients. RESULTS We identified at least one somatic alteration in 97.3% of the patients. We found that internal tandem duplication in FLT3 (FLT3-ITD), partial tandem duplication in MLL (MLL-PTD), and mutations in ASXL1 and PHF6 were associated with reduced overall survival (P = 0.001 for FLT3-ITD, P = 0.009 for MLL-PTD, P = 0.05 for ASXL1, and P = 0.006 for PHF6); CEBPA and IDH2 mutations were associated with improved overall survival (P = 0.05 for CEBPA and P = 0.01 for IDH2). The favorable effect of NPM1 mutations was restricted to patients with co-occurring NPM1 and IDH1 or IDH2 mutations. We identified genetic predictors of outcome that improved risk stratification among patients with AML, independently of age, white-cell count, induction dose, and post-remission therapy, and validated the significance of these predictors in an independent cohort. High-dose daunorubicin, as compared with standarddose daunorubicin, improved the rate of survival among patients with DNMT3A or NPM1 mutations or MLL translocations (P = 0.001) but not among patients with wild-type DNMT3A, NPM1, and MLL (P = 0.67). CONCLUSIONS We found that DNMT3A and NPM1 mutations and MLL translocations predicted an improved outcome with high-dose induction chemotherapy in patients with AML. These findings suggest that mutational profiling could potentially be used for risk stratification and to inform prognostic and therapeutic decisions regarding patients with AML. (Funded by the National Cancer Institute and others.) C1 [Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, Leukemia Serv, Dept Med, New York, NY 10065 USA. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Cheng, Janice; Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10065 USA. [Figueroa, Maria E.; Melnick, Ari] Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, New York, NY USA. [Racevskis, Janis; Gallagher, Robert E.; Paietta, Elisabeth] Montefiore Med Ctr, New York, NY USA. [Van Vlierberghe, Pieter; Ferrando, Adolfo] Columbia Univ, Inst Canc Genet, New York, NY USA. [Van Vlierberghe, Pieter; Ferrando, Adolfo] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Van Vlierberghe, Pieter; Ferrando, Adolfo] Columbia Univ, Dept Pathol, New York, NY USA. [van den Brink, Marcel R. M.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA. [Fernandez, Hugo] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Blood & Bone Marrow Transplantat, Tampa, FL 33682 USA. [Sun, Zhuoxin] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Cherry, Athena] Stanford Hosp & Clin, Dept Pathol, Palo Alto, CA USA. [Vance, Gail] Indiana Univ Sch Med, Dept Med & Mol Genet, Bloomington, IN USA. [Higgins, Rodney R.] Abbott NW Hosp, Allina Cytogenet Lab, Minneapolis, MN 55407 USA. [Ketterling, Rhett P.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Litzow, Mark] Mayo Clin, Coll Med, Dept Hematol & Oncol, Rochester, MN USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Sch Med, Div Hematol Oncol, Cleveland, OH 44106 USA. [Rowe, Jacob M.] Technion Israel Inst Technol, Jerusalem, Israel. [Rowe, Jacob M.] Shaare Zedek Med Ctr, Jerusalem, Israel. [Luger, Selina] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, Leukemia Serv, Dept Med, 1275 York Ave,Box 20, New York, NY 10065 USA. EM leviner@mskcc.org RI Gonen, Mithat/E-4826-2012; Van Vlierberghe, Pieter/G-8894-2013; OI Van Vlierberghe, Pieter/0000-0001-9063-7205; Dolgalev, Igor/0000-0003-4451-126X; Abdel-Wahab, Omar/0000-0002-3907-6171 FU National Cancer Institute (NCI) Physical Sciences Oncology Center [U54CA143798-01]; Gabrielle's Angel Fund; Starr Cancer Consortium; Memorial Sloan-Kettering Cancer Center; American Society; Leukemia and Lymphoma Society; Fund for Scientific Research (FWO) Flanders; Leukemia and Lymphoma Society Specialized Center; Sackler Center for Biomedical and Physical Sciences; Howard Hughes Medical Institute; NCI [CA21115, CA56771, CA114737] FX Supported by grants from the National Cancer Institute (NCI) Physical Sciences Oncology Center (U54CA143798-01, to Dr. Levine), the Gabrielle's Angel Fund (to Dr. Levine), and the Starr Cancer Consortium (to Drs. Levine and Melnick) and funding from the Peter Solomon Fund at Memorial Sloan-Kettering Cancer Center. Mr. Patel is supported by an American Society of Hematology Trainee Research Award; Dr. Figueroa is funded by a Leukemia and Lymphoma Society Special Fellow Award; Drs. Van Vlierberghe and Abdel-Wahab are American Society of Hematology Basic Research Fellows; Dr. Van Vlierberghe is supported by the Fund for Scientific Research (FWO) Flanders; Dr. Melnick is funded by a Leukemia and Lymphoma Society Specialized Center of Research Award and Translational Research Program Award and is a Burroughs Wellcome Clinical Translational Scholar and a Scholar of the Leukemia and Lymphoma Society; Drs. Figueroa and Melnick are also supported by the Sackler Center for Biomedical and Physical Sciences; Dr. Levine is the recipient of an Early Career Award from the Howard Hughes Medical Institute; Dr. Paietta is supported by NCI grants CA21115 and CA114737; Dr. Gallagher is supported by NCI grant CA56771; and Dr. Ferrando is funded by a Leukemia and Lymphoma Society Scholar Award. NR 24 TC 670 Z9 696 U1 9 U2 54 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 22 PY 2012 VL 366 IS 12 BP 1079 EP 1089 DI 10.1056/NEJMoa1112304 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 912BO UT WOS:000301769700007 PM 22417203 ER PT J AU Kaufman, DS Zietman, AL McDougal, WS Dahl, DM Harisinghani, MG Wu, CL AF Kaufman, Donald S. Zietman, Anthony L. McDougal, W. Scott Dahl, Douglas M. Harisinghani, Mukesh G. Wu, Chin-Lee TI Case 9-2012: A 67-Year-Old Man with a Persistently Elevated PSA Level SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PROSTATE-CANCER; BIOPSY C1 [Kaufman, Donald S.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. [Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [McDougal, W. Scott; Dahl, Douglas M.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kaufman, Donald S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zietman, Anthony L.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [McDougal, W. Scott; Dahl, Douglas M.] Harvard Univ, Sch Med, Dept Urol, Boston, MA USA. [Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kaufman, DS (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 22 PY 2012 VL 366 IS 12 BP 1143 EP 1150 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 912BO UT WOS:000301769700014 PM 22435374 ER PT J AU Ruff, CT Giugliano, RP Antman, EM Murphy, SA Lotan, C Heuer, H Merkely, B Baracioli, L Schersten, F Seabro-Gomes, R Braunwald, E Wiviott, SD AF Ruff, Christian T. Giugliano, Robert P. Antman, Elliott M. Murphy, Sabina A. Lotan, Chaim Heuer, Herbertus Bela Merkely Baracioli, Luciano Schersten, Fredrik Seabro-Gomes, Ricardo Braunwald, Eugene Wiviott, Stephen D. CA TRITON-TIMI 38 Investigators TI Safety and efficacy of prasugrel compared with clopidogrel in different regions of the world SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Prasugrel; Clopidogrel; TRITON-TIMI 38; Regional differences; HDI ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; CARDIOVASCULAR CLINICAL-TRIALS; OPTIMIZING PLATELET INHIBITION; 2007 FOCUSED UPDATE; INTERNATIONAL DIFFERENCES; TASK-FORCE; INTERREGIONAL DIFFERENCES; THERAPEUTIC OUTCOMES AB Background: Among patients with acute coronary syndrome(ACS), demographics, procedural characteristics and adjunctive medications differ globally. We examined whether there were differential effects of prasugrel compared with clopidogrel in the multinational TRITON-TIMI 38 study. Methods: We divided the enrollment into 5 pre-specified geographic regions. Patients were randomized to prasugrel or clopidogrel without regard to country of enrollment. End points are expressed as Kaplan-Meier failure estimates through 15 months. Heterogeneity was evaluated using Cox proportional hazards model. Additional sensitivity analyses were performed by dividing countries into categories based on the Human Development Index (HDI), which is a composite measure of social and economic development. Results: 13,608 patients were enrolled. Clinical characteristics including age, comorbidities, ACS presentation, stent types, and adjunctive medications differed broadly among regions. Despite these differences, no regional heterogeneity was observed with prasugrel compared to clopidogrel in the reduction of ischemic events (HR range: 0.76-0.87, p(interaction)>0.10 for each) and stent thrombosis (HR range: 0.34-0.72, p(interaction)>0.10 for each) or in the increased rate of non-CABG TIMI major bleeding (HR range: 1.16-1.76, p(interaction)>0.10 for each). There was a consistent trend in net clinical benefit (all cause death/MI/stroke/non-CABG TIMI major bleeding) favoring prasugrel (HR range: 0.81-0.97, p(interaction)>0.10 for each). Consistent results were also observed regarding the safety and efficacy of prasugrel compared with clopidogrel in both developed and developing countries. Conclusions: Despite differences in patient demographics, procedural techniques and adjunctive medications, consistent reduction in ischemic events and increased bleeding were seen with prasugrel compared with clopidogrel throughout the world. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Ruff, Christian T.; Giugliano, Robert P.; Antman, Elliott M.; Murphy, Sabina A.; Wiviott, Stephen D.; TRITON-TIMI 38 Investigators] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA. [Lotan, Chaim] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. [Heuer, Herbertus] St Johannes Hosp Dortmund, Dortmund, Germany. [Bela Merkely] Semmelweis Egyet, Budapest, Hungary. [Baracioli, Luciano] FMUSP, Inst Coracao, Sao Paulo, Brazil. [Schersten, Fredrik] Helsingborgs Lasarett, Dept Med, Helsingborg, Sweden. [Seabro-Gomes, Ricardo] Inst Coracao, Carnaxide, Portugal. RP Ruff, CT (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp,Dept Med,Med Sch, 75 Francis St, Boston, MA 02115 USA. EM cruff@partners.org NR 38 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAR 22 PY 2012 VL 155 IS 3 BP 424 EP 429 DI 10.1016/j.ijcard.2010.10.040 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 899TU UT WOS:000300840000022 PM 21093072 ER PT J AU Atkinson, W Forghani, R Wojtkiewicz, GR Pulli, B Iwamoto, Y Ueno, T Waterman, P Truelove, J Oklu, R Chen, JW AF Atkinson, Wendy Forghani, Reza Wojtkiewicz, Gregory R. Pulli, Benjamin Iwamoto, Yoshiko Ueno, Takuya Waterman, Peter Truelove, Jessica Oklu, Rahmi Chen, John W. TI Ligation of the Jugular Veins Does Not Result in Brain Inflammation or Demyelination in Mice SO PLOS ONE LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CEREBROSPINAL VENOUS INSUFFICIENCY; MULTIPLE-SCLEROSIS; MEDICAL PROGRESS; IRON DEPOSITION; MYELOPEROXIDASE; MOUSE; FLOW; PATHOGENESIS; AGENTS AB An alternative hypothesis has been proposed implicating chronic cerebrospinal venous insufficiency (CCSVI) as a potential cause of multiple sclerosis (MS). We aimed to evaluate the validity of this hypothesis in a controlled animal model. Animal experiments were approved by the institutional animal care committee. The jugular veins in SJL mice were ligated bilaterally (n = 20), and the mice were observed for up to six months after ligation. Sham-operated mice (n = 15) and mice induced with experimental autoimmune encephalomyelitis (n = 8) were used as negative and positive controls, respectively. The animals were evaluated using CT venography and Tc-99m-exametazime to assess for structural and hemodynamic changes. Imaging was performed to evaluate for signs of blood-brain barrier (BBB) breakdown and neuroinflammation. Flow cytometry and histopathology were performed to assess inflammatory cell populations and demyelination. There were both structural changes (stenosis, collaterals) in the jugular venous drainage and hemodynamic disturbances in the brain on Tc99m-exametazime scintigraphy (p = 0.024). In the JVL mice, gadolinium MRI and immunofluorescence imaging for barrier molecules did not reveal evidence of BBB breakdown (p = 0.58). Myeloperoxidase, matrix metalloproteinase, and protease molecular imaging did not reveal signs of increased neuroinflammation (all p>0.05). Flow cytometry and histopathology also did not reveal increase in inflammatory cell infiltration or population shifts. No evidence of demyelination was found, and the mice remained without clinical signs. Despite the structural and hemodynamic changes, we did not identify changes in the BBB permeability, neuroinflammation, demyelination, or clinical signs in the JVL group compared to the sham group. Therefore, our murine model does not support CCSVI as a cause of demyelinating diseases such as multiple sclerosis. C1 [Atkinson, Wendy; Forghani, Reza; Wojtkiewicz, Gregory R.; Pulli, Benjamin; Iwamoto, Yoshiko; Ueno, Takuya; Waterman, Peter; Truelove, Jessica; Chen, John W.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Atkinson, Wendy; Forghani, Reza; Wojtkiewicz, Gregory R.; Pulli, Benjamin; Iwamoto, Yoshiko; Ueno, Takuya; Waterman, Peter; Truelove, Jessica; Chen, John W.] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA USA. [Forghani, Reza; Chen, John W.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. [Oklu, Rahmi] Massachusetts Gen Hosp, Dept Radiol, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Forghani, Reza] Sir Mortimer B Davis Jewish Hosp, Montreal, PQ H3T 1E2, Canada. [Forghani, Reza] McGill Univ, Montreal, PQ, Canada. RP Atkinson, W (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM jwchen@mgh.harvard.edu OI Forghani, Reza/0000-0002-8572-1864 FU National Institutes of Health [R01-NS070835, R01-NS072167] FX This study was funded in part by the National Institutes of Health (R01-NS070835 and R01-NS072167 to JWC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. NR 30 TC 5 Z9 5 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 21 PY 2012 VL 7 IS 3 AR e33671 DI 10.1371/journal.pone.0033671 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 939YN UT WOS:000303857100035 PM 22457780 ER PT J AU Niers, JM Chen, JW Lewandrowski, G Kerami, M Garanger, E Wojtkiewicz, G Waterman, P Keliher, E Weissleder, R Tannous, BA AF Niers, Johanna M. Chen, John W. Lewandrowski, Grant Kerami, Mariam Garanger, Elisabeth Wojtkiewicz, Greg Waterman, Peter Keliher, Edmund Weissleder, Ralph Tannous, Bakhos A. TI Single Reporter for Targeted Multimodal in Vivo Imaging SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CELL-SURFACE PROTEINS; GENE-THERAPY; METABOLIC BIOTINYLATION; FLUORESCENT PROTEIN; GAUSSIA LUCIFERASE; Y-90 BIOTIN; EXPRESSION; RADIOIMMUNOTHERAPY; BIOTECHNOLOGY; VECTORS AB We have developed a multifaceted, highly specific reporter for multimodal in vivo imaging and applied it for detection of brain tumors. A metabolically biotinylated, membrane-bound form of Gaussia luciferase was synthesized, termed mbGluc-biotin. We engineered glioma cells to express this reporter and showed that brain tumor formation can be temporally imaged by bioluminescence following systemic administration of coelenterazine. Brain tumors expressing this reporter had high sensitivity for detection by magnetic resonance and fluorescence tomographic imaging upon injection of streptavidin conjugated to magnetic nanoparticles or fluorophore, respectively. Moreover, single photon emission computed tomography showed enhanced imaging of these tumors upon injection with streptavidin complexed to wIn-DTPA-biotin. This work shows for the first time a single small reporter (similar to 40 kDa) which can be monitored with most available molecular imaging modalities and can be extended for single cell imaging using intravital microscopy, allowing real-time tracking of any cell expressing it in vivo. C1 [Niers, Johanna M.; Lewandrowski, Grant; Kerami, Mariam; Tannous, Bakhos A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurosci Ctr,Expt Therapeut & Mol Ima, Boston, MA 02115 USA. [Chen, John W.; Garanger, Elisabeth; Wojtkiewicz, Greg; Waterman, Peter; Keliher, Edmund; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Chen, John W.; Wojtkiewicz, Greg; Waterman, Peter; Keliher, Edmund; Weissleder, Ralph; Tannous, Bakhos A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Dept Radiol, Boston, MA USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Niers, Johanna M.; Kerami, Mariam] Canc Ctr Amsterdam, VU Med Ctr, Dept Neurosurg, Neurooncol Res Grp, NL-1007 MB Amsterdam, Netherlands. RP Tannous, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurosci Ctr,Expt Therapeut & Mol Ima, Boston, MA 02115 USA. EM btannous@hms.harvard.edu FU NIH/NCI [P50CA86355, 4R00CA126839]; NIH/NINDS [P30NS045776, R01NS070835, R01NS072167, K08HL081170] FX This work was supported partly by grants from NIH/NCI P50CA86355 (R.W. and B.A.T.) and 4R00CA126839 (B.A.T.) as well as NIH/NINDS P30NS045776 (B.A.T.), R01NS070835 (J.W.C.), R01NS072167 (J.W.C.), and K08HL081170 (J.W.C.). We would like to thank Miss Danielle Morse and Jorien Koelen for technical assistance. NR 43 TC 20 Z9 20 U1 1 U2 43 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 21 PY 2012 VL 134 IS 11 BP 5149 EP 5156 DI 10.1021/ja209868g PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 917PZ UT WOS:000302191900028 PM 22397453 ER PT J AU Walker, TG Salazar, GM Waltman, AC AF Walker, T. Gregory Salazar, Gloria M. Waltman, Arthur C. TI Angiographic evaluation and management of acute gastrointestinal hemorrhage SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Angiodysplasia; Aneurysm; Digital subtraction angiography; Contrast media; Hemorrhage; Radionuclide angiography; Therapeutic embolization ID SUPERSELECTIVE MICROCOIL EMBOLIZATION; ARTERIAL INFUSION; VASOPRESSIN; ARTERIOGRAPHY; EXPERIENCE AB Although most cases of acute nonvariceal gastrointestinal hemorrhage either spontaneously resolve or respond to medical management or endoscopic treatment, there are still a significant number of patients who require emergency angiography and transcatheter treatment. Evaluation with noninvasive imaging such as nuclear scintigraphy or computed tomography may localize the bleeding source and/or confirm active hemorrhage prior to angiography. Any angiographic evaluation should begin with selective catheterization of the artery supplying the most likely site of bleeding, as determined by the available clinical, endoscopic and imaging data. If a hemorrhage source is identified, superselective catheterization followed by transcatheter microcoil embolization is usually the most effective means of successfully controlling hemorrhage while minimizing potential complications. This is now well-recognized as a viable and safe alternative to emergency surgery. In selected situations transcatheter intra-arterial infusion of vasopressin may also be useful in controlling acute gastrointestinal bleeding. One must be aware of the various side effects and potential complications associated with this treatment, however, and recognize the high re-bleeding rate. In this article we review the current role of angiography, transcatheter arterial embolization and infusion therapy in the evaluation and management of nonvariceal gastrointestinal hemorrhage. (C) 2012 Baishideng. All rights reserved. C1 [Walker, T. Gregory; Salazar, Gloria M.; Waltman, Arthur C.] Harvard Univ, Sch Med, Div Vasc Imaging & Intervent, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Walker, TG (reprint author), Harvard Univ, Sch Med, Div Vasc Imaging & Intervent, Massachusetts Gen Hosp, 55 Fruit St,GRB 290A, Boston, MA 02114 USA. EM tgwalker@partners.org NR 28 TC 23 Z9 26 U1 1 U2 2 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAR 21 PY 2012 VL 18 IS 11 BP 1191 EP 1201 DI 10.3748/wjg.v18.i11.1191 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 917PM UT WOS:000302190400007 PM 22468082 ER PT J AU Shah, AA Butler, RB Romanowski, J Goel, D Karadagli, D Warner, JJP AF Shah, Anup A. Butler, R. Bryan Romanowski, James Goel, Danny Karadagli, Dimitrios Warner, Jon J. P. TI Short-Term Complications of the Latarjet Procedure SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID RECURRENT SHOULDER INSTABILITY; ANTERIOR INSTABILITY; BRISTOW PROCEDURE; NEUROLOGIC COMPLICATIONS; CORACOID TRANSFER; BRACHIAL-PLEXUS; BONE LOSS; DISLOCATION; MANAGEMENT; SURGERY AB Background: Although the results of the Latarjet procedure have been reported previously, there is little literature regarding the early complications of this procedure. The purpose of this study was to report our experience with the Latarjet procedure for glenohumeral instability and to highlight the initial complications that may occur following this procedure. Methods: Forty-seven patients (forty-eight shoulders) underwent the Latarjet procedure for anterior glenohumeral instability between January 2005 and January 2010. All shoulders had some osseous deficiency of the anterior glenoid rim or had undergone an unsuccessful prior soft-tissue Bankart repair. The minimum duration of patient follow-up was six months. Results: Forty-five shoulders were available for follow-up. The overall complication rate was 25% (twelve of the original forty-eight shoulders). Complications were divided into three groups: infection, recurrent glenohumeral instability, and neurologic injury. A superficial infection developed in three shoulders (6%); in all cases, the infection resolved following irrigation and debridement and administration of antibiotics for up to four weeks. Four shoulders (8%) developed recurrent glenohumeral instability; this occurred within eight months in two shoulders and at nineteen and forty-two months postoperatively in the other two. Five procedures (10%) resulted in a neurologic injury. Two of these involved the musculocutaneous nerve, one involved the radial nerve, and two involved the axillary nerve. The three musculocutaneous and radial nerve injuries involved sensory neurapraxia that resolved fully within two months. Both of the patients with axillary nerve dysfunction continued to have persistent sensory disturbances and one continued to have residual weakness that had not yet resolved fully at the time of the final follow-up. Conclusions: The overall complication rate of 25% is higher than that reported in the literature. Although most of these complications resolved completely, two patients continued to have residual neurologic symptoms. Patients should be informed of the risk of complications associated with the Latarjet procedure, although most of the potential complications will resolve. C1 [Shah, Anup A.; Butler, R. Bryan; Romanowski, James; Goel, Danny; Warner, Jon J. P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shah, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,Yawkey Bldg 3G, Boston, MA 02114 USA. EM jwarner@partners.org NR 22 TC 56 Z9 59 U1 3 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR 21 PY 2012 VL 94A IS 6 BP 495 EP 501 DI 10.2106/JBJS.J.01830 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 913PA UT WOS:000301888700003 PM 22318222 ER PT J AU Dzhala, V Valeeva, G Glykys, J Khazipov, R Staley, K AF Dzhala, Volodymyr Valeeva, Guzel Glykys, Joseph Khazipov, Rustem Staley, Kevin TI Traumatic Alterations in GABA Signaling Disrupt Hippocampal Network Activity in the Developing Brain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CATION-CHLORIDE COTRANSPORTERS; GIANT DEPOLARIZING POTENTIALS; GRAMICIDIN-PERFORATED-PATCH; NEONATAL-RAT HIPPOCAMPUS; TEMPORAL-LOBE EPILEPSY; K-CL COTRANSPORTER; IN-VITRO ISCHEMIA; EXCITATORY ACTIONS; INTRACELLULAR CHLORIDE; ELECTROGRAPHIC SEIZURES AB Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl-](i)) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl-](i) correlated with disruption of neural processes and biomarkers of cell injury. Traumatized neurons with higher [Cl-](i) demonstrated excitatory GABA signaling, remained synaptically active, and facilitated network activity as assayed by the frequency of extracellular action potentials and spontaneous network-driven oscillations. These data support a more inhibitory role for GABA in the unperturbed immature brain, demonstrate the utility of the acute brain slice preparation for the study of the consequences of trauma, and provide potential mechanisms for both GABA-mediated excitatory network events in the slice preparation and early post-traumatic seizures. C1 [Dzhala, Volodymyr; Glykys, Joseph; Staley, Kevin] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dzhala, Volodymyr; Glykys, Joseph; Staley, Kevin] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Valeeva, Guzel; Khazipov, Rustem] Natl Inst Hlth & Med Res, INSERM, U901, F-13273 Marseille, France. [Valeeva, Guzel; Khazipov, Rustem] Kazan Fed Univ, Kazan 420008, Russia. RP Staley, K (reprint author), MIND, Dept Neurol, MGH 16th St,CNY B-114,Room 2600, Charlestown, MA 02129 USA. EM kstaley@partners.org RI Khazipov, Roustem/M-1834-2016; Valeeva, Guzel/B-2864-2014 OI Khazipov, Roustem/0000-0002-6763-2841; Valeeva, Guzel/0000-0001-6745-059X FU U.S. National Institutes of Health; National Institute of Neurological Disorders and Stroke [NS 40109-06]; FRM; Agence National de la Recherche; RF Government [11.G34.31.0075]; Russian Foundation for Basic Research FX This work was supported by the U.S. National Institutes of Health and National Institute of Neurological Disorders and Stroke Grant NS 40109-06 to K. S., by FRM, Agence National de la Recherche, and RF Government 11.G34.31.0075 grants to R. K., and Russian Foundation for Basic Research grant to G. V. We thank our colleagues for discussion of the manuscript. NR 91 TC 50 Z9 51 U1 1 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 21 PY 2012 VL 32 IS 12 BP 4017 EP 4031 DI 10.1523/JNEUROSCI.5139-11.2012 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 916RB UT WOS:000302119800007 PM 22442068 ER PT J AU Usenovic, M Tresse, E Mazzulli, JR Taylor, JP Krainc, D AF Usenovic, Marija Tresse, Emilie Mazzulli, Joseph R. Taylor, J. Paul Krainc, Dimitri TI Deficiency of ATP13A2 Leads to Lysosomal Dysfunction, alpha-Synuclein Accumulation, and Neurotoxicity SO JOURNAL OF NEUROSCIENCE LA English DT Article ID CHAPERONE-MEDIATED AUTOPHAGY; KUFOR-RAKEB SYNDROME; P-TYPE ATPASE; PARKINSONS-DISEASE; MUTATIONS; TOXICITY; DEGRADATION; PROTEASOME; MATURATION; DISORDERS AB The autophagy-lysosomal pathway plays an important role in the clearance of long-lived proteins and dysfunctional organelles. Lysosomal dysfunction has been implicated in several neurodegenerative disorders including Parkinson's disease and related synucleinopathies that are characterized by accumulations of alpha-synuclein in Lewy bodies. Recent identification of mutations in genes linked to lysosomal function and neurodegeneration has offered a unique opportunity to directly examine the role of lysosomes in disease pathogenesis. Mutations in lysosomal membrane protein ATP13A2 (PARK9) cause familial Kufor-Rakeb syndrome characterized by early-onset parkinsonism, pyramidal degeneration and dementia. While previous data suggested a role of ATP13A2 in alpha-synuclein misfolding and toxicity, the mechanistic link has not been established. Here we report that loss of ATP13A2 in human fibroblasts from patients with Kufor-Rakeb syndrome or in mouse primary neurons leads to impaired lysosomal degradation capacity. This lysosomal dysfunction results in accumulation of alpha-synuclein and toxicity in primary cortical neurons. Importantly, silencing of endogenous alpha-synuclein attenuated the toxicity in ATP13A2-depleted neurons, suggesting that loss of ATP13A2 mediates neurotoxicity at least in part via the accumulation of alpha-synuclein. Our findings implicate lysosomal dysfunction in the pathogenesis of Kufor-Rakeb syndrome and suggest that upregulation of lysosomal function and downregulation of alpha-synuclein represent important therapeutic strategies for this disorder. C1 [Usenovic, Marija; Mazzulli, Joseph R.; Krainc, Dimitri] MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Usenovic, Marija; Mazzulli, Joseph R.; Krainc, Dimitri] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Usenovic, Marija] Mediterranean Inst Life Sci, Split 2100, Croatia. [Tresse, Emilie; Taylor, J. Paul] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. RP Krainc, D (reprint author), MassGen Inst Neurodegenerat Dis, 114 16th St,Room 2008, Charlestown, MA 02129 USA. EM krainc@helix.mgh.harvard.edu FU NIH [R01NS051303, R01AG031587] FX This work was supported by NIH Grant R01NS051303 (to D. K.). J.P.T. and E. T. were supported by NIH Grant R01AG031587. We thank Drs. Christine Klein for patient fibroblasts, Carolyn M. Sue for ATP13A2-GFP construct, Thomas J. Diefenbach for assistance with confocal microscopy, and Isabella Palazzolo, Hyunkyung Jeong, and other members of Krainc laboratory for helpful suggestions and discussions. NR 28 TC 90 Z9 91 U1 2 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 21 PY 2012 VL 32 IS 12 BP 4240 EP 4246 DI 10.1523/JNEUROSCI.5575-11.2012 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 916RB UT WOS:000302119800025 PM 22442086 ER PT J AU Regan, MM Leyland-Jones, B Bouzyk, M Pagani, O Tang, WN Kammler, R Dell'Orto, P Biasi, MO Thurlimann, B Lyng, MB Ditzel, HJ Neven, P Debled, M Maibach, R Price, KN Gelber, RD Coates, AS Goldhirsch, A Rae, JM Viale, G AF Regan, Meredith M. Leyland-Jones, Brian Bouzyk, Mark Pagani, Olivia Tang, Weining Kammler, Roswitha Dell'Orto, Patrizia Biasi, Maria Olivia Thuerlimann, Beat Lyng, Maria B. Ditzel, Henrik J. Neven, Patrick Debled, Marc Maibach, Rudolf Price, Karen N. Gelber, Richard D. Coates, Alan S. Goldhirsch, Aron Rae, James M. Viale, Giuseppe CA Breast Int Grp BIG 1-98 Collaborat TI CYP2D6 Genotype and Tamoxifen Response in Postmenopausal Women with Endocrine-Responsive Breast Cancer: The Breast International Group 1-98 Trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HOT FLASHES; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; THERAPY; RECURRENCE; METABOLITE; ENDOXIFEN; OUTCOMES; RISK; BIOTRANSFORMATION AB Background Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer. Cytochrome P450 2D6 (CYP2D6) enzyme metabolizes tamoxifen to clinically active metabolites, and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy. In this study, we investigated the clinical relevance of CYP2D6 polymorphisms. Methods We obtained tumor tissues and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor positive breast cancer who enrolled in the randomized, phase III double-blind Breast International Group (BIG) 1-98 trial between March 1998 and May 2003 and received tamoxifen and/or letrozole treatment. Extracted DNA was used for genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain reaction based methods. Genotype combinations were used to categorize CYP2D6 metabolism phenotypes as poor, intermediate, and extensive metabolizers (PM, IM, and EM, respectively; n = 4393 patients). Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval (referred to as recurrence) and treatment-induced hot flushes according to randomized endocrine treatment and previous chemotherapy were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results No association between CYP2D6 metabolism phenotypes and breast cancer-free interval was observed among patients who received tamoxifen monotherapy without previous chemotherapy (P = .35). PM or IM phenotype had a non-statistically significantly reduced risk of breast cancer recurrence compared with EM phenotype (PM or IM vs EM, HR of recurrence = 0.86, 95% CI = 0.60 to 1.24). CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes (P = .020). Both PM and IM phenotypes had an increased risk of tamoxifen-induced hot flushes compared with EM phenotype (PM vs EM, HR of hot flushes = 1.24, 95% CI = 0.96 to 1.59; IM vs EM, HR of hot flushes = 1.23, 95% CI = 1.05 to 1.43). Conclusions CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes, contrary to the hypothesis. The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxifen. C1 [Regan, Meredith M.; Price, Karen N.; Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02215 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA USA. [Leyland-Jones, Brian; Bouzyk, Mark] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Bouzyk, Mark] AKESOgen Inc, Atlanta, GA USA. [Pagani, Olivia] Inst Oncol So Switzerland, Viganello, Switzerland. [Pagani, Olivia] Osped Italiano, Dept Med Oncol Clin Res, Viganello, Switzerland. [Pagani, Olivia; Thuerlimann, Beat] Swiss Grp Clin Canc Res, Bern, Switzerland. [Tang, Weining] Emory Univ, Emory Biomarker Serv Ctr, Winship Canc Inst, Atlanta, GA 30322 USA. [Tang, Weining] Omega Biotek Inc, Norcross, GA USA. [Kammler, Roswitha; Maibach, Rudolf] IBCSG Coordinating Ctr, Bern, Switzerland. [Kammler, Roswitha] IBCSG Cent Pathol Off, Bern, Switzerland. [Dell'Orto, Patrizia; Viale, Giuseppe] IBCSG Cent Pathol Off, Milan, Italy. [Dell'Orto, Patrizia; Biasi, Maria Olivia; Viale, Giuseppe] European Inst Oncol, Div Pathol & Lab Med, Milan, Italy. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Lyng, Maria B.; Ditzel, Henrik J.] Univ So Denmark, Dept Canc & Inflammat, Inst Mol Med, Odense, Denmark. [Lyng, Maria B.; Ditzel, Henrik J.] Danish Breast Canc Cooperat Grp, Copenhagen, Denmark. Odense Univ Hosp, Dept Oncol, DK-5000 Odense, Denmark. [Neven, Patrick] UZ Leuven, Multidisciplinary Breast Unit, Dept Gynecol Oncol, Louvain, Belgium. [Debled, Marc] SW Comprehens Canc Ctr, Dept Med Oncol, Inst Bergonie, Bordeaux, France. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Coates, Alan S.] IBCSG, Sydney, NSW, Australia. [Coates, Alan S.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Goldhirsch, Aron] European Inst Oncol, Dept Med, Milan, Italy. [Goldhirsch, Aron] St Anna Clin, Swiss Ctr Breast Hlth, Lugano, Switzerland. [Rae, James M.] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Viale, Giuseppe] Univ Milan, Milan, Italy. RP Regan, MM (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM mregan@jimmy.harvard.edu; leyland@emory.edu OI Ditzel, Henrik J./0000-0003-3927-5135 FU Susan G. Komen for the Cure [KG080081]; Novartis; IBCSG: Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); United States National Institutes of Health National Cancer Institute [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland; Pfizer, Inc FX The translational research, including DNA extraction and genotyping, was funded by Susan G. Komen for the Cure Promise Grant (KG080081 to GV, OP, MMR). The Breast International Group (BEG) 1-98 trial was funded by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Other support for the IBCSG: Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); United States National Institutes of Health National Cancer Institute (CA-75362 to RDG); Cancer Research Switzerland/Oncosuisse; and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK).; The BIG 1-98 trial was funded by Novartis, who contracted with the IBCSG for provision of services related to the conduct and management of the trial and provided partial support for collection and review of tumor blocks. Dr A. Goldhirsch, Dr A. S. Coates, and Dr R. D. Gelber are responsible for the scientific management of the IBCSG. Dr G. Viale is responsible for management of the IBCSG Central Pathology Office. Dr J. M. Rae receives research funding from Pfizer, Inc, and has served on an Advisory Board for Olema Pharmaceuticals. Dr B. Thurlimann owns stock in Novartis. The remaining authors have no conflicts to declare. NR 35 TC 166 Z9 171 U1 1 U2 17 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 21 PY 2012 VL 104 IS 6 BP 441 EP 451 DI 10.1093/jnci/djs125 PG 11 WC Oncology SC Oncology GA 913PF UT WOS:000301889200008 PM 22395644 ER PT J AU Roberts, PJ Bisi, JE Strum, JC Combest, AJ Darr, DB Usary, JE Zamboni, WC Wong, KK Perou, CM Sharpless, NE AF Roberts, Patrick J. Bisi, John E. Strum, Jay C. Combest, Austin J. Darr, David B. Usary, Jerry E. Zamboni, William C. Wong, Kwok-Kin Perou, Charles M. Sharpless, Norman E. TI Multiple Roles of Cyclin-Dependent Kinase 4/6 Inhibitors in Cancer Therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; COLONY-STIMULATING FACTORS; METASTATIC BREAST-CANCER; PLACEBO-CONTROLLED TRIAL; PHASE-III TRIAL; LARGE T-ANTIGEN; CDK4/6 INHIBITION; GENE-EXPRESSION; DOUBLE-BLIND; BASAL-LIKE AB Background Cyclin-dependent kinases (CDKs) regulate cell proliferation and coordinate the cell cycle checkpoint response to DNA damage. Although inhibitors with varying selectivity to specific CDK family members have been developed, selective CDK4/6 inhibitors have emerged as the most attractive antineoplastic agents because of the importance of CDK4/6 activity in regulating cell proliferation and the toxic effects associated with inhibition of other CDKs (eg, CDK1 and CDK2). Methods FVB/N wild-type mice (n = 13) were used to evaluate carboplatin-induced myelosuppression in bone marrow by complete blood cell counts after treatment with the CDK4/6 inhibitor PD0332991. Genetically engineered murine models of retinoblastoma (Rb)-competent (MMTV-c-neu) and Rb-incompetent (C3-TAg) breast cancer (n = 16 MMTV-c-neu mice in the carboplatin plus vehicle control group, n = 17 MMTV-c-neu mice in the carboplatin plus PD0332991 group, n = 17 C3-TAg mice in the carboplatin plus vehicle control group, and n = 14 C3-TAg mice in the carboplatin plus PD0332991 group) were used to investigate the antitumor activity of PD0332991 alone or in combination with chemotherapy. All statistical tests were two-sided. Results Coadministration of PD0332991 with carboplatin compared with carboplatin alone in FVB/N wild-type mice increased hematocrit (51.2% vs 33.5%, difference = 17.7%, 95% confidence interval [CI] = -26.7% to -8.6%, P <. 001), platelet counts (1321 vs 758.5 thousand cells per mu L, difference = 562.5 thousand cells per mu L, 95% CI = -902.8 to -222.6, P = .002), myeloid cells (granulocytes and monocytes; 3.1 vs 1.6 thousand cells per mu L, difference = 1.5 thousand cells per mu L, 95% CI = -2.23 to -0.67, P < .001), and lymphocytes (7.9 vs 5.4 thousand cells per mu L, difference = 562.5 thousand cells per mu L, 95% CI = -4.75 to -0.18, P = .02). Daily administration of PD0332991 exhibited antitumor activity in MMTV-c-neu mice as a single agent. However, the combination of carboplatin plus PD0332991 decreased antitumor activity compared with carboplatin alone in Rb-competent mice (mean percent change in tumor volume at day 21 = -52.6% vs 3.7% for carboplatin and carboplatin plus PD0332991, respectively, difference = 56.3%, 95% CI = -109.0% to -3.6%, P = .04). In contrast, Rb-deficient tumors in C3-Tag mice were resistant to PD0332991, and coadministration of PD0332991 plus carboplatin had no effect on in vivo tumor growth (mean percent change in tumor volume at day 21 = 118.8% and 109.1% for carboplatin and carboplatin plus PD0332991, respectively, difference = 9.7%, 95% CI = -183.5% to 202.9%, P = .92). Finally, in tumor-bearing mice, coadministration of PD0332991 with carboplatin provided statistically significant protection of platelets (P = .04). Conclusion We believe that the present data support a possible role for CDK4/6 inhibitors in a majority of patients with advanced cancer: to either inhibit tumor growth in CDK4/6-dependent tumors or ameliorate the dose-limiting toxicities of chemotherapy in CDK4/6-indepdendent tumors. Our data also suggest CDK4/6 inhibitors should not be combined with DNA-damaging therapies, such as carboplatin, to treat tumors that require CDK4/6 activity for proliferation. C1 [Roberts, Patrick J.; Darr, David B.; Usary, Jerry E.; Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Roberts, Patrick J.; Perou, Charles M.; Sharpless, Norman E.] Univ N Carolina, Dept Genet, Sch Med, Chapel Hill, NC 27599 USA. [Sharpless, Norman E.] Univ N Carolina, Dept Med, Sch Med, Chapel Hill, NC 27599 USA. [Combest, Austin J.; Zamboni, William C.] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Bisi, John E.; Strum, Jay C.] G Zero Therapeut, Chapel Hill, NC USA. [Zamboni, William C.] Univ N Carolina, Inst Pharmacogen & Individualized Therapy, Chapel Hill, NC 27599 USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Perou, Charles M.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Sharpless, NE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, CB 7295, Chapel Hill, NC 27599 USA. EM nes@med.unc.edu OI wong, kwok kin/0000-0001-6323-235X; Perou, Charles/0000-0001-9827-2247 FU Golfers Against Cancer Foundation; Ellison Medical Foundation; Burroughs Wellcome Fund [1006673]; National Institutes of Health [RO1 P01-ES014635, UO1-CA141576, P50-CA58223-09A1, RO1-CA148761]; University of North Carolina Lineberger Comprehensive Cancer Center; American Cancer Society [PF-10-239-01-TBG] FX This work was supported by the University of North Carolina Lineberger Comprehensive Cancer Center Mouse Phase I Unit, and grants from the Golfers Against Cancer Foundation (to N.E.S and C.M.P), the Ellison Medical Foundation (to N.E.S), the Burroughs Wellcome Fund (1006673 to N.E.S), the National Institutes of Health (RO1 P01-ES014635 and UO1-CA141576 to N.E.S; P50-CA58223-09A1 and RO1-CA148761 to C.M.P), the University Cancer Research Fund from the University of North Carolina Lineberger Comprehensive Cancer Center (to N.E.S and W.C.Z), and the American Cancer Society (PF-10-239-01-TBG to P.J.R). NR 74 TC 89 Z9 93 U1 2 U2 29 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 21 PY 2012 VL 104 IS 6 BP 476 EP 487 DI 10.1093/jnci/djs002 PG 12 WC Oncology SC Oncology GA 913PF UT WOS:000301889200011 PM 22302033 ER PT J AU Dutta, J Ahn, S Li, CQ Cherry, SR Leahy, RM AF Dutta, Joyita Ahn, Sangtae Li, Changqing Cherry, Simon R. Leahy, Richard M. TI Joint L-1 and total variation regularization for fluorescence molecular tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DIFFUSE OPTICAL TOMOGRAPHY; RADIATIVE-TRANSFER EQUATION; TOTAL VARIATION MINIMIZATION; ORDERED SUBSETS ALGORITHMS; LINEAR INVERSE PROBLEMS; IMAGE-RECONSTRUCTION; TRANSMISSION TOMOGRAPHY; THRESHOLDING ALGORITHM; EM ALGORITHM; MOUSE ATLAS AB Fluorescence molecular tomography (FMT) is an imaging modality that exploits the specificity of fluorescent biomarkers to enable 3D visualization of molecular targets and pathways in vivo in small animals. Owing to the high degree of absorption and scattering of light through tissue, the FMT inverse problem is inherently ill-conditioned making image reconstruction highly susceptible to the effects of noise and numerical errors. Appropriate priors or penalties are needed to facilitate reconstruction and to restrict the search space to a specific solution set. Typically, fluorescent probes are locally concentrated within specific areas of interest (e. g., inside tumors). The commonly used L-2 norm penalty generates the minimum energy solution, which tends to be spread out in space. Instead, we present here an approach involving a combination of the L-1 and total variation norm penalties, the former to suppress spurious background signals and enforce sparsity and the latter to preserve local smoothness and piecewise constancy in the reconstructed images. We have developed a surrogate-based optimization method for minimizing the joint penalties. The method was validated using both simulated and experimental data obtained from a mouse-shaped phantom mimicking tissue optical properties and containing two embedded fluorescent sources. Fluorescence data were collected using a 3D FMT setup that uses an EMCCD camera for image acquisition and a conical mirror for full-surface viewing. A range of performance metrics was utilized to evaluate our simulation results and to compare our method with the L-1, L-2 and total variation norm penalty-based approaches. The experimental results were assessed using the Dice similarity coefficients computed after co-registration with a CT image of the phantom. C1 [Dutta, Joyita; Ahn, Sangtae; Leahy, Richard M.] Univ So Calif, Dept Elect Engn Syst, Inst Signal & Image Proc, Los Angeles, CA 90089 USA. [Dutta, Joyita] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Li, Changqing; Cherry, Simon R.] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. RP Dutta, J (reprint author), Univ So Calif, Dept Elect Engn Syst, Inst Signal & Image Proc, Los Angeles, CA 90089 USA. EM Dutta.Joyita@mgh.harvard.edu; leahy@sipi.usc.edu RI Li, Changqing/F-4671-2010 FU National Cancer Institute [R01CA121783, R44CA138243] FX We thank Dr Anand A Joshi at the University of Southern California for assistance with the DigiWarp tool for atlas warping. This work was supported by the National Cancer Institute under grants R01CA121783 and R44CA138243. NR 62 TC 42 Z9 42 U1 1 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 21 PY 2012 VL 57 IS 6 BP 1459 EP 1476 DI 10.1088/0031-9155/57/6/1459 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 906PF UT WOS:000301358000001 PM 22390906 ER PT J AU Shusharina, N Sharp, G AF Shusharina, Nadezhda Sharp, Gregory TI Analytic regularization for landmark-based image registration SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIAL BASIS FUNCTIONS; THIN-PLATE SPLINES; ELASTIC REGISTRATION; NONRIGID REGISTRATION; MEDICAL IMAGES; DEFORMATIONS AB Landmark-based registration using radial basis functions (RBF) is an efficient and mathematically transparent method for the registration of medical images. To ensure invertibility and diffeomorphism of the RBF-based vector field, various regularization schemes have been suggested. Here, we report a novel analytic method of RBF regularization and demonstrate its power for Gaussian RBF. Our analytic formula can be used to obtain a regularized vector field from the solution of a system of linear equations, exactly as in traditional RBF, and can be generalized to any RBF with infinite support. We statistically validate the method on global registration of synthetic and pulmonary images. Furthermore, we present several clinical examples of multistage intensity/landmark-based registrations, where regularized Gaussian RBF are successful in correcting locally misregistered areas resulting from automatic B-spline registration. The intended ultimate application of our method is rapid, interactive local correction of deformable registration with a small number of mouse clicks. C1 [Shusharina, Nadezhda; Sharp, Gregory] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Shusharina, N (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM nshusharina@partners.org FU NIH [NCI 6-PO1CA21239, NCI-C06CA059267]; National Alliance for Medical Image Computing (NA-MIC); National Institutes of Health through the NIH [2-U54EB005149-06] FX The authors would like to thank the DIR-Lab team for sharing their thoracic CT data with landmark annotations, which we used for statistical validation. Funding for this work was provided by an Ira J Spiro translational research award, by the NIH NCI 6-PO1CA21239 and by the Federal share of program income earned by MGH on NIH NCI-C06CA059267. This work is part of the National Alliance for Medical Image Computing (NA-MIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant 2-U54EB005149-06. Information on the National Centers for Biomedical Computing can be obtained from http://nihroadmap.nih.gov/bioinformatics. NR 32 TC 10 Z9 10 U1 1 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 21 PY 2012 VL 57 IS 6 BP 1477 EP 1498 DI 10.1088/0031-9155/57/6/1477 PG 22 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 906PF UT WOS:000301358000002 PM 22390947 ER PT J AU Bandrowski, AE Cachat, J Li, Y Muller, HM Sternberg, PW Ciccarese, P Clark, T Marenco, L Wang, R Astakhov, V Grethe, JS Martone, ME AF Bandrowski, A. E. Cachat, J. Li, Y. Mueller, H. M. Sternberg, P. W. Ciccarese, P. Clark, T. Marenco, L. Wang, R. Astakhov, V. Grethe, J. S. Martone, M. E. TI A hybrid human and machine resource curation pipeline for the Neuroscience Information Framework SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article AB The breadth of information resources available to researchers on the Internet continues to expand, particularly in light of recently implemented data-sharing policies required by funding agencies. However, the nature of dense, multifaceted neuroscience data and the design of contemporary search engine systems makes efficient, reliable and relevant discovery of such information a significant challenge. This challenge is specifically pertinent for online databases, whose dynamic content is 'hidden' from search engines. The Neuroscience Information Framework (NIF; http://www.neuinfo.org) was funded by the NIH Blueprint for Neuroscience Research to address the problem of finding and utilizing neuroscience-relevant resources such as software tools, data sets, experimental animals and antibodies across the Internet. From the outset, NIF sought to provide an accounting of available resources, whereas developing technical solutions to finding, accessing and utilizing them. The curators therefore, are tasked with identifying and registering resources, examining data, writing configuration files to index and display data and keeping the contents current. In the initial phases of the project, all aspects of the registration and curation processes were manual. However, as the number of resources grew, manual curation became impractical. This report describes our experiences and successes with developing automated resource discovery and semiautomated type characterization with text-mining scripts that facilitate curation team efforts to discover, integrate and display new content. We also describe the DISCO framework, a suite of automated web services that significantly reduce manual curation efforts to periodically check for resource updates. Lastly, we discuss DOMEO, a semi-automated annotation tool that improves the discovery and curation of resources that are not necessarily website-based (i.e. reagents, software tools). Although the ultimate goal of automation was to reduce the workload of the curators, it has resulted in valuable analytic by-products that address accessibility, use and citation of resources that can now be shared with resource owners and the larger scientific community. C1 [Bandrowski, A. E.; Cachat, J.; Astakhov, V.; Grethe, J. S.; Martone, M. E.] Univ Calif San Diego, Ctr Res Biol Syst, Pasadena, CA 91125 USA. [Li, Y.; Mueller, H. M.; Sternberg, P. W.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Ciccarese, P.; Clark, T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ciccarese, P.; Clark, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marenco, L.; Wang, R.] Yale Univ, Sch Med, Ctr Med Informat, New Haven, CT 06520 USA. RP Bandrowski, AE (reprint author), Univ Calif San Diego, Ctr Res Biol Syst, Pasadena, CA 91125 USA. EM abandrowski@ucsd.edu RI Cachat, Jonathan/B-3719-2010; Muller, Hans-Michael/J-9624-2015; OI Cachat, Jonathan/0000-0002-6504-0869; Grethe, Jeffrey/0000-0001-5212-7052; Martone, Maryann/0000-0002-8406-3871; Bandrowski, Anita/0000-0002-5497-0243; Clark, Timothy/0000-0003-4060-7360 FU NIH Blueprint for Neuroscience Research; National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services [HHSN271200577531C] FX This work was supported by and has been funded in whole or in part through the NIH Blueprint for Neuroscience Research with Federal funds from the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services [Contract Number HHSN271200577531C]. P. W. S. is an Investigator with the Howard Hughes Medical Institute. NR 13 TC 9 Z9 9 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD MAR 20 PY 2012 AR bas005 DI 10.1093/database/bas005 PG 11 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 954BO UT WOS:000304920200003 ER PT J AU Hall, DE Prochazka, AV Fink, AS AF Hall, Daniel E. Prochazka, Allan V. Fink, Aaron S. TI Informed consent for clinical treatment SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Review ID MEDICAL-ETHICS CURRICULUM; DECISION-MAKING; SURGICAL RESIDENTS; BREAST-CANCER; ELECTROCONVULSIVE-THERAPY; PATIENTS PERCEPTIONS; QUALITATIVE-ANALYSIS; PILOT PROJECT; PATIENTS WANT; SURGERY C1 [Fink, Aaron S.] Vet Affairs Med Ctr Atlanta, Surg Serv, Decatur, GA USA. [Fink, Aaron S.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Prochazka, Allan V.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Prochazka, Allan V.] Denver Vet Affairs Med Ctr, Ambulatory Care, Denver, CO USA. [Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Hall, Daniel E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. RP Fink, AS (reprint author), Vet Affairs Med Ctr Atlanta, Surg Serv, Decatur, GA USA. EM afink01@comcast.net RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 FU HSRD VA [CDA 08-281] NR 77 TC 29 Z9 31 U1 5 U2 15 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 0820-3946 EI 1488-2329 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD MAR 20 PY 2012 VL 184 IS 5 BP 533 EP 540 DI 10.1503/cmaj.112120 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 930OT UT WOS:000303149700030 PM 22392947 ER PT J AU Qaseem, A Chou, R Humphrey, LL Shekelle, P AF Qaseem, Amir Chou, Roger Humphrey, Linda L. Shekelle, Paul TI Venous Thromboembolism Prophylaxis in Hospitalized Medical Patients RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID PUBLICATION BIAS; FUNNEL PLOT C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. [Chou, Roger; Humphrey, Linda L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Shekelle, Paul] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, Philadelphia, PA 19106 USA. NR 4 TC 1 Z9 1 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 20 PY 2012 VL 156 IS 6 BP 474 EP 475 DI 10.7326/0003-4819-156-6-201203200-00020 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 930PF UT WOS:000303150900025 ER PT J AU Sleijfer, S Wagner, AJ AF Sleijfer, Stefan Wagner, Andrew J. TI The Challenge of Choosing Appropriate End Points in Single-Arm Phase II Studies of Rare Diseases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CELL LUNG-CANCER; SORAFENIB; CARCINOMA; SURVIVAL; CHORDOMA C1 [Sleijfer, Stefan] Erasmus Univ, Med Ctr, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands. [Wagner, Andrew J.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Sleijfer, S (reprint author), Erasmus Univ, Med Ctr, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands. NR 11 TC 12 Z9 12 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 2012 VL 30 IS 9 BP 896 EP 898 DI 10.1200/JCO.2011.40.6942 PG 4 WC Oncology SC Oncology GA 923OK UT WOS:000302628400004 PM 22331936 ER PT J AU Kleinerman, RA Yu, CL Little, MP Li, Y Abramson, D Seddon, J Tucker, MA AF Kleinerman, Ruth A. Yu, Chu-ling Little, Mark P. Li, Yi Abramson, David Seddon, Johanna Tucker, Margaret A. TI Variation of Second Cancer Risk by Family History of Retinoblastoma Among Long-Term Survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEREDITARY RETINOBLASTOMA; RB1 MUTATIONS; FOLLOW-UP; RADIOTHERAPY; MORTALITY; SARCOMAS; GENE AB Purpose To evaluate the risk of second cancer (SC) in long-term survivors of retinoblastoma (Rb) according to classification of germline mutation, based on family history of Rb and laterality. Patients and Methods We assembled a cohort of 1,852 1-year survivors of Rb (bilateral, n = 1,036; unilateral, n = 816). SCs were ascertained by medical records and self-reports and confirmed by pathology reports. Classification of RB1 germline mutation, inherited or de novo, was inferred by laterality of Rb and positive family history of Rb. Standardized incidence ratios and cumulative incidence for all SCs combined and for soft tissue sarcomas, bone cancers, and melanoma were calculated. The influence of host-and therapy-related risk factors for SC was assessed by Poisson regression for bilateral survivors. Results We observed a relative risk (RR) of 1.37 (95% CI, 1.00 to 1.86) for SCs in bilateral survivors associated with a family history of Rb, adjusted for treatment, age, and length of follow-up. The risk for melanoma was significantly elevated for survivors with a family history of Rb (RR, 3.08; 95% CI, 1.23 to 7.16), but risks for bone or soft tissue sarcomas were not elevated. The cumulative incidence of SCs 50 years after diagnosis of bilateral Rb, with adjustment for competing risk of death, was significantly higher for survivors with a family history (47%; 95% CI, 35% to 59%) than survivors without a family history (38%; 95% CI, 32% to 44%; P = .004). Conclusion Rb survivors with bilateral disease and an inherited germline mutation are at slightly higher risk of an SC compared with those with a de novo germline mutation, in particular melanoma, perhaps because of shared genetic alterations. J Clin Oncol 30: 950-957. (C) 2012 by American Society of Clinical Oncology C1 [Kleinerman, Ruth A.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Seddon, Johanna] Tufts Univ New England Med Ctr, Boston, MA USA. [Abramson, David] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, EPS 7044,6120 Execut Blvd, Rockville, MD 20852 USA. EM Kleinerr@mail.nih.gov RI Tucker, Margaret/B-4297-2015; OI Kleinerman, Ruth/0000-0001-7415-2478; Little, Mark/0000-0003-0980-7567 FU National Institutes of Health; National Cancer Institute FX Supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. NR 27 TC 31 Z9 32 U1 0 U2 1 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 2012 VL 30 IS 9 BP 950 EP 957 DI 10.1200/JCO.2011.37.0239 PG 8 WC Oncology SC Oncology GA 923OK UT WOS:000302628400014 PM 22355046 ER PT J AU Win, AK Young, JP Lindor, NM Tucker, KM Ahnen, DJ Young, GP Buchanan, DD Clendenning, M Giles, GG Winship, I Macrae, FA Goldblatt, J Southey, MC Arnold, J Thibodeau, SN Gunawardena, SR Bapat, B Baron, JA Casey, G Gallinger, S Le Marchand, L Newcomb, PA Haile, RW Hopper, JL Jenkins, MA AF Win, Aung Ko Young, Joanne P. Lindor, Noralane M. Tucker, Katherine M. Ahnen, Dennis J. Young, Graeme P. Buchanan, Daniel D. Clendenning, Mark Giles, Graham G. Winship, Ingrid Macrae, Finlay A. Goldblatt, Jack Southey, Melissa C. Arnold, Julie Thibodeau, Stephen N. Gunawardena, Shanaka R. Bapat, Bharati Baron, John A. Casey, Graham Gallinger, Steven Le Marchand, Loic Newcomb, Polly A. Haile, Robert W. Hopper, John L. Jenkins, Mark A. TI Colorectal and Other Cancer Risks for Carriers and Noncarriers From Families With a DNA Mismatch Repair Gene Mutation: A Prospective Cohort Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYNCH-SYNDROME; BREAST-CANCER; COLON-CANCER; POLYMORPHISMS; INDIVIDUALS; ONSET; HNPCC; HMLH1; DIAGNOSIS; VARIANTS AB Purpose To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. Patients and Methods We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Results Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P = .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97). Conclusion We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives. J Clin Oncol 30: 958-964. (C) 2012 by American Society of Clinical Oncology C1 [Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia. [Winship, Ingrid; Macrae, Finlay A.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia. [Young, Joanne P.; Buchanan, Daniel D.; Clendenning, Mark] Queensland Inst Med Res, Herston, Qld 4006, Australia. [Young, Joanne P.] Univ Queensland, Sch Med, Herston, Qld, Australia. [Tucker, Katherine M.] Prince Wales Hosp, Hereditary Canc Clin, Randwick, NSW 2031, Australia. [Young, Graeme P.] Flinders Univ S Australia, Flinders Ctr Canc Prevent & Control, Adelaide, SA, Australia. [Goldblatt, Jack] Univ Western Australia, Genet Serv Western Australia, Perth, WA 6009, Australia. [Goldblatt, Jack] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6009, Australia. [Arnold, Julie] Auckland City Hosp, New Zealand Familial Gastrointestinal Canc Regist, Auckland, New Zealand. [Bapat, Bharati; Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Bapat, Bharati] Univ Toronto, Toronto, ON, Canada. [Gallinger, Steven] Canc Care Ontario, Toronto, ON, Canada. [Lindor, Noralane M.; Thibodeau, Stephen N.; Gunawardena, Shanaka R.] Mayo Clin, Rochester, MN USA. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver Vet Affairs Med Ctr, Denver, CO USA. [Baron, John A.] Univ N Carolina, Chapel Hill, NC USA. [Casey, Graham; Haile, Robert W.] Univ So Calif, Los Angeles, CA USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Jenkins, MA (reprint author), Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, 207 Bouverie St,Level 3, Melbourne, Vic 3010, Australia. EM m.jenkins@unimelb.edu.au RI Gallinger, Steven/E-4575-2013; Bapat, Bharati/B-5839-2014; Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Giles, Graham/0000-0003-4946-9099; Win, Aung Ko/0000-0002-2794-5261; Buchanan, Daniel/0000-0003-2225-6675; Winship, Ingrid/0000-0001-8535-6003 FU NCI NIH HHS [U01 CA074794, P30 CA015704, U01 CA074783, U01 CA074799, U01 CA074800, U01 CA074806, U01 CA097735] NR 44 TC 123 Z9 128 U1 0 U2 18 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 2012 VL 30 IS 9 BP 958 EP 964 DI 10.1200/JCO.2011.39.5590 PG 7 WC Oncology SC Oncology GA 923OK UT WOS:000302628400015 PM 22331944 ER PT J AU Patel, UD Garg, AX Krumholz, HM Shlipak, MG Coca, SG Sint, K Thiessen-Philbrook, H Koyner, JL Swaminathan, M Passik, CS Parikh, CR AF Patel, Uptal D. Garg, Amit X. Krumholz, Harlan M. Shlipak, Michael G. Coca, Steven G. Sint, Kyaw Thiessen-Philbrook, Heather Koyner, Jay L. Swaminathan, Madhav Passik, Cary S. Parikh, Chirag R. CA Translational Res Investigating TI Preoperative Serum Brain Natriuretic Peptide and Risk of Acute Kidney Injury After Cardiac Surgery SO CIRCULATION LA English DT Article DE acute kidney injury; cardiac surgical procedures; creatinine; natriuretic peptide, brain ID DECOMPENSATED HEART-FAILURE; GLOMERULAR-FILTRATION-RATE; RENAL-FUNCTION; SURGICAL-PROCEDURES; NONCARDIAC SURGERY; PROSPECTIVE COHORT; VENOUS CONGESTION; DYSFUNCTION; OUTCOMES; METAANALYSIS AB Background-Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery. Methods and Results-The Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) study enrolled 1139 adults undergoing cardiac surgery at 6 hospitals from 2007 to 2009 who were selected for high AKI risk. Preoperative BNP was categorized into quintiles. AKI was common with the use of Acute Kidney Injury Network definitions; at least mild AKI was a >= 0.3-mg/dL or 50% rise in creatinine (n=407, 36%), and severe AKI was either a doubling of creatinine or the requirement of acute renal replacement therapy (n=58, 5.1%). In analyses adjusted for preoperative characteristics, preoperative BNP was a strong and independent predictor of mild and severe AKI. Compared with the lowest BNP quintile, the highest quintile had significantly higher risk of at least mild AKI (risk ratio, 1.87; 95% confidence interval, 1.40-2.49) and severe AKI (risk ratio, 3.17; 95% confidence interval, 1.06-9.48). After adjustment for clinical predictors, the addition of BNP improved the area under the curve to predict at least mild AKI (0.67-0.69; P=0.02) and severe AKI (0.73-0.75; P=0.11). Compared with clinical parameters alone, BNP modestly improved risk prediction of AKI cases into lower and higher risk (continuous net reclassification index; at least mild AKI: risk ratio, 0.183; 95% confidence interval, 0.061-0.314; severe AKI: risk ratio, 0.231; 95% confidence interval, 0.067-0.506). Conclusions-Preoperative BNP level is associated with postoperative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, preoperative BNP may be a valuable component of future efforts to improve preoperative risk stratification and discrimination among surgical candidates. C1 [Patel, Uptal D.] Duke Univ, Sch Med, Durham VA Med Ctr, Durham, NC USA. [Patel, Uptal D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Garg, Amit X.; Thiessen-Philbrook, Heather] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Krumholz, Harlan M.; Coca, Steven G.; Sint, Kyaw; Parikh, Chirag R.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Coca, Steven G.; Parikh, Chirag R.] Vet Affairs Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Koyner, Jay L.] Univ Chicago, Dept Med, Nephrol Sect, Pritzker Sch Med, Chicago, IL 60637 USA. [Swaminathan, Madhav] Duke Univ, Sch Med, Dept Anesthesia, Durham, NC USA. [Passik, Cary S.] Danbury Hosp, Dept Surg, Danbury, CT USA. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35 A,Room 21, West Haven, CT 06516 USA. EM chirag.parikh@yale.edu FU American Heart Association; National Heart, Lung, and Blood Institute [R01HL-085757]; National Institutes of Health from the National Center for Research Resources [UL1 RR024139] FX The research reported in this article was supported by the American Heart Association Clinical Development award and grant R01HL-085757 (to Dr Parikh) from the National Heart, Lung, and Blood Institute. The study was also supported by National Institutes of Health Clinical and Translational Science Award grant UL1 RR024139 (to Yale University) from the National Center for Research Resources. The plasma BNP assay was donated by Biosite. The granting agencies and Biosite, Inc did not participate in the protocol development, analysis, and interpretation of the results. NR 44 TC 30 Z9 37 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 20 PY 2012 VL 125 IS 11 BP 1347 EP U94 DI 10.1161/CIRCULATIONAHA.111.029686 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 916PN UT WOS:000302115800012 PM 22322531 ER PT J AU Kim, W Lao, QZ Shin, YK Carlson, OD Lee, EK Gorospe, M Kulkarni, RN Egan, JM AF Kim, Wook Lao, Qizong Shin, Yu-Kyong Carlson, Olga D. Lee, Eun Kyung Gorospe, Myriam Kulkarni, Rohit N. Egan, Josephine M. TI Cannabinoids Induce Pancreatic beta-Cell Death by Directly Inhibiting Insulin Receptor Activation SO SCIENCE SIGNALING LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; ENDOCANNABINOID SYSTEM; CB1 RECEPTOR; CYTOPLASMIC LOCALIZATION; DIABETES-MELLITUS; TYROSINE RESIDUES; CYCLE PROGRESSION; INDUCED APOPTOSIS; CANCER CELLS; LIPID RAFTS AB Cannabinoid 1 (CB1) receptors have been previously detected in pancreatic beta cells, where they attenuate insulin action. We now report that CB1 receptors form a heteromeric complex with insulin receptors and the heterotrimeric guanosine triphosphate-binding protein alpha subunit G alpha(i). G alpha(i) inhibited the kinase activity of the insulin receptor in beta cells by directly binding to the activation loop in the tyrosine kinase domain of the receptor. Consequently, phosphorylation of proapoptotic protein Bad was reduced and its apoptotic activity was stimulated, leading to beta-cell death. Pharmacological blockade or genetic deficiency of CB1 receptors enhanced insulin receptor signaling after injury, leading to reduced blood glucose concentrations and activation of Bad, which increased beta-cell survival. These findings provide direct evidence of physical and functional interactions between CB1 and insulin receptors and suggest a mechanism whereby peripherally acting CB1 receptor antagonists improve insulin action in insulin-sensitive tissues independent of the other metabolic effects of CB1 receptors. C1 [Kim, Wook; Lao, Qizong; Shin, Yu-Kyong; Carlson, Olga D.; Gorospe, Myriam; Egan, Josephine M.] NIA, NIH, Baltimore, MD 21224 USA. [Lee, Eun Kyung] Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 137701, South Korea. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Egan, JM (reprint author), NIA, NIH, Baltimore, MD 21224 USA. EM eganj@grc.nia.nih.gov FU NIA/NIH; National Research Foundation of Korea (NRF); Korea government (MEST) [20110013116]; Catholic Medical Center Research Foundation; NIH [RO1 DK 67536, 68721] FX This work was supported by the Intramural Research Program of the NIA/NIH. E.K.L. is supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (20110013116) and the Catholic Medical Center Research Foundation. R.N.K. is supported by NIH RO1 DK 67536 and 68721. NR 57 TC 26 Z9 26 U1 1 U2 4 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 20 PY 2012 VL 5 IS 216 AR ra23 DI 10.1126/scisignal.2002519 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 916RQ UT WOS:000302121300003 PM 22434934 ER PT J AU Rheinbay, E Louis, DN Bernstein, BE Suva, ML AF Rheinbay, Esther Louis, David N. Bernstein, Bradley E. Suva, Mario L. TI A Tell-Tail Sign of Chromatin: Histone Mutations Drive Pediatric Glioblastoma SO CANCER CELL LA English DT Editorial Material ID EPIGENOME; GLIOMAS; H3.3 AB Recent genomic analyses of pediatric glioblastoma, a poorly understood tumor with dismal outcome, have identified mutations in histone H3 variants that affect critical amino acids in the tail. The findings extend discoveries of chromatin regulator inactivation and gain-of-function mutations by documenting alteration of a modifiable histone residue in human cancer. C1 [Rheinbay, Esther; Bernstein, Bradley E.; Suva, Mario L.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Rheinbay, Esther; Louis, David N.; Bernstein, Bradley E.; Suva, Mario L.] Massachusetts Gen Hosp, Ctr Canc Res, Dept Pathol, Boston, MA 02114 USA. [Rheinbay, Esther; Louis, David N.; Bernstein, Bradley E.; Suva, Mario L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rheinbay, Esther; Bernstein, Bradley E.; Suva, Mario L.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Rheinbay, Esther] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. RP Bernstein, BE (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. EM bernstein.bradley@mgh.harvard.edu RI Waha, Andreas/J-2950-2014 FU NCI NIH HHS [R01 CA057683] NR 10 TC 9 Z9 9 U1 0 U2 1 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 20 PY 2012 VL 21 IS 3 BP 329 EP 331 DI 10.1016/j.ccr.2012.03.001 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 913YH UT WOS:000301912800007 PM 22439930 ER PT J AU Zhu, SZ Lee, JS Guo, F Shin, J Perez-Atayde, AR Kutok, JL Rodig, SJ Neuberg, DS Helman, D Feng, H Stewart, RA Wang, WC George, RE Kanki, JP Look, AT AF Zhu, Shizhen Lee, Jeong-Soo Guo, Feng Shin, Jimann Perez-Atayde, Antonio R. Kutok, Jeffery L. Rodig, Scott J. Neuberg, Donna S. Helman, Daniel Feng, Hui Stewart, Rodney A. Wang, Wenchao George, Rani E. Kanki, John P. Look, A. Thomas TI Activated ALK Collaborates with MYCN in Neuroblastoma Pathogenesis SO CANCER CELL LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; SYMPATHETIC-NERVOUS-SYSTEM; ELECTRON-MICROSCOPY; AUTONOMIC NEURONS; TUMOR INITIATION; ZEBRAFISH; MUTATIONS; CANCER; GENE; DIFFERENTIATION AB Amplification of the MYCN oncogene in childhood neuroblastoma is often accompanied by mutational activation of ALK (anaplastic lymphoma kinase), suggesting their pathogenic cooperation. We generated a transgenic zebrafish model of neuroblastoma in which MYCN-induced tumors arise from a subpopulation of neuroblasts that migrate into the adrenal medulla analog following organogenesis. Coexpression of activated ALK with MYCN in this model triples the disease penetrance and markedly accelerates tumor onset. MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and ultimately triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells. Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma. C1 [Zhu, Shizhen; Lee, Jeong-Soo; Guo, Feng; Shin, Jimann; Helman, Daniel; Feng, Hui; Stewart, Rodney A.; Wang, Wenchao; George, Rani E.; Kanki, John P.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Perez-Atayde, Antonio R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA. [Kutok, Jeffery L.; Rodig, Scott J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Neuberg, Donna S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [George, Rani E.; Look, A. Thomas] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Feng, Hui/0000-0003-1318-821X; Stewart, Rodney/0000-0003-1220-1830 FU National Cancer Institute, NIH [CA104605, K99CA134743]; Children's Tumor Foundation; Neuroblastoma Foundation; Friends for Life; Hope Street Kids Foundation; Durand Family Fund for Pediatric Neuroblastoma Research; David A. Abraham Fund; Pediatric Low Grade Astrocytoma Foundation; NIH/NINDS [R00 NS058608]; National Institutes of Health; Children's Oncology Group FX This work was supported by a grant CA104605 from the National Cancer Institute, NIH (A.T.L.), a Young Investigator Award from Children's Tumor Foundation and Neuroblastoma Foundation (J.S.L.), a fellowship from the Friends for Life (S.Z., R.E.G.), a fellowship from the Hope Street Kids Foundation (J.S.L.), a fellowship from Durand Family Fund for Pediatric Neuroblastoma Research (J.S.L.), a fellowship from the David A. Abraham Fund and Pediatric Low Grade Astrocytoma Foundation (J.S.), an award K99CA134743 from the National Cancer Institute, NIH (H.F.), an award R00 NS058608 from NIH/NINDS (R.A.S.), and a grant from the National Institutes of Health and the Children's Oncology Group (R.E.G.). We thank John Gilbert for editing the manuscript and critical comments, and Greg Molind, Lu Zhang, Derek Walsh, and John P. Lyons for excellent care of our zebrafish facility. NR 43 TC 82 Z9 84 U1 2 U2 17 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 20 PY 2012 VL 21 IS 3 BP 362 EP 373 DI 10.1016/j.ccr.2012.02.010 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 913YH UT WOS:000301912800010 PM 22439933 ER PT J AU Shi, Z Ruvkun, G AF Shi, Zhen Ruvkun, Gary TI The mevalonate pathway regulates microRNA activity in Caenorhabditis elegans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS-RNA REPLICATION; C-ELEGANS; PROTEIN; FAMILY; LIN-14; GENES; GERANYLGERANYLATION; DIFFERENTIATION; COMPONENTS; ASYMMETRY AB The mevalonate pathway is highly conserved and mediates the production of isoprenoids, which feed into biosynthetic pathways for sterols, dolichol, ubiquinone, heme, isopentenyl adenine, and prenylated proteins. We found that in Caenorhabditis elegans, the nonsterol biosynthetic outputs of the mevalonate pathway are required for the activity of microRNAs (miRNAs) in silencing their target mRNAs. Inactivation of genes that mediate multiple steps of the mevalonate pathway causes derepression of several miRNA target genes, with no disruption of the miRNA levels, suggesting a role in miRNA-induced silencing complex activity. Dolichol phosphate, synthesized from the mevalonate pathway, functions as a lipid carrier of the oligosaccharide moiety destined for protein N-linked glycosylation. Inhibition of the dolichol pathway of protein N-glycosylation also causes derepression of miRNA target mRNAs. The proteins that mediate miRNA repression are therefore likely to be regulated by N-glycosylation. Conversely, drugs such as statins, which inhibit the mevalonate pathway, may compromise miRNA repression as well as the more commonly considered cholesterol biosynthesis. C1 [Shi, Zhen; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Shi, Zhen] Harvard Univ, Sch Med, Biol Sci Dent Med Program, Boston, MA 02115 USA. [Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU National Institutes of Health [R01-GM44619]; American Heart Association FX We thank G. R. laboratory members, in particular G. Hayes, for constructive suggestions and thoughtful critiques of the work; T. Montgomery for kindly providing the worm strain for ALG-1 IP; M. Newman for helping with mass spectrometry; and Y. Kang for help with sequencing RNAi clones. We thank F. Slack for the [alg-1p::gfp::alg-1] strain, and the Caenorhabditis Genetics Center and the Mitani laboratory for other worm strains. Z.S. is supported by an American Heart Association predoctoral fellowship. This work was supported by National Institutes of Health Grant R01-GM44619 (to G.R.). NR 38 TC 13 Z9 13 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 20 PY 2012 VL 109 IS 12 BP 4568 EP 4573 DI 10.1073/pnas.1202421109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 911JH UT WOS:000301712600047 PM 22396595 ER PT J AU Chen, X Yu, YM Mi, LZ Walz, T Springer, TA AF Chen, Xing Yu, Yamei Mi, Li-Zhi Walz, Thomas Springer, Timothy A. TI Molecular basis for complement recognition by integrin alpha(X)beta(2) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ARG-GLY-ASP; I-DOMAIN; LIGAND-BINDING; COMPONENT C3; MAC-1 CD11B/CD18; STRUCTURAL BASIS; CR3 CD11B/CD18; BETA-PROPELLER; TYPE-3 CR3; RECEPTOR AB Integrin alpha(X)beta(2) functions as complement receptor for iC3b and mediates recognition and phagocytosis of pathogens. We used negative-stain EM to examine the alpha(X)beta(2) interaction with iC3b. EM class averages of alpha(X)beta(2) in complex with iC3b define the binding sites on both the integrin and iC3b. iC3b contains C3c and thioester domain moieties linked by a long flexible linker. The binding site is on the key ring of the C3c moiety, at the interface between the MG3 and MG4 domains. Similar complexes are seen between alpha(X)beta(2) and the C3c fragment. alpha(X)beta(2) binds through the aX aI domain, on the face known to bear the metal ion-dependent adhesion site, at the opposite end of the aI domain from its site of insertion in the beta-propeller domain. C1 [Chen, Xing; Yu, Yamei; Mi, Li-Zhi; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Chen, Xing; Yu, Yamei; Mi, Li-Zhi; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Mi, Li-Zhi/B-1371-2016 OI Mi, Li-Zhi/0000-0001-9907-5245 FU National Institutes of Health [AI72765] FX We thank A. Koksal for calculations for Fig. S5. This work was supported by National Institutes of Health Grant AI72765. X. C. is a Pfizer Fellow of the Life Sciences Research Foundation. T. W. is an investigator in the Howard Hughes Medical Institute. NR 42 TC 21 Z9 22 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 20 PY 2012 VL 109 IS 12 BP 4586 EP 4591 DI 10.1073/pnas.1202051109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 911JH UT WOS:000301712600050 PM 22393018 ER PT J AU Tearney, GJ Regar, E Akasaka, T Adriaenssens, T Barlis, P Bezerra, HG Bouma, B Bruining, N Cho, JM Chowdhary, S Costa, MA de Silva, R Dijkstra, J Di Mario, C Dudeck, D Falk, E Feldman, MD Fitzgerald, P Garcia, H Gonzalo, N Granada, JF Guagliumi, G Holm, NR Honda, Y Ikeno, F Kawasaki, M Kochman, J Koltowski, L Kubo, T Kume, T Kyono, H Lam, CCS Lamouche, G Lee, DP Leon, MB Maehara, A Manfrini, O Mintz, GS Mizuno, K Morel, MA Nadkarni, S Okura, H Otake, H Pietrasik, A Prati, F Raber, L Radu, MD Rieber, J Riga, M Rollins, A Rosenberg, M Sirbu, V Serruys, PWJC Shimada, K Shinke, T Shite, J Siegel, E Sonada, S Suter, M Takarada, S Tanaka, A Terashima, M Troels, T Uemura, S Ughi, GJ van Beusekom, HMM van der Steen, AFW van Es, GA van Soest, G Virmani, R Waxman, S Weissman, NJ Weisz, G AF Tearney, Guillermo J. Regar, Evelyn Akasaka, Takashi Adriaenssens, Tom Barlis, Peter Bezerra, Hiram G. Bouma, Brett Bruining, Nico Cho, Jin-man Chowdhary, Saqib Costa, Marco A. de Silva, Ranil Dijkstra, Jouke Di Mario, Carlo Dudeck, Darius Falk, Erlin Feldman, Marc D. Fitzgerald, Peter Garcia, Hector Gonzalo, Nieves Granada, Juan F. Guagliumi, Giulio Holm, Niels R. Honda, Yasuhiro Ikeno, Fumiaki Kawasaki, Masanori Kochman, Janusz Koltowski, Lukasz Kubo, Takashi Kume, Teruyoshi Kyono, Hiroyuki Lam, Cheung Chi Simon Lamouche, Guy Lee, David P. Leon, Martin B. Maehara, Akiko Manfrini, Olivia Mintz, Gary S. Mizuno, Kyiouchi Morel, Marie-angele Nadkarni, Seemantini Okura, Hiroyuki Otake, Hiromasa Pietrasik, Arkadiusz Prati, Francesco Raeber, Lorenz Radu, Maria D. Rieber, Johannes Riga, Maria Rollins, Andrew Rosenberg, Mireille Sirbu, Vasile Serruys, Patrick W. J. C. Shimada, Kenei Shinke, Toshiro Shite, Junya Siegel, Eliot Sonada, Shinjo Suter, Melissa Takarada, Shigeho Tanaka, Atsushi Terashima, Mitsuyasu Troels, Thim Uemura, Shiro Ughi, Giovanni J. van Beusekom, Heleen M. M. van der Steen, Antonius F. W. van Es, Gerrit-Ann van Soest, Gijs Virmani, Renu Waxman, Sergio Weissman, Neil J. Weisz, Giora TI Consensus Standards for Acquisition, Measurement, and Reporting of Intravascular Optical Coherence Tomography Studies A Report From the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atherosclerosis; consensus document; coronary artery; intravascular ultrasound; optical coherence tomography ID REPRODUCIBILITY; LESIONS; SAFETY; SYSTEM AB Objectives The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Background Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of similar to 10 mu m, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. Methods The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Results Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. Conclusions This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data. (J Am Coll Cardiol 2012;59:1058-72) (C) 2012 by the American College of Cardiology Foundation C1 [Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Regar, Evelyn] Erasmus MC, Rotterdam, Netherlands. [Akasaka, Takashi] Wakayama Sch Med, Wakayama, Japan. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR703, Boston, MA 02114 USA. EM gtearney@partners.org RI Dijkstra, Jouke/C-2917-2012; Koltowski, Lukasz/J-7398-2012; van Soest, Gijs/B-4881-2008; Falk, Erling/A-7475-2015; 刘, 李陆/H-8469-2015; OI Dijkstra, Jouke/0000-0002-8666-3731; Koltowski, Lukasz/0000-0003-0477-2094; Falk, Erling/0000-0001-8566-9974; Holm, Niels/0000-0002-2316-3107; Ughi, Giovanni J./0000-0003-3354-0698 FU Merck; Boston Scientific; Center for Integration of Medicine & Innovative Technology; Abbott Vascular Japan; St. Jude Medical Japan; Goodman Inc.; Boston Scientific Inc. FX Drs. Tearney, Regar, and Akasaka are co-chairs of the International Working Group for Intravascular OCT Standardization and Validation (IWG-IVOCT) and co-chairs of the Writing Committee for this document. The IWG-IVOCT effort has been partially sponsored by gifts and educational grants from Merck, Boston Scientific, and the Center for Integration of Medicine & Innovative Technology. Dr. Akasaka is on the clinical advisory board of St. Jude Medical and Terumo Inc.; and has received research funding from Abbott Vascular Japan, St. Jude Medical Japan, Goodman Inc., and Boston Scientific Inc. All members of the Writing Committee, as well as their affiliations and relationships with industry, are listed in the Online Supplementary Material. NR 13 TC 375 Z9 387 U1 5 U2 54 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 20 PY 2012 VL 59 IS 12 BP 1058 EP 1072 DI 10.1016/j.jacc.2011.09.079 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 907UA UT WOS:000301443000003 PM 22421299 ER PT J AU Kostis, WJ Jang, IK AF Kostis, William J. Jang, Ik-Kyung TI Platelet Disaggregation After Coronary Stent Thrombosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material C1 [Kostis, William J.; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02215 USA. RP Kostis, WJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 20 PY 2012 VL 59 IS 12 BP 1119 EP 1119 DI 10.1016/j.jacc.2011.09.080 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 907UA UT WOS:000301443000011 PM 22421307 ER PT J AU Neely, BA Soper, JL Greig, DJ Carlin, KP Favre, EG Gulland, FMD Almeida, JS Janech, MG AF Neely, Benjamin A. Soper, Jennifer L. Greig, Denise J. Carlin, Kevin P. Favre, Elizabeth G. Gulland, Frances M. D. Almeida, Jonas S. Janech, Michael G. TI Serum profiling by MALDI-TOF mass spectrometry as a diagnostic tool for domoic acid toxicosis in California sea lions SO PROTEOME SCIENCE LA English DT Article DE Serum peptides; Neural network; Zalophus californianus; Neurotoxin ID MAGNETIC BEAD SEPARATION; ZALOPHUS-CALIFORNIANUS; CEREBROSPINAL-FLUID; CLINICAL SIGNS; BIOMARKERS; PEPTIDOME; MORTALITY; SCLEROSIS; TOXICITY; PROTEOME AB Background: There are currently no reliable markers of acute domoic acid toxicosis (DAT) for California sea lions. We investigated whether patterns of serum peptides could diagnose acute DAT. Serum peptides were analyzed by MALDI-TOF mass spectrometry from 107 sea lions (acute DAT n = 34; non-DAT n = 73). Artificial neural networks (ANN) were trained using MALDI-TOF data. Individual peaks and neural networks were qualified using an independent test set (n = 20). Results: No single peak was a good classifier of acute DAT, and ANN models were the best predictors of acute DAT. Performance measures for a single median ANN were: sensitivity, 100%; specificity, 60%; positive predictive value, 71%; negative predictive value, 100%. When 101 ANNs were combined and allowed to vote for the outcome, the performance measures were: sensitivity, 30%; specificity, 100%; positive predictive value, 100%; negative predictive value, 59%. Conclusions: These results suggest that MALDI-TOF peptide profiling and neural networks can perform either as a highly sensitive (100% negative predictive value) or a highly specific (100% positive predictive value) diagnostic tool for acute DAT. This also suggests that machine learning directed by populations of predictive models offer the ability to modulate the predictive effort into a specific type of error. C1 [Neely, Benjamin A.; Janech, Michael G.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Soper, Jennifer L.; Greig, Denise J.; Gulland, Frances M. D.] Marine Mammal Ctr, Sausalito, CA USA. [Carlin, Kevin P.] Natl Marine Mammal Fdn, San Diego, CA USA. [Almeida, Jonas S.] Univ Alabama Birmingham, Dept Pathol, Div Informat, Birmingham, AL 35294 USA. [Janech, Michael G.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. [Favre, Elizabeth G.] Med Univ S Carolina, Dept Anesthesia & Perioperat Med, Charleston, SC 29425 USA. RP Janech, MG (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. EM janechmg@musc.edu OI Neely, Benjamin/0000-0001-6120-7695; Janech, Michael/0000-0002-3202-4811 FU Office of Naval Research [N00014-08-1-0341] FX The authors would like to thank all of the staff and volunteers at the Marine Mammal Center, and especially Bill Van Bonn, for their expertise and assistance. We also thank the members of the US Navy Marine Mammal Program and National Marine Mammal Foundation, especially Cynthia Smith, for their help in acquiring samples. We wish to thank John Arthur for his critical comments and advice. We would also acknowledge the members of the Nephrology Proteomics Laboratory for their technical support, as well as Jennifer Bethard at the MUSC Mass Spectrometry Facility for her expertise. We also thank Guiseppe Cardillo for providing assistance in ROC curve calculations, and Paul Nietert for statistical consultation provided through the Clinical Translational Science Award program at MUSC. Funding for this work was provided by the Office of Naval Research (N00014-08-1-0341). NR 36 TC 7 Z9 7 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-5956 J9 PROTEOME SCI JI Proteome Sci. PD MAR 19 PY 2012 VL 10 AR 18 DI 10.1186/1477-5956-10-18 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 933QH UT WOS:000303376600001 PM 22429742 ER PT J AU Tompkins, RG AF Tompkins, Ronald G. TI Survival of children with burn injuries SO LANCET LA English DT Editorial Material ID ASSOCIATION/SHRINERS-HOSPITALS; QUESTIONNAIRE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Tompkins, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM rtompkins@partners.org FU NIGMS NIH HHS [P50 GM021700, U54 GM062119] NR 11 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAR 17 PY 2012 VL 379 IS 9820 BP 983 EP 984 DI 10.1016/S0140-6736(11)61626-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 911JE UT WOS:000301712300010 PM 22296811 ER PT J AU Cheng, CY Reich, D Haiman, CA Tandon, A Patterson, N Elizabeth, S Akylbekova, EL Brancati, FL Coresh, J Boerwinkle, E Altshuler, D Taylor, HA Henderson, BE Wilson, JG Kao, WHL AF Cheng, Ching-Yu Reich, David Haiman, Christopher A. Tandon, Arti Patterson, Nick Elizabeth, Selvin Akylbekova, Ermeg L. Brancati, Frederick L. Coresh, Josef Boerwinkle, Eric Altshuler, David Taylor, Herman A. Henderson, Brian E. Wilson, James G. Kao, W. H. Linda TI African Ancestry and Its Correlation to Type 2 Diabetes in African Americans: A Genetic Admixture Analysis in Three US Population Cohorts SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER RISK; INSULIN-RESISTANCE; ATHEROSCLEROSIS RISK; MULTIETHNIC COHORT; JACKSON HEART; SOCIOECONOMIC-STATUS; SUSCEPTIBILITY LOCI; DISEASE GENES; SENSITIVITY AB The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES), suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without) from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1) determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2) identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference = 1.6%, P<0.001). The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13-1.55), after adjustment for age, sex, study, body mass index (BMI), and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD = 4.0) and 13q14.3 (Z score = 4.5, P = 6.6x10(-6)). In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in diabetes risk. C1 [Cheng, Ching-Yu; Elizabeth, Selvin; Brancati, Frederick L.; Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. [Elizabeth, Selvin; Brancati, Frederick L.; Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Brancati, Frederick L.; Kao, W. H. Linda] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Cheng, Ching-Yu] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore. [Cheng, Ching-Yu] Natl Univ Singapore, Yong Loo Lin Sch Med, Saw Swee Hock Sch Publ Hlth, Singapore 117595, Singapore. [Cheng, Ching-Yu] Duke NUS Grad Med Sch, Singapore, Singapore. [Cheng, Ching-Yu] Singapore Eye Res Inst, Singapore, Singapore. [Reich, David; Tandon, Arti] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Reich, David; Tandon, Arti; Patterson, Nick; Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Akylbekova, Ermeg L.] Jackson State Univ, Jackson Heart Study Anal Grp, Jackson, MS USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Taylor, Herman A.] Jackson State Univ, Tougaloo Coll, Jackson, MS USA. RP Cheng, CY (reprint author), Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. EM wkao@jhsph.edu RI Cheng, Ching-Yu/K-7017-2013; Altshuler, David/A-4476-2009 OI Cheng, Ching-Yu/0000-0003-0655-885X; Altshuler, David/0000-0002-7250-4107 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HV-48195, R01-HL-084107, N01-HC-95170, N01-HC-95171, N01-HC-95172]; National Institute of Diabetes and Digestive and Kidney Diseases [R21DK073482, K01DK067207]; Center for Inherited Disease Research (CIDR); United States National Institutes of Health (NIH) [N01-HG-65403]; National Center on Minority Health and Health Disparities; National Cancer Institute [CA63464, CA54281]; Burroughs Wellcome Career Development Award in the Biomedical Sciences; NIH [U01-HG004168, P60DK079637] FX The ARIC Study was carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021 and N01-HC-55022, with support for this analysis by the National Institute of Diabetes and Digestive and Kidney Diseases R21DK073482 and K01DK067207 (WHLK). Genotyping for the ARIC study was carried out by the Johns Hopkins University under federal contract number (N01-HV-48195) from the NHLBI and by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the United States National Institutes of Health (NIH) to the Johns Hopkins University, Contract Number N01-HG-65403. Research support for JHS studies was provided by R01-HL-084107 (JGW) from the NHLBI and contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172 from the NHLBI and the National Center on Minority Health and Health Disparities. The MEC Study was supported by the National Cancer Institute grants CA63464 and CA54281. DR is supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences and DR, NP and AT were supported by NIH grant U01-HG004168. FB was supported by NIH grant P60DK079637. The funding sources played no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 58 TC 26 Z9 26 U1 0 U2 2 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 16 PY 2012 VL 7 IS 3 AR e32840 DI 10.1371/journal.pone.0032840 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 932RV UT WOS:000303309100015 PM 22438884 ER PT J AU Kawada-Matsuo, M Mazda, Y Oogai, Y Kajiya, M Kawai, T Yamada, S Miyawaki, S Oho, T Komatsuzawa, H AF Kawada-Matsuo, Miki Mazda, Yusuke Oogai, Yuichi Kajiya, Mikihito Kawai, Toshihisa Yamada, Sakuo Miyawaki, Shouichi Oho, Takahiko Komatsuzawa, Hitoshi TI GlmS and NagB Regulate Amino Sugar Metabolism in Opposing Directions and Affect Streptococcus mutans Virulence SO PLOS ONE LA English DT Article ID SURFACE PROTEIN ANTIGEN; ESCHERICHIA-COLI; COORDINATED REGULATION; ORAL STREPTOCOCCI; GENE-EXPRESSION; FAMILY ADHESINS; ACID TOLERANCE; BINDING; MECHANISMS; IDENTIFICATION AB Streptococcus mutans is a cariogenic pathogen that produces an extracellular polysaccharide (glucan) from dietary sugars, which allows it to establish a reproductive niche and secrete acids that degrade tooth enamel. While two enzymes (GlmS and NagB) are known to be key factors affecting the entrance of amino sugars into glycolysis and cell wall synthesis in several other bacteria, their roles in S. mutans remain unclear. Therefore, we investigated the roles of GlmS and NagB in S. mutans sugar metabolism and determined whether they have an effect on virulence. NagB expression increased in the presence of GlcNAc while GlmS expression decreased, suggesting that the regulation of these enzymes, which functionally oppose one another, is dependent on the concentration of environmental GlcNAc. A glmS-inactivated mutant could not grow in the absence of GlcNAc, while nagB-inactivated mutant growth was decreased in the presence of GlcNAc. Also, nagB inactivation was found to decrease the expression of virulence factors, including cell-surface protein antigen and glucosyltransferase, and to decrease biofilm formation and saliva-induced S. mutans aggregation, while glmS inactivation had the opposite effects on virulence factor expression and bacterial aggregation. Our results suggest that GlmS and NagB function in sugar metabolism in opposing directions, increasing and decreasing S. mutans virulence, respectively. C1 [Kawada-Matsuo, Miki; Mazda, Yusuke; Oogai, Yuichi; Komatsuzawa, Hitoshi] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Oral Microbiol, Kagoshima 890, Japan. [Mazda, Yusuke; Miyawaki, Shouichi] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Orthodont, Kagoshima 890, Japan. [Oho, Takahiko] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Prevent Dent, Kagoshima 890, Japan. [Kajiya, Mikihito; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Boston, MA USA. [Yamada, Sakuo] Kawasaki Med Univ, Dept Microbiol, Okayama, Japan. [Yamada, Sakuo] Kawasaki Med Welf, Dept Clin Nutr, Okayama, Japan. RP Kawada-Matsuo, M (reprint author), Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Oral Microbiol, Kagoshima 890, Japan. EM hkomatsu@dent.kagoshima-u.ac.jp NR 40 TC 14 Z9 14 U1 1 U2 8 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 16 PY 2012 VL 7 IS 3 AR e33382 DI 10.1371/journal.pone.0033382 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 932RV UT WOS:000303309100037 PM 22438919 ER PT J AU Ofengeim, D Shi, P Miao, BC Fan, J Xia, XF Fan, YB Lipinski, MM Hashimoto, T Polydoro, M Yuan, JY Wong, STC Degterev, A AF Ofengeim, Dimitry Shi, Peng Miao, Benchun Fan, Jing Xia, Xiaofeng Fan, Yubo Lipinski, Marta M. Hashimoto, Tadafumi Polydoro, Manuela Yuan, Junying Wong, Stephen T. C. Degterev, Alexei TI Identification of Small Molecule Inhibitors of Neurite Loss Induced by A beta peptide using High Content Screening SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY; RHOA INHIBITION; NSAID USE; PROTEIN; MEMORY; NAPROXEN; MICE AB Multiple lines of evidence indicate a strong relationship between A beta peptide-induced neurite degeneration and the progressive loss of cognitive functions in Alzheimer disease (AD) patients and in AD animal models. This prompted us to develop a high content screening assay (HCS) and Neurite Image Quantitator (NeuriteIQ) software to quantify the loss of neuronal projections induced by A beta peptide neurons and enable us to identify new classes of neurite-protective small molecules, which may represent new leads for AD drug discovery. We identified thirty-six inhibitors of A beta-induced neurite loss in the 1,040-compound National Institute of Neurological Disorders and Stroke (NINDS) custom collection of known bioactives and FDA approved drugs. Activity clustering showed that non-steroidal anti-inflammatory drugs (NSAIDs) were significantly enriched among the hits. Notably, NSAIDs have previously attracted significant attention as potential drugs for AD; however their mechanism of action remains controversial. Our data revealed that cyclooxygenase-2 (COX-2) expression was increased following A beta treatment. Furthermore, multiple distinct classes of COX inhibitors efficiently blocked neurite loss in primary neurons, suggesting that increased COX activity contributes to A beta peptide-induced neurite loss. Finally, we discovered that the detrimental effect of COX activity on neurite integrity may be mediated through the inhibition of peroxisome proliferator-activated receptor gamma(PPAR gamma) activity. Overall, our work establishes the feasibility of identifying small molecule inhibitors of A beta-induced neurite loss using the NeuriteIQ pipeline and provides novel insights into the mechanisms of neuroprotection by NSAIDs. C1 [Shi, Peng; Fan, Jing; Xia, Xiaofeng; Fan, Yubo; Wong, Stephen T. C.] Methodist Hosp, Res Inst, Dept Syst Med & Bioengn, Houston, TX 77030 USA. [Ofengeim, Dimitry; Lipinski, Marta M.; Yuan, Junying] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Miao, Benchun; Degterev, Alexei] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. [Hashimoto, Tadafumi; Polydoro, Manuela] Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Wong, STC (reprint author), Cornell Univ, Weill Cornell Med Coll, Ithaca, NY 14853 USA. EM alexei.degterev@tufts.edu FU National Institutes of Health [R01AG028928, NIH R01 LM009161]; John S Dunn Research Foundation; TT and WF Chao Family Foundation; Smith Family Award for Excellence in Biomedical Research FX This work was supported, in whole or in part, by National Institutes of Health Grants R01AG028928, NIH R01 LM009161, John S Dunn Research Foundation, TT and WF Chao Family Foundation (to S. T. C. W.), and Smith Family Award for Excellence in Biomedical Research (to A. D.). NR 30 TC 11 Z9 13 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 16 PY 2012 VL 287 IS 12 BP 8714 EP 8723 DI 10.1074/jbc.M111.290957 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912KV UT WOS:000301797800005 PM 22277654 ER EF