FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kim, KW Lee, JM Jeon, YS Kang, SE Baek, JH Han, JK Choi, BI Bang, YJ Kiefer, B Block, KT Ji, HJ Bauer, S Kim, C AF Kim, Kyung Won Lee, Jeong Min Jeon, Yong Sik Kang, Sung Eun Baek, Jee Hyun Han, Joon Koo Choi, Byung Ihn Bang, Yung-Jue Kiefer, Berthold Block, Kai Tobias Ji, Hyunjun Bauer, Simon Kim, Chin TI Free-breathing dynamic contrast-enhanced MRI of the abdomen and chest using a radial gradient echo sequence with K-space weighted image contrast (KWIC) SO EUROPEAN RADIOLOGY LA English DT Article DE Dynamic contrast-enhanced MRI; Radial MRI; Free-breathing; K-space; Perfusion ID TUBULIN POLYMERIZATION INHIBITOR; PROJECTION RECONSTRUCTION; DCE-MRI; LIVER; ANGIOGRAPHY; RESOLUTION; TUMORS AB To evaluate the feasibility of free-breathing, dynamic contrast-enhanced (DCE) MRI of the abdomen and thorax using the radial-gradient-echo sequence with k-space weighted image contrast (KWIC) reconstruction. Institutional review board approval was obtained. Fourteen patients underwent free-breathing radial DCE-MRI. Radial MRI yielded full-frame images by gridding all k-space data and time-resolved subframe images by using KWIC reconstruction technique. Using subframe KWIC images, voxel-wise perfusion maps were created. For comparison, the breath-hold conventional Cartesian 3D-gradient-echo sequence (VIBE) was also performed during the equilibrium phase. The image qualities of radial and conventional VIBE images were compared quantitatively and qualitatively. Radial DCE-MRI provided high spatial resolution (1.4 x 1.4 mm) and temporal resolution (4.1 s for subframe images) allowing voxel-wise perfusion mapping with negligible motion or streaking artefacts. There were no significant differences in SNR between full-frame radial images and conventional VIBE images (79.08 vs 74.80, P > 0.05). Overall image quality score of full-frame radial images was slightly lower than that of conventional VIBE images (3.88 +/- 0.59 vs. 4.31 +/- 0.97, P < 0.05), but provided clinically useful images. The free-breathing radial DCE-MRI can provide high spatial and temporal resolution while maintaining reasonably high image quality and thus is a feasible technique for DCE-MRI in the abdomen and thorax. aEuro cent Dynamic contrast-enhanced magnetic resonance imaging (DCE) MRI is important in oncological imaging aEuro cent Radial MRI with k-space weighted image contrast (KWIC) reconstruction offers potential improvements aEuro cent Radial DCE-MRI provides good image quality, reduced artefacts and high spatial/temporal resolution. C1 [Kim, Kyung Won; Lee, Jeong Min; Jeon, Yong Sik; Kang, Sung Eun; Baek, Jee Hyun; Han, Joon Koo; Choi, Byung Ihn] Seoul Natl Univ Hosp, Dept Radiol, Seoul 110744, South Korea. [Bang, Yung-Jue] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Kim, Kyung Won] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kiefer, Berthold; Block, Kai Tobias; Ji, Hyunjun; Bauer, Simon] Siemens Healthcare, Erlangen, Germany. [Kim, Chin] Chong Kun Dang Pharmaceut, Seoul, South Korea. [Lee, Jeong Min] Seoul Natl Univ, Coll Med, Dept Radiol, Seoul 110744, South Korea. [Lee, Jeong Min] Seoul Natl Univ, Coll Med, Inst Radiat Med, Seoul 110744, South Korea. RP Lee, JM (reprint author), Seoul Natl Univ, Coll Med, Dept Radiol, 28 Yeongon Dong, Seoul 110744, South Korea. EM jmsh@snu.ac.kr RI Bang, Yung Jue/J-2759-2012 FU National Research Foundation of Korea (NRF); Korean government [2011-0026127]; Korea Health and Medical Technology R&D Project, Ministry for Health, Welfare Family Affairs [A100895, A100265] FX This work was partly supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2011-0026127) and partly supported by grants of the Korea Health and Medical Technology R&D Project, Ministry for Health, Welfare & Family Affairs (A100895, A100265). We thank Bonnie Hami, M. A., for her editorial assistance. We also thank Peter Gall, PhD., for technical advice about Tissue4D software. Four coauthors (Berthold Kiefer, Kai Tobias Block, Hyunjun Ji, and Simon Bauer) are employees of Siemens Healthcare, and one coauthor (Chin Kim) is an employee of Chong Kun Dang Pharmaceuticals. Siemens Medical Systems provided the radial VIBE sequence as well as technical advice. We thank Chong Kun Dang Pharmaceuticals for allowing us to use MRI data of patients enrolled in their ongoing clinical trial (NCT01028859). NR 28 TC 23 Z9 23 U1 3 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD MAY PY 2013 VL 23 IS 5 BP 1352 EP 1360 DI 10.1007/s00330-012-2699-4 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 123YC UT WOS:000317427500025 PM 23187728 ER PT J AU Luo, H Zhang, LH Liu, XD Leung, FW Liu, ZG Wang, XP Xue, L Wu, KC Fan, DM Pan, YL Guo, XG AF Luo, Hui Zhang, Linhui Liu, Xiaodong Leung, Felix W. Liu, Zhiguo Wang, Xiangping Xue, Ling Wu, Kaichun Fan, Daiming Pan, Yanglin Guo, Xuegang TI Water exchange enhanced cecal intubation in potentially difficult colonoscopy. Unsedated patients with prior abdominal or pelvic surgery: a prospective, randomized, controlled trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLORECTAL-CANCER; INCOMPLETE COLONOSCOPY; SEDATION; IMMERSION; METAANALYSIS; PREVENTION; VETERANS; STANDARD AB Background: Colonoscopy is widely used for management of colorectal diseases. A history of abdominal or pelvic surgery is a well-recognized factor associated with difficult colonoscopy. Although water exchange colonoscopy (WEC) was effective in small groups of male U.S. veterans with such a history, its application in other cultural settings is uncertain. Objective: To investigate the application of WEC in such patients. Design: Prospective, randomized, controlled, patient-blinded study. Setting: Tertiary-care referral center in China. Patients: Outpatients with prior abdominal or pelvic surgery undergoing unsedated diagnostic, screening, or surveillance colonoscopy. Intervention: Patients were randomized to examination by either WEC or conventional air colonoscopy (AC). Main Outcome Measurements: Cecal intubation rate. Results: A total of 110 patients were randomized to the WEC (n = 55) or AC (n = 55) group. WEC significantly increased the cecal intubation rate (92.7% vs 76.4%; P = .033). The maximum pain scores (+/- standard deviation) were 2.1 +/- 1.8 (WEC) and 4.6 +/- 1.7 (AC), respectively (P < .001). Multivariate analysis showed that the colonoscopy method was the only independent predictor of failed colonoscopy (odds ratio 11.44, 95% confidence interval, 1.35-97.09). A higher proportion of patients examined by WEC would be willing to have a repeat unsedated colonoscopy (90.9% vs 72.7%, P = .013). Limitations: Single center; unblinded but experienced endoscopists. Conclusion: This randomized, controlled trial confirms that the water exchange method significantly enhanced cecal intubation in potentially difficult colonoscopy in unsedated patients with prior abdominal or pelvic surgery. The lower pain scores and higher proportion accepting repeat of the unsedated option suggest that WEC is promising. It may enhances compliance with colonoscopy in specific populations. (Clinical trial registration number: NCT01485133.) (Gastrointest Endosc 2013; 77:767-73.) C1 [Luo, Hui; Zhang, Linhui; Liu, Xiaodong; Liu, Zhiguo; Wang, Xiangping; Wu, Kaichun; Fan, Daiming; Pan, Yanglin; Guo, Xuegang] Fourth Mil Med Univ, Xijing Hosp Digest Dis, Xian 710032, Peoples R China. [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Xue, Ling] Jinan Mil Gen Hosp, Dept Cardiol, Jinan, Peoples R China. RP Guo, XG (reprint author), Fourth Mil Med Univ, Xijing Hosp Digest Dis, 169 Changle West Rd, Xian 710032, Peoples R China. OI liu, zhiguo/0000-0002-8485-7356 FU National Natural Science Foundation of China [81172288]; Science Foundation of the Ministry of Education; Technology Innovation Foundation of Xijing Hospital FX This work was supported in part by the National Natural Science Foundation of China (81172288). Y. Pan received support from the Science Foundation of the Ministry of Education. X. Guo received support from the Technology Innovation Foundation of Xijing Hospital. No other financial relationships relevant to this publication were disclosed. NR 28 TC 15 Z9 16 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2013 VL 77 IS 5 BP 767 EP 773 DI 10.1016/j.gie.2012.12.007 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 122XY UT WOS:000317353100015 PM 23394837 ER PT J AU Daglilar, ES Yoon, WJ Mino-Kenudson, M Brugge, WR AF Daglilar, Ebubekir S. Yoon, Won Jae Mino-Kenudson, Mari Brugge, William R. TI Controlled swine bile duct ablation with a bipolar radiofrequency catheter SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID HEPATOCELLULAR-CARCINOMA; SURGICAL RESECTION; ESOPHAGUS; PORCINE; LIVER; SIZE; VIVO AB Background: Radiofrequency (RF) power is capable of ablation of neoplastic tissue arising from Barrett's esophagus. Endoscopic catheter bipolar RF ablation is a new technique for ablation of neoplastic tissue in the bile duct. Objective: To determine the effect of RF power on bile duct and solid organ histology. Design: Nonsurvival animal study. Setting: Academic center. Patients: This study involved 4 Yorkshire farm swine. Intervention: After we made a midline laparotomy incision, a bipolar RF catheter was placed with 3 power (5, 7, 10 W) and voltage settings (66, 132, 190 V) in the bile duct and solid organs (liver, spleen, kidney, and pancreas). Gross and histologic examinations were performed. Main Outcome Measurements: Depth of ablation in the bile duct wall, characteristics of the ablation in the solid organs. Results: An endoscopic bipolar RF catheter produced incomplete (bile duct), patchy ablation (pancreas) with 5 watts, intramural (bile duct) or confluent ablation with 7 watts, and transmural (bile duct) ablation at 10 W. The depth of ablation in the bile duct was 0.9 +/- 0.3, 1.5 +/- 0.2, 2.3 +/- 0.6 mm at 5, 7, and 10 W, respectively (analysis of variance; P = .02). Histologic ablation was not achieved in the liver, although gross changes were seen. Limitations: Animal study, normal bile duct. Conclusion: RF energy applied to the bile duct or solid organs resulted in controlled ablation with a linear relationship between the depth of ablation in the bile duct and RF power. C1 [Daglilar, Ebubekir S.; Yoon, Won Jae; Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. FU RedPath, Inc. FX The radiofrequency ablation catheters were provided by Emcision Ltd. W. Brugge is a consultant for Xlumena and received grant support from RedPath, Inc. No other financial relationships relevant to this publication were disclosed. NR 11 TC 6 Z9 9 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2013 VL 77 IS 5 BP 815 EP 819 DI 10.1016/j.gie.2013.01.005 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 122XY UT WOS:000317353100022 PM 23582532 ER PT J AU Celik, C Bastu, E Abali, R Alpsoy, S Guzel, EC Aydemir, B Yeh, J AF Celik, Cem Bastu, Ercan Abali, Remzi Alpsoy, Seref Guzel, Eda Celik Aydemir, Birsen Yeh, John TI The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome SO GYNECOLOGICAL ENDOCRINOLOGY LA English DT Article DE Brachial artery flow mediated dilation; carotid intima-media thickness; copper; homocysteine; polycystic ovary syndrome ID CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS; ENDOTHELIUM; DEFICIENCY AB This study investigates copper (Cu) levels and vascular dysfunction in lean women with polycystic ovary syndrome (PCOS). 44 subjects with PCOS, diagnosed according to Rotterdam criteria, and 42 healthy subjects matched for body mass index and age. Comparison of serum Cu, homocysteine, carotid intima-media thickness (CIMT), brachial artery flow mediated dilation (FMD) was carried out between PCOS patients and the control group. Clinical study was done in Namik Kemal University School of Medicine. The CIMT and concentration of Cu in PCOS patients was significantly higher than the healthy controls. FMD levels in PCOS patients were significantly lower than those in controls. In PCOS patients, CIMT was correlated with estrogen and Cu levels. However, FMD was correlated with age and Cu levels. Among these contributing factors, Cu levels were correlated with a change in CIMT and FMD. CIMT and FMD in PCOS patients were related to Cu levels as well as several cardiovascular risk factors. Thus, increased Cu levels may be responsible for the increased risk of early vascular disease in women with PCOS. C1 [Celik, Cem; Abali, Remzi] Namik Kemal Univ, Fac Med, Dept Gynecol & Obstet, Tekirdag, Turkey. [Bastu, Ercan] Istanbul Univ, Fac Med, Dept Gynecol & Obstet, Istanbul, Turkey. [Alpsoy, Seref] Sakarya Univ, Fac Med, Dept Cardiol, Sakarya, Turkey. [Guzel, Eda Celik] Sakarya Univ, Fac Med, Dept Biophys, Sakarya, Turkey. [Aydemir, Birsen] Istanbul Univ, Cerrahpasa Fac Med, Dept Biophys, Istanbul, Turkey. [Yeh, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Celik, C (reprint author), Namik Kemal Univ, Fac Med, Dept Gynecol & Obstet, 100 Yil Mah Barbaros Cad,132, Tekirdag, Turkey. EM cemcel@yahoo.com NR 27 TC 6 Z9 6 U1 1 U2 12 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0951-3590 J9 GYNECOL ENDOCRINOL JI Gynecol. Endocrinol. PD MAY PY 2013 VL 29 IS 5 BP 488 EP 491 DI 10.3109/09513590.2013.774361 PG 4 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA 117MA UT WOS:000316956300020 PM 23480818 ER PT J AU Chien, WD Lin, HW Deschler, DG AF Chien, Wade Lin, Harrison W. Deschler, Daniel G. TI Serial suture ligation glossectomy for squamous cell carcinoma in the setting of a massive lymphovascular malformation SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE lymphovascular malformation; squamous cell carcinoma; oral cavity; suture ligation; cancer ID VASCULAR MALFORMATIONS; LYMPHANGIOMAS; HEMANGIOMAS; CHILDREN; CANCER; BASE; HEAD; NECK AB Background We describe a novel surgical technique for resection of squamous cell carcinoma in the setting of a massive tongue lymphovascular malformation (LVM). Methods and Results A 75-year-old man with a history of long-standing massive LVM of the tongue presented with a 4-cm squamous cell carcinoma of the involved oral tongue. Given the aberrant vascular anatomy of this lesion, traditional surgical treatment could not be undertaken. Therefore, serial suture ligation was performed over a 2-week period, allowing complete excision of the squamous cell carcinoma and a large portion of the tongue LVM with minimal morbidity. Return to preoperative functional status was likewise achieved. Conclusion Serial suture ligation glossectomy is a simple and effective technique for treating the uncommon case of squamous cell carcinoma of the tongue in the setting of a massive LVM. (c) 2012 Wiley Periodicals, Inc. Head Neck, 2013 C1 [Lin, Harrison W.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Lin, HW (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. EM harrison_lin@meei.harvard.edu NR 12 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAY PY 2013 VL 35 IS 5 BP E157 EP E160 DI 10.1002/hed.22010 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 122FQ UT WOS:000317304000005 PM 22307803 ER PT J AU Albers, CE Haefeli, PC Zimmermann, H de Moya, M Exadaktylos, AK AF Albers, C. E. Haefeli, P. C. Zimmermann, H. de Moya, M. Exadaktylos, A. K. TI Can handheld micropower impulse radar technology be used to detect pneumothorax? Initial experience in a European trauma centre SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Pneumothorax; Detection; Micropower impulse radar; Sensitivity; Specificity; Trauma centre; Preclinical; Quality control; Device performance; Thorax drain; Chest tube; MIR ID EXTENDED FOCUSED ASSESSMENT; EMERGENCY-DEPARTMENT; ULTRASOUND DETECTION; PHYSICAL-EXAMINATION; THORACIC SONOGRAPHY; BLUNT TRAUMA; CHEST TRAUMA; X-RAY; DIAGNOSIS; ULTRASONOGRAPHY AB Background: Pneumothoraces are a common injury pattern in emergency medicine. Rapid and safe identification can reduce morbidity and mortality. A new handheld, battery powered device, the Pneumoscan (CE 561036, PneumoSonics Inc., Cleveland, OH, USA), using micropower impulse radar (MIR) technology, has recently been introduced in Europe for the rapid and reliable detection of PTX. However, this technology has not yet been tested in trauma patients. This is the first quality control evaluation to report on emergency room performance of a new device used in the trauma setting. Material and methods: This study was performed at a Level I trauma centre in Switzerland. All patients with thoracic trauma and undergoing chest X-ray and CT-scan were eligible for the study. Readings were performed before the chest X-ray and CT scan. The patients had eight lung fields tested (four on each side). All readings with the Pneumoscan were performed by two junior residents in our department who had previously received an instructional tutorial of 15 min. The qualitative MIR results were blinded, and stored on the device. We then compared the results of the MIR to those of the clinical examination, chest X-ray and CT-scan. Results: 50 patients were included, with a mean age of 46 (SD 17) years. Seven patients presented with PTX diagnosed by CT; six of these were detected by Pneumoscan, leading to an overall sensitivity of 85.7 (95% confidence interval 42.1-99.6)%. Only two of seven PTX were found during clinical examination and on chest X-ray (sensitivity 28.6 (95% CI 3.7-71.0)%). Of the remaining 43 of 50 patients without PTX, one false-positive PTX was found by the Pneumoscan, resulting in a specificity of 97.7 (95% CI 87.7-99.9)%. Discussion: The Pneumoscan is an easy to use handheld technology with reliable results. In this series, the sensitivity to detect a PTX by the Pneumoscan was higher than by clinical examination and chest X-ray. Further studies with higher case numbers and a prospective study design are needed to confirm our findings. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Albers, C. E.; Haefeli, P. C.; Zimmermann, H.; Exadaktylos, A. K.] Univ Bern, Inselspital, Univ Hosp Bern, Dept Emergency Med, CH-3010 Bern, Switzerland. [Albers, C. E.; Haefeli, P. C.; Zimmermann, H.; Exadaktylos, A. K.] Univ Bern, CH-3010 Bern, Switzerland. [de Moya, M.] Massachusetts Gen Hosp, Div Trauma, Boston, MA 02114 USA. RP Exadaktylos, AK (reprint author), Univ Hosp Bern, Dept Emergency Med, Freiburgstr, CH-3010 Bern, Switzerland. EM christoph.albers@insel.ch; pascal.haefeli@insel.ch; heinz.zimmermann@insel.ch; mdemoya@partners.org; exadaktylos@exadaktylos.ch FU PneumoSonics Inc. (Cleveland, Ohio) FX Our unit has been equipped by the company with one hand held device. Some financial support was received by PneumoSonics Inc. (Cleveland, Ohio) towards a department based general trauma research grant. The company was not granted any intellectual properties of the data nor did the company have any rights to influence data selection, evaluation, or discussion. The company was not involved in drafting the paper. NR 25 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD MAY PY 2013 VL 44 IS 5 BP 650 EP 654 DI 10.1016/j.injury.2012.02.001 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 122VE UT WOS:000317345400015 PM 22385903 ER PT J AU Thase, ME Montgomery, S Papakostas, GI Bauer, M Trivedi, MH Svedsater, H Locklear, JC Gustafsson, U Datto, C Eriksson, H AF Thase, Michael E. Montgomery, Stuart Papakostas, George I. Bauer, Michael Trivedi, Madhukar H. Svedsaeter, Henrik Locklear, Julie C. Gustafsson, Urban Datto, Catherine Eriksson, Hans TI Quetiapine XR monotherapy in major depressive disorder: a pooled analysis to assess the influence of baseline severity on efficacy SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE atypical antipsychotic; extended-release quetiapine fumarate; major depressive disorder; monotherapy; severe depression; severity ID DOUBLE-BLIND; FUMARATE MONOTHERAPY; MILD DEPRESSION; ESCITALOPRAM; ANTIDEPRESSANTS; METAANALYSIS; TOLERABILITY; VENLAFAXINE; CITALOPRAM; EPISODE AB The efficacy of quetiapine XR was investigated in patients with major depressive disorder and differing levels of baseline severity. Pooled data from four placebo-controlled monotherapy studies of quetiapine XR (50-300 mg/day) were analyzed. Post-hoc analyses were carried out to assess change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) total score at endpoint (week 6 or 8) to week 1, and response (>= 50% reduction in MADRS total score) and remission (MADRS total scorer <= 10) rates at endpoint for all patients and six baseline severity cohorts (MADRS total score >= 24, >= 26, >= 28, >= 30, >= 32, and >= 34). In total, 1752 patients (all patients) were evaluated (MADRS score at baseline: >= 24, n= 1601; >= 26, n= 1467; >= 28, n= 1269; >= 30, n= 1038; >= 32, n= 745; and >= 34, n= 500). At endpoint, quetiapine XR reduced MADRS total score in all patients (P < 0.001) and each severity cohort (>= 24, >= 26, >= 28, >= 30, and >= 32, P < 0.001; >= 34, P < 0.01) versus placebo. Quetiapine XR also improved MADRS total score at week 1, response rates for each severity cohort, and remission rates in five out of six severity cohorts, versus placebo. Quetiapine XR monotherapy showed antidepressant effects in patients with major depressive disorder across different levels of baseline severity. Int Clin Psychopharmacol 28: 113-120 (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Thase, Michael E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Papakostas, George I.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Trivedi, Madhukar H.] UT Southwestern Med Ctr Dallas, Dept Psychiat, Dallas, TX USA. [Svedsaeter, Henrik; Locklear, Julie C.; Gustafsson, Urban; Eriksson, Hans] AstraZeneca, Wilmington, DE USA. [Datto, Catherine] AstraZeneca, Wilmington, DE USA. [Montgomery, Stuart] Univ London, Imperial Coll, London, England. [Bauer, Michael] Univ Hosp Carl Gustav Carus, Dept Psychiat & Psychotherapy, Dresden, Germany. RP Thase, ME (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3535 Market St, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU AstraZeneca FX The authors thank Simon Vass, PhD, from Complete Medical Communications, who provided medical writing support, funded by AstraZeneca. NR 33 TC 2 Z9 2 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD MAY PY 2013 VL 28 IS 3 BP 113 EP 120 DI 10.1097/YIC.0b013e32835fb971 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 115ZI UT WOS:000316850500001 PM 23485955 ER PT J AU de Miguel-Yanes, JM Porneala, B Pencina, MJ Fox, CS Florez, JC Siscovick, DS Dupuis, J Meigs, JB AF de Miguel-Yanes, Jose M. Porneala, Bianca Pencina, Michael J. Fox, Caroline S. Florez, Jose C. Siscovick, David S. Dupuis, Josee Meigs, James B. TI Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study SO JOURNAL OF HYPERTENSION LA English DT Article DE fasting glucose; Framingham; genes; genetic risk scores; hypertension; hypertension treatment; interaction test; single nucleotide polymorphisms; type 2 diabetes mellitus ID GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; CARDIOVASCULAR EVENTS; SUSCEPTIBILITY LOCI; THIAZIDE DIURETICS; GENETIC-VARIATION; HEART-DISEASE; FOLLOW-UP; MELLITUS; METAANALYSIS AB Objective: To test whether pancreatic beta-cell genetic frailty and hypertension (HTN) interact in their associations with change over time in fasting glucose (Delta FG) or type 2 diabetes mellitus (T2D) risk. Methods and results: We pooled data from 3471 Framingham Offspring Study participants into six similar to 4-year periods (15 852 person-examinations; mean age 52; 54% women). We defined two genetic exposures reflecting beta-cell genetic risk burden: single nucleotide polymorphism (SNP) score counts of fasting glucose-associated and T2D-associated risk alleles at 16 and 33 putative beta-cell loci, respectively; and three HTN exposures: HTN versus no-HTN; treated versus untreated HTN; and five mutually exclusive antihypertensive categories (beta-blockers, thiazides, renin-angiotensin system agents, combinations, others) versus untreated HTN. We tested similar to 4-year mean Delta FG or odds of T2D by per-risk allele score change and HTN category, seeking genetic score-by-HTN interaction. Genetic scores increased similar to 4-year Delta FG (0.6 mg/dl per-risk allele; P = 8.9 x 10(-16)) and T2D-risk (similar to 17% per-risk allele; P = 2.1 x 10(-7)). As compared to no-HTN, HTN conferred higher Delta FG (2.6 versus 1.7 mg/dl; P < 0.0001) and T2D-risk [odds ratio (OR) - 2.9, 95% confidence interval (CI) 2.8-3.0; P < 0.0001]. As compared to untreated HTN, treated HTN conferred higher Delta FG (3.4 versus 3.0 mg/dl; P < 0.0001) and T2D-risk (OR = 1.4, 95% CI 1.3-1.5; P = 0.02). Beta-blockers (OR = 1.6, 95% CI 1.1-2.4), combinations (OR = 1.6, 95% CI 1.1-2.5), and others (OR = 2.0, 95% CI 1.4-2.9) increased T2D-risk (all P < 0.02). In joint models including interaction terms, all genetic score-by-HTN interaction terms were P value greater than 0.05. In joint models without interaction, fasting glucose-SNP or T2D-SNP genetic scores (both P < 0.001) and HTN (P < 0.0001) independently increased Delta FG or T2D-risk. Conclusion: HTN, HTN treatment, and common fasting glucose-SNP genetic score/T2D-SNP genetic score independently predicted Delta FG and T2D incidence, but did not modify each other's association with Delta FG or T2D risk. C1 [de Miguel-Yanes, Jose M.] Univ Complutense Madrid, Hosp Gregorio Maranon, Madrid, Spain. [de Miguel-Yanes, Jose M.] Hosp Sureste, Madrid, Spain. [Porneala, Bianca; Meigs, James B.] Boston Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. [Pencina, Michael J.; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Fox, Caroline S.; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP de Miguel-Yanes, JM (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Dupuis, Josee/0000-0003-2871-3603 FU National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616, K24 DK080140]; Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health; Boston University School of Medicine; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affimetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center FX This study was supported by National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616 and K24 DK080140 and the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SHARe Project, itself supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract from Affimetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analyses (LinGA - II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. NR 48 TC 0 Z9 0 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD MAY PY 2013 VL 31 IS 5 BP 1001 EP 1009 DI 10.1097/HJH.0b013e32835f5a83 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 119RL UT WOS:000317115000023 PM 23425704 ER PT J AU Hartwell, KJ Maria, MMMS Twal, WO Shaftman, S DeSantis, SM McRae-Clark, AL Brady, KT AF Hartwell, Karen J. Maria, Megan M. Moran-Santa Twal, Waleed O. Shaftman, Stephanie DeSantis, Stacia M. McRae-Clark, Aimee L. Brady, Kathleen T. TI Association of elevated cytokines with childhood adversity in a sample of healthy adults SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Life stress; Biological stress; Innate immunity; Cytokines; C-reactive protein ID POSTTRAUMATIC-STRESS-DISORDER; C-REACTIVE PROTEIN; PITUITARY-ADRENAL AXIS; NECROSIS-FACTOR-ALPHA; EARLY-LIFE ADVERSITY; PSYCHOLOGICAL STRESS; TNF-ALPHA; PLASMA INTERLEUKIN-6; MAJOR DEPRESSION; MENTAL STRESS AB Objective: Childhood trauma has been associated adult stress-related disorders. However, little is known about physiologic alterations in adults with a history of early life trauma that do not have current psychiatric or medical diagnoses. In this study, the relationships between childhood adversity and cytokine and C-reactive protein (CRP) levels in healthy adults were examined. Method: Participants included men (n = 18) and women (n = 20) who did not meet DSM-IV criteria for Axis I psychiatric disorders or any major medical illness. Cytokine and CRP levels were obtained from baseline blood samples. Subjects completed the Early Trauma Inventory Self Report (ETI-SR). The primary outcomes included serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL1-beta), and CRP levels. In addition, the mean numbers of traumatic experiences (sexual, physical, emotional, general, and the summed total) were measured. Results: Significant positive associations were found between the total ETI score and IL-6 (p = 0.05), IL1-beta (p < 0.05), and TNF-alpha (p = 0.01). Significant positive correlations were found between the number of general traumas and IL1-beta (p < 0.05), TNF-alpha (p < 0.05), and IL-6 (p < 0.01). Neither the total number of traumas nor any of the trauma subscales were significantly associated with CRP levels. Conclusions: The positive association between childhood trauma and basal cytokine levels supports the extant literature demonstrating the long-term impact of childhood trauma and stress on homeostatic systems. Importantly, this association was found in healthy adults, suggesting that these alterations may precede the development of significant stress-related psychiatric disorder or disease. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Hartwell, Karen J.; Maria, Megan M. Moran-Santa; McRae-Clark, Aimee L.; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Neurosci, Clin Neurosci Div, Charleston, SC 29425 USA. [Hartwell, Karen J.; Brady, Kathleen T.] Ralph H Johnson VAMC, Charleston, SC 29401 USA. [Twal, Waleed O.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Shaftman, Stephanie; DeSantis, Stacia M.] Med Univ S Carolina, Dept Biostat & Epidemiol, Charleston, SC 29425 USA. RP Maria, MMMS (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Neurosci, Clin Neurosci Div, 125 Doughty St, Charleston, SC 29425 USA. EM moranm@musc.edu RI McRae-Clark, Aimee/I-3341-2013 OI McRae-Clark, Aimee/0000-0002-9774-318X FU NIDA [P50 DA016511-07]; NIH-NCRR [M01 RR01070-30]; Abbott; GlaxoSmithKline; Forest; Wyeth-Ayerst; Bristol-Myers Squibb; Eli Lilly; Shire FX Funding for this study was provided by NIDA P50 DA016511-07 and NIH-NCRR M01 RR01070-30. The NIDA and the NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.; Authors Hartwell, Moran-Santa Maria, Shaftman, Twal, and DeSantis have no relevant financial relationships with a commercial interest to disclose. Kathleen Brady has no current conflicts of interest. Past relationships include the following: Past Consultant: Pfizer, Eli Lilly, Abbott, GlaxoSmithKline, Forest, Ovation, Marinus, Novartis; Past Speakers' Bureau: Pfizer, Eli Lilly, Abbott, GlaxoSmithKline, Forest; Past Research Support: Abbott, GlaxoSmithKline, Forest, Wyeth-Ayerst; Past Scientific Advisory Board: Embera NeuroTherapeutics; Past Independent Contractor: Medscape; Past Investigator: Titan Pharmaceuticals. Aimee McRae-Clark has no current conflicts of interest. Past relationships include: Past Research Support: Bristol-Myers Squibb, Eli Lilly, Wyeth-Ayerst, Shire, and GlaxoSmithKline. NR 75 TC 17 Z9 18 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAY PY 2013 VL 47 IS 5 BP 604 EP 610 DI 10.1016/j.jpsychires.2013.01.008 PG 7 WC Psychiatry SC Psychiatry GA 124EU UT WOS:000317447400007 PM 23415658 ER PT J AU Ho, LL Sinha, A Verzi, M Bernt, KM Armstrong, SA Shivdasani, RA AF Ho, Li-Lun Sinha, Amit Verzi, Michael Bernt, Kathrin M. Armstrong, Scott A. Shivdasani, Ramesh A. TI DOT1L-Mediated H3K79 Methylation in Chromatin Is Dispensable for Wnt Pathway-Specific and Other Intestinal Epithelial Functions SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MIXED-LINEAGE LEUKEMIA; STEM-CELLS; HISTONE H3; TRANSCRIPTIONAL ELONGATION; LYSINE METHYLATION; MAMMALIAN-CELLS; IN-VIVO; DOT1L; GENE; EXPRESSION AB Methylation of H3K79 is associated with chromatin at expressed genes, though it is unclear if this histone modification is required for transcription of all genes. Recent studies suggest that Wnt-responsive genes depend particularly on H3K79 methylation, which is catalyzed by the methyltransferase DOT1L. Human leukemias carrying MLL gene rearrangements show DOT1L-mediated H3K79 methylation and aberrant expression of leukemogenic genes. DOT1L inhibitors reverse these effects, but their clinical use is potentially limited by toxicity in Wnt-dependent tissues such as intestinal epithelium. Genome-wide positioning of the H3K79me2 mark in Lgr5(+) mouse intestinal stem cells and mature intestinal villus epithelium correlated with expression levels of all transcripts and not with Wnt-responsive genes per se. Selective Dot1l disruption in Lgr5(+) stem cells or in whole intestinal epithelium eliminated H3K79me2 from the respective compartments, allowing genetic evaluation of DOT1L requirements. The absence of methylated H3K79 did not impair health, intestinal homeostasis, or expression of Wnt target genes in crypt epithelium for up to 4 months, despite increased crypt cell apoptosis. Global transcript profiles in Dot1l-null cells were barely altered. Thus, H3K79 methylation is not essential for transcription of Wnt-responsive or other intestinal genes, and intestinal toxicity is not imperative when DOT1L is rendered inactive in vivo. C1 [Ho, Li-Lun; Verzi, Michael; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ho, Li-Lun; Verzi, Michael; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Ho, Li-Lun; Verzi, Michael; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ho, Li-Lun; Verzi, Michael; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sinha, Amit; Bernt, Kathrin M.; Armstrong, Scott A.] Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Sinha, Amit; Bernt, Kathrin M.; Armstrong, Scott A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu RI Bernt, Kathrin/L-1826-2016 OI Bernt, Kathrin/0000-0002-5400-0482 FU National Institutes of Health [R01DK082889, R01CA140575, K01DK088868, RC2CA148222, P50CA127003] FX This work was supported by National Institutes of Health grants R01DK082889 (R.A.S.), R01CA140575 (S.A.A.), K01DK088868 (M.V.), RC2CA148222 (R.A.S. and S.A.A.), and P50CA127003. NR 58 TC 12 Z9 14 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2013 VL 33 IS 9 BP 1735 EP 1745 DI 10.1128/MCB.01463-12 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 121VS UT WOS:000317273300005 PM 23428873 ER PT J AU Li, J Li, X Liu, E Copeland, P Freudenreich, O Goff, DC Henderson, DC Song, XQ Fan, XD AF Li, Jie Li, Xue Liu, Emily Copeland, Paul Freudenreich, Oliver Goff, Donald C. Henderson, David C. Song, Xueqin Fan, Xiaoduo TI No effect of adjunctive, repeated dose intranasal insulin treatment on body metabolism in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Intranasal insulin; Schizophrenia; Body composition; Lipids ID RESTING ENERGY-EXPENDITURE; PIK3C3 PROMOTER VARIANT; FOOD-INTAKE; DIFFERENTIAL SENSITIVITY; INTRAVENTRICULAR INSULIN; GLUCOSE-TOLERANCE; WEIGHT-GAIN; BRAIN; OBESITY; MEN AB Objective: This study examined the effect of adjunctive intranasal insulin therapy on body metabolism in patients with schizophrenia. Method: Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder and had been on stable dose of antipsychotic agent for at least one month. In an 8-week randomized, double-blind, placebo-controlled study, subjects received either intranasal insulin (40 IU 4 times per day) or placebo. The whole body dual-energy X-ray absorptiometry (DXA) was used to assess body composition. Lipid particles were assessed using nuclear magnetic resonance (NMR) spectroscopy. All assessments were conducted at baseline, and repeated at week 8. Results: A total number of 39 subjects completed the study (18 in the insulin group, 21 in the placebo group). There were no significant differences between the two groups in week 8 changes for body weight, body mass index, waist circumference, as well as various measures of lipid particles (p's>0.100). The DXA assessment showed no significant differences between the two groups in week 8 changes for fat mass, lean mass or total mass (p's>0.100). Conclusion: In the present study, adjunctive therapy of intranasal insulin did not seem to improve body metabolism in patients with schizophrenia. The implications for future studies were discussed. (C) 2013 Elsevier B.V. All rights reserved. C1 [Li, Jie; Song, Xueqin; Fan, Xiaoduo] Univ Massachusetts, Sch Med, Psychot Disorders Program, UMass Mem Med Ctr, Worcester, MA 01605 USA. [Li, Jie] Tianjin Med Univ, Dept Psychiat, Tianjin, Peoples R China. [Li, Xue; Song, Xueqin] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou 450052, Peoples R China. [Liu, Emily] Partners Community Healthcare Inc, Haverhill, MA USA. [Copeland, Paul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Freudenreich, Oliver; Henderson, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schizophrenia Program, Boston, MA USA. [Goff, Donald C.] NYU, Sch Med, Dept Psychiat, New York, NY USA. RP Song, XQ (reprint author), Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Worcester, MA 01605 USA. EM xueqin.song@umassmed.edu; xiaoduo.fan@umassmed.edu FU National Institutes of Health [5K23MH082098]; NARSAD; National Institutes of Health, National Center for Research Resources General Clinical Research Centers Program (MGH Clinical Research Center) [M01-RR-01066, UL1 RR025758-01]; Eli Lilly and Company; Eli Lilly; AstraZeneca; Bristol-Myer-Squibb; Janssen; Pfizer; Cephalon; Bristol-Myers Squibb; Indevus Pharmaceuticals; H. Lundbeck; Schering-Plough; Takeda; Biovail; Sovay; Hoffman-La Roche; Cypress; Dainippon Sumitomo; Abbott Laboratories; Genentech; Novartis; PamLab; GlaxoSmithKline; Endo Pharmaceuticals; Solvay; Covance; Alkermis FX This study was supported by grant 5K23MH082098 from the National Institutes of Health (Dr. Fan), the NARSAD Young Investigator Award (Dr. Fan), grant M01-RR-01066 and grant UL1 RR025758-01 from the National Institutes of Health, National Center for Research Resources General Clinical Research Centers Program (MGH Clinical Research Center), and an investigator initiated trial grant from the Eli Lilly and Company (Dr. Fan).; Dr. Fan has received research support or honoraria from Eli Lilly, AstraZeneca, Bristol-Myer-Squibb, Janssen, and Pfizer. Dr. Freudenreich has received research support or honoraria from AstraZeneca, Bristol-Myer-Squibb, Janssen, Eli Lilly, Cephalon and Pfizer. Dr. Goff has received research support or honoraria from Bristol-Myers Squibb, Indevus Pharmaceuticals, H. Lundbeck, Schering-Plough, Eli Lilly, Takeda, Biovail, Sovay, Hoffman-La Roche, Cypress, Dainippon Sumitomo, Abbott Laboratories, Genentech, Pfizer, Janssen, Novartis, PamLab, and GlaxoSmithKline and Endo Pharmaceuticals. He served on a DSMB for Otsuka. Dr. Henderson has received research support or honoraria from Takeda, Janssen, Solvay, Novartis, Covance, Alkermis, and Pfizer. Dr. Copeland serves as a consultant for Sanofi. Drs. J Li, X Li, Liu, Song report no competing interests. NR 41 TC 3 Z9 3 U1 1 U2 6 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 MAY PY 2013 VL 146 IS 1-3 BP 40 EP 45 DI 10.1016/j.schres.2013.01.034 PG 6 WC Psychiatry SC Psychiatry GA 122RU UT WOS:000317336500007 PM 23434504 ER PT J AU Woodberry, KA McFarlane, WR Giuliano, AJ Verdi, MB Cook, WL Faraone, SV Seidman, LJ AF Woodberry, Kristen A. McFarlane, William R. Giuliano, Anthony J. Verdi, Mary B. Cook, William L. Faraone, Stephen V. Seidman, Larry J. TI Change in neuropsychological functioning over one year in youth at clinical high risk for psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Prodrome; Cognition; Longitudinal; Schizophrenia; Decline; PIER ID ASSERTIVE COMMUNITY TREATMENT; SMELL IDENTIFICATION TEST; 1ST EPISODE; FOLLOW-UP; 1ST-EPISODE SCHIZOPHRENIA; TEST-PERFORMANCE; INDIVIDUALS; GENETICS; PRODROME; PEOPLE AB Schizophrenia and related psychotic disorders are associated with significant neuropsychological (NP) impairments. Yet the onset and developmental evolution of these impairments remains incompletely characterized. This study examined NP functioning over one year in a sample of youth at clinical high risk (CHR) for psychosis participating in a treatment study. We assessed functioning across six cognitive domains at two time points in a sample of 53 CHR and 32 healthy comparison (HC) subjects. Linear regression of HC one-year scores was used to predict one-year performance for CHR from baseline scores and relevant demographic variables. We used raw scores and MANOVAs of the standardized residuals to test for progressive impairment over time. NP functioning of CHR at one year fell significantly below predicted levels. Effects were largest and most consistent for a failure of normative improvement on tests of executive function. CHR who reached the highest positive symptom rating (6, severe and psychotic) on the Structured Interview of Prodromal Syndromes after the baseline assessment (n=10/53) demonstrated a particularly large (d=-1.89), although non-significant, discrepancy between observed and predicted one-year verbal memory test performance. Findings suggest that, although much of the cognitive impairment associated with psychosis is present prior to the full expression of the psychotic syndrome, some progressive NP impairments may accompany risk for psychosis and be greatest for those who develop psychotic level symptoms. (C) 2013 Elsevier B.V. All rights reserved. C1 [Woodberry, Kristen A.; Giuliano, Anthony J.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA USA. [Woodberry, Kristen A.; Giuliano, Anthony J.; Seidman, Larry J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [McFarlane, William R.; Verdi, Mary B.; Cook, William L.] Maine Med Ctr, Dept Psychiat, Portland, ME 04102 USA. [Faraone, Stephen V.] SUNY Syracuse, Med Genet Res Ctr, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Syracuse, Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. RP Woodberry, KA (reprint author), Commonwealth Res Ctr, 75 Fenwood Rd, Boston, MA 02115 USA. EM kwoodber@bidmc.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU Sackler Scholar Programme in Psychobiology; Harvard Graduate Society Dissertation Completion Fellowship; Commonwealth Research Center of the Massachusetts Department of Mental Health [SCDMH82101008006]; NIMH [NIMH P50 MH080272-02, NIMH 1 U01 MH081928-01A1, RO1MH065367]; Sidney R. Baer Jr. Foundation; Robert Wood Johnson Foundation FX Kristen Woodberry was supported by the Sackler Scholar Programme in Psychobiology and a Harvard Graduate Society Dissertation Completion Fellowship. Kristen Woodberry, Anthony Giuliano, and Larry Seidman were also supported by the Commonwealth Research Center of the Massachusetts Department of Mental Health (SCDMH82101008006), NIMH funding to Larry Seidman, PI: (clinical core of NIMH P50 MH080272-02 [McCarley overall PI], NIMH 1 U01 MH081928-01A1), and the Sidney R. Baer Jr. Foundation. Mary Verdi, William Cook, and William McFarlane were supported by funding to the PIER program, William McFarlane, PI: (NIMH RO1MH065367) and the Robert Wood Johnson Foundation. NR 62 TC 10 Z9 11 U1 10 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2013 VL 146 IS 1-3 BP 87 EP 94 DI 10.1016/j.schres.2013.01.017 PG 8 WC Psychiatry SC Psychiatry GA 122RU UT WOS:000317336500014 PM 23434505 ER PT J AU Oribe, N Hirano, Y Kanba, S del Re, EC Seidman, LJ Mesholam-Gately, R Spencer, KM McCarley, RW Niznikiewicz, MA AF Oribe, Naoya Hirano, Yoji Kanba, Shigenobu del Re, Elisabetta C. Seidman, Larry J. Mesholam-Gately, Raquelle Spencer, Kevin M. McCarley, Robert W. Niznikiewicz, Margaret A. TI Early and late stages of visual processing in individuals in prodromal state and first episode schizophrenia: An ERP study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE EEG; Prodromal state; P300; N1; P1; Schizophrenia ID ULTRA-HIGH RISK; NEURAL ANOMALIES; P300 AMPLITUDE; PSYCHOSIS; SYMPTOMS; DEFICITS; SCALE AB Background: P300 deficits in schizophrenia patients are well established, especially in the auditory modality. Several studies have also reported P300 abnormalities in schizophrenia in visual tasks, but these findings are inconsistent. Furthermore, reports on P300 in visual modality in prodromal subjects are very limited. While P300 indexes relatively late and complex cognitive functions such as context updating in working memory, sensory-evoked components such as the P1/N1 primarily index early stages of perceptual processing. Several previous studies suggest that P300 reduction in schizophrenia patients may be dissociable from these earlier components. Therefore, in this study, we measured the P300 component as well as the P1/N1 in a visual odd-ball paradigm in prodromal subjects and first episode schizophrenia patients, and compared them with those of healthy controls. Method: Visual P300 and P1/N1 were obtained from prodromal (PRO, n=23), first episode schizophrenia patients (SZ, n=17), and healthy control subjects (HC, n=31), who silently counted infrequent target stimuli ("X") amid standard stimuli ("Y") presented on the screen while 64-channel EEG was recorded. Results: Both PRO and SZ subjects showed reduced P300 amplitudes and delayed P300 peak latencies in comparison to control subjects. On the other hand, N1 amplitude was significantly reduced only in SZ but not in PRO. Increased severity of positive symptoms was significantly associated with smaller P300 amplitude in PRO. Conclusions: These results suggest that visual P300 is affected already at the prodromal stage and could be a marker of the prodromal phase of schizophrenia. Published by Elsevier B. V. C1 [Oribe, Naoya; Hirano, Yoji; del Re, Elisabetta C.; Spencer, Kevin M.; McCarley, Robert W.; Niznikiewicz, Margaret A.] Harvard Univ, Clin Neurosci Div, VA Boston Healthcare Syst, Brockton Div,Dept Psychiat,Lab Neurosci,Med Sch, Brockton, MA 02301 USA. [Oribe, Naoya; Hirano, Yoji; Kanba, Shigenobu] Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Fukuoka 812, Japan. [Seidman, Larry J.; Mesholam-Gately, Raquelle] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Niznikiewicz, MA (reprint author), Boston VA Healthcare Syst, Brockton Div, Lab Neurosci, Dept Psychiat,Clin Neurosci Div, 940 Belmont St, Brockton, MA 02301 USA. EM Margaret_Niznikiewicz@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Spencer, Kevin/0000-0002-5500-7627 FU (Boston CIDAR) from National Institutes of Health [P50 MH080272, R01 MH40799]; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation [S2208]; Japan Society for the Promotion of Science [22791129]; Fund for Pharmacopsychiatry Research from SENSHIN Medical Research Foundation FX This work was supported in part by P50 MH080272 (Boston CIDAR, RWM PI) and R01 MH40799 (RWM) from National Institutes of Health; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation S2208 (SK) and Grant-in-Aid for Young Scientists B 22791129 (YH) from Japan Society for the Promotion of Science; Fund for Pharmacopsychiatry Research (YH) from SENSHIN Medical Research Foundation. NR 29 TC 9 Z9 10 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2013 VL 146 IS 1-3 BP 95 EP 102 DI 10.1016/j.schres.2013.01.015 PG 8 WC Psychiatry SC Psychiatry GA 122RU UT WOS:000317336500015 PM 23433503 ER PT J AU Romo-Nava, F Hoogenboom, WS Pelavin, PE Alvarado, JL Bobrow, H MacMaster, FP Keshavan, M McCarley, RW Shenton, ME AF Romo-Nava, F. Hoogenboom, W. S. Pelavin, P. E. Alvarado, J. L. Bobrow, H. MacMaster, F. P. Keshavan, M. McCarley, R. W. Shenton, M. E. TI Pituitary volume in schizophrenia spectrum disorders SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; First-episode; Schizotypal; Pituitary volume; MRI ID SCHIZOTYPAL PERSONALITY-DISORDER; FIRST EPISODE SCHIZOPHRENIA; ADRENAL AXIS FUNCTION; GRAY-MATTER VOLUME; LEFT TEMPORAL-LOBE; 1ST-EPISODE SCHIZOPHRENIA; GYRUS VOLUME; MRI ABNORMALITIES; NEGATIVE SYMPTOMS; PLANUM TEMPORALE AB Introduction: There is converging evidence supporting hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in schizophrenia spectrum disorders (SSD), such as schizotypal personality disorder (SPD), first-episode schizophrenia (FESZ) and chronic schizophrenia (CHSZ). Such an aberrant HPA activity might have volumetric consequences on the pituitary gland. However, previous magnetic resonance imaging (MRI) studies assessing pituitary volume (PV) in SSD are conflicting. The main objective of this study was to examine further PV in SSD. Methods: PV were manually traced on structural MRIs in 137 subjects, including subjects with SPD (n = 40), FESZ (n = 15), CHSZ (n = 15), and HC (n = 67). We used an ANCOVA to test PV between groups and gender while controlling for inter-subject variability in age, years of education, socioeconomic status, and whole brain volume. Results: Overall, women had larger PV than men, and within the male sample all SSD subjects had smaller PV than HC, statistically significant only for the SPD group. In addition, dose of medication, illness duration and age of onset were not associated with PV. Conclusion: Chronic untreated HPA hyperactivity might account for smaller PV in SPD subjects, whereas the absence of PV changes in FESZ and CHSZ patients might be related to the normalizing effects of antipsychotics on PV. SPD studies offer a way to examine HPA related alterations in SSD without the potential confounds of medication effects. Published by Elsevier B.V. C1 [Romo-Nava, F.; Hoogenboom, W. S.; Pelavin, P. E.; Alvarado, J. L.; Bobrow, H.; McCarley, R. W.; Shenton, M. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Romo-Nava, F.] Univ Nacl Autonoma Mexico, Fac Med, Dept Psiquiatria & Salud Mental, Mexico City 04510, DF, Mexico. [MacMaster, F. P.] Univ Calgary, Calgary, AB, Canada. [Keshavan, M.] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Hosp MMCH, Boston, MA 02115 USA. [McCarley, R. W.; Shenton, M. E.] Harvard Univ, Sch Med, VA Boston HealthCare Syst,Brockton Div, Clin Neurosci Div,Lab Neurosci,Dept Psychiat, Boston, MA 02115 USA. [Romo-Nava, F.] Inst Nacl Psiquiatria Dr Ramon de la Fuente, Clin Trastornos Afect, Mexico City, DF, Mexico. RP Shenton, ME (reprint author), Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02215 USA. EM shenton@bwh.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU US Department of Veterans Affairs; VA Schizophrenia Center; US National Institutes of Health [R01 MH050740, K05 MH070047, P50 MH080272-CIDAR, R01 MH040799, R01 MH052807, R01 MH064023] FX This work was supported, in part, by grants from the US Department of Veterans Affairs (Merit Review Awards to MES and RWM, and the VA Schizophrenia Center Grant to RWM and MES), the US National Institutes of Health (R01 MH050740 and K05 MH070047 to MES; P50 MH080272-CIDAR award to MES and RWM; R01 MH040799 and R01 MH052807 to RWM; and R01 MH064023 to MK), and the Cuthbertson and Fischer Chair in Paediatric Mental Health (to FPM). NR 53 TC 6 Z9 6 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2013 VL 146 IS 1-3 BP 301 EP 307 DI 10.1016/j.schres.2013.02.024 PG 7 WC Psychiatry SC Psychiatry GA 122RU UT WOS:000317336500045 PM 23522905 ER PT J AU Rissling, AJ Park, SH Young, JW Rissling, MB Sugar, CA Sprock, J Mathias, DJ Pela, M Sharp, RF Braff, DL Light, GA AF Rissling, Anthony J. Park, Sung-Hyouk Young, Jared W. Rissling, Michelle B. Sugar, Catherine A. Sprock, Joyce Mathias, Daniel J. Pela, Marlena Sharp, Richard F. Braff, David L. Light, Gregory A. TI Demand and modality of directed attention modulate "pre-attentive" sensory processes in schizophrenia patients and nonpsychiatric controls SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Attention; Event related potential; Modulation; Mismatch negativity; P300 ID EVENT-RELATED POTENTIALS; MISMATCH NEGATIVITY GENERATION; SELECTIVE-ATTENTION; TREATING SCHIZOPHRENIA; 1ST-EPISODE PSYCHOSIS; CLINICAL-TRIALS; TASK DEMANDS; HIGH-RISK; DEFICITS; BRAIN AB Background: Mismatch negativity(MNN) and P3a are event related potential (ERP) measures of early sensory information processing. These components are usually conceptualized as being "pre-attentive" and therefore immune to changes with variations in attentional functioning. This study aimed to determine whether manipulations of attention influence the amplitudes and latencies of MMN and P3a and, if so, the extent to which these early sensory processes govern concurrent behavioral vigilance performance in schizophrenia patients and normal subjects. Methods: Schizophrenia patients (SZ; n = 20) and Nonpsychiatric Control Subjects (NCS; n = 20) underwent auditory ERP testing to assess MMN and P3a across 4 EEG recording sessions in which attentional demand (low vs. high) and sensory modality of directed attention (visual vs. auditory) were experimentally varied. Results: Across conditions, SZ patients exhibited deficits in MMN and P3a amplitudes. Significant amplitude and latency modulation were observed in both SZ and NCS but there were no group-by-condition interactions. The amount of MMN amplitude attenuation from low-to high-demand tasks was significantly associated with increased vigilance performance in both SZ and NCS groups (r = -0.67 and r = -0.60). Several other robust associations were also observed among neurophysiologic, clinical and cognitive variables. Conclusions: Attentional demand and modality of directed attention significantly influence the amplitude and latencies of "pre-attentive" ERP components in both SZ and NCS. Deficits in MMN and P3a were not "normalized" when attention was directed to the auditory stimuli in schizophrenia patients. The adaptive modulation of early sensory information processing appears to govern concurrent attentional task performance. The temporal window reflecting automatic sensory discrimination as indexed as MMN and P3a may serve as a gateway to some higher order cognitive operations necessary for psychosocial functioning. Published by Elsevier B.V. C1 [Rissling, Anthony J.; Park, Sung-Hyouk; Young, Jared W.; Rissling, Michelle B.; Sprock, Joyce; Mathias, Daniel J.; Pela, Marlena; Sharp, Richard F.; Braff, David L.; Light, Gregory A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Park, Sung-Hyouk] Chookryoung Evangel Hosp, Dept Psychiat, Namyangju, Gyeonggi, South Korea. [Young, Jared W.; Sprock, Joyce; Mathias, Daniel J.; Pela, Marlena; Braff, David L.; Light, Gregory A.] VA San Diego Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, San Diego, CA USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. [Sugar, Catherine A.] Greater Los Angeles VA Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, Los Angeles, CA USA. RP Light, GA (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM glight@ucsd.edu FU National Institute of Mental Health [MH079777, MH042228, MH065571]; Department of Veteran Affairs (VISN 22 Mental Illness Research, Education, and Clinical Center); NARSAD FX This work was supported by the National Institute of Mental Health (MH079777, MH042228 and MH065571), the Department of Veteran Affairs (VISN 22 Mental Illness Research, Education, and Clinical Center) and NARSAD. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 99 TC 22 Z9 22 U1 2 U2 16 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 MAY PY 2013 VL 146 IS 1-3 BP 326 EP 335 DI 10.1016/j.schres.2013.01.035 PG 10 WC Psychiatry SC Psychiatry GA 122RU UT WOS:000317336500049 PM 23490760 ER PT J AU Shores, M AF Shores, Molly TI TESTOSTERONE AT THE HEART OF DISEASE - THE ASSOCIATION BETWEEN TESTOSTERONE AND CARDIOVASCULAR EVENTS SO ANDROLOGY LA English DT Meeting Abstract C1 [Shores, Molly] Univ Washington, Seattle, WA 98195 USA. [Shores, Molly] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 J9 ANDROLOGY-US JI Andrology PD MAY PY 2013 VL 1 SU 2 SI SI BP 33 EP 33 PG 1 WC Andrology SC Endocrinology & Metabolism GA 116WD UT WOS:000316912900013 ER PT J AU Jarrett, RB Minhajuddin, A Kangas, JL Friedman, ES Callan, JA Thase, ME AF Jarrett, Robin B. Minhajuddin, Abu Kangas, Julie L. Friedman, Edward S. Callan, Judith A. Thase, Michael E. TI Acute phase cognitive therapy for recurrent major depressive disorder: Who drops out and how much do patient skills influence response? SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Depression; Cognitive therapy; Predictors; Patient skills; Response patterns; Attrition ID COLLABORATIVE RESEARCH-PROGRAM; BEHAVIORAL THERAPY; PRIVATE-PRACTICE; MOOD DISORDERS; NIMH-TREATMENT; PREDICTORS; INVENTORY; VARIABLES; ALLIANCE; PHARMACOTHERAPY AB Objective: The aims were to predict cognitive therapy (CT) noncompletion and to determine, relative to other putative predictors, the extent to which the patient skills in CT for recurrent major depressive disorder predicted response in a large, two-site trial. Method: Among 523 outpatients aged 18-70, exposed to 12-14 weeks of CT, 21.6% dropped out. Of the 410 completers, 26.1% did not respond. To predict these outcomes, we conducted logistic regression analyses of demographics, pre-treatment illness characteristics and psychosocial measures, and mid-treatment therapeutic alliance. Results: The 17-item Hamilton Rating Scale for Depression (HRSD17) scores at entry predicted dropout and nonresponse. Patients working for pay, of non-Hispanic white race, who were older, or had more education were significantly more likely to complete. Controlling for HRSD17, significant predictors of nonresponse included: lower scores on the Skills of Cognitive Therapy-Observer Version (SoCT-O), not working for pay, history of only two depressive episodes, greater pre-treatment social impairment. Mid-phase symptom reduction was a strong predictor of final outcome. Conclusions: These prognostic indicators forecast which patients tend to be optimal candidates for standard CT, as well as which patients may benefit from changes in therapy, its focus, or from alternate modalities of treatment. Pending replication, the findings underscore the importance of promoting patients' understanding and use of CT skills, as well as reducing depressive symptoms early. Future research may determine the extent to which these findings generalize to other therapies, providers who vary in competency, and patients with other depressive subtypes or disorders. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Jarrett, Robin B.; Kangas, Julie L.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Minhajuddin, Abu] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Friedman, Edward S.; Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Callan, Judith A.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15260 USA. [Thase, Michael E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Jarrett, RB (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Robin.Jarrett@UTSouthwestern.edu FU NCATS NIH HHS [KL2 TR000146, UL1 TR000005]; NIMH NIH HHS [R01 MH069619, K24 MH001571, R01 MH058356, R01 MH058397, R01 MH069618]; NINR NIH HHS [T32 NR008857] NR 50 TC 17 Z9 17 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD MAY PY 2013 VL 51 IS 4-5 BP 221 EP 230 DI 10.1016/j.brat.2013.01.006 PG 10 WC Psychology, Clinical SC Psychology GA 115RW UT WOS:000316830600006 PM 23485420 ER PT J AU Neuhaus, V Swellengrebel, CHJ Bossen, JKJ Ring, D AF Neuhaus, Valentin Swellengrebel, Christiaan H. J. Bossen, Jeroen K. J. Ring, David TI What are the Factors Influencing Outcome Among Patients Admitted to a Hospital With a Proximal Humeral Fracture? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID BODY-MASS INDEX; HIP FRACTURE; NONCARDIAC SURGERY; KNEE ARTHROPLASTY; CARDIAC EVENTS; RISK-FACTORS; MORTALITY; PREDICTORS; CARE; HEMIARTHROPLASTY AB Fracture of the proximal humerus is common in older patients during the decline of their physical health. Our purpose was to evaluate the association between specific risk factors in patients with fractures of the proximal humerus and any inpatient adverse events, mortality, and discharge to a short-term or long-term care facility. The National Hospital Discharge Survey (NHDS) provided estimates of all adult patients who were admitted to hospitals after fractures of the proximal humerus in the United States between 1990 and 2007. The influences of sex, age, days of care, diagnosis and procedures (based on ICD-9 codes) on inpatient adverse events and death, and discharge to a short-term or long-term care facility, were studied in bivariate and multivariable analyses. Among an estimated 867,282 patients admitted for proximal humerus fractures, 20% experienced adverse events, and 2.3% died in the hospital. Older age, concomitant femur and femoral neck fractures or head trauma, operative fracture care, congestive heart failure, and chronic alcoholism were associated with inpatient adverse events. Intubation, acute myocardial infarctions, malignancies, and skull fractures were associated with inpatient deaths. Older age, lower limb fractures, specific comorbidities (obesity, congestive heart failure, dementia), and inpatient adverse events (pneumonia, anemia treated with transfusion) were associated with discharges to short-term or long-term care facilities. Knowledge of risk factors for inpatient adverse events, mortality, and discharge to facilities can help make treatment decisions, improve overall care, discharge planning, and resource utilization for patients with proximal humeral fractures. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Neuhaus, Valentin; Swellengrebel, Christiaan H. J.; Bossen, Jeroen K. J.; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 35 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2013 VL 471 IS 5 BP 1698 EP 1706 DI 10.1007/s11999-013-2876-z PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 117NB UT WOS:000316959100043 PM 23456187 ER PT J AU Neuhaus, V King, J Hageman, MG Ring, DC AF Neuhaus, Valentin King, John Hageman, Michiel G. Ring, David C. TI Charlson Comorbidity Indices and In-hospital Deaths in Patients with Hip Fractures SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID EXCESS MORTALITY; TRAUMATIC INJURY; ELDERLY-PATIENTS; RISK; COMPLICATIONS; VALIDATION; PREDICTORS; COHORT; STABILIZATION; INFORMATION AB The Charlson Comorbidity Index (CCI) and its modifications are comorbidity-based measures that predict mortality. It was developed for patients without trauma and inconsistently predicted mortality and adverse events in several previous studies of patients with trauma. We therefore (1) determined whether the three different CCIs were predictors for in-hospital deaths in patients with hip fractures, (2) verified if the CCI mortality prediction had changed with time, (3) evaluated other predictors of in-hospital death in patients with hip fractures, and (4) determined if the CCI has predicted in-hospital adverse events. We retrospectively reviewed a nationwide probability sample survey, the National Hospital Discharge Survey. More than 6 million adult patients with hip fractures and their associated comorbidities were scored by the original 1987 CCI, the 1994 age-adjusted CCI, and the 2011 updated, reweighted CCI. The three mortality indices' predictive values and predictors of in-hospital adverse events were compared. For patients with hip fractures, all three CCI variations predicted in-hospital mortality. The receiver operating curves (ROC) of the models were less than 0.68, but they improved when we used statistical models that included age, sex, concomitant injuries, and other comorbidities not contained in the CCI models (ROC > 0.74). The age-adjusted CCI accuracy was slightly better than the other two CCIs. Adverse events during hospital stays were associated with a higher CCI, pertrochanteric fracture (versus transcervical), abdominal, chest, or head trauma, atrial fibrillation, multiple fractures, female sex, and longer hospital stays; however, the accuracy of this model was poor (ROC = 0.65). While all three CCI variations predicted in-hospital mortality in patients with hip fractures, other factors may be of value in patients with trauma. C1 [Neuhaus, Valentin; King, John; Hageman, Michiel G.; Ring, David C.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 NR 33 TC 33 Z9 35 U1 0 U2 6 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 MAY PY 2013 VL 471 IS 5 BP 1712 EP 1719 DI 10.1007/s11999-012-2705-9 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 117NB UT WOS:000316959100045 PM 23179125 ER PT J AU Kazer, MW Psutka, SP Latini, DM Bailey, DE AF Kazer, Meredith W. Psutka, Sarah P. Latini, David M. Bailey, Donald E., Jr. TI Psychosocial aspects of active surveillance SO CURRENT OPINION IN UROLOGY LA English DT Review DE anxiety; psychosocial disease burden; self-management; support; uncertainty ID RISK PROSTATE-CANCER; QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; MEN; UNCERTAINTY; MANAGEMENT; CARCINOMA; INTERVENTION; ACCEPTANCE; SELECTION AB Purpose of review To summarize the literature on psychosocial responses to active surveillance as well as educational and support strategies to promote adherence. Recent findings There are two prevalent responses among men undergoing active surveillance; anxiety and uncertainty. The education of a patient about low-risk prostate cancer as well as the inquiry by the physician into patient's priorities and goals with respect to their prostate cancer diagnosis provide opportunities to facilitate a collaborative relationship between the physician and the patient. Supplemental support services for men undergoing active surveillance, including support groups and Internet-based interventions continue to be researched in relation to their role in promoting adherence to active surveillance. Summary Active surveillance continues to remain a highly valued management approach for men with early stage prostate cancer. However, it is suggested that the psychosocial burden of living with prostate cancer plays a substantial role in adherence to active surveillance and outcomes of men with the disease. Effective clinician education and counseling, as well as the referral for supplemental support services must be implemented and documented in future research studies and clinical practice. C1 [Kazer, Meredith W.] Fairfield Univ, Sch Nursing, Fairfield, CT 06824 USA. [Psutka, Sarah P.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Bailey, Donald E., Jr.] Duke Univ, Sch Nursing, Duke Ctr Aging, Durham, NC USA. RP Kazer, MW (reprint author), Fairfield Univ, Sch Nursing, 1073 North Benson Rd Fairfield, Fairfield, CT 06824 USA. EM mkazer@fairfield.edu OI Latini, David/0000-0002-6161-4861 NR 35 TC 16 Z9 16 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD MAY PY 2013 VL 23 IS 3 BP 273 EP 277 DI 10.1097/MOU.0b013e32835eff24 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 118SP UT WOS:000317046400014 PM 23422588 ER PT J AU Macrae, F Ahnen, DJ AF Macrae, Finlay Ahnen, Dennis J. TI Acceleration in colorectal carcinogenesis: the hare, the tortoise or myth? SO GUT LA English DT Editorial Material ID MUTYH-ASSOCIATED POLYPOSIS; SURVEILLANCE COLONOSCOPY; COLON-CANCER; ADENOMAS C1 [Macrae, Finlay] Royal Melbourne Hosp, Dept Colorectal Med & Genet, Melbourne, Vic 3050, Australia. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver VA Med Ctr, Denver, CO USA. RP Macrae, F (reprint author), Royal Melbourne Hosp, Dept Colorectal Med & Genet, POB 2010, Melbourne, Vic 3050, Australia. EM Finlay.macrae@mh.org.au NR 20 TC 1 Z9 1 U1 0 U2 5 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 MAY PY 2013 VL 62 IS 5 BP 657 EP 659 DI 10.1136/gutjnl-2012-302880 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 117YV UT WOS:000316990200001 PM 22961679 ER PT J AU Thomas, MP Lieberman, J AF Thomas, Marshall P. Lieberman, Judy TI Live or let die: posttranscriptional gene regulation in cell stress and cell death SO IMMUNOLOGICAL REVIEWS LA English DT Review DE stress; apoptosis; pre-mRNA splicing; translation; miRNA ID ENDOPLASMIC-RETICULUM STRESS; MESSENGER-RNA DECAY; THIOREDOXIN-INTERACTING PROTEIN; INITIATION-FACTOR MODIFICATIONS; DNA-DAMAGE RESPONSE; TRANSLATION INITIATION; ER STRESS; MAMMALIAN-CELLS; HEAT-SHOCK; INDUCED APOPTOSIS AB Studies of the regulation of gene expression historically focused on transcription. However, during stress and apoptosis, profound gene expression changes occur more rapidly and globally than is possible by regulating transcription. Posttranscriptional changes in mRNA processing and translation in response to diverse stresses shut down most protein translation to conserve energy and lead to rapid remodeling of the proteome to promote repair. Pre-mRNA splicing and mRNA stability are fundamentally altered under some stress conditions. Stress pathways coordinate a cytoprotective repair response, while simultaneously initiating signaling that can ultimately trigger cell death. How the cell mediates the decision between repair and apoptosis is largely not understood. In some stresses, microRNAs may tip the balance. Here, we review what is known about posttranscriptional gene regulation during stress, focusing on what is still unknown and how new technologies might be used to understand what changes are most physiologically important in different forms of stress and death. C1 [Thomas, Marshall P.; Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Thomas, Marshall P.; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), 200 Longwood Ave,WAB 255, Boston, MA 02115 USA. EM judy.lieberman@childrens.harvard.edu RI Lieberman, Judy/A-2717-2015 NR 128 TC 16 Z9 17 U1 1 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD MAY PY 2013 VL 253 SI SI BP 237 EP 252 DI 10.1111/imr.12052 PG 16 WC Immunology SC Immunology GA 119DX UT WOS:000317078800017 PM 23550650 ER PT J AU Montgomery, AE Hill, LL Kane, V Culhane, DP AF Montgomery, Ann Elizabeth Hill, Lindsay L. Kane, Vincent Culhane, Dennis P. TI HOUSING CHRONICALLY HOMELESS VETERANS: EVALUATING THE EFFICACY OF A HOUSING FIRST APPROACH TO HUD-VASH SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article ID PSYCHIATRIC DISABILITIES; MENTAL-ILLNESS; INDIVIDUALS; COMMUNITY; SUPPORTS AB Rapidly placing homeless Veterans with severe mental illness into permanent housing is one important goal of the U.S. Department of Housing and Urban Development-Veterans Affairs Supportive Housing (HUD-VASH) program; however, no research has tested whether an explicit organizational alignment of this goal with revised practices could improve outcomes. A demonstration project initiated in 2010 to reform housing placement practices in a metropolitan area enabled researchers to compare an explicit Housing First programoffering immediate permanent housing without requiring treatment compliance, abstinence, or housing readinesswith a treatment-first program for 177 homeless Veterans. The Housing First initiative successfully reduced time to housing placement, from 223 to 35 days, housing retention rates were significantly higher among Housing First tenants, and emergency room use declined significantly among the Housing First cohort. The results suggest that a national Housing First model for the VA would be associated with improved outcomes for Veterans experiencing homelessness. C1 [Montgomery, Ann Elizabeth; Hill, Lindsay L.; Kane, Vincent; Culhane, Dennis P.] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Washington, DC USA. RP Montgomery, AE (reprint author), Natl Ctr Homelessness Vet, 4100 Chester Ave,Suite 201, Philadelphia, PA 19104 USA. EM montga@upenn.edu NR 14 TC 8 Z9 8 U1 0 U2 33 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD MAY PY 2013 VL 41 IS 4 BP 505 EP 514 DI 10.1002/jcop.21554 PG 10 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 113TW UT WOS:000316692600009 ER PT J AU Vassoler, FM McCarthy, DM White, SL Darnell, SB Sangrey, GR Schmidt, HD Bhide, PG Pierce, RC Sadri-Vakili, G AF Vassoler, F. M. McCarthy, D. M. White, S. L. Darnell, S. B. Sangrey, G. R. Schmidt, H. D. Bhide, P. G. Pierce, R. C. Sadri-Vakili, G. TI Alterations in the epigenome and BDNF expression in response to self-administration or in utero exposure to cocaine are heritable SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Darnell, S. B.; Sangrey, G. R.; Sadri-Vakili, G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Vassoler, F. M.; White, S. L.; Schmidt, H. D.; Pierce, R. C.] Univ Penn, Philadelphia, PA 19104 USA. [McCarthy, D. M.; Bhide, P. G.] Florida State Univ, Tallahassee, FL 32306 USA. NR 0 TC 0 Z9 0 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 19 EP 20 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700034 ER PT J AU Sakadzic, S Mandeville, ET Devor, A Yaseen, MA Musacchiia, JJ Gagnon, L Ayata, C Lo, EH Dale, AM Vinogradov, SA Boas, DA AF Sakadzic, S. Mandeville, E. T. Devor, A. Yaseen, M. A. Musacchiia, J. J. Gagnon, L. Ayata, C. Lo, E. H. Dale, A. M. Vinogradov, S. A. Boas, D. A. TI High resolution in vivo recordings of brain oxygen metabolism SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Sakadzic, S.; Mandeville, E. T.; Devor, A.; Yaseen, M. A.; Musacchiia, J. J.; Gagnon, L.; Ayata, C.; Lo, E. H.; Boas, D. A.] Massachusetts Gen Hosp, Charlestown, MA USA. [Devor, A.; Dale, A. M.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Vinogradov, S. A.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 47 EP 47 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700087 ER PT J AU Kaplan, JM AF Kaplan, J. M. TI Tuning the kinetics of synaptic responses: mechanisms regulating release kinetics in C. elegans SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Kaplan, J. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 55 EP 55 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700104 ER PT J AU Huillard, E Alberta, J Phillips, JJ Griveau, A Kho, A Kane, M Wong, M Chang, S Harrington, EP Israel, M Stiles, CD Rowitch, DR AF Huillard, E. Alberta, J. Phillips, J. J. Griveau, A. Kho, A. Kane, M. Wong, M. Chang, S. Harrington, E. P. Israel, M. Stiles, C. D. Rowitch, D. R. TI ID4 function Antagonizes Olig1 and Olig2 to suppress aggressive gliomagenesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Huillard, E.; Griveau, A.; Wong, M.; Chang, S.; Harrington, E. P.; Rowitch, D. R.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Huillard, E.; Griveau, A.; Wong, M.; Chang, S.; Harrington, E. P.; Rowitch, D. R.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Huillard, E.; Phillips, J. J.; Griveau, A.; Wong, M.; Chang, S.; Harrington, E. P.; Rowitch, D. R.] Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA USA. [Alberta, J.; Kane, M.; Stiles, C. D.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kho, A.] Childrens Hosp Informat Program, Boston, MA USA. [Israel, M.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Genet, Hanover, NH 03756 USA. [Israel, M.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pediat, Hanover, NH 03756 USA. [Huillard, E.] CNRS, CR ICM, UMR7225, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 101 EP 101 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700200 ER PT J AU Mayes, DA Rizvi, TA MIller, SJ Ciraolo, GM Stemmer-Rachamimov, AO Ratner, N AF Mayes, D. A. Rizvi, T. A. MIller, S. J. Ciraolo, G. M. Stemmer-Rachamimov, A. O. Ratner, N. TI Antioxidant rescue of Nf1/Ras-induced defects in myelin and vasculature SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Mayes, D. A.; Rizvi, T. A.; MIller, S. J.; Ciraolo, G. M.; Ratner, N.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Stemmer-Rachamimov, A. O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stemmer-Rachamimov, A. O.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 205 EP 205 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700464 ER PT J AU Paintlia, AS Paintlia, MK Singh, AK Singh, I AF Paintlia, A. S. Paintlia, M. K. Singh, A. K. Singh, I. TI Rho family GTPase inhibition protects immature oligodendrocytes against cytokine toxicity via PPAR-alfa dependent mechanism SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Paintlia, A. S.; Paintlia, M. K.; Singh, I.] Med Univ S Carolina, Charleston, SC USA. [Singh, A. K.] Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 206 EP 206 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700468 ER PT J AU Yu, J Zhu, H Gattoni-Celli, S Kindy, MS AF Yu, J. Zhu, H. Gattoni-Celli, S. Kindy, M. S. TI Pim-1 kinase inhibits pathological injury by promoting neuroprotective signaling SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Yu, J.; Zhu, H.; Gattoni-Celli, S.; Kindy, M. S.] Med Univ S Carolina, Charleston, SC USA. [Gattoni-Celli, S.; Kindy, M. S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 214 EP 214 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700487 ER PT J AU Khan, M Dhammu, TS Shunmugavel, A Paintlia, M Singh, AK Singh, I AF Khan, M. Dhammu, T. S. Shunmugavel, A. Paintlia, M. Singh, A. K. Singh, I. TI S-Nitrosoglutathione stimulates mediators of neurorepair following cerebral ischemia reperfusion injury in rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Khan, M.; Dhammu, T. S.; Shunmugavel, A.; Paintlia, M.; Singh, I.] Med Univ S Carolina, Charleston, SC 29425 USA. [Singh, A. K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 216 EP 216 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700493 ER PT J AU Joshi, SK Liu, XH Samagh, SP Lovett, DH Bodine, SC Kim, HT Feeley, BT AF Joshi, Sunil K. Liu, Xuhui Samagh, Sanjum P. Lovett, David H. Bodine, Sue C. Kim, Hubert T. Feeley, Brian T. TI mTOR regulates fatty infiltration through SREBP-1 and PPAR gamma after a combined massive rotator cuff tear and suprascapular nerve injury in rats SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE rotator cuff tear; fatty infiltration; Akt; mTOR signaling; SREBP-1; PPAR gamma ID ADIPOSE-TISSUE; MUSCLE ATROPHY; ANIMAL-MODEL; STEM-CELL; EXPRESSION; REPAIR; SUPRASPINATUS; ADIPOCYTE; RAPAMYCIN; GROWTH AB Rotator cuff tears (RCTs) are among the most common injuries seen in orthopedic patients. Chronic tears can result in the development of muscular atrophy and fatty infiltration. Despite the prevalence of RCTs, little is known about the underlying molecular pathways that produce these changes. Recently, we have shown that mammalian target of rapamycin (mTOR) signaling plays an important role in muscle atrophy that results from massive RCTs in a rat model. The purpose of this study was therefore to extend our understanding of mTOR signaling and evaluate its role in fatty infiltration after a combined tendon transection and suprascapular nerve denervation surgery. Akt/mTOR signaling was significantly increased and resulted in the up-regulation of two transcription factors: SREBP-1 and PPAR gamma. We also saw an increase in expression of adipogenic markers: C/EBP-alpha and FASN. Upon treatment with rapamycin, an inhibitor of mTOR, we observed a decrease in mTOR signaling, activity of transcription factors, and reduction in fatty infiltration. Therefore, our study suggests that mTOR signaling mediates rotator cuff fatty infiltration via SREBP-1 and PPAR gamma. Clinically, our finding may alter current treatment methods to address rotator cuff fatty infiltration. (c) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 724730, 2013 C1 [Joshi, Sunil K.; Liu, Xuhui; Lovett, David H.; Kim, Hubert T.; Feeley, Brian T.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Vet Affairs, San Francisco, CA 94153 USA. [Liu, Xuhui; Samagh, Sanjum P.; Kim, Hubert T.; Feeley, Brian T.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94153 USA. [Lovett, David H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94153 USA. [Bodine, Sue C.] Univ Calif Davis, Dept Physiol & Membrane Biol, Davis, CA 95616 USA. RP Feeley, BT (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Vet Affairs, 1500 Owens Ave, San Francisco, CA 94153 USA. EM feeleyb@orthosurg.ucsf.edu FU Orthopaedic Research & Education Foundation (OREF) FX Grant sponsor: Orthopaedic Research & Education Foundation (OREF). NR 40 TC 19 Z9 19 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2013 VL 31 IS 5 BP 724 EP 730 DI 10.1002/jor.22254 PG 7 WC Orthopedics SC Orthopedics GA 117RK UT WOS:000316970600010 PM 23239524 ER PT J AU Fiellin, DA McGinnis, KA Maisto, SA Justice, AC Bryant, K AF Fiellin, David A. McGinnis, Kathleen A. Maisto, Stephen A. Justice, Amy C. Bryant, Kendall TI Measuring Alcohol Consumption Using Timeline Followback in Non-Treatment-Seeking Medical Clinic Patients With and Without HIV Infection: 7-, 14-, or 30-day Recall SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID QUICK DRINKING SCREEN; VETERANS; INTOXICATION; INDIVIDUALS; ADHERENCE; INTERVIEW; DRINKERS; CARE AB Objective: The measurement of alcohol consumption is an essential component of research in patients at risk for or infected with HIV. Daily estimation measures such as the Timeline Followback (TLFB) have been validated, yet the optimal time window and its performance in non-treatment-seeking medical clinic subjects and among those with HIV are not known. Method: In 1,519 HIV-infected and 1,612 uninfected men receiving medical care in general medical or infectious disease clinics, we compared the association between 7-, 14-, and 30-day TLFB reports, obtained via telephone, of alcohol consumption using Spearman's correlation coefficients. To evaluate agreement between 7-, 14-, and 30-day reports of heavy episodic drinking, we evaluated percent agreement, sensitivity, and kappa statistics, considering 30-day report as the gold standard. Results: The estimated prevalence of heavy episodic drinking was progressively higher for longer TLFB intervals (7 days: 6.3%; 14 days: 8.0%; 30 days: 9.5%). Correlation coefficients with 30-day TLFB were higher for 14 days (.94) than for 7 days (.86) overall (p < .001) and among HIV-infected (.94 vs. .86, p < .001) and uninfected (.95 vs. .87, p < 001). Correlations were similar by HIV status. When considered overall and by HIV status, the sensitivity, percent agreement, and kappa statistics are better for heavy episodic drinking based on 14 days compared with 7 days. Conclusions: A TLFB for alcohol consumption of 14 days is preferable to 7 days for non-treatment-seeking patients in medical clinics with and without HIV infection when compared with 30 days. (J Stud. Alcohol Drugs, 74, 500-504, 2013) C1 [Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. [Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Publ Hlth, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [McGinnis, Kathleen A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Maisto, Stephen A.] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Bryant, Kendall] NIAAA, Bethesda, MD 90034 USA. RP Fiellin, DA (reprint author), Yale Univ, Sch Med, 367 Cedar St,POB 208093, New Haven, CT 06520 USA. EM david.fiellin@yale.edu OI Fiellin, David/0000-0002-4006-010X FU National Institute on Alcohol Abuse and Alcoholism [U10AA013566, U01AA020795, U01AA020790, U24AA020794] FX This research was supported by National Institute on Alcohol Abuse and Alcoholism Grants U10AA013566, U01AA020795, U01AA020790, and U24AA020794. The views are not those of the Department of Veterans Affairs or of the United States Government. NR 25 TC 4 Z9 4 U1 4 U2 11 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAY PY 2013 VL 74 IS 3 BP 500 EP 504 PG 5 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 113CR UT WOS:000316644300018 PM 23490581 ER PT J AU Saidi, RF Elias, N Hertl, M Kawai, T Cosimi, AB Ko, DSC AF Saidi, Reza F. Elias, Nahel Hertl, Martin Kawai, Tatsuo Cosimi, A. Benedict Ko, Dicken S. C. TI Urinary reconstruction after kidney transplantation: Pyeloureterostomy or ureteroneocystostomy SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Kidney transplantation; Urinary reconstruction; Complications ID RENAL-TRANSPLANTATION; UROLOGICAL COMPLICATIONS; EXTRAVESICAL URETERONEOCYSTOSTOMY; EXTERNAL URETERONEOCYSTOSTOMY; URETEROVESICAL ANASTOMOSIS; URETERAL COMPLICATIONS; EXPERIENCE; RECIPIENTS; URETEROURETEROSTOMY; URETEROSTOMY AB Purpose: Ureteroneocystostomy (UCN) is the most widely used urinary reconstruction technique during kidney transplantation. Disadvantages of this technique include a high incidence of hematuria and reflux, plus the potential for obstruction resulting from distal ureteral fibrosis. Pyeloureterostomy (PU) avoids these complications but increases the technical complexity. Methods: Between January 1990 and December 2005, 1066 adults patients underwent kidney transplantations; 768 patients (72.1%) had urinary reconstruction by PU and 298 (27.9%) underwent UNC. Results: Patients in the PU group underwent simultaneous ipsilateral native nephrectomy. The operative time was longer in the PU group compared with the UNC group: 210 +/- 36 min versus 182 +/- 24 min (P < 0.001). Overall surgical complications in the PU group were comparable to those in the UNC group (9.5% versus 12.3%). The urinary complication rate was also comparable in both groups: 3.2% (25 of 768) in the PU group and 5% (15 of 298) in the UNC group. However, urinary obstruction comprised 60% of urinary complications in the UNC group, compared with 32% in the PU group (P < 0.01). We treated most urinary complications non-operatively. However, 24% of patients (six of 25) in the PU group needed operative intervention or revision for ureteral reconstruction, compared with 46.6% (seven of 15) in the UNC group (P < 0.01). Conclusions: Pyeloureterostomy is a safe and effective method for urinary tract reconstruction in renal transplantation. Pyeloureterostomy should be part of every transplant surgeon's armamentarium. (C) 2013 Elsevier Inc. All rights reserved. C1 [Saidi, Reza F.] Univ Massachusetts, Sch Med, Dept Surg, Div Organ Transplantat, Worcester, MA 01655 USA. [Elias, Nahel; Hertl, Martin; Kawai, Tatsuo; Cosimi, A. Benedict; Ko, Dicken S. C.] Harvard Univ, Sch Med, Dept Surg, Transplantat Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Saidi, RF (reprint author), Univ Massachusetts, Sch Med, Dept Surg, Div Organ Transplantat, 55 Lake Ave North,S6-426, Worcester, MA 01655 USA. EM reza.saidi@umassmemorial.org NR 32 TC 2 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 1 PY 2013 VL 181 IS 1 BP 156 EP 159 DI 10.1016/j.jss.2012.05.043 PG 4 WC Surgery SC Surgery GA 115BX UT WOS:000316788400032 PM 22683078 ER PT J AU Subramanian, A Clapp, ML Hicks, SC Awad, SS Liang, MK AF Subramanian, Anuradha Clapp, Marissa L. Hicks, Stephanie C. Awad, Samir S. Liang, Mike K. TI Laparoscopic ventral hernia repair: Primary versus secondary hernias SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Hernia; Incisional hernia; Ventral hernia; Umbilical hernia; Epigatric hernia; Spigelian hernia; Laparoscopy; Laparoscopic; Recurrence ID INCISIONAL HERNIA; RECURRENCE; EXPERIENCE AB Background: Most studies regarding laparoscopic ventral hernia repair (LVHR) have merged primary hernias (PHs) and secondary (incisional) hernias (SHs) into one group of ventral hernias. This grouping could produce falsely favorable results for LVHR. Our objective was to review and compare the outcomes of laparoscopic repair of PHs and SHs. Methods: A retrospective chart review of patients from 2000 to 2010 identified the cases of LVHR at two affiliated institutions. The demographics, comorbidities, type of hernia (PH versus SH), and short- and long-term complications were analyzed. The postoperative pain, cosmetic satisfaction, and Activities Assessment Scale scores were assessed by telephone survey. Results: A total of 201 cases of LVHR were identified: 73 PHs (36%) and 128 SHs (64%). No difference was found in the mean age between the two groups. The PH group had a greater percentage of black patients (34% versus 14%; P < 0.05), and the SH group had a greater percentage of white patients (85% versus 65%; P < 0.05). More female patients had SHs (34% versus 14%; P < 0.05), and more male patients had PHs (86% versus 66%; P < 0.05). More patients in the SH group had chronic obstructive pulmonary disease (19% versus 7%; P < 0.05) and prostate disease (32% versus 9%; P < 0.05). Overall, the SHs were larger (37.9 +/- 4.9 cm(2) versus 11.5 +/- 1.9 cm(2); P < 0.01). No differences were found in early postoperative complications, including pneumonia, urinary tract infection, surgical site infection, and seromas between the two groups. However, those with SHs had a greater incidence of recurrence (16% versus 5%; P < 0.05) and mesh explantation (7% versus 0%; P < 0.05). The patients who also under went SH repairs had greater postoperative pain scores when followed up for a median of 25 mo than those who underwent PH repairs when followed up for a median of 24 mo (3.5 +/- 0.4 versus 1.8 +/- 0.4; P < 0.05). More patients in the SH group had chronic pain issues (26% versus 5%; P = 0.0003) and had lower satisfaction scores (7.5 +/- 0.3 versus 8.6 +/- 0.3; P < 0.05). Overall, the Activities Assessment Scale scores were not significantly different. Conclusions: Our data have demonstrated that PHs and SHs are different. LVHR of SHs is associated with increased recurrence, greater postoperative pain scores, chronic pain issues, and lower patient satisfaction scores. We recommend that future studies evaluate LVHR for PHs separate from those for SHs. Published by Elsevier Inc. C1 [Subramanian, Anuradha; Clapp, Marissa L.; Awad, Samir S.; Liang, Mike K.] Baylor Coll Med, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Hicks, Stephanie C.] Rice Univ, Dept Stat, Houston, TX 77251 USA. RP Liang, MK (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, 2002 Holcomble Blvd,OCL 112, Houston, TX 77030 USA. EM ml3@bcm.edu RI Liang, Mike/L-8493-2015 OI Hicks, Stephanie/0000-0002-7858-0231; Liang, Mike/0000-0001-7063-7291 NR 19 TC 12 Z9 12 U1 0 U2 8 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 MAY 1 PY 2013 VL 181 IS 1 BP E1 EP E5 DI 10.1016/j.jss.2012.06.028 PG 5 WC Surgery SC Surgery GA 115BX UT WOS:000316788400001 PM 22795342 ER PT J AU Watson, AMM Prasad, KM Klei, L Wood, JA Yolken, RH Gur, RC Bradford, LD Calkins, ME Richard, J Edwards, N Savage, RM Allen, TB Kwentus, J McEvoy, JP Santos, AB Wiener, HW Go, RCP Perry, RT Nasrallah, HA Gur, RE Devlin, B Nimgaonkar, VL AF Watson, A. M. M. Prasad, K. M. Klei, L. Wood, J. A. Yolken, R. H. Gur, R. C. Bradford, L. D. Calkins, M. E. Richard, J. Edwards, N. Savage, R. M. Allen, T. B. Kwentus, J. McEvoy, J. P. Santos, A. B. Wiener, H. W. Go, R. C. P. Perry, R. T. Nasrallah, H. A. Gur, R. E. Devlin, B. Nimgaonkar, V. L. TI Persistent infection with neurotropic herpes viruses and cognitive impairment SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Cognition; cytomegalovirus; HSV-1; HSV-2; schizophrenia ID ALZHEIMERS-DISEASE BRAINS; SIMPLEX-VIRUS; CYTOMEGALOVIRUS-INFECTION; SCHIZOPHRENIA PAARTNERS; PRINCIPAL-COMPONENTS; AFRICAN-AMERICANS; LINKAGE ANALYSIS; EXPLORE RISKS; TYPE-1; HERITABILITY AB Background. Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n = 1852). Method. Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens. Results. PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 x 10(-5) and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (beta = -0.25, p = 7.28 x 10(-10)). There were no significant interactions between exposure and group status. Conclusions. Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status. C1 [Watson, A. M. M.; Prasad, K. M.; Klei, L.; Wood, J. A.; Nimgaonkar, V. L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Yolken, R. H.] Johns Hopkins Univ, Sch Med, Stanley Div Dev Neurovirol, Baltimore, MD USA. [Gur, R. C.; Calkins, M. E.; Richard, J.; Gur, R. E.] Univ Penn, Dept Psychiat, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Gur, R. C.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Bradford, L. D.] Morehouse Sch Med, Dept Psychiat, Atlanta, GA 30310 USA. [Edwards, N.] Univ Tennessee, Coll Med, Dept Psychiat, Memphis, TN USA. [Savage, R. M.] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. [Allen, T. B.; McEvoy, J. P.] Duke Univ, John Umstead Hosp, Med Ctr, Butner, NC USA. [Kwentus, J.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [Santos, A. B.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Wiener, H. W.; Go, R. C. P.; Perry, R. T.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Nasrallah, H. A.] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. [Nasrallah, H. A.] Univ Cincinnati, Coll Med, Dept Behav Neurosci, Cincinnati, OH USA. [Devlin, B.; Nimgaonkar, V. L.] Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA USA. [Devlin, B.; Nimgaonkar, V. L.] Western Psychiat Inst & Clin, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Nimgaonkar, VL (reprint author), TDH, Room 441,3811 OHara St, Pittsburgh, PA 15213 USA. EM nimga@pitt.edu OI Prasad, Konasale/0000-0003-0245-1393 FU National Institute of Mental Health at the National Institute of Health [RO1] [MH66006, R01 MH66278, R01 MH-066049, R01MH66181-03, R01 MH66121, R01 MH066005, R01 MH66050, R01 MH66263, RO1 MH66004, K08 MH79364]; University of Mississippi; Eli Lilly; AstraZeneca; Pfizer; Bristol Meyers; Johnson Johnson; Takeda FX This work was supported by the National Institute of Mental Health at the National Institute of Health [RO1 grant numbers: MH66006 (L.D.B.), R01 MH66278 (B.D.), R01 MH-066049 (N.E.), R01MH66181-03 (R.C.P.G.), R01 MH66121 (R.E.G.), R01 MH066005 (J.K.), R01 MH66050 (J.P.M.), R01 MH66263 (V.L.N.), RO1 MH66004 (A.S.) and K08 MH79364 (M.E.C.).; Dr Kwentus receives grant support through collaborations of the University of Mississippi with Eli Lilly, AstraZeneca, Pfizer, Bristol Meyers, Johnson & Johnson and Takeda. NR 45 TC 10 Z9 10 U1 3 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAY PY 2013 VL 43 IS 5 BP 1023 EP 1031 DI 10.1017/S003329171200195X PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 119AC UT WOS:000317067800012 PM 22975221 ER PT J AU Morra, L Zade, D McGlinchey, RE Milberg, WP AF Morra, L. Zade, D. McGlinchey, R. E. Milberg, W. P. TI Normal aging and cognition: The unacknowledged contribution of cerebrovascular risk factors SO AGING NEUROPSYCHOLOGY AND COGNITION LA English DT Article DE Aging; Cognition; Cerebrovascular; Risk; Geriatric; Neuropsychology ID BLOOD-PRESSURE; WHITE-MATTER; OLDER-ADULTS; CARDIOVASCULAR RISK; VASCULAR RISK; UNITED-STATES; SELF-REPORT; DIFFERENTIAL VULNERABILITY; DOPAMINERGIC SYSTEM; WORKING-MEMORY AB Despite the widespread assumption that cognitive decline is an inherent part of the normal aging process, research suggests that part of the variance in age-related cognitive decline is attributable to modifiable factors common in geriatric populations such as cerebrovascular risk factors. We completed a literature search using Science Citation Index and evaluated the most cited articles from the last 10 years to determine the extent to which investigations of normal aging and cognition account for the influence of cerebrovascular risk factors. We found that the majority of the most frequently cited literature does not adequately account for the contribution of cerebrovascular risk factors and therefore, it is possible that many conclusions about normal aging and cognition are flawed or incomplete. Further investigation of the role of cerebrovascular risk factors in age-related cognitive decline is imperative to more accurately understand the effect of aging on cognition. C1 [Morra, L.; Zade, D.; McGlinchey, R. E.; Milberg, W. P.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA USA. [Morra, L.; Zade, D.; McGlinchey, R. E.; Milberg, W. P.] VA Boston Healthcare Syst, GRECC, Boston, MA USA. [Zade, D.; McGlinchey, R. E.; Milberg, W. P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Morra, L.] SUNY Binghamton, Dept Clin Psychol, Binghamton, NY USA. RP Morra, L (reprint author), SUNY Binghamton, Dept Psychol, POB 6000,Clearview Halll, Binghamton, NY 13902 USA. EM lmorra1@binghamton.edu RI McGlinchey, Regina/R-1971-2016 NR 79 TC 3 Z9 3 U1 1 U2 18 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1382-5585 J9 AGING NEUROPSYCHOL C JI Aging Neuropsychol. Cogn. PD MAY 1 PY 2013 VL 20 IS 3 BP 271 EP 297 DI 10.1080/13825585.2012.693905 PG 27 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 109CC UT WOS:000316341800002 ER PT J AU Kim, KY Cho, HJ Yu, SN Kim, SH Yu, HS Park, YM Mirkheshti, N Kim, SY Song, CS Chatterjee, B Ahn, SC AF Kim, Kwang-Youn Cho, Hyo-Jin Yu, Sun-Nyoung Kim, Sang-Hun Yu, Hak-Sun Park, Yeong-Min Mirkheshti, Nooshin Kim, So Young Song, Chung Seog Chatterjee, Bandana Ahn, Soon-Cheol TI Interplay of reactive oxygen species, intracellular Ca2+ and mitochondrial homeostasis in the apoptosis of prostate cancer cells by deoxypodophyllotoxin SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE DEOXYPODOPHYLLOTOXIN (DPT); APOPTOSIS; MITOCHONDRIAL MEMBRANE POTENTIAL (MMP); REACTIVE OXYGEN SPECIES (ROS); Ca2+OVERLOAD ID EARLY EVENT; HYPERPOLARIZATION; CHEMOTHERAPY; DYSFUNCTION; INDUCTION; DAMAGE AB The limited treatment option for recurrent prostate cancer and the eventual resistance to conventional chemotherapy drugs has fueled continued interest in finding new anti-neoplastic agents of natural product origin. We previously reported anti-proliferative activity of deoxypodophyllotoxin (DPT) on human prostate cancer cells. Using the PC-3 cell model of human prostate cancer, the present study reveals that DPT induced apoptosis via a caspase-3-dependent pathway that is activated due to dysregulated mitochondrial function. DPT-treated cells showed accumulation of the reactive oxygen species (ROS), intracellular Cai2+ surge, increased mitochondrial membrane potential (MMP, m), Bax protein translocation to mitochondria and cytochrome c release to the cytoplasm. This resulted in caspase-3 activation, which in turn induced apoptosis. The antioxidant N-acetylcysteine (NAC) reduced ROS accumulation, MMP and Cai2+ surge, on the other hand the Ca2+ chelator BAPTA inhibited the Cai2+ overload and MMP without affecting the increase of ROS, indicating that the generation of ROS occurred prior to Ca2+ flux. This suggested that both ROS and Cai2+ signaling play roles in the increased MMP via Cai2+-dependent and/or -independent mechanisms, since m elevation was reversed by NAC and BAPTA. This study provides the first evidence for the involvement of both ROS- and Cai2+-activated signals in the disruption of mitochondrial homeostasis and the precedence of ROS production over the failure of Ca2+ flux homeostasis. J. Cell. Biochem. 114: 11241134, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Kim, Kwang-Youn; Yu, Sun-Nyoung; Kim, Sang-Hun; Park, Yeong-Min; Ahn, Soon-Cheol] Pusan Natl Univ, Sch Med, Dept Microbiol & Immunol, Yangsan 626870, South Korea. [Cho, Hyo-Jin] Ajou Univ, Sch Med, Brain Dis Res Ctr, Suwon 443749, South Korea. [Yu, Hak-Sun] Pusan Natl Univ, Sch Med, Dept Parasitol, Yangsan 626870, South Korea. [Mirkheshti, Nooshin; Kim, So Young; Song, Chung Seog; Chatterjee, Bandana; Ahn, Soon-Cheol] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78245 USA. [Mirkheshti, Nooshin; Kim, So Young; Song, Chung Seog; Chatterjee, Bandana; Ahn, Soon-Cheol] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, San Antonio, TX 78245 USA. [Chatterjee, Bandana] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Ahn, Soon-Cheol] Pusan Natl Univ, Med Res Inst, Yangsan 626870, South Korea. RP Chatterjee, B (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM chatterjee@uthscsa.edu; ahnsc@pusan.ac.kr FU National Research Foundation of Korea (NRF) [2012R1A1A2022587]; US Department of Veterans Affairs [1I01BX000280]; Basic Science Research Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2012R1A1A2022587] FX Grant sponsor: National Research Foundation of Korea (NRF); Grant number: 2012R1A1A2022587; Grant sponsor: US Department of Veterans Affairs 1I01BX000280.; This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A2022587) and by a Merit Review grant (1I01BX000280) from the US Department of Veterans Affairs. B. C. is a VA Senior Research Career Scientist. NR 21 TC 18 Z9 18 U1 1 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY PY 2013 VL 114 IS 5 BP 1124 EP 1134 DI 10.1002/jcb.24455 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 108YL UT WOS:000316332200018 PM 23192945 ER PT J AU Brown, MC Drottar, M Benson, TE Darrow, K AF Brown, M. Christian Drottar, Marie Benson, Thane E. Darrow, Keith TI Commissural axons of the mouse cochlear nucleus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE auditory brainstem; inhibitory synapse; glycine; electron microscopy; binaural balance; multipolar cell ID AUDITORY-NERVE FIBERS; CONTRALATERAL SOUND; FUNCTIONAL-PROPERTIES; OLIVOCOCHLEAR BUNDLE; BINAURAL INTERACTION; CENTRAL PROJECTIONS; MULTIPOLAR CELLS; STELLATE CELLS; BRAIN-STEM; GUINEA-PIG AB The axons of commissural neurons that project from one cochlear nucleus to the other were studied after labeling with anterograde tracer. Injections were made into the dorsal subdivision of the cochlear nucleus in order to restrict labeling only to the group of commissural neurons that gave off collaterals to, or were located in, this subdivision. The number of labeled commissural axons in each injection was correlated with the number of labeled radiate multipolar neurons, suggesting radiate neurons as the predominant origin of the axons. The radiate commissural axons are thick and myelinated, and they exit the dorsal acoustic stria of the injected cochlear nucleus to cross the brainstem in the dorsal half, near the crossing position of the olivocochlear bundle. They enter the opposite cochlear nucleus via the dorsal and ventral acoustic stria and at its medial border. Reconstructions of single axons demonstrate that terminations are mostly in the core and typically within a single subdivision of the cochlear nucleus. Extents of termination range from narrow to broad along both the dorsoventral (i.e., tonotopic) and the rostrocaudal dimensions. In the electron microscope, labeled swellings form synapses that are symmetric (in that there is little postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons do not appear to include excitatory commissural axons that end in edge regions of the nucleus. Radiate commissural axons could mediate the broadband inhibition observed in responses to contralateral sound, and they may balance input from the two ears with a quick time course. J. Comp. Neurol. 521:16831696, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Brown, M. Christian; Drottar, Marie; Benson, Thane E.; Darrow, Keith] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Brown, M. Christian] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Darrow, Keith] Worcester State Univ, Dept Commun Sci & Disorders, Worcester, MA 01602 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM chris_brown@meei.harvard.edu FU National Institute of Deafness and Other Communication Disorders [DC01089] FX Grant sponsor: National Institute of Deafness and Other Communication Disorders; Grant number: DC01089 (to M.C.B.). NR 58 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 1 PY 2013 VL 521 IS 7 BP 1683 EP 1696 DI 10.1002/cne.23257 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 110DI UT WOS:000316421900013 PM 23124982 ER PT J AU Causse, M Peran, P Dehais, F Caravasso, CF Zeffiro, T Sabatini, U Pastor, J AF Causse, Mickael Peran, Patrice Dehais, Frederic Caravasso, Chiara Falletta Zeffiro, Thomas Sabatini, Umberto Pastor, Josette TI Affective decision making under uncertainty during a plausible aviation task: An fMRI study SO NEUROIMAGE LA English DT Article DE Reward and punishment; Dorsolateral prefrontal cortex; Risk-taking; Emotion; Aviation safety ID ANTERIOR CINGULATE CORTEX; PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; WORKLOAD ASSESSMENT; EXECUTIVE FUNCTIONS; RISK-TAKING; PERFORMANCE; BEHAVIOR; FLIGHT; VALIDATION AB In aeronautics, plan continuation error (PCE) represents failure to revise a flight plan despite emerging evidence suggesting that it is no longer safe. Assuming that PCE may be associated with a shift from cold to hot reasoning, we hypothesized that this transition may result from a large range of strong negative emotional influences linked with the decision to abort a landing and circle for a repeat attempt, referred to as a "go-around". We investigated this hypothesis by combining functional neuroimaging with an ecologically valid aviation task performed under contextual variation in incentive and situational uncertainty. Our goal was to identify regional brain activity related to the sorts of conservative or liberal decision-making strategies engaged when participants were both exposed to a financial payoff matrix constructed to bias responses in favor of landing acceptance, while they were simultaneously experiencing maximum levels of uncertainty related to high levels of stimulus ambiguity. Combined with the observed behavioral outcomes, our neuroimaging results revealed a shift from cold to hot decision making in response to high uncertainty when participants were exposed to the financial incentive. Most notably, while we observed activity increases in response to uncertainty in many frontal regions such as dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), less overall activity was observed when the reward was combined with uncertainty. Moreover, participants with poor decision making, quantified as a lower discriminability index d', exhibited riskier behavior coupled with lower activity in the right DLPFC. These outcomes suggest a disruptive effect of biased financial incentive and high uncertainty on the rational decision-making neural network, and consequently, on decision relevance. (C) 2013 Elsevier Inc. All rights reserved. C1 [Causse, Mickael; Dehais, Frederic] Univ Toulouse, Inst Super Aeronaut & Espace, Dept Math, F-31055 Toulouse 4, France. [Causse, Mickael; Peran, Patrice; Pastor, Josette] Fac Med Toulouse, INSERM, Imagerie Cerebrale & Handicaps Neurol UMR 825, F-31059 Toulouse, France. [Causse, Mickael; Peran, Patrice; Pastor, Josette] Univ Toulouse, UPS, CHU Purpan, Imagerie Cerebrale & Handicaps Neurol UMR 825, F-31059 Toulouse 9, France. [Peran, Patrice; Caravasso, Chiara Falletta; Sabatini, Umberto] IRCCS Santa Lucia Fdn, Dept Radiol, I-00149 Rome, Italy. [Zeffiro, Thomas] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. RP Causse, M (reprint author), Univ Toulouse, Inst Super Aeronaut & Espace, Dept Math, 10 Ave E Belin, F-31055 Toulouse 4, France. EM mickael.causse@isae.fr RI Peran, Patrice/N-7561-2015; OI Peran, Patrice/0000-0001-7200-0139; Dehais, frederic/0000-0003-0854-7919 NR 57 TC 9 Z9 9 U1 3 U2 41 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2013 VL 71 BP 19 EP 29 DI 10.1016/j.neuroimage.2012.12.060 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 106OM UT WOS:000316154400003 PM 23313780 ER PT J AU Katon, WJ Young, BA Russo, J Lin, EHB Ciechanowski, P Ludman, EJ Von Korff, MR AF Katon, Wayne J. Young, Bessie A. Russo, Joan Lin, Elizabeth H. B. Ciechanowski, Paul Ludman, Evette J. Von Korff, Michael R. TI Association of Depression With Increased Risk of Severe Hypoglycemic Episodes in Patients With Diabetes SO ANNALS OF FAMILY MEDICINE LA English DT Article DE depression; diabetes; hypoglycemia; mental health ID PROSPECTIVE COHORT; SELF-CARE; TYPE-2; COMPLICATIONS; INSULIN; SULFONYLUREAS; MORTALITY; DEMENTIA; MELLITUS; ADULTS AB PURPOSE Although psychosocial and clinical factors have been found to be associated with hypoglycemic episodes in patients with diabetes, few studies have examined the association of depression with severe hypoglycemic episodes. This study examined the prospective association of depression with risk of hypoglycemic episodes requiring either an emergency department visit or hospitalization. METHODS In a longitudinal cohort study, a sample of 4,117 patients with diabetes enrolled between 2000 and 2002 were observed from 2005 to 2007. Meeting major depression criteria on the Patient Health Questionnaire-9 was the exposure of interest, and the outcome of interest was an International Classification of Disease, Ninth Revision code for a hypoglycemic episode requiring an emergency department visit or hospitalization. Proportional hazard models were used to analyze the association of baseline depression and risk of one or more severe hypoglycemic episodes. Poisson regression was used to determine whether depression status was associated with the number of hypoglycemic episodes. RESULTS After adjusting for sociodemographic, clinical measures of diabetes severity, non-diabetes-related medical comorbidity, prior hypoglycemic episodes, and health risk behaviors, depressed compared with nondepressed patients who had diabetes had a significantly higher risk of a severe hypoglycemic episode (hazard ratio = 1.42, 95% CI, 1.03-1.96) and a greater number of hypoglycemic episodes (odds ratio = 1.34, 95% CI, 1.03-1.74). CONCLUSION Depression was significantly associated with time to first severe hypoglycemic episode and number of hypoglycemic episodes. Research assessing whether recognition and effective treatment of depression among persons with diabetes prevents severe hypoglycemic episodes is needed. C1 [Katon, Wayne J.; Russo, Joan; Ciechanowski, Paul] Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. [Young, Bessie A.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Kidney Res Inst, Seattle, WA USA. [Lin, Elizabeth H. B.; Ludman, Evette J.; Von Korff, Michael R.] Grp Hlth Res Inst, Seattle, WA USA. RP Katon, WJ (reprint author), 1959 NE Pacific St, Seattle, WA 98195 USA. EM wkaton@u.washington.edu FU Services Division of the National Institute of Mental Health [MH069741, MH073686] FX Supported by grants MH069741 (Katon) and MH073686 (Von Korff) from the Services Division of the National Institute of Mental Health. NR 28 TC 28 Z9 29 U1 0 U2 11 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD MAY-JUN PY 2013 VL 11 IS 3 BP 245 EP 250 DI 10.1370/afm.1501 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AI3WS UT WOS:000336796600010 PM 23690324 ER PT J AU McAllister, JW Cooley, WC Van Cleave, J Boudreau, AA Kuhlthau, K AF McAllister, Jeanne W. Cooley, W. Carl Van Cleave, Jeanne Boudreau, Alexy Arauz Kuhlthau, Karen TI Medical Home Transformation in Pediatric Primary Care-What Drives Change? SO ANNALS OF FAMILY MEDICINE LA English DT Article DE change, organizational; children with special health care needs; disabled children; medical home; practice-based research; primary care; transformation ID FAMILY-CENTERED CARE; HEALTH-CARE; COORDINATION; CHILDREN; NEEDS; QUALITY; INDEX AB PURPOSE The aim of this study was to characterize essential factors to the medical home transformation of high-performing pediatric primary care practices 6 to 7 years after their participation in a national medical home learning collaborative. METHODS We evaluated the 12 primary care practice teams having the highest Medical Home Index (MHI) scores after participation in a national medical home learning collaborative with current MHI scores, a clinician staff questionnaire (assessing adaptive reserve), and semistructured interviews. We reviewed factors that emerged from interviews and analyzed domains and subdomains for their agreement with MHI and adaptive reserve domains and subthemes using a process of triangulation. RESULTS At 6 to 7 years after learning collaborative participation, 4 essential medical home attributes emerged as drivers of transformation: (1) a culture of quality improvement, (2) family-centered care with parents as improvement partners, (3) team-based care, and (4) care coordination. These high-performing practices developed comprehensive, family-centered, planned care processes including flexible access options, population approaches, and shared care plans. Eleven practices evolved to employ care coordinators. Family satisfaction appeared to stem from better access, care, and safety, and having a strong relationship with their health care team. Physician and staff satisfaction was high even while leadership activities strained personal time. CONCLUSIONS Participation in a medical home learning collaborative stimulated, but did not complete, medical home changes in 12 pediatric practices. Medical home transformation required continuous development, ongoing quality improvement, family partnership skills, an attitude of teamwork, and strong care coordination functions. C1 [McAllister, Jeanne W.; Cooley, W. Carl] Crotched Mt Fdn, Ctr Med Home Improvement, Concord, NH 03301 USA. [Van Cleave, Jeanne; Boudreau, Alexy Arauz; Kuhlthau, Karen] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. RP McAllister, JW (reprint author), Crotched Mt Fdn, Ctr Med Home Improvement, 8 Low Ave,Ste 1, Concord, NH 03301 USA. EM mcallisterjeanne3@gmail.com FU Agency for Healthcare Research and Quality (AHRQ) [R18HS019157-01]; US Maternal and Child Health Bureau (USMCHB), Division for Children with Special Health Care Needs (CSHCN); state Title V Program; NIMH [K23MH083885, R25MH080916] FX This work was supported by Agency for Healthcare Research and Quality (AHRQ) grant R18HS019157-01 and in part by the US Maternal and Child Health Bureau (USMCHB), Division for Children with Special Health Care Needs (CSHCN). The medical home learning collaborative described herein was funded under a cooperative agreement with the USMCHB CSHCN. Participation of each practice team was supported by their state Title V Program dedicated to the care of CSHCN. Additional funding support included NIMH grant K23MH083885 and NIMH grant R25MH080916. NR 32 TC 14 Z9 14 U1 1 U2 12 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA SN 1544-1709 EI 1544-1717 J9 ANN FAM MED JI Ann. Fam. Med. PD MAY-JUN PY 2013 VL 11 SU 1 BP S90 EP S98 DI 10.1370/afm.1528 PG 9 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AI3XE UT WOS:000336798200013 PM 23690392 ER PT J AU Schalock, PC AF Schalock, Peter C. TI Pragmatism and the Evaluation of Metal Hypersensitivity Reactions SO DERMATITIS LA English DT Article ID IMPLANTS AB Evaluating patients with potential metal hypersensitivity reactions is challenging. Clear evidence-based guidelines based on randomized studies are lacking. A pragmatic approach to evaluation of these patients is useful due to this lack of evidence. Patch testing remains the gold standard for evaluating type IV reactions on the skin and is also likely the best test for metal reactions to implanted devices until more hard data is available. C1 [Schalock, Peter C.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schalock, PC (reprint author), Massachusetts Gen Hosp, Dept Dermatol, BAR622 55 Fruit St, Boston, MA 02114 USA. EM schalock.prof@gmail.com OI Schalock, Peter/0000-0001-8953-4639 NR 5 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1710-3568 EI 2162-5220 J9 DERMATITIS JI Dermatitis PD MAY-JUN PY 2013 VL 24 IS 3 BP 104 EP 105 DI 10.1097/DER.0b013e3182979762 PG 2 WC Dermatology SC Dermatology GA AG5LD UT WOS:000335459600002 PM 23665837 ER PT J AU Ambrosy, A Chioncel, O Vinereanu, D Bubenek, S Deleanu, D Filipescu, D Vaduganathan, M Greene, S Macarie, C Gheorghiade, M AF Ambrosy, A. Chioncel, O. Vinereanu, D. Bubenek, S. Deleanu, D. Filipescu, D. Vaduganathan, M. Greene, S. Macarie, C. Gheorghiade, M. TI The association between Triglycerides at admission and mortality in patients hospitalized for heart failure: an analysis of the RO-AHFS Registry SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Ambrosy, A.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Chioncel, O.; Bubenek, S.; Deleanu, D.; Filipescu, D.; Macarie, C.] Inst Cardiovasc Dis Prof Dr CC Iliescu, Bucharest, Romania. [Vinereanu, D.] Emergency Hosp Bucharest, Bucharest, Romania. [Vaduganathan, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greene, S.; Gheorghiade, M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2013 VL 12 SU 1 BP S298 EP S298 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC4KE UT WOS:000332489101410 ER PT J AU Chioncel, O Ambrosy, AP Vinereanu, D Bubenek, S Deleanu, D Petris, A Vaduganathan, M Greene, S Macarie, C Gheorghiade, M AF Chioncel, O. Ambrosy, A. P. Vinereanu, D. Bubenek, S. Deleanu, D. Petris, A. Vaduganathan, M. Greene, S. Macarie, C. Gheorghiade, M. TI The association between total cholesterol at admission and mortality in patients hospitalized for heart failure: an analysis of the RO-AHFS registry SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Chioncel, O.; Bubenek, S.; Deleanu, D.; Macarie, C.] Inst Cardiovasc Dis Prof Dr CC Iliescu, Bucharest, Romania. [Ambrosy, A. P.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Vinereanu, D.] Univ Bucharest, Bucharest, Romania. [Petris, A.] St Spiridon Univ Hosp, Iasi, Romania. [Vaduganathan, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Greene, S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gheorghiade, M.] NW Mem Hosp, Cardiovasc Inst, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2013 VL 12 SU 1 BP S297 EP S298 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC4KE UT WOS:000332489101409 ER PT J AU De Berardinis, B Zancla, B Magrini, L Gaggin, HK Salerno, G Cardelli, P Januzzi, JJ Di Somma, S AF De Berardinis, B. Zancla, B. Magrini, L. Gaggin, H. K. Salerno, G. Cardelli, P. Januzzi, J. J. Di Somma, S. TI In-hospital and 30 days predictive value of Worsening Renal Function (WRF) and Galectin 3 (Gal 3) in patients with acute heart failure in emergency department SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [De Berardinis, B.; Zancla, B.; Magrini, L.; Salerno, G.; Cardelli, P.; Di Somma, S.] Univ Roma La Sapienza, St Andrea Hosp, Fac Med 2, I-00185 Rome, Italy. [Gaggin, H. K.; Januzzi, J. J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2013 VL 12 SU 1 BP S201 EP S201 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC4KE UT WOS:000332489101006 ER PT J AU Mark, A Luis, G Robert, L Igor, P AF Mark, Arokiaraj Luis, Guerrero Robert, Levine Igor, Palacios TI A cardiac resynchronization therapy method to augment ventricular contraction using polymer based actuators and mitral regurgitation control devices over pacing wire- Investigational Results SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Mark, Arokiaraj] Pondicherry Inst Med Sci, Pondicherry, India. [Luis, Guerrero; Robert, Levine; Igor, Palacios] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2013 VL 12 SU 1 BP S73 EP S73 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC4KE UT WOS:000332489100275 ER PT J AU Matura, LA Mcdonough, A Carroll, DL AF Matura, L. A. Mcdonough, A. Carroll, D. L. TI Are predictors of health-related quality of life in pulmonary arterial hypertension different for women and men? SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Matura, L. A.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Mcdonough, A.] Univ Massachusetts, Lowell, MA USA. [Carroll, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2013 VL 12 SU 1 BP S85 EP S85 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC4KE UT WOS:000332489100325 ER PT J AU Shah, A Kraigher-Krainer, E Pieske, B Zile, M Voors, A Bransford, T Lefkowitz, M Packer, M Mcmurray, J Solomon, S AF Shah, A. Kraigher-Krainer, E. Pieske, B. Zile, M. Voors, A. Bransford, T. Lefkowitz, M. Packer, M. Mcmurray, J. Solomon, S. TI Relationship of NT-proBNP to systolic and diastolic function in HFpEF: Findings from the PARAMOUNT trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Shah, A.; Solomon, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kraigher-Krainer, E.; Pieske, B.] Med Univ Graz, Graz, Austria. [Zile, M.] Med Univ S Carolina, Charleston, SC USA. [Zile, M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Voors, A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Bransford, T.; Lefkowitz, M.] Novartis Pharmaceut, E Hanover, NJ USA. [Packer, M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Mcmurray, J.] Univ Glasgow, Div Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2013 VL 12 SU 1 BP S275 EP S276 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC4KE UT WOS:000332489101312 ER PT J AU Suter, T Gianni, L Krop, I Xu, N Smitt, M Dang, C AF Suter, T. Gianni, L. Krop, I. Xu, N. Smitt, M. Dang, C. TI Cardiac safety of trastuzumab emtansine (T-DM1), a novel cancer drug linking trastuzumab to a chemotherapeutic agent for early-stage HER2-positive breast cancer SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Suter, T.] Univ Hosp Bern, Swiss Cardiovasc Ctr, CH-3010 Bern, Switzerland. [Gianni, L.] San Raffaele Hosp IRCCS, Milan, Italy. [Krop, I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Xu, N.; Smitt, M.] Genentech Inc, San Francisco, CA 94080 USA. [Dang, C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2013 VL 12 SU 1 BP S101 EP S101 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC4KE UT WOS:000332489100390 ER PT J AU Swinnen, M Hermans, H Vandenwijngaert, S Pokreisz, P Caluwe, E Gillijns, H Van de Werf, F Bloch, KD Janssens, S AF Swinnen, M. Hermans, H. Vandenwijngaert, S. Pokreisz, P. Caluwe, E. Gillijns, H. Van de Werf, F. Bloch, K. D. Janssens, S. TI MicroRNA signatures in left ventricular hypertrophy SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Meeting Abstract C1 [Swinnen, M.; Hermans, H.; Vandenwijngaert, S.; Pokreisz, P.; Caluwe, E.; Gillijns, H.; Van de Werf, F.; Janssens, S.] Katholieke Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium. [Bloch, K. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bloch, K. D.] Harvard Univ, Sch Med, Dep Anesthesia Crit Care & Paine Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAY PY 2013 VL 12 SU 1 BP S59 EP S59 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC4KE UT WOS:000332489100220 ER PT J AU Camargo, CA Guana, A Wang, S Simons, FER AF Camargo, Carlos A., Jr. Guana, Adriana Wang, Sheldon Simons, F. Estelle R. TI Auvi-Q Versus EpiPen: Preferences of Adults, Caregivers, and Children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Epinephrine autoinjector; Adrenaline autoinjector; Auvi-Q; EpiPen; User preference; Anaphylaxis; Caregivers; Children; Adults; Allergy AB BACKGROUND: Auvi-Q is a novel epinephrine autoinjector (EAI) that provides audio and visual cues for patients at risk for life-threatening allergic reactions. OBJECTIVE: We tested the preference for Auvi-Q or EpiPen with regard to method of instruction, preference to carry, device size, and device shape. METHODS: This large, multicenter, simulated-use study evaluated whether adults (aged 18-65 years), caregivers (parents/guardians aged 18-65 years of children aged 5-17 years), and children (aged 11-17 years), with and without experience in using an EAI, had a preference for the current design of Auvi-Q or the current design of EpiPen. Participants were given a scenario that involved anaphylaxis and were instructed to simulate use of an EAI. They received and tested each device individually according to the randomization assignment. After testing both devices, they completed a survey to indicate their preference for Auvi-Q versus EpiPen. RESULTS: Among all 693 participants combined, Auvi-Q was preferred over EpiPen on all study end points (P < .001). For experienced and inexperienced participants in all 3 groups (adults, caregivers, and children), Auvi-Q was preferred over EpiPen for method of instruction, preference to carry, and device size (all P < .001). The preference for Auvi-Q device shape was not significant among experienced children (P = .10); however, it was significant for inexperienced children (P = .04) and highly significant for experienced and inexperienced adults and caregivers (P < .001). CONCLUSION: In this large multicenter, simulated-use study, Auvi-Q was preferred over EpiPen by experienced and inexperienced adults, caregivers, and children. (C) 2013 American Academy of Allergy, Asthma & Immunology C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Guana, Adriana; Wang, Sheldon] Sanofi US, US Med Affairs, Gen Therapeut, Bridgewater, MA USA. [Simons, F. Estelle R.] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada. [Simons, F. Estelle R.] Univ Manitoba, Dept Immunol, Winnipeg, MB, Canada. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Ste 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU Sanofi US FX We thank Jeff Butler (Sanofi US) and the Lieberman Research Group for assistance in conducting the study. We also thank Pieter van Bokhoven, PhD, of Excerpta Medica, funded by Sanofi US, for writing/editorial support. NR 17 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD MAY-JUN PY 2013 VL 1 IS 3 BP 266 EP + DI 10.1016/j.jaip.2013.02.004 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA V38WV UT WOS:000209374400008 PM 24565484 ER PT J AU Kohli, P Giugliano, RP AF Kohli, Payal Giugliano, Robert P. TI Low-Density Lipoprotein Lowering in 2013 by Nonstatin Agents: The Discovery and Development of Promising Novel Targeted Therapies SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Review DE dyslipidemia; hypercholesterolemia ID ESTER TRANSFER PROTEIN; SUBTILISIN/KEXIN TYPE 9; TRIGLYCERIDE TRANSFER PROTEIN; SINGLE-DOSE PHARMACOKINETICS; STATIN-INTOLERANT PATIENTS; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; B SYNTHESIS INHIBITOR; LAPLACE-TIMI 57; MONOCLONAL-ANTIBODY AB Dyslipidemia is a major risk factor for the development of coronary artery disease, a leading cause of morbidity and mortality worldwide. Lowering low-density lipoprotein (LDL) has significantly reduced the risk of death and other major cardiovascular events, and statins remain the therapy of choice. However, as some patients are limited by the side effects of statins, cannot achieve their target LDL on statin therapy, or have other abnormalities in their lipid profile, alternative agents are being developed. In this review, we highlight the major classes of novel nonstatin LDL-lowering agents that are currently in various stages of development. Although many hold great promise, the results of large Phase III trials will be needed to definitely establish the efficacy, safety, and clinical utility of these agents in the general population. C1 [Kohli, Payal; Giugliano, Robert P.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Kohli, Payal; Giugliano, Robert P.] Harvard Univ, Sch Med, Boston, MA USA. [Kohli, Payal] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org FU Amgen FX The author(s) declared a potential conflict of interest as follows: Both authors participated in the LAPLACE-TIMI 57 trial sponsored by Amgen. Dr Kohli has served on the advisory board for Daiichi-Sankyo. Dr Giugliano has received honoraria for consulting from Amgen, Regeneron, and Sanofi. NR 66 TC 1 Z9 1 U1 0 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 EI 1940-4034 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD MAY PY 2013 VL 18 IS 3 BP 199 EP 210 DI 10.1177/1074248413480270 PG 12 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 123YG UT WOS:000317428000002 PM 23580658 ER PT J AU Dutta, J El Fakhri, G Huang, C Petibon, Y Reese, T Li, QZ AF Dutta, Joyita El Fakhri, Georges Huang, Chuan Petibon, Yoann Reese, Timothy Li, Quanzheng TI Respiratory motion compensated pulmonary imaging using simultaneous PET-MR SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 [Dutta, Joyita; El Fakhri, Georges; Huang, Chuan; Petibon, Yoann; Reese, Timothy; Li, Quanzheng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol,Ctr Adv Med Imaging Sci,NMMI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2013 VL 54 SU 2 MA 45 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V40KY UT WOS:000209478700039 ER PT J AU Esfahani, S Heidari, P Sheth, R Mahmood, U AF Esfahani, Shadi Heidari, Pedram Sheth, Rahul Mahmood, Umar TI Non-invasive imaging of C-MET receptor for delineation of liver metastasis of colorectal cancer SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 [Esfahani, Shadi; Heidari, Pedram; Sheth, Rahul; Mahmood, Umar] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2013 VL 54 SU 2 MA 2 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V40KY UT WOS:000209478700003 ER PT J AU Huang, C Ackerman, J Petibon, Y Brady, T El Fakhri, G Ouyang, JS AF Huang, Chuan Ackerman, Jerome Petibon, Yoann Brady, Thomas El Fakhri, Georges Ouyang, Jinsong TI Real-time 3D motion tracking using MR micro-coils for PET imaging SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 [Huang, Chuan; Petibon, Yoann; Brady, Thomas; El Fakhri, Georges; Ouyang, Jinsong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Adv Med Imaging Sci,NMMI,Radiol, Boston, MA USA. [Ackerman, Jerome] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2013 VL 54 SU 2 MA 44 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V40KY UT WOS:000209478700038 ER PT J AU Li, H El Fakhri, G Li, QZ AF Li, Hao El Fakhri, Georges Li, Quanzheng TI Direct MAP estimation of attenuation sinogram using TOF PET emission data SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 [Li, Hao; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, NMMI, Ctr Adv Med Imaging Sci, Radiol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2013 VL 54 SU 2 MA 47 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V40KY UT WOS:000209478700041 ER PT J AU Pamarthy, S Bohnen, N Assaly, WB Gross, M Fig, L AF Pamarthy, Sarika Bohnen, Nicolaas Assaly, Wessam Bou Gross, Milton Fig, Lorraine TI MRI for correlative imaging of the nigrostriatal dopaminergic system: A guide for nuclear medicine physicians SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 [Pamarthy, Sarika; Bohnen, Nicolaas] Univ Michigan, Radiol Nucl Med, Ann Arbor, MI 48109 USA. [Assaly, Wessam Bou; Gross, Milton; Fig, Lorraine] US Dept Vet Affairs, Nucl Med, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2013 VL 54 SU 2 MA 1282 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V40KY UT WOS:000209478700103 ER PT J AU Angin, M King, M Addo, MM AF Angin, Mathieu King, Melanie Addo, Marylyn Martina TI New Tools to Expand Regulatory T Cells from HIV-1-infected Individuals SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Infection; Issue 75; Infectious Diseases; Medicine; Immunology; Virology; Cellular Biology; Molecular Biology; Lymphocytes; T-Lymphocytes; Regulatory; HIV; Culture Techniques; flow cytometry; cell culture; Treg expansion; regulatory T cells; CD4+T cells; Tregs; HIV-1; virus; HIV-1 infection; AIDS; clinical techniques AB CD4+ Regulatory T cells (Tregs) are potent immune modulators and serve an important function in human immune homeostasis. Depletion of Tregs has led to measurable increases in antigen-specific T cell responses in vaccine settings for cancer and infectious pathogens. However, their role in HIV-1 immuno-pathogenesis remains controversial, as they could either serve to suppress deleterious HIV-1-associated immune activation and thus slow HIV-1 disease progression or alternatively suppress HIV-1-specific immunity and thereby promote virus spread. Understanding and modulating Treg function in the context of HIV-1 could lead to potential new strategies for immunotherapy or HIV vaccines. However, important open questions remain on their role in the context of HIV-1 infection, which needs to be carefully studied. Representing roughly 5% of human CD4+ T cells in the peripheral blood, studying the Treg population has proven to be difficult, especially in HIV-1 infected individuals where HIV-1-associated CD4 T cell and with that Treg depletion occurs. The characterization of regulatory T cells in individuals with advanced HIV-1 disease or tissue samples, for which only very small biological samples can be obtained, is therefore extremely challenging. We propose a technical solution to overcome these limitations using isolation and expansion of Tregs from HIV-1-positive individuals. Here we describe an easy and robust method to successfully expand Tregs isolated from HIV-1-infected individuals in vitro. Flow-sorted CD3+ CD4+ CD25+ CD127(low) Tregs were stimulated with anti-CD3/anti-CD28 coated beads and cultured in the presence of IL-2. The expanded Tregs expressed high levels of FOXP3, CTLA4 and HELIOS compared to conventional T cells and were shown to be highly suppressive. Easier access to large numbers of Tregs will allow researchers to address important questions concerning their role in HIV-1 immunopathogenesis. We believe answering these questions may provide useful insight for the development of an effective HIV-1 vaccine. C1 [Angin, Mathieu; King, Melanie; Addo, Marylyn Martina] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. [Addo, Marylyn Martina] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Addo, MM (reprint author), Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. EM maddo@partners.org OI Angin, Mathieu/0000-0002-6867-4680 FU Elisabeth Glaser Pediatric AIDS Foundation (Pediatric HIV Vaccine Program) [MV-00-9-900-1429-0-00]; MGH/ECOR (Physician Scientist Development Award); NIH NIAID [KO8219 AI074405, AI074405-03S1]; Harvard University Center for AIDS Research (CFAR); NIH [P30 AI060354]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; FIC; OARBill & Melinda Gates Foundation; Terry and Susan Ragon Foundation FX This work was supported in part by research funding from the Elisabeth Glaser Pediatric AIDS Foundation (Pediatric HIV Vaccine Program Award MV-00-9-900-1429-0-00 to MMA), MGH/ECOR (Physician Scientist Development Award to MMA), NIH NIAID (KO8219 AI074405 and AI074405-03S1 to MMA), and the Harvard University Center for AIDS Research (CFAR), an NIH funded program (P30 AI060354) which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR. These studies were furthermore supported by the Bill & Melinda Gates Foundation and the Terry and Susan Ragon Foundation. NR 30 TC 1 Z9 2 U1 2 U2 5 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD MAY PY 2013 IS 75 AR UNSP e50244 DI 10.3791/50244 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36RE UT WOS:000209227700026 PM 23748671 ER PT J AU Rigotti, NA AF Rigotti, Nancy A. TI Smoking cessation in patients with respiratory disease: existing treatments and future directions SO LANCET RESPIRATORY MEDICINE LA English DT Review ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; SUSTAINED-RELEASE BUPROPION; NICOTINE REPLACEMENT THERAPY; AMERICAN THORACIC SOCIETY; RECEPTOR PARTIAL AGONIST; AIR-FLOW LIMITATION; CLINICAL-TRIAL; UNITED-STATES; GENERAL-PRACTICE AB Tobacco use is a leading cause of preventable death worldwide. Respiratory diseases, including chronic obstructive pulmonary disease (COPD) and lung cancer, account for a large proportion of tobacco-related deaths. Smoking cessation benefits almost all smokers, irrespective of the age at which they quit, making smoking cessation a core component of prevention and treatment of respiratory diseases. Evidence shows that psychosocial counselling and pharmacotherapy are effective smoking cessation methods and are most effective when used together. The first-line drugs licensed to aid smoking cessation (nicotine replacement therapy, bupropion, and varenicline) are effective in patients with COPD. Efforts are underway to improve the efficacy of existing treatments and increase the proportion of smokers who try to quit, and who use treatment when doing so. However, existing smoking cessation counselling and drugs are among the most cost-effective clinical preventive services available. Incorporation of such treatment into routine clinical practice is essential for provision of high-quality care to all patients, especially those with respiratory disease. C1 [Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nrigotti@partners.org NR 86 TC 17 Z9 18 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD MAY PY 2013 VL 1 IS 3 BP 241 EP 250 DI 10.1016/S2213-2600(13)70063-8 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AQ3JL UT WOS:000342688600021 PM 24429130 ER PT J AU Zeidan, A Zhuoxin, S Prebet, T Greenberg, P Juckett, M Smith, M Paietta, E Gabrilove, J Erba, H Gore, S Tallman, M AF Zeidan, A. Zhuoxin, S. Prebet, T. Greenberg, P. Juckett, M. Smith, M. Paietta, E. Gabrilove, J. Erba, H. Gore, S. Tallman, M. TI Application of the French Prognostic Score to assess overall survival in a US-based cohort of patients treated with azacitidine SO LEUKEMIA RESEARCH LA English DT Meeting Abstract C1 [Zeidan, A.; Gore, S.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Zhuoxin, S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Prebet, T.] Dept Hematol, Paris, France. [Prebet, T.] Aix Marseille Univ, Marseille, France. [Greenberg, P.] Stanford Univ, Ctr Canc, Div Hematol, Stanford, CA 94305 USA. [Juckett, M.] Univ Wisconsin, Oncol, Madison, WI USA. [Smith, M.] Cleveland Clin, Oncol, Cleveland, OH 44106 USA. [Paietta, E.] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA. [Gabrilove, J.] Mt Sinai Sch Med, Oncol, New York, NY USA. [Erba, H.] Univ Alabama Birmingham, Oncol, Birmingham, AL USA. [Tallman, M.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2013 VL 37 SU 1 MA P-124 BP S79 EP S80 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA V40RR UT WOS:000209496200171 ER PT J AU Corcoran, RB Cheng, KA Hata, AN Faber, AC Ebi, H Coffee, EM Greninger, P Brown, RD Godfrey, JT Cohoon, TJ Song, Y Lifshits, E Shioda, T Dias-Santagata, D Singh, A Settleman, J Benes, CH Mino-Kenudson, M Wong, KK Engelman, JA AF Corcoran, Ryan B. Cheng, Katherine A. Hata, Aaron N. Faber, Anthony C. Ebi, Hiromichi Coffee, Erin M. Greninger, Patricia Brown, Ronald D. Godfrey, Jason T. Cohoon, Travis J. Song, Youngchul Lifshits, Eugene Shioda, Toshi Dias-Santagata, Dora Singh, Anurag Settleman, Jeffrey Benes, Cyril H. Mino-Kenudson, Mari Wong, Kwok-Kin Engelman, Jeffrey A. TI Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS-mutant cancer models SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Corcoran, Ryan B.; Hata, Aaron N.; Faber, Anthony C.; Ebi, Hiromichi; Coffee, Erin M.; Greninger, Patricia; Brown, Ronald D.; Godfrey, Jason T.; Song, Youngchul; Lifshits, Eugene; Shioda, Toshi; Dias-Santagata, Dora; Benes, Cyril H.; Mino-Kenudson, Mari; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Cheng, Katherine A.; Cohoon, Travis J.; Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Singh, Anurag] Boston Univ, Boston, MA 02215 USA. [Settleman, Jeffrey] Genentech Inc, San Francisco, CA 94080 USA. OI wong, kwok kin/0000-0001-6323-235X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2013 VL 12 IS 5 SU S MA PR09 DI 10.1158/1535-7163.PMS-PR09 PG 1 WC Oncology SC Oncology GA V40RW UT WOS:000209496700078 ER PT J AU Johannessen, CM Johnson, LA Piccioni, F Townes, A Frederick, DT Flaherty, KT Wargo, JA Root, DE Garraway, LA AF Johannessen, Cory M. Johnson, Laura A. Piccioni, Federica Townes, Aisha Frederick, Dennie T. Flaherty, Keith T. Wargo, Jennifer A. Root, David E. Garraway, Levi A. TI A cyclic AMP-regulated melanocyte lineage program confers resistance to MAP kinase pathway inhibition SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Johannessen, Cory M.; Johnson, Laura A.; Piccioni, Federica; Townes, Aisha; Root, David E.; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Frederick, Dennie T.; Flaherty, Keith T.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2013 VL 12 IS 5 SU S MA PR10 DI 10.1158/1535-7163.PMS-PR10 PG 1 WC Oncology SC Oncology GA V40RW UT WOS:000209496700079 ER PT J AU Kawasumi, M Bradner, JE Tolliday, N Thibodeau, R Sloan, H Brummond, KM Nghiem, P AF Kawasumi, Masaoki Bradner, James E. Tolliday, Nicola Thibodeau, Renee Sloan, Heather Brummond, Kay M. Nghiem, Paul TI A chemical genetic screen identifies novel ATM/ATR pathway inhibitors that sensitize p53-deficient cells to DNA-damaging agents without affecting ATR kinase catalytic activity SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Kawasumi, Masaoki; Thibodeau, Renee; Sloan, Heather; Nghiem, Paul] Univ Washington, Seattle, WA 98195 USA. [Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tolliday, Nicola] Broad Inst MIT & Harvard, Cambridge, MA USA. [Brummond, Kay M.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2013 VL 12 IS 5 SU S MA B04 DI 10.1158/1535-7163.PMS-B04 PG 1 WC Oncology SC Oncology GA V40RW UT WOS:000209496700030 ER PT J AU Hsieh, DT Thiele, EA AF Hsieh, David T. Thiele, Elizabeth A. TI Efficacy and safety of rufinamide in pediatric epilepsy SO THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS LA English DT Review DE anticonvulsants; epilepsy; Lennox-Gastaut syndrome; rufinamide ID LENNOX-GASTAUT-SYNDROME; ADD-ON RUFINAMIDE; DOUBLE-BLIND; REFRACTORY EPILEPSY; LONG-TERM; CHILDREN; SEIZURES; TOLERABILITY; TRIAL; POPULATION AB Rufinamide is a novel anticonvulsant medication approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of seizures associated with Lennox-Gastaut syndrome in patients 4 years of age and older, based upon clinical trials demonstrating clinical efficacy and tolerability. Rufinamide is especially effective for tonic-atonic seizures in Lennox-Gastaut syndrome, but is subsequently proving to be safe and effective in clinical practice for a broad patient population with refractory epilepsy. Although further research and clinical experience is needed, rufinamide holds the promise to positively impact the care of children with epilepsy. In this review, we review the use of rufinamide in pediatric epilepsy, with a focus on efficacy and safety. C1 [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA. [Hsieh, David T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org NR 42 TC 8 Z9 8 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1756-2856 EI 1756-2864 J9 THER ADV NEUROL DISO JI Ther. Adv. Neurol. Disord. PD MAY PY 2013 VL 6 IS 3 BP 189 EP 198 DI 10.1177/1756285613481083 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AH0QI UT WOS:000335824800004 PM 23634191 ER PT J AU Pinsky, PF Zhu, C Skates, SJ Black, A Partridge, E Buys, SS Berg, CD AF Pinsky, Paul F. Zhu, Claire Skates, Steve J. Black, Amanda Partridge, Edward Buys, Saundra S. Berg, Christine D. TI Potential effect of the risk of ovarian cancer algorithm (ROCA) on the mortality outcome of the Prostate, Lung, Colorectal and Ovarian (PLCO) trial SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ovarian cancer; Prostate; Lung; Colorectal and Ovarian (PLCO) cancer trial; risk of ovarian cancer algorithm (ROCA); screening; mortality AB Recently, the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial reported no mortality benefit for annual screening with CA-125 and transvaginal ultrasound (TVU). Currently ongoing is the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), which utilizes the risk of ovarian cancer algorithm (ROCA), a statistical tool that considers current and past CA125 values to determine ovarian cancer risk. In contrast, PLCO used a single cutoff for CA125, based on current levels alone. We investigated whether having had used ROCA in PLCO could have, under optimal assumptions, resulted in a significant mortality benefit by applying ROCA to PLCO CA125 screening values. A best-case scenario assumed that all cancers showing a positive screen result earlier with ROCA than under the PLCO protocol would have avoided mortality; under a stage-shift scenario, such women were assigned survival equivalent to Stage I/II screen-detected cases. Updated PLCO data show 132 intervention arm ovarian cancer deaths versus 119 in usual care (relative risk, RR = 1.11). Forty-three ovarian cancer cases, 25 fatal, would have been detected earlier with ROCA, with a median (minimum) advance time for fatal cases of 344 (147) days. Best-case and stage-shift scenarios gave 25 and 19 deaths prevented with ROCA, for RRs of 0.90 (95% CI: 0.691.17) and 0.95 (95% CI: 0.741.23), respectively. Having utilized ROCA in PLCO would not have led to a significant mortality benefit of screening. However, ROCA could still show a significant effect in other screening trials, including UKCTOCS. C1 [Pinsky, Paul F.; Zhu, Claire; Berg, Christine D.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Skates, Steve J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Black, Amanda] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Partridge, Edward] Univ Alabama Birmingham, Birmingham, AL USA. [Buys, Saundra S.] Univ Utah, Salt Lake City, UT USA. RP Pinsky, PF (reprint author), 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov RI Berg , Christine/K-1047-2014 NR 9 TC 16 Z9 16 U1 0 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2013 VL 132 IS 9 BP 2127 EP 2133 DI 10.1002/ijc.27909 PG 7 WC Oncology SC Oncology GA 092KV UT WOS:000315121100016 PM 23065684 ER PT J AU Pavlova, NN Pallasch, C Elia, AEH Braun, CJ Westbrook, TF Hemann, M Elledge, SJ AF Pavlova, Natalya N. Pallasch, Christian Elia, Andrew E. H. Braun, Christian J. Westbrook, Thomas F. Hemann, Michael Elledge, Stephen J. TI A role for PVRL4-driven cell-cell interactions in tumorigenesis SO ELIFE LA English DT Article ID CIRCULATING TUMOR-CELLS; BREAST-CANCER; LUNG-CANCER; EXPRESSION; NECTIN-4; METASTASIS; CARCINOMA; MIGRATION; INTEGRIN-BETA-4; IDENTIFICATION AB During all stages of tumor progression, cancer cells are subjected to inappropriate extracellular matrix environments and must undergo adaptive changes in order to evade growth constraints associated with the loss of matrix attachment. A gain of function screen for genes that enable proliferation independently of matrix anchorage identified a cell adhesion molecule PVRL4 (poliovirus-receptor-like 4), also known as Nectin-4. PVRL4 promotes anchorage-independence by driving cell-to-cell attachment and matrix-independent integrin beta 4/SHP-2/c-Src activation. Solid tumors frequently have copy number gains of the PVRL4 locus and some have focal amplifications. We demonstrate that the transformation of breast cancer cells is dependent on PVRL4. Furthermore, growth of orthotopically implanted tumors in vivo is inhibited by blocking PVRL4-driven cell-to-cell attachment with monoclonal antibodies, demonstrating a novel strategy for targeted therapy of cancer. C1 [Pavlova, Natalya N.; Elia, Andrew E. H.; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Pavlova, Natalya N.; Elia, Andrew E. H.; Elledge, Stephen J.] Brigham & Womens Hosp, Howard Hughes Med Inst, Div Genet, Boston, MA 02115 USA. [Pallasch, Christian; Braun, Christian J.; Hemann, Michael] MIT, Koch Inst Integrat Canc Res, Dept Biol, Boston, MA USA. [Elia, Andrew E. H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Westbrook, Thomas F.] Baylor Coll Med, Dan L Duncan Canc Ctr, Dept Pediat,Dept Mol & Human Genet, Verna & Marrs McLean Dept Biochem & Mol Biol, Boston, MA USA. RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM selledge@genetics.med.harvard.edu RI Braun, Christoph/J-4160-2014; OI Braun, Christoph/0000-0002-7836-4010; Pallasch, Christian P./0000-0001-5675-6905 FU Department of Defense BCRP; Howard Hughes Medical Institute FX Department of Defense BCRP Stephen Elledge; Howard Hughes Medical Institute Stephen Elledge NR 44 TC 22 Z9 22 U1 0 U2 1 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD APR 30 PY 2013 VL 2 AR e00358 DI 10.7554/eLife.00358 PG 24 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 274OB UT WOS:000328614700001 PM 23682311 ER PT J AU McAndrew, LM D'Andrea, E Lu, SE Abbi, B Yan, GW Engel, C Quigley, KS AF McAndrew, Lisa M. D'Andrea, Elizabeth Lu, Shou-En Abbi, Bhavna Yan, Grace W. Engel, Charles Quigley, Karen S. TI What pre-deployment and early post-deployment factors predict health function after combat deployment?: a prospective longitudinal study of Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) soldiers SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article DE Health function; Quality of life; Veterans; Military; Prospective; SF-36; Iraq; Afghanistan; Combat ID POSTTRAUMATIC-STRESS-DISORDER; OF-VETERANS-AFFAIRS; MENTAL-HEALTH; PHYSICAL HEALTH; SOCIAL SUPPORT; WAR VETERANS; VIETNAM VETERANS; SOMATIC SYMPTOMS; CARE UTILIZATION; AFGHANISTAN AB Background: Physical and mental function are strong indicators of disability and mortality. OEF/OIF Veterans returning from deployment have been found to have poorer function than soldiers who have not deployed; however the reasons for this are unknown. Methods: A prospective cohort of 790 soldiers was assessed both pre- and immediately after deployment to determine predictors of physical and mental function after war. Results: On average, OEF/OIF Veterans showed significant declines in both physical (t=6.65, p<.0001) and mental function (t=7.11, p<.0001). After controlling for pre-deployment function, poorer physical function after deployment was associated with older age, more physical symptoms, blunted systolic blood pressure reactivity and being injured. After controlling for pre-deployment function, poorer mental function after deployment was associated with younger age, lower social desirability, lower social support, greater physical symptoms and greater PTSD symptoms. Conclusions: Combat deployment was associated with an immediate decline in both mental and physical function. The relationship of combat deployment to function is complex and influenced by demographic, psychosocial, physiological and experiential factors. Social support and physical symptoms emerged as potentially modifiable factors. C1 [McAndrew, Lisa M.; Abbi, Bhavna; Yan, Grace W.] Dept Vet Affairs, NJ War Related Illness & Injury Study Ctr, E Orange, NJ 07018 USA. [McAndrew, Lisa M.; Lu, Shou-En] Univ Med & Dent New Jersey, Sch Publ Hlth, Piscataway, NJ 08854 USA. [D'Andrea, Elizabeth] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Engel, Charles] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Psychiat, Bethesda, MD 20814 USA. [Quigley, Karen S.] Bedford Mem Hosp, Dept Vet Affairs, Bedford, MA USA. [Quigley, Karen S.] Northeastern Univ, Interdisciplinary Affect Sci Lab, Boston, MA USA. RP McAndrew, LM (reprint author), Dept Vet Affairs, NJ War Related Illness & Injury Study Ctr, 385 Tremont Ave Mailstop 129, E Orange, NJ 07018 USA. EM Lisa.mcandrew@va.gov FU Department of Veterans Affairs, Health Services Research & Development Service [IIR 0202-296]; NJ War Related Illness and Injury Study Center; NJ REAP [REA 03-021]; Deployment Health Clinical Center, Walter Reed Army Medical Center FX This study was supported by grants from the Department of Veterans Affairs, Health Services Research & Development Service (IIR 0202-296 to K. Quigley); the NJ War Related Illness and Injury Study Center, the NJ REAP (REA 03-021); and the Deployment Health Clinical Center, Walter Reed Army Medical Center. NR 52 TC 10 Z9 10 U1 3 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD APR 30 PY 2013 VL 11 AR 73 DI 10.1186/1477-7525-11-73 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 178NR UT WOS:000321455200001 PM 23631419 ER PT J AU Menden, MP Iorio, F Garnett, M McDermott, U Benes, CH Ballester, PJ Saez-Rodriguez, J AF Menden, Michael P. Iorio, Francesco Garnett, Mathew McDermott, Ultan Benes, Cyril H. Ballester, Pedro J. Saez-Rodriguez, Julio TI Machine Learning Prediction of Cancer Cell Sensitivity to Drugs Based on Genomic and Chemical Properties SO PLOS ONE LA English DT Article ID GENE-EXPRESSION SIGNATURES; INTEGRATIVE ANALYSIS; DISCOVERY DATABASES; ANTICANCER ACTIVITY; SMALL MOLECULES; LINE SET; INHIBITION; PATTERNS; COMPARE; QSAR AB Predicting the response of a specific cancer to a therapy is a major goal in modern oncology that should ultimately lead to a personalised treatment. High-throughput screenings of potentially active compounds against a panel of genomically heterogeneous cancer cell lines have unveiled multiple relationships between genomic alterations and drug responses. Various computational approaches have been proposed to predict sensitivity based on genomic features, while others have used the chemical properties of the drugs to ascertain their effect. In an effort to integrate these complementary approaches, we developed machine learning models to predict the response of cancer cell lines to drug treatment, quantified through IC50 values, based on both the genomic features of the cell lines and the chemical properties of the considered drugs. Models predicted IC50 values in a 8-fold cross-validation and an independent blind test with coefficient of determination R-2 of 0.72 and 0.64 respectively. Furthermore, models were able to predict with comparable accuracy (R-2 of 0.61) IC50s of cell lines from a tissue not used in the training stage. Our in silico models can be used to optimise the experimental design of drug-cell screenings by estimating a large proportion of missing IC50 values rather than experimentally measuring them. The implications of our results go beyond virtual drug screening design: potentially thousands of drugs could be probed in silico to systematically test their potential efficacy as anti-tumour agents based on their structure, thus providing a computational framework to identify new drug repositioning opportunities as well as ultimately be useful for personalized medicine by linking the genomic traits of patients to drug sensitivity. C1 [Menden, Michael P.; Iorio, Francesco; Ballester, Pedro J.; Saez-Rodriguez, Julio] Wellcome Trust Genome Campus Cambridge, European Bioinformat Inst, Cambridge, England. [Iorio, Francesco; Garnett, Mathew; McDermott, Ultan] Wellcome Trust Genome Campus Cambridge, Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England. [Benes, Cyril H.] Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA USA. [Benes, Cyril H.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Ballester, PJ (reprint author), Wellcome Trust Genome Campus Cambridge, European Bioinformat Inst, Cambridge, England. EM pedro.ballester@ebi.ac.uk; saezrodriguez@ebi.ac.uk RI Ballester, Pedro/A-1148-2008; OI Ballester, Pedro/0000-0002-4078-743X; Iorio, Francesco/0000-0001-7063-8913; McDermott, Ultan/0000-0001-9032-4700; Saez-Rodriguez, Julio/0000-0002-8552-8976 FU European Molecular Biology Laboratory PhD programme; Sanger/European Bioinformatics Institute ESPOD programme; Medical Research Council Methodology Research Fellowship; Wellcome Trust grant; Cancer Research UK FX This work was funded by the European Molecular Biology Laboratory PhD programme to MPM, the Sanger/European Bioinformatics Institute ESPOD programme to FI, a Medical Research Council Methodology Research Fellowship to PJB, a Wellcome Trust grant to MG and CHB, and Cancer Research UK to UM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 40 Z9 40 U1 3 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 30 PY 2013 VL 8 IS 4 AR e61318 DI 10.1371/journal.pone.0061318 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146GG UT WOS:000319077300006 PM 23646105 ER PT J AU Cesana, M Daley, GQ AF Cesana, Marcella Daley, George Q. TI Deciphering the rules of ceRNA networks SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID MICRORNA SPONGES; RNAS C1 [Cesana, Marcella; Daley, George Q.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. [Cesana, Marcella; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cesana, Marcella; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Cesana, Marcella; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Cesana, Marcella; Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Cesana, Marcella; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Boston Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU Howard Hughes Medical Institute; NHGRI NIH HHS [P50 HG005550]; NHLBI NIH HHS [U01 HL100001, UO1-HL100001]; NIAID NIH HHS [R01 AI100887]; NIDDK NIH HHS [R24 DK092760, R24-DK092760, RC4 DK090913, RC4DK 090913]; NIGMS NIH HHS [P01 GM099117] NR 13 TC 17 Z9 17 U1 1 U2 27 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 2013 VL 110 IS 18 BP 7112 EP 7113 DI 10.1073/pnas.1305322110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 140UV UT WOS:000318682300014 PM 23620514 ER PT J AU Ueno, K Hirata, H Shahryari, V Deng, G Tanaka, Y Tabatabai, ZL Hinoda, Y Dahiya, R AF Ueno, K. Hirata, H. Shahryari, V. Deng, G. Tanaka, Y. Tabatabai, Z. L. Hinoda, Y. Dahiya, R. TI microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE prostate cancer; miRNA-183; Dkk-3; SMAD4 ID GROWTH-FACTOR-BETA; DPC4 SMAD4; EXPRESSION; CELLS; GENE; PROGRESSION; CARCINOMA; RISK; APOPTOSIS; DEATH AB Background: The purpose of this study was to identify prostate cancer (PC) oncogenic microRNAs (miRs) based on miR microarray and to investigate whether these oncogenic miRs may be useful as PC biomarkers. Methods: Initially, we carried out miR microarray and real-time PCR using RWPE-1, PC-3, DU-145 and LNCaP cells. To investigate the function of miR-183, we used a miR-183 knockdown inhibitor in cell growth and wound-healing assays. We used several algorithms and confirmed that they are directly regulated by miR-183. Results: We identified three potential oncogenic miRs (miR-146a, miR-183 and miR-767-5P). The expression of miR-183 in PC cells (PC-3, DU-145 and LNCaP) was upregulated compared with RWPE-1 cells. MiR-183 expression was also significantly higher in PC tissues compared with that in matched normal prostate tissues. Additionally, miR-183 expression was correlated with higher prostate-specific antigen, higher pT and shorter overall survival. MiR-183 knockdown decreased cell growth and motility in PC cells and significantly decreased prostate tumour growth in in vivo nude mice experiments. We identified Dkk-3 and SMAD4 as potential target genes of miR-183. Conclusion: Our data suggest that oncogenic miR-183 may be useful as a new PC biomarker and that inhibition of miR-183 expression may be therapeutically beneficial as a PC treatment. C1 [Ueno, K.; Hirata, H.; Shahryari, V.; Deng, G.; Tanaka, Y.; Dahiya, R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Urol, San Francisco, CA 94121 USA. [Tabatabai, Z. L.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. [Hinoda, Y.] Yamaguchi Univ, Grad Sch Med, Dept Oncol & Lab Med, Ube, Yamaguchi 755, Japan. RP Dahiya, R (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Urol, 4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urology.ucsf.edu FU National Center for Research Resources of the National Institutes of Health [R01CA138642, R01CA130860, R01CA160079]; VA Merit Review grants; VA Program Project FX We thank Dr Roger Erickson for his support and assistance with the preparation of the manuscript. This study was supported by National Center for Research Resources of the National Institutes of Health through Grant Number R01CA138642, R01CA130860, R01CA160079, VA Merit Review grants and VA Program Project. NR 31 TC 45 Z9 49 U1 0 U2 5 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 APR 30 PY 2013 VL 108 IS 8 BP 1659 EP 1667 DI 10.1038/bjc.2013.125 PG 9 WC Oncology SC Oncology GA 137AJ UT WOS:000318406400014 PM 23538390 ER PT J AU Nallamothu, BK Spertus, JA Lansky, AJ Cohen, DJ Jones, PG Kureshi, F Dehmer, GJ Drozda, JP Walsh, MN Brush, JE Koenig, GC Waites, TF Gantt, S Kichura, G Chazal, RA O'Brien, PK Valentine, CM Rumsfeld, JS Reiber, JHC Elmore, JG Krumholz, RA Weaver, WD Krumholz, HM AF Nallamothu, Brahmajee K. Spertus, John A. Lansky, Alexandra J. Cohen, David J. Jones, Philip G. Kureshi, Faraz Dehmer, Gregory J. Drozda, Joseph P., Jr. Walsh, Mary Norine Brush, John E., Jr. Koenig, Gerald C. Waites, Thad F. Gantt, Scott Kichura, George Chazal, Richard A. O'Brien, Peter K. Valentine, C. Michael Rumsfeld, John S. Reiber, Johan H. C. Elmore, Joann G. Krumholz, Richard A. Weaver, W. Douglas Krumholz, Harlan M. TI Comparison of Clinical Interpretation With Visual Assessment and Quantitative Coronary Angiography in Patients Undergoing Percutaneous Coronary Intervention in Contemporary Practice The Assessing Angiography (A2) Project SO CIRCULATION LA English DT Article DE coronary angiography; health policy; outcome assessment (health care); percutaneous coronary intervention; quality improvement ID COMPUTER-AIDED DETECTION; ASSOCIATION TASK-FORCE; CARDIOVASCULAR ANGIOGRAPHY; CARDIAC-CATHETERIZATION; SCREENING MAMMOGRAPHY; PRACTICE GUIDELINES; LESION SEVERITY; STENOSIS; ARTERIOGRAMS; VARIABILITY AB Background-Studies conducted decades ago described substantial disagreement and errors in physicians' angiographic interpretation of coronary stenosis severity. Despite the potential implications of such findings, no large-scale efforts to measure or improve clinical interpretation were subsequently undertaken. Methods and Results-We compared clinical interpretation of stenosis severity in coronary lesions with an independent assessment using quantitative coronary angiography (QCA) in 175 randomly selected patients undergoing elective percutaneous coronary intervention at 7 US hospitals in 2011. To assess agreement, we calculated mean difference in percent diameter stenosis between clinical interpretation and QCA and a Cohen weighted kappa statistic. Of 216 treated lesions, median percent diameter stenosis was 80.0% (quartiles 1 and 3, 80.0% and 90.0%), with 213 (98.6%) assessed as >= 70%. Mean difference in percent diameter stenosis between clinical interpretation and QCA was 8.2 +/- 8.4%, reflecting an average higher percent diameter stenosis by clinical interpretation (P<0.001). A weighted kappa of 0.27 (95% confidence interval, 0.18-0.36) was found between the 2 measurements. Of 213 lesions considered >= 70% by clinical interpretation, 56 (26.3%) were <70% by QCA, although none were <50%. Differences between the 2 measurements were largest for intermediate lesions by QCA (50% to <70%), with variation existing across sites. Conclusions-Physicians tended to assess coronary lesions treated with percutaneous coronary intervention as more severe than measurements by QCA. Almost all treated lesions were >= 70% by clinical interpretation, whereas approximately one quarter were <70% by QCA. These findings suggest opportunities to improve clinical interpretation of coronary angiography. (Circulation. 2013;127:1793-1800.) C1 [Nallamothu, Brahmajee K.] Ann Arbor VA Ctr Clin Management & Res, Ann Arbor, CT USA. [Nallamothu, Brahmajee K.] Univ Michigan Hlth Syst, Ann Arbor, CT USA. [Spertus, John A.; Cohen, David J.; Jones, Philip G.; Kureshi, Faraz] St Lukes Mid Amer Heart Inst, Kansas City, CT USA. [Spertus, John A.; Cohen, David J.; Jones, Philip G.; Kureshi, Faraz] Univ Missouri Kansas City, Kansas City, CT USA. [Lansky, Alexandra J.] Yale Univ, Sch Med, New Haven, CT USA. [Dehmer, Gregory J.] Texas A&M Univ, Coll Med, Hlth Sci Ctr, Temple, TX 76508 USA. [Dehmer, Gregory J.] Scott & White Healthcare, Temple, TX USA. [Drozda, Joseph P., Jr.; Kichura, George] Mercy Hlth, St Louis, MO USA. [Walsh, Mary Norine] St Vincent Heart Ctr Indiana, Indianapolis, VA USA. [Brush, John E., Jr.] Sentara Cardiovasc Res Inst, Norfolk, VA USA. [Brush, John E., Jr.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Koenig, Gerald C.; Weaver, W. Douglas] Henry Ford Hlth Syst, Detroit, MI USA. [Waites, Thad F.; Weaver, W. Douglas] Wayne State Univ, Detroit, MI USA. [Waites, Thad F.] Forrest Gen, Hattiesburg, MS USA. [Chazal, Richard A.] Lee Mem Hlth Syst, Ft Myers, FL USA. [O'Brien, Peter K.; Valentine, C. Michael] Centra Lynchburg Gen Hosp, Lynchburg, VA USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Reiber, Johan H. C.] Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands. [Elmore, Joann G.] Univ Washington, Dept Med, Seattle, FL USA. [Krumholz, Richard A.] ImageCor, Bradenton, FL USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Internal Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Ctr Outcomes Res & Evaluat, New Haven, CT USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Adm, New Haven, CT USA. RP Nallamothu, BK (reprint author), Univ Michigan, Ctr Cardiovasc, SPC 5869,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM bnallamo@umich.edu FU Aetna, Inc.; National Institutes of Health [T32HL110837]; Yale University, from Medtronic; National Heart, Lung, and Blood Institute [U01 HL105270-03] FX Dr Spertus reports grant funding from Aetna, Inc. Dr Cohen reports consulting income from United Healthcare. Dr Kureshi received support from National Institutes of Health grant T32HL110837. Dr Walsh reports consulting income from United Healthcare and Eli Lilly. Dr Chazal reports being a member of the Scientific Advisory Board of United Healthcare. Dr Rumsfeld reports being the chief science officer for the NCDR. Dr Reiber reports being the president and chief executive officer of Medis, which provides software for the quantification of cardiovascular images. Dr Richard Krumholz reports being the General Manager of ImageCor, a company focused on improving clinical interpretation of medical imaging. Dr Harlan Krumholz reports equity interest in ImageCor and being chair of the Scientific Advisory Board of United Healthcare and a recipient of a research grant, through Yale University, from Medtronic. Dr Harlan Krumholz also is supported by grant U01 HL105270-03 (Center for Cardiovascular Outcomes Research at Yale University) from the National Heart, Lung, and Blood Institute. The other authors report no conflicts. NR 32 TC 34 Z9 35 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 30 PY 2013 VL 127 IS 17 BP 1793 EP + DI 10.1161/CIRCULATIONAHA.113.001952 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 134MT UT WOS:000318215000013 PM 23470859 ER PT J AU Beaudoin, J Handschumacher, MD Zeng, X Hung, JD Morris, EL Levine, RA Schwammenthal, E AF Beaudoin, Jonathan Handschumacher, Mark D. Zeng, Xin Hung, Judy Morris, Eleanor L. Levine, Robert A. Schwammenthal, Ehud TI Mitral Valve Enlargement in Chronic Aortic Regurgitation as a Compensatory Mechanism to Prevent Functional Mitral Regurgitation in the Dilated Left Ventricle SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE aortic regurgitation; functional mitral regurgitation; valvular disease ID ACUTE MYOCARDIAL-INFARCTION; NATURAL-HISTORY; HEART-FAILURE; EXTRACELLULAR-MATRIX; DOPPLER-ECHOCARDIOGRAPHY; ASYMPTOMATIC PATIENTS; LEAFLET ADAPTATION; CARDIOMYOPATHY; OVERLOAD; DISEASE AB Objectives The aim of this study was to test the hypothesis that mitral valve (MV) enlargement occurring in chronic aortic regurgitation (AR) prevents functional mitral regurgitation (FMR). Background Chronic AR causes left ventricular (LV) dilation, creating the potential for FMR. However, FMR is typically absent during compensated AR despite substantial LV enlargement. Increased mitral leaflet area has been identified in AR, but it is unknown whether increased MV size can represent a compensatory mechanism capable of preventing FMR. Methods Database review of 816 patients with at least moderate AR evaluated the prevalence of FMR. A total of 90 patients were enrolled prospectively for 3-dimensional echocardiography (30 AR, 30 FMR, and 30 controls) to assess MV geometry including total leaflet area. Results FMR was present in 5.6% of AR patients by database review. Prospectively, only 1 AR patient had more than mild FMR despite increased LV end-diastolic volume (82 +/- 22, 86 +/- 23, and 51 +/- 12 cm(3)/m(2), respectively, for AR, FMR vs. control patients; p < 0.01) and similar sphericity index, annular area, and tethering distances compared with FMR. Total MV area was largest in AR (31.3% greater than normal), increasing significantly more than in FMR. The ratio of valve size to closure area was maintained in AR, whereas decreases in this ratio and LV ejection fraction independently predicted FMR. Conclusions FMR prevalence is low in chronic AR. MV leaflet area is significantly increased compared with control and FMR patients, preserving a normal relationship to the area needed for closure in the dilated LV. Understanding the mechanisms underlying this adaptation could lead to new therapeutic interventions to prevent FMR. (J Am Coll Cardiol 2013;61:1809-16) (C) 2013 by the American College of Cardiology Foundation C1 [Beaudoin, Jonathan; Handschumacher, Mark D.; Zeng, Xin; Hung, Judy; Morris, Eleanor L.; Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Beaudoin, Jonathan; Handschumacher, Mark D.; Zeng, Xin; Hung, Judy; Morris, Eleanor L.; Levine, Robert A.] Harvard Univ, Sch Med, Boston, MA USA. [Schwammenthal, Ehud] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. RP Schwammenthal, E (reprint author), Chaim Sheba Med Ctr, Ctr Heart, IL-52621 Tel Hashomer, Israel. EM ehudsc@gmail.com FU AHA [10POST4580055]; Leducq Foundation, Paris, France [07CVD04]; NIH [K24 HL67434, R01 HL109506] FX Dr. Beaudoin is funded by an AHA-Founders Affiliate post-doctoral fellowship grant 10POST4580055. Supported in part by grant 07CVD04 of the Leducq Foundation, Paris, France, for the Leducq Transatlantic MITRAL Network, and by NIH K24 HL67434 and R01 HL109506. Dr. Schwammenthal is a consultant to Medtronic Ventor Technologies Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 45 TC 24 Z9 25 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 30 PY 2013 VL 61 IS 17 BP 1809 EP 1816 DI 10.1016/j.jacc.2013.01.064 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 129LT UT WOS:000317842200009 PM 23500248 ER PT J AU Hage, FG AlJaroudi, W Aggarwal, H Bhatia, V Miller, J Doppalapudi, H Wazni, O Iskandrian, AE AF Hage, Fadi G. AlJaroudi, Wael Aggarwal, Himanshu Bhatia, Vikas Miller, John Doppalapudi, Harish Wazni, Oussama Iskandrian, Ami E. TI Outcomes of patients with chronic kidney disease and implantable cardiac defibrillator: Primary versus secondary prevention SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Chronic kidney disease; Implantable cardiac defibrillator; Mortality; Primary prevention; Secondary prevention; Sudden cardiac death ID GLOMERULAR-FILTRATION-RATE; CORONARY-ARTERY-DISEASE; SERUM CREATININE VALUES; CARDIOVERTER-DEFIBRILLATOR; RENAL-FUNCTION; INDEPENDENT PREDICTOR; SUDDEN-DEATH; MORTALITY; THERAPY; IMPACT AB Background: Chronic kidney disease (CKD) is associated with worse survival in patients with implantable cardiac defibrillators (ICDs). This study examined the association of outcomes with CKD in patients receiving an ICD for primary versus secondary prevention. Methods: The study included 696 patients who underwent ICD placement for clinical reasons (59% primary, 41% secondary prevention) at the University of Alabama at Birmingham between January 2002 and September 2007. CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m(2) but not on dialysis. Outcomes of interest included overall mortality and first appropriate ICD therapy (shocks or anti-tachycardia pacing). Results: After a follow-up of 50 +/- 24 months, 213 patients died (31%) and 111 (16%) received appropriate ICD therapy. Patients with CKD had higher mortality than patients with no CKD in the primary (43% vs. 15%, p<0.001) and secondary prevention (37% vs. 23%, p=0.003) groups. Patients with CKD were at higher risk of receiving an appropriate ICD therapy than patients without CKD in the primary (p<0.001) but not secondary prevention (p=0.9) cohort. After adjusting for age, gender and multiple risk factors, CKD was independently associated with all-cause mortality and ICD therapy in the primary prevention group (HR 2.08 [1.34-3.23] and 3.53 [1.75-7.10], p=0.001 and <0.0001, respectively) but not in the secondary prevention group (HR 1.27 [0.81-2.00], and 0.63 [0.35-1.13], p=0.3 and 0.2, respectively). Conclusions: CKD is independently associated with increased mortality and appropriate ICD therapy in patients undergoing ICD implantation for primary but not secondary prevention. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Hage, Fadi G.; Doppalapudi, Harish; Iskandrian, Ami E.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. [AlJaroudi, Wael; Wazni, Oussama] Cleveland Clin, Div Cardiovasc Med, Sect Imaging, Cleveland, OH USA. [Aggarwal, Himanshu; Bhatia, Vikas; Miller, John] Univ Alabama Birmingham, Dept Med, Div Internal Med, Birmingham, AL 35294 USA. RP Hage, FG (reprint author), Zeigler Res Bldg 1024,1530 3rd AVE S, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 19 TC 8 Z9 8 U1 0 U2 2 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 APR 30 PY 2013 VL 165 IS 1 BP 113 EP 116 DI 10.1016/j.ijcard.2011.07.087 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 122VU UT WOS:000317347100026 PM 21862150 ER PT J AU Martinelli, R Kamei, M Sage, PT Massol, R Varghese, L Sciuto, T Toporsian, M Dvorak, AM Kirchhausen, T Springer, TA Carman, CV AF Martinelli, Roberta Kamei, Masataka Sage, Peter T. Massol, Ramiro Varghese, Laya Sciuto, Tracey Toporsian, Mourad Dvorak, Ann M. Kirchhausen, Tomas Springer, Timothy A. Carman, Christopher V. TI Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INVADOSOME-LIKE PROTRUSIONS; MEMBRANE TENSION; NAD(P)H OXIDASE; BLOOD-CELLS; NEUTROPHIL EXTRAVASATION; TRANSCELLULAR DIAPEDESIS; LEUKOCYTE DIAPEDESIS; ENDOTHELIAL-CELLS; FOCAL ADHESIONS; STRESS FIBERS AB Basic mechanisms by which cellular barriers sense and respond to integrity disruptions remain poorly understood. Despite its tenuous structure and constitutive exposure to disruptive strains, the vascular endothelium exhibits robust barrier function. We show that in response to micrometer-scale disruptions induced by transmigrating leukocytes, endothelial cells generate unique ventral lamellipodia that propagate via integrins toward and across these "micro-wounds" to close them. This novel actin remodeling activity progressively healed multiple micro-wounds in succession and changed direction during this process. Mechanical probe-induced micro-wounding of both endothelia and epithelia suggests that ventral lamellipodia formed as a response to force imbalance and specifically loss of isometric tension. Ventral lamellipodia were enriched in the Rac1 effectors cortactin, IQGAP, and p47Phox and exhibited localized production of hydrogen peroxide. Together with Apr2/3, these were functionally required for effective micro-wound healing. We propose that barrier disruptions are detected as local release of isometric tension/force unloading, which is directly coupled to reactive oxygen species-dependent self-restorative actin remodeling dynamics. C1 [Martinelli, Roberta; Kamei, Masataka; Sage, Peter T.; Varghese, Laya; Toporsian, Mourad; Carman, Christopher V.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Ctr Vasc Biol Res, Boston, MA 02215 USA. [Sciuto, Tracey; Dvorak, Ann M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol,Ctr Vasc Biol Res, Boston, MA 02215 USA. [Massol, Ramiro; Kirchhausen, Tomas; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Kirchhausen, Tomas; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Carman, CV (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Ctr Vasc Biol Res, Boston, MA 02215 USA. EM ccarman@bidmc.harvard.edu RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU National Institutes of Health [R01 GM075252, R01 CA31798, R01 HL104006] FX This work was supported by National Institutes of Health grants R01 GM075252 (T. Kirchhausen), R01 CA31798 (T.A. Springer), and R01 HL104006 (C.V. Carman). NR 78 TC 36 Z9 36 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 29 PY 2013 VL 201 IS 3 BP 449 EP 465 DI 10.1083/jcb.201209077 PG 17 WC Cell Biology SC Cell Biology GA 134MU UT WOS:000318215100010 PM 23629967 ER PT J AU Salmon, DA Proschan, M Forshee, R Gargiullo, P Bleser, W Burwen, DR Cunningham, F Garman, P Greene, SK Lee, GM Vellozzi, C Yih, WK Gellin, B Lurie, N AF Salmon, Daniel A. Proschan, Michael Forshee, Richard Gargiullo, Paul Bleser, William Burwen, Dale R. Cunningham, Francesca Garman, Patrick Greene, Sharon K. Lee, Grace M. Vellozzi, Claudia Yih, W. Katherine Gellin, Bruce Lurie, Nicole CA H1N1 GBS Meta-Anal Working Grp TI Association between Guillain-Barre syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis SO LANCET LA English DT Article ID SAFETY DATALINK PROJECT; PRACTICE RESEARCH DATABASE; UNITED-STATES; IMMUNIZATION-SAFETY; VACCINATION; SURVEILLANCE; RECEIPT; PROGRAM; KINGDOM; COHORT AB Background The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barre syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barre syndrome is a rare but serious health disorder in which a person's own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barre syndrome. Methods Data were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barre syndrome per million vaccinations. We used a self-controlled risk-interval design. Findings Influenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barre syndrome (incidence rate ratio 2.35, 95% CI 1.42-4.01, p=0.0003). This finding translated to about 1.6 excess cases of Guillain-Barre syndrome per million people vaccinated. Interpretation The modest risk of Guillain-Barre syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks. C1 [Salmon, Daniel A.; Bleser, William; Gellin, Bruce] Dept Hlth & Human Serv, Natl Vaccine Program Off, Off Assistant Secretary Hlth, Washington, DC USA. [Lurie, Nicole] Dept Hlth & Human Serv, Washington, DC USA. [Salmon, Daniel A.] Johns Hopkins Bloomberg Sch Publ Hlth, Inst Vaccine Safety, Baltimore, MD 21205 USA. [Proschan, Michael] NIH, Bethesda, MD 20892 USA. [Forshee, Richard; Burwen, Dale R.] US FDA, Rockville, MD 20857 USA. [Gargiullo, Paul; Vellozzi, Claudia] Ctr Dis Control & Prevent, Atlanta, GA USA. [Cunningham, Francesca] US Dept Vet Affairs, Hines, IL USA. [Garman, Patrick] US Dept Def, Washington, DC 20305 USA. [Greene, Sharon K.; Lee, Grace M.; Yih, W. Katherine] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Greene, Sharon K.; Lee, Grace M.; Yih, W. Katherine] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Salmon, DA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Inst Vaccine Safety, Baltimore, MD 21205 USA. EM dsalmon@jhsph.edu OI Jacobsen, Steven/0000-0002-8174-8533; Bleser, William/0000-0002-4640-8680 FU US Federal Government FX US Federal Government. NR 40 TC 55 Z9 55 U1 0 U2 74 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 27 PY 2013 VL 381 IS 9876 BP 1461 EP 1468 DI 10.1016/S0140-6736(12)62189-8 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 139TK UT WOS:000318607300035 PM 23498095 ER PT J AU Tsai, TY Li, JS Wang, SB Lin, H Malchau, H Li, GA Rubash, H Kwon, YM AF Tsai, Tsung-Yuan Li, Jing-Sheng Wang, Shaobai Lin, Hao Malchau, Henrik Li, Guoan Rubash, Harry Kwon, Young-Min TI A novel dual fluoroscopic imaging method for determination of THA kinematics: In-vitro and in-vivo study SO JOURNAL OF BIOMECHANICS LA English DT Article DE Total hip arthroplasty; Kinematics; Fluoroscope; Validation; Non-invasive ID TOTAL HIP-ARTHROPLASTY; SINGLE-PLANE FLUOROSCOPY; METAL-ON-METAL; MATCHING METHOD; JOINT; SYSTEM; REGISTRATION; SEPARATION; WALKING; IMAGES AB Accurate measurement of six-degrees-of-freedom in-vivo kinematics of the total hip arthroplasty (THA) is essential in gaining insights into in-vivo THA performance. The objective of this study was to validate a novel dual fluoroscopy imaging system (DFIS) for determination of the THA kinematics using both in-vitro and in-vivo approaches. The in-vitro validation utilized cadaveric hip specimens to compare the THA motion using the DFIS technique with those measured by a radiostereometric analysis (RSA). The differences between the DFIS technique and the RSA were within 033 +/- 0.81 mm (mean +/- SD) in translation and 0.45 +/- 0.65 degrees in rotation during dynamic motion of the hips. In the in-vivo validation, the THA kinematics of two patients during a treadmill gait was assessed for the feasibility/repeatability of the DFIS technique in measurement of THA kinematics. The poses of the THAs during the treadmill gait was measured using the DFIS technique with the maximum standard deviation of 0.35 mm in translation and of 0.55 degrees in rotation. This study demonstrated that the DFIS technique has comparable accuracy of the RSA and is highly repeatable for measurement of dynamic THA motion, suggesting that the DFIS is a promising tool in evaluating the in-vivo THA biomechanics during functional activities. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Tsai, Tsung-Yuan; Li, Jing-Sheng; Wang, Shaobai; Lin, Hao; Malchau, Henrik; Li, Guoan; Rubash, Harry; Kwon, Young-Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. [Lin, Hao] Fujian Prov Hosp, Trauma Dept, Fuzhou 350001, Fujian, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM gli1@partners.org OI Malchau, Henrik/0000-0002-4291-2441; Tsai, Tsung-Yuan/0000-0003-1522-2987 FU Department of Orthopaedic Surgery/MGH FX Department of Orthopaedic Surgery/MGH, Mako Medical Ethical approval: Research protocol has been reviewed and approved by Massachusetts General Hospital IRB. NR 36 TC 11 Z9 12 U1 0 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD APR 26 PY 2013 VL 46 IS 7 BP 1300 EP 1304 DI 10.1016/j.jbiomech.2013.02.010 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 139LI UT WOS:000318583800012 PM 23497800 ER PT J AU Wang, JM Ma, CJ Li, GY Wu, XY Thayer, P Greer, P Smith, AM High, KP Moorman, JP Yao, ZQ AF Wang, Jia M. Ma, Cheng J. Li, Guang Y. Wu, Xiao Y. Thayer, Penny Greer, Pamela Smith, Ashley M. High, Kevin P. Moorman, Jonathan P. Yao, Zhi Q. TI Tim-3 alters the balance of IL-12/IL-23 and drives T(H)17 cells: Role in hepatitis B vaccine failure during hepatitis C infection SO VACCINE LA English DT Article DE Tim-3; IL-12; IL-23; IL-17; Hepatitis B vaccine; Hepatitis C infection ID VIRUS CORE PROTEIN; T-CELL; ELEVATED FREQUENCIES; IMMUNE-RESPONSE; LIVER-DISEASE; EXPRESSION; IL-23; CYTOKINE; PD-1; INDIVIDUALS AB Hepatitis B virus (HBV) vaccination is recommended for individuals with hepatitis C virus (HCV) infection given their shared risk factors and increased liver-related morbidity and mortality upon super-infection. Vaccine responses in this setting are often blunted, with poor response rates to HBV vaccinations in chronically HCV-infected individuals compared to healthy subjects. In this study, we investigated the role of T cell immunoglobulin mucin domain-3 (Tim-3)-mediated immune regulation in HBV vaccine responses during HCV infection. We found that Tim-3, a marker for T cell exhaustion, was over-expressed on monocytes, leading to a differential regulation of IL-12/IL-23 production which in turn T(H)17 cell accumulation, in HCV-infected HBV vaccine non-responders compared to HCV-infected HBV vaccine responders or healthy subjects (HS). Importantly, ex vivo blockade of Tim-3 signaling corrected the imbalance of IL-12/IL-23 as well as the IL-17 bias observed in HBV vaccine non-responders during HCV infection. These results suggest that Tim-3-mediated dysregulation of innate to adaptive immune responses is involved in HBV vaccine failure in individuals with chronic HCV infection, raising the possibility that blocking this negative signaling pathway might improve the success rate of HBV immunization in the setting of chronic viral infection. Published by Elsevier Ltd. C1 [Thayer, Penny; Greer, Pamela; Smith, Ashley M.; Moorman, Jonathan P.; Yao, Zhi Q.] US Dept Vet Affairs, James H Quillen VA Med Ctr, Hepatitis HCV HIV Program, Johnson City, TN USA. [Wang, Jia M.; Ma, Cheng J.; Li, Guang Y.; Wu, Xiao Y.; Moorman, Jonathan P.; Yao, Zhi Q.] E Tennessee State Univ, James H Quillen Coll Med, Dept Internal Med, Div Infect Dis, Johnson City, TN 37614 USA. [Wang, Jia M.] Soochow Univ, Sch Med, Dept Biochem & Mol Biol, Suzhou, Peoples R China. [High, Kevin P.] Wake Forest Univ, Baptist Med Ctr, Infect Dis Sect, Dept Internal Med, Winston Salem, NC 27109 USA. RP Moorman, JP (reprint author), E Tennessee State Univ, Coll Med, Dept Internal Med, Div Infect Dis, Johnson City, TN 37614 USA. EM Moorman@etsu.edu RI sebastianovitsch, stepan/G-8507-2013 FU NIH NIDDK [R01DK093526]; Wake Forrest University; East Tennessee State University FX This work was supported by an NIH NIDDK grant to ZQY/JPM (R01DK093526) and by a Wake Forrest University and East Tennessee State University Collaborative Research Pilot Award. This publication is the result of work supported with resources and the use of facilities at the James H. Quillen Veterans Affairs Medical Center. The contents in this publication do not represent the views of the Department of Veterans Affairs or the United States Government. NR 58 TC 10 Z9 13 U1 0 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 26 PY 2013 VL 31 IS 18 BP 2238 EP 2245 DI 10.1016/j.vaccine.2013.03.003 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 135ZP UT WOS:000318329500004 PM 23499521 ER PT J AU Agus, DB Alexander, JF Arap, W Ashili, S Aslan, JE Austin, RH Backman, V Bethel, KJ Bonneau, R Chen, WC Chen-Tanyolac, C Choi, NC Curley, SA Dallas, M Damania, D Davies, PCW Decuzzi, P Dickinson, L Estevez-Salmeron, L Estrella, V Ferrari, M Fischbach, C Foo, J Fraley, SI Frantz, C Fuhrmann, A Gascard, P Gatenby, RA Geng, Y Gerecht, S Gillies, RJ Godin, B Grady, WM Greenfield, A Hemphill, C Hempstead, BL Hielscher, A Hillis, WD Holland, EC Ibrahim-Hashim, A Jacks, T Johnson, RH Joo, A Katz, JE Kelbauskas, L Kesselman, C King, MR Konstantopoulos, K Kraning-Rush, CM Kuhn, P Kung, K Kwee, B Lakins, JN Lambert, G Liao, D Licht, JD Liphardt, JT Liu, LY Lloyd, MC Lyubimova, A Mallick, P Marko, J McCarty, OJT Meldrum, DR Michor, F Mumenthaler, SM Nandakumar, V O'Halloran, TV Oh, S Pasqualini, R Paszek, MJ Philips, KG Poultney, CS Rana, K Reinhart-King, CA Ros, R Semenza, GL Senechal, P Shuler, ML Srinivasan, S Staunton, JR Stypula, Y Subramanian, H Tlsty, TD Tormoen, GW Tseng, Y van Oudenaarden, A Verbridge, SS Wan, JC Weaver, VM Widom, J Will, C Wirtz, D Wojtkowiak, J Wu, PH AF Agus, David B. Alexander, Jenolyn F. Arap, Wadih Ashili, Shashanka Aslan, Joseph E. Austin, Robert H. Backman, Vadim Bethel, Kelly J. Bonneau, Richard Chen, Wei-Chiang Chen-Tanyolac, Chira Choi, Nathan C. Curley, Steven A. Dallas, Matthew Damania, Dhwanil Davies, Paul C. W. Decuzzi, Paolo Dickinson, Laura Estevez-Salmeron, Luis Estrella, Veronica Ferrari, Mauro Fischbach, Claudia Foo, Jasmine Fraley, Stephanie I. Frantz, Christian Fuhrmann, Alexander Gascard, Philippe Gatenby, Robert A. Geng, Yue Gerecht, Sharon Gillies, Robert J. Godin, Biana Grady, William M. Greenfield, Alex Hemphill, Courtney Hempstead, Barbara L. Hielscher, Abigail Hillis, W. Daniel Holland, Eric C. Ibrahim-Hashim, Arig Jacks, Tyler Johnson, Roger H. Joo, Ahyoung Katz, Jonathan E. Kelbauskas, Laimonas Kesselman, Carl King, Michael R. Konstantopoulos, Konstantinos Kraning-Rush, Casey M. Kuhn, Peter Kung, Kevin Kwee, Brian Lakins, Johnathon N. Lambert, Guillaume Liao, David Licht, Jonathan D. Liphardt, Jan T. Liu, Liyu Lloyd, Mark C. Lyubimova, Anna Mallick, Parag Marko, John McCarty, Owen J. T. Meldrum, Deirdre R. Michor, Franziska Mumenthaler, Shannon M. Nandakumar, Vivek O'Halloran, Thomas V. Oh, Steve Pasqualini, Renata Paszek, Matthew J. Philips, Kevin G. Poultney, Christopher S. Rana, Kuldeepsinh Reinhart-King, Cynthia A. Ros, Robert Semenza, Gregg L. Senechal, Patti Shuler, Michael L. Srinivasan, Srimeenakshi Staunton, Jack R. Stypula, Yolanda Subramanian, Hariharan Tlsty, Thea D. Tormoen, Garth W. Tseng, Yiider van Oudenaarden, Alexander Verbridge, Scott S. Wan, Jenny C. Weaver, Valerie M. Widom, Jonathan Will, Christine Wirtz, Denis Wojtkowiak, Jonathan Wu, Pei-Hsun CA Phys Sci Oncology Ctr Network TI A physical sciences network characterization of non-tumorigenic and metastatic cells SO SCIENTIFIC REPORTS LA English DT Article ID HYPOXIA-INDUCED METASTASIS; BREAST-CANCER; LYSYL OXIDASE; ADHESION; PROGRESSION; MIGRATION; PROTEIN; MORPHOLOGY; MECHANISM; SURVIVAL AB To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis. C1 [Agus, David B.; Choi, Nathan C.; Hillis, W. Daniel; Joo, Ahyoung; Katz, Jonathan E.; Mallick, Parag; Mumenthaler, Shannon M.; Wan, Jenny C.] Univ So Calif, Keck Sch Med, Ctr Appl Mol Med, Los Angeles, CA 90033 USA. [Alexander, Jenolyn F.; Decuzzi, Paolo; Ferrari, Mauro; Godin, Biana; Srinivasan, Srimeenakshi] Methodist Hosp, Dept Nanomed, Res Inst, Houston, TX 77030 USA. [Arap, Wadih; Pasqualini, Renata] Univ Texas MD Anderson Canc Ctr, David H Koch Ctr, Houston, TX 77030 USA. [Ashili, Shashanka; Hemphill, Courtney; Johnson, Roger H.; Kelbauskas, Laimonas; Meldrum, Deirdre R.; Nandakumar, Vivek; Senechal, Patti] Arizona State Univ, Ctr Biosignatures Discovery Automat, Biodesign Inst, Tempe, AZ 85287 USA. [Aslan, Joseph E.; McCarty, Owen J. T.; Philips, Kevin G.; Tormoen, Garth W.] Oregon Hlth & Sci Univ, Dept Biomed Engn, Sch Med, Portland, OR 97239 USA. [Aslan, Joseph E.; McCarty, Owen J. T.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Sch Med, Portland, OR 97239 USA. [Austin, Robert H.; Lambert, Guillaume; Liu, Liyu] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA. [Backman, Vadim; Damania, Dhwanil; Stypula, Yolanda; Subramanian, Hariharan] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Bethel, Kelly J.] Scripps Clin, Dept Pathol, La Jolla, CA 92037 USA. [Bonneau, Richard; Greenfield, Alex; Poultney, Christopher S.] NYU, Dept Biol, Dept Comp Sci, New York, NY 10003 USA. [Chen, Wei-Chiang; Dallas, Matthew; Dickinson, Laura; Fraley, Stephanie I.; Gerecht, Sharon; Hielscher, Abigail; Konstantopoulos, Konstantinos; Tseng, Yiider; Wirtz, Denis; Wu, Pei-Hsun] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. [Chen-Tanyolac, Chira; Estevez-Salmeron, Luis; Gascard, Philippe; Liao, David; Oh, Steve; Tlsty, Thea D.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Chen-Tanyolac, Chira; Estevez-Salmeron, Luis; Gascard, Philippe; Liao, David; Oh, Steve; Tlsty, Thea D.] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Curley, Steven A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Davies, Paul C. W.] Arizona State Univ, Beyond Ctr Fundamental Concepts Sci, Tempe, AZ 85287 USA. [Estrella, Veronica; Gatenby, Robert A.; Gillies, Robert J.; Ibrahim-Hashim, Arig; Lloyd, Mark C.; Wojtkowiak, Jonathan] H Lee Moffitt Canc Ctr & Res Inst, Dept Radiol, Tampa, FL 33612 USA. [Estrella, Veronica; Gatenby, Robert A.; Gillies, Robert J.; Ibrahim-Hashim, Arig; Lloyd, Mark C.; Wojtkowiak, Jonathan] H Lee Moffitt Canc Ctr & Res Inst, Dept Integrated Math Oncol, Tampa, FL 33612 USA. [Fischbach, Claudia; Geng, Yue; King, Michael R.; Kraning-Rush, Casey M.; Kwee, Brian; Rana, Kuldeepsinh; Reinhart-King, Cynthia A.; Shuler, Michael L.; Verbridge, Scott S.] Cornell Univ, Dept Biomed Engn, Ithaca, NY 14853 USA. [Foo, Jasmine] Univ Minnesota Twin Cities, Sch Math, Minneapolis, MN 55455 USA. [Frantz, Christian; Lakins, Johnathon N.; Paszek, Matthew J.; Weaver, Valerie M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Frantz, Christian; Lakins, Johnathon N.; Paszek, Matthew J.; Weaver, Valerie M.] Univ Calif San Francisco, Ctr Bioengn & Tissue Regenerat, San Francisco, CA 94143 USA. [Fuhrmann, Alexander; Ros, Robert; Staunton, Jack R.] Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA. [Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Grady, William M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Hempstead, Barbara L.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Hillis, W. Daniel] Appl Minds Inc, Glendale, CA 91201 USA. [Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, Dept Neurosurg, New York, NY 10065 USA. [Jacks, Tyler; van Oudenaarden, Alexander] MIT, Dept Biol, Cambridge, MA 02139 USA. [Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Kesselman, Carl] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA. [Kuhn, Peter] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. [Kung, Kevin; Lyubimova, Anna; van Oudenaarden, Alexander] MIT, Dept Phys, Cambridge, MA 02139 USA. [Licht, Jonathan D.; Will, Christine] Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Liphardt, Jan T.] Univ Calif Berkeley, Dept Phys, Biophys Grad Grp, Berkeley, CA 94720 USA. [Liphardt, Jan T.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. [Lloyd, Mark C.] H Lee Moffitt Canc Ctr & Res Inst, Dept Analyt Microscopy, Tampa, FL 33612 USA. [Mallick, Parag] Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA. [Marko, John; Widom, Jonathan] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [O'Halloran, Thomas V.] Northwestern Univ, Dept Chem, Chem Life Proc Inst, Evanston, IL 60208 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Vasc Program, Inst Cell Engn, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. [Shuler, Michael L.] Cornell Univ, Sch Chem & Biomol Engn, Ithaca, NY 14853 USA. [Weaver, Valerie M.] Univ Calif San Francisco, Dept Anat, Dept Bioengn & Therapeut Sci, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Weaver, Valerie M.] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Wirtz, D (reprint author), Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. EM wirtz@jhu.edu RI Decuzzi, Paolo/F-1899-2016; Backman, Vadim/B-6689-2009; Fischbach, Claudia/C-8550-2009; Rana, Kuldeepsinh/G-3262-2010; Konstantopoulos, Konstantinos/A-7045-2011; Staunton, Jack/G-3786-2010; Ros, Robert/G-2154-2012; Reinhart-King, Cynthia/A-9264-2016 OI Gillies, Robert/0000-0002-8888-7747; Aslan, Joseph/0000-0002-8873-0387; Decuzzi, Paolo/0000-0001-6050-4188; Ashili, Shashanka/0000-0001-6335-0954; Kesselman, Carl/0000-0003-0917-1562; , /0000-0001-7080-9196; Rana, Kuldeepsinh/0000-0001-8808-8518; Staunton, Jack/0000-0001-9773-8025; Reinhart-King, Cynthia/0000-0001-6959-3914 FU United States National Cancer Institute [U54CA143862, U54CA143876, U54CA143798, U54CA143970, U54CA143868, U54CA143874, U54CA143837, U54CA143869, U54CA143803, U54CA143906, U54CA143836, U54CA143907] FX We thank Jack R. Staunton and Denis Wirtz for taking leadership in preparing this manuscript, and we thank Thea D. Tlsty and Barbara L. Hempstead for their input on the choice of cell lines for this project. Thiswork was supported by the following grants from the United States National Cancer Institute: U54CA143862 to P. C. W. D., U54CA143876 to M. L. S., U54CA143798 to F. M., U54CA143970 to R. A. G., U54CA143868 to D. W., U54CA143874 to A. V. O., U54CA143837 to M. F., U54CA143869 to T. V. O., U54CA143803 to R. H. A., U54CA143906 to P. K., U54CA143836 to J. T. L., and U54CA143907 to W. D. H. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 41 TC 46 Z9 46 U1 8 U2 112 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 26 PY 2013 VL 3 AR 1449 DI 10.1038/srep01449 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132IO UT WOS:000318061300001 ER PT J AU Field, JJ Lin, G Okam, MM Majerus, E Keefer, J Onyekwere, O Ross, A Campigotto, F Neuberg, D Linden, J Nathan, DG AF Field, Joshua J. Lin, Gene Okam, Maureen M. Majerus, Elaine Keefer, Jeffrey Onyekwere, Onyinye Ross, Ainsley Campigotto, Federico Neuberg, Donna Linden, Joel Nathan, David G. TI Sickle cell vaso-occlusion causes activation of iNKT cells that is decreased by the adenosine A(2A) receptor agonist regadenoson SO BLOOD LA English DT Article ID KILLER T-CELLS; NF-KAPPA-B; PULMONARY INFLAMMATION; VASCULAR ENDOTHELIUM; NKT CELLS; DISEASE; MONOCYTES; ADHESION; PRIAPISM; CRISIS AB Adenosine A(2A) receptor (A(2A)R) agonists reduce invariant natural killer T (iNKT) cell activation and decrease inflammation in sickle cell disease (SCD) mice. We conducted a phase 1 trial of the A(2A)R agonist regadenoson in adults with SCD. The target dose was 1.44 mu g/kg/h. iNKT cell activation was evaluated using antibodies targeting the p65 subunit of nuclear factor-kappa B (phospho-NF-kappa B p65), interferon-gamma (IFN-gamma), and A(2A)R. Regadenoson was administered to 27 adults with SCD. We examined 21 patients at steady state and 6 during painful vaso-occlusive crises (pVOC). iNKT cell activation was also measured in 14 African-American controls. During pVOC, the fraction of iNKT cells demonstrating increased phospho-NF-kappa B p65 and A(2A)R expression was significantly higher compared with controls (P < .01) and steady-state patients (P < .05). IFN-gamma expression was also significantly higher compared with controls (P = .02). After a 24-hour infusion of regadenoson during pVOC, phospho-NF-kappa B p65 activation in iNKT cells decreased compared to baseline by a median of 48% (P = .03) to levels similar to controls and steady-state SCD. No toxicities were identified. Infusional regadenoson administered to adults with SCD at 1.44 mu g/kg/h during pVOC decreases activation of iNKT cells without toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01085201. C1 [Field, Joshua J.] Blood Ctr SE Wisconsin Inc, Milwaukee, WI 53226 USA. [Field, Joshua J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Lin, Gene; Linden, Joel] La Jolla Inst Allergy & Immunol, San Diego, CA USA. [Okam, Maureen M.; Ross, Ainsley] Brigham & Womens Hosp, Boston, MA 02115 USA. [Okam, Maureen M.; Nathan, David G.] Harvard Univ, Sch Med, Boston, MA USA. [Majerus, Elaine] Washington Univ, Sch Med, St Louis, MO USA. [Keefer, Jeffrey] Johns Hopkins Sch Med, Baltimore, MD USA. [Onyekwere, Onyinye] Howard Univ, Coll Med, Washington, DC USA. [Campigotto, Federico; Neuberg, Donna; Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nathan, David G.] Boston Childrens Hosp, Boston, MA USA. RP Field, JJ (reprint author), Blood Ctr SE Wisconsin Inc, 8733 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM joshua.field@bcw.edu FU National Heart, Lung, and Blood Institute [RC2HL101367, R34HL108757]; Astellas Pharma; Clinical and Translational Science Awards FX This study was supported by National Heart, Lung, and Blood Institute grants RC2HL101367 and R34HL108757 and a grant from Astellas Pharma (D.G.N.). The authors also acknowledge the support provided by Clinical and Translational Science Awards at all participating institutions. NR 26 TC 35 Z9 35 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 25 PY 2013 VL 121 IS 17 BP 3329 EP 3334 DI 10.1182/blood-2012-11-465963 PG 6 WC Hematology SC Hematology GA 183QG UT WOS:000321831600008 PM 23377438 ER PT J AU Ouyang, J Plutschow, A von Strandmann, EP Reiners, KS Ponader, S Rabinovich, GA Neuberg, D Engert, A Shipp, MA AF Ouyang, Jing Pluetschow, Annette von Strandmann, Elke Pogge Reiners, Katrin S. Ponader, Sabine Rabinovich, Gabriel A. Neuberg, Donna Engert, Andreas Shipp, Margaret A. TI Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma SO BLOOD LA English DT Article ID GLYCAN INTERACTIONS; IMMUNE PRIVILEGE; PROGNOSTIC SCORE; DISEASE; EXPRESSION AB Galectin-1 (Gal1) is a member of a highly conserved family of carbohydrate-binding proteins. It modulates innate and adaptive immune responses and fosters tumor-immune escape. Hodgkin lymphoma (HL) Reed-Sternberg cells overexpress and secrete Gal1, which selectively kills T helper (Th)1 and Th17 cells and cytotoxic T cells and promotes the immunosuppressive Th2/regulatory T-cell-predominant HL microenvironment. We developed a sandwich enzyme-linked immunosorbent assay and assessed serum Gal1 levels in 293 newly diagnosed, previously untreated patients with classical HL (cHL) enrolled in 3 risk-adapted clinical trials. Serum Gal1 levels were significantly higher in patients with cHL than in normal controls (P < .0001). Gal1 serum levels also increased with Ann Arbor stage (P = .012), areas of nodal involvement (P < .0001), and the International Prognostic Score (2-7, P = .019). We conclude that Gal1 serum levels are significantly associated with tumor burden and related clinical features in newly diagnosed cHL patients. C1 [Ouyang, Jing; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Pluetschow, Annette; Ponader, Sabine; Engert, Andreas] Univ Hosp Cologne, German Hodgkin Study Grp, Cologne, Germany. [von Strandmann, Elke Pogge; Reiners, Katrin S.] Univ Hosp Cologne, Lab Immunotherapy, Cologne, Germany. [Rabinovich, Gabriel A.] Consejo Nacl Invest Cient & Tecn, Lab Inmunopatol, Inst Biol & Med Expt, Buenos Aires, DF, Argentina. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02215 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM margaret_shipp@dfci.harvard.edu FU Leukemia and Lymphoma Society (SCOR) [7009-12]; DFG [SFB832, TP19] FX This work was supported by the Leukemia and Lymphoma Society (SCOR #7009-12) (M. A. S.) and (DFG #SFB832, TP19) (E.P.v.S.). NR 17 TC 20 Z9 20 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 25 PY 2013 VL 121 IS 17 BP 3431 EP 3433 DI 10.1182/blood-2012-12-474569 PG 3 WC Hematology SC Hematology GA 183QG UT WOS:000321831600019 PM 23444403 ER PT J AU Bai, XY Feldman, NE Chmura, K Ovrutsky, AR Su, WL Griffin, L Pyeon, D McGibney, MT Strand, MJ Numata, M Murakami, S Gaido, L Honda, JR Kinney, WH Oberley-Deegan, RE Voelker, DR Ordway, DJ Chan, ED AF Bai, Xiyuan Feldman, Nicole E. Chmura, Kathryn Ovrutsky, Alida R. Su, Wen-Lin Griffin, Laura Pyeon, Dohun McGibney, Mischa T. Strand, Matthew J. Numata, Mari Murakami, Seiji Gaido, Loretta Honda, Jennifer R. Kinney, William H. Oberley-Deegan, Rebecca E. Voelker, Dennis R. Ordway, Diane J. Chan, Edward D. TI Inhibition of Nuclear Factor-Kappa B Activation Decreases Survival of Mycobacterium tuberculosis in Human Macrophages SO PLOS ONE LA English DT Article ID TUMOR-NECROSIS-FACTOR; DRUG-RESISTANT TUBERCULOSIS; TOLL-LIKE RECEPTORS; NITRIC-OXIDE; TRANSCRIPTION FACTOR; HOST-DEFENSE; TNF-ALPHA; ALVEOLAR MACROPHAGES; MURINE MACROPHAGES; INTERLEUKIN-8 GENE AB Nuclear factor-kappa B (NF kappa B) is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NF kappa B has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NF kappa B are more likely to succumb to Mycobacterium tuberculosis (MTB). However, the role of NF kappa B in host defense in humans is not fully understood. We sought to examine the role of NFkB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NF kappa B activation using BAY 11-7082 (BAY, an inhibitor of I kappa B alpha kinase) or an adenovirus construct with a dominant-negative IkBa significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NF kappa B inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NF kappa B inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy. C1 [Bai, Xiyuan; Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [Bai, Xiyuan; Feldman, Nicole E.; Chmura, Kathryn; Ovrutsky, Alida R.; McGibney, Mischa T.; Strand, Matthew J.; Numata, Mari; Murakami, Seiji; Honda, Jennifer R.; Kinney, William H.; Oberley-Deegan, Rebecca E.; Voelker, Dennis R.; Chan, Edward D.] Natl Jewish Hlth, Dept Med & Acad Affairs, Denver, CO USA. [Bai, Xiyuan; Chmura, Kathryn; Ovrutsky, Alida R.; Honda, Jennifer R.; Kinney, William H.; Chan, Edward D.] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Gaido, Loretta] Denver Hlth Med Ctr, Denver, CO USA. [Griffin, Laura; Pyeon, Dohun] Univ Colorado, Sch Med, Dept Microbiol, Aurora, CO USA. [Su, Wen-Lin] Natl Def Med Ctr, Dept Med, Tri Serv Gen Hosp, Taipei, Taiwan. [Ordway, Diane J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. RP Bai, XY (reprint author), Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. EM baix@njhealth.org; chane@njhealth.org FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development [1 I01 BX001028-01A2]; National Institutes of Health (NIH) [PHL073907]; General Clinical Research Center Program Grant [M01-RR00051] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development 1 I01 BX001028-01A2 (to EDC), National Institutes of Health (NIH) PHL073907 (to DRV), and General Clinical Research Center Program Grant No. M01-RR00051. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 75 TC 13 Z9 14 U1 1 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 25 PY 2013 VL 8 IS 4 AR e61925 DI 10.1371/journal.pone.0061925 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 136DM UT WOS:000318341400027 PM 23634218 ER PT J AU Howe, K Clark, MD Torroja, CF Torrance, J Berthelot, C Muffato, M Collins, JE Humphray, S McLaren, K Matthews, L McLaren, S Sealy, I Caccamo, M Churcher, C Scott, C Barrett, JC Koch, R Rauch, GJ White, S Chow, W Kilian, B Quintais, LT Guerra-Assuncao, JA Zhou, Y Gu, Y Yen, J Vogel, JH Eyre, T Redmond, S Banerjee, R Chi, JX Fu, BY Langley, E Maguire, SF Laird, GK Lloyd, D Kenyon, E Donaldson, S Sehra, H Almeida-King, J Loveland, J Trevanion, S Jones, M Quail, M Willey, D Hunt, A Burton, J Sims, S McLay, K Plumb, B Davis, J Clee, C Oliver, K Clark, R Riddle, C Eliott, D Threadgold, G Harden, G Ware, D Mortimer, B Kerry, G Heath, P Phillimore, B Tracey, A Corby, N Dunn, M Johnson, C Wood, J Clark, S Pelan, S Griffiths, G Smith, M Glithero, R Howden, P Barker, N Stevens, C Harley, J Holt, K Panagiotidis, G Lovell, J Beasley, H Henderson, C Gordon, D Auger, K Wright, D Collins, J Raisen, C Dyer, L Leung, K Robertson, L Ambridge, K Leongamornlert, D McGuire, S Gilderthorp, R Griffiths, C Manthravadi, D Nichol, S Barker, G Whitehead, S Kay, M Brown, J Murnane, C Gray, E Humphries, M Sycamore, N Barker, D Saunders, D Wallis, J Babbage, A Hammond, S Mashreghi-Mohammadi, M Barr, L Martin, S Wray, P Ellington, A Matthews, N Ellwood, M Woodmansey, R Clark, G Cooper, J Tromans, A Grafham, D Skuce, C Pandian, R Andrews, R Harrison, E Kimberley, A Garnett, J Fosker, N Hall, R Garner, P Kelly, D Bird, C Palmer, S Gehring, I Berger, A Dooley, CM Ersan-Urun, Z Eser, C Geiger, H Geisler, M Karotki, L Kirn, A Konantz, J Konantz, M Oberlander, M Rudolph-Geiger, S Teucke, M Osoegawa, K Zhu, BL Rapp, A Widaa, S Langford, C Yang, FT Carter, NP Harrow, J Ning, ZM Herrero, J Searle, SMJ Enright, A Geisler, R Plasterk, RHA Lee, C Westerfield, M de Jong, PJ Zon, LI Postlethwait, JH Nusslein-Volhard, C Hubbard, TJP Crollius, HR Rogers, J Stemple, DL AF Howe, Kerstin Clark, Matthew D. Torroja, Carlos F. Torrance, James Berthelot, Camille Muffato, Matthieu Collins, John E. Humphray, Sean McLaren, Karen Matthews, Lucy McLaren, Stuart Sealy, Ian Caccamo, Mario Churcher, Carol Scott, Carol Barrett, Jeffrey C. Koch, Romke Rauch, Gerd-Joerg White, Simon Chow, William Kilian, Britt Quintais, Leonor T. Guerra-Assuncao, Jose A. Zhou, Yi Gu, Yong Yen, Jennifer Vogel, Jan-Hinnerk Eyre, Tina Redmond, Seth Banerjee, Ruby Chi, Jianxiang Fu, Beiyuan Langley, Elizabeth Maguire, Sean F. Laird, Gavin K. Lloyd, David Kenyon, Emma Donaldson, Sarah Sehra, Harminder Almeida-King, Jeff Loveland, Jane Trevanion, Stephen Jones, Matt Quail, Mike Willey, Dave Hunt, Adrienne Burton, John Sims, Sarah McLay, Kirsten Plumb, Bob Davis, Joy Clee, Chris Oliver, Karen Clark, Richard Riddle, Clare Eliott, David Threadgold, Glen Harden, Glenn Ware, Darren Mortimer, Beverly Kerry, Giselle Heath, Paul Phillimore, Benjamin Tracey, Alan Corby, Nicole Dunn, Matthew Johnson, Christopher Wood, Jonathan Clark, Susan Pelan, Sarah Griffiths, Guy Smith, Michelle Glithero, Rebecca Howden, Philip Barker, Nicholas Stevens, Christopher Harley, Joanna Holt, Karen Panagiotidis, Georgios Lovell, Jamieson Beasley, Helen Henderson, Carl Gordon, Daria Auger, Katherine Wright, Deborah Collins, Joanna Raisen, Claire Dyer, Lauren Leung, Kenric Robertson, Lauren Ambridge, Kirsty Leongamornlert, Daniel McGuire, Sarah Gilderthorp, Ruth Griffiths, Coline Manthravadi, Deepa Nichol, Sarah Barker, Gary Whitehead, Siobhan Kay, Michael Brown, Jacqueline Murnane, Clare Gray, Emma Humphries, Matthew Sycamore, Neil Barker, Darren Saunders, David Wallis, Justene Babbage, Anne Hammond, Sian Mashreghi-Mohammadi, Maryam Barr, Lucy Martin, Sancha Wray, Paul Ellington, Andrew Matthews, Nicholas Ellwood, Matthew Woodmansey, Rebecca Clark, Graham Cooper, James Tromans, Anthony Grafham, Darren Skuce, Carl Pandian, Richard Andrews, Robert Harrison, Elliot Kimberley, Andrew Garnett, Jane Fosker, Nigel Hall, Rebekah Garner, Patrick Kelly, Daniel Bird, Christine Palmer, Sophie Gehring, Ines Berger, Andrea Dooley, Christopher M. Ersan-Ueruen, Zuebeyde Eser, Cigdem Geiger, Horst Geisler, Maria Karotki, Lena Kirn, Anette Konantz, Judith Konantz, Martina Oberlaender, Martina Rudolph-Geiger, Silke Teucke, Mathias Osoegawa, Kazutoyo Zhu, Baoli Rapp, Amanda Widaa, Sara Langford, Cordelia Yang, Fengtang Carter, Nigel P. Harrow, Jennifer Ning, Zemin Herrero, Javier Searle, Steve M. J. Enright, Anton Geisler, Robert Plasterk, Ronald H. A. Lee, Charles Westerfield, Monte de Jong, Pieter J. Zon, Leonard I. Postlethwait, John H. Nuesslein-Volhard, Christiane Hubbard, Tim J. P. Crollius, Hugues Roest Rogers, Jane Stemple, Derek L. TI The zebrafish reference genome sequence and its relationship to the human genome SO NATURE LA English DT Article ID DANIO-RERIO; DUPLICATION; EVOLUTION; FISH; GENE; MUTATIONS; VERTEBRATES; REVEALS; MAP AB Zebrafish have become a popular organism for the study of vertebrate gene function(1,2). The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease(3-5). However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes(6), the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination. C1 [Howe, Kerstin; Clark, Matthew D.; Torroja, Carlos F.; Torrance, James; Collins, John E.; Humphray, Sean; McLaren, Karen; Matthews, Lucy; McLaren, Stuart; Sealy, Ian; Churcher, Carol; Scott, Carol; Barrett, Jeffrey C.; White, Simon; Chow, William; Kilian, Britt; Gu, Yong; Yen, Jennifer; Vogel, Jan-Hinnerk; Eyre, Tina; Redmond, Seth; Banerjee, Ruby; Chi, Jianxiang; Fu, Beiyuan; Langley, Elizabeth; Maguire, Sean F.; Laird, Gavin K.; Lloyd, David; Kenyon, Emma; Donaldson, Sarah; Sehra, Harminder; Almeida-King, Jeff; Loveland, Jane; Trevanion, Stephen; Jones, Matt; Quail, Mike; Willey, Dave; Hunt, Adrienne; Burton, John; Sims, Sarah; McLay, Kirsten; Plumb, Bob; Davis, Joy; Clee, Chris; Oliver, Karen; Clark, Richard; Riddle, Clare; Eliott, David; Threadgold, Glen; Harden, Glenn; Ware, Darren; Mortimer, Beverly; Kerry, Giselle; Heath, Paul; Phillimore, Benjamin; Tracey, Alan; Corby, Nicole; Dunn, Matthew; Johnson, Christopher; Wood, Jonathan; Clark, Susan; Pelan, Sarah; Griffiths, Guy; Smith, Michelle; Glithero, Rebecca; Howden, Philip; Barker, Nicholas; Stevens, Christopher; Harley, Joanna; Holt, Karen; Panagiotidis, Georgios; Lovell, Jamieson; Beasley, Helen; Henderson, Carl; Gordon, Daria; Auger, Katherine; Wright, Deborah; Collins, Joanna; Raisen, Claire; Dyer, Lauren; Leung, Kenric; Robertson, Lauren; Ambridge, Kirsty; Leongamornlert, Daniel; McGuire, Sarah; Gilderthorp, Ruth; Griffiths, Coline; Manthravadi, Deepa; Nichol, Sarah; Barker, Gary; Whitehead, Siobhan; Kay, Michael; Brown, Jacqueline; Murnane, Clare; Gray, Emma; Humphries, Matthew; Sycamore, Neil; Barker, Darren; Saunders, David; Wallis, Justene; Babbage, Anne; Hammond, Sian; Mashreghi-Mohammadi, Maryam; Barr, Lucy; Martin, Sancha; Wray, Paul; Ellington, Andrew; Matthews, Nicholas; Ellwood, Matthew; Woodmansey, Rebecca; Clark, Graham; Cooper, James; Tromans, Anthony; Grafham, Darren; Skuce, Carl; Pandian, Richard; Andrews, Robert; Harrison, Elliot; Kimberley, Andrew; Garnett, Jane; Fosker, Nigel; Hall, Rebekah; Garner, Patrick; Kelly, Daniel; Bird, Christine; Palmer, Sophie; Berger, Andrea; Dooley, Christopher M.; Widaa, Sara; Langford, Cordelia; Yang, Fengtang; Carter, Nigel P.; Harrow, Jennifer; Ning, Zemin; Searle, Steve M. J.; Hubbard, Tim J. P.; Rogers, Jane; Stemple, Derek L.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Clark, Matthew D.; Caccamo, Mario; Rogers, Jane] Genome Anal Ctr, Norwich NR4 7UH, Norfolk, England. [Torroja, Carlos F.] Ctr Nacl Invest Cardiovasc, Bioinformat Unit, Madrid 28029, Spain. [Berthelot, Camille; Crollius, Hugues Roest] ENS, Inst Biol, IBENS, F-75005 Paris, France. [Berthelot, Camille; Crollius, Hugues Roest] INSERM, U1024, F-75005 Paris, France. [Berthelot, Camille; Crollius, Hugues Roest] CNRS, UMR 8197, F-75005 Paris, France. [Muffato, Matthieu; Quintais, Leonor T.; Guerra-Assuncao, Jose A.; Herrero, Javier; Enright, Anton] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England. [Humphray, Sean] Illumina Cambridge, Saffron Walden CB10 1XL, Essex, England. [Koch, Romke; Plasterk, Ronald H. A.] Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. [Rauch, Gerd-Joerg; Gehring, Ines; Berger, Andrea; Dooley, Christopher M.; Ersan-Ueruen, Zuebeyde; Eser, Cigdem; Geiger, Horst; Geisler, Maria; Karotki, Lena; Kirn, Anette; Konantz, Judith; Konantz, Martina; Oberlaender, Martina; Rudolph-Geiger, Silke; Teucke, Mathias; Geisler, Robert; Nuesslein-Volhard, Christiane] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany. [Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. [Zhou, Yi; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Osoegawa, Kazutoyo; Zhu, Baoli; de Jong, Pieter J.] Childrens Hosp Oakland, Oakland, CA 94609 USA. [Rapp, Amanda; Westerfield, Monte; Postlethwait, John H.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. [Geisler, Robert] KIT, ITG, D-76344 Eggenstein Leopoldshafen, Germany. [Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lee, Charles] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stemple, DL (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. EM ds4@sanger.ac.uk RI sebastianovitsch, stepan/G-8507-2013; Torroja, Carlos/N-6022-2014; Ning, Zemin/D-2411-2013; Hubbard, Tim/C-2567-2008; Vogel, Jan-Hinnerk/C-4582-2013; OI Stemple, Derek/0000-0002-8296-9928; Muffato, Matthieu/0000-0002-7860-3560; Chow, William/0000-0002-9056-201X; ROEST CROLLIUS, Hugues/0000-0002-8209-173X; Ning, Zemin/0000-0003-4359-776X; Guerra-Assuncao, Jose Afonso/0000-0001-6593-403X; Almeida-King, Jeff/0000-0002-3716-4880; Herrero, Javier/0000-0001-7313-717X; Barrett, Jeffrey/0000-0002-1152-370X; Enright, Anton/0000-0002-6090-3100; Leongamornlert, Daniel/0000-0002-3486-3168; Martin, Sancha/0000-0001-6213-5259; Hunt, Adrienne/0000-0002-1227-0310; Cooper, James/0000-0002-4932-1740; Torroja, Carlos/0000-0001-8914-3400; Hubbard, Tim/0000-0002-1767-9318; Kilian, Britt/0000-0003-1493-2768; Kerry, Giselle/0000-0002-2380-6707; Howe, Kerstin/0000-0003-2237-513X; Berthelot, Camille/0000-0001-5054-2690; Trevanion, Stephen/0000-0002-4862-3333 FU National Institutes of Health (NIH) [R01 GM085318, P01 HD22486, R01 OD011116, R01 RR020833, 1 R01 DK55377-01A1]; European Commission [LSHG-CT-2003-503496, HEALTH-F4-2010-242048]; German Human Genome Project (DHGP) [01 KW 9627, 01 KW 9919]; Wellcome Trust [098051] FX We wish to thank R. Durbin, E. Birney, A. Scally, C. P. Ponting, E. Busch-Nentwich and R. Kettleborough for helpful discussions, as well as F. L. Marlow and P. Aanstad for critical reading and helpful comments on manuscripts. We thank the zebrafish information network (ZFIN) for funding part of the manual annotation of the zebrafish genome and the ZFIN staff for support with gene nomenclature and other genome issues. We also thank the Genome Reference Consortium for the maintenance and improvement of the zebrafish genome assembly. We are indebted to the Ensembl team for providing a browser and database that greatly facilitated the use and the analyses of the zebrafish genome. We thank A. Pirani at Affymetrix for genotyping advice support, and the Zebrafish International Resource Center (ZIRC) for distributing the SAT strain. J.H.P. was supported by the National Institutes of Health (NIH) grant R01 GM085318 (to J.H.P.), NIH grant P01 HD22486 (to J.H.P.) and R01 OD011116 (later changed to R01 RR020833) (to J.H.P.). We would like to acknowledge the support of the European Commission's Sixth Framework Programme (contract no. LSHG-CT-2003-503496, ZF-MODELS) and Seventh Framework Programme (grant no. HEALTH-F4-2010-242048, ZF-HEALTH). R. G. was supported by the German Human Genome Project (DHGP Grant 01 KW 9627 and 01 KW 9919). C. N.-V., G.-J.R. and R. G. were supported by the NIH (NIH grant 1 R01 DK55377-01A1). The Zebrafish Genome Project at the Wellcome Trust Sanger Institute was funded by Wellcome Trust grant number 098051. NR 30 TC 588 Z9 1607 U1 59 U2 351 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 25 PY 2013 VL 496 IS 7446 BP 498 EP 503 DI 10.1038/nature12111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 131HU UT WOS:000317984400040 PM 23594743 ER PT J AU Montgomery, TA Ruvkun, G AF Montgomery, Taiowa A. Ruvkun, Gary TI MicroRNAs Visit the ER SO CELL LA English DT Editorial Material ID MIRNA; PROTEIN; FAMILY; DECAY AB Little is known about where microRNAs (miRNAs) regulate their targets within the cell. In this issue, Li et al. identify a new player in the plant miRNA pathway that implicates the endoplasmic reticulum in miRNA-mediated gene silencing. C1 [Montgomery, Taiowa A.; Ruvkun, Gary] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Montgomery, Taiowa/0000-0001-7857-3253 NR 10 TC 1 Z9 1 U1 0 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 25 PY 2013 VL 153 IS 3 BP 511 EP 512 DI 10.1016/j.cell.2013.04.014 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 132JK UT WOS:000318063500004 PM 23622236 ER PT J AU Baca, SC Prandi, D Lawrence, MS Mosquera, JM Romanel, A Drier, Y Park, K Kitabayashi, N MacDonald, TY Ghandi, M Van Allen, E Kryukov, GV Sboner, A Theurillat, JP Soong, TD Nickerson, E Auclair, D Tewari, A Beltran, H Onofrio, RC Boysen, G Guiducci, C Barbieri, CE Cibulskis, K Sivachenko, A Carter, SL Saksena, G Voet, D Ramos, AH Winckler, W Cipicchio, M Ardlie, K Kantoff, PW Berger, MF Gabriel, SB Golub, TR Meyerson, M Lander, ES Elemento, O Getz, G Demichelis, F Rubin, MA Garraway, LA AF Baca, Sylvan C. Prandi, Davide Lawrence, Michael S. Mosquera, Juan Miguel Romanel, Alessandro Drier, Yotam Park, Kyung Kitabayashi, Naoki MacDonald, Theresa Y. Ghandi, Mahmoud Van Allen, Eliezer Kryukov, Gregory V. Sboner, Andrea Theurillat, Jean-Philippe Soong, T. David Nickerson, Elizabeth Auclair, Daniel Tewari, Ashutosh Beltran, Himisha Onofrio, Robert C. Boysen, Gunther Guiducci, Candace Barbieri, Christopher E. Cibulskis, Kristian Sivachenko, Andrey Carter, Scott L. Saksena, Gordon Voet, Douglas Ramos, Alex H. Winckler, Wendy Cipicchio, Michelle Ardlie, Kristin Kantoff, Philip W. Berger, Michael F. Gabriel, Stacey B. Golub, Todd R. Meyerson, Matthew Lander, Eric S. Elemento, Olivier Getz, Gad Demichelis, Francesca Rubin, Mark A. Garraway, Levi A. TI Punctuated Evolution of Prostate Cancer Genomes SO CELL LA English DT Article ID TMPRSS2-ERG FUSION; REARRANGEMENTS; MUTATIONS; CHD1; SAMPLES; EVENT AB The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term "chromoplexy," frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. C1 [Baca, Sylvan C.; Kryukov, Gregory V.; Ramos, Alex H.; Kantoff, Philip W.; Meyerson, Matthew; Lander, Eric S.; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Baca, Sylvan C.; Lawrence, Michael S.; Drier, Yotam; Ghandi, Mahmoud; Van Allen, Eliezer; Kryukov, Gregory V.; Theurillat, Jean-Philippe; Nickerson, Elizabeth; Auclair, Daniel; Onofrio, Robert C.; Guiducci, Candace; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L.; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Winckler, Wendy; Cipicchio, Michelle; Ardlie, Kristin; Gabriel, Stacey B.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Baca, Sylvan C.; Van Allen, Eliezer; Kantoff, Philip W.; Meyerson, Matthew; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Golub, Todd R.; Meyerson, Matthew; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Prandi, Davide; Romanel, Alessandro; Demichelis, Francesca] Univ Trento, Ctr Integrat Biol, I-38123 Povo, Trento, Italy. [Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. [Mosquera, Juan Miguel; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y.; Sboner, Andrea; Boysen, Gunther; Barbieri, Christopher E.; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Sboner, Andrea; Soong, T. David; Elemento, Olivier; Demichelis, Francesca] Weill Cornell Med Coll, Dept Physiol & Biophys, Inst Computat Biomed, New York, NY 10065 USA. [Tewari, Ashutosh] Weill Cornell Med Coll, Lefrak Ctr Robot Surg, New York, NY 10065 USA. [Tewari, Ashutosh] Weill Cornell Med Coll, Ctr Prostate Canc Res & Clin Care, New York, NY 10065 USA. [Tewari, Ashutosh; Barbieri, Christopher E.; Rubin, Mark A.] Weill Cornell Med Coll, Brady Fdn Dept Urol, New York, NY 10065 USA. [Beltran, Himisha] Weill Cornell Med Coll, Div Hematol & Med Oncol, Dept Med, New York, NY 10065 USA. [Kryukov, Gregory V.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Berger, Michael F.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Demichelis, F (reprint author), Univ Trento, Ctr Integrat Biol, I-38123 Povo, Trento, Italy. EM demichelis@science.unitn.it; levi_garraway@dfci.harvard.edu RI Kryukov, Gregory/A-9592-2008; Sboner, Andrea/C-6487-2008; Drier, Yotam/K-5208-2012; OI Romanel, Alessandro/0000-0003-4855-8620; Sboner, Andrea/0000-0001-6915-3070; Drier, Yotam/0000-0003-1725-2995; Van Allen, Eliezer/0000-0002-0201-4444; Barbieri, Christopher/0000-0002-0381-1947; Prandi, Davide/0000-0001-9885-6074; Boysen, Gunther/0000-0002-7610-6085; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631; Ghandi, Mahmoud/0000-0003-1897-2265 FU US National Human Genome Research Institute (NHGRI) Large Scale Sequencing Program [U54 HG003067]; Kohlberg Foundation; Starr Cancer Consortium; Prostate Cancer Foundation; US Department of Defense Synergy Awards [PC101020]; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (US National Institutes of Health [NIH]) [P50 CA090381]; US National Cancer Institute, Early Detection Research Network [U01CA111275]; NCI EDRN; US National Cancer Institute [R01 CA125612]; Fondazione Trentina per la Ricerca sui Tumori; Swiss Science Foundation [PASMP3_134379/1]; National Institute of General Medical Sciences [T32GM007753]; US NIH Director's New Innovator Award [DP2OD002750]; Novartis; [PC094516] FX We thank the members of the Broad Institute Genome Sequencing Platform for their part in this work. This study was supported by the US National Human Genome Research Institute (NHGRI) Large Scale Sequencing Program (U54 HG003067 to the Broad Institute, E.S.L.), the Kohlberg Foundation (L.A.G.), the Starr Cancer Consortium (M.A.R., F.D., A.T., G.G., and L.A.G.), the Prostate Cancer Foundation (M.A.R.), US Department of Defense Synergy Awards (PC101020 to F.D., L.A.G., and M.A.R.) and a New Investigator Award (PC094516 to F.D.), the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (US National Institutes of Health [NIH] P50 CA090381), the US National Cancer Institute, Early Detection Research Network (U01CA111275 and NCI EDRN to F.D. and M.A.R.), the US National Cancer Institute (R01 CA125612 to F.D. and M.A.R.), the Fondazione Trentina per la Ricerca sui Tumori (F.D.), the Swiss Science Foundation (PASMP3_134379/1 to J.-P.T.), the National Institute of General Medical Sciences (T32GM007753 to S.C.B.), and a US NIH Director's New Innovator Award (DP2OD002750 to L.A.G.). L.A.G. is an equity holder and consultant in Foundation Medicine, a consultant to Novartis and Millenium/Takeda, and a recipient of a grant from Novartis. NR 38 TC 315 Z9 321 U1 5 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 25 PY 2013 VL 153 IS 3 BP 666 EP 677 DI 10.1016/j.cell.2013.03.021 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 132JK UT WOS:000318063500018 PM 23622249 ER PT J AU Shen, L Wu, H Diep, D Yamaguchi, S D'Alessio, AC Fung, HL Zhang, K Zhang, Y AF Shen, Li Wu, Hao Diep, Dinh Yamaguchi, Shinpei D'Alessio, Ana C. Fung, Ho-Lim Zhang, Kun Zhang, Yi TI Genome-wide Analysis Reveals TET- and TDG-Dependent 5-Methylcytosine Oxidation Dynamics SO CELL LA English DT Article ID EMBRYONIC STEM-CELLS; THYMINE DNA GLYCOSYLASE; GENE-EXPRESSION; POSTNATAL-DEVELOPMENT; METHYLATION PATTERNS; BASE-RESOLUTION; MAMMALIAN DNA; 5-HYDROXYMETHYLCYTOSINE; DEMETHYLATION; CHROMATIN AB TET dioxygenases successively oxidize 5-methylcytosine (5mC) in mammalian genomes to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC/5caC can be excised and repaired to regenerate unmodified cytosines by thymine-DNA glycosylase (TDG) and base excision repair (BER) pathway, but it is unclear to what extent and at which part of the genome this active demethylation process takes place. Here, we have generated genome-wide distribution maps of 5hmC/5fC/5caC using modification-specific antibodies in wild-type and Tdg-deficient mouse embryonic stem cells (ESCs). In wild-type mouse ESCs, 5fC/5caC accumulates to detectable levels at major satellite repeats but not at nonrepetitive loci. In contrast, Tdg depletion in mouse ESCs causes marked accumulation of 5fC and 5caC at a large number of proximal and distal gene regulatory elements. Thus, these results reveal the genome-wide view of iterative 5mC oxidation dynamics and indicate that TET/TDG-dependent active DNA demethylation process occurs extensively in the mammalian genome. C1 [Shen, Li; Wu, Hao; Yamaguchi, Shinpei; D'Alessio, Ana C.; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Shen, Li; Wu, Hao; Yamaguchi, Shinpei; D'Alessio, Ana C.; Zhang, Yi] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA. [Shen, Li; Wu, Hao; Yamaguchi, Shinpei; D'Alessio, Ana C.; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Wu, Hao] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Diep, Dinh; Fung, Ho-Lim; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Wu, H (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, WAB-149G,200 Longwood Ave, Boston, MA 02115 USA. EM haowu7@gmail.com; yzhang@genetics.med.harvard.edu RI Wu, Hao/G-4145-2013; OI Wu, Hao/0000-0002-1256-6891; Yamaguchi, Shinpei/0000-0002-9377-4835 FU NIH [U01DK089565, R01GM097253]; Jane Coffin Childs Funds for Medical Research FX We thank Drs. Jin He and Falong Lu for their helpful discussions. This project is supported by NIH grant U01DK089565 (to Y.Z.) and R01GM097253 (to K.Z.). H.W. is supported by a postdoctoral fellowship (Merck Fellow) from Jane Coffin Childs Funds for Medical Research. D.D. is a CIRM predoctoral fellow. Y.Z. is an investigator of the Howard Hughes Medical Institute. NR 73 TC 199 Z9 200 U1 10 U2 80 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 25 PY 2013 VL 153 IS 3 BP 692 EP 706 DI 10.1016/j.cell.2013.04.002 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 132JK UT WOS:000318063500020 PM 23602152 ER PT J AU Zhang, B Gaiteri, C Bodea, LG Wang, Z McElwee, J Podtelezhnikov, AA Zhang, CS Xie, T Tran, L Dobrin, R Fluder, E Clurman, B Melquist, S Narayanan, M Suver, C Shah, H Mahajan, M Gillis, T Mysore, J MacDonald, ME Lamb, JR Bennett, DA Molony, C Stone, DJ Gudnason, V Myers, AJ Schadt, EE Neumann, H Zhu, J Emilsson, V AF Zhang, Bin Gaiteri, Chris Bodea, Liviu-Gabriel Wang, Zhi McElwee, Joshua Podtelezhnikov, Alexei A. Zhang, Chunsheng Xie, Tao Tran, Linh Dobrin, Radu Fluder, Eugene Clurman, Bruce Melquist, Stacey Narayanan, Manikandan Suver, Christine Shah, Hardik Mahajan, Milind Gillis, Tammy Mysore, Jayalakshmi MacDonald, Marcy E. Lamb, John R. Bennett, David A. Molony, Cliona Stone, David J. Gudnason, Vilmundur Myers, Amanda J. Schadt, Eric E. Neumann, Harald Zhu, Jun Emilsson, Valur TI Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer's Disease SO CELL LA English DT Article ID MOLECULAR NETWORKS; HUMAN BRAIN; EXPRESSION; DYSFUNCTION; MICROGLIA; RISK AB The genetics of complex disease produce alterations in the molecular interactions of cellular pathways whose collective effect may become clear through the organized structure of molecular networks. To characterize molecular systems associated with late-onset Alzheimer's disease (LOAD), we constructed gene-regulatory networks in 1,647 postmortem brain tissues from LOAD patients and nondemented subjects, and we demonstrate that LOAD reconfigures specific portions of the molecular interaction structure. Through an integrative network-based approach, we rank-ordered these network structures for relevance to LOAD pathology, highlighting an immune- and microglia-specific module that is dominated by genes involved in pathogen phagocytosis, contains TYROBP as a key regulator, and is upregulated in LOAD. Mouse microglia cells overexpressing intact or truncated TYROBP revealed expression changes that significantly overlapped the human brain TYROBP network. Thus the causal network structure is a useful predictor of response to gene perturbations and presents a framework to test models of disease mechanisms underlying LOAD. C1 [Zhang, Bin; Shah, Hardik; Mahajan, Milind; Schadt, Eric E.; Zhu, Jun] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Zhang, Bin; Shah, Hardik; Mahajan, Milind; Schadt, Eric E.; Zhu, Jun] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Zhang, Bin; Mahajan, Milind; Schadt, Eric E.; Zhu, Jun] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA. [Zhang, Bin; Gaiteri, Chris; Wang, Zhi; Tran, Linh; Suver, Christine] Sage Bionetworks, Seattle, WA 98109 USA. [Bodea, Liviu-Gabriel; Neumann, Harald] Univ Bonn, Neural Regenerat Grp, Inst Reconstruct Neurobiol, D-53127 Bonn, Germany. [McElwee, Joshua; Zhang, Chunsheng; Xie, Tao; Dobrin, Radu; Fluder, Eugene; Melquist, Stacey; Narayanan, Manikandan; Molony, Cliona] Merck & Co Inc, Merck Res Labs, Boston, MA 02115 USA. [Podtelezhnikov, Alexei A.; Stone, David J.] Merck & Co Inc, Merck Res Labs, West Point, PA 19486 USA. [Clurman, Bruce] Fred Hutch Canc Res Ctr, Seattle, WA 98109 USA. [Gillis, Tammy; Mysore, Jayalakshmi; MacDonald, Marcy E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lamb, John R.] GNF Novartis, San Diego, CA 92121 USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimer Dis Ctr, Chicago, IL 60612 USA. [Gudnason, Vilmundur; Emilsson, Valur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Gudnason, Vilmundur; Emilsson, Valur] Univ Iceland, IS-201 Kopavogur, Iceland. [Myers, Amanda J.] Univ Miami, Miller Sch Med, Div Neurosci, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. RP Zhang, B (reprint author), Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, 1425 Madison Ave, New York, NY 10029 USA. EM bin.zhang@mssm.edu; valur@hjarta.is RI Myers, Amanda/B-1796-2010; Bodea, Liviu/F-9480-2012; Gudnason, Vilmundur/K-6885-2015; Neumann, Harald/A-9718-2010; OI Myers, Amanda/0000-0002-3100-9396; Bodea, Liviu/0000-0002-9604-9524; Gudnason, Vilmundur/0000-0001-5696-0084; Neumann, Harald/0000-0002-5071-5202; Suver, Christine/0000-0002-2986-385X; Dobrin, Radu/0000-0002-3336-0091 FU Hertie-Foundation; Deutsche Forschungsgemeinschaft [FOR1336, SFB704, KFO177]; DFG; National Institutes of Health [R01 AG034504, R01 AG030146, P30 AG10161, R01 AG17917, R01 AG15819, K08 AG034290, R01 AG11101, NS032765]; Illinois Department of Public Health; University of Miami; Miller School of Medicine FX H.N. and L.-G.B. were supported by the Hertie-Foundation and the Deutsche Forschungsgemeinschaft (FOR1336, SFB704, KFO177). H.N. is a member of the DFG-funded excellence cluster ImmunoSensation. We thank Jessica Schumacher and Rita Hass for technical assistance. We are grateful to the HBTRC for the generous gift of human postmortem brain samples. The authors are also grateful to the participants in the Religious Orders Study and the Memory and Aging Project. This work is supported by the National Institutes of Health (R01 AG034504, R01 AG030146, P30 AG10161, R01 AG17917, R01 AG15819, K08 AG034290, P30 AG10161, R01 AG11101, and NS032765), the Illinois Department of Public Health, and start-up funding from the University of Miami, Miller School of Medicine. J.M., A.A.P., C.Z., T.X., R.D., E.F., S.M., M.N., C.M., and D.J.S. are employees and shareholders of Merck & Co., Inc. J.R.L. is an employee and shareholder of Novartis. NR 41 TC 300 Z9 303 U1 13 U2 101 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 25 PY 2013 VL 153 IS 3 BP 707 EP 720 DI 10.1016/j.cell.2013.03.030 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 132JK UT WOS:000318063500021 PM 23622250 ER PT J AU Lee, PCW Dodart, JC Aron, L Finley, LW Bronson, RT Haigis, MC Yankner, BA Harper, JW AF Lee, Peter C. W. Dodart, Jean-Cosme Aron, Liviu Finley, Lydia W. Bronson, Roderick T. Haigis, Marcia C. Yankner, Bruce A. Harper, J. Wade TI Altered Social Behavior and Neuronal Development in Mice Lacking the Uba6-Use1 Ubiquitin Transfer System SO MOLECULAR CELL LA English DT Article ID DENDRITIC SPINE MORPHOLOGY; END RULE PATHWAY; HIPPOCAMPAL-NEURONS; PROTEIN LIGASE; DEGRADATION; ENZYME; PLASTICITY; COMPLEX; SYNAPSE; E2 AB The Uba6 (E1)-Use1 (E2) ubiquitin transfer cascade is a poorly understood alternative arm of the ubiquitin proteasome system (UPS) and is required for mouse embryonic development, independent of the canonical Uba1-E2-E3 pathway. Loss of neuronal Uba6 during embryonic development results in altered patterning of neurons in the hippocampus and the annygdala, decreased dendritic spine density, and numerous behavioral disorders. The levels of the E3 ubiquitin ligase Ube3a (E6-AP) and Shank3, both linked with dendritic spine function, are elevated in the amygdala of Uba6-deficient mice, while levels of the Ube3a substrate Arc are reduced. Uba6 and Use1 promote proteasomal turnover of Ube3a in mouse embryo fibroblasts (MEFs) and catalyze Ube3a ubiquitylation in vitro. These activities occur in parallel with an independent pathway involving Uba1-UbcH7, but in a spatially distinct manner in MEFs. These data reveal an unanticipated role for Uba6 in neuronal development, spine architecture, mouse behavior, and turnover of Ube3a. C1 [Lee, Peter C. W.; Finley, Lydia W.; Haigis, Marcia C.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Dodart, Jean-Cosme] Harvard Univ, Sch Med, Harvard Neurodiscovery Ctr, Boston, MA 02115 USA. [Aron, Liviu; Yankner, Bruce A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Rodent Pathol Core, Boston, MA 02115 USA. [Dodart, Jean-Cosme] Univ Ulsan, Coll Med, Dept Biomed Sci, Seoul, South Korea. RP Lee, PCW (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM peter_lee@hms.harvard.edu; wade_harper@hms.harvard.edu FU Millennium Pharmaceuticals, Inc.; NIH [AG011085] FX We thank L.-H. Tsai and J. Graeff for advice; P. Howley for reagents; D. Finley for purified proteasomes; the Nikon Imaging Center at Harvard Medical School for microscopy support; and J. Bolen, J. Brownell, L. Dick, and B. Amidon for numerous discussions. This work was supported by grants to J.W.H. from Millennium Pharmaceuticals, Inc. and the NIH (AG011085). J.W.H. is a consultant for Millenium Pharmaceutics. NR 39 TC 12 Z9 12 U1 0 U2 8 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 APR 25 PY 2013 VL 50 IS 2 BP 172 EP 184 DI 10.1016/j.molcel.2013.02.014 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 134KH UT WOS:000318208600004 PM 23499007 ER PT J AU Snyder, EL Watanabe, H Magendantz, M Hoersch, S Chen, TA Wang, DG Crowley, D Whittaker, CA Meyerson, M Kimura, S Jacks, T AF Snyder, Eric L. Watanabe, Hideo Magendantz, Margaret Hoersch, Sebastian Chen, Tiffany A. Wang, Diana G. Crowley, Denise Whittaker, Charles A. Meyerson, Matthew Kimura, Shioko Jacks, Tyler TI Nkx2-1 Represses a Latent Gastric Differentiation Program in Lung Adenocarcinoma SO MOLECULAR CELL LA English DT Article ID NUCLEAR FACTOR 4-ALPHA; THYROID TRANSCRIPTION FACTOR-1; K-RAS; BRONCHIOLOALVEOLAR CARCINOMA; PULMONARY ADENOCARCINOMA; EPIGENETIC SIGNATURES; EPITHELIAL-CELLS; GENE-EXPRESSION; IN-VIVO; CANCER AB Tissue-specific differentiation programs become dysregulated during cancer evolution. The transcription factor Nkx2-1 is a master regulator of pulmonary differentiation that is downregulated in poorly differentiated lung adenocarcinoma. Here we use conditional murine genetics to determine how the identity of lung epithelial cells changes upon loss of their master cell-fate regulator. Nkx2-1 deletion in normal and neoplastic lungs causes not only loss of pulmonary identity but also conversion to a gastric lineage. Nkx2-1 is likely to maintain pulmonary identity by recruiting transcription factors Foxa1 and Foxa2 to lung-specific loci, thus preventing them from binding gastrointestinal targets. Nkx2-1-negative murine lung tumors mimic mucinous human lung adenocarcinomas, which express gastric markers. Loss of the gastrointestinal transcription factor Hnf4 alpha leads to derepression of the embryonal proto-oncogene Hmga2 in Nkx2-1-negative tumors. These observations suggest that loss of both active and latent differentiation programs is required for tumors to reach a primitive, poorly differentiated state. C1 [Snyder, Eric L.; Magendantz, Margaret; Hoersch, Sebastian; Chen, Tiffany A.; Wang, Diana G.; Crowley, Denise; Whittaker, Charles A.; Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. [Crowley, Denise; Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA. [Snyder, Eric L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Watanabe, Hideo; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Watanabe, Hideo; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Watanabe, Hideo; Meyerson, Matthew] Broad Inst Harvard, Canc Program, Cambridge, MA 02142 USA. [Watanabe, Hideo; Meyerson, Matthew] MIT, Cambridge, MA 02142 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Jacks, T (reprint author), MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. EM tjacks@mit.edu FU Burroughs Wellcome Fund; National Institutes of Health [U01-CA84306, K08-CA154784-01]; Howard Hughes Medical Institute; Ludwig Center for Molecular Oncology at MIT; National Cancer Institute [P30-CA14051] FX We thank N. Dimitrova, D. Feldser, and M. Mendoza for critical reading of the manuscript; the Swanson Biotechnology Center for histology, Illumina sequencing, and bioinformatic support; the BioMicro Center for library preparation and Illumina sequencing; L. Sholl and L. Chirieac for assistance with human lung adenocarcinoma collection; and M. Winslow and the entire Jacks Lab for helpful discussions. E.L.S. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. This work was supported by National Institutes of Health grants U01-CA84306 (to T.J.) and K08-CA154784-01 (to E.L.S.), the Howard Hughes Medical Institute, the Ludwig Center for Molecular Oncology at MIT, and in part by the Cancer Center Support (core) grant P30-CA14051 from the National Cancer Institute. T.J. is the David H. Koch Professor of Biology and a Daniel K. Ludwig Scholar. NR 65 TC 48 Z9 48 U1 1 U2 10 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 APR 25 PY 2013 VL 50 IS 2 BP 185 EP 199 DI 10.1016/j.molcel.2013.02.018 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 134KH UT WOS:000318208600005 PM 23523371 ER PT J AU Jin, C Rajabi, H Rodrigo, CM Porco, JA Kufe, D AF Jin, C. Rajabi, H. Rodrigo, C. M. Porco, J. A., Jr. Kufe, D. TI Targeting the eIF4A RNA helicase blocks translation of the MUC1-C oncoprotein SO ONCOGENE LA English DT Article DE MUC1-C; translation; AKT; mTOR; PDCD4; silvestrol ID GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR PROTEIN; MESSENGER-RNA; MOLECULAR-MECHANISMS; CARCINOMA ANTIGEN; REGULATORY LOOP; MAMMARY-GLAND; BETA-CATENIN; CANCER CELLS; ACTIVATION AB The oncogenic MUC1 C-terminal subunit (MUC1-C) subunit is aberrantly overexpressed in most human breast cancers by mechanisms that are not well understood. The present studies demonstrate that stimulation of non-malignant MCF-10A cells with epidermal growth factor (EGF) or heregulin (HRG) results in marked upregulation of MUC1-C translation. Growth factor-induced MUC1-C translation was found to be mediated by PI3K -> AKT, and not by MEK -> ERK1/2, signaling. We also show that activation of the mammalian target of rapamycin complex 1 (mTORC1)-> ribosomal protein S6 kinase 1 (S6K1) pathway decreases tumor suppressor programmed cell death protein 4 (PDCD4), an inhibitor of the eIF4A RNA helicase, and contributes to the induction of MUC1-C translation. In concert with these results, treatment of growth factor-stimulated MCF-10A cells with the eIF4A RNA helicase inhibitors, silvestrol and CR-1-31-B, blocked increases in MUC1-C abundance. The functional significance of the increase in MUC1-C translation is supported by the demonstration that MUC1-C, in turn, forms complexes with EGF receptor (EGFR) and promotes EGFR-mediated activation of the PI3K -> AKT pathway and the induction of growth. Compared with MCF-10A cells, constitutive overexpression of MUC1-C in breast cancer cells was unaffected by EGF stimulation, but was blocked by inhibiting PI3K -> AKT signaling. The overexpression of MUC1-C in breast cancer cells was also inhibited by blocking eIF4A RNA helicase activity with silvestrol and CR-1-31-B. These findings indicate that EGF-induced MUC1-C expression is mediated by the PI3K -> AKT pathway and the eIF4A RNA helicase, and that this response promotes EGFR signaling in an autoinductive loop. The findings also indicate that targeting the eIF4A RNA helicase is a novel approach for blocking MUC1-C overexpression in breast cancer cells. Oncogene (2013) 32, 2179-2188; doi:10.1038/onc.2012.236; published online 11 June 2012 C1 [Jin, C.; Rajabi, H.; Kufe, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodrigo, C. M.; Porco, J. A., Jr.] Boston Univ, Dept Chem, Ctr Chem Methodol & Lib Dev, Boston, MA 02215 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Dana 830, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute [CA97098, CA42802, CA100707]; National Institutes of Health Grant [GM-073855]; American Cancer Society [PF-11-077-01-CDD] FX This work was supported by the National Cancer Institute Grants CA97098, CA42802 and CA100707; the National Institutes of Health Grant GM-073855 (JAP), and a postdoctoral fellowship from the American Cancer Society PF-11-077-01-CDD (CMR). NR 44 TC 11 Z9 13 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 25 PY 2013 VL 32 IS 17 BP 2179 EP 2188 DI 10.1038/onc.2012.236 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 132JD UT WOS:000318062800007 PM 22689062 ER PT J AU Kelly, MJ Sagar, P Klepeis, VE AF Kelly, Michael J. Sagar, Pallavi Klepeis, Veronica E. TI Case 13-2013: A 6-Year-Old Girl with Bone and Joint Pain and Abdominal Distention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CLINICAL-FEATURES; CHILDHOOD; LYMPHOMA; CHILDREN; NEUROBLASTOMA; DISEASE; TUMOR C1 [Kelly, Michael J.] Tufts Univ, Sch Med, Div Pediat Hematol Oncol, Dept Pediat,Floating Hosp Children,Tufts Med Ctr, Boston, MA 02111 USA. [Kelly, Michael J.] Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. [Sagar, Pallavi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Klepeis, Veronica E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sagar, Pallavi] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Klepeis, Veronica E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kelly, MJ (reprint author), Tufts Univ, Sch Med, Div Pediat Hematol Oncol, Dept Pediat,Floating Hosp Children,Tufts Med Ctr, Boston, MA 02111 USA. NR 19 TC 0 Z9 0 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 25 PY 2013 VL 368 IS 17 BP 1636 EP 1645 DI 10.1056/NEJMcpc1208151 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 130YK UT WOS:000317956300013 PM 23614590 ER PT J AU Kasmar, AG Turner, MT AF Kasmar, Anne G. Turner, Marie T. TI Case 3-2013: A Woman with Abdominal Pain and Distention after Peritoneal Dialysis Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID TUBERCULOSIS; ETHAMBUTOL C1 [Kasmar, Anne G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Turner, Marie T.] Lemuel Shattuck Hosp, Boston, MA USA. RP Kasmar, AG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIAID NIH HHS [K08 AI089858] NR 3 TC 0 Z9 0 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 APR 25 PY 2013 VL 368 IS 17 BP 1656 EP 1657 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 130YK UT WOS:000317956300025 PM 23614601 ER PT J AU Shimamoto, SA Ryapolova-Webb, ES Ostrem, JL Galifianakis, NB Miller, KJ Starr, PA AF Shimamoto, Shoichi A. Ryapolova-Webb, Elena S. Ostrem, Jill L. Galifianakis, Nicholas B. Miller, Kai J. Starr, Philip A. TI Subthalamic Nucleus Neurons Are Synchronized to Primary Motor Cortex Local Field Potentials in Parkinson's Disease SO JOURNAL OF NEUROSCIENCE LA English DT Article ID DEEP BRAIN-STIMULATION; BASAL GANGLIA; OSCILLATORY ACTIVITY; SENSORIMOTOR CORTEX; BETA-OSCILLATIONS; GLOBUS-PALLIDUS; CEREBRAL-CORTEX; SPECTRAL-ANALYSIS; DOPAMINE; SPIKE AB In Parkinson's disease (PD), striatal dopamine denervation results in a cascade of abnormalities in the single-unit activity of downstream basal ganglia nuclei that include increased firing rate, altered firing patterns, and increased oscillatory activity. However, the effects of these abnormalities on cortical function are poorly understood. Here, in humans undergoing deep brain stimulator implantation surgery, we use the novel technique of subdural electrocorticography in combination with subthalamic nucleus (STN) single-unit recording to study basal ganglia-cortex interactions at the millisecond time scale. We show that in patients with PD, STN spiking is synchronized with primary motor cortex (M1) local field potentials in two distinct patterns: first, STN spikes are phase-synchronized with M1 rhythms in the theta, alpha, or beta (4-30 Hz) bands. Second, STN spikes are synchronized with M1 gamma activity over a broad spectral range (50-200Hz). The amplitude of STN spike-synchronized gamma activity in M1 is itself rhythmically modulated by the phase of a lower-frequency rhythm (phase-amplitude coupling), such that "waves" of phase-synchronized gamma activity precede the occurrence of STN spikes. We show the disease specificity of these phenomena in PD, by comparison with STN-M1 paired recordings performed in a group of patients with a different disorder, primary craniocervical dystonia. Our findings support a model of the basal ganglia-thalamocortical loop in PD in which gamma activity in primary motor cortex, modulated by the phase of low-frequency rhythms, drives STN unit discharge. C1 [Shimamoto, Shoichi A.; Ryapolova-Webb, Elena S.; Starr, Philip A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Ostrem, Jill L.; Galifianakis, Nicholas B.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Galifianakis, Nicholas B.; Starr, Philip A.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Care Ctr, San Francisco, CA 94143 USA. [Miller, Kai J.] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. RP Starr, PA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 779 Moffitt,505 Parnassus Ave, San Francisco, CA 94143 USA. EM starrp@neurosurg.ucsf.edu FU National Institutes of Health [R01NS069779]; Dystonia Medical Research Foundation FX This work was supported by the National Institutes of Health (Grant R01NS069779 to P. A. S.), and the Dystonia Medical Research Foundation. We thank Leslie Markun and Marta San Luciano for assistance with clinical data and statistical analyses, and Coralie de Hemptinne for critical review of the paper. NR 63 TC 45 Z9 46 U1 4 U2 22 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 24 PY 2013 VL 33 IS 17 BP 7220 EP 7233 DI 10.1523/JNEUROSCI.4676-12.2013 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 137EW UT WOS:000318419300011 PM 23616531 ER PT J AU Bleier, BS Kohman, RE Feldman, RE Ramanlal, S Han, X AF Bleier, Benjamin S. Kohman, Richie E. Feldman, Rachel E. Ramanlal, Shreshtha Han, Xue TI Permeabilization of the Blood-Brain Barrier via Mucosal Engrafting: Implications for Drug Delivery to the Brain SO PLOS ONE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; DOUBLE-BLIND; MODEL; FLUORESCEIN; GDNF AB Utilization of neuropharmaceuticals for central nervous system(CNS) disease is highly limited due to the blood-brain barrier(BBB) which restricts molecules larger than 500Da from reaching the CNS. The development of a reliable method to bypass the BBB would represent an enormous advance in neuropharmacology enabling the use of many potential disease modifying therapies. Previous attempts such as transcranial catheter implantation have proven to be temporary and associated with multiple complications. Here we describe a novel method of creating a semipermeable window in the BBB using purely autologous tissues to allow for high molecular weight(HMW) drug delivery to the CNS. This approach is inspired by recent advances in human endoscopic transnasal skull base surgical techniques and involves engrafting semipermeable nasal mucosa within a surgical defect in the BBB. The mucosal graft thereby creates a permanent transmucosal conduit for drugs to access the CNS. The main objective of this study was to develop a murine model of this technique and use it to evaluate transmucosal permeability for the purpose of direct drug delivery to the brain. Using this model we demonstrate that mucosal grafts allow for the transport of molecules up to 500 kDa directly to the brain in both a time and molecular weight dependent fashion. Markers up to 40 kDa were found within the striatum suggesting a potential role for this technique in the treatment of Parkinson's disease. This proof of principle study demonstrates that mucosal engrafting represents the first permanent and stable method of bypassing the BBB thereby providing a pathway for HMW therapeutics directly into the CNS. C1 [Bleier, Benjamin S.; Feldman, Rachel E.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Kohman, Richie E.; Ramanlal, Shreshtha; Han, Xue] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM benjamin_bleier@meei.harvard.edu FU Michael J. Fox Foundation for Parkinson's Research 2011 Rapid Response Innovations Awards Program FX This study was funded by the Michael J. Fox Foundation for Parkinson's Research 2011 Rapid Response Innovations Awards Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 10 Z9 10 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 APR 24 PY 2013 VL 8 IS 4 AR e61694 DI 10.1371/journal.pone.0061694 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 136DE UT WOS:000318340400041 PM 23637885 ER PT J AU Sukhotinsky, I Chan, AM Ahmed, OJ Rao, VR Gradinaru, V Ramakrishnan, C Deisseroth, K Majewska, AK Cash, SS AF Sukhotinsky, Inna Chan, Alexander M. Ahmed, Omar J. Rao, Vikram R. Gradinaru, Viviana Ramakrishnan, Charu Deisseroth, Karl Majewska, Ania K. Cash, Sydney S. TI Optogenetic Delay of Status Epilepticus Onset in an In Vivo Rodent Epilepsy Model SO PLOS ONE LA English DT Article ID TEMPORAL-LOBE EPILEPSY; ANTIEPILEPTIC DRUGS; NEURAL CIRCUITRY; OPTICAL CONTROL; TREATED RATS; PILOCARPINE; SEIZURES; LITHIUM; PATHOGENESIS; INJURY AB Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR), a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues. C1 [Sukhotinsky, Inna; Chan, Alexander M.; Ahmed, Omar J.; Rao, Vikram R.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Sukhotinsky, Inna; Chan, Alexander M.; Ahmed, Omar J.; Rao, Vikram R.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Alexander M.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gradinaru, Viviana; Ramakrishnan, Charu; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Majewska, Ania K.] Univ Rochester, Ctr Visual Sci, Dept Neurobiol & Anat, Rochester, NY 14627 USA. RP Cash, SS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM scash@partners.org OI Ramakrishnan, Charu/0000-0002-3474-6332 FU DOD [W81xWH-09-1-0480] FX DOD grant # W81xWH-09-1-0480. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 23 Z9 24 U1 0 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 24 PY 2013 VL 8 IS 4 AR e62013 DI 10.1371/journal.pone.0062013 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 136DE UT WOS:000318340400068 PM 23637949 ER PT J AU Zhang, XL Kuo, C Moore, A Ran, CZ AF Zhang, Xueli Kuo, Chaincy Moore, Anna Ran, Chongzhao TI In Vivo Optical Imaging of Interscapular Brown Adipose Tissue with F-18-FDG via Cerenkov Luminescence Imaging SO PLOS ONE LA English DT Article ID POSITRON-EMITTING RADIOTRACERS; ENERGY-EXPENDITURE; ADULT HUMANS; FAT; OBESITY; MICE; THERMOGENESIS; RADIONUCLIDES; ADIPOGENESIS; TOMOGRAPHY AB Objective: Brown adipose tissue (BAT), a specialized tissue for thermogenesis, plays important roles for metabolism and energy expenditure. Recent studies validated BAT's presence in human adults, making it an important re-emerging target for various pathologies. During this validation, PET images with F-18-FDG showed significant uptake of F-18-FDG by BAT under certain conditions. Here, we demonstrated that Cerenkov luminescence imaging (CLI) using F-18-FDG could be utilized for in vivo optical imaging of BAT in mice. Methods: Mice were injected with F-18-FDG and imaged 60 minutes later with open filter and 2 minute acquisition. In vivo activation of BAT was performed by norepinephrine and cold treatment under isoflurane or ketamine anesthesia. Spectral unmixing and 3D imaging reconstruction were conducted with multiple-filter CLI images. Results: 1) It was feasible to use CLI with F-18-FDG to image interscapular BAT in mice, with the majority of the signal (>85%) at the interscapular site originating from BAT; 2) The method was reliable because excellent correlations between in vivo CLI, ex vivo CLI, and ex vivo radioactivity were observed; 3) CLI could be used for monitoring BAT activation under different conditions; 4) CLI signals from the group under short-term isoflurane anesthesia were significantly higher than that from the group under long-term anesthesia; 5) The CLI spectrum of F-18-FDG with a peak at 640 nm in BAT after spectral unmixing reflected the actual context of BAT; 6) Finally 3D reconstruction images showed excellent correlation between the source of the light signal and the location and physical shape of BAT. Conclusion: CLI with F-18-FDG is a feasible and reliable method for imaging BAT in mice. Compared to PET imaging, CLI is significantly cheaper, faster for 2D planar imaging and easier to use. We believe that this method could be used as an important tool for researchers investigating BAT. C1 [Zhang, Xueli; Moore, Anna; Ran, Chongzhao] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol,Mol Imaging La, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Zhang, Xueli] China Pharmaceut Univ, Sch Pharm, Ctr Drug Discovery, Nanjing, Jiangsu, Peoples R China. [Kuo, Chaincy] Caliper, Alameda, CA USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol,Mol Imaging La, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. EM amoore@helix.mgh.harvard.edu; cran@nmr.mgh.harvard.edu RI Kuo, Chaincy/G-2403-2015; Kuo, Chaincy/H-9475-2016 OI Kuo, Chaincy/0000-0001-7958-8764 FU NCRR NIH HHS [S10 RR025504] NR 55 TC 15 Z9 16 U1 1 U2 25 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 24 PY 2013 VL 8 IS 4 AR e62007 DI 10.1371/journal.pone.0062007 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 136DE UT WOS:000318340400066 PM 23637947 ER PT J AU Pomerantz, M Freedman, ML AF Pomerantz, Mark Freedman, Matthew L. TI Clinical Uncertainty of Prostate Cancer Genetic Risk Panels SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; MEN C1 [Pomerantz, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Freedman, Matthew L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Med Oncol Serv, Boston, MA 02115 USA. RP Pomerantz, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM freedman@broadinstitute.org NR 10 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 24 PY 2013 VL 5 IS 182 AR 182ed6 DI 10.1126/scitranslmed.3004696 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 131TF UT WOS:000318018300001 PM 23616119 ER PT J AU Gu, LY Dai, Y Xu, J Mallipattu, S Kaufman, L Klotman, PE He, JC Chuang, PY AF Gu, Leyi Dai, Yan Xu, Jin Mallipattu, Sandeep Kaufman, Lewis Klotman, Paul E. He, John C. Chuang, Peter Y. TI Deletion of podocyte STAT3 mitigates the entire spectrum of HIV-1-associated nephropathy SO AIDS LA English DT Article DE dedifferentiation; glomerular disease; HIV-1-associated nephropathy; kidney; podocyte; STAT3 ID HIV-ASSOCIATED NEPHROPATHY; ANTIRETROVIRAL THERAPY; DIABETIC-NEPHROPATHY; SIGNAL TRANSDUCER; KIDNEY; MICE; EXPRESSION; GLOMERULI; INFECTION; ACTIVATOR AB Objective: HIV-1 gene expression in kidney epithelial cells is thought to be responsible for the pathogenesis of HIV-1-associated nephropathy (HIVAN). Signal transducer and activator of transcription (STAT) 3 signaling is activated in podocytes of patients with HIVAN and drives the dedifferentiation and proliferation of podocytes in culture. We confirm here that deletion of podocyte STAT3 is sufficient to mitigate the glomerular as well as tubulointerstitial findings of HIVAN. Methods: To demonstrate the functional role of podocyte STAT3 in the pathogenesis of HIVAN we compared the development of HIVAN in Tg26 HIV-transgenic mice with and without deletion of STAT3 in the podocyte. Results: Tg26 mice with podocyte-specific STAT3 deletion developed significantly less weight loss, albuminuria, and renal function impairment compared to Tg26 mice without STAT3 deletion. Tg26 mice with podocyte STAT3 deletion also had significantly less glomerular collapse, sclerosis, epithelial cell hyperplasia, podocyte dedifferentiation, and proinflammatory STAT3 target gene expression; and tubulointerstitial changes of HIVAN, including tubular atrophy, degeneration, apoptosis, and lymphocyte infiltration, were also significantly reduced compared to Tg26 mice without STAT3 deletion. Conclusion: Development of glomerular as well as tubulointerstitial injuries in the Tg26 HIVAN model is dependent on podocyte STAT3 expression. Inhibition of STAT3 could be a potential adjunctive therapy for the treatment of HIVAN. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:1091-1098 C1 [Gu, Leyi; Dai, Yan; Xu, Jin; Mallipattu, Sandeep; Kaufman, Lewis; He, John C.; Chuang, Peter Y.] Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA. [Gu, Leyi] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Div Renal, Shanghai 200030, Peoples R China. [Gu, Leyi] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Mol Cell Lab Kidney Dis, Shanghai 200030, Peoples R China. [Dai, Yan] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Sch Med, Div Nephrol, Shanghai 200030, Peoples R China. [Klotman, Paul E.] Baylor Coll Med, Houston, TX 77030 USA. [He, John C.] James J Peter Vet Affairs Med Ctr, Renal Sect, Bronx, NY USA. RP Chuang, PY (reprint author), Mt Sinai Sch Med, Dept Med, Div Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM peter.chuang@mssm.edu RI Mallipattu , Sandeep/M-7009-2014 FU NIH [1R01DK078897, 1R01DK088541-01A1, 5K08DK082760, R01DK078897, K08DK082760, R01DK088541-01A1, RC4DK090860, P01DK056492]; Veterans Affairs Merit Review Award [1I01BX000345] FX J.C.H. is supported by NIH 1R01DK078897 and 1R01DK088541-01A1 and a Veterans Affairs Merit Review Award 1I01BX000345; P.Y.C. is supported by NIH 5K08DK082760.; Source of Support: NIH R01DK078897, K08DK082760, R01DK088541-01A1, RC4DK090860, P01DK056492 and Veterans Affairs Merit Review Award 1I01BX000345. NR 31 TC 16 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 24 PY 2013 VL 27 IS 7 BP 1091 EP 1098 DI 10.1097/QAD.0b013e32835f1ea1 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 124QE UT WOS:000317479500005 PM 23343908 ER PT J AU London, MJ Hur, K Schwartz, GG Henderson, WG AF London, Martin J. Hur, Kwan Schwartz, Gregory G. Henderson, William G. TI Association of Perioperative beta-Blockade With Mortality and Cardiovascular Morbidity Following Major Noncardiac Surgery SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OF-VETERANS-AFFAIRS; QUALITY IMPROVEMENT PROGRAM; VASCULAR-SURGERY; AMERICAN-COLLEGE; PRACTICE GUIDELINES; HEART-ASSOCIATION; SURGICAL CARE; OUTCOMES; RISK; THERAPY AB Importance The effectiveness of perioperative beta-blockade in patients undergoing noncardiac surgery remains controversial. Objective To determine the associations of early perioperative exposure to beta-blockers with 30-day postoperative outcome in patients undergoing noncardiac surgery. Design, Setting, and Patients A retrospective cohort analysis evaluating exposure to beta-blockers on the day of or following major noncardiac surgery among a population-based sample of 136 745 patients who were 1: 1 matched on propensity scores (37 805 matched pairs) treated at 104 VA medical centers from January 2005 through August 2010. Main Outcomes and Measures All cause 30-day mortality and cardiac morbidity (cardiac arrest or Q-wave myocardial infarction). Results Overall 55 138 patients (40.3%) were exposed to beta-blockers. Exposure was higher in the 66.7% of 13 863 patients undergoing vascular surgery (95% CI, 65.9%-67.5%) than in the 37.4% of 122 882 patients undergoing nonvascular surgery (95% CI, 37.1%-37.6%; P<.001). Exposure increased as Revised Cardiac Risk Index factors increased, with 25.3% (95% CI, 24.9%-25.6%) of those with no risk vs 71.3% (95% CI, 69.5%-73.2%) of those with 4 risk factors or more exposed to beta-blockers (P<.001). Death occurred among 1.1% (95% CI, 1.1%-1.2%) and cardiac morbidity occurred among 0.9% (95% CI, 0.8%-0.9%) of patients. In the propensity matched cohort, exposure was associated with lower mortality (relative risk [RR], 0.73; 95% CI, 0.65-0.83; P<.001; number need to treat [NNT], 241; 95% CI, 173-397). When stratified by cumulative numbers of Revised Cardiac Risk Index factors, beta-blocker exposure was associated with significantly lower mortality among patients with 2 factors (RR, 0.63 [95% CI, 0.50-0.80]; P<.001; NNT, 105 [95% CI, 69-212]), 3 factors (RR, 0.54 [95% CI, 0.39-0.73]; P<.001; NNT, 41 [95% CI, 28-80]), or 4 factors or more (RR, 0.40 [95% CI, 0.25-0.73]; P<.001; NNT, 18 [95% CI, 12-34]). This association was limited to patients undergoing nonvascular surgery. beta-Blocker exposure was also associated with a lower rate of nonfatal Q-wave infarction or cardiac arrest (RR, 0.67 [95% CI, 0.57-0.79]; P<.001; NNT, 339 [95% CI, 240-582]), again limited to patients undergoing nonvascular surgery. Conclusions and Relevance Among propensity-matched patients undergoing noncardiac, nonvascular surgery, perioperative beta-blocker exposure was associated with lower rates of 30-day all-cause mortality in patients with 2 or more Revised Cardiac Risk Index factors. Our findings support use of a cumulative number of Revised Cardiac Risk Index predictors in decision making regarding institution and continuation of perioperative beta-blockade. A multicenter randomized trial involving patients at a low to intermediate risk by these factors would be of interest to validate these observational findings. JAMA. 0;0(16):1704-1713 www.jama.com C1 [London, Martin J.] US Dept Vet Affairs Med Ctr, Dept Anesthesia & Perioperat Care, San Francisco, CA USA. [London, Martin J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hur, Kwan] US Dept Vet Affairs Med Ctr, Ctr Medicat Safety, Pharm Benefits Management Serv, Hines, IL USA. [Schwartz, Gregory G.] US Dept Vet Affairs Med Ctr, Cardiol Sect, Denver, CO USA. [Schwartz, Gregory G.] Univ Colorado, Denver, CO 80202 USA. [Henderson, William G.] Colorado Sch Publ Hlth, Hlth Outcomes Program, Aurora, CO USA. [Henderson, William G.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. RP London, MJ (reprint author), San Francisco VA Med Ctr, Dept Anesthesia & Perioperat Care, 4150 Clement St, San Francisco, CA 94121 USA. EM londonm@anesthesia.ucsf.edu FU Anesthesia Patient Safety Foundation FX This study was supported by a grant from the Anesthesia Patient Safety Foundation. NR 37 TC 87 Z9 88 U1 3 U2 9 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 APR 24 PY 2013 VL 309 IS 16 BP 1704 EP 1713 DI 10.1001/jama.2013.4135 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 130IG UT WOS:000317906700027 PM 23613075 ER PT J AU Neely, LA Audeh, M Phung, NA Min, M Suchocki, A Plourde, D Blanco, M Demas, V Skewis, LR Anagnostou, T Coleman, JJ Wellman, P Mylonakis, E Lowery, TJ AF Neely, Lori A. Audeh, Mark Nu Ai Phung Min, Michael Suchocki, Adam Plourde, Daniella Blanco, Matthew Demas, Vasiliki Skewis, Lynell R. Anagnostou, Theodora Coleman, Jeffrey J. Wellman, Parris Mylonakis, Eleftherios Lowery, Thomas J. TI T2 Magnetic Resonance Enables Nanoparticle-Mediated Rapid Detection of Candidemia in Whole Blood SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID POLYMERASE-CHAIN-REACTION; INVASIVE CANDIDIASIS; PCR AMPLIFICATION; FUNGAL-INFECTIONS; CULTURE-SYSTEM; IDENTIFICATION; PATHOGENS; DIAGNOSIS; GUIDELINES; INITIATION AB Candida spp. cause both local and disseminated infections in immunocompromised patients. Bloodstream infections of Candida spp., known as "candidemia," are associated with a high mortality rate (40%), which is mainly attributed to the long diagnostic time required by blood culture. We introduce a diagnostic platform based on T2 magnetic resonance (T2MR), which is capable of sensitive and rapid detection of fungal targets in whole blood. In our approach, blood-compatible polymerase chain reaction is followed by hybridization of the amplified pathogen DNA to capture probe-decorated nanoparticles. Hybridization yields nanoparticle microclusters that cause large changes in the sample's T2MR signal. With this T2MR-based method, Candida spp. can be detected directly in whole blood, thus eliminating the need for analyte purification. Using a small, portable T2MR detection device, we were able to rapidly, accurately, and reproducibly detect five Candida species within human whole blood with a limit of detection of 1 colony-forming unit/ml and a time to result of < 3 hours. Spiked blood samples showed 98% positive agreement and 100% negative agreement between T2MR and blood culture. Additionally, performance of the assay was evaluated on 21 blinded clinical specimens collected serially. This study shows that the nanoparticle-and T2MR-based detection method is rapid and amenable to automation and offers clinicians the opportunity to detect and identify multiple human pathogens within hours of sample collection. C1 [Neely, Lori A.; Audeh, Mark; Nu Ai Phung; Min, Michael; Suchocki, Adam; Plourde, Daniella; Blanco, Matthew; Demas, Vasiliki; Skewis, Lynell R.; Wellman, Parris; Lowery, Thomas J.] T2 Biosyst, Lexington, MA 02421 USA. [Anagnostou, Theodora; Coleman, Jeffrey J.; Mylonakis, Eleftherios] Brown Univ, Div Infect Dis, Providence, RI 02906 USA. [Coleman, Jeffrey J.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Coleman, Jeffrey J.; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lowery, TJ (reprint author), T2 Biosyst, Lexington, MA 02421 USA. EM tlowery@t2biosystems.com RI Coleman, Jeffrey/E-2981-2015 FU T2 Biosystems Inc. FX This work was funded by T2 Biosystems Inc. NR 39 TC 44 Z9 44 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 24 PY 2013 VL 5 IS 182 AR 182ra54 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 131TF UT WOS:000318018300006 PM 23616121 ER PT J AU Sadreyev, RI Yildirim, E Pinter, SF Lee, JT AF Sadreyev, Ruslan I. Yildirim, Eda Pinter, Stefan F. Lee, Jeannie T. TI Bimodal quantitative relationships between histone modifications for X-linked and autosomal loci SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryonic stem cells; allele-specific ChIP-seq ID EMBRYONIC STEM-CELLS; GENE-EXPRESSION; CHROMOSOME INACTIVATION; LYSINE-27 METHYLATION; DOSAGE COMPENSATION; CHROMATIN-STRUCTURE; RNA-SEQ; GENOME; TRANSCRIPTION; STATES AB Gene expression is controlled by coordinated action of many epigenetic mechanisms including covalent histone modifications. Although numerous recurrent patterns of colocalized histone modifications have been associated with specific gene expression states, interrelationships between individual modifications are largely unknown. Here, we analyze quantitative relationships between colocalized histone marks during embryonic stem cell (ESC) differentiation and find that, for autosomal genes, these densities follow bimodal patterns. Analysis of repressive H3K27me3 and activating H3K4me3 modifications reveals the expected anti-correlation between them at active promoters but an unexpected positive correlation at inactive promoters. The two trends connect in a region corresponding to bivalent genes. Interestingly, this region is characterized by maximal H3K27 methylation. Resolving gene bivalency during ESC differentiation does not conform to the expected model of two marks as counteracting and competing forces. Although activated genes acquire H3K4me3 and lose H3K27me3, repressed genes lose H3K4me3 without gaining H3K27me3. The behavior of X-linked genes also deviates from expected models. Allele-specific analysis of chromatin modifications during X-chromosome inactivation (XCI) suggests that the silencing machinery focuses on active genes and depletion of H3K4me3 and that H3K27me3 is most significant during establishment of gene silencing. Our analysis reveals nontrivial relationships between H3K4me3 and H3K27me3, reveals unique aspects of gene bivalency, and demonstrates that XCI does not conform neatly to autosomal models. C1 [Sadreyev, Ruslan I.; Yildirim, Eda; Pinter, Stefan F.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sadreyev, Ruslan I.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Yildirim, Eda; Pinter, Stefan F.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Yildirim, Eda; Pinter, Stefan F.; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Yildirim, Eda/0000-0002-4796-3854; Pinter, Stefan/0000-0003-4750-1403 FU Massachusetts General Hospital Executive Committee on Research Medical Discovery Fund; Deutsche Forschungsgemeinschaft; National Institutes of Health [RO1-GM090278] FX We thank the J.T.L. laboratory and Brad Bernstein for valuable discussion. This work was supported by the Massachusetts General Hospital Executive Committee on Research Medical Discovery Fund (E.Y.), Deutsche Forschungsgemeinschaft (S.F.P.), and National Institutes of Health Grant RO1-GM090278 (to J.T.L.). J.T.L. is an investigator of the Howard Hughes Medical Institute. NR 36 TC 4 Z9 4 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 23 PY 2013 VL 110 IS 17 BP 6949 EP 6954 DI 10.1073/pnas.1216449110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 140TE UT WOS:000318677300075 PM 23564346 ER PT J AU Kaliannan, K Hamarneh, SR Economopoulos, KP Alam, SN Moaven, O Patel, P Malo, NS Ray, M Abtahi, SM Muhammad, N Raychowdhury, A Teshager, A Mohamed, MMR Moss, AK Ahmed, R Hakimian, S Narisawa, S Millan, JL Hohmann, E Warren, HS Bhan, AK Malo, MS Hodin, RA AF Kaliannan, Kanakaraju Hamarneh, Sulaiman R. Economopoulos, Konstantinos P. Alam, Sayeda Nasrin Moaven, Omeed Patel, Palak Malo, Nondita S. Ray, Madhury Abtahi, Seyed M. Muhammad, Nur Raychowdhury, Atri Teshager, Abeba Mohamed, Mussa M. Rafat Moss, Angela K. Ahmed, Rizwan Hakimian, Shahrad Narisawa, Sonoko Millan, Jose Luis Hohmann, Elizabeth Warren, H. Shaw Bhan, Atul K. Malo, Madhu S. Hodin, Richard A. TI Intestinal alkaline phosphatase prevents metabolic syndrome in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atherosclerosis; cytokines; diabetes; dysbiosis; steatosis ID HIGH-FAT DIET; GUT MICROBIOTA; INDUCED OBESITY; INSULIN-RESISTANCE; INFLAMMATION; ENDOTOXEMIA; MECHANISMS; LIPOPOLYSACCHARIDE; DISEASE; ADULTS AB Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans. C1 [Kaliannan, Kanakaraju; Hamarneh, Sulaiman R.; Economopoulos, Konstantinos P.; Alam, Sayeda Nasrin; Moaven, Omeed; Patel, Palak; Malo, Nondita S.; Ray, Madhury; Abtahi, Seyed M.; Muhammad, Nur; Raychowdhury, Atri; Teshager, Abeba; Mohamed, Mussa M. Rafat; Moss, Angela K.; Ahmed, Rizwan; Hakimian, Shahrad; Malo, Madhu S.; Hodin, Richard A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Narisawa, Sonoko; Millan, Jose Luis] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA 92037 USA. [Hohmann, Elizabeth; Warren, H. Shaw] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med & Pediat,Infect Dis Unit, Boston, MA 02114 USA. [Bhan, Atul K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Malo, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM mmalo@partners.org RI kaliannan, kanakaraju/P-9094-2014; OI Economopoulos, Konstantinos/0000-0003-4856-0405; Moaven, Omeed/0000-0002-0560-0457; Kuhnen, Angela/0000-0003-4944-9143 FU National Institutes of Health (NIH) [R01DK050623, R01DK047186, 2P30 DK43351]; Junior Faculty Award from the MGH Department of Surgery; Grand Challenge Exploration Grant from the Bill and Melinda Gates Foundation FX We thank Dr. Hang Lee (Department of Biostatistics, MGH) for help with statistical analyses. This work was supported by National Institutes of Health (NIH) Grants R01DK050623 and R01DK047186 (to R.A.H.), a Junior Faculty Award (to M.S.M.) from the MGH Department of Surgery, and a Grand Challenge Exploration Grant from the Bill and Melinda Gates Foundation (to M.S.M.). The work was also supported by NIH Grant 2P30 DK43351 to the Center for the Study of Inflammatory Bowel Disease, MGH. NR 31 TC 46 Z9 47 U1 0 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 23 PY 2013 VL 110 IS 17 BP 7003 EP 7008 DI 10.1073/pnas.1220180110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 140TE UT WOS:000318677300084 PM 23569246 ER PT J AU Fosbol, EL Zhao, Y Shahian, DM Grover, FL Edwards, FH Peterson, ED AF Fosbol, Emil L. Zhao, Yue Shahian, David M. Grover, Frederick L. Edwards, Fred H. Peterson, Eric D. TI Repeat Coronary Revascularization After Coronary Artery Bypass Surgery in Older Adults The Society of Thoracic Surgeons' National Experience, 1991-2007 SO CIRCULATION LA English DT Article DE aged; coronary artery bypass surgery; revascularization ID SAPHENOUS-VEIN GRAFTS; 5-YEAR OUTCOMES; SURVIVAL; PATENCY; PREDICTORS; DATABASE; REGISTRY; TRIAL AB Background-A major advantage of coronary artery bypass graft surgery (CABG) relative to percutaneous coronary intervention is its durability, yet there is a paucity of information on rates and predictors of repeat coronary revascularization after CABG in the modern era. Methods and Results-We included patients >= 65 years from the Society of Thoracic Surgeons' National Adult Cardiac Surgery Database who were undergoing first-time isolated CABG from 1991 to 2007 (n=723 134, median age 73 years). After linking to Medicare claims data, long-term outcomes of CABG (up to 18 years after surgery) were examined by use of cumulative incidence curves. Multivariable Cox proportional hazard analysis was used to identify factors associated with 1- and 5-year repeat revascularization trends and variability. We found that the overall 18-year survival rate was 20%. Cumulative incidences of any repeat revascularization (percutaneous coronary intervention or CABG, yet most often percutaneous coronary intervention) were 2%, 7%, 13%, and 16% at 1, 5, 10, and 18 years after surgery, respectively. The rates of repeat CABG procedures were quite low for all time points (0.1%, 0.6%, 1.3%, and 1.7%, respectively). Female sex, disease severity represented by a history of percutaneous coronary intervention, preoperative dialysis, and partial revascularization were strongly associated with a higher revascularization rate, whereas advanced age, left main disease, and smoking were associated with a lower rate. There was approximately a 2-fold variation in repeat revascularization rates across centers at 1 year (interquartile range 1.7-3.6%) and 5 years (interquartile range 6.7-12.0%). Conclusions-Repeat revascularization is performed infrequently among older patients who undergo CABG; however, these rates vary substantially by patient subgroups and among providers. (Circulation. 2013; 127:1656-1663.) C1 [Fosbol, Emil L.; Zhao, Yue; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Qual & Safety, Boston, MA USA. [Grover, Frederick L.] Univ Colorado, Sch Med, Div Cardiothorac Surg, Denver, CO USA. [Grover, Frederick L.] Denver VA Med Ctr, Surg Serv, Denver, CO USA. [Edwards, Fred H.] Univ Florida, Dept Cardiothorac Surg, Jacksonville, FL USA. RP Fosbol, EL (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 7461,Terrace Level, Durham, NC 27705 USA. EM emil.fosbol@duke.edu FU American Heart Association-Pharmaceutical Roundtable; Eli Lilly Company; Ortho-McNeil-Janssen Pharmaceuticals, Inc; Society of Thoracic Surgeons; American Heart Association; American College of Cardiology; AstraZeneca; Boehringer Ingelheim; Genentech; Johnson Johnson; Pfizer; Sanofi-Aventis; WebMD FX This work was supported by an award from the American Heart Association-Pharmaceutical Roundtable and David and Stevie Spina.; Dr Peterson reports the receipt of research funding from Eli Lilly & Company, Ortho-McNeil-Janssen Pharmaceuticals, Inc, Society of Thoracic Surgeons, American Heart Association, and the American College of Cardiology (all significant) and consulting fees from AstraZeneca, Boehringer Ingelheim, Genentech, Johnson & Johnson, Ortho-McNeil-Janssen Pharmaceuticals, Inc, Pfizer, Sanofi-Aventis, and WebMD (all modest). All of Dr Peterson's disclosures can be found online at www.dcri.org. The remaining authors have no conflicts to disclose. NR 16 TC 2 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 23 PY 2013 VL 127 IS 16 BP 1656 EP + DI 10.1161/CIRCULATIONAHA.113.001882 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131XM UT WOS:000318031800008 PM 23532630 ER PT J AU Regan, S Losina, E Chetty, S Giddy, J Walensky, RP Ross, D Holst, H Katz, JN Freedberg, KA Bassett, IV AF Regan, Susan Losina, Elena Chetty, Senica Giddy, Janet Walensky, Rochelle P. Ross, Douglas Holst, Helga Katz, Jeffrey N. Freedberg, Kenneth A. Bassett, Ingrid V. TI Factors Associated with Self-Reported Repeat HIV Testing after a Negative Result in Durban, South Africa SO PLOS ONE LA English DT Article ID ANTIRETROVIRAL THERAPY; SEXUAL-BEHAVIOR; CARE; INFECTION; DIAGNOSIS; OUTPATIENT; BARRIERS; PROGRAM; IMPACT; COHORT AB Background: Routine screening for HIV infection leads to early detection and treatment. We examined patient characteristics associated with repeated screening in a high prevalence country. Methods: We analyzed data from a cohort of 5,229 adults presenting for rapid HIV testing in the outpatient departments of 2 South African hospitals from November 2006 to August 2010. Patients were eligible if they were >= 18 years, reported no previous diagnosis with HIV infection, and not pregnant. Before testing, participants completed a questionnaire including gender, age, HIV testing history, health status, and knowledge about HIV and acquaintances with HIV. Enrollment HIV test results and CD4 counts were abstracted from the medical record. We present prevalence of HIV infection and median CD4 counts by HIV testing history (first-time vs. repeat). We estimated adjusted relative risks (ARR's) for repeat testing by demographics, health status, and knowledge of HIV and others with HIV in a generalized linear model. Results: Of 4,877 participants with HIV test results available, 26% (N = 1258) were repeat testers. Repeat testers were less likely than first-time testers to be HIV-infected (34% vs. 54%, p < 0.001). Median CD4 count was higher among repeat than first-time testers (201/uL vs. 147/uL, p < 0.001). Among those HIV negative at enrollment (N = 2,499), repeat testing was more common among those with family or friends living with HIV (ARR 1.50, 95% CI: 1.33-1.68), women (ARR: 1.24, 95% CI: 1.11-1.40), and those self-reporting very good health (ARR: 1.28, 95% CI: 1.12-1.45). Conclusions: In this high prevalence setting, repeat testing was common among those undergoing HIV screening, and was associated with female sex, lower prevalence of HIV infection, and higher CD4 counts at diagnosis. C1 [Regan, Susan; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Losina, Elena; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA. [Losina, Elena; Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Chetty, Senica; Giddy, Janet; Holst, Helga] McCord Hosp, Durban, South Africa. [Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Ross, Douglas] St Marys Hosp, Durban, South Africa. [Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res CFAR, Boston, MA 02115 USA. [Katz, Jeffrey N.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Regan, Susan; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. RP Regan, S (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM sregan@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X; Regan, Susan/0000-0003-0940-2017 FU National Institute of Allergy and Infectious Disease [K23 AI068458, K24 AI062476]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute of Mental Health [R01 MH090326, R01 MH073445]; Claflin Distinguished Scholar Award; Burke Global Health Fellowship; Harvard Catalyst [UL1 RR 025758] FX This work was supported by the National Institute of Allergy and Infectious Disease: K23 AI068458; K24 AI062476; the Harvard University Center for AIDS Research P30 AI060354; the National Institute of Mental Health: R01 MH090326; R01 MH073445; the Claflin Distinguished Scholar Award, the Burke Global Health Fellowship, and the Harvard Catalyst (UL1 RR 025758). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 7 Z9 7 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 APR 23 PY 2013 VL 8 IS 4 AR e62362 DI 10.1371/journal.pone.0062362 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 131QH UT WOS:000318008400172 PM 23626808 ER PT J AU Shah, RV Abbasi, SA Heydari, B Rickers, C Jacobs, DR Wang, L Kwong, RY Bluemke, DA Lima, JAC Jerosch-Herold, M AF Shah, Ravi V. Abbasi, Siddique A. Heydari, Bobak Rickers, Carsten Jacobs, David R., Jr. Wang, Lu Kwong, Raymond Y. Bluemke, David A. Lima, Joao A. C. Jerosch-Herold, Michael TI Insulin Resistance, Subclinical Left Ventricular Remodeling, and the Obesity Paradox MESA (Multi-Ethnic Study of Atherosclerosis) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE LV remodeling; MESA; metabolic syndrome; obesity ID INCIDENT CARDIOVASCULAR EVENTS; HEART-FAILURE RISK; METABOLIC SYNDROME; BARIATRIC SURGERY; SYSTOLIC FUNCTION; ABDOMINAL FAT; DISEASE; INFLAMMATION; DYSFUNCTION; MASS AB Objectives This study assessed whether impaired fasting glucose (IFG), insulin resistance, and waist-to-hip ratio (WHR) had effects on cardiac remodeling, independent of obesity, in the MESA (Multi-Ethnic Study of Atherosclerosis) trial. Background Recent studies have suggested that central obesity and insulin resistance may be primary mediators of obesity-related cardiac remodeling independent of body mass index (BMI). Methods We investigated 4,364 subjects without diabetes in the MESA trial. IFG (100 to 125 mg/dl) or insulin resistance (by homeostatic model assessment of insulin resistance [HOMA-IR]) and WHR were used for cardiometabolic phenotyping. Multivariate linear regression analysis was used to determine the effects of the cardiometabolic markers on left ventricular (LV) remodeling, assessed primarily through the LV mass-to-volume ratio obtained by cine cardiac magnetic resonance imaging. Results Individuals with IFG were more likely to be older and hypertensive, with increased prevalence of cardiometabolic risk factors regardless of BMI. In each quartile of BMI, subjects with above-median HOMA-IR, above-median WHR, or IFG had a higher LV mass-to-volume ratio (p < 0.05 for all). HOMA-IR (p < 0.0001), WHR (p < 0.0001), and the presence of IFG (p = 0.04), but not BMI (p = 0.24), were independently associated with LV mass-to-volume ratio after adjustment for age, sex, hypertension, race, and dyslipidemia. Conclusions Insulin resistance and WHR were associated with concentric LV remodeling independent of BMI. These results support the emerging hypothesis that the cardiometabolic phenotype, defined by insulin resistance and central obesity, may play a critical role in LV remodeling independently of BMI. (J Am Coll Cardiol 2013;61:1698-706) (C) 2013 by the American College of Cardiology Foundation C1 [Shah, Ravi V.; Abbasi, Siddique A.; Heydari, Bobak; Kwong, Raymond Y.; Jerosch-Herold, Michael] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Lab, Boston, MA 02115 USA. [Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Rickers, Carsten] Univ Hosp Schleswig Holstein, Dept Pediat Cardiol, Kiel, Germany. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Wang, Lu] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02115 USA. [Bluemke, David A.; Lima, Joao A. C.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA. [Jerosch-Herold, Michael] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Jerosch-Herold, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St,L1-RA050, Boston, MA 02115 USA. EM mjerosch-herold@partners.org OI Abbasi, Siddique/0000-0002-9601-7565; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; American Heart Association [11POST000002]; Heart Failure National Institutes of Health Clinical Research Network [U01-HL084877]; [R01-HL-65580] FX The MESA trial was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. Dr. Shah is supported by an American Heart Association post-doctoral fellowship award (11POST000002) and a training grant from the Heart Failure National Institutes of Health Clinical Research Network (U01-HL084877). Dr. Jerosch-Herold receives support through contract R01-HL-65580. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 36 TC 18 Z9 19 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 23 PY 2013 VL 61 IS 16 BP 1698 EP 1706 DI 10.1016/j.jacc.2013.01.053 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 125WZ UT WOS:000317573900007 PM 23500236 ER PT J AU Packer, DL Kowal, RC Wheelan, KR Irwin, JM Champagne, J Guerra, PG Dubuc, M Reddy, V Nelson, L Holcomb, RG Lehmann, JW Ruskin, JN AF Packer, Douglas L. Kowal, Robert C. Wheelan, Kevin R. Irwin, James M. Champagne, Jean Guerra, Peter G. Dubuc, Marc Reddy, Vivek Nelson, Linda Holcomb, Richard G. Lehmann, John W. Ruskin, Jeremy N. CA STOP AF Cryoablation Investigators TI Cryoballoon Ablation of Pulmonary Veins for Paroxysmal Atrial Fibrillation First Results of the North American Arctic Front (STOP AF) Pivotal Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; cryoballoon ablation ID ANTIARRHYTHMIC-DRUG THERAPY; CATHETER ABLATION; RADIOFREQUENCY ABLATION; RANDOMIZED-TRIAL; ESOPHAGEAL FISTULA; FOLLOW-UP; SAFETY; EFFICACY; MULTICENTER; SYSTEM AB Objectives This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology designed to achieve single-delivery pulmonary vein (PV) isolation. Background Standard radiofrequency ablation is effective in eliminating atrial fibrillation (AF) but requires multiple lesion delivery at the risk of significant complications. Methods Patients with documented symptomatic paroxysmal AF and previously failed therapy with >= 1 membrane active antiarrhythmic drug underwent 2: 1 randomization to either cryoballoon ablation (n = 163) or drug therapy (n = 82). A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary. Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months. Results Patients had highly symptomatic AF (78% paroxysmal, 22% early persistent) and experienced failure of at least one antiarrhythmic drug. Cryoablation produced acute isolation of three or more PVs in 98.2% and all four PVs in 97.6% of patients. PVs isolation was achieved with the balloon catheter alone in 83%. At 12 months, treatment success was 69.9% (114 of 163) of cryoblation patients compared with 7.3% of antiarrhythmic drug patients (absolute difference, 62.6% [p < 0.001]). Sixty-five (79%) drug-treated patients crossed over to cryoablation during 12 months of study follow-up due to recurrent, symptomatic AF, constituting drug treatment failure. There were 7 of the resulting 228 cryoablated patients (3.1%) with a >75% reduction in PV area during 12 months of follow-up. Twenty-nine of 259 procedures (11.2%) were associated with phrenic nerve palsy as determined by radiographic screening; 25 of these had resolved by 12 months. Cryoablation patients had significantly improved symptoms at 12 months. Conclusions The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF, for whom at least one antiarrhythmic drug has failed, with risks within accepted standards for ablation therapy. (A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [Stop AF]; NCT00523978) (J Am Coll Cardiol 2013;61:1713-23) (C) 2013 by the American College of Cardiology Foundation C1 [Packer, Douglas L.] Mayo Clin, Rochester, MN 55905 USA. [Kowal, Robert C.; Wheelan, Kevin R.] Baylor Heart & Vasc Hosp, Dallas, TX USA. [Irwin, James M.] Bay Heart Grp, Tampa, FL USA. [Champagne, Jean] Inst Univ Cardiol & Pneumol Quebec, Electrophysiol EP Quebec City, Quebec City, PQ, Canada. [Guerra, Peter G.; Dubuc, Marc] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Reddy, Vivek] Mt Sinai Sch Med, New York, NY USA. [Nelson, Linda] Medtronic Inc, Minneapolis, MN USA. [Holcomb, Richard G.] Stat Consulting, Minneapolis, MN USA. [Lehmann, John W.] Lehmann Consulting, Med Monitor, Wayland, MA USA. [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Packer, DL (reprint author), Mayo Clin, St Marys Hosp, 2-416 Alfred Bldg,1216 2nd St,SW, Rochester, MN 55905 USA. EM packer@mayo.edu FU St. Jude Medical; Medtronic; Medtronic/CryoCath FX Dr. Kowal is a Medtronic advisor; and teaches at Arctic Front Programs. Dr. Wheelan receives honoraria as a Medtronic consultant and has stock ownership. Dr. Irwin contracts with Medtronic to train other EPs in the use of Arctic Front. Dr. Guerra is a Sanofi-Aventis board member and receives payment for lectures, including service on speakers bureaus at St. Jude Medical and Medtronic. Dr. Dubuc received a research grant, consulting fees and/or honoraria, and payment for lectures, including service on speakers' bureau, from Medtronic/CryoCath. Dr. Reddy is a consultant for Medtronic. Dr. Lehmann is an hourly consultant with Medtronic for STOP AF clinical trial design and implementation and holds patents assigned to Medtronics, although no royalties or benefits are received. Dr. Ruskin receives research grants from Medtronic/CryoCath, Biosense Webster, Boston Scientific, and St. Jude Medical; is an advisory board member for Medtronic/CryoCath and CardioFocus (no personal compensation) and a board member for Pfizer, Biosense Webster, CardioInsight Scientific, and Sequel (no personal compensation); a compensated consultant with Astellas/Cardiome, GE Healthcare, Sanofi-Aventis, Medtronic, Portola, MedIQ, and Third Rock Ventures; and receives honoraria for lectures from Med-IQ and holds stock/options with Portola. Dr. Nelson is an employee of Medtronic, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 33 TC 197 Z9 205 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 23 PY 2013 VL 61 IS 16 BP 1713 EP 1723 DI 10.1016/j.jacc.2012.11.064 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 125WZ UT WOS:000317573900009 PM 23500312 ER PT J AU Freiberg, MS Chang, CCH Kuller, LH Skanderson, M Lowy, E Kraemer, KL Butt, AA Goetz, MB Leaf, D Oursler, KA Rimland, D Barradas, MR Brown, S Gibert, C McGinnis, K Crothers, K Sico, J Crane, H Warner, A Gottlieb, S Gottdiener, J Tracy, RP Budoff, M Watson, C Armah, KA Doebler, D Bryant, K Justice, AC AF Freiberg, Matthew S. Chang, Chung-Chou H. Kuller, Lewis H. Skanderson, Melissa Lowy, Elliott Kraemer, Kevin L. Butt, Adeel A. Goetz, Matthew Bidwell Leaf, David Oursler, Kris Ann Rimland, David Barradas, Maria Rodriguez Brown, Sheldon Gibert, Cynthia McGinnis, Kathy Crothers, Kristina Sico, Jason Crane, Heidi Warner, Alberta Gottlieb, Stephen Gottdiener, John Tracy, Russell P. Budoff, Matthew Watson, Courtney Armah, Kaku A. Doebler, Donna Bryant, Kendall Justice, Amy C. TI HIV Infection and the Risk of Acute Myocardial Infarction SO JAMA INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; REGIONAL ADIPOSE-TISSUE; ANTIRETROVIRAL THERAPY; CARDIOVASCULAR-DISEASE; VETERANS; HEALTH; COHORT; PREVALENCE; ADULTS; MEN AB Importance: Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatalAMIevents, any potential association between HIV status and AMI may be confounded. Objective: To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care. Design and Setting: Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009. Participants: After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI. Main Outcome Measure: Acute myocardial infarction. Results: We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P<.05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66). Conclusions and Relevance: Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors. C1 [Freiberg, Matthew S.; Chang, Chung-Chou H.; Kraemer, Kevin L.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Freiberg, Matthew S.; Chang, Chung-Chou H.; Kuller, Lewis H.; Armah, Kaku A.; Doebler, Donna] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Skanderson, Melissa; McGinnis, Kathy; Sico, Jason; Justice, Amy C.] West Haven Vet Adm, Med Ctr, Vet Affairs VA Connecticut Hlth Care Syst, West Haven, CT USA. [Sico, Jason; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Lowy, Elliott] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Lowy, Elliott] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Crothers, Kristina; Crane, Heidi] Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. [Goetz, Matthew Bidwell; Leaf, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Goetz, Matthew Bidwell; Leaf, David; Warner, Alberta] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Budoff, Matthew] Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Oursler, Kris Ann; Gottlieb, Stephen; Gottdiener, John] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Oursler, Kris Ann] Baltimore VA Hlth Care Syst, Baltimore, MD USA. [Bryant, Kendall] NIAAA, Bethesda, MD 90034 USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Barradas, Maria Rodriguez] Baylor Coll Med, Houston, TX 77030 USA. [Barradas, Maria Rodriguez] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Brown, Sheldon] James J Peters VA Med Ctr, Bronx, NY USA. [Brown, Sheldon] Mt Sinai Sch Med, New York, NY USA. [Gibert, Cynthia] George Washington Univ, Sch Med, Washington, DC USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Burlington, VT 05405 USA. [Watson, Courtney] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. RP Freiberg, MS (reprint author), Univ Pittsburgh, Sch Med, 230 McKee Pl,Ste 600, Pittsburgh, PA 15213 USA. EM Freibergms@upmc.edu OI Goetz, Matthew/0000-0003-4542-992X; Crothers, Kristina/0000-0001-9702-0371 FU Merck [P08569 MIISP 39996]; National Heart, Lung, and Blood Institute [HL095136-04]; National Institute on Alcohol Abuse and Alcoholism at the National Institutes of Health [AA013566-10, AA020790, AA020794] FX Dr Butt reports that he received Investigator-Initiated Studies Program grant P08569 MIISP 39996 from Merck and gave a scientific talk for Gilead in 2011.; This work was supported by grant HL095136-04 from the National Heart, Lung, and Blood Institute and grants AA013566-10, AA020790, and AA020794 from the National Institute on Alcohol Abuse and Alcoholism at the National Institutes of Health. NR 40 TC 261 Z9 264 U1 5 U2 30 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR 22 PY 2013 VL 173 IS 8 BP 614 EP 622 DI 10.1001/jamainternmed.2013.3728 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 159IR UT WOS:000320039600002 PM 23459863 ER PT J AU Sen, S Kranzler, HR Didwania, AK Schwartz, AC Amarnath, S Kolars, JC Dalack, GW Nichols, B Guille, C AF Sen, Srijan Kranzler, Henry R. Didwania, Aashish K. Schwartz, Ann C. Amarnath, Sudha Kolars, Joseph C. Dalack, Gregory W. Nichols, Breck Guille, Constance TI Effects of the 2011 Duty Hour Reforms on Interns and Their Patients A Prospective Longitudinal Cohort Study SO JAMA INTERNAL MEDICINE LA English DT Article ID RESIDENTS WORK HOURS; MEDICAL ERRORS; ACCREDITATION-COUNCIL; 1ST-YEAR RESIDENTS; ADVERSE EVENTS; FOLLOW-UP; SLEEP; LIMITS; DEPRESSION; EDUCATION AB Importance: In 2003, the first phase of duty hour requirements for US residency programs recommended by the Accreditation Council for Graduate Medical Education (ACGME) was implemented. Evidence suggests that this first phase of duty hour requirements resulted in a modest improvement in resident well-being and patient safety. To build on these initial changes, the ACGME recommended a new set of duty hour requirements that took effect in July 2011. Objective: To determine the effects of the 2011 duty hour reforms on first-year residents (interns) and their patients. Design: As part of the Intern Health Study, we conducted a longitudinal cohort study comparing interns serving before (2009 and 2010) and interns serving after (2011) the implementation of the new duty hour requirements. Setting: Fifty-one residency programs at 14 university and community-based GME institutions. Participants: A total of 2323 medical interns. Main Outcome Measures: Self-reported duty hours, hours of sleep, depressive symptoms, well-being, and medical errors at 3, 6, 9, and 12 months of the internship year. Results: Fifty-eight percent of invited interns chose to participate in the study. Reported duty hours decreased from an average of 67.0 hours per week before the new rules to 64.3 hours per week after the new rules were instituted (P < .001). Despite the decrease in duty hours, there were no significant changes in hours slept (6.8.-> 7.0; P = .17), depressive symptoms (5.8.-> 5.7; P =. 55) or wellbeing score (48.5 -> 48.4; P = .86) reported by interns. With the new duty hour rules, the percentage of interns who reported concern about making a serious medical error increased from 19.9% to 23.3% (P = .007). Conclusions and Relevance: Although interns report working fewer hours under the new duty hour restrictions, this decrease has not been accompanied by an increase in hours of sleep or an improvement in depressive symptoms or well-being but has been accompanied by an unanticipated increase in self-reported medical errors. C1 [Sen, Srijan; Dalack, Gregory W.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Kolars, Joseph C.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Kranzler, Henry R.] Perelman Sch Med, Dept Psychiat, Philadelphia, PA USA. [Kranzler, Henry R.] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Didwania, Aashish K.] Northwestern Univ Feinberg Sch Med, Dept Internal Med, Chicago, IL USA. [Schwartz, Ann C.] Emory Univ Sch Med, Dept Psychiat, Atlanta, GA USA. [Amarnath, Sudha] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. [Nichols, Breck] Los Angeles Cty Univ Southern Calif Med Ctr, Keck Univ Southern Calif Sch Med, Dept Pediat, Los Angeles, CA USA. [Nichols, Breck] Los Angeles Cty Univ So Calif Med Ctr, Keck Univ Southern Calif Sch Med, Dept Med, Los Angeles, CA USA. [Guille, Constance] Med Univ S Carolina, Dept Psychiat, Charleston, SC USA. RP Sen, S (reprint author), Univ Michigan, Dept Psychiat, 5047 BSRB,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM srijan@umich.edu RI Sen, Srijan/J-8053-2013 FU American Foundation for Suicide Prevention; National Center for Research Resources [UL1RR024986]; National Institute of Mental Health [MH095109]; National Institute on Alcohol Abuse and Alcoholism [AA013736]; Lilly; Lundbeck; Abbott; Pfizer FX The project was supported by the following grants: a Young Investigator Grant from the American Foundation for Suicide Prevention (Dr Sen), UL1RR024986 from the National Center for Research Resources (Dr Sen), MH095109 from the National Institute of Mental Health (Dr Sen), and AA013736 from the National Institute on Alcohol Abuse and Alcoholism (Dr Kranzler).; Dr Krantzler has been a consultant or advisory board member for Alkermes, Lilly, Lundbeck, Pfizer, and Roche. He is also a member of the American Society of Clinical Psychopharmacology, which is supported by Lilly, Lundbeck, Abbott, and Pfizer. NR 40 TC 40 Z9 40 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR 22 PY 2013 VL 173 IS 8 BP 657 EP 662 DI 10.1001/jamainternmed.2013.351 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 159IR UT WOS:000320039600011 PM 23529201 ER PT J AU Gellad, WF Yealy, D Fine, M AF Gellad, Walid F. Yealy, Donald Fine, Michael TI Computers and the Diagnosis of Pneumonia SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID COMMUNITY-ACQUIRED PNEUMONIA; OUTCOMES C1 [Gellad, Walid F.; Fine, Michael] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Gellad, Walid F.; Fine, Michael] Univ Pittsburgh, Dept Med, Div Gen Med, Pittsburgh, PA USA. [Yealy, Donald] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA USA. RP Gellad, WF (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM walid.gellad@va.gov NR 8 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 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR 22 PY 2013 VL 173 IS 8 BP 701 EP 702 DI 10.1001/jamainternmed.2013.4083 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 159IR UT WOS:000320039600022 PM 23553079 ER PT J AU Singh, H Spitzmueller, C Petersen, NJ Sawhney, MK Sittig, DF AF Singh, Hardeep Spitzmueller, Christiane Petersen, Nancy J. Sawhney, Mona K. Sittig, Dean F. TI Information Overload and Missed Test Results in Electronic Health Record-Based Settings SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Singh, Hardeep; Petersen, Nancy J.; Sawhney, Mona K.] Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA Hlth Serv Res & Dev Ctr Excellence, Ctr Inquiry Improve Outpatient Safety Effect Elec, Houston, TX 77030 USA. [Singh, Hardeep; Petersen, Nancy J.; Sawhney, Mona K.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Spitzmueller, Christiane] Univ Houston, Dept Psychol, Houston, TX USA. [Sittig, Dean F.] Univ Texas Hlth Sci Ctr, Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] Univ Texas Hlth Sci Ctr, Univ Texas Mem Hermann Ctr Healthcare Qual & Safe, Houston, TX USA. RP Singh, H (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU NCI NIH HHS [K23 CA125585, K23CA125585] NR 11 TC 34 Z9 34 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR 22 PY 2013 VL 173 IS 8 BP 702 EP 704 DI 10.1001/2013.jamainternmed.61 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 159IR UT WOS:000320039600023 PM 23460235 ER PT J AU Shuman, AG Li, X Halpin, CF Rauch, SD Telian, SA AF Shuman, Andrew G. Li, Xue Halpin, Chris F. Rauch, Steven D. Telian, Steven A. TI Tuning Fork Testing in Sudden Sensorineural Hearing Loss SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Shuman, Andrew G.] Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY 10021 USA. [Li, Xue] Hines VA Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. [Halpin, Chris F.; Rauch, Steven D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Telian, Steven A.] Univ Michigan Med Sch, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. RP Telian, SA (reprint author), Univ Michigan Med Sch, Dept Otolaryngol Head & Neck Surg, Taubman Ctr 1904, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM telian@umich.edu FU NIDCD NIH HHS [U01 DC006296] NR 7 TC 0 Z9 1 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR 22 PY 2013 VL 173 IS 8 BP 706 EP 707 DI 10.1001/jamainternmed.2013.2813 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 159IR UT WOS:000320039600025 PM 23529707 ER PT J AU Barteneva, NS Fasler-Kan, E Bernimoulin, M Stern, JNH Ponomarev, ED Duckett, L Vorobjev, IA AF Barteneva, Natasha S. Fasler-Kan, Elizaveta Bernimoulin, Michael Stern, Joel N. H. Ponomarev, Eugeny D. Duckett, Larry Vorobjev, Ivan A. TI Circulating microparticles: square the circle SO BMC CELL BIOLOGY LA English DT Review DE Circulating; Microparticles; Exosomes; Microvesicles; Disease; Diagnostics; Therapy ID CELL-DERIVED MICROPARTICLES; MEMBRANE PHOSPHOLIPID ASYMMETRY; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; RESPIRATORY-DISTRESS-SYNDROME; HUMAN ATHEROSCLEROTIC PLAQUES; ENDOTHELIAL PROGENITOR CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; DYNAMIC LIGHT-SCATTERING; TISSUE FACTOR ACTIVITY; PLATELET-RICH PLASMA AB Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. C1 [Barteneva, Natasha S.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Barteneva, Natasha S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Fasler-Kan, Elizaveta] Univ Appl Sci Northwestern Switzerland FHNW, Inst Chem & Bioanalyt, Muttenz, Switzerland. [Fasler-Kan, Elizaveta] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland. [Bernimoulin, Michael] Univ Hosp Geneva, Div Hematol, Geneva, Switzerland. [Stern, Joel N. H.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Ponomarev, Eugeny D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Ponomarev, Eugeny D.] Chinese Univ Hong Kong, Themat Res Program Neurodegenerat, Shatin, Hong Kong, Peoples R China. [Duckett, Larry] BD Biosci Inc, San Jose, CA USA. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, Fac Biol, AN Belozersky Inst Physicochem Biol, Moscow, Russia. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, Fac Biol, Dept Cell Biol, Moscow, Russia. RP Barteneva, NS (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, D-249,200 Longwood Ave, Boston, MA 02115 USA. EM Natasha.Barteneva@childrens.harvard.edu OI Stern, Joel N.H./0000-0002-1259-2256 FU Harvard Pilot Grant; Immune Disease Institute; Russian Foundation for Basic Research [11-01517a, 11-01749a] FX We are thankful to Luke Jasenosky and Aleksandra Gorelova (Harvard University) for editorial help with the manuscript. NSB was supported by a Harvard Pilot Grant and the Immune Disease Institute, and IAV was supported by Russian Foundation for Basic Research grants 11-01517a and 11-01749a. NR 230 TC 70 Z9 73 U1 1 U2 49 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD APR 22 PY 2013 VL 14 AR 23 DI 10.1186/1471-2121-14-23 PG 21 WC Cell Biology SC Cell Biology GA 144AJ UT WOS:000318911100002 PM 23607880 ER PT J AU Deo, AJ Goldszer, IM Li, SY DiBitetto, JV Henteleff, R Sampson, A Lewis, DA Penzes, P Sweet, RA AF Deo, Anthony J. Goldszer, Isaac M. Li, Siyu DiBitetto, James V. Henteleff, Ruth Sampson, Allan Lewis, David A. Penzes, Peter Sweet, Robert A. TI PAK1 Protein Expression in the Auditory Cortex of Schizophrenia Subjects SO PLOS ONE LA English DT Article ID DENDRITIC SPINE DENSITY; CORTICAL PYRAMIDAL NEURONS; PREFRONTAL CORTEX; IN-VIVO; KINASE; MORPHOGENESIS; SPINOPHILIN; MECHANISMS; DEFICITS; GENERATION AB Deficits in auditory processing are among the best documented endophenotypes in schizophrenia, possibly due to loss of excitatory synaptic connections. Dendritic spines, the principal post-synaptic target of excitatory projections, are reduced in schizophrenia. p21-activated kinase 1 (PAK1) regulates both the actin cytoskeleton and dendritic spine density, and is a downstream effector of both kalirin and CDC42, both of which have altered expression in schizophrenia. This study sought to determine if there is decreased auditory cortex PAK1 protein expression in schizophrenia through the use of quantitative western blots of 25 schizophrenia subjects and matched controls. There was no significant change in PAK1 level detected in the schizophrenia subjects in our cohort. PAK1 protein levels within subject pairs correlated positively with prior measures of total kalirin protein in the same pairs. PAK1 level also correlated with levels of a marker of dendritic spines, spinophilin. These latter two findings suggest that the lack of change in PAK1 level in schizophrenia is not due to limited sensitivity of our assay to detect meaningful differences in PAK1 protein expression. Future studies are needed to evaluate whether alterations in PAK1 phosphorylation states, or alterations in protein expression of other members of the PAK family, are present in schizophrenia. C1 [Deo, Anthony J.; Goldszer, Isaac M.; DiBitetto, James V.; Henteleff, Ruth; Lewis, David A.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15213 USA. [Deo, Anthony J.] Univ Pittsburgh, Sch Med, Phys Scientist Training Program, Pittsburgh, PA USA. [Li, Siyu; Sampson, Allan] Univ Pittsburgh, Dept Stat, Pittsburgh, PA USA. [Lewis, David A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. [Penzes, Peter] Northwestern Univ, Dept Physiol, Feinberg Sch Med, Chicago, IL 60611 USA. [Penzes, Peter] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Translat Neurosci Program, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu RI Lewis, David/G-4053-2014; Penzes, Peter/L-3987-2016 OI Lewis, David/0000-0002-3225-6778; Penzes, Peter/0000-0001-5449-1640 FU National Institutes of Mental Health [MH071533, MH084053, MH071316]; Doris Duke Charitable Foundation; Johnson & Johnson Pharmaceutical Research and Development FX This work was supported by grants MH071533, MH084053 and MH071316 from the National Institutes of Mental Health. Anthony Deo was supported by a Clinical Research Fellow grant from the Doris Duke Charitable Foundation to the University of Pittsburgh School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Allan R. Sampson is a paid statistical consultant on design and analysis issues to Johnson & Johnson Pharmaceutical Research and Development. This does not alter his adherence to all the PLOS ONE policies on sharing data and materials. NR 44 TC 5 Z9 6 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 22 PY 2013 VL 8 IS 4 AR e59458 DI 10.1371/journal.pone.0059458 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130JR UT WOS:000317911500002 PM 23613712 ER PT J AU Eswaran, J Horvath, A Godbole, S Reddy, SD Mudvari, P Ohshiro, K Cyanam, D Nair, S Fuqua, SAW Polyak, K Florea, LD Kumar, R AF Eswaran, Jeyanthy Horvath, Anelia Godbole, Sucheta Reddy, Sirigiri Divijendra Mudvari, Prakriti Ohshiro, Kazufumi Cyanam, Dinesh Nair, Sujit Fuqua, Suzanne A. W. Polyak, Kornelia Florea, Liliana D. Kumar, Rakesh TI RNA sequencing of cancer reveals novel splicing alterations SO SCIENTIFIC REPORTS LA English DT Article ID PRE-MESSENGER-RNA; BREAST-CANCER; SEQ; EXPRESSION; GENOME; BETA; P53; PREDISPOSITION; QUANTIFICATION; IDENTIFICATION AB Breast cancer transcriptome acquires a myriad of regulation changes, and splicing is critical for the cell to "tailor-make'' specific functional transcripts. We systematically revealed splicing signatures of the three most common types of breast tumors using RNA sequencing: TNBC, non-TNBC and HER2-positive breast cancer. We discovered subtype specific differentially spliced genes and splice isoforms not previously recognized in human transcriptome. Further, we showed that exon skip and intron retention are predominant splice events in breast cancer. In addition, we found that differential expression of primary transcripts and promoter switching are significantly deregulated in breast cancer compared to normal breast. We validated the presence of novel hybrid isoforms of critical molecules like CDK4, LARP1, ADD3, and PHLPP2. Our study provides the first comprehensive portrait of transcriptional and splicing signatures specific to breast cancer sub-types, as well as previously unknown transcripts that prompt the need for complete annotation of tissue and disease specific transcriptome. C1 [Eswaran, Jeyanthy; Horvath, Anelia; Godbole, Sucheta; Mudvari, Prakriti; Cyanam, Dinesh; Kumar, Rakesh] George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA. [Eswaran, Jeyanthy; Horvath, Anelia; Reddy, Sirigiri Divijendra; Ohshiro, Kazufumi; Nair, Sujit; Kumar, Rakesh] George Washington Univ, Dept Biochem & Mol Med, Washington, DC 20037 USA. [Fuqua, Suzanne A. W.] Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. [Polyak, Kornelia] Harvard Univ, Dept Med Oncol, Brigham & Womens Hosp, Dana Farber Canc Inst,Sch Med, Boston, MA 02215 USA. [Florea, Liliana D.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. RP Kumar, R (reprint author), George Washington Univ, McCormick Genom & Prote Ctr, Washington, DC 20037 USA. EM bcmrxk@gwu.edu RI sirigiri, divijendra reddy/E-1031-2017 OI sirigiri, divijendra reddy/0000-0003-4657-2285 FU McCormick Genomic and Proteomics Center FX This work is supported by the McCormick Genomic and Proteomics Center. NR 54 TC 59 Z9 61 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD APR 22 PY 2013 VL 3 AR 1689 DI 10.1038/srep01689 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 129BZ UT WOS:000317814700001 PM 23604310 ER PT J AU Evens, AM Hong, FX AF Evens, Andrew M. Hong, Fangxin TI How Can Outcomes Be Improved for Older Patients With Hodgkin Lymphoma? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID EPSTEIN-BARR-VIRUS; INVOLVED-FIELD RADIOTHERAPY; LONG-TERM SURVIVAL; ELDERLY-PATIENTS; DISEASE PATIENTS; CUMULATIVE INCIDENCE; POPULATION; CHEMOTHERAPY; BLEOMYCIN; DOXORUBICIN C1 [Evens, Andrew M.] Univ Massachusetts Med Sch, Worcester, MA USA. [Evens, Andrew M.] Univ Massachusetts Mem Canc Ctr, Worcester, MA USA. [Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Evens, AM (reprint author), Univ Massachusetts Med Sch, Worcester, MA USA. NR 41 TC 4 Z9 4 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 APR 20 PY 2013 VL 31 IS 12 BP 1502 EP 1505 DI 10.1200/JCO.2012.47.3058 PG 4 WC Oncology SC Oncology GA 129IC UT WOS:000317831500011 PM 23509323 ER PT J AU Storb, R Gyurkocza, B Storer, BE Sorror, ML Blume, K Niederwieser, D Chauncey, TR Pulsipher, MA Petersen, FB Sahebi, F Agura, ED Hari, P Bruno, B McSweeney, PA Maris, MB Maziarz, RT Langston, AA Bethge, W Vindelov, L Franke, GN Laport, GG Yeager, AM Hubel, K Deeg, HJ Georges, GE Flowers, MED Martin, PJ Mielcarek, M Woolfrey, AE Maloney, DG Sandmaier, BM AF Storb, Rainer Gyurkocza, Boglarka Storer, Barry E. Sorror, Mohamed L. Blume, Karl Niederwieser, Dietger Chauncey, Thomas R. Pulsipher, Michael A. Petersen, Finn B. Sahebi, Firoozeh Agura, Edward D. Hari, Parameswaran Bruno, Benedetto McSweeney, Peter A. Maris, Michael B. Maziarz, Richard T. Langston, Amelia A. Bethge, Wolfgang Vindelov, Lars Franke, Georg-Nikolaus Laport, Ginna G. Yeager, Andrew M. Huebel, Kai Deeg, H. Joachim Georges, George E. Flowers, Mary E. D. Martin, Paul J. Mielcarek, Marco Woolfrey, Ann E. Maloney, David G. Sandmaier, Brenda M. TI Graft-Versus-Host Disease and Graft-Versus-Tumor Effects After Allogeneic Hematopoietic Cell Transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; MATCHED UNRELATED DONORS; TOTAL-BODY IRRADIATION; HEMATOLOGIC MALIGNANCIES; MYELOGENOUS LEUKEMIA; RISK; OUTCOMES; RELAPSE; HCT; IMMUNOSUPPRESSION AB Purpose We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graft-versus-host disease (GVHD) not augmented by regimen-related toxicities. Patients and Methods Patients received low-dose total-body irradiation +/- fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of >= 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years). Results Depending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM. Conclusion Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD. J Clin Oncol 31:1530-1538. (C) 2013 by American Society of Clinical Oncology C1 [Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E.; Sorror, Mohamed L.; Deeg, H. Joachim; Georges, George E.; Flowers, Mary E. D.; Martin, Paul J.; Mielcarek, Marco; Woolfrey, Ann E.; Maloney, David G.; Sandmaier, Brenda M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E.; Sorror, Mohamed L.; Chauncey, Thomas R.; Deeg, H. Joachim; Georges, George E.; Flowers, Mary E. D.; Martin, Paul J.; Mielcarek, Marco; Woolfrey, Ann E.; Maloney, David G.; Sandmaier, Brenda M.] Univ Washington, Seattle, WA 98195 USA. [Chauncey, Thomas R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Blume, Karl; Laport, Ginna G.] Stanford Univ, Palo Alto, CA 94304 USA. [Sahebi, Firoozeh] City Hope Kaiser Permanente Med Grp, Duarte, CA USA. [Pulsipher, Michael A.] Univ Utah, Salt Lake City, UT USA. [Petersen, Finn B.] Intermt Hlth Care LDS Hosp, Salt Lake City, UT USA. [Agura, Edward D.] Baylor Univ, Dallas, TX USA. [Hari, Parameswaran] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [McSweeney, Peter A.; Maris, Michael B.] Colorado Blood Canc Inst Presbyterian St Lukes, Denver, CO USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR USA. [Langston, Amelia A.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Yeager, Andrew M.] Univ Arizona Canc Ctr, Tucson, AZ USA. [Niederwieser, Dietger; Franke, Georg-Nikolaus] Univ Leipzig, D-04109 Leipzig, Germany. [Bethge, Wolfgang] Univ Tubingen, Tubingen, Germany. [Huebel, Kai] Univ Hosp Cologne, Cologne, Germany. [Bruno, Benedetto] Univ Turin, Turin, Italy. [Vindelov, Lars] Univ Copenhagen Rigshosp, Copenhagen, Denmark. RP Storb, R (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,Mail Stop D1-100,POB 19024, Seattle, WA 98109 USA. EM rstorb@fhcrc.org OI Gyurkocza, Boglarka/0000-0002-2933-2119; Hari, Parameswaran/0000-0002-8800-297X FU National Institutes of Health, Bethesda, MD [P01 HL036444, P01 CA078902, P01 CA018029, P30 CA015704, P30 CA023074, R01 HL108307, R00 HL088021]; Leukemia/Lymphoma Society [7008-08]; Laura Landro Salomon Endowment Fund; Danish Cancer Society; Lundbeck Foundation; Ricerca Finalizzata; Compagnia di San Paolo and Comitato Gigi Ghirotti FX Supported by Grants No. P01 HL036444, P01 CA078902, P01 CA018029, P30 CA015704, P30 CA023074, R01 HL108307, and R00 HL088021 from the National Institutes of Health, Bethesda, MD. Further support came from grants from the Leukemia/Lymphoma Society (Grant No. 7008-08), the Laura Landro Salomon Endowment Fund, the Danish Cancer Society, the Lundbeck Foundation, the Ricerca Finalizzata 2008-2009, and the Compagnia di San Paolo and Comitato Gigi Ghirotti. NR 39 TC 71 Z9 73 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2013 VL 31 IS 12 BP 1530 EP 1538 DI 10.1200/JCO.2012.45.0247 PG 9 WC Oncology SC Oncology GA 129IC UT WOS:000317831500015 PM 23478054 ER PT J AU Mayer, RJ AF Mayer, Robert J. TI Disease-Free Survival in Colon Cancer: Still Relevant After All These Years! Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID ADJUVANT CHEMOTHERAPY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2013 VL 31 IS 12 BP 1612 EP 1613 DI 10.1200/JCO.2012.47.8859 PG 3 WC Oncology SC Oncology GA 129IC UT WOS:000317831500029 PM 23734371 ER PT J AU Smoller, JW Craddock, N Kendler, K Lee, PH Neale, BM Nurnberger, JI Ripke, S Santangelo, S Sullivan, PF AF Smoller, Jordan W. Craddock, Nicholas Kendler, Kenneth Lee, Phil Hyoun Neale, Benjamin M. Nurnberger, John I. Ripke, Stephan Santangelo, Susan Sullivan, Patrick F. CA Psychiatric Genomics Consortium TI Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis SO LANCET LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; AUTISM SPECTRUM DISORDERS; BIPOLAR DISORDER; GENE-EXPRESSION; SCHIZOPHRENIA; ASSOCIATION; METAANALYSIS; POPULATION; CACNA1C; DEPRESSION AB Background Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. Methods We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. Findings SNPs at four loci surpassed the cutoff for genome-wide significance (p<5x10(-8)) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers. Interpretation Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause. C1 [Smoller, Jordan W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Simches Res Bldg, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu RI Holmans, Peter/F-4518-2015; Mattheisen, Manuel/B-4949-2012; Ruderfer, Douglas/M-5795-2016; Lohoff, Falk/M-7951-2016; BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Lesch, Klaus-Peter/J-4906-2013; Wray, Naomi/C-8639-2015; Franke, Barbara/D-4836-2009; Sonuga-Barke, Edmund/D-9137-2011; Breen, Gerome/A-5540-2010; Medland, Sarah/C-7630-2013; Hansen, Thomas/O-5965-2014; Kuntsi, Jonna/G-9750-2011; van Grootheest, Gerard/C-6942-2014; Sigurdsson, Engilbert/D-2486-2014; Kahler, Anna/J-2874-2012; Nolen, Willem/E-9006-2014; Zhang, Peng/N-2920-2014 OI Anney, Richard/0000-0002-6083-407X; Agartz, Ingrid/0000-0002-9839-5391; Nothen, Markus/0000-0002-8770-2464; Andreassen, Ole A./0000-0002-4461-3568; Thapar, Anita/0000-0002-3689-737X; Etain, Bruno/0000-0002-5377-1488; Visscher, Peter/0000-0002-2143-8760; Pickard, Benjamin/0000-0002-2374-6329; de Geus, Eco/0000-0001-6022-2666; Hamilton, Steven/0000-0001-8106-6260; Backlund, Lena/0000-0001-9399-5024; Zammit, Stanley/0000-0002-2647-9211; Jamain, Stephane/0000-0002-4321-4100; Greenwood, Tiffany/0000-0002-6080-6503; KELLER, MATTHEW/0000-0002-6075-9882; lichtenstein, paul/0000-0003-3037-5287; Stefansson, Hreinn/0000-0002-9331-6666; Holmans, Peter/0000-0003-0870-9412; Mattheisen, Manuel/0000-0002-8442-493X; Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; Lesch, Klaus-Peter/0000-0001-8348-153X; Wray, Naomi/0000-0001-7421-3357; Craig, Ian/0000-0002-4063-1005; Bergen, Sarah/0000-0002-5888-0034; Tozzi, Federica/0000-0002-3536-2920; McMahon, Francis/0000-0002-9469-305X; MacIntyre, Donald J/0000-0001-6963-1335; Franke, Barbara/0000-0003-4375-6572; Breen, Gerome/0000-0003-2053-1792; Medland, Sarah/0000-0003-1382-380X; Hansen, Thomas/0000-0001-6703-7762; van Grootheest, Gerard/0000-0003-4350-6661; Sigurdsson, Engilbert/0000-0001-9404-7982; Zhang, Peng/0000-0003-1182-1392 FU NIMH [U01 MH085520]; National Institutes of Health (USA); National Institute of Mental Health FX National Institute of Mental Health.; We thank the study participants, and the research staff at the many study sites. This work was supported by NIMH grant U01 MH085520. Numerous grants from the National Institutes of Health (USA), and similar numbers of government grants from other countries, and substantial private and foundation support enabled this work. NR 50 TC 609 Z9 614 U1 30 U2 271 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 20 PY 2013 VL 381 IS 9875 BP 1371 EP 1379 DI 10.1016/S0140-6736(12)62129-1 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 130EF UT WOS:000317894800034 PM 23453885 ER PT J AU Hart, RA Cabalo, A Bess, S Akbarnia, BA Boachie-Adjei, O Burton, D Cunningham, ME Gupta, M Hostin, R Kebaish, K Klineberg, E Mundis, G Shaffrey, C Smith, JS Wood, K AF Hart, Robert A. Cabalo, Adam Bess, Shay Akbarnia, Behrooz A. Boachie-Adjei, Oheneba Burton, Douglas Cunningham, Matthew E. Gupta, Munish Hostin, Richard Kebaish, Khaled Klineberg, Eric Mundis, Gregory Shaffrey, Christopher Smith, Justin S. Wood, Kirkham CA Int Spine Study Grp TI Comparison of Patient and Surgeon Perceptions of Adverse Events After Adult Spinal Deformity Surgery SO SPINE LA English DT Article DE adverse events; outcomes; scoliosis; spinal fusion; spine surgery ID HEALTH SURVEY SF-36; COMPLICATIONS; SCOLIOSIS; OUTCOMES; RELIABILITY; AGE; MORTALITY; VALIDITY; FUSIONS; QUALITY AB Study Design. Survey based on complication scenarios. Objective. To assess and compare perceived potential impacts of various perioperative adverse events by both surgeons and patients. Summary of Background Data. Incidence of adverse events after adult spinal deformity surgery remains substantial. Patient-centered outcomes tools measuring the impact of these events have not been developed. An important first step is to assess the perceptions of surgeons and patients regarding the impact of these events on surgical outcome and quality of life. Methods. Descriptions of 22 potential adverse events of surgery (heart attack, stroke, spinal cord injury, nerve root injury, cauda equina injury, blindness, dural tear, blood transfusion, deep vein thrombosis, pulmonary embolism, superficial infection, deep infection, lung failure, urinary tract infection, nonunion, adjacent segment disease, persistent deformity, implant failure, death, renal failure, gastrointestinal complications, and sexual dysfunction) were presented to 14 spinal surgeons and 16 adult patients with spinal deformity. Impact scores were assigned to each complication on the basis of perceptions of overall severity, satisfaction with surgery, and effect on quality of life. Impact scores were compared between surgeons and patients with a Wilcoxon/Kruskal-Wallis test. Results. Mean impact scores varied from 0.9 (blood transfusion) to 10.0 (death) among surgeons and 2.3 (urinary tract infection) to 9.2 (stroke) among patients. Patients' scores were consistently higher (P < 0.05) than surgeons in all 3 categories for 6 potential adverse events: stroke, lung failure, heart attack, pulmonary embolism, dural tear, and blood transfusion. Three additional complications (renal failure, non-union, and deep vein thrombosis) were rated higher in 1 or 2 categories by patients. Conclusion. There was substantial variation in how both surgeons and patients perceived impacts of various adverse events after spine surgery. Patients generally perceived the impact of adverse events to be greater than surgeons. Patient-centered descriptions of adverse events would provide a more complete description of surgical outcomes. C1 [Hart, Robert A.; Cabalo, Adam] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Bess, Shay] Rocky Mt Hosp Children, Denver, CO USA. [Akbarnia, Behrooz A.; Mundis, Gregory] San Diego Ctr Spinal Disorders, La Jolla, CA USA. [Boachie-Adjei, Oheneba; Cunningham, Matthew E.] Hosp Special Surg, New York, NY 10021 USA. [Burton, Douglas; Klineberg, Eric] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Gupta, Munish] Univ Calif Davis, Sacramento, CA 95817 USA. [Hostin, Richard] Baylor Scoliosis Ctr, Plano, TX USA. [Kebaish, Khaled] Johns Hopkins Univ, Baltimore, MD USA. [Shaffrey, Christopher; Smith, Justin S.] Univ Virginia, Charlottesville, VA USA. [Int Spine Study Grp] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hart, RA (reprint author), Oregon Hlth & Sci Univ, Sam Jackson Hall,Ste 2360,3181 SW Sam Jackson Pk, Portland, OR 97239 USA. EM hartro@ohsu.edu RI sebastianovitsch, stepan/G-8507-2013; OI bess, shay/0000-0002-9697-8999 FU Depuy Spine; Children's Research Foundation FX Depuy Spine and Children's Research Foundation funds were received to support this work. NR 33 TC 6 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 20 PY 2013 VL 38 IS 9 BP 732 EP 736 DI 10.1097/BRS.0b013e31827ae242 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 130JH UT WOS:000317910300013 PM 24477053 ER PT J AU Luo, NL Wang, XD Zhang, W Garvey, WT Fu, YC AF Luo, Nanlan Wang, Xiangdong Zhang, Wei Garvey, W. T. Fu, Yuchang TI AdR1-TG/TALLYHO mice have improved lipid accumulation and insulin sensitivity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Adiponectin receptor; TALLYHO mouse model; Diabetes ID MONOCYTE-DERIVED MACROPHAGES; PIMA INDIAN POPULATION; MOUSE MODEL; ADIPONECTIN RECEPTORS; METABOLIC SYNDROME; DIABETES RESEARCH; OBESITY; GLUCOSE; DISEASE; PROTEIN AB Background: Overexpression of adiponectin receptor 1 in macrophages can physiologically modulate metabolic activities in vivo by enhancing adiponectin actions in distal metabolically active tissues. To investigate the effects of enhanced adiponectin actions in TALLYHO (TH) diabetic mouse model, we crossed the adiponectin receptor 1 macrophage-specific transgenic mice (AdR1-TG) with the TALLYHO diabetic mice (TH) to examine the changes of lipid accumulation and insulin sensitivity in these mice. Methods: AdR1-TG/TH and the control WT/TH mice were fed either normal diet or high fat diet for 28 weeks. Whole body weights of these mice were measured and mouse sera were analyzed for the levels of cholesterol, triglyceride, and free fatty acids. Glucose tolerance testing (GTT) and insulin tolerance testing (ITT) in these mice were performed to investigate systemic insulin sensitivity in vivo. Molecular markers for insulin signaling pathway in mouse skeletal muscle tissues, IRS-1 and AKT, were examined. Mouse serum insulin levels were measured and Sirt1 gene expression in mouse pancreatic tissues was also quantified related to the insulin secretion. The Caspase 3 protein levels were analyzed by Western blot methods. Results: Compared to the control WT/TH mice, AdR1-TG/TH mice showed significantly lower body weights under either normal diet or high fat diet and the mouse serum levels of cholesterol, triglyceride and free fatty acids were significantly decreased in the transgenic crossed mice when compared to those from the control mice. Improved GTF and ITT tests indicating increased systemic insulin sensitivity in the transgenic crossed mice demonstrated the enhanced adiponectin actions on the systemic metabolism in vivo. The increases of insulin secretion and its related gene expression were also detected in the transgenic crossed mice. In contrast, the control mice showed hypertrophy pancreases companying with high apoptosis gene expression. These results suggest that enhanced adiponectin actions by overexpressing adiponectin receptor 1 in macrophages can provide unique interactions with the metabolic tissues/cells, improving lipid accumulation and insulin sensitivity in TALLYHO diabetic mice. (C) 2013 Elsevier Inc. All rights reserved. C1 [Luo, Nanlan; Zhang, Wei; Garvey, W. T.; Fu, Yuchang] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Wang, Xiangdong] Shandong Univ, Inst Cell Biol, Jinan 250012, Peoples R China. [Garvey, W. T.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Fu, YC (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Shelby Bldg 1213,1825 Univ Blvd, Birmingham, AL 35294 USA. EM yfu@uab.edu FU American Diabetes Association [1-07-RA-49, 1-13-IN-19]; NIH [DK-083562] FX We are grateful to the UAB Diabetes Research and Training Center for providing outstanding core services (NIH P30 DK-56336). This work was supported by grants from American Diabetes Association (1-07-RA-49 and 1-13-IN-19) to Y.F., and grant from NIH (DK-083562) to T.G. NR 29 TC 2 Z9 3 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 19 PY 2013 VL 433 IS 4 BP 567 EP 572 DI 10.1016/j.bbrc.2013.03.030 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 135AT UT WOS:000318259100037 PM 23523784 ER PT J AU Baker, A Braggio, E Jacobus, S Jung, S Larson, D Therneau, T Dispenzieri, A Van Wier, SA Ahmann, G Levy, J Perkins, L Kim, S Henderson, K Vesole, D Rajkumar, SV Jelinek, DF Carpten, J Fonseca, R AF Baker, Angela Braggio, Esteban Jacobus, Susanna Jung, Sungwon Larson, Dirk Therneau, Terry Dispenzieri, Angela Van Wier, Scott A. Ahmann, Gregory Levy, Joan Perkins, Louise Kim, Seungchan Henderson, Kimberly Vesole, David Rajkumar, S. Vincent Jelinek, Diane F. Carpten, John Fonseca, Rafael TI Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach SO BLOOD LA English DT Article ID UNDETERMINED SIGNIFICANCE MGUS; COOPERATIVE-ONCOLOGY-GROUP; MONOCLONAL GAMMOPATHY; PROGNOSTIC-SIGNIFICANCE; CHROMOSOME-13 ABNORMALITIES; INTERGROUPE FRANCOPHONE; EXPRESSION; RISK; DELETIONS; CLASSIFICATION AB Epidemiological data have suggested that African American (AA) persons are twice as likely to be diagnosed with multiple myeloma (MM) compared with European American (EA) persons. Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from 3 studies and 353 EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs 52%; P = .032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based on gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients. ECOG E4A03 is registered with ClinicalTrials.gov, number NCT00098475. ECOG E9487 is a companion validation set to the ECOG study E9486 and is registered with the National Institutes of Health, National Cancer Institute, Clinical Trials (PDQ), number EST-9486. C1 [Baker, Angela; Jung, Sungwon; Kim, Seungchan; Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA. [Braggio, Esteban; Van Wier, Scott A.; Ahmann, Gregory; Fonseca, Rafael] Mayo Clin Scottsdale, Scottsdale, AZ 85259 USA. [Jacobus, Susanna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Larson, Dirk; Therneau, Terry; Dispenzieri, Angela; Henderson, Kimberly; Rajkumar, S. Vincent; Jelinek, Diane F.] Mayo Clin Rochester, Rochester, MN USA. [Levy, Joan; Perkins, Louise] Multiple Myeloma Res Fdn, Norwalk, CT USA. [Vesole, David] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. RP Fonseca, R (reprint author), Mayo Clin Scottsdale, 13400 East Shea Blvd,Collaborat Res Bldg,3-006, Scottsdale, AZ 85259 USA. EM fonseca.rafael@mayo.edu OI Rajkumar, S. Vincent/0000-0002-5862-1833; Fonseca, Rafael/0000-0002-5938-3769; Dispenzieri, Angela/0000-0001-8780-9512 FU Multiple Myeloma Research Consortium [SPORE CA90297052, P01 CA62242, R01 CA83724, ECOG CA 21115T]; Predolin Foundation; Mayo Clinic Cancer Center; Mayo Foundation; Damon Runyon Cancer Research Fund; Medtronic; Otsuka; Celgene; Genzyme; BMS; AMGEN; Cylene; Onyx FX This work was supported by the Multiple Myeloma Research Consortium (grants SPORE CA90297052, P01 CA62242, R01 CA83724, and ECOG CA 21115T); Predolin Foundation; Mayo Clinic Cancer Center; and the Mayo Foundation. This research was also funded in part by Damon Runyon Cancer Research Fund (to R.F.).; Relevant to this work, Dr Fonseca has received a patent for the prognostication of MM based on genetic categorization of the disease. He has received consulting fees from Medtronic, Otsuka, Celgene, Genzyme, BMS, and AMGEN. He also has sponsored research from Cylene and Onyx. The remaining authors declare no competing financial interests. NR 42 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 18 PY 2013 VL 121 IS 16 BP 3147 EP 3152 DI 10.1182/blood-2012-07-443606 PG 6 WC Hematology SC Hematology GA 183PK UT WOS:000321829200015 PM 23422747 ER PT J AU Rychert, J Jones, L McGrath, G Bazner, S Rosenberg, ES AF Rychert, Jenna Jones, Lindsay McGrath, Graham Bazner, Sue Rosenberg, Eric S. TI A monoclonal antibody against lymphocyte function-associated antigen-1 decreases HIV-1 replication by inducing the secretion of an antiviral soluble factor SO VIROLOGY JOURNAL LA English DT Article DE HIV-1; LFA-1; Monoclonal antibody therapy ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTES; CELLS; EPITOPES; VIRIONS; LFA-1; INDIVIDUALS; COMPONENTS; INFECTION; RESPONSES AB Background: Lymphocyte Function-Associated Antigen-1 (LFA-1) likely plays a role in the pathogenesis of against HIV-1 and is known to facilitate cell-to-cell transmission of the virus. A monoclonal antibody specific for LFA-1 (Cytolin (R)) was evaluated as a potential therapeutic in pilot studies performed in the mid-1990s. These uncontrolled human studies suggested that administration of this anti-LFA-1 antibody to HIV-1 infected individuals could provide a modest benefit by decreasing circulating HIV-1 RNA and increasing CD4+ T cell counts. At the time, it was proposed that when bound to cytolytic T cells, the antibody inhibited lysis of activated CD4+ T cells. Given the renewed interest in monoclonal antibody therapy for HIV-1 infected individuals, we investigated possible mechanisms of action of this antibody in vitro. Methods: To assess whether this anti-LFA-1 antibody binds to HIV-1, a virus capture assay was performed. Binding of the antibody to cells was assessed using flow cytometry. Inhibition of HIV-1 replication was determined in culture by measuring the amount of p24 produced by ELISA. After co-culture of the antibody with peripheral blood mononuclear cells, supernatants were assayed for cytokines and chemokines using various immunoassays. Results: Our experiments demonstrate that anti-LFA-1 antibody binds to CCR5 and CXCR4 utilizing strains of HIV-1. It also binds to CD8+ T cells and dendritic cells. When bound to virus prior to infection, there is no decrease in HIV-1 replication, suggesting it does not directly inhibit viral replication via virus binding. When bound to cells, it does not inhibit lysis of CD4+ T cells, as was originally hypothesized. Binding to cells does appear to induce the production of a soluble factor that inhibits HIV-1 replication. We determined that this soluble factor was not any of the cytokines or chemokines with known anti-HIV-1 activity. Further, the antibody does not appear to induce any common immune modulating cytokines or chemokines. Conclusions: These results suggest that one possible mechanism of action of this anti-LFA-1 antibody is to inhibit HIV-1 replication via the production of a soluble antiviral factor that is induced upon binding to cells. C1 [Rychert, Jenna] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rychert, J (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM jrychert@partners.org FU Cytodyn FX This study was funded by Cytodyn. The study design, subject recruitment, and experiments were conceived of and carried out by members of the study team without input from the company. NR 27 TC 1 Z9 2 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD APR 18 PY 2013 VL 10 AR 120 DI 10.1186/1743-422X-10-120 PG 10 WC Virology SC Virology GA 141WS UT WOS:000318757800001 PM 23594747 ER PT J AU Michaud, DS Siddiq, A Cox, DG Backes, DM Calboli, FCF Sughrue, ME Gaziano, JM Ma, J Stampfer, M Tworoger, SS Hunter, DJ Camargo, CA Parsa, AT AF Michaud, Dominique S. Siddiq, Afshan Cox, David G. Backes, Danielle M. Calboli, Federico C. F. Sughrue, Michael E. Gaziano, J. Michael Ma, Jing Stampfer, Meir Tworoger, Shelley S. Hunter, David J. Camargo, Carlos A., Jr. Parsa, Andrew T. TI Mannose-Binding Lectin 2 Gene and Risk of Adult Glioma SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; HUMAN-PAPILLOMAVIRUS INFECTION; CANCER RISK; FUNCTIONAL POLYMORPHISMS; UNRELATED INDIVIDUALS; BREAST-CANCER; MBL2; WOMEN; SUSCEPTIBILITY; POPULATION AB Background and Aims: The immune system is likely to play a key role in the etiology of gliomas. Genetic polymorphisms in the mannose-binding lectin gene, a key activator in the lectin complement pathway, have been associated with risk of several cancers. Methods: To examine the role of the lectin complement pathway, we combined data from prospectively collected cohorts with available DNA specimens. Using a nested case-control design, we genotyped 85 single nucleotide polymorphisms (SNPs) in 9 genes in the lectin complement pathway and 3 additional SNPs in MBL2 were tested post hoc). Initial SNPs were selected using tagging SNPs for haplotypes; the second group of SNPs for MBL2 was selected based on functional SNPs related to phenotype. Associations were examined using logistic regression analysis. All statistical tests were two-sided. Nominal p-values are presented and are not corrected for multiple comparisons. Results: A total of 143 glioma cases and 419 controls were available for this analysis. Statistically significant associations were observed for two SNPs in the mannose-binding lectin 2 (ML2) gene and risk of glioma (rs1982266 and rs1800450, test for trend p = 0.003 and p = 0.04, respectively, using the additive model). One of these SNPs, rs1800450, was associated with a 58% increase in glioma risk among those carrying one or two mutated alleles (odds ratio = 1.58, 95% confidence interval = 0.99-2.54), compared to those homozygous for the wild type allele. Conclusions: Overall, our findings suggest that MBL may play a role in the etiology of glioma. Future studies are needed to confirm these findings which may be due to chance, and if reproduced, to determine mechanisms that link glioma pathogenesis with the MBL complement pathway. C1 [Michaud, Dominique S.; Backes, Danielle M.] Brown Univ, Brown Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Michaud, Dominique S.; Siddiq, Afshan; Cox, David G.; Calboli, Federico C. F.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, London, England. [Cox, David G.] UCBL1, CNRS UMR 5286, INSERM U1052, Lyon Canc Res Ctr, Lyon, France. [Sughrue, Michael E.] Univ Oklahoma, Dept Neurol Surg, Norma, OK USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Ma, Jing; Stampfer, Meir; Tworoger, Shelley S.; Hunter, David J.; Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Div, Med Network, Boston, MA 02115 USA. [Ma, Jing; Stampfer, Meir; Tworoger, Shelley S.; Hunter, David J.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Stampfer, Meir; Tworoger, Shelley S.; Hunter, David J.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Stampfer, Meir; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Parsa, Andrew T.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. RP Michaud, DS (reprint author), Brown Univ, Brown Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. EM Dominique_Michaud@brown.edu RI Michaud, Dominique/I-5231-2014; Cox, David/A-2023-2009; OI Cox, David/0000-0002-2152-9259; Tworoger, Shelley/0000-0002-6986-7046 FU National Institutes of Health [R01 CA114205, P01 CA097193, P01 CA087969, P01 CA055075-] FX This work was supported by the National Institutes of Health (R01 CA114205; P01 CA097193; P01 CA087969; P01 CA055075-). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 2 Z9 2 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 APR 18 PY 2013 VL 8 IS 4 AR e61117 DI 10.1371/journal.pone.0061117 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130IU UT WOS:000317908700014 PM 23637788 ER PT J AU Shanmugasundaram, K Block, K Nayak, BK Livi, CB Venkatachalam, MA Sudarshan, S AF Shanmugasundaram, K. Block, K. Nayak, B. K. Livi, C. B. Venkatachalam, M. A. Sudarshan, S. TI PI3K regulation of the SKP-2/p27 axis through mTORC2 SO ONCOGENE LA English DT Article DE p27; SKP-2; mTOR; RICTOR ID RENAL-CELL CARCINOMA; RAPAMYCIN COMPLEX 2; PROTEIN-KINASE B; TISSUE MICROARRAY; SUBCELLULAR-LOCALIZATION; CYTOPLASMIC LOCALIZATION; AKT PHOSPHORYLATION; MAMMALIAN TARGET; UBIQUITIN LIGASE; SKP2 AB The cyclin-dependent kinase inhibitor p27 is a key regulator of cell-cycle progression. Its expression and localization are altered in several types of malignancies, which has prognostic significance in cancers such as renal cell carcinoma (RCC). S-phase kinase-associated protein 2 (SKP-2) is an F-box protein that is part of the SKP-1/Cul1/F-box ubiquitin ligase complex that targets nuclear p27 among many other cell-cycle proteins for proteosomal degradation. Its overexpression has been observed in several tumor types. Signaling by phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) has previously been shown to regulate the SKP-2/p27 axis. Recent evidence suggests that PI3K signaling may activate mammalian target of rapamycin complex 2 (mTORC2) activity. As PI3K signaling is known to regulate SKP-2 and p27, we sought to determine whether these effects were mediated by mTORC2. Here we provide additional genetic evidence that PI3K signaling activates mTORC2 kinase activity. We also demonstrate a novel role for mTORC2 in the modulation of nuclear p27 levels. In particular, mTORC2 signaling promotes the reduction of nuclear p27 protein levels through the increased protein expression of SKP-2. These are the first data to demonstrate a role for mTOR in the regulation of SKP-2. In concordance with these findings, mTORC2 activity promotes cell proliferation of RCC cells at the G1-S interphase of the cell cycle. Collectively, these data implicate mTORC2 signaling in the regulation of the SKP-2/p27 axis, a signaling node commonly altered in cancer. Oncogene (2013) 32, 2027-2036; doi:10.1038/onc.2012.226; published online 25 June 2012 C1 [Shanmugasundaram, K.; Sudarshan, S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Block, K.; Nayak, B. K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Livi, C. B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Venkatachalam, M. A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Block, K.] Audie L Murphy Mem Hosp Div, South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Sudarshan, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, 7703 Floyd Curl Dr,MC 7845, San Antonio, TX 78229 USA. EM sudarshan@uthscsa.edu FU Cancer Therapy and Research Center (CTRC) at the University of Texas Health Science Center [NIH P30 CA054174-17]; NIH [K08 CA138774, R01 NCI CA131272]; Voelcker Fund Young Investigator Award; AUA Foundation/Astellas Rising Star Award; Veterans Administration Career Development Award [CDA-2] FX This work was supported in part by the Cancer Therapy and Research Center (CTRC) at the University of Texas Health Science Center (NIH P30 CA054174-17). SS is supported by NIH K08 CA138774, Voelcker Fund Young Investigator Award, AUA Foundation/Astellas Rising Star Award and a special gift from Mr Charles Butt and the employees of HEB. KB is supported by Veterans Administration Career Development Award (CDA-2) and NIH R01 NCI CA131272. We thank Z David Sharp for critical review of the manuscript. We thank William Friedrichs and Korri Weldon for technical assistance. NR 43 TC 12 Z9 14 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 18 PY 2013 VL 32 IS 16 BP 2027 EP 2036 DI 10.1038/onc.2012.226 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 130LY UT WOS:000317919900004 PM 22733130 ER PT J AU Hunt, DP Muse, VV Pitman, MB AF Hunt, Daniel P. Muse, Victorine V. Pitman, Martha B. TI Case 12-2013: An 18-Year-Old Woman with Pulmonary Infiltrates and Respiratory Failure Herpes simplex virus type 1 pneumonia. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EPSTEIN-BARR-VIRUS; INFECTIOUS-MONONUCLEOSIS; TULAREMIA; MARIJUANA C1 [Hunt, Daniel P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Pitman, Martha B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hunt, Daniel P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Muse, Victorine V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Pitman, Martha B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hunt, DP (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 17 TC 0 Z9 0 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 18 PY 2013 VL 368 IS 16 BP 1537 EP 1545 DI 10.1056/NEJMcpc1209608 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 126HC UT WOS:000317603300013 PM 23594007 ER PT J AU Kirienko, NV Kirienko, DR Larkins-Ford, J Wahlby, C Ruvkun, G Ausubel, FM AF Kirienko, Natalia V. Kirienko, Daniel R. Larkins-Ford, Jonah Wahlby, Carolina Ruvkun, Gary Ausubel, Frederick M. TI Pseudomonas aeruginosa Disrupts Caenorhabditis elegans Iron Homeostasis, Causing a Hypoxic Response and Death SO CELL HOST & MICROBE LA English DT Article ID SENSOR KINASE KINB; CYSTIC-FIBROSIS; VIRULENCE FACTORS; REGULATES VIRULENCE; HUMAN-SERUM; INFECTION; BACTERIAL; MODEL; PATHOGENESIS; SIDEROPHORES AB The opportunistic pathogen Pseudomonas aeruginosa causes serious human infections, but effective treatments and the mechanisms mediating pathogenesis remain elusive. Caenorhabditis elegans shares innate immune pathways with humans, making it invaluable to investigate infection. To determine how P. aeruginosa disrupts host biology, we studied how P. aeruginosa kills C. elegans in a liquid-based pathogenesis model. We found that P. aeruginosa-mediated killing does not require quorum-sensing pathways or host colonization. A chemical genetic screen revealed that iron chelators alleviate P. aeruginosa-mediated killing. Consistent with a role for iron in P. aeruginosa pathogenesis, the bacterial siderophore pyoverdin was required for virulence and was sufficient to induce a hypoxic response and death in the absence of bacteria. Loss of the C. elegans hypoxia-inducing factor HIF-1, which regulates iron homeostasis, exacerbated P. aeruginosa pathogenesis, further linking hypoxia and killing. As pyoverdin is indispensable for virulence in mice, pyoverdin-mediated hypoxia is likely to be relevant in human pathogenesis. C1 [Kirienko, Natalia V.; Kirienko, Daniel R.; Larkins-Ford, Jonah; Ruvkun, Gary; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kirienko, Natalia V.; Kirienko, Daniel R.; Ruvkun, Gary; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Wahlby, Carolina] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Wahlby, Carolina] Uppsala Univ, Ctr Image Anal, SciLifeLab, S-75105 Uppsala, Sweden. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU Massachusetts Biomedical Research Corporation Tosteson Postdoctoral Fellowship Award; National Institutes of Health [F32 AI100501, R01 AI085581, R01 GM095672, T32 DA013911, U54 AI057159] FX We are grateful to L. Rahme, L. Dietrich, D. Newman, D. Hung, I. Schalk, S. Lory, C. Manoil, and D. Haas for providing bacterial strains and the Caenorhabditis Genetics Center for worm strains. We also wish to express our gratitude to V. Mootha and V. Cracan for helpful discussions. We thank members of the Ausubel and Ruvkun labs for critical reading of the manuscript and experimental advice. Finally, we wish to express our gratitude to S. Chiang and the staff of the NSRB for providing resources and facilities for high-throughput screening. This study was supported by the Massachusetts Biomedical Research Corporation Tosteson Postdoctoral Fellowship Award to N.V.K. and by the following grants from the National Institutes of Health: F32 AI100501 awarded to N.V.K., R01 AI085581 awarded to F. M. A., R01 GM095672 awarded to C. W., T32 DA013911 awarded to D. R. K., and U54 AI057159 awarded to N.S.R.B. NR 64 TC 35 Z9 38 U1 2 U2 32 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 EI 1934-6069 J9 CELL HOST MICROBE JI Cell Host Microbe PD APR 17 PY 2013 VL 13 IS 4 BP 406 EP 416 DI 10.1016/j.chom.2013.03.003 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AA1IT UT WOS:000330850500006 PM 23601103 ER PT J AU Hipple, B Nabi-Burza, E Hall, N Regan, S Winickoff, JP AF Hipple, Bethany Nabi-Burza, Emara Hall, Nicole Regan, Susan Winickoff, Jonathan P. TI Distance-based training in two community health centers to address tobacco smoke exposure of children SO BMC PEDIATRICS LA English DT Article DE Tobacco smoke exposure; Secondhand smoke; Tobacco control; Online education; Community health centers; Parental smoking; Tobacco cessation ID PARENTS QUIT SMOKING; HOMES; CARE AB Background: The CEASE (Clinical Effort Against Secondhand Smoke Exposure) intervention was developed to help pediatricians routinely and effectively address the harms of family smoking behaviors. Based on paper versions of CEASE, we partnered with the American Academy of Pediatrics' online education department and developed a completely distance-based training, including an online CME training, handouts and education materials for families, and phone and email support. Methods: The pediatric offices of two low income health clinics with primarily Medicaid populations were selected for the study. Pre and post intervention data by survey of the parents was collected in both practices (Practice 1 n = 470; Practice 2 n = 177). The primary outcome for this study was a comparison of rates of clinician's asking and advising parents about smoking and smoke-free home and cars. Results: Exit surveys of parents revealed statistically significant increases in rates of clinicians asking about parental smoking (22% vs. 41%), smoke-free rules (25% vs. 44%), and asking about other smoking household members (26% vs. 48%). Conclusions: Through a completely distance based intervention, we were able to train pediatricians who see low income children to ask parents about smoking, smoke-free home and car rules, and whether other household members smoke. Implementing a system to routinely ask about family tobacco use and smoke-free home and car rules is a first step to effectively addressing tobacco in a pediatric office setting. By knowing which family members use tobacco, pediatricians can take the next steps to help families become completely tobacco-free. C1 [Hipple, Bethany; Nabi-Burza, Emara; Hall, Nicole; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02144 USA. [Winickoff, Jonathan P.] Amer Acad Pediat, AAP Richmond Ctr Excellence, Elk Grove Village, IL USA. [Hipple, Bethany; Nabi-Burza, Emara; Hall, Nicole; Regan, Susan; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02144 USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, 50 Staniford St Suite 901, Boston, MA 02144 USA. EM jwinickoff@partners.org OI Regan, Susan/0000-0003-0940-2017 FU Clinical Innovator Award from the Flight Attendant Medical Research Institute; AAP Julius B. Richmond Center; American Academy of Pediatrics' PediaLink Online Center for Lifelong Learning; Massachusetts Tobacco Cessation and Prevention Program FX This study was supported by a Clinical Innovator Award from the Flight Attendant Medical Research Institute. The study was also supported by the AAP Julius B. Richmond Center and the American Academy of Pediatrics' PediaLink Online Center for Lifelong Learning. The video included in the module was supported by the Massachusetts Tobacco Cessation and Prevention Program. NR 19 TC 3 Z9 3 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2431 J9 BMC PEDIATR JI BMC Pediatr. PD APR 17 PY 2013 VL 13 AR 56 DI 10.1186/1471-2431-13-56 PG 7 WC Pediatrics SC Pediatrics GA 139VQ UT WOS:000318613500001 PM 23594832 ER PT J AU Wachter, F Grunert, M Blaj, C Weinstock, DM Jeremias, I Ehrhardt, H AF Wachter, Franziska Grunert, Michaela Blaj, Cristina Weinstock, David M. Jeremias, Irmela Ehrhardt, Harald TI Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling SO CELL COMMUNICATION AND SIGNALING LA English DT Article DE p53; Mutant p53; Extrinsic; Intrinsic; TRAIL; Doxorubicin; Apoptosis ID DNA-BINDING COOPERATIVITY; MUTANT P53; GENE-EXPRESSION; VINCA ALKALOIDS; CANCER; TRANSCRIPTION; SUPPRESSION; ACTIVATION; MUTATIONS; CASPASE-8 AB Background: The p53 protein is the best studied target in human cancer. For decades, p53 has been believed to act mainly as a tumor suppressor and by transcriptional regulation. Only recently, the complex and diverse function of p53 has attracted more attention. Using several molecular approaches, we studied the impact of different p53 variants on extrinsic and intrinsic apoptosis signaling. Results: We reproduced the previously published results within intrinsic apoptosis induction: while wild-type p53 promoted cell death, different p53 mutations reduced apoptosis sensitivity. The prediction of the impact of the p53 status on the extrinsic cell death induction was much more complex. The presence of p53 in tumor cell lines and primary xenograft tumor cells resulted in either augmented, unchanged or reduced cell death. The substitution of wild-type p53 by mutant p53 did not affect the extrinsic apoptosis inducing capacity. Conclusions: In summary, we have identified a non-expected impact of p53 on extrinsic cell death induction. We suggest that the impact of the p53 status of tumor cells on extrinsic apoptosis signaling should be studied in detail especially in the context of therapeutic approaches that aim to restore p53 function to facilitate cell death via the extrinsic apoptosis pathway. C1 [Wachter, Franziska; Grunert, Michaela; Blaj, Cristina; Jeremias, Irmela; Ehrhardt, Harald] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, D-81377 Munich, Germany. [Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jeremias, Irmela] Univ Munich, Dr von Haunersches Kinderspital, Dept Hematol Oncol, D-80337 Munich, Germany. [Ehrhardt, Harald] Univ Munich, Perinatal Ctr, Univ Childrens Hosp, Div Neonatol, D-81377 Munich, Germany. RP Ehrhardt, H (reprint author), German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Marchioninistr 25, D-81377 Munich, Germany. EM Harald.Ehrhardt@helmholtz-muenchen.de RI Jeremias, Irmela/C-6090-2015; OI Ehrhardt, Harald/0000-0003-4587-1734 NR 39 TC 3 Z9 3 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-811X J9 CELL COMMUN SIGNAL JI Cell Commun. Signal. PD APR 17 PY 2013 VL 11 AR 27 DI 10.1186/1478-811X-11-27 PG 10 WC Cell Biology SC Cell Biology GA 139UM UT WOS:000318610400001 PM 23594441 ER PT J AU Berry, JD Shefner, JM Conwit, R Schoenfeld, D Keroack, M Felsenstein, D Krivickas, L David, WS Vriesendorp, F Pestronk, A Caress, JB Katz, J Simpson, E Rosenfeld, J Pascuzzi, R Glass, J Rezania, K Rothstein, JD Greenblatt, DJ Cudkowicz, ME AF Berry, James D. Shefner, Jeremy M. Conwit, Robin Schoenfeld, David Keroack, Myles Felsenstein, Donna Krivickas, Lisa David, William S. Vriesendorp, Francine Pestronk, Alan Caress, James B. Katz, Jonathan Simpson, Ericka Rosenfeld, Jeffrey Pascuzzi, Robert Glass, Jonathan Rezania, Kourosh Rothstein, Jeffrey D. Greenblatt, David J. Cudkowicz, Merit E. CA Northeast ALS Consortium TI Design and Initial Results of a Multi-Phase Randomized Trial of Ceftriaxone in Amyotrophic Lateral Sclerosis SO PLOS ONE LA English DT Article ID INCREASES GLUTAMATE UPTAKE; CEREBROSPINAL-FLUID; UP-REGULATION; LYME-DISEASE; MODEL; EXPRESSION; SURVIVAL; HISTORY; STROKE; EAAT2 AB Objective: Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability for 20-weeks. Analysis of the pharmacokinetics, tolerability, and safety was used to determine the ceftriaxone dosage for Stage 3 efficacy testing. Methods: In Stage 1, 66 subjects at ten clinical sites were enrolled and randomized equally into three study groups receiving intravenous placebo, ceftriaxone 2 grams daily or ceftriaxone 4 grams daily divided BID. Participants provided serum and cerebrospinal fluid for pharmacokinetic analysis on study day 7. Participants continued their assigned treatment in Stage 2. The Data and Safety Monitoring Board (DSMB) reviewed the data after the last participants completed 20 weeks on study drug. Results: Stage 1 analysis revealed linear pharmacokinetics, and CSF trough levels for both dosage levels exceeding the pre-specified target trough level of 1 mu M (0.55 mu g/mL). Tolerability (Stages 1 and 2) results showed that ceftriaxone at dosages up to 4 grams/day was well tolerated at 20 weeks. Biliary adverse events were more common with ceftriaxone but not dose-dependent and improved with ursodeoxycholic (ursodiol) therapy. Conclusions: The goals of Stages 1 and 2 of the ceftriaxone trial were successfully achieved. Based on the pre-specified decision rules, the DSMB recommended the use of ceftriaxone 4 g/d (divided BID) for Stage 3, which recently closed. C1 [Berry, James D.; Krivickas, Lisa; David, William S.; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst, Boston, MA 02115 USA. [Shefner, Jeremy M.; Vriesendorp, Francine] SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. [Conwit, Robin] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Keroack, Myles] Marshfield Clin Fdn Med Res & Educ, Dept Gastroenterol, Eau Claire, WI USA. [Felsenstein, Donna] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit,Dept Med, Boston, MA USA. [Pestronk, Alan] Washington Univ, Dept Neurol, St Louis, MO USA. [Caress, James B.] Wake Forest Univ, Dept Neurol, Winston Salem, NC 27109 USA. [Katz, Jonathan] Calif Pacific Med Ctr, Dept Neurol, San Francisco, CA USA. [Simpson, Ericka] Methodist Neurol Inst, Dept Neurol, Houston, TX USA. [Rosenfeld, Jeffrey] Univ Calif San Francisco, Inst Neurosci, Dept Neurol, Fresno, CA USA. [Pascuzzi, Robert] Indiana Univ, Dept Neurol, Indianapolis, IN 46204 USA. [Glass, Jonathan] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Rezania, Kourosh] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Rothstein, Jeffrey D.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Greenblatt, David J.] Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. RP Berry, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Res Inst, Boston, MA 02115 USA. EM jdberry@partners.org OI Caress, James/0000-0002-5814-6083 FU National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health [U01 NS049640-05]; Institute of Clinical and Translational Sciences [UL1 TR000448]; Muscular Dystrophy Association; ALS Association; ALS Therapy Alliance; Cytokinetics; Biogen Idec; Sanofi Aventis; Neuraltus; AstraZeneca; Roche; CytRx; ISIS; Euroimmune; Allere; Focus; Biokit; BioRad; Diasorin; Chronic Fatigue Initiative; National Institutes of Health; Neuromuscular Research Fund; Insmed; Knopp; Genzyme; GSK; Ultragenyx Sanofi; National Institute of Neurological Disorders and Stroke; Department of Defense; P2ALS; Robert Packard Center for ALS Research at Johns Hopkins FX Support for this research was provided by a grant from the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (U01 NS049640-05) and from the Institute of Clinical and Translational Sciences (UL1 TR000448). The funders (NINDS) were involved in data and safety monitoring throughout the trial and approved safety analysis plans. They did not have a role in the decision to publish. RC is an employee of NINDS and was involved in the preparation of the manuscript.; JDB has served as a consultant to Biogen Idec and as a paid speaker for Oakstone Publishing. He receives research report from the Muscular Dystrophy Association and ALS Therapy Alliance. JMS has served as a consultant to Biogen Idec, Cytokinetics, Trophos, ISIS, Glaxo Smith Kline, and receives research support from the Muscular Dystrophy Association, ALS Association, ALS Therapy Alliance, Cytokinetics, Biogen Idec, Sanofi Aventis, Neuraltus. RC is employed at the National Institute of Neurological Disorders and Stroke. DS, over the last 24 months, has served as a biostatistical consultant to Averion, Inc, Gerson Lehrman Group, Guidepoint Global, Neuronova, Cytokinetics, Glaxo Smith Kline, Merck, Aggennix, Pfizer, Biogen Idec, and Elan. He has received research support from AstraZeneca, Roche, CytRx, and ISIS. MK has no relevant disclosures to report. DF has received research funds from Euroimmune, Allere, Focus, Biokit, BioRad and Diasorin, Chronic Fatigue Initiative. LK has no relevant disclosures to report. WSD has no relevant disclosures to report. FV has no relevant disclosures to report. AP receives revenue related to antibody patent licenses from Athena; owns stock in Johnson & Johnson; directs the Washington University Neuromuscular Clinical Laboratory which performs antibody testing; and receives research support from the National Institutes of Health, Muscular Dystrophy Association, Neuromuscular Research Fund, Insmed, Knopp, Cytokinetics, Biogen Idec, ISIS, Genzyme, GSK, Ultragenyx & Sanofi. JBC has no relevant disclosures to report. JK has no relevant disclosures to report. ES has no relevant disclosures to report. JR has served on scientific advisory boards and/or as a consultant for Hill-ROM Inc, Cytokinetics and Avanir Pharmaceuticals. RP has no relevant disclosures to report. JG receives research support from the Muscular Dystrophy Association and from the National Institute of Neurological Disorders and Stroke. KR has no relevant disclosures to report. JR has research funding from National Institutes of Health, Department of Defense, P2ALS, Muscular Dystrophy Association, Robert Packard Center for ALS Research at Johns Hopkins. He has acted as a consultant to Biogen Idec, Cytokinetics and Psyadon Pharmaceuticals, Inc. DJG has no relevant disclosures to report. MEC served on DSMB for Synapse and Trophos and was a consultant for TEVA, Millenium, GlaxoSmithKline and Biogen. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. NR 30 TC 39 Z9 39 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 17 PY 2013 VL 8 IS 4 AR e61177 DI 10.1371/journal.pone.0061177 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130IK UT WOS:000317907200036 PM 23613806 ER PT J AU Lane, RF Steele, JW Cai, DM Ehrlich, ME Attie, AD Gandy, S AF Lane, Rachel F. Steele, John W. Cai, Dongming Ehrlich, Michelle E. Attie, Alan D. Gandy, Sam TI Protein Sorting Motifs in the Cytoplasmic Tail of SorCS1 Control Generation of Alzheimer's Amyloid-beta Peptide SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PRECURSOR PROTEIN; RETROMER COMPLEX; DOWN-SYNDROME; DISEASE; VARIANTS; SORL1; TRAFFICKING; ASSOCIATION; RECEPTOR; NEURODEGENERATION AB Endosomal sorting of the Alzheimer amyloid precursor protein (APP) plays a key role in the biogenesis of the amyloid-beta (A beta) peptide. Genetic lesions underlying Alzheimer's disease (AD) can act by interfering with this physiological process. Specifically, proteins involved in trafficking between endosomal compartments and the trans-Golgi network (TGN) [including the retromer complex (Vps35, Vps26) and its putative receptors (sortilin, SorL1, SorCS1)] have been implicated in the molecular pathology of late-onset AD. Previously, we demonstrated a role for SorCS1 in APP metabolism and A beta production and, while we implicated a role for the retromer in this regulation, the underlying mechanism remained poorly understood. Here, we provide evidence for a motif within the SorCS1c cytoplasmic tail that, when manipulated, results in perturbed sorting of APP and/or its fragments to endosomal compartments, decreased retrograde TGN trafficking, and increased A beta production in H4 neuroglioma cells. These perturbations apparently do not involve turnover of the cell surface APP pool, but rather they involve intracellular APP and/or its fragments, downstream of APP endocytosis. C1 [Lane, Rachel F.; Steele, John W.; Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Neurol & Psychiat, New York, NY 10029 USA. [Lane, Rachel F.; Steele, John W.; Gandy, Sam] Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Lane, Rachel F.] Alzheimers Drug Discovery Fdn, New York, NY 10019 USA. [Steele, John W.] Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. [Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Pediat & Neurol, New York, NY 10029 USA. [Attie, Alan D.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Cai, Dongming; Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Lane, RF (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol & Psychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM rlane@alzdiscovery.org; Samuel.gandy@mssm.edu FU National Institutes of Health (NIH) [NS075685]; Cure Alzheimer's Fund; U.S. Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases [DK58037, DK66369]; American Diabetes Association Research Award; National Institute of General Medical Sciences [T32GM062754]; NIH-National Cancer Institute [5R24 CA095823-04]; National Science Foundation [DBI-9724504]; NIH Shared Instrumentation Grant [1 S10 RR0 9145-01] FX This research was supported by National Institutes of Health (NIH) Grant NS075685 (to S. G.), the Cure Alzheimer's Fund (to S. G.), the U.S. Department of Veterans Affairs (to S. G.), National Institute of Diabetes and Digestive and Kidney Diseases Grants DK58037 and DK66369 (to A. D. A.), and an American Diabetes Association Research Award (to M. E. E). J.W.S. was a trainee in the Integrated Pharmacological Sciences Training Program supported by Grant T32GM062754 from the National Institute of General Medical Sciences to Terry Krulwich (Icahn School of Medicine at Mount Sinai). Confocal laser scanning microscopy was performed at the Icahn School of Medicine at Mount Sinai Microscopy Shared Resource Facility, supported with funding from NIH-National Cancer Institute Shared Resources Grant 5R24 CA095823-04, National Science Foundation Major Research Instrumentation Grant DBI-9724504, and NIH Shared Instrumentation Grant 1 S10 RR0 9145-01. We thank Rudolph E. Tanzi for cDNA constructs. NR 35 TC 15 Z9 15 U1 0 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 17 PY 2013 VL 33 IS 16 BP 7099 EP 7107 DI 10.1523/JNEUROSCI.5270-12.2013 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 127TZ UT WOS:000317723000040 PM 23595767 ER PT J AU Hassol, A Biddinger, P Zane, R AF Hassol, Andrea Biddinger, Paul Zane, Richard TI Hospital Evacuation Decisions in Emergency Situations SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Hassol, Andrea] ABT Associates Inc, Cambridge, MA 02138 USA. [Biddinger, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zane, Richard] Univ Colorado, Sch Med, Dept Emergency Med, Denver, CO USA. RP Hassol, A (reprint author), ABT Associates Inc, Cambridge, MA 02138 USA. EM an-drea_hassol@abtassoc.com RI bebarta, vikhyat/K-3476-2015 NR 3 TC 2 Z9 2 U1 0 U2 9 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 APR 17 PY 2013 VL 309 IS 15 BP 1585 EP 1586 DI 10.1001/jama.2013.2470 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 126FY UT WOS:000317599500015 PM 23592100 ER PT J AU Eappen, S Lane, BH Rosenberg, B Lipsitz, SA Sadoff, D Matheson, D Berry, WR Lester, M Gawande, AA AF Eappen, Sunil Lane, Bennett H. Rosenberg, Barry Lipsitz, Stuart A. Sadoff, David Matheson, Dave Berry, William R. Lester, Mark Gawande, Atul A. TI Relationship Between Occurrence of Surgical Complications and Hospital Finances SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; LENGTH-OF-STAY; POSTOPERATIVE COMPLICATIONS; SAFETY CHECKLIST; ADVERSE EVENTS; RISK-FACTORS; SURGERY; COSTS; PERFORMANCE; MORTALITY AB Importance The effect of surgical complications on hospital finances is unclear. Objective To determine the relationship between major surgical complications and per-encounter hospital costs and revenues by payer type. Design, Setting, and Participants Retrospective analysis of administrative data for all inpatient surgical discharges during 2010 from a nonprofit 12-hospital system in the southern United States. Discharges were categorized by principal procedure and occurrence of 1 or more postsurgical complications, using International Classification of Diseases, Ninth Revision, diagnosis and procedure codes. Nine common surgical procedures and 10 major complications across 4 payer types were analyzed. Hospital costs and revenue at discharge were obtained from hospital accounting systems and classified by payer type. Main Outcomes and Measures Hospital costs, revenues, and contribution margin (defined as revenue minus variable expenses) were compared for patients with and without surgical complications according to payer type. Results Of 34 256 surgical discharges, 1820 patients (5.3%; 95% CI, 4.4%-6.4%) experienced 1 or more postsurgical complications. Compared with absence of complications, complications were associated with a $39 017 (95% CI, $20 069-$50 394; P<.001) higher contribution margin per patient with private insurance ($55 953 vs $16 936) and a $1749 (95% CI, $976-$3287; P<.001) higher contribution margin per patient with Medicare ($3629 vs $1880). For this hospital system in which private insurers covered 40% of patients (13 544), Medicare covered 45% (15 406), Medicaid covered 4% (1336), and self-payment covered 6% (2202), occurrence of complications was associated with an $8084 (95% CI, $4903-$9740; P<.001) higher contribution margin per patient ($15 726 vs $7642) and with a $7435 lower per-patient total margin (95% CI, $5103-$10 507; P<.001) ($1013 vs -$6422). Conclusions and Relevance In this hospital system, the occurrence of postsurgical complications was associated with a higher per-encounter hospital contribution margin for patients covered by Medicare and private insurance but a lower one for patients covered by Medicaid and who self-paid. Depending on payer mix, many hospitals have the potential for adverse near-term financial consequences for decreasing postsurgical complications. JAMA. 2013;309(15):1599-1606 www.jama.com C1 [Eappen, Sunil] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. [Lane, Bennett H.; Rosenberg, Barry; Sadoff, David; Matheson, Dave] Boston Consulting Grp Inc, Boston, MA USA. [Lipsitz, Stuart A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Berry, William R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lester, Mark] Texas Hlth Resources, Arlington, TX USA. [Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Gawande, Atul A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gawande, AA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave,Kresge Bldg,Room 400, Boston, MA 02115 USA. EM agawande@hsph.harvard.edu OI Gawande, Atul/0000-0002-1824-9176 FU Boston Consulting Group; Texas Health Resources FX This research was supported by funding from the Boston Consulting Group and Texas Health Resources. NR 48 TC 67 Z9 69 U1 0 U2 17 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 APR 17 PY 2013 VL 309 IS 15 BP 1599 EP 1606 DI 10.1001/jama.2013.2773 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 126FY UT WOS:000317599500023 PM 23592104 ER PT J AU Weiner, SJ Schwartz, A Sharma, G Binns-Calvey, A Ashley, N Kelly, B Dayal, A Patel, S Weaver, FM Harris, I AF Weiner, Saul J. Schwartz, Alan Sharma, Gunjan Binns-Calvey, Amy Ashley, Naomi Kelly, Brendan Dayal, Amit Patel, Sonal Weaver, Frances M. Harris, Ilene TI Patient-Centered Decision Making and Health Care Outcomes An Observational Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID INTERACTION ANALYSIS SYSTEM; CONTEXTUAL ERRORS; COMMUNICATION AB Background: Patient-centered decision making (PCDM) is the process of identifying clinically relevant, patient-specific circumstances and behaviors to formulate a contextually appropriate care plan. Objective: To ascertain whether encounters in which PCDM occurs are followed by improved health care outcomes compared with encounters where there is inattention to patient context. Design: Patients surreptitiously audio-recorded encounters with their physicians. Medical records of these encounters were then screened for "contextual red flags," such as deteriorating self-management of a chronic condition, that could reflect such underlying contextual factors as competing responsibilities or loss of social support. When a contextual factor was identified, either as a result of physician questioning or because a patient volunteered information, physicians were scored on the basis of whether they adapted the care plan to it. Setting: Internal medicine clinics at 2 Veterans Affairs facilities. Participants: 774 patients audio-recorded encounters with 139 resident physicians. Measurements: Individualized outcome measures were based on the contextual red flag, such as improved blood pressure control in a patient presenting with hypertension and loss of medication coverage. Outcome coders were blinded to physician performance. Results: Among 548 contextual red flags, 208 contextual factors were confirmed, either when physicians probed or patients volunteered information. Physician attention to contextual factors (both probing for them and addressing them in care plans) varied according to the presenting contextual red flags. Outcome data were available for 157 contextual factors, of which PCDM was found to address 96. Of these, health care outcomes improved in 68 (71%), compared with 28 (46%) of the 61 that were not addressed by PCDM (P = 0.002). Limitation: The extent to which the findings can be generalized to other clinical settings is unknown. Conclusion: Attention to patient needs and circumstances when planning care is associated with improved health care outcomes. C1 Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA. [Weiner, Saul J.] Univ Illinois, Chicago, IL 60607 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Durham Vet Affairs Med Ctr, Durham, NC USA. RP Weiner, SJ (reprint author), Univ Illinois, 2730 UH MC 103,601 South Morgan, Chicago, IL 60607 USA. EM sweiner@uic.edu OI Schwartz, Alan/0000-0003-3809-6637 FU U.S. Department of Veterans Affairs, Health Services Research & Development Service FX U.S. Department of Veterans Affairs, Health Services Research & Development Service. NR 15 TC 42 Z9 43 U1 2 U2 22 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 APR 16 PY 2013 VL 158 IS 8 BP 573 EP + DI 10.7326/0003-4819-158-8-201304160-00001 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 132IW UT WOS:000318062100013 PM 23588745 ER PT J AU Martinez, ME Ahnen, D Greenberg, ER AF Martinez, Maria Elena Ahnen, Dennis Greenberg, E. Robert TI One-Year Risk for Advanced Colorectal Neoplasia RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Martinez, Maria Elena] Moores Canc Ctr, La Jolla, CA USA. [Martinez, Maria Elena] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Ahnen, Dennis] Denver Vet Affairs Med Ctr, Denver, CO USA. [Ahnen, Dennis] Univ Colorado, Sch Med, Denver, CO USA. [Greenberg, E. Robert] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Martinez, ME (reprint author), Moores Canc Ctr, La Jolla, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 16 PY 2013 VL 158 IS 8 BP 639 EP 639 DI 10.7326/0003-4819-158-8-201304160-00019 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 132IW UT WOS:000318062100028 PM 23588762 ER PT J AU Zhu, J Ofek, G Yang, YP Zhang, BS Louder, MK Lu, G McKee, K Pancera, M Skinner, J Zhang, ZH Parks, R Eudailey, J Lloyd, KE Blinn, J Alam, SM Haynes, BF Simek, M Burton, DR Koff, WC Mullikin, JC Mascola, JR Shapiro, L Kwong, PD AF Zhu, Jiang Ofek, Gilad Yang, Yongping Zhang, Baoshan Louder, Mark K. Lu, Gabriel McKee, Krisha Pancera, Marie Skinner, Jeff Zhang, Zhenhai Parks, Robert Eudailey, Joshua Lloyd, Krissey E. Blinn, Julie Alam, S. Munir Haynes, Barton F. Simek, Melissa Burton, Dennis R. Koff, Wayne C. Mullikin, James C. Mascola, John R. Shapiro, Lawrence Kwong, Peter D. CA NISC Comparative Sequencing Progra TI Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antibody-affinity maturation; antibodyomics; B-cell ontogeny; DNA sequencing; immunological tolerance ID NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; HIV-1; BROAD; IDENTIFICATION; TECHNOLOGIES; INDIVIDUALS; CARDIOLIPIN; REPERTOIRE; SELECTION AB Next-generation sequencing of antibody transcripts from HIV-1-infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing and identity/divergence grid sampling to analyze heavy- and light-chain sequences from donor N152, the source of the broadly neutralizing antibody 10E8. We identified variants with up to 28% difference in amino acid sequence. Heavy- and light-chain phylogenetic trees of identified 10E8 variants displayed similar architectures, and 10E8 variants reconstituted from matched and unmatched phylogenetic branches displayed significantly lower autoreactivity when matched. To test the generality of phylogenetic pairing, we analyzed donor International AIDS Vaccine Initiative 84, the source of antibodies PGT141-145. Heavy- and light-chain phylogenetic trees of PGT141-145 somatic variants also displayed remarkably similar architectures; in this case, branch pairings could be anchored by known PGT141-145 antibodies. Altogether, our findings suggest that phylogenetic matching of heavy and light chains can provide a means to approximate natural pairings. C1 [Zhu, Jiang; Ofek, Gilad; Yang, Yongping; Zhang, Baoshan; Louder, Mark K.; Lu, Gabriel; McKee, Krisha; Pancera, Marie; Mascola, John R.; Shapiro, Lawrence; Kwong, Peter D.] NHGRI, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Skinner, Jeff] NHGRI, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA. [Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Zhang, Zhenhai; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E.; Blinn, Julie; Alam, S. Munir; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Simek, Melissa; Koff, Wayne C.] IAVI, New York, NY 10004 USA. [Zhu, Jiang; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Zhu, Jiang; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Cambridge, MA 02139 USA. [Burton, Dennis R.] Harvard, Cambridge, MA 02139 USA. RP Shapiro, L (reprint author), NHGRI, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM lss8@columbia.edu; pdkwong@nih.gov OI Skinner, Jeff/0000-0001-5697-0442 FU Vaccine Research Center, National Institute of Allergy and Infectious Diseases; National Human Genome Research Institute, National Institutes of Health; International AIDS Vaccine Initiative; Center for HIV/AIDS Vaccine Immunology-Immunogen Design, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health [UM1 AI100645] FX We thank H. Coleman, M. Park, B. Schmidt, and A. Young for 454 pyrosequencing at the National Institutes of Health Intramural Sequencing Center (NISC); J. Huang, L. Laub, and M. Connors for donor N152 materials and sequence of 10E8; J. Stuckey for assistance with figures; and Rahul Kohli and members of the Structural Biology Section and Structural Bioinformatics Core, Vaccine Research Center, for discussions or comments on the manuscript. Support for this work was provided by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases; the National Human Genome Research Institute, National Institutes of Health; the International AIDS Vaccine Initiative; and Center for HIV/AIDS Vaccine Immunology-Immunogen Design Grant UM1 AI100645 (to B.F.H.) from the Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 29 TC 58 Z9 58 U1 1 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 2013 VL 110 IS 16 BP 6470 EP 6475 DI 10.1073/pnas.1219320110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132BA UT WOS:000318041500054 PM 23536288 ER PT J AU Xu, J Bauer, DE Kerenyi, MA Vo, TD Hou, S Hsu, YJ Yao, HL Trowbridge, JJ Mandel, G Orkin, SH AF Xu, Jian Bauer, Daniel E. Kerenyi, Marc A. Vo, Thuy D. Hou, Serena Hsu, Yu-Jung Yao, Huilan Trowbridge, Jennifer J. Mandel, Gail Orkin, Stuart H. TI Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene regulation; globin switching; hematopoiesis ID SICKLE-CELL-DISEASE; TRANSCRIPTION FACTOR; GENE-EXPRESSION; DEMETHYLASE 1; GAMMA-GLOBIN; MICE; DIFFERENTIATION; ELEMENT; TARGET; STEM AB Reactivation of fetal hemoglobin (HbF) in adults ameliorates the severity of the common beta-globin disorders. The transcription factor BCL11A is a critical modulator of hemoglobin switching and HbF silencing, yet the molecular mechanism through which BCL11A coordinates the developmental switch is incompletely understood. Particularly, the identities of BCL11A cooperating protein complexes and their roles in HbF expression and erythroid development remain largely unknown. Here we determine the interacting partner proteins of BCL11A in erythroid cells by a proteomic screen. BCL11A is found within multiprotein complexes consisting of erythroid transcription factors, transcriptional corepressors, and chromatin-modifying enzymes. We show that the lysine-specific demethylase 1 and repressor element-1 silencing transcription factor corepressor 1 (LSD1/CoREST) histone demethylase complex interacts with BCL11A and is required for full developmental silencing of mouse embryonic beta-like globin genes and human gamma-globin genes in adult erythroid cells in vivo. In addition, LSD1 is essential for normal erythroid development. Furthermore, the DNA methyltransferase 1 (DNMT1) is identified as a BCL11A-associated protein in the proteomic screen. DNMT1 is required to maintain HbF silencing in primary human adult erythroid cells. DNMT1 haploinsufficiency combined with BCL11A deficiency further enhances gamma-globin expression in adult animals. Our findings provide important insights into the mechanistic roles of BCL11A in HbF silencing and clues for therapeutic targeting of BCL11A in beta-hemoglobinopathies. C1 [Xu, Jian; Bauer, Daniel E.; Kerenyi, Marc A.; Vo, Thuy D.; Hou, Serena; Hsu, Yu-Jung; Trowbridge, Jennifer J.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Xu, Jian; Bauer, Daniel E.; Kerenyi, Marc A.; Vo, Thuy D.; Hou, Serena; Hsu, Yu-Jung; Trowbridge, Jennifer J.; Orkin, Stuart H.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. [Yao, Huilan; Mandel, Gail] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Vollum Inst, Portland, OR 97239 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIDDK [K01DK093543] FX We thank K. Peterson for providing beta-YAC mice. We thank D.R. Higgs, D.A. Williams, L.I. Zon, A.B. Cantor, V.G. Sankaran, H. Huang, and A. Woo for helpful advice and discussions. This work was supported by funding from the National Institutes of Health (to S.H.O. and G.M.), including a Center of Excellence in Molecular Hematology Award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (to S.H.O.). S.H.O. and G.M. are Investigators of the Howard Hughes Medical Institute (HHMI). J.X. is an HHMI-Helen Hay Whitney Foundation fellow and is supported by NIDDK Career Development Award K01DK093543. NR 29 TC 51 Z9 51 U1 2 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 2013 VL 110 IS 16 BP 6518 EP 6523 DI 10.1073/pnas.1303976110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132BA UT WOS:000318041500062 PM 23576758 ER PT J AU Zhang, GD Panigrahy, D Mahakian, LM Yang, J Liu, JY Lee, KSS Wettersten, HI Ulu, A Hu, XW Tam, S Hwang, SH Ingham, ES Kieran, MW Weiss, RH Ferrara, KW Hammock, BD AF Zhang, Guodong Panigrahy, Dipak Mahakian, Lisa M. Yang, Jun Liu, Jun-Yan Lee, Kin Sing Stephen Wettersten, Hiromi I. Ulu, Arzu Hu, Xiaowen Tam, Sarah Hwang, Sung Hee Ingham, Elizabeth S. Kieran, Mark W. Weiss, Robert H. Ferrara, Katherine W. Hammock, Bruce D. TI Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; BREAST-CANCER; MACULAR DEGENERATION; IN-VIVO; FISH CONSUMPTION; CYTOCHROME-P450; CARCINOMA; HYDROLASE; VEGF; RISK AB Epidemiological and preclinical evidence supports that omega-3 dietary fatty acids (fish oil) reduce the risks of macular degeneration and cancers, but the mechanisms by which these omega-3 lipids inhibit angiogenesis and tumorigenesis are poorly understood. Here we show that epoxydocosapentaenoic acids (EDPs), which are lipid mediators produced by cytochrome P450 epoxygenases from omega-3 fatty acid docosahexaenoic acid, inhibit VEGF- and fibroblast growth factor 2-induced angiogenesis in vivo, and suppress endothelial cell migration and protease production in vitro via a VEGF receptor 2-dependent mechanism. When EDPs (0.05 mg.kg(-1).d(-1)) are coadministered with a low-dose soluble epoxide hydrolase inhibitor, EDPs are stabilized in circulation, causing similar to 70% inhibition of primary tumor growth and metastasis. Contrary to the effects of EDPs, the corresponding metabolites derived from omega-6 arachidonic acid, epoxyeicosatrienoic acids, increase angiogenesis and tumor progression. These results designate epoxyeicosatrienoic acids and EDPs as unique endogenous mediators of an angiogenic switch to regulate tumorigenesis and implicate a unique mechanistic linkage between omega-3 and omega-6 fatty acids and cancers. C1 [Zhang, Guodong; Yang, Jun; Liu, Jun-Yan; Lee, Kin Sing Stephen; Ulu, Arzu; Hwang, Sung Hee; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Zhang, Guodong; Yang, Jun; Liu, Jun-Yan; Lee, Kin Sing Stephen; Ulu, Arzu; Hwang, Sung Hee; Weiss, Robert H.; Hammock, Bruce D.] Univ Calif Davis, Ctr Comprehens Canc, Davis, CA 95616 USA. [Panigrahy, Dipak; Kieran, Mark W.] Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Panigrahy, Dipak] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Mahakian, Lisa M.; Hu, Xiaowen; Tam, Sarah; Ingham, Elizabeth S.; Ferrara, Katherine W.] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Wettersten, Hiromi I.; Weiss, Robert H.] Univ Calif Davis, Dept Internal Med, Div Nephrol, Davis, CA 95616 USA. [Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Weiss, Robert H.] US Dept Vet Affairs, Med Ctr, Sacramento, CA 95655 USA. RP Hammock, BD (reprint author), Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. EM bdhammock@ucdavis.edu RI Hu, Xiaowen/I-5997-2013; Liu, Jun-Yan/D-8890-2014; Yang, Jun/B-2262-2010; Lee, Kin Sing Stephen/I-9476-2012; OI Hu, Xiaowen/0000-0002-4295-0747; Yang, Jun/0000-0002-4630-3838; Lee, Kin Sing Stephen/0000-0003-4541-3063; Kieran, Mark/0000-0003-2184-7692; Zhang, Guodong/0000-0001-7780-5470; Ferrara, Katherine/0000-0002-4976-9107 FU National Institute on Environmental Health Sciences [P42 ES04699, R01 CA134659, R01 CA103828]; University of California Davis; Stop and Shop Pediatric Brain Tumor Fund; C.J. Buckley Pediatric Brain Tumor Fund; Medical Service of the US Department of Veterans' Affairs; [R01 ES02710]; [R01 CA148633]; [R01 CA135401]; [R01 DK082690] FX We thank R. Isseroff and H. Yang for microscopy, Y. Wang for ELISA, B. Inceoglu and K. Nithipatikom for discussions, and A. Kheirolomoom and J. Yang for technical assistance. We acknowledge support from R01 ES02710 and National Institute on Environmental Health Sciences Superfund P42 ES04699 (to B.D.H.); R01 CA134659, R01 CA103828, and Research Investments in the Sciences and Engineering (RISE) Program of University of California Davis (K.W.F.); R01 CA148633 (to D.P.); Stop and Shop Pediatric Brain Tumor Fund and the C.J. Buckley Pediatric Brain Tumor Fund (M.W.K.); and R01 CA135401, R01 DK082690, and the Medical Service of the US Department of Veterans' Affairs (R.H.W.). B.D.H. is a George and Judy Marcus Senior Fellow of the American Asthma Society. NR 51 TC 87 Z9 89 U1 2 U2 53 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 2013 VL 110 IS 16 BP 6530 EP 6535 DI 10.1073/pnas.1304321110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132BA UT WOS:000318041500064 PM 23553837 ER PT J AU Rardin, MJ Newman, JC Held, JM Cusack, MP Sorensen, DJ Li, BA Schilling, B Mooney, SD Kahn, CR Verdin, E Gibson, BW AF Rardin, Matthew J. Newman, John C. Held, Jason M. Cusack, Michael P. Sorensen, Dylan J. Li, Biao Schilling, Birgit Mooney, Sean D. Kahn, C. Ronald Verdin, Eric Gibson, Bradford W. TI Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALPHA-KETOGLUTARATE-DEHYDROGENASE; FATTY-ACID OXIDATION; CALORIE RESTRICTION; PROTEIN ACETYLATION; STRESS; DEACETYLATION; NEURODEGENERATION; QUANTIFICATION; OPPOSES; CYCLE AB Large-scale proteomic approaches have identified numerous mitochondrial acetylated proteins; however in most cases, their regulation by acetyltransferases and deacetylases remains unclear. Sirtuin 3 (SIRT3) is an NAD(+)-dependent mitochondrial protein deacetylase that has been shown to regulate a limited number of enzymes in key metabolic pathways. Here, we use a rigorous label-free quantitative MS approach (called MS1 Filtering) to analyze changes in lysine acetylation from mouse liver mitochondria in the absence of SIRT3. Among 483 proteins, a total of 2,187 unique sites of lysine acetylation were identified after affinity enrichment. MS1 Filtering revealed that lysine acetylation of 283 sites in 136 proteins was significantly increased in the absence of SIRT3 (at least twofold). A subset of these sites was independently validated using selected reaction monitoring MS. These data show that SIRT3 regulates acetylation on multiple proteins, often at multiple sites, across several metabolic pathways including fatty acid oxidation, ketogenesis, amino acid catabolism, and the urea and tricarboxylic acid cycles, as well as mitochondrial regulatory proteins. The widespread modification of key metabolic pathways greatly expands the number of known substrates and sites that are targeted by SIRT3 and establishes SIRT3 as a global regulator of mitochondrial protein acetylation with the capability of coordinating cellular responses to nutrient status and energy homeostasis. C1 [Rardin, Matthew J.; Held, Jason M.; Cusack, Michael P.; Sorensen, Dylan J.; Li, Biao; Schilling, Birgit; Mooney, Sean D.; Gibson, Bradford W.] Buck Inst Res Aging, Novato, CA 94945 USA. [Newman, John C.; Verdin, Eric] Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA. [Newman, John C.; Verdin, Eric] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu; bgibson@buckinstitute.org RI Newman, John/L-8112-2013; OI Verdin, Eric/0000-0003-3703-3183; Held, Jason/0000-0001-8024-2736 FU National Institutes of Health [T32AG000266, PL1 AG032118, R24 DK085610]; Shared Instrumentation Grant [S10 RR024615] FX This work was supported by National Institutes of Health Grants T32AG000266 (to M.J.R.), PL1 AG032118 (to B. W. G.), and R24 DK085610 (to E. V.). This work was also supported in part by the Shared Instrumentation Grant S10 RR024615 (to B. W. G.) and the generous access of a TripleTOF 5600 by AB SCIEX at the Buck Institute. NR 37 TC 130 Z9 422 U1 6 U2 81 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 2013 VL 110 IS 16 BP 6601 EP 6606 DI 10.1073/pnas.1302961110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 132BA UT WOS:000318041500076 PM 23576753 ER PT J AU Gaweska, HM Taylor, AB Hart, PJ Fitzpatrick, PF AF Gaweska, Helena M. Taylor, Alexander B. Hart, P. John Fitzpatrick, Paul F. TI Structure of the Flavoprotein Tryptophan 2-Monooxygenase, a Key Enzyme in the Formation of Galls in Plants SO BIOCHEMISTRY LA English DT Article ID MONOAMINE-OXIDASE-B; MAIZE POLYAMINE OXIDASE; L-PHENYLALANINE OXIDASE; CONSERVED ACTIVE-SITE; PSEUDOMONAS SP P-501; AMINO-ACID OXIDASE; CROWN-GALL; CRYSTAL-STRUCTURE; CATALYTIC MECHANISM; INDOLEACETIC-ACID AB The flavoprotein tryptophan 2-monooxygenase catalyzes the oxidative decarboxylation of tryptophan to yield indole-3-acetamide. This is the initial step in the biosynthesis of the plant growth hormone indole-acetic acid by bacterial pathogens that cause crown gall and related diseases. The structure of the enzyme from Pseudomonas savastanoi has been determined by X-ray diffraction methods to a resolution of 1.95 A. The overall structure of the protein shows that it has the same fold as members of the monoamine oxidase family of flavoproteins, with the greatest similarities to the L-amino acid oxidases. The location of bound indole-3-acetamide in the active site allows identification of residues responsible for substrate binding and specificity. Two residues in the enzyme are conserved in all members of the monoamine oxidase family, Lys365 and Trp466. The K365M mutation decreases the k(cat) and k(cat)/K-Trp values by 60000- and 2 million-fold, respectively. The deuterium kinetic isotope effect increases to 3.2, consistent with carbon-hydrogen bond cleavage becoming rate-limiting in the mutant enzyme. The W466F mutation decreases the k(cat) value <2-fold and the k(cat)/K-Trp, value only 5-fold, while the W466M mutation results in an enzyme lacking Flavin and detectable activity. This is consistent with a role for Trp466 in maintaining the structure of the flavin-binding site in the more conserved FAD domain. C1 [Gaweska, Helena M.; Taylor, Alexander B.; Hart, P. John; Fitzpatrick, Paul F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, Audie Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Fitzpatrick, PF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. EM fitzpatrick@biochem.uthscsa.edu FU National Institutes of Health [R01 GM058698, F32 GM097762]; Welch Foundation [AQ-1399] FX This work was supported in part by National Institutes of Health Grants R01 GM058698 to P.F.F. and F32 GM097762 to H.M.G. and by The Welch Foundation Grant AQ-1399 to P.J.H. NR 50 TC 6 Z9 7 U1 3 U2 33 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 16 PY 2013 VL 52 IS 15 BP 2620 EP 2626 DI 10.1021/bi4001563 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 128UG UT WOS:000317794600013 PM 23521653 ER PT J AU Dai, N Wang, WY Patterson, SE Bleecker, AB AF Dai, Ning Wang, Wuyi Patterson, Sara E. Bleecker, Anthony B. TI The TMK Subfamily of Receptor-Like Kinases in Arabidopsis Display an Essential Role in Growth and a Reduced Sensitivity to Auxin SO PLOS ONE LA English DT Article ID ETR1 ETHYLENE RECEPTOR; PROTEIN-KINASE; CELL ELONGATION; SIGNAL-TRANSDUCTION; GENE ENCODES; SIZE CONTROL; ERECTA GENE; THALIANA; PLANT; EXPRESSION AB Mechanisms that govern the size of plant organs are not well understood but believed to involve both sensing and signaling at the cellular level. We have isolated loss-of-function mutations in the four genes comprising the transmembrane kinase TMK subfamily of receptor-like kinases (RLKs) in Arabidopsis. These TMKs have an extracellular leucine-rich-repeat motif, a single transmembrane region, and a cytoplasmic kinase domain. While single mutants do not display discernable phenotypes, unique double and triple mutant combinations result in a severe reduction in organ size and a substantial retardation in growth. The quadruple mutant displays even greater severity of all phenotypes and is infertile. The kinematic studies of root, hypocotyl, and stamen filament growth reveal that the TMKs specifically control cell expansion. In leaves, TMKs control both cell expansion and cell proliferation. In addition, in the tmk double mutants, roots and hypocotyls show reduced sensitivity to applied auxin, lateral root induction and activation of the auxin response reporter DR5: GUS. Thus, taken together with the structural and biochemical evidence, TMKs appear to orchestrate plant growth by regulation of both cell expansion and cell proliferation, and as a component of auxin signaling. C1 [Dai, Ning; Wang, Wuyi; Bleecker, Anthony B.] Univ Wisconsin, Dept Bot, Madison, WI USA. [Dai, Ning; Wang, Wuyi; Bleecker, Anthony B.] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. [Patterson, Sara E.] Univ Wisconsin, Dept Hort, Madison, WI 53706 USA. RP Dai, N (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ning@molbio.mgh.harvard.edu; spatters@wisc.edu FU Department of Energy [DE-FG02-91ER20029] FX This project was funded by a Department of Energy grant (DE-FG02-91ER20029) to ABB and SEP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 16 Z9 23 U1 0 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 16 PY 2013 VL 8 IS 4 AR e60990 DI 10.1371/journal.pone.0060990 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130DR UT WOS:000317893400032 PM 23613767 ER PT J AU Channick, RN AF Channick, Richard N. TI Combination Therapy in Pulmonary Arterial Hypertension SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONTINUOUS INTRAVENOUS EPOPROSTENOL; SMOOTH-MUSCLE-CELLS; INHALED ILOPROST; BOSENTAN THERAPY; ORAL SILDENAFIL; EFFICACY; TREPROSTINIL; SURVIVAL; TRIAL; PROSTACYCLIN AB Many potential therapeutic options are now available for patients with pulmonary arterial hypertension. Interest has emerged in using therapies in various combinations. Retrospective experience has suggested that this approach is common and can be efficacious. Data are emerging supporting the benefit of combination therapy; however, limitations and questions remain about this strategy. This report reviewed the rationale for combination therapy and summarized the results from clinical trials. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111[suppl]:16C-20C) C1 [Channick, Richard N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Pulm Hypertens & Thromboendarterect Program, Boston, MA USA. RP Channick, RN (reprint author), Massachusetts Gen Hosp, Pulm Hypertens & Thromboendarterect Program, 55 Fruit St,Cox 2, Boston, MA 02114 USA. EM RChannick@Partners.org FU Gilead Sciences, Inc. FX Publication of this supplement was supported by an educational grant from Gilead Sciences, Inc. NR 38 TC 3 Z9 3 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 16 PY 2013 VL 111 IS 8 SU S BP 16C EP 20C DI 10.1016/j.amjcard.2013.01.320 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 130CP UT WOS:000317890600004 PM 23558025 ER PT J AU Michaelson, MD Zhu, AX Ryan, DP McDermott, DF Shapiro, GI Tye, L Chen, I Stephenson, P Patyna, S Ruiz-Garcia, A Schwarzberg, AB AF Michaelson, M. D. Zhu, A. X. Ryan, D. P. McDermott, D. F. Shapiro, G. I. Tye, L. Chen, I. Stephenson, P. Patyna, S. Ruiz-Garcia, A. Schwarzberg, A. B. TI Sunitinib in combination with gemcitabine for advanced solid tumours: a phase I dose-finding study SO BRITISH JOURNAL OF CANCER LA English DT Article DE sunitinib; gemcitabine; combination; pharmacokinetics; solid tumours ID RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; METASTATIC BREAST-CANCER; LUNG-CANCER; INTERFERON-ALPHA; III TRIAL; SARCOMATOID DIFFERENTIATION; NEUROENDOCRINE TUMORS; PRECLINICAL MODELS AB Background: This phase I, dose-finding study determined the maximum tolerated dose (MTD), safety, and pharmacokinetics of sunitinib plus gemcitabine in patients with advanced solid tumours. Methods: Two schedules with sunitinib (25-50mg per day) and IV gemcitabine (750-1250 mg m(-2)) in escalating doses were studied. First, patients received sunitinib on a 4-weeks-on-2-weeks-off schedule (Schedule 4/2) plus gemcitabine on days 1, 8, 22, and 29. Second, patients received sunitinib on a 2-weeks-on-1-week-off schedule (Schedule 2/1) plus gemcitabine on days 1 and 8. The primary endpoint was determination of MTD and tolerability. Results: Forty-four patients received the combination (Schedule 4/2, n = 8; Schedule 2/1, n = 36). With no dose-limiting toxicities (DLTs) at maximum dose levels on Schedule 2/1, MTD was not reached. Grade 4 treatment-related AEs and laboratory abnormalities included cerebrovascular accident, hypertension, and pulmonary embolism (n 1 each), and neutropenia (n = 3), thrombocytopenia and increased uric acid (both n 2), and lymphopenia (n = 1). There were no clinically significant drug-drug interactions. Antitumor activity occurred across dose levels and tumour types. In poor-risk and/or high-grade renal cell carcinoma patients (n = 12), 5 had partial responses and 7 stable disease >= 6 weeks. Conclusion: Sunitinib plus gemcitabine on Schedule 2/1 with growth factor support was well tolerated and safely administered at maximum doses of each drug, without significant drug-drug interactions. C1 [Michaelson, M. D.; Zhu, A. X.; Ryan, D. P.; Schwarzberg, A. B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Tye, L.; Chen, I.; Patyna, S.; Ruiz-Garcia, A.] Pfizer Oncol, La Jolla, CA 92121 USA. [Stephenson, P.] Rho Inc, Chapel Hill, NC 27517 USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7, Boston, MA 02114 USA. EM dmichaelson1@partners.org RI Ruiz-Garcia, Ana/O-8252-2014 OI Ruiz-Garcia, Ana/0000-0002-5462-3110 FU Pfizer, Inc.; Pfizer FX This study was sponsored by Pfizer, Inc. We thank all of the participating patients and their families, as well as the investigators, research nurses, study coordinators, and operations staff. Medical writing support was provided by Andy Gannon and Lisa Cheyne at ACUMED (Tytherington, UK) and was funded by Pfizer Inc.; AXZ and McD have reported receiving consultant or advisory fees from Pfizer. LT, SP, and AR-G are full-time employees of Pfizer and hold Pfizer stock. The remaining authors declare no conflict of interest. NR 47 TC 13 Z9 13 U1 0 U2 4 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 APR 16 PY 2013 VL 108 IS 7 BP 1393 EP 1401 DI 10.1038/bjc.2013.96 PG 9 WC Oncology SC Oncology GA 127WU UT WOS:000317730400001 PM 23511559 ER PT J AU Ahearn, TU Pettersson, A Stack, EC Ma, J Gerke, T Meisner, A Pollak, MN Finn, S Stampfer, MJ Loda, M Giovannucci, EL Mucci, LA AF Ahearn, Thomas U. Pettersson, Andreas Stack, Edward C. Ma, Jing Gerke, Travis Meisner, Allison Pollak, Michael N. Finn, Stephen Stampfer, Meir J. Loda, Massimo Giovannucci, Edward L. Mucci, Lorelei A. TI The IGF/insulin signaling axis TMPRSS2:ERG and prostate cancer survival. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Ahearn, Thomas U.; Pettersson, Andreas; Gerke, Travis; Meisner, Allison; Stampfer, Meir J.; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Stack, Edward C.; Ma, Jing; Finn, Stephen; Loda, Massimo] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pollak, Michael N.] McGill Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB-28 DI 10.1158/1538-7445.AM2013-LB-28 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601043 ER PT J AU Alimzhanov, M Solban, N Lee, M Philbrook, P Wang, XE Wei, L Song, JX Signoretti, S Pearsall, RS Sherman, ML Kumar, R Bhatt, RS AF Alimzhanov, Marat Solban, Nicolas Lee, Michael Philbrook, Phaethon Wang, Xiaoen Wei, Lin Song, Jiaxi Signoretti, Sabina Pearsall, R. Scott Sherman, Matthew L. Kumar, Ravindra Bhatt, Rupal S. TI Inhibiting the ALK1/BMP9 signaling pathway with dalantercept as an antiangiogenic therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Alimzhanov, Marat; Solban, Nicolas; Lee, Michael; Philbrook, Phaethon; Pearsall, R. Scott; Sherman, Matthew L.; Kumar, Ravindra] Acceleron Pharma, Cambridge, MA USA. [Wang, Xiaoen; Wei, Lin; Song, Jiaxi; Signoretti, Sabina; Bhatt, Rupal S.] Beth Israel Deaconess Med Ctr, Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 5080 DI 10.1158/1538-7445.AM2013-5080 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220605176 ER PT J AU Atreya, CE Song, EK Messersmith, W Purkey, A Bagby, S Quackenbush, K Kelley, RK Kwak, E Ryan, D Venook, A Arcaroli, JJ AF Atreya, Chloe E. Song, Eun-Kee Messersmith, Wells Purkey, Alicia Bagby, Stacey Quackenbush, Kevin Kelley, Robin K. Kwak, Eunice Ryan, David Venook, Alan Arcaroli, John J. TI Potent antitumor activity of XL184 (cabozantinib), a c-MET and VEGFR2 inhibitor, in colorectal cancer patient-derived tumor explant models. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Atreya, Chloe E.; Kelley, Robin K.; Venook, Alan] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Song, Eun-Kee; Messersmith, Wells; Purkey, Alicia; Bagby, Stacey; Quackenbush, Kevin; Arcaroli, John J.] Univ Colorado Denver, Aurora, CO USA. [Kwak, Eunice; Ryan, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kwak, Eunice; Ryan, David] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB302 DI 10.1158/1538-7445.AM2013-LB-302 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601227 ER PT J AU Baca, SC Prandi, D Lawrence, MS Mosquera, JM Romanei, A Drier, Y Park, K Kitabayashi, N MacDonald, TY Van Allen, E Kryukov, GV Theurillat, JP Soong, TD Nickerson, E Auclair, D Tewari, A Beltran, H Onofrio, RC Boysen, G Guiducci, C Barbieri, CE Cibulskis, K Sivachenko, A Carter, SL Voet, D Saksena, G Cipicchio, MR Ardlie, K Kantoff, PW Berger, MF Gabriel, SB Golub, TR Meyerson, M Lander, ES Elemento, O Getz, G Demichelis, F Rubin, MA Garraway, LA AF Baca, Sylvan C. Prandi, Davide Lawrence, Michael S. Mosquera, Juan Miguel Romanei, Alessandro Drier, Yotam Park, Kyung Kitabayashi, Naoki MacDonald, Theresa Y. Van Allen, Eliezer Kryukov, Gregory V. Theurillat, Jean-Philippe Soong, T. David Nickerson, Elizabeth Auclair, Daniel Tewari, Ashutosh Beltran, Himisha Onofrio, Robert C. Boysen, Gunther Guiducci, Candace Barbieri, Christopher E. Cibulskis, Kristian Sivachenko, Andrey Carter, Scott L. Voet, Douglas Saksena, Gordon Cipicchio, Michelle R. Ardlie, Kristin Kantoff, Philip W. Berger, Michael F. Gabriel, Stacey B. Golub, Todd R. Meyerson, Matthew Lander, Eric S. Elemento, Olivier Getz, Gad Demichelis, Francesca Rubin, Mark A. Garraway, Levi A. TI Punctuated evolution of prostate cancer genomes SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Baca, Sylvan C.; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prandi, Davide; Romanei, Alessandro; Demichelis, Francesca] Ctr Integrat Biol, Trento, Italy. [Lawrence, Michael S.; Van Allen, Eliezer; Kryukov, Gregory V.; Theurillat, Jean-Philippe; Nickerson, Elizabeth; Auclair, Daniel; Onofrio, Robert C.; Guiducci, Candace; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L.; Voet, Douglas; Saksena, Gordon; Cipicchio, Michelle R.; Ardlie, Kristin; Gabriel, Stacey B.; Golub, Todd R.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Garraway, Levi A.] Broad Inst, Cambridge, MA USA. [Mosquera, Juan Miguel; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y.; Soong, T. David; Tewari, Ashutosh; Beltran, Himisha; Boysen, Gunther; Barbieri, Christopher E.; Elemento, Olivier; Rubin, Mark A.] Weill Cornell Med Coll, New York, NY USA. [Drier, Yotam] Weizmann Inst Sci, IL-76100 Rehovot, Israel. [Berger, Michael F.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4601 DI 10.1158/1538-7445.AM2013-4601 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604187 ER PT J AU Baselga, J Piccart, M Rugo, H Chen, D Burris, HA Campone, M Noguchi, S Perez, A Deleu, I Shtivelband, M Provencher, L Derti, A Huang, A McDonald, R Kalfoglou, C Robinson, D Taran, T Sahmoud, T Lebwohl, D Hortobagyi, GN AF Baselga, Jose Piccart, Martine Rugo, Hope Chen, David Burris, Howard A. Campone, Mario Noguchi, Shinzaburo Perez, Alejandra Deleu, Inas Shtivelband, Mikhail Provencher, Louise Derti, Adnan Huang, Alan McDonald, Rob Kalfoglou, Creton Robinson, Douglas Taran, Tetiana Sahmoud, Tarek Lebwohl, David Hortobagyi, Gabriel N. TI Assessment of genetic alterations using next-generation sequencing in postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the BOLERO-2 phase III trial SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Baselga, Jose] Harvard Univ, Sch Med, Boston, MA USA. [Piccart, Martine] Univ Libre Brussels, Inst Jules Bordet, Brussels, Belgium. [Rugo, Hope] Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. [Chen, David; Kalfoglou, Creton; Taran, Tetiana] Novartis Pharmaceut, Florham Pk, NJ USA. [Burris, Howard A.] Sarah Cannori Res Inst, Nashville, TN USA. [Campone, Mario] Ctr Rech Cancerol, Inst Cancerol Ouest Rene Gauducheau, Nantes, St Herblain, France. [Noguchi, Shinzaburo] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. [Perez, Alejandra] Mem Canc Inst, Hollywood, FL USA. [Deleu, Inas] AZ Maria Middelares, Ghent, Belgium. [Shtivelband, Mikhail] Ironwood Canc & Res Ctr, Chandler, AZ USA. [Provencher, Louise] CHU Quebec, Hop St Sacrement, Quebec City, PQ, Canada. [Derti, Adnan; Huang, Alan; McDonald, Rob; Robinson, Douglas] Novartis Inst BioMed Res Inc, Cambridge, MA USA. [Sahmoud, Tarek; Lebwohl, David] Novartis Pharmaceut, E Hanover, NJ USA. [Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4564 DI 10.1158/1538-7445.AM2013-4564 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604164 ER PT J AU Baselga, J Verma, S Ro, J Huober, J Guardino, E Fang, L Olsen, S Phillips, GL de Haas, S Pegram, M AF Baselga, Jose Verma, Sunil Ro, Jungsil Huober, Jens Guardino, Ellie Fang, Liang Olsen, Steven Phillips, Gail Lewis de Haas, Sanne Pegram, Mark TI Relationship between tumor biomarkers (BM) and efficacy in EMILIA, a phase III study of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC). SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Baselga, Jose] Massachusetts Gen Hosp, Canc Ctr Adm, Boston, MA 02114 USA. [Verma, Sunil] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Ro, Jungsil] Natl Canc Ctr, Ctr Breast Canc, Goyang Si, Gyeonggi Do, South Korea. [Huober, Jens] Univ Dusseldorf, Dusseldorf, Germany. [Guardino, Ellie; Fang, Liang; Olsen, Steven; Phillips, Gail Lewis] Genentech Inc, San Francisco, CA 94080 USA. [Guardino, Ellie] Stanford Univ, San Francisco, CA USA. [de Haas, Sanne] F Hoffmann La Roche, Basel, Switzerland. [Pegram, Mark] Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 4 Z9 4 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB63 DI 10.1158/1538-7445.AM2013-LB-63 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601311 ER PT J AU Beaver, JA Valda, P Jelovac, D Higgins, MJ Park, BH AF Beaver, Julia A. Valda, Patricia Jelovac, Danijela Higgins, Michaela J. Park, Ben H. TI Plasma tumor DNA: Changing the paradigm for administering systemic therapies. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Beaver, Julia A.; Valda, Patricia; Jelovac, Danijela; Park, Ben H.] Johns Hopkins Univ, Baltimore, MD USA. [Higgins, Michaela J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA SY1101 DI 10.1158/1538-7445.AM2013-SY11-01 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601369 ER PT J AU Bhatnagar, N Luther, W Sharma, B Liu, QS Gray, N George, RE AF Bhatnagar, Namrata Luther, William Sharma, Bandana Liu, Qingsong Gray, Nathanael George, Rani E. TI The AXL tyrosine kinase receptor contributes to ALK-inhibitor resistance in neuroblastoma. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Bhatnagar, Namrata; Luther, William; Sharma, Bandana; Liu, Qingsong; Gray, Nathanael; George, Rani E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4454 DI 10.1158/1538-7445.AM2013-4454 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604059 ER PT J AU Birkbak, NJ Kochupurakkal, B Izarzugaza, JMG Li, Y Liu, J Szallasi, Z Matulonis, U Richardson, AL Iglehart, JD Wang, ZGC AF Birkbak, Nicolai Juul Kochupurakkal, Bose Izarzugaza, Jose M. G. Li, Yang Liu, Joyce Szallasi, Zoltan Matulonis, Ursula Richardson, Andrea L. Iglehart, J. Dirk Wang, Zhigang C. TI Exome mutation burden predicts clinical outcome in ovarian cancer carrying mutated BRCA1 and BRCA2 genes SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Birkbak, Nicolai Juul; Izarzugaza, Jose M. G.] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Kochupurakkal, Bose; Li, Yang; Liu, Joyce; Matulonis, Ursula; Iglehart, J. Dirk; Wang, Zhigang C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Szallasi, Zoltan] Harvard Univ, Sch Med, Childrens Hosp Informat Program Harvard MIT Div H, Boston, MA USA. [Richardson, Andrea L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Izarzugaza, Jose /N-4503-2014 OI Izarzugaza, Jose /0000-0003-1754-5122 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB255 DI 10.1158/1538-7445.AM2013-LB-255 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601184 ER PT J AU Blackburn, JS Liu, S Dobrinski, K Ranalli, J Martinez, S Lee, C Langenau, D AF Blackburn, Jessica S. Liu, Sali Dobrinski, Kimberly Ranalli, Jayme Martinez, Sarah Lee, Charles Langenau, David TI Single cell evolution of AKT pathway activation drives T-cell acute lymphoblastic leukemia relapse SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Blackburn, Jessica S.; Liu, Sali; Ranalli, Jayme; Martinez, Sarah; Langenau, David] Massachusetts Gen Hosp, Charlestown, MA USA. [Dobrinski, Kimberly; Lee, Charles] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3805 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603039 ER PT J AU Boeke, CE Eliassen, AH Chen, WY Cho, E Holmes, MD Rosner, B Willett, WC Tamimi, RM AF Boeke, Caroline E. Eliassen, A. Heather Chen, Wendy Y. Cho, Eunyoung Holmes, Michelle D. Rosner, Bernard Willett, Walter C. Tamimi, Rulla M. TI Dietary fat and cholesterol intake in relation to fatal breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Boeke, Caroline E.; Eliassen, A. Heather; Holmes, Michelle D.; Rosner, Bernard; Willett, Walter C.; Tamimi, Rulla M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Boeke, Caroline E.; Eliassen, A. Heather; Chen, Wendy Y.; Cho, Eunyoung; Holmes, Michelle D.; Rosner, Bernard; Willett, Walter C.; Tamimi, Rulla M.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Eliassen, A. Heather; Holmes, Michelle D.; Rosner, Bernard; Willett, Walter C.; Tamimi, Rulla M.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 144 DI 10.1158/1538-7445.AM2013-144 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600060 ER PT J AU Boucher, Y Martin, JD Tolaney, SM Seano, G Goel, S Ancukiewicz, M Isakoff, SJ Winer, EP Krop, IE Jain, RK AF Boucher, Yves Martin, John D. Tolaney, Sara M. Seano, Giogio Goel, Shom Ancukiewicz, Marek Isakoff, Steven J. Winer, Eric P. Krop, Ian E. Jain, Rakesh K. TI Tissue biomarkers and interstitial fluid pressure in a phase II study of preoperative (preop) bevacizumab (bev) followed by dose-dense doxorubicin (A)/cyclophosphamide (C)/paclitaxel (T) in combination with bey in HER2-negative operable breast cancer (BC) SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Boucher, Yves; Isakoff, Steven J.; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Martin, John D.] Massachusetts Gen Hosp, MIT, Boston, MA 02114 USA. [Tolaney, Sara M.; Winer, Eric P.; Krop, Ian E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Seano, Giogio] Harvard Univ, Sch Med, Boston, MA USA. [Goel, Shom] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ancukiewicz, Marek] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB76 DI 10.1158/1538-7445.AM2013-LB-76 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601323 ER PT J AU Carter, SL Landau, DA Stojanov, P McKenna, A Cibulskis, K Lawrence, MS Lohr, J Stevenson, K Neuberg, D Meyerson, M Wu, CJ Getz, G AF Carter, Scott L. Landau, Dan-Avi Stojanov, Petar McKenna, Aaron Cibulskis, Kristian Lawrence, Michael S. Lohr, Jens Stevenson, Kristen Neuberg, Donna Meyerson, Matthew Wu, Catherine J. Getz, Gad TI Analysis of clonal evolution in cancer using whole exome sequence data reveals that subclonal driver mutations predict poor prognosis in chronic lymphocytic leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Carter, Scott L.; Stojanov, Petar; McKenna, Aaron; Cibulskis, Kristian; Lawrence, Michael S.; Getz, Gad] Broad Inst, Cambridge, MA USA. [Landau, Dan-Avi; Lohr, Jens; Stevenson, Kristen; Neuberg, Donna; Meyerson, Matthew; Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4600 DI 10.1158/1538-7445.AM2013-4600 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604186 ER PT J AU Casper, JA Bielenberg, DR Cheng, J Schmidt, B Hammock, BD Zeldin, DC Kieran, MW Panigrahy, D AF Casper, Jessica A. Bielenberg, Diane R. Cheng, Jennifer Schmidt, Birgitta Hammock, Bruce D. Zeldin, Darryl C. Kieran, Mark W. Panigrahy, Dipak TI Cytochrome P450-derived eicosanoids regulate pancreatic cancer and metastasis. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Casper, Jessica A.; Bielenberg, Diane R.; Schmidt, Birgitta; Panigrahy, Dipak] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Cheng, Jennifer; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Hammock, Bruce D.] Univ Calif Davis, Davis, CA 95616 USA. [Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3952 DI 10.1158/1538-7445.AM2013-3952 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603186 ER PT J AU Chang, DK Han, T Clark, RA Zhu, Q Kupper, TS Marasco, WA AF Chang, DeKuan Han, Thomas Clark, Rachael A. Zhu, Quan Kupper, Thomas S. Marasco, Wayne A. TI A humanized, high affinity anti-CCR4 antibody for immunotherapy of cutaneous T cell lymphoma and characterization on T cell function SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Chang, DeKuan; Han, Thomas; Zhu, Quan; Marasco, Wayne A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Clark, Rachael A.; Kupper, Thomas S.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4754 DI 10.1158/1538-7445.AM2013-4754 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604335 ER PT J AU Chen, YA Chen, ZH Permuth-Wev, J Tsai, YY Lin, HY Qu, XT Lawrenson, K Fenstermacher, D Phelan, CM Monteiro, A Gayther, SA Narod, SA Sutphen, R Birrer, MJ Wentzensen, N Schildkraut, JM Goode, EL Pharoah, P Sellers, T AF Chen, Yian Ann Chen, Zhihua Permuth-Wev, Jennifer Tsai, Ya-Yu Lin, Hui-Yi Qu, Xiaotao Lawrenson, Kate Fenstermacher, David Phelan, Catherine M. Monteiro, Alvaro Gayther, Simon A. Narod, Steven A. Sutphen, Rebecca Birrer, Michael J. Wentzensen, Nicolas Schildkraut, Joellen M. Goode, Ellen L. Pharoah, Paul Sellers, Thomas TI Variants in long non-coding RNAs are associated with epithelial ovarian cancer risk in a pooled analysis of three genome-wide association studies. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Chen, Yian Ann; Chen, Zhihua; Permuth-Wev, Jennifer; Tsai, Ya-Yu; Lin, Hui-Yi; Qu, Xiaotao; Fenstermacher, David; Phelan, Catherine M.; Monteiro, Alvaro; Sellers, Thomas] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Lawrenson, Kate; Gayther, Simon A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Narod, Steven A.] Univ Toronto, Toronto, ON, Canada. [Sutphen, Rebecca] Univ S Florida, Tampa, FL USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wentzensen, Nicolas] NCI, Bethesda, MD 20892 USA. [Schildkraut, Joellen M.] Duke Univ, Med Ctr, Durham, NC USA. [Goode, Ellen L.] Mayo Clin, Coll Med, Rochester, MN USA. [Pharoah, Paul] Univ Cambridge, Cambridge, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4579 DI 10.1158/1538-7445.AM2013-4579 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600314 ER PT J AU Chin, YMR Balk, S Toker, A AF Chin, Yuet Ming Rebecca Balk, Steve Toker, Alex TI Akt2-specific signaling in prostate cancer maintenance SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Chin, Yuet Ming Rebecca; Balk, Steve; Toker, Alex] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4090 DI 10.1158/1538-7445.AM2013-4090 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603320 ER PT J AU Choi, SH Lee, HJ Jin, YB Lee, M Kim, J Yoon, SS Lee, YS Lee, YJ AF Choi, Seo-Hyun Lee, Hae-June Jin, Yeung Bae Lee, Minyoung Kim, Joon Yoon, Sam S. Lee, Yun-Sil Lee, Yoon-Jin TI MMP9 processing of HSBP1 regulates tumor metastases SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Choi, Seo-Hyun] Korea Univ, Korea Inst Radiol & Med Sci, Seoul, South Korea. [Lee, Hae-June; Lee, Minyoung; Lee, Yoon-Jin] Korea Inst Radiol & Med Sci, Seoul, South Korea. [Jin, Yeung Bae] Korea Atom Energy Res Inst, Adv Radiat Technol Inst, Jeongeup, South Korea. [Kim, Joon] Korea Univ, Seoul, South Korea. [Yoon, Sam S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yoon, Sam S.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Yun-Sil] Ewha Womans Univ, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3873 DI 10.1158/1538-7445.AM2013-3873 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603107 ER PT J AU Choy, E Butrynski, J Harmon, D Morgan, J George, S Wagner, A D'Adamo, D Cote, G Rubinstein, Y Benes, C Haber, D Baselga, J Demetri, G AF Choy, Edwin Butrynski, James Harmon, David Morgan, Jeffrey George, Suzanne Wagner, Andrew D'Adamo, David Cote, Greg Rubinstein, Yael Benes, Cyril Haber, Daniel Baselga, Jose Demetri, George TI Translation of preclinical predictive sensitivity of Ewing sarcoma to PARP inhibition: Phase II study of olaparib in adult patients with recurrent/metastatic Ewing sarcoma following failure of prior chemotherapy. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Choy, Edwin; Harmon, David; Cote, Greg; Benes, Cyril; Haber, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Butrynski, James; Morgan, Jeffrey; George, Suzanne; Wagner, Andrew; D'Adamo, David; Rubinstein, Yael; Demetri, George] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB174 DI 10.1158/1538-7445.AM2013-LB-174 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601109 ER PT J AU Choy, E Balasubramanian, S Butrynski, J Morgan, J Sirisawad, M Mani, C George, S Wagner, A Harmon, D Rubinstein, Y Duan, ZF Hornicek, F Demetri, G AF Choy, Edwin Balasubramanian, Sriram Butrynski, James Morgan, Jeffrey Sirisawad, Mint Mani, Chitra George, Suzanne Wagner, Andrew Harmon, David Rubinstein, Yael Duan, Zhenfeng Hornicek, Francis Demetri, George TI Phase I dose escalation study of abexinostat and doxorubicin in patients with metastatic sarcomas. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Choy, Edwin; Harmon, David; Duan, Zhenfeng; Hornicek, Francis] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Balasubramanian, Sriram; Sirisawad, Mint; Mani, Chitra] Pharmacyclics, Sunnyvale, CA USA. [Butrynski, James; Morgan, Jeffrey; George, Suzanne; Wagner, Andrew; Rubinstein, Yael; Demetri, George] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB167 DI 10.1158/1538-7445.AM2013-LB-167 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601103 ER PT J AU Corcoran, RB Rothenberg, SM Hata, AN Faber, AC Winokur, D Piris, A Nazarian, RM Brown, RD Godfrey, JT Mino-Kenudson, M Settleman, J Wargo, JA Flaherty, KT Haber, DA Engelman, JA AF Corcoran, Ryan B. Rothenberg, Stephen M. Hata, Aaron N. Faber, Anthony C. Winokur, Daniel Piris, Adriano Nazarian, Rosalynn M. Brown, Ronald D. Godfrey, Jason T. Mino-Kenudson, Mari Settleman, Jeffrey Wargo, Jennifer A. Flaherty, Keith T. Haber, Daniel A. Engelman, Jeffrey a TI Rapid assessment of TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF mutant melanoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Corcoran, Ryan B.; Rothenberg, Stephen M.; Hata, Aaron N.; Wargo, Jennifer A.; Flaherty, Keith T.; Haber, Daniel A.; Engelman, Jeffrey a] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faber, Anthony C.; Winokur, Daniel; Brown, Ronald D.; Godfrey, Jason T.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Piris, Adriano; Nazarian, Rosalynn M.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Settleman, Jeffrey] Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4568 DI 10.1158/1538-7445.AM2013-4568 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604168 ER PT J AU Damle, RN Temburni, S Aggarwal, P O'Brien, S Barrientos, J Brown, JR Flinn, IW Barr, P Burger, J Friedberg, JW Rai, KR Chang, B James, D Buggy, J Chiorazzi, N AF Damle, Rajendra N. Temburni, Sonal Aggarwal, Prachi O'Brien, Susan Barrientos, Jacqueline Brown, Jennifer R. Flinn, Ian W. Barr, Paul Burger, Jan Friedberg, Jonathan W. Rai, Kanti R. Chang, Betty James, Danelle Buggy, Joseph Chiorazzi, Nicholas TI Changes in immune cell populations in relapsed/refractory CLL patients treated with a Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), in combination with Bendamustine and Rituximab (BR) SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Damle, Rajendra N.; Temburni, Sonal; Aggarwal, Prachi; Chiorazzi, Nicholas] Feinstein Inst Med Res, Manhasset, NY USA. [O'Brien, Susan; Burger, Jan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Barrientos, Jacqueline; Rai, Kanti R.] Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Flinn, Ian W.] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. [Barr, Paul; Friedberg, Jonathan W.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Chang, Betty; James, Danelle; Buggy, Joseph] Pharmacyclics Inc, Sunnyvale, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3531 DI 10.1158/1538-7445.AM2013-3531 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220602235 ER PT J AU Demetri, GD Jeffers, M Reichardt, P Kang, YK Blay, JY Rutkowski, P Gelderblom, H Hohenberger, P Leahy, M von Mehren, M Joensuu, H Badalamenti, G Blackstein, M Le Cesne, A Schoffski, P Maki, RG Bauer, S Nguyen, BB Xu, JM Nishida, T Chung, J Lathia, CD Kappeler, C Kuss, I Laurent, D Casali, PG AF Demetri, George D. Jeffers, Michael Reichardt, Peter Kang, Yoon-Koo Blay, Jean-Yves Rutkowski, Piotr Gelderblom, Hans Hohenberger, Peter Leahy, Michael von Mehren, Margaret Joensuu, Heikki Badalamenti, Giuseppe Blackstein, Martin Le Cesne, Axel Schoffski, Patrick Maki, Robert G. Bauer, Sebastian Binh Bui Nguyen Xu, Jianming Nishida, Toshirou Chung, John Lathia, Chetan D. Kappeler, Christian Kuss, Iris Laurent, Dirk Casali, Paolo G. TI Detection of oncogenic kinase mutations in circulating plasma DNA and correlation with clinical benefit in the phase III GRID study of regorafenib vs placebo in TKI-refractory metastatic GIST. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jeffers, Michael] Bayer HealthCare, Montville, NJ USA. [Reichardt, Peter] HELIOS Klin, Dept Hematol Oncol & Palliat Med, Bad Saarow Pieskow, Germany. [Kang, Yoon-Koo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Blay, Jean-Yves] Ctr Leon Berard, Leon, France. [Blay, Jean-Yves] Univ Claude Bernard, Leon, France. [Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Gelderblom, Hans] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Hohenberger, Peter] Univ Mannheim, Med Ctr, Div Surg Oncol & Thorac Surg, D-68131 Mannheim, Germany. [Leahy, Michael] Christie NHS Fdn Trust, Manchester, Lancs, England. [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Joensuu, Heikki] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Badalamenti, Giuseppe] Univ Palermo, Dept Oncol, Palermo, Italy. [Blackstein, Martin] Mt Sinai Hosp, Med Oncol Unit, Toronto, ON M5G 1X5, Canada. [Le Cesne, Axel] Inst Gustave Roussy, Dept Med, Paris, France. [Schoffski, Patrick] Katholieke Univ Leuven Hosp, Dept Gen Med Oncol, Louvain, Belgium. [Maki, Robert G.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauer, Sebastian] Univ Duisburg Essen, West German Canc Ctr, Sarcoma Ctr, Essen, Germany. [Binh Bui Nguyen] Inst Bergonie, Bordeaux, France. [Xu, Jianming] Acad Mil Med Sci, Affiliated Hosp Canc Ctr, Beijing, Peoples R China. [Nishida, Toshirou] Osaka Police Hosp, Dept Surg, Osaka, Japan. [Chung, John] Bayer Healthcare Pharmaceut, Wayne, NJ USA. [Lathia, Chetan D.] Alexion Pharmaceut, Cheshire, CT USA. [Kappeler, Christian; Kuss, Iris; Laurent, Dirk] Bayer Pharma AG, Berlin, Germany. [Casali, Paolo G.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB295 DI 10.1158/1538-7445.AM2013-LB-295 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601220 ER PT J AU Dranoff, G AF Dranoff, Glenn TI Engineering improved cancer vaccines. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Dranoff, Glenn] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA SY2704 DI 10.1158/1538-7445.AM2013-SY27-04 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601397 ER PT J AU Drew, L Engelman, J Katayama, R McDermott, B Saeh, J Scarpitti, M Shaw, A Shen, MH Wang, SP Smith, G AF Drew, Lisa Engelman, Jeffrey Katayama, Ryohei McDermott, Brenda Saeh, Jamal Scarpitti, Meghan Shaw, Alice Shen, Minhui Wang, Suping Smith, Graeme TI Concurrent roles for IGF1R and EGFR in driving acquired resistance to crizotinib and ability to overcome with a combination of the ALK/IGF1R inhibitor AZD3463 and Iressa. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Drew, Lisa; McDermott, Brenda; Saeh, Jamal; Scarpitti, Meghan; Shen, Minhui; Wang, Suping] AstraZeneca R&D Boston, Waltham, MA USA. [Engelman, Jeffrey; Shaw, Alice] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Katayama, Ryohei] Japanese Fdn Canc Res, Tokyo, Japan. [Smith, Graeme] AstraZeneca R&D Alderley Pk, Macclesfield, Cheshire, England. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4465 DI 10.1158/1538-7445.AM2013-4465 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604070 ER PT J AU Duda, DG Tolaney, SM Ancukiewicz, M Winer, EP Krop, IE Jain, RK AF Duda, Dan G. Tolaney, Sara M. Ancukiewicz, Marek Winer, Eric P. Krop, Ian E. Jain, Rakesh K. TI A study of circulating biomarkers of angiogenesis and inflammation in ER plus breast cancer (BC) versus triple-negative breast cancer (TNBC) patients enrolled in a phase II study of preoperative treatment with 1 cycle of Bevacizumab followed by standard chemo SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Duda, Dan G.; Ancukiewicz, Marek; Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tolaney, Sara M.; Winer, Eric P.; Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB81 DI 10.1158/1538-7445.AM2013-LB-81 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601328 ER PT J AU Edwards, AL Gavathiotis, E LaBelle, JL Braun, CR Opoku-Nsiah, K Bird, GH Walensky, LD AF Edwards, Amanda L. Gavathiotis, Evripidis LaBelle, James L. Braun, Craig R. Opoku-Nsiah, Kwadwo Bird, Gregory H. Walensky, Loren D. TI Multimodal activation of apoptosis by a hydrocarbon-stapled PUMA BH3 helix SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Edwards, Amanda L.; Opoku-Nsiah, Kwadwo; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gavathiotis, Evripidis] Albert Einstein Coll Med, Bronx, NY 10467 USA. [LaBelle, James L.] Univ Chicago Med, Chicago, IL USA. [Braun, Craig R.] Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4611 DI 10.1158/1538-7445.AM2013-4611 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604197 ER PT J AU Emblem, KE Mouridsen, K Bjornerud, A Farrar, CT Jennings, D Borra, RJH Wen, PY Ivy, P Batchelor, TT Rosen, BR Jain, RK Sorensen, AG AF Emblem, Kyrre E. Mouridsen, Kim Bjornerud, Atle Farrar, Christian T. Jennings, Dominique Borra, Ronald J. H. Wen, Patrick Y. Ivy, Percy Batchelor, Tracy T. Rosen, Bruce R. Jain, Rakesh K. Sorensen, A. Gregory TI Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Emblem, Kyrre E.; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Rosen, Bruce R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Emblem, Kyrre E.; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Rosen, Bruce R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Mouridsen, Kim] Univ Aarhus, Ctr Functionally Integrat Neurosci, Aarhus, Denmark. [Mouridsen, Kim] Univ Aarhus, MINDLab, Aarhus, Denmark. [Bjornerud, Atle] Oslo Univ Hosp, Intervent Ctr, Oslo, Norway. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Ivy, Percy] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Sorensen, A. Gregory] Siemens Healthcare Hlth Serv, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB297 DI 10.1158/1538-7445.AM2013-LB-297 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601222 ER PT J AU Emerling, BM Benes, C Bell, E Poulogiannis, G Courtney, K Lui, H Choo-Wing, R Bellinger, G Soltoff, S Cantley, L AF Emerling, Brooke M. Benes, Cyril Bell, Eric Poulogiannis, George Courtney, Kevin Lui, Hui Choo-Wing, Rayman Bellinger, Gary Soltoff, Stephen Cantley, Lewis TI Identification of CDCP1 as a HIF-2 alpha target gene involved in the regulation of cancer cell migration and metastasis SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Emerling, Brooke M.; Poulogiannis, George; Lui, Hui; Choo-Wing, Rayman; Bellinger, Gary; Cantley, Lewis] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Benes, Cyril] Harvard Univ, Sch Med, Boston, MA USA. [Bell, Eric] MIT, Cambridge, MA 02139 USA. [Courtney, Kevin] UT Southwestern, Dallas, TX USA. [Soltoff, Stephen] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4588 DI 10.1158/1538-7445.AM2013-4588 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604174 ER PT J AU Fuchs, CS Tomasek, J Cho, JY Filip, D Passalacqua, R Goswami, C Safran, H Dos Santos, LV Aprile, G Ferry, D Melichar, B Tehfe, M Topuzov, E Tabernero, J Zalcberg, JR Chau, I Koshiji, M Hsu, YZ Schwartz, J Ajani, J AF Fuchs, Charles S. Tomasek, Jiri Cho, Jae Yong Filip, Dumitru Passalacqua, Rodolfo Goswami, Chancal Safran, Howard Dos Santos, Lucas Vieira Aprile, Giuseppe Ferry, David Melichar, Bohuslav Tehfe, Moustapha Topuzov, Eldar Tabernero, Josep Raymond Zalcberg, John Chau, Ian Koshiji, Minori Hsu, Yanzhi Schwartz, Jonathan Ajani, Jaffer TI REGARD: A phase III, randomized, double-blind trial of ramucirumab and best supportive care (BSC) versus placebo and BSC in the treatment of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line p SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tomasek, Jiri] Masaryk Mem Canc Inst, Brno, Czech Republic. [Cho, Jae Yong] Gangnam Severance Hosp, Seoul, South Korea. [Filip, Dumitru] Spitalul Judetean Urgenta, Baia Mare, Romania. [Passalacqua, Rodolfo] Ist Ospitalieri, Cremona, Italy. [Goswami, Chancal] BP Poddar Hosp & Med Res, Bengal, India. [Safran, Howard] Brown Univ, Sch Med, Providence, RI 02912 USA. [Dos Santos, Lucas Vieira] Hosp Canc Barretos, Barretos, Brazil. [Aprile, Giuseppe] Univ & Gen Hosp, Dept Oncol, Udine, Italy. [Ferry, David] New Cross Hosp, Wolverhampton, W Midlands, England. [Melichar, Bohuslav] Palacky Univ, Sch Med, CR-77147 Olomouc, Czech Republic. [Melichar, Bohuslav] Palacky Univ, Teaching Hosp, CR-77147 Olomouc, Czech Republic. [Tehfe, Moustapha] Hop Notre Dame CHUM, Montreal, PQ, Canada. [Topuzov, Eldar] GOU VPO St Petersburg SMA, St Petersburg, Russia. [Tabernero, Josep] Vall dHebron Univ Hosp, Barcelona, Spain. [Raymond Zalcberg, John] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Raymond Zalcberg, John] Univ Melbourne, Melbourne, Vic, Australia. [Chau, Ian] Royal Marsden Hosp, Surrey, England. [Koshiji, Minori; Hsu, Yanzhi; Schwartz, Jonathan] Eli Lilly & Co, Bridgewater, NJ USA. [Ajani, Jaffer] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB67 DI 10.1158/1538-7445.AM2013-LB-67 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601315 ER PT J AU Ge, RB Wang, ZW Olumi, AF AF Ge Rongbin Wang, Zongwei Olumi, Aria F. TI Metformin has an anticancer effect by repressing TWIST/N-cadherin signaling SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Ge Rongbin; Wang, Zongwei; Olumi, Aria F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4965 DI 10.1158/1538-7445.AM2013-4965 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220605063 ER PT J AU Gordon, MS Hamid, O Powderly, J Anderson, M Fine, G Mokatrin, A Kowanetz, M Maya, L Irving, BA Chen, DS Hodi, FS AF Gordon, Michael S. Hamid, Omid Powderly, John Anderson, Maria Fine, Gregg Mokatrin, Ahmad Kowanetz, Marcin Maya, Leabman Irving, Bryan A. Chen, Daniel S. Hodi, F. Stephen TI A phase I study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Gordon, Michael S.] Premiere Oncol Arizona, Scottsdale, AZ USA. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Powderly, John] Carolina BioOncol Inst, Huntersville, NC USA. [Anderson, Maria; Fine, Gregg; Mokatrin, Ahmad; Kowanetz, Marcin; Maya, Leabman; Irving, Bryan A.; Chen, Daniel S.] Genentech Inc, San Francisco, CA 94080 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB288 DI 10.1158/1538-7445.AM2013-LB-288 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601213 ER PT J AU Haber, DA Yu, M Ozkumar, E Ting, D Miyamoto, D Lee, R Shah, A Bardia, A Stott, S Toner, M Maheswaran, S AF Haber, Daniel A. Yu, Min Ozkumar, Emre Ting, David Miyamoto, David Lee, Richard Shah, Ajay Bardia, Aditya Stott, Shannon Toner, Mehmet Maheswaran, Shyamala TI Molecular characterization of single circulating tumor cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Haber, Daniel A.; Yu, Min; Ozkumar, Emre; Ting, David; Miyamoto, David; Lee, Richard; Shah, Ajay; Bardia, Aditya; Stott, Shannon; Toner, Mehmet; Maheswaran, Shyamala] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA SY3001 DI 10.1158/1538-7445.AM2013-SY30-01 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220602002 ER PT J AU Hansen, JE Chan, G Liu, YF Hegan, DC Dalal, S Dray, E Kwon, Y Xu, YY Xu, XH Peterson-Roth, E Geiger, E Liu, YL Gera, J Sweasy, JB Sung, P Rockwell, S Nishimura, RN Weisbart, RH Glazer, PM AF Hansen, James E. Chan, Grace Liu, Yanfeng Hegan, Denise C. Dalal, Shibani Dray, Eloise Kwon, Youngho Xu, Yuanyuan Xu, Xiaohua Peterson-Roth, Elizabeth Geiger, Erik Liu, Yilun Gera, Joseph Sweasy, Joann B. Sung, Patrick Rockwell, Sara Nishimura, Robert N. Weisbart, Richard H. Glazer, Peter M. TI Lupus antibody-based cancer therapy. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Hansen, James E.; Liu, Yanfeng; Hegan, Denise C.; Dalal, Shibani; Dray, Eloise; Kwon, Youngho; Xu, Yuanyuan; Peterson-Roth, Elizabeth; Geiger, Erik; Sweasy, Joann B.; Sung, Patrick; Rockwell, Sara; Glazer, Peter M.] Yale Univ, Sch Med, New Haven, CT USA. [Chan, Grace; Gera, Joseph; Nishimura, Robert N.; Weisbart, Richard H.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. [Xu, Xiaohua; Liu, Yilun] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. RI Dray, Eloise/E-3938-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4319 DI 10.1158/1538-7445.AM2013-4319 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603326 ER PT J AU He, L Torres-Lockhart, K Forster, N Ramakrishnan, S Greninger, P Garnett, MJ McDermott, U Rothenberg, SM Benes, C Ellisen, L AF He, Lei Torres-Lockhart, Kristine Forster, Nicole Ramakrishnan, Saranya Greninger, Patricia Garnett, Mathew J. McDermott, Ultan Rothenberg, S. Michael Benes, Cyril Ellisen, Leif TI Mcl-1 and FBW7 control a dominant survival pathway underlying HDAC and BcI-2 inhibitor synergy in squamous cell carcinoma. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [He, Lei; Torres-Lockhart, Kristine; Forster, Nicole; Ramakrishnan, Saranya; Greninger, Patricia; Rothenberg, S. Michael; Benes, Cyril; Ellisen, Leif] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Garnett, Mathew J.; McDermott, Ultan] Wellcome Trust Sanger Inst, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB212 DI 10.1158/1538-7445.AM2013-LB-212 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601142 ER PT J AU Hettmer, S Schinzel, A Hahn, WC Wagers, A AF Hettmer, Simone Schinzel, Anna Hahn, William C. Wagers, Amy TI Target identification in rhabdomyosarcomas induced in mouse skeletal muscle SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Hettmer, Simone; Schinzel, Anna; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wagers, Amy] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3812 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603045 ER PT J AU Hu, H Wulf, G Juvekar, A Dittmer, DP Fingeroth, J AF Hu, Hai Wulf, Gerburg Juvekar, Ashish Dittmer, Dirk P. Fingeroth, Joyce TI EBV infection of mammary epithelial cells promotes malignant transformation SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Hu, Hai; Wulf, Gerburg; Juvekar, Ashish] BIDMC, Boston, MA USA. [Dittmer, Dirk P.] Univ N Carolina, Chapel Hill, NC USA. [Fingeroth, Joyce] HMS, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4781 DI 10.1158/1538-7445.AM2013-4781 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604343 ER PT J AU Huang, FW Hodis, E Xu, MJ Kryukov, G Chin, L Garraway, LA AF Huang, Franklin W. Hodis, Eran Xu, Mary Jue Kryukov, Gregory Chin, Lynda Garraway, Levi A. TI The identification of recurrent non-coding mutations in melanoma. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Huang, Franklin W.; Hodis, Eran; Xu, Mary Jue; Kryukov, Gregory; Garraway, Levi A.] Dana Farber Canc Inst, Broad Inst, Boston, MA 02115 USA. [Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB228 DI 10.1158/1538-7445.AM2013-LB-228 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601157 ER PT J AU Huang, YH Yuan, JP Righi, E Duda, DG Fukumura, D Poznanasky, MC Jain, RK AF Huang, Yuhui Yuan, Jianping Righi, Elda Duda, Dan G. Fukumura, Dai Poznanasky, Mark C. Jain, Rakesh K. TI Vascular normalization as an emerging strategy to enhance cancer immunotherapy SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Huang, Yuhui; Yuan, Jianping; Righi, Elda; Duda, Dan G.; Fukumura, Dai; Poznanasky, Mark C.; Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB344 DI 10.1158/1538-7445.AM2013-LB-344 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601269 ER PT J AU Infante, JR Gandi, L Shapiro, G Rizvi, N Burris, HA Bendell, JC Baselga, J Hsu, K von Richter, O Locatelli, G Asatiani, E Heist, RS AF Infante, Jeffrey R. Gandi, Leena Shapiro, Geoffrey Rizvi, Naiyer Burris, Howard A. Bendell, Johanna C. Baselga, Jose Hsu, Karl von Richter, Oliver Locatelli, Giuseppe Asatiani, Ekaterine Heist, Rebecca S. TI Combination of the MEK inhibitor, pimasertib (MSC1936369B), and the PI3K/mTOR inhibitor, SAR245409, in patients with advanced solid tumors: Results of a phase Ib dose-escalation trial. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Infante, Jeffrey R.; Burris, Howard A.; Bendell, Johanna C.] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA. [Gandi, Leena; Shapiro, Geoffrey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rizvi, Naiyer] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Baselga, Jose; Heist, Rebecca S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hsu, Karl] Sanofi, Cambridge, MA USA. [von Richter, Oliver] Merck KGaA, Global Exploratory Med, Darmstadt, Germany. [Locatelli, Giuseppe] Merck KGaA, Global Res & Early Dev, Darmstadt, Germany. [Asatiani, Ekaterine] Merck Serono SA, Geneva, Switzerland. RI von Richter, Oliver/O-6412-2016 OI von Richter, Oliver/0000-0002-5262-9922 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB147 DI 10.1158/1538-7445.AM2013-LB-147 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601086 ER PT J AU Irimia, D AF Irimia, Daniel TI Self-guided migration of cancer epithelial cells in confined environment. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Irimia, Daniel] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3779 DI 10.1158/1538-7445.AM2013-3779 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603013 ER PT J AU Jamin, Y Glass, L Hallsworth, A George, RE Koh, DM Pearson, ADJ Chesler, L Robinson, SP AF Jamin, Yann Glass, Laura Hallsworth, Albert George, Rani E. Koh, Dow-Mu Pearson, Andrew D. J. Chesler, Louis Robinson, Simon P. TI Intrinsic susceptibility magnetic resonance imaging identifies tumors with ALKF1174L mutation in transgenic murine models of high-risk neuroblastoma. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Jamin, Yann; Glass, Laura; Hallsworth, Albert; Koh, Dow-Mu; Pearson, Andrew D. J.; Chesler, Louis; Robinson, Simon P.] Inst Canc Res, Sutton, Surrey, England. [George, Rani E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [George, Rani E.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 5037 DI 10.1158/1538-7445.AM2013-5037 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220605133 ER PT J AU Jones, DTW Hutter, B Jager, N Korshunov, A Kool, M Lambert, SR Quang, DAK Fontebasso, AM Ryzhova, M Warnatz, HJ Zichner, T Korbel, JO Wolf, S Yaspo, ML Ligon, KL Kieran, MW Brors, B Feisberg, J Reifenberger, G Collins, VP Jabado, N Elis, R Lichter, P Pfister, SM AF Jones, David T. W. Hutter, Barbara Jaeger, Natalie Korshunov, Andrey Kool, Marcel Lambert, Sally R. Dong Anh Khuong Quang Fontebasso, Adam M. Ryzhova, Marina Warnatz, Hans-Joerg Zichner, Thomas Korbel, Jan O. Wolf, Stephan Yaspo, Marie-Laure Ligon, Keith L. Kieran, Mark W. Brors, Benedikt Feisberg, Joerg Reifenberger, Guido Collins, V. Peter Jabado, Nada Elis, Roland Lichter, Peter Pfister, Stefan M. CA ICGC PedBrain Tumor Project TI Recurrent FGFR1 hotspot mutations represent a novel therapeutic target in childhood astrocytorna SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Jones, David T. W.; Hutter, Barbara; Jaeger, Natalie; Kool, Marcel; Wolf, Stephan; Brors, Benedikt; Elis, Roland; Lichter, Peter; Pfister, Stefan M.] German Canc Res Ctr, Heidelberg, Germany. [Korshunov, Andrey] Heidelberg Univ, Heidelberg, Germany. [Lambert, Sally R.; Collins, V. Peter] Univ Cambridge, Cambridge, England. [Dong Anh Khuong Quang; Fontebasso, Adam M.; Jabado, Nada] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada. [Ryzhova, Marina] Burdenko Neurosurg Inst, Moscow, Russia. [Warnatz, Hans-Joerg; Yaspo, Marie-Laure] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Zichner, Thomas; Korbel, Jan O.] European Mol Biol Lab, D-69012 Heidelberg, Germany. [Ligon, Keith L.; Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Feisberg, Joerg; Reifenberger, Guido] Univ Dusseldorf, Dusseldorf, Germany. RI Kool, Marcel/H-2541-2013; Pfister, Stefan/F-6860-2013 OI Pfister, Stefan/0000-0002-5447-5322 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4594 DI 10.1158/1538-7445.AM2013-4594 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604180 ER PT J AU Juric, D Dienstmann, R Cervantes, A Hidalgo, M Messersmith, W Blumenschein, G Baselga, J Tabernero, J Roda, D Calles, A Jimeno, A Amler, L Stern, H Sanabria, S Penuel, E Pirzkall, A AF Juric, Dejan Dienstmann, Rodrigo Cervantes, Andres Hidalgo, Manuel Messersmith, Wells Blumenschein, George Baselga, Jose Tabernero, Josep Roda, Desamparados Calles, Antonio Jimeno, Antonio Amler, Lukas Stern, Howard Sanabria, Sandra Penuel, Elicia Pirzkall, Andrea TI Pharmacodynamic (PD) assessment of drug activity in tumor tissue from patients (pts) enrolled in a Phase I study of MEHD7945A (MEHD), a first-in-class HER3/EGFR dual action antibody, in pts with locally advanced or metastatic epithelial tumors. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Juric, Dejan; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Dienstmann, Rodrigo; Tabernero, Josep] Vall dHebron Inst Oncol, Dept Med Oncol, Barcelona, Spain. [Cervantes, Andres; Roda, Desamparados] Univ Valencia, INCLIVA Hlth Res Inst, Valencia, Spain. [Hidalgo, Manuel; Calles, Antonio] Spanish Natl Canc Res Ctr, Gastrointestinal Canc Clin Res Unit, Madrid, Spain. [Messersmith, Wells; Jimeno, Antonio] Univ Colorado, Ctr Canc, Div Med Oncol, Denver, CO 80262 USA. [Blumenschein, George] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Amler, Lukas; Stern, Howard; Sanabria, Sandra; Penuel, Elicia; Pirzkall, Andrea] Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3363 DI 10.1158/1538-7445.AM2013-3363 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220602070 ER PT J AU Juric, D Krop, I Ramanathan, RK Xiao, J Sanabria, S Wilson, TR Choi, YJ Parmar, H Hsu, J Baselga, J Von Hoff, DD AF Juric, Dejan Krop, Ian Ramanathan, Ramesh K. Xiao, Jim Sanabria, Sandra Wilson, Timothy R. Choi, YounJeong Parmar, Hema Hsu, Jerry Baselga, Jose Von Hoff, Daniel D. TI GDC-0032, a beta isoform-sparing PI3K inhibitor: Results of a first-in-human phase la dose escalation study. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Juric, Dejan; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Krop, Ian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ramanathan, Ramesh K.; Von Hoff, Daniel D.] Virginia G Piper Canc Ctr TGen, Scottsdale, AZ USA. [Xiao, Jim; Sanabria, Sandra; Wilson, Timothy R.; Choi, YounJeong; Parmar, Hema; Hsu, Jerry] Genentech Inc, San Francisco, CA 94080 USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB64 DI 10.1158/1538-7445.AM2013-LB-64 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601312 ER PT J AU Katayama, R Aoyama, A Yamori, T Qi, J Ohara, T Song, YC Engelman, JA Fujita, N AF Katayama, Ryohei Aoyama, Aki Yamori, Takao Qi, Jie Ohara, Tomoko Song, Youngchul Engelman, Jeffrey A. Fujita, Naoya TI Antitumor activity of Tivantinib (ARQ 197) is due to inhibition of tubulin polymerization in addition to c-Met inhibition. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Katayama, Ryohei; Aoyama, Aki; Yamori, Takao; Ohara, Tomoko; Fujita, Naoya] Japanese Fdn Canc Res, Tokyo, Japan. [Qi, Jie; Song, Youngchul; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4348 DI 10.1158/1538-7445.AM2013-4348 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603355 ER PT J AU Katiyar, SK Vaid, M AF Katiyar, Santosh K. Vaid, Mudit TI Bioactive phytochemical proanthocyanidins target beta-catenin signaling in preventing invasive potential of human melanoma cells. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Katiyar, Santosh K.; Vaid, Mudit] Univ Alabama Birmingham, Birmingham, AL USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3683 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220602319 ER PT J AU Katiyar, SK Vaid, M AF Katiyar, Santosh K. Vaid, Mudit TI Bioactive phytochemical proanthocyanidins target beta-catenin signaling in preventing invasive potential of human melanoma cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Katiyar, Santosh K.; Vaid, Mudit] Univ Alabama Birmingham, Birmingham, AL USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3683 DI 10.1158/1538-7445.AM2013-3683 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600303 ER PT J AU Kleiman, LB Krebs, A Kim, S Hong, TS Haigis, KM AF Kleiman, Laura B. Krebs, Angela Kim, Stephen Hong, Theodore S. Haigis, Kevin M. TI Identification and characterization of small molecule inhibitors that radiosensitize K-RAS mutant rectal cancers SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Kleiman, Laura B.; Krebs, Angela; Kim, Stephen; Hong, Theodore S.; Haigis, Kevin M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4440 DI 10.1158/1538-7445.AM2013-4440 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604045 ER PT J AU Kohlenberg, JD Chen, YL Best, B Storz, P Peterson, RT Silverstein, R Ren, B AF Kohlenberg, Jacob D. Chen, Yiliang Best, Brad Storz, Peter Peterson, Randall T. Silverstein, Roy Ren, Bin TI A novel LPA-PKD1-FoxO1 pathway in endothelial cells provides an angiogenic switch via down-regulation of CD36 transcription and induction of arteriogenic responses SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Kohlenberg, Jacob D.] Med Coll Wisconsin, MD Program, Milwaukee, WI 53226 USA. [Chen, Yiliang; Best, Brad] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA. [Storz, Peter] Mayo Clin, Mayo Clin Comprehens Canc Ctr, Dept Canc Biol, Jacksonville, FL 32224 USA. [Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. [Silverstein, Roy] Med Coll Wisconsin, Blood Ctr Wisconsin, Dept Med, Blood Res Inst, Milwaukee, WI 53226 USA. [Silverstein, Roy; Ren, Bin] Med Coll Wisconsin, Tumor Microenvironm Res Program, Ctr Canc, Milwaukee, WI 53226 USA. [Ren, Bin] Med Coll Wisconsin, Blood Ctr Wisconsin, Blood Res Inst, Div Hematol & Oncol, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB338 DI 10.1158/1538-7445.AM2013-LB-338 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601262 ER PT J AU Labidi-Galy, I Clauss, A Ng, V Duraisamy, S Ganesan, S Drapkin, R AF Labidi-Galy, Intidhar Clauss, Adam Ng, Vivian Duraisamy, Sekhar Ganesan, Shridar Drapkin, Ronny TI Elafin is a candidate biomarker that underlies the similarities between basal-like breast cancer and ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Labidi-Galy, Intidhar; Clauss, Adam; Ng, Vivian; Duraisamy, Sekhar; Drapkin, Ronny] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ganesan, Shridar] Canc Inst New Jersey, New Brunswick, NJ USA. RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3455 DI 10.1158/1538-7445.AM2013-3455 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220602161 ER PT J AU Li, J Zhu, S Kozono, D Futulan, D Gonda, D Kushwaha, D Kahle, K Elledge, S Chen, CC AF Li, Jie Zhu, Shan Kozono, David Futulan, Diahnn Gonda, David Kushwaha, Deepa Kahle, Kristopher Elledge, Stephen Chen, Clark C. TI ShRNA-based cellular proliferation signaling analysis revealed DRD2 as a novel therapeutic target for glioblastoma. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Li, Jie; Futulan, Diahnn; Gonda, David; Chen, Clark C.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Zhu, Shan; Kozono, David; Kushwaha, Deepa] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Instabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. [Kahle, Kristopher; Elledge, Stephen] Harvard Univ, Sch Med, Dept Genet, Div Genom Instabil & DNA Repair, Boston, MA USA. RI Li, Jie/L-1737-2015 OI Li, Jie/0000-0002-0590-9817 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4366 DI 10.1158/1538-7445.AM2013-4366 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603373 ER PT J AU Li, WQ Han, JL Widlund, H Correll, M Wang, YY Quackenbush, J Mihm, M Canales, AL Golub, T Hoshida, Y Hunter, D Murphy, G Kupper, T Qureshi, A AF Li, Wenqing Han, Jiali Widlund, Hans Correll, Mick Wang, Yaoyu Quackenbush, John Mihm, Martin Canales, Alvaro Laga Golub, Todd Hoshida, Yujin Hunter, David Murphy, George Kupper, Thomas Qureshi, Abrar TI CXCR4 pathway associated with family history of melanoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Li, Wenqing; Han, Jiali; Widlund, Hans; Canales, Alvaro Laga; Hunter, David; Murphy, George; Kupper, Thomas; Qureshi, Abrar] Harvard Univ, Sch Med, Boston, MA USA. [Correll, Mick; Wang, Yaoyu; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mihm, Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Golub, Todd; Hoshida, Yujin] Harvard Univ, Sch Med, Broad Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 1347 DI 10.1158/1538-7445.AM2013-1347 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600131 ER PT J AU Lu-Emerson, C Snuderl, M Kirkpatrick, ND Goveia, J Taylor, J Davidson, C Huang, YH Riedemann, L Ivy, SP Duda, GD Ancukiewicz, M Plotkin, SR Chi, A Gerstner, ER Eichler, AF Dietrich, J Stemmer-Rachamimov, AO Batchelor, TT Jain, RK AF Lu-Emerson, Christine Snuderl, Matija Kirkpatrick, Nathaniel D. Goveia, Jermaine Taylor, Jennie Davidson, Christian Huang, Yuhui Riedemann, Lars Ivy, S. Percy Duda, G. Dan Ancukiewicz, Marek Plotkin, Scott R. Chi, Andrew Gerstner, Elizabeth R. Eichler, April F. Dietrich, Jorg Stemmer-Rachamimov, Anat O. Batchelor, Tracy T. Jain, Rakesh K. TI Increase in tumor-associated macrophages (TAMs) after antiangiogenic therapy is associated with poor survival in recurrent glioblastoma (GBM) patients SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Lu-Emerson, Christine] Maine Med Ctr, Scarborough, ME USA. [Snuderl, Matija] NYU, Langone Med Ctr, New York, NY USA. [Kirkpatrick, Nathaniel D.; Goveia, Jermaine; Taylor, Jennie; Davidson, Christian; Huang, Yuhui; Riedemann, Lars; Duda, G. Dan; Ancukiewicz, Marek; Plotkin, Scott R.; Chi, Andrew; Gerstner, Elizabeth R.; Eichler, April F.; Dietrich, Jorg; Stemmer-Rachamimov, Anat O.; Batchelor, Tracy T.; Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ivy, S. Percy] NCI, Bethesda, MD 20892 USA. RI Riedemann, Lars/J-5725-2014; OI Riedemann, Lars/0000-0002-9510-1845; Snuderl, Matija/0000-0003-0752-0917 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB339 DI 10.1158/1538-7445.AM2013-LB-339 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601263 ER PT J AU Lui, VWY Van Allen, E Li, H Zhang, F Zeng, Y Johnson, JT Garraway, LA Mills, GB Grandis, JR AF Lui, Vivian W. Y. Van Allen, Eliezer Li, Hua Zhang, Fan Zeng, Yan Johnson, Jonas T. Garraway, Levi A. Mills, Gordon B. Grandis, Jennifer Rubin TI Whole exome sequencing links MAPK1 mutation to exquisite sensitivity to brief erlotinib monotherapy in head and neck cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Lui, Vivian W. Y.; Li, Hua; Zeng, Yan; Johnson, Jonas T.; Grandis, Jennifer Rubin] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Van Allen, Eliezer; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. RI Lui, Vivian/I-5458-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4565 DI 10.1158/1538-7445.AM2013-4565 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604165 ER PT J AU Maertens, O Johnson, B Hollstein, P Frederick, D Cooper, Z Messiaen, L Bronson, R McMahon, M Granter, S Flaherty, K Wargo, J Marais, R Cichowski, K AF Maertens, Ophella Johnson, Bryan Hollstein, Pablo Frederick, Dennie Cooper, Zachary Messiaen, Ludwine Bronson, Roderick McMahon, Martin Granter, Scott Flaherty, Keith Wargo, Jennier Marais, Richard Cichowski, Karen TI Elucidating distinct roles for NF1 in melanomagenesis. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Maertens, Ophella; Johnson, Bryan; Hollstein, Pablo; Bronson, Roderick; Granter, Scott; Cichowski, Karen] Brigham & Womens Hosp, Boston, MA USA. [Maertens, Ophella; Johnson, Bryan; Hollstein, Pablo; Bronson, Roderick; Granter, Scott; Cichowski, Karen] Harvard Med Sch, Boston, MA USA. [Frederick, Dennie; Cooper, Zachary; Flaherty, Keith; Wargo, Jennier] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Messiaen, Ludwine] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 5201 DI 10.1158/1538-7445.AM2013-5201 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220605295 ER PT J AU McEachern, KA Cao, YC DuPont, R Pablo, L McCoon, P Cortes, JE DeAngelo, DJ Minden, MD Hewes, B Brown, JL Barrett, C AF McEachern, Kristen A. Cao, Yichen DuPont, Rachel Pablo, Lourdes McCoon, Patricia Cortes, Jorge E. DeAngelo, Daniel J. Minden, Mark D. Hewes, Becker Brown, Jeffrey L. Barrett, Carl TI AZD1208 PIM kinase inhibitor - Preliminary evidence of target pathway inhibition in Phase I clinical trials of AML SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [McEachern, Kristen A.; Cao, Yichen; DuPont, Rachel; Pablo, Lourdes; McCoon, Patricia; Hewes, Becker; Brown, Jeffrey L.; Barrett, Carl] AstraZeneca R&D Boston, Waltham, MA USA. [Cortes, Jorge E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Minden, Mark D.] Princess Margaret Canc Ctr, Toronto, ON, Canada. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3516 DI 10.1158/1538-7445.AM2013-3516 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220602220 ER PT J AU Miao, BC Zhang, JM Ji, ZY Njauw, CN Taylor, M Kumar, R Gray, N Tsao, HS AF Miao, Benchun Zhang, Jianming Ji, Zhenyu Njauw, Ching Ni Taylor, Michael Kumar, Raj Gray, Nathanael Tsao, Hensin TI Pharmacologic inhibition of EphA2 in NRAS and BRAF mutant melanomas. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Miao, Benchun; Ji, Zhenyu; Njauw, Ching Ni; Taylor, Michael; Kumar, Raj; Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhang, Jianming; Gray, Nathanael] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 5605 DI 10.1158/1538-7445.AM2013-5605 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220606083 ER PT J AU Mitchell-Ryan, SK Wang, L Orr, S Kugel, S Cherian, C Gangjee, A Matherly, LH AF Mitchell-Ryan, Shermaine K. Wang, Lei Orr, Steven Kugel, Sita Cherian, Christina Gangjee, Aleem Matherly, Larry H. TI Novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate regioisomers target folate receptor alpha positive ovarian cancer cells via inhibition of de novo purine nucleotide biosynthesis SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Mitchell-Ryan, Shermaine K.; Matherly, Larry H.] Wayne State Univ, Sch Med, Detroit, MI USA. [Wang, Lei; Gangjee, Aleem] Duquesne Univ, Pittsburgh, PA 15219 USA. [Orr, Steven; Cherian, Christina] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Kugel, Sita] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 5494 DI 10.1158/1538-7445.AM2013-5494 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220605373 ER PT J AU Montero, J Letai, A AF Montero, Joan Letai, Anthony TI Personalizing cancer therapy using dynamic BH3 profiling SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Montero, Joan; Letai, Anthony] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4569 DI 10.1158/1538-7445.AM2013-4569 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604169 ER PT J AU Mudge, DK Serhan, K Bielenberg, DR Hwang, SH Hammock, BD Kieran, MW Panigrahy, D AF Mudge, Dayna K. Serhan, Karolina Bielenberg, Diane R. Hwang, Sung Hee Hammock, Bruce D. Kieran, Mark W. Panigrahy, Dipak TI Control of tumor lymphangiogenesis by epoxyeicosanoids SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Mudge, Dayna K.; Serhan, Karolina; Bielenberg, Diane R.; Panigrahy, Dipak] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Hwang, Sung Hee; Hammock, Bruce D.] Univ Calif Davis, Davis, CA 95616 USA. [Kieran, Mark W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4961 DI 10.1158/1538-7445.AM2013-4961 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220605059 ER PT J AU Muvaffak, A Pan, Q Middleton, R Morris, E Fernandez, R Lim, J Dolinski, B Nguyen, TT Strack, P Yan, HY Chung, R Wu, S Zriang, WQ Hulton, C Hirsch, H Nagashimo, K Wang, Y AF Muvaffak, Asli Pan, Qi Middleton, Richard Morris, Erick Fernandez, Rafael Lim, Jonwong Dolinski, Brian Nguyen, Thi T. Strack, Peter Yan, Haiyan Chung, Rossana Wu, Stephen Zriang, Weiqun Hulton, Chris Hirsch, Heather Nagashimo, Kumiko Wang, Yan TI Evaluating TBK1 as a cancer therapeutic target in cancer cell lines with activated IRF3 SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Muvaffak, Asli; Pan, Qi; Middleton, Richard; Yan, Haiyan; Chung, Rossana; Wu, Stephen; Zriang, Weiqun; Hulton, Chris] Dana Farber Canc Inst, Beifer Inst Appl Canc Sci, Boston, MA 02115 USA. [Morris, Erick; Fernandez, Rafael; Lim, Jonwong; Dolinski, Brian; Nguyen, Thi T.; Strack, Peter; Hirsch, Heather; Nagashimo, Kumiko; Wang, Yan] Merck Res Labs, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4372 DI 10.1156/1538-7445.M2013-4372 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603379 ER PT J AU Namba, T Tian, F Chu, KK Hwang, SY Lee, SW AF Namba, Takushi Tian, Fang Chu, Kiki Hwang, So-Young Lee, Sam W. TI CDIP-BAP31 complex bridges endoplasmic reticulum and mitochondria during ER-stress mediated apoptosis SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4605 DI 10.1158/1538-7445.AM2013-4605 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604191 ER PT J AU Nimptsch, K Zhang, XH Giovannucci, E Cassidy, A O'Reilly, EJ Pischon, T Rimm, EB Lin, J Willett, WC Fuchs, CS Wu, K AF Nimptsch, Katharina Zhang, Xuehong Giovannucci, Edward Cassidy, Aedin O'Reilly, Ellis J. Pischon, Tobias Rimm, Eric B. Lin, Jennifer Willett, Walter C. Fuchs, Charles S. Wu, Kana TI Habitual intake of total flavonoids and flavonoid subclasses and risk of colorectal cancer in men and women SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Nimptsch, Katharina; Pischon, Tobias] Max Delbruck Ctr Mol Med, Berlin, Germany. [Zhang, Xuehong] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Zhang, Xuehong] Harvard Univ, Sch Med, Boston, MA USA. [Giovannucci, Edward; O'Reilly, Ellis J.; Rimm, Eric B.; Willett, Walter C.; Wu, Kana] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cassidy, Aedin] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Lin, Jennifer] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4820 DI 10.1158/1538-7445.AM2013-4820 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600353 ER PT J AU Norris, MD Gamble, LD Murray, J Purqato, S Miiazzo, G Ashton, LJ Oberthuer, A London, WB Hogarty, MD Fischer, M Ziegler, D Marshall, GM Perini, G Haber, M AF Norris, Murray D. Gamble, Laura D. Murray, Jayne Purqato, Stefania Miiazzo, Giorgio Ashton, Lesley J. Oberthuer, Andrei London, Wendy B. Hogarty, Mike D. Fischer, Mattias Ziegler, David Marshall, Glenn M. Perini, Giovanni Haber, Michelle TI MYCN coordinately regulates the entire polyamine gene pathway to drive polyamine biosynthesis in neuroblastoma, with expression of every synthetic and catabolic polyamine pathway gene being highly prognostic of clinical outcome SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Norris, Murray D.; Gamble, Laura D.; Murray, Jayne; Ashton, Lesley J.; Haber, Michelle] Childrens Canc Inst Australia, Sydney, NSW, Australia. [Purqato, Stefania; Miiazzo, Giorgio] Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy. [Oberthuer, Andrei; Fischer, Mattias] Univ Cologne, Dept Pediat Oncol & Hematol, Childrens Hosp Cologne, Cologne, Germany. [London, Wendy B.] Dana Farber Harvard Canc Ctr, Childrens Oncol Grp Stat, Boston, MA USA. [London, Wendy B.] Dana Farber Harvard Canc Ctr, Ctr Data, Boston, MA USA. [London, Wendy B.] Childrens Hosp, Boston, MA 02115 USA. [Hogarty, Mike D.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ziegler, David; Marshall, Glenn M.] Sydney Childrens Hosp, Sydney, NSW, Australia. [Ziegler, David; Marshall, Glenn M.] Childrens Canc Inst Australia, Sydney, NSW, Australia. [Perini, Giovanni] Univ Bologna, Interdept Ctr Ind Res HST ICIR, Bologna, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3808 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603042 ER PT J AU Ojesina, AI Lichtenstein, L Ambrogio, L Cibulskis, K Freeman, S Pedamallu, CS Bertelsen, B Imaz, I Vazquez, K Guadarrama, AS Trevino, V Romero-Cordoba, S Duke, F Kaplan, B Rodriguez, I Castilla, ME Woie, K Bjorge, L Wik, E Halle, MK Hoivik, E Krakstad, C Macias, GG Rodriguez, MDLG Vazquez, J Rodea, C Cravioto, A Cortes, ML Greulich, H Crum, CP Akslen, L Saldana, HB Melendez-Zajgla, J Getz, G Salvesen, HB Meyerson, ML AF Ojesina, Akinyemi I. Lichtenstein, Lee Ambrogio, Lauren Cibulskis, Kristian Freeman, Samuel Pedamallu, Chandra Sekhar Bertelsen, Bjorn Imaz, Ivan Vazquez, Karla Salido Guadarrama, Alberto Trevino, Victor Romero-Cordoba, Sandra Duke, Fujiko Kaplan, Bethany Rodriguez, Iram Espinosa Castilla, Magali Woie, Katherine Bjorge, Line Wik, Elisabeth Halle, Mari K. Hoivik, Erling Krakstad, Camilla Gomez Macias, Gabriela Garza Rodriguez, Maria de Lourdes Vazquez, Jorge Rodea, Carlos Cravioto, Adrian Cortes, Maria L. Greulich, Heidi Crum, Christopher P. Akslen, Lars Barrera Saldana, Hugo Melendez-Zajgla, Jorge Getz, Gad Salvesen, Helga B. Meyerson, Matthew L. TI Landscape of human and viral genomic alterations in cervical carcinomas SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Meyerson, Matthew L.] Dana Farber Canc Inst, Broad Inst, Cambridge, MA USA. [Lichtenstein, Lee; Ambrogio, Lauren; Cibulskis, Kristian; Freeman, Samuel; Bertelsen, Bjorn; Cortes, Maria L.; Getz, Gad] Broad Inst, Cambridge, MA USA. [Bertelsen, Bjorn; Woie, Katherine; Bjorge, Line; Wik, Elisabeth; Halle, Mari K.; Hoivik, Erling; Krakstad, Camilla; Akslen, Lars; Salvesen, Helga B.] Haukeland Hosp, Bergen, Norway. [Imaz, Ivan; Vazquez, Karla; Salido Guadarrama, Alberto; Romero-Cordoba, Sandra; Espinosa Castilla, Magali; Melendez-Zajgla, Jorge] Inst Nacl Med Genom, Mexico City, DF, Mexico. [Trevino, Victor] Inst Tecnol & Estudios Super, Monterrey, Mexico. [Duke, Fujiko; Kaplan, Bethany] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodriguez, Iram; Barrera Saldana, Hugo] Univ Autonoma Nuevo Leon, Monterrey, Mexico. [Gomez Macias, Gabriela] Univ Autonoma Nuevo Leon, Mexico City, DF, Mexico. [Vazquez, Jorge; Rodea, Carlos; Cravioto, Adrian] Ctr Med Nacl SXXI, Mexico City, DF, Mexico. [Crum, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Trevino, Victor/C-9219-2009; Romero-Cordoba, Sandra Lorena/A-2246-2014; Akslen, Lars /C-1202-2017; Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017 OI Trevino, Victor/0000-0002-7472-9844; Ojesina, Akinyemi/0000-0003-0755-3639; Romero-Cordoba, Sandra Lorena/0000-0002-5591-696X; Akslen, Lars /0000-0003-2710-9543; Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4604 DI 10.1158/1538-7445.AM2013-4604 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604190 ER PT J AU Ondracek, RP Mohler, JL Pilarz, C McEvoy, S Kasza, K Morrison, C Marshall, J AF Ondracek, Rochelle P. Mohler, James L. Pilarz, Catherine McEvoy, Sarah Kasza, Karin Morrison, Carl Marshall, James TI Comparison of manual and automated scoring of androgen receptor staining in prostate tissue SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Ondracek, Rochelle P.; Mohler, James L.; McEvoy, Sarah; Kasza, Karin; Morrison, Carl; Marshall, James] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Pilarz, Catherine] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4852 DI 10.1158/1538-7445.AM2013-4852 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600384 ER PT J AU Polyak, K AF Polyak, Kornelia TI Regulators of in situ to invasive breast carcinoma progression. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Polyak, Kornelia] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA SY0201 DI 10.1158/1538-7445.AM2013-SY02-01 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601353 ER PT J AU Pugh, TJ Yu, WY Yang, JD Ambrogio, L Carter, SL Kiezun, A McKenna, A Giannikopoulos, P Getz, G Messinger, Y Meyerson, M Hill, DA AF Pugh, Trevor J. Yu, Weiying Yang, Jiandong Ambrogio, Lauren Carter, Scott L. Kiezun, Adam McKenna, Aaron Giannikopoulos, Petros Getz, Gad Messinger, Yoav Meyerson, Matthew Hill, D. Ashley TI Progressive biallelic loss of TP53 is associated with progression of pleuropulmonary blastoma initiated by germline loss and somatic mutation of DICER1 SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Pugh, Trevor J.; Ambrogio, Lauren; Carter, Scott L.; Kiezun, Adam; McKenna, Aaron; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA USA. [Yu, Weiying; Yang, Jiandong; Hill, D. Ashley] Childrens Natl Med Ctr, Ctr Genet Med Res, Washington, DC 20010 USA. [Yu, Weiying; Yang, Jiandong; Hill, D. Ashley] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. [Giannikopoulos, Petros] Canc Therapeut Innovat Grp, New York, NY USA. [Messinger, Yoav] Childrens Hosp, Minneapolis, MN USA. [Messinger, Yoav] Clin Minnesota, Minneapolis, MN USA. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3806 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603040 ER PT J AU Puissant, A Frumm, SM Alexe, G Bassii, CF Qi, J Chanthery, YH Nekritz, EA Zeid, R Gustafson, WC Greninger, P Garnett, MJ McDermott, U Benes, CH Kung, AL Weiss, WA Bradner, JE Stegmaier, K AF Puissant, Alexandre Frumm, Stacey M. Alexe, Gabriela Bassii, Christopher F. Qi, Jun Chanthery, Yvan H. Nekritz, Erin A. Zeid, Rhamy Gustafson, W. Clay Greninger, Patricia Garnett, Matthew J. McDermott, Ultan Benes, Cyril H. Kung, Andrew L. Weiss, William A. Bradner, James E. Stegmaier, Kimberly TI Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Puissant, Alexandre; Frumm, Stacey M.; Alexe, Gabriela; Bassii, Christopher F.; Qi, Jun; Chanthery, Yvan H.; Nekritz, Erin A.; Zeid, Rhamy; Gustafson, W. Clay; Greninger, Patricia; Garnett, Matthew J.; McDermott, Ultan; Benes, Cyril H.; Kung, Andrew L.; Weiss, William A.; Bradner, James E.; Stegmaier, Kimberly] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4622 DI 10.1158/1538-7445.AM2013-4622 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604208 ER PT J AU Raamanathan, A Lu, Z Bast, RC Skates, SJ AF Raamanathan, Archana Lu, Zhen Bast, Robert C. Skates, Steven J. TI Intra-person and inter-person biomarker variation for modeling longitudinal values of ovarian cancer early detection biomarkers. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Raamanathan, Archana; Lu, Zhen; Bast, Robert C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Skates, Steven J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skates, Steven J.] Harvard Univ, Sch Med, Boston, MA USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3473 DI 10.1158/1538-7445.AM2013-3473 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220602178 ER PT J AU Roberts, CWM AF Roberts, Charles W. M. TI The SWI/SNF chromatin remodeling complex is frequently mutated in cancer: Mechanisms and potential therapeutic insights. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Roberts, Charles W. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA SY0701 DI 10.1158/1538-7445.AM2013-SY07-01 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601363 ER PT J AU Rodon, J Juric, D Gonzalez-Angulo, AM Bendell, J Berlin, J Bootle, D Gravelin, K Huang, A Derti, A Lehar, J Wurthner, J Boehm, M van Allen, E Wagle, N Garraway, LA Yelensky, R Stephens, PJ Miller, VA Schlegel, R Quadt, C Baselga, J AF Rodon, Jordi Juric, Dejan Gonzalez-Angulo, Ana-Maria Bendell, Johanna Berlin, Jordan Bootle, Douglas Gravelin, Kathlene Huang, Alan Derti, Adnan Lehar, Joseph Wuerthner, Jens Boehm, Markus van Allen, Eliezer Wagle, Nikhil Garraway, Levi A. Yelensky, Roman Stephens, Philip J. Miller, Vincent A. Schlegel, Robert Quadt, Cornelia Baselga, Jose TI Towards defining the genetic framework for clinical response to treatment with BYL719, a PI3Kalpha-specific inhibitor. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Rodon, Jordi] Vail dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain. [Juric, Dejan] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Gonzalez-Angulo, Ana-Maria] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bendell, Johanna] Sarah Cannon Res Inst, Nashville, TN USA. [Berlin, Jordan] Vanderbilt Canc Ctr, Nashville, TN USA. [Bootle, Douglas; Wuerthner, Jens; Boehm, Markus; Quadt, Cornelia] Novartis Pharma AG, Oncol Translat Med, Basel, Switzerland. [Gravelin, Kathlene; Huang, Alan; Derti, Adnan; Lehar, Joseph; Schlegel, Robert] NIBR Inc, Oncol Translat Med, Cambridge, MA USA. [van Allen, Eliezer; Wagle, Nikhil; Garraway, Levi A.] Broad Inst, Cambridge, MA USA. [Yelensky, Roman; Stephens, Philip J.; Miller, Vincent A.] Fdn Med Inc, Cambridge, MA USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB65 DI 10.1158/1538-7445.AM2013-LB-65 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601313 ER PT J AU Russo, V Raccosta, L Fontana, R Maggioni, D Lanterna, C Paniccia, A Musumeci, A Doglioni, C Leiva, A Villablanca, EJ Mora, R Chiricozzi, E Ciampa, MG Mauri, L Prinetti, A Sonino, S Trincavelli, ML Daniele, S Martini, C Steffensen, K Gustafsson, JA Feo, SG Bordignon, C Traversari, C Sozzani, S AF Russo, Vincenzo Raccosta, Laura Fontana, Raffaella Maggioni, Daniela Lanterna, Claudia Paniccia, Aida Musumeci, Andrea Doglioni, Claudio Leiva, Andrea Villablanca, Eduardo J. Mora, Rodrigo Chiricozzi, Elena Ciampa, Maria Grazia Mauri, Laura Prinetti, Alessandro Sonino, Sandro Trincavelli, Maria Letizia Daniele, Simona Martini, Claudia Steffensen, Knut Gustafsson, Jan-Ake Feo, Safive Gozalvo Bordignon, Claudio Traversari, Catia Sozzani, Silvano TI The Oxysterol-CXCR2 axis plays a key role in the recruitment of tumor promoting neutrophils SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Russo, Vincenzo; Raccosta, Laura; Fontana, Raffaella; Maggioni, Daniela; Lanterna, Claudia; Paniccia, Aida; Musumeci, Andrea; Doglioni, Claudio; Leiva, Andrea] Ist Sci San Raffaele, I-20132 Milan, Italy. [Villablanca, Eduardo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mora, Rodrigo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chiricozzi, Elena; Ciampa, Maria Grazia; Mauri, Laura; Prinetti, Alessandro; Sonino, Sandro] Univ Milan, Milan, Italy. [Trincavelli, Maria Letizia; Daniele, Simona; Martini, Claudia] Univ Pisa, Pisa, Italy. [Steffensen, Knut] Karolinska Inst, Huddinge, Sweden. [Gustafsson, Jan-Ake] Univ Houston, Huddhoustoninge, TX USA. [Feo, Safive Gozalvo] Humanitas Clin & Res Ctr, Milan, Italy. [Bordignon, Claudio; Traversari, Catia] MolMed SpA, Milan, Italy. [Sozzani, Silvano] Univ Brescia, Brescia, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB346 DI 10.1158/1538-7445.AM2013-LB-346 PG 2 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601271 ER PT J AU Sasaki, MM Skol, AD Pugh, TJ Meyerson, M Onel, K AF Sasaki, Mark M. Skol, Andrew D. Pugh, Trevor J. Meyerson, Matthew Onel, Kenan TI Whole exome sequencing analysis of familial Medulloblastoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Sasaki, Mark M.; Skol, Andrew D.; Onel, Kenan] Univ Chicago, Chicago, IL 60637 USA. [Pugh, Trevor J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4018 DI 10.1158/1538-7445.AM2013-4018 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603250 ER PT J AU Scaltriti, M Tao, J Juric, D Auricchio, N Castel, P Morse, N Kim, P Singh, S Hazra, S Hembrough, T Burrows, J Baselga, J AF Scaltriti, Maurizio Tao, Jessica Juric, Dejan Auricchio, Neil Castel, Pau Morse, Natasha Kim, Phillip Singh, Sharat Hazra, Saswati Hembrough, Todd Burrows, Jon Baselga, Jose TI Combined blockade of PI3K/AKT and EGFR/HER3 enhances antitumor activity in triple negative breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Scaltriti, Maurizio; Castel, Pau; Morse, Natasha; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Tao, Jessica; Juric, Dejan; Auricchio, Neil] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kim, Phillip; Singh, Sharat; Hazra, Saswati] Prometheus Lab Therapeut & Diagnost, San Diego, CA USA. [Hembrough, Todd; Burrows, Jon] OncoPlexDx, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4471 DI 10.1158/1538-7445.AM2013-4471 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604076 ER PT J AU Serra, V Eichhorn, PJA Garcia-Garcia, C Ibrahim, Y Prudkin, L Rodriguez, O Marlow, S Prat, A Hahn, WC Baselga, J AF Serra, Violeta Eichhorn, Pieter J. A. Garcia-Garcia, Celina Ibrahim, Yasir Prudkin, Ludmila Rodriguez, Olga Marlow, Sara Prat, Aleix Hahn, William C. Baselga, Jose TI p90RSK mediates resistance to PI3K-pathway inhibitors in breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Serra, Violeta; Garcia-Garcia, Celina; Ibrahim, Yasir; Prudkin, Ludmila; Rodriguez, Olga; Prat, Aleix] Vall dHebron Inst Oncol, Barcelona, Spain. [Eichhorn, Pieter J. A.; Marlow, Sara] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Baselga, Jose] MSKCC, New York, NY USA. RI Prat, Aleix/P-8561-2014 OI Prat, Aleix/0000-0003-2377-540X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4452 DI 10.1158/1538-7445.AM2013-4452 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604057 ER PT J AU Shapiro, GI Hilton, J Cleary, JM Tolaney, SM Ghandi, L Kwak, EL Clark, JW Wolanski, A Bell, T Schulz, J Frame, S Saladino, C Hogben, M Rodig, SJ Chiao, JH Blake, D AF Shapiro, Geoffrey I. Hilton, John Cleary, James M. Tolaney, Sara M. Ghandi, Leena Kwak, Eunice L. Clark, Jeffrey W. Wolanski, Andrew Bell, Tracy Schulz, John Frame, Sheelagh Saladino, Chiara Hogben, Morag Rodig, Scott J. Chiao, Judy H. Blake, David TI Responses to sequential sapacitabine and seliciclib in patients with BRCA-deficient solid tumors. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Shapiro, Geoffrey I.; Hilton, John; Cleary, James M.; Tolaney, Sara M.; Ghandi, Leena; Wolanski, Andrew; Bell, Tracy; Schulz, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kwak, Eunice L.; Clark, Jeffrey W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Frame, Sheelagh; Saladino, Chiara; Hogben, Morag; Chiao, Judy H.; Blake, David] Cyclacel Ltd, Dundee, Scotland. [Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB202 DI 10.1158/1538-7445.AM2013-LB-202 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601133 ER PT J AU Shaw, DL Lin, CY Oakley, RP Semenkovich, NP Qi, J Bradner, JE AF Shaw, Daniel L. Lin, Charles Y. Oakley, Richard P. Semenkovich, Nicholas P. Qi, Jun Bradner, James E. TI Open innovation drug discovery: A study in JQ1. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Shaw, Daniel L.; Lin, Charles Y.; Oakley, Richard P.; Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Semenkovich, Nicholas P.] Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB-2 DI 10.1158/1538-7445.AM2013-LB-2 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601019 ER PT J AU Song, MY Wu, KN Ogino, S Fuchs, CS Giovannucci, EL Chan, AT AF Song, Mingyang Wu, Kana Ogino, Shuji Fuchs, Charles S. Giovannucci, Edward L. Chan, Andrew T. TI A prospective study of plasma inflammatory markers and risk of colorectal cancer in men SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Song, Mingyang; Wu, Kana; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ogino, Shuji; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji; Fuchs, Charles S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 103 DI 10.1158/1538-7445.AM2013-103 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600074 ER PT J AU Stojenov, P Carter, SL Rosshandler, II Sivachenko, A Guadarrama, AS Vazquez, K Cordoba, SR Cibulskis, K Sougnez, C Voet, D Saksena, G Lichtenstein, L Zou, L Frazer, S Stewart, C Beroukhim, R Meyerson, M Lawrence, MS Getz, G AF Stojenov, Petar Carter, Scott L. Rosshandler, Ivan Imaz Sivachenko, Andrey Guadarrama, Alberto Salido Vazquez, Karie Cordoba, Sandra Romero Cibulskis, Kristian Sougnez, Carrie Voet, Douglas Saksena, Gordon Lichtenstein, Lee Zou, Lihua Frazer, Scott Stewart, Chip Beroukhim, Rameen Meyerson, Matthew Lawrence, Michael S. Getz, Gad TI Analysis of formalin-fixed paraffin-embedded (FFPE) samples. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Stojenov, Petar; Carter, Scott L.; Sivachenko, Andrey; Cibulskis, Kristian; Sougnez, Carrie; Voet, Douglas; Saksena, Gordon; Lichtenstein, Lee; Zou, Lihua; Frazer, Scott; Stewart, Chip; Lawrence, Michael S.; Getz, Gad] Broad Inst, Cambridge, MA USA. [Rosshandler, Ivan Imaz; Guadarrama, Alberto Salido; Vazquez, Karie; Cordoba, Sandra Romero] INMEGEN, Mexico City, DF, Mexico. [Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 5135 DI 10.1158/1538-7445.AM2013-5135 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220605231 ER PT J AU Stylianopoulos, T Martin, JD Jain, S Snuderl, M Chauhan, VP Munn, LL Boucher, Y Jain, RK AF Stylianopoulos, Triantafyllos Martin, John D. Jain, Saloni Snuderl, Matija Chauhan, Vikash P. Munn, Lance L. Boucher, Yves Jain, Rakesh K. TI Evolution of physical forces in the tumor microenvironment and implications for therapeutic resistance SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Stylianopoulos, Triantafyllos] Univ Cyprus, Nicosia, Cyprus. [Martin, John D.; Jain, Saloni; Snuderl, Matija; Chauhan, Vikash P.; Munn, Lance L.; Boucher, Yves; Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martin, John D.; Jain, Saloni; Snuderl, Matija; Chauhan, Vikash P.; Munn, Lance L.; Boucher, Yves; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB348 DI 10.1158/1538-7445.AM2013-LB-348 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601273 ER PT J AU Sweeney, CJ Zukotynski, K Wang, XD Wick, A Fredericks, A Lam, B Kantoff, P AF Sweeney, Christopher J. Zukotynski, Katherine Wang, Xiaodong Wick, Andrew Fredericks, Amanda Lam, Bon Kantoff, Philip TI Cabozantinib (cabo) plus abiraterone (abi) combination therapy in castration resistant prostate cancer (CRPC): preclinical evaluation and interim results of an investigator-sponsored phase 1 clinical study. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Sweeney, Christopher J.; Zukotynski, Katherine; Wang, Xiaodong; Wick, Andrew; Fredericks, Amanda; Lam, Bon; Kantoff, Philip] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB166 DI 10.1158/1538-7445.AM2013-LB-166 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601102 ER PT J AU Tanizaki, J Okamoto, I Okabe, T Sakai, K Tanaka, K Hayashi, H Kaneda, H Takezawa, K Nishio, K Nakagawa, K AF Tanizaki, Junko Okamoto, Isamu Okabe, Takafumi Sakai, Kazuko Tanaka, Kaoru Hayashi, Hidetoshi Kaneda, Hiroyasu Takezawa, Ken Nishio, Kazuto Nakagawa, Kazuhiko TI Activation of HER Family signaling as a mechanism of acquired resistance to ALK Inhibitors in EML4-ALK-positive Non-Small Cell Lung Cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Tanizaki, Junko] Dana Farber Canc Inst, Boston, MA 02115 USA. [Okamoto, Isamu; Okabe, Takafumi; Sakai, Kazuko; Tanaka, Kaoru; Hayashi, Hidetoshi; Kaneda, Hiroyasu; Takezawa, Ken; Nishio, Kazuto; Nakagawa, Kazuhiko] Kinki Univ, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4446 DI 10.1158/1538-7445.AM2013-4446 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604051 ER PT J AU Tavera, LE Westerling, T Brown, M AF Tavera, Luz E. Westerling, Thomas Brown, Myles TI Genome-wide analysis of the vitamin D receptor (VDR) binding sites reveals vitamin D role modulating autophagy and metabolism in luminal-like breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Tavera, Luz E.; Westerling, Thomas; Brown, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3562 DI 10.1158/1538-7445.AM2013-3562 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600214 ER PT J AU Tobi, M Weinstein, D Vizgoft, E Pedersen, S AF Tobi, Martin Weinstein, Douglas Vizgoft, Emma Pedersen, Susanne TI Anti-adenoma Adnab-9 antibody recognizes a serum GI cancer candidate biomarker SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Tobi, Martin; Weinstein, Douglas] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Vizgoft, Emma; Pedersen, Susanne] Clin Genom, N Ryde, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 3499 DI 10.1158/1538-7445.AM2013-3499 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220602203 ER PT J AU Van Allen, EM Wagle, N Keizun, A Kryukov, G McKenna, A Huang, F Hiller, E Rainville, I Auclair, D Ambroaio, L Gray, S Joffe, S Getz, G Garber, J Garraway, L AF Van Allen, Eliezer M. Wagle, Nikhil Keizun, Adam Kryukov, Gregory McKenna, Aaron Huang, Franklin Hiller, Elaine Rainville, Irene Auclair, Daniel Ambroaio, Lauren Gray, Stacy Joffe, Steven Getz, Gad Garber, Judy Garraway, Levi TI An integrated germline analysis platform for comprehensive clinical cancer genomics SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Van Allen, Eliezer M.; Wagle, Nikhil; Huang, Franklin; Hiller, Elaine; Rainville, Irene; Gray, Stacy; Joffe, Steven; Garber, Judy; Garraway, Levi] Dana Farber Canc Inst, Brookline, MA USA. [Keizun, Adam; Kryukov, Gregory; Auclair, Daniel; Ambroaio, Lauren; Getz, Gad] Broad Inst, Cambridge, MA USA. [McKenna, Aaron] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 2570 DI 10.1158/1538-7445.AM2013-2570 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600208 ER PT J AU Walensky, LD AF Walensky, Loren D. TI Stapled helical peptides to dissect and target oncogenic protein interactions. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Walensky, Loren D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA SY0603 DI 10.1158/1538-7445.AM2013-SY06-03 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601362 ER PT J AU Wang, YY Sabbatino, F Ferrone, S Wang, XH AF Wang, Yangyang Sabbatino, Francesco Ferrone, Soldano Wang, Xinhui TI Inhibition of TNBC cell growth by CSPG4-specific mAb 225.28 with a Sonic Hedgehog pathway inhibitor. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4741 DI 10.1158/1538-7445.AM2013-4741 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220604323 ER PT J AU Wong, J Harris, J Rodriguez-Galindo, C Johnson, K AF Wong, Jeannette Harris, Jenine Rodriguez-Galindo, Carlos Johnson, Kimberly TI Incidence trends of childhood and adolescent melanoma in the United States from 1973-2009 SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Wong, Jeannette] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Harris, Jenine] Washington Univ, St Louis, MO USA. [Rodriguez-Galindo, Carlos] Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Johnson, Kimberly] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 2530 DI 10.1158/1538-7445.AM2013-2530 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600169 ER PT J AU Xicola, RMM Doyle, B Rawson, J Garre, P Abuli, A Lee, E Murugappan, S Bessa, X Bujanda, L Balaguer, F Castellvi-Bel, S Clofent, J Alenda, C Jover, R Ruiz-Ponte, C Singal, S Andreu, M Carracedo, A Castells, A Ellis, N Caldes, T LLor, X AF Xicola, Rosa M. Munoz Doyle, Brian Rawson, Jamie Garre, Pilar Abuli, Anna Lee, Esther Murugappan, Sathyaraj Bessa, Xavier Bujanda, Luis Balaguer, Francesc Castellvi-Bel, Sergi Clofent, Juan Alenda, Cristina Jover, Rodrigo Ruiz-Ponte, Clara Singal, Sapna Andreu, Montserrat Carracedo, Angel Castells, Antoni Ellis, Nathan Caldes, Trinidad LLor, Xavier TI Implication of the 3 ' UTR region of TGF beta R1 with MSS HNPCC and sporadic colorectal cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Xicola, Rosa M. Munoz; Doyle, Brian; Rawson, Jamie; Lee, Esther; Murugappan, Sathyaraj; Ellis, Nathan; LLor, Xavier] UIC, Chicago, IL USA. [Garre, Pilar] Hosp Clin San Carlos, Madrid, Spain. [Abuli, Anna; Bessa, Xavier; Andreu, Montserrat] Hosp del Mar, Barcelona, Spain. [Bujanda, Luis] Hosp Donostia, Donostia San Sebastian, Spain. [Balaguer, Francesc; Castellvi-Bel, Sergi; Castells, Antoni] Hosp Clin Barcelona, Barcelona, Spain. [Clofent, Juan] Hosp Sagunto, Valencia, Spain. [Alenda, Cristina; Jover, Rodrigo] Hosp Gen Univ Alacant, Alicante, Spain. [Ruiz-Ponte, Clara; Carracedo, Angel] Univ Santiago de Compostela, Santiago De Compostela, Spain. [Singal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Caldes, Trinidad] Hosp Clin San Carlos, Madrid, Spain. RI Ruiz-Ponte, Clara/I-3849-2015; BALAGUER, FRANCESC/G-2389-2016 OI Ruiz-Ponte, Clara/0000-0002-2200-0162; NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 1334 DI 10.1158/1538-7445.AM2013-1334 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600119 ER PT J AU Zhang, XH Wu, K Cho, E Ma, J Chan, AT Gao, X Willett, WC Fuchs, CS Giovannucci, EL AF Zhang, Xuehong Wu, Kana Cho, Eunyoung Ma, Jing Chan, Andrew T. Gao, Xiang Willett, Walter C. Fuchs, Charles S. Giovannucci, Edward L. TI Prospective cohort studies of bowel movement frequency and laxative use and colorectal cancer incidence in US women and men SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Zhang, Xuehong; Cho, Eunyoung; Ma, Jing; Chan, Andrew T.; Gao, Xiang; Willett, Walter C.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zhang, Xuehong; Cho, Eunyoung; Ma, Jing; Chan, Andrew T.; Gao, Xiang; Willett, Walter C.; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Kana; Gao, Xiang; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4822 DI 10.1158/1538-7445.AM2013-4822 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220600355 ER PT J AU Zon, LI AF Zon, Leonard I. TI Transcriptional regulation and epigenetics in zebrafish cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.] Childrens Hosp, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, HHMI,Harvard Stem Cell Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA SY1601 DI 10.1158/1538-7445.AM2013-SY16-01 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601377 ER PT J AU Cabral, FC Krajewski, KM Kim, KW Ramaiya, NH Jagannathan, JP AF Cabral, Fernanda C. Krajewski, Katherine M. Kim, Kyung Won Ramaiya, Nikhil H. Jagannathan, Jyothi P. TI Peritoneal lymphomatosis: CT and PET/CT findings and how to differentiate between carcinomatosis and sarcomatosis SO CANCER IMAGING LA English DT Review DE Peritoneal lymphomatosis; extranodal lymphoma; peritoneal sarcomatosis; peritoneal carcinomatosis; positron emission tomography ID IMAGING FINDINGS AB Peritoneal lymphomatosis is a rare manifestation of lymphoma, seen most frequently with non-Hodgkin lymphoma, and it is important to be familiar with this condition, because early diagnosis directly affects the management of patients. This review illustrates the spectrum of imaging findings in peritoneal lymphomatosis, highlighting the use of positron emission tomography/computed tomography, showing common and uncommon subtypes of lymphoma associated with this entity, and how to differentiate it from peritoneal carcinomatosis and peritoneal sarcomatosis. C1 [Cabral, Fernanda C.; Krajewski, Katherine M.; Kim, Kyung Won; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Imaging,Sch Med, Boston, MA 02115 USA. RP Cabral, FC (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM fcabral@partners.org NR 11 TC 5 Z9 5 U1 0 U2 1 PU E-MED PI LONDON PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND SN 1470-7330 J9 CANCER IMAGING JI Cancer Imaging PD APR 15 PY 2013 VL 13 IS 2 BP 162 EP 170 DI 10.1102/1470-7330.2013.0018 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 173DM UT WOS:000321058300003 PM 23598428 ER PT J AU Boulant, S Stanifer, M Kural, C Cureton, DK Massol, R Nibert, ML Kirchhausen, T AF Boulant, Steeve Stanifer, Megan Kural, Comert Cureton, David K. Massol, Ramiro Nibert, Max L. Kirchhausen, Tomas TI Similar uptake but different trafficking and escape routes of reovirus virions and infectious subvirion particles imaged in polarized Madin-Darby canine kidney cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CAPSID PROTEIN MU-1; NONENVELOPED VIRUS; MAMMALIAN REOVIRUS; SIGMA-1 PROTEIN; SIALIC-ACID; CRYOELECTRON MICROSCOPY; MONOCLONAL-ANTIBODIES; MEMBRANE PENETRATION; ADHESION MOLECULE; TYPE-1 REOVIRUS AB Polarized epithelial cells that line the digestive, respiratory, and genitourinary tracts form a barrier that many viruses must breach to infect their hosts. Current understanding of cell entry by mammalian reovirus (MRV) virions and infectious subvirion particles (ISVPs), generated from MRV virions by extracellular proteolysis in the digestive tract, are mostly derived from in vitro studies with nonpolarized cells. Recent live-cell imaging advances allow us for the first time to visualize events at the apical surface of polarized cells. In this study, we used spinning-disk confocal fluorescence microscopy with high temporal and spatial resolution to follow the uptake and trafficking dynamics of single MRV virions and ISVPs at the apical surface of live polarized Madin-Darby canine kidney cells. Both types of particles were internalized by clathrin-mediated endocytosis, but virions and ISVPs exhibited strikingly different trafficking after uptake. While virions reached early and late endosomes, ISVPs did not and instead escaped the endocytic pathway from an earlier location. This study highlights the broad advantages of using live-cell imaging combined with single-particle tracking for identifying key steps in cell entry by viruses. C1 [Boulant, Steeve; Kural, Comert; Cureton, David K.; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Boulant, Steeve; Kural, Comert; Cureton, David K.; Kirchhausen, Tomas] Program Cellular & Mol Med, Boston, MA 02115 USA. [Massol, Ramiro] Boston Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Boulant, Steeve; Stanifer, Megan; Cureton, David K.; Nibert, Max L.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. RP Boulant, S (reprint author), Heidelberg Univ, Schaller Res Grp, D-69120 Heidelberg, Germany. EM s.boulant@dkfz-heidelberg.de FU National Institutes of Health [NIH] [U54-AI057159, R01-GM075252, R56-AI067445]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Diseases; Harvard Digestive Disease Consortium Feasibility Award; GlaxoSmithKline fellowship; C.H.S. Foundation FX We thank E. Marino (supported by National Institutes of Health [NIH] grant U54-AI057159, New England Regional Center of Excellence in Biodefense and Emerging Infectious Diseases) for maintaining the imaging resource used in this study. This work was additionally supported by NIH grants R01-GM075252 (T.K.) and R56-AI067445 (M.L.N). S.B. was also supported by a Harvard Digestive Disease Consortium Feasibility Award, a GlaxoSmithKline fellowship, and the C.H.S. Foundation. NR 63 TC 11 Z9 11 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR 15 PY 2013 VL 24 IS 8 BP 1196 EP 1207 DI 10.1091/mbc.E12-12-0852 PG 12 WC Cell Biology SC Cell Biology GA 174BO UT WOS:000321127900011 PM 23427267 ER PT J AU Powis, KM McElrath, TF Hughes, MD Ogwu, A Souda, S Datwyler, SA von Widenfelt, E Moyo, S Nadas, M Makhema, J Machakaire, E Lockman, S Essex, M Shapiro, RL AF Powis, Kathleen M. McElrath, Thomas F. Hughes, Michael D. Ogwu, Anthony Souda, Sajini Datwyler, Saul A. von Widenfelt, Erik Moyo, Sikhulile Nadas, Marisa Makhema, Joseph Machakaire, Esther Lockman, Shahin Essex, Max Shapiro, Roger L. TI High Viral Load and Elevated Angiogenic Markers Associated With Increased Risk of Preeclampsia Among Women Initiating Highly Active Antiretroviral Therapy in Pregnancy in the Mma Bana Study, Botswana SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; viral load; pregnancy; preeclampsia; HAART ID GROWTH-FACTOR; RECEPTOR; AUTOANTIBODIES; INFANTS; DEATH AB Background: Risk factors associated with preeclampsia in HIV-infected women remain largely unknown. Systemic angiogenic imbalance contributes to preeclampsia in HIV-uninfected women, but changes in angiogenic markers after highly active antiretroviral therapy (HAART) initiation have not been studied. Methods: The Mma Bana study randomized 560 HIV-infected, HAART-naive pregnant women with CD4 counts >= 200 cells per cubic millimeter between 26 and 34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine or abacavir/zidovudine/lamivudine. Another 170 participants with CD4 counts less than 200 cells per cubic millimeter initiated nevirapine/zidovudine/lamivudine between 18 and 34 weeks gestation. Characteristics of 11 women who developed preeclampsia were compared with the remaining 722 Mma Bana participants who delivered using logistic regression. Plasma samples drawn at HAART initiation and 1 month later from 60 women without preeclampsia and at HAART initiation for all 11 preeclamptic women were assayed for placental growth factor (PlGF) and soluble FMS toll-like tyrosine kinase-1 (sFlt-1). Results: Pre-HAART viral load greater than 100,000 copies per milliliter was associated with preeclampsia (odds ratio: 5.8, 95% confidence interval: 1.8 to 19.4, P = 0.004). Median pre-HAART PlGF level was lower and sFlt-1 was higher in women who developed preeclampsia vs those who did not (130 vs 992 pg/mL, P = 0.001; 17.5 vs 9.4 pg/mL, P = 0.03, respectively). In multivariate analysis, PlGF and viral load remained significantly associated with preeclampsia. No significant changes in angiogenic factors were noted after 1 month of HAART treatment among non-preeclamptic women. Conclusions: Pre-HAART viral load greater than 100,000 copies per milliliter and PlGF predicted preeclampsia among women starting HAART in pregnancy. Among non-preeclamptic women, HAART treatment did not significantly alter levels of PlGF or sFlt-1 after 1 month of treatment. C1 [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Powis, Kathleen M.; Lockman, Shahin; Essex, Max; Shapiro, Roger L.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Powis, Kathleen M.; Ogwu, Anthony; von Widenfelt, Erik; Moyo, Sikhulile; Makhema, Joseph; Lockman, Shahin; Essex, Max; Shapiro, Roger L.] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [McElrath, Thomas F.] Brigham & Womens Hosp, Div Maternal Fetal Med, Boston, MA 02115 USA. [Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Souda, Sajini] Univ Botswana, Sch Med, Gaborone, Botswana. [Datwyler, Saul A.] Abbott Labs, Abbott Pk, IL 60064 USA. [Nadas, Marisa] Boston Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02118 USA. [Machakaire, Esther] Ctr Dis Control Botswana, Gaborone, Botswana. [Lockman, Shahin] Brigham & Womens Hosp, Infect Dis Unit, Boston, MA 02115 USA. [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Powis, KM (reprint author), 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM kpowis@partners.org RI Moyo, Sikhulile/E-1464-2015 OI Moyo, Sikhulile/0000-0003-3821-4592 FU National Institute of Allergy and Infectious Diseases [U01-AI066454]; Brigham; Women's Global Women's Health; Harvard University Center for AIDS Research grant [P30 AI060354]; National Institute of Child Health and Human Development grant [1K23HD070774-01A1]; Fogarty AITRP grant [D43 TW000004] FX Supported by a grant (U01-AI066454) from the National Institute of Allergy and Infectious Diseases. Funding support from Brigham and Women's Global Women's Health Fellowship supported K.M.P.'s salary during the Mma Bana study and M.N.'s salary during manuscript preparation. K.M P. received salary support from Harvard University Center for AIDS Research grant (P30 AI060354) and National Institute of Child Health and Human Development grant (1K23HD070774-01A1) during the period of manuscript preparation. The Fogarty AITRP grant (D43 TW000004) provided funding for A.O. and S.M. Mma Bana study drugs were provided by Abbott Pharmaceuticals, GlaxoSmithKline, and the government of Botswana. NR 29 TC 11 Z9 12 U1 0 U2 6 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 15 PY 2013 VL 62 IS 5 BP 517 EP 524 DI 10.1097/QAI.0b013e318286d77e PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 146SS UT WOS:000319111800014 PM 23344545 ER PT J AU Plank, RM Ndubuka, NO Wirth, KE Mwambona, JT Kebaabetswe, P Bassil, B Lesetedi, C Magetse, J Nkgau, M Makhema, J Mmalane, M Creek, T Powis, KM Shapiro, R Lockman, S AF Plank, Rebeca M. Ndubuka, Nnamdi O. Wirth, Kathleen E. Mwambona, Janet T. Kebaabetswe, Poloko Bassil, Barbara Lesetedi, Chiapo Magetse, Jane Nkgau, Maggie Makhema, Joseph Mmalane, Mompati Creek, Tracy Powis, Kathleen M. Shapiro, Roger Lockman, Shahin TI A Randomized Trial of Mogen Clamp Versus Plastibell for Neonatal Male Circumcision in Botswana SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE neonatal circumcision; Mogen clamp; plastibell; male circumcision; HIV prevention; Botswana ID INFANT MALE CIRCUMCISION; HIV PREVENTION; COMPLICATIONS; SUCROSE; KENYA; PAIN; MEN AB Background: Male circumcision can reduce the risk of heterosexually acquired HIV-1 infection in men. Neonatal male circumcision (NMC) has many potential advantages over circumcision at older ages, but little is known about its feasibility and safety in resource-limited settings. Methods: We performed a randomized trial in southeastern Botswana of Mogen clamp and Plastibell, 2 commonly used devices for NMC. Follow-up visits occurred at 6 weeks and 4 months postpartum. Adverse events, parental satisfaction, and staff impressions were recorded. Results: Of 302 male neonates randomized, 300 (99%) underwent circumcision, 153 (51%) with Mogen clamp, and 147 (49%) with Plastibell. There were no major adverse events in the Mogen clamp arm, but there were 2 major adverse events in the Plastibell arm (both were a proximally migrated ring that had to be removed by study staff). Minor adverse events were more common with the Mogen clamp compared with the Plastibell, specifically removal of too little skin and formation of skin bridges or adhesions (12 versus 1 and 11 versus 3, respectively, all P < 0.05). Five (3%) infants in the Mogen clamp arm and none in the Plastibell arm had minor bleeding (P = 0.03). More than 94% of mothers reported being highly or completely satisfied with the procedure. Conclusions: NMC can be performed in Botswana with a low rate of adverse events and high parental satisfaction. Although the risk of migration and retention of the Plastibell is small, the Mogen clamp may be safer for NMC in regions where immediate emergent medical attention is not available. C1 [Plank, Rebeca M.; Lockman, Shahin] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Plank, Rebeca M.; Powis, Kathleen M.; Shapiro, Roger; Lockman, Shahin] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Cambridge, MA 02138 USA. [Plank, Rebeca M.; Ndubuka, Nnamdi O.; Wirth, Kathleen E.; Magetse, Jane; Nkgau, Maggie; Makhema, Joseph; Mmalane, Mompati; Powis, Kathleen M.; Shapiro, Roger; Lockman, Shahin] Botswana Harvard Sch Publ Hlth AIDS Initiat Partn, Gaborone, Botswana. [Wirth, Kathleen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Kebaabetswe, Poloko] Univ Botswana, Sch Med, Gaborone, Botswana. [Creek, Tracy] Childrens Healthcare Atlanta, Atlanta, GA USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Powis, Kathleen M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Shapiro, Roger] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA USA. RP Plank, RM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A-4, Boston, MA 02115 USA. EM rplank@partners.org FU NIH from the National Institutes of Allergy and Infectious Diseases [5K23AI084579]; President's Emergency Plan for AIDS Relief (PEPFAR) [U2GPS000941-01]; [08-P0157] FX Supported by NIH 5K23AI084579 from the National Institutes of Allergy and Infectious Diseases (R.M.P.). The study was supported through the President's Emergency Plan for AIDS Relief (PEPFAR) grant U2GPS000941-01, Program No 08-P0157. The content is solely the responsibility of the authors and does not necessarily represent the official views of PEPFAR or the National Institutes of Health. NR 28 TC 19 Z9 21 U1 0 U2 2 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 15 PY 2013 VL 62 IS 5 BP E131 EP E137 DI 10.1097/QAI.0b013e318285d449 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 146SS UT WOS:000319111800002 PM 23314413 ER PT J AU Trautner, BW Bhimani, RD Amspoker, AB Hysong, SJ Garza, A Kelly, PA Payne, VL Naik, AD AF Trautner, Barbara W. Bhimani, Rupal D. Amspoker, Amber B. Hysong, Sylvia J. Garza, Armandina Kelly, P. Adam Payne, Velma L. Naik, Aanand D. TI Development and validation of an algorithm to recalibrate mental models and reduce diagnostic errors associated with catheter-associated bacteriuria SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Catheter-associated bacteriuria; Urinary tract infections; Evidence based guidelines; Diagnostic errors ID URINARY-TRACT-INFECTION; ASYMPTOMATIC BACTERIURIA; INAPPROPRIATE TREATMENT; DISEASES-SOCIETY; NURSING-HOMES; GUIDELINES; CARE; ADULTS; INTERVENTION; RESIDENTS AB Background: Overtreatment of catheter-associated bacteriuria is a quality and safety problem, despite the availability of evidence-based guidelines. Little is known about how guidelines-based knowledge is integrated into clinicians' mental models for diagnosing catheter-associated urinary tract infection (CA-UTI). The objectives of this research were to better understand clinicians' mental models for CA-UTI, and to develop and validate an algorithm to improve diagnostic accuracy for CA-UTI. Methods: We conducted two phases of this research project. In phase one, 10 clinicians assessed and diagnosed four patient cases of catheter associated bacteriuria (n= 40 total cases). We assessed the clinical cues used when diagnosing these cases to determine if the mental models were IDSA guideline compliant. In phase two, we developed a diagnostic algorithm derived from the IDSA guidelines. IDSA guideline authors and non-expert clinicians evaluated the algorithm for content and face validity. In order to determine if diagnostic accuracy improved using the algorithm, we had experts and non-experts diagnose 71 cases of bacteriuria. Results: Only 21 (53%) diagnoses made by clinicians without the algorithm were guidelines-concordant with fair inter-rater reliability between clinicians (Fleiss' kappa = 0.35, 95% Confidence Intervals (CIs) = 0.21 and 0.50). Evidence suggests that clinicians' mental models are inappropriately constructed in that clinicians endorsed guidelines-discordant cues as influential in their decision-making: pyuria, systemic leukocytosis, organism type and number, weakness, and elderly or frail patient. Using the algorithm, inter-rater reliability between the expert and each non-expert was substantial (Cohen's kappa = 0.72, 95% CIs = 0.52 and 0.93 between the expert and non-expert # 1 and 0.80, 95% CIs = 0.61 and 0.99 between the expert and non-expert # 2). Conclusions: Diagnostic errors occur when clinicians' mental models for catheter-associated bacteriuria include cues that are guidelines-discordant for CA-UTI. The understanding we gained of clinicians' mental models, especially diagnostic errors, and the algorithm developed to address these errors will inform interventions to improve the accuracy and reliability of CA-UTI diagnoses. C1 [Trautner, Barbara W.; Amspoker, Amber B.; Hysong, Sylvia J.; Garza, Armandina; Payne, Velma L.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Trautner, Barbara W.; Bhimani, Rupal D.; Amspoker, Amber B.; Hysong, Sylvia J.; Garza, Armandina; Naik, Aanand D.] Baylor Coll Med, Dept Internal Med, Houston, TX 77030 USA. [Kelly, P. Adam] Tulane Univ, Sch Med, Dept Internal Med, New Orleans, LA 70112 USA. [Trautner, Barbara W.] Michael E DeBakey VA Med Ctr 152, Houston, TX 77030 USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. EM anaik@bcm.edu RI Hysong, Sylvia/B-8420-2008 OI Hysong, Sylvia/0000-0002-9063-5207 FU Veterans Administration, Health Services Research and Development Program [IIR 09-104]; Houston VA HSR& D Center of Excellence [HFP90-020]; VA Rehabilitation Research and Development career development award [B4623] FX This work was supported by a grant from the Veterans Administration, Health Services Research and Development Program (IIR 09-104, Trautner PI) and with resources and use of facilities at the Houston VA HSR& D Center of Excellence (HFP90-020) at the Michael E. DeBakey VA. Dr. Trautner received support from a VA Rehabilitation Research and Development career development award (B4623). Dr. Payne receives support from the Office of Academic Affiliations, post-doctoral fellowship program in Health Services Research. Dr. Naik received additional support from a Doris Duke Charitable Foundation Clinical Scientist Development Award. NR 28 TC 17 Z9 18 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD APR 15 PY 2013 VL 13 AR 48 DI 10.1186/1472-6947-13-48 PG 9 WC Medical Informatics SC Medical Informatics GA 151FR UT WOS:000319446600001 PM 23587259 ER PT J AU Geng, Y Sicinski, P AF Geng, Yan Sicinski, Piotr TI Differences in regulation and function of E-cyclins in human cancer cells SO CELL CYCLE LA English DT News Item DE E-type cyclins; cyclin E1; cyclin E2; cell cycle; genomic instability; breast cancer ID INSTABILITY C1 [Sicinski, Piotr] Dana Farber Canc Inst, Dept Genet, Harvard Med Sch, Dept Canc Biol, Boston, MA 02115 USA. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Genet, Harvard Med Sch, Dept Canc Biol, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [R01 CA108950] NR 8 TC 4 Z9 4 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 15 PY 2013 VL 12 IS 8 BP 1165 EP 1165 DI 10.4161/cc.24487 PG 1 WC Cell Biology SC Cell Biology GA 132KX UT WOS:000318067700008 PM 23549169 ER PT J AU Leone, E Morelli, E Di Martino, MT Amodio, N Foresta, U Gulla, A Rossi, M Neri, A Giordano, A Munshi, NC Anderson, KC Tagliaferri, P Tassone, P AF Leone, Emanuela Morelli, Eugenio Di Martino, Maria T. Amodio, Nicola Foresta, Umberto Gulla, Annamaria Rossi, Marco Neri, Antonino Giordano, Antonio Munshi, Nikhil C. Anderson, Kenneth C. Tagliaferri, Pierosandro Tassone, Pierfrancesco TI Targeting miR-21 Inhibits In Vitro and In Vivo Multiple Myeloma Cell Growth SO CLINICAL CANCER RESEARCH LA English DT Article ID BONE-MARROW MICROENVIRONMENT; SUPER-ANTAGONIST SANT7; ANTITUMOR-ACTIVITY; INDUCED APOPTOSIS; GENE-EXPRESSION; CANCER; MICRORNAS; DEXAMETHASONE; IDENTIFICATION; PATHOGENESIS AB Purpose: Deregulated expression of miRNAs plays a role in the pathogenesis and progression of multiple myeloma. Among upregulated miRNAs, miR-21 has oncogenic potential and therefore represents an attractive target for the treatment of multiple myeloma. Experimental Design: Here, we investigated the in vitro and in vivo anti-multiple myeloma activity of miR-21 inhibitors. Results: Either transient-enforced expression or lentivirus-based constitutive expression of miR-21 inhibitors triggered significant growth inhibition of primary patient multiple myeloma cells or interleukin-6-dependent/independent multiple myeloma cell lines and overcame the protective activity of human bone marrow stromal cells. Conversely, transfection of miR-21 mimics significantly increased proliferation of multiple myeloma cells, showing its tumor-promoting potential in multiple myeloma. Importantly, upregulation of miR-21 canonical validated targets (PTEN, Rho-B, and BTG2), together with functional impairment of both AKT and extracellular signal-regulated kinase signaling, were achieved by transfection of miR-21 inhibitors into multiple myeloma cells. In vivo delivery of miR-21 inhibitors in severe combined immunodeficient mice bearing human multiple myeloma xenografts expressing miR-21 induced significant antitumor activity. Upregulation of PTEN and downregulation of p-AKT were observed in retrieved xenografts following treatment with miR-21 inhibitors. Conclusion: Our findings show the first evidence that in vivo antagonism of miR-21 exerts anti-multiple myeloma activity, providing the rationale for clinical development of miR-21 inhibitors in this still incurable disease. Clin Cancer Res; 19(8); 2096-106. (C) 2013 AACR. C1 [Leone, Emanuela; Morelli, Eugenio; Di Martino, Maria T.; Amodio, Nicola; Foresta, Umberto; Gulla, Annamaria; Rossi, Marco; Tagliaferri, Pierosandro; Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Med Oncol Unit, I-88100 Catanzaro, Italy. [Leone, Emanuela; Morelli, Eugenio; Di Martino, Maria T.; Amodio, Nicola; Foresta, Umberto; Gulla, Annamaria; Rossi, Marco; Tagliaferri, Pierosandro; Tassone, Pierfrancesco] T Campanella Canc Ctr, Catanzaro, Italy. [Neri, Antonino] Univ Milan, Dept Med Sci, IRCCS Policlin Fdn, Milan, Italy. [Giordano, Antonio] Univ Siena, Human Pathol & Oncol Dept, I-53100 Siena, Italy. [Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, Boston, MA USA. [Giordano, Antonio; Tassone, Pierfrancesco] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA. RP Tassone, P (reprint author), Magna Graecia Univ Catanzaro, Viale Europa, I-88100 Catanzaro, Italy. EM tassone@unicz.it RI Amodio, Nicola/K-7335-2016; Giordano, Antonio/F-1927-2010; OI Amodio, Nicola/0000-0002-1345-4410; Giordano, Antonio/0000-0002-5959-016X; neri, antonino/0000-0001-9047-5912; ROSSI, Marco/0000-0002-7258-475X FU Italian Association for Cancer Research (AIRC) [9980] FX This work has been supported by funds of Italian Association for Cancer Research (AIRC), Principal Inverstigator: P. Tassone "Special Program Molecular Clinical Oncology-5 per mille" n. 9980, 2010/15. KCA is an American Cancer Society Clinical Research Professor. NR 50 TC 55 Z9 58 U1 4 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2013 VL 19 IS 8 BP 2096 EP 2106 DI 10.1158/1078-0432.CCR-12-3325 PG 11 WC Oncology SC Oncology GA 126FG UT WOS:000317597500019 PM 23446999 ER PT J AU Vachon, CM Suman, VJ Brandt, KR Kosel, ML Buzdar, AU Olson, JE Wu, FF Flickinger, LM Ursin, G Elliott, CR Shepherd, L Weinshilboum, RM Goss, PE Ingle, JN AF Vachon, Celine M. Suman, Vera J. Brandt, Kathleen R. Kosel, Matthew L. Buzdar, Aman U. Olson, Janet E. Wu, Fang-Fang Flickinger, Lynn M. Ursin, Giske Elliott, Catherine R. Shepherd, Lois Weinshilboum, Richard M. Goss, Paul E. Ingle, James N. TI Mammographic Breast Density Response to Aromatase Inhibition SO CLINICAL CANCER RESEARCH LA English DT Article ID HORMONE REPLACEMENT THERAPY; CARCINOMA IN-SITU; POSTMENOPAUSAL WOMEN; CANCER RISK; SEX STEROIDS; TAMOXIFEN; LETROZOLE; ANASTROZOLE; ESTROGEN; REDUCTION AB Purpose: Mammographic breast density (MBD) is decreased by tamoxifen, but the effect of aromatase inhibitors is less clear. Experimental Design: We enrolled early-stage postmenopausal patients with breast cancer initiating adjuvant aromatase inhibitor therapy and ascertained mammograms before and at an average 10 months of aromatase inhibitor therapy. We matched cases to healthy postmenopausal women (controls) from a large mammography screening cohort on age, baseline body mass index, baseline MBD, and interval between mammograms. We estimated change in MBD using a computer-assisted thresholding program (Cumulus) and compared differences between cases and matched controls. Results: In predominantly White women (96%), we found 14% of the 387 eligible cases had a MBD reduction of at least 5% after an average of 10 months of aromatase inhibitor therapy. MBD reductions were associated with higher baseline MBD, aromatase inhibitor use for more than 12 months, and prior postmenopausal hormone use. Comparing each case with her matched control, there was no evidence of an association of change in MBD with aromatase inhibitor therapy [median case-control difference among 369 pairs was -0.1% (10th and 90th percentile: -5.9%, 5.2%) P = 0.51]. Case-control differences were similar by type of aromatase inhibitor (P's 0.41 and 0.56); prior use of postmenopausal hormones (P = 0.85); baseline MBD (P = 0.55); and length of aromatase inhibitor therapy (P = 0.08). Conclusions: In postmenopausal women treated with aromatase inhibitors, 14% of cases had a MBD reduction of more than 5%, but these decreases did not differ from matched controls. These data suggest that MBD is not a clinically useful biomarker for predicting the value of aromatase inhibitor therapy in White postmenopausal women. Clin Cancer Res; 19(8); 2144-53. (C) 2013 AACR. C1 [Vachon, Celine M.; Suman, Vera J.; Brandt, Kathleen R.; Kosel, Matthew L.; Olson, Janet E.; Wu, Fang-Fang; Flickinger, Lynn M.; Weinshilboum, Richard M.; Ingle, James N.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ursin, Giske] Univ Oslo, Oslo, Norway. [Ursin, Giske] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Elliott, Catherine R.; Shepherd, Lois] Queens Univ, Clin Trials Grp, NCIC, Kingston, ON, Canada. [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Vachon, CM (reprint author), Mayo Clin, Dept Hlth Sci Res, Charlton 6-239,200 1st St SW, Rochester, MN 55905 USA. EM vachon.celine@mayo.edu FU NIH, Specialized Program of Research Excellence (SPORE) in Breast Cancer [P50 CA116201, R01 CA97396, R01 CA140286]; Mayo Pharmacogenomics Research Network (PGRN) [U01 GM61388]; Avon Foundation, New York FX This study was supported, in part, by grants from the NIH, Specialized Program of Research Excellence (SPORE) in Breast Cancer, P50 CA116201, R01 CA97396, R01 CA140286, and Mayo Pharmacogenomics Research Network (PGRN), U01 GM61388. P. E. Goss is supported by the Avon Foundation, New York. NR 56 TC 11 Z9 11 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2013 VL 19 IS 8 BP 2144 EP 2153 DI 10.1158/1078-0432.CCR-12-2789 PG 10 WC Oncology SC Oncology GA 126FG UT WOS:000317597500023 PM 23468058 ER PT J AU Robert, C Schadendorf, D Messina, M Hodi, FS O'Day, S AF Robert, Caroline Schadendorf, Dirk Messina, Marianne Hodi, F. Stephen O'Day, Steven CA MDX010-20 Investigators TI Efficacy and Safety of Retreatment with Ipilimumab in Patients with Pretreated Advanced Melanoma Who Progressed after Initially Achieving Disease Control SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTI-CTLA-4 ANTIBODIES; METASTATIC MELANOMA; ADVERSE EVENTS; PHASE-II; CANCER; IMMUNOTHERAPY; ANTIGEN-4; THERAPY; MANAGEMENT; BLOCKADE AB Purpose: Ipilimumab is a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) that has been shown to improve survival in patients with pretreated, advanced melanoma in a phase III trial. Some patients in this study who initially responded to ipilimumab treatment but later progressed were eligible for retreatment with their original randomized regimen. Here, outcomes for these patients concerning baseline characteristics, best overall response, and disease control rate are assessed and considered with respect to the overall study population. Experimental Design: In the phase III study, 676 pretreated patients were randomly allocated to treatment with ipilimumab 3 mg/kg plus gp100 vaccine, ipilimumab 3 mg/kg plus placebo, or gp100 vaccine alone. Of these patients, 32 had a partial or complete objective response or stable disease after treatment and met the eligibility criteria for retreatment, although a total of 40 patients were retreated. Results: Best overall response rates (complete responses plus partial responses) for 31 retreatment-eligible patients in the ipilimumab plus gp100 and ipilimumab plus placebo groups were 3 of 23 (13.0%) and 3 of 8 (37.5%), respectively, and disease control rates were 65.2% and 75.0%. No new types of toxicities occurred during retreatment and most events were mild-to-moderate. Conclusion: Ipilimumab provided durable objective responses and/or stable disease in qualifying patients who received retreatment upon disease progression with a similar toxicity profile to that seen during their original treatment regimen. Clin Cancer Res; 19(8); 2232-9. (C) 2013 AACR. C1 [Robert, Caroline] Inst Gustave Roussy, F-94805 Villejuif, France. [Schadendorf, Dirk] Univ Hosp Essen, Essen, Germany. [Messina, Marianne] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Day, Steven] Beverly Hills Canc Ctr, Beverly Hills, CA USA. RP Robert, C (reprint author), Inst Gustave Roussy, Dept Med, 39 Rue Camille Desmoulins, F-94805 Villejuif, France. EM caroline.robert@igr.fr FU Bristol-Myers Squibb; Bristol-Myers Squibb [NCT00094653] FX C. Robert is a consultant/advisory board member of Bristol-Myers Squibb, Roche, GlaxoSmithKline, and Merck. D. Schadendorf has honoraria from speakers' bureau from Bristol-Myers Squibb and is a consultant/advisory board member of Bristol-Myers Squibb, Roche, Novartis, GlaxoSmithKline, and Amgen. F. S. Hodi has commercial research support and is a consultant/advisory board member of Bristol-Myers Squibb. S. O'Day has a commercial research grant, honoraria from speakers' bureau, and is a consultant/advisory board member of Bristol-Myers Squibb. No potential conflicts of interest were disclosed by the other author.; The MDX010-20 study (trial registration ID: NCT00094653) was funded by Bristol-Myers Squibb. Editorial and writing assistance was provided by StemScientific, funded by Bristol-Myers Squibb. NR 30 TC 58 Z9 58 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2013 VL 19 IS 8 BP 2232 EP 2239 DI 10.1158/1078-0432.CCR-12-3080 PG 8 WC Oncology SC Oncology GA 126FG UT WOS:000317597500032 PM 23444228 ER PT J AU Losman, JA Kaelin, WG AF Losman, Julie-Aurore Kaelin, William G., Jr. TI What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer SO GENES & DEVELOPMENT LA English DT Review DE 2-oxoglutarate-dependent dioxygenase; cancer metabolism; chondrosarcoma; glioma; isocitrate dehydrogenase; leukemia ID ACUTE MYELOID-LEUKEMIA; NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE; CELL SELF-RENEWAL; HEMATOPOIETIC STEM-CELLS; TRICARBOXYLIC-ACID CYCLE; TET2 MUTATIONS; D-2-HYDROXYGLUTARIC ACIDURIA; MYELODYSPLASTIC SYNDROMES; TCA CYCLE; IN-VIVO AB Mutations in metabolic enzymes, including isocitrate dehydrogenase 1 (IDH1) and IDH2, in cancer strongly implicate altered metabolism in tumorigenesis. IDH1 and IDH2 catalyze the interconversion of isocitrate and 2-oxoglutarate (2OG). 2OG is a TCA cycle intermediate and an essential cofactor for many enzymes, including JmjC domain-containing histone demethylases, TET 5-methylcytosine hydroxylases, and EglN prolyl-4-hydroxylases. Cancer-associated IDH mutations alter the enzymes such that they reduce 2OG to the structurally similar metabolite (R)-2-hydroxyglutarate [(R)-2HG]. Here we review what is known about the molecular mechanisms of transformation by mutant IDH and discuss their implications for the development of targeted therapies to treat IDH mutant malignancies. C1 [Losman, Julie-Aurore; Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA. [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA. EM william_kaelin@dfci.harvard.edu FU NIH; Breast Cancer Research Foundation; HHMI FX We thank Dr. Matthew Vander Heiden, Dr. Rafael Bejar, and Dr. Samuel McBrayer for critical reading of the manuscript. We apologize to colleagues whose work was not cited due to space limitations or oversight. Please bring errors and egregious omissions to our attention. W.G.K. consults for, and owns equity in, Fibrogen, which is developing EglN inhibitors, and Agios, which is targeting cancer metabolism. Supported by grants from NIH, HHMI, and the Breast Cancer Research Foundation. NR 182 TC 133 Z9 135 U1 5 U2 53 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2013 VL 27 IS 8 BP 836 EP 852 DI 10.1101/gad.217406.113 PG 17 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 134NB UT WOS:000318215800002 PM 23630074 ER PT J AU Hou, JB Jia, HB Huang, XT Yu, H Ren, XF Fang, Y Han, ZG Yang, S Meng, LB Zhang, SS Yu, B Jang, IK AF Hou, Jingbo Jia, Haibo Huang, Xingtao Yu, Huai Ren, Xuefeng Fang, Yan Han, Zhigang Yang, Shuang Meng, Lingbo Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI Optical Coherence Tomographic Observations of Polytetrafluoroethylene-Covered Sirolimus-Eluting Coronary Arterial Stent SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FOLLOW-UP; IMPLANTATION; ANEURYSM; GRAFTS; ANGINA; TRIAL AB The aim of this study was to evaluate neointimal coverage obtained using a new method of polytetrafluoroethylene-covered stent (PCS) implantation combined with underlying longer sirolimus-eluting stent (SES) implantation using optical coherence tomography. Nine patients were enrolled in this study, including patients with coronary artery perforations, original coronary aneurysms, and acquired coronary aneurysms after drug-eluting stent implantation. All patients were first treated with long SES implantation and then with focal PCS implantation. Postprocedural and follow-up angiographic and optical coherence tomographic examinations were performed in all patients, and intravascular ultrasound was performed in 5 patients. All patients were asymptomatic during follow-up, without recurrent angina. There was no stent-edge or stent-segment binary restenosis. Values of late loss for proximal SES segments, PCS segments, and distal SES segments were similar (0.09, 0.07, and 0.04 mm, respectively, p = 0.8113). The mean neointimal thickness of PCS was less than that of proximal and distal SES. However, no malapposed cross sections or uncovered cross sections were found in PCS segments compared with SES segments (p = 0.0011). In conclusion, the combination of PCS and underlying longer SES implantation can offer better angiographic follow-up results. High-resolution optical coherence tomography provided convincing proof of full neointimal coverage of PCS. This new method of combined PCS and SES implantation may be a better choice compared with direct PCS implantation in certain clinical settings. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:1117-1122) C1 [Hou, Jingbo; Jia, Haibo; Huang, Xingtao; Yu, Huai; Ren, Xuefeng; Fang, Yan; Han, Zhigang; Yang, Shuang; Meng, Lingbo; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Hou, Jingbo; Jia, Haibo; Huang, Xingtao; Yu, Huai; Ren, Xuefeng; Fang, Yan; Han, Zhigang; Yang, Shuang; Meng, Lingbo; Yu, Bo] Chinese Minist Educ, Key Lab Myocardial Ischemia, Harbin, Peoples R China. [Zhang, Shaosong] LightLab Imaging, Westford, MA USA. [Zhang, Shaosong] St Jude Med, St Paul, MN USA. [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. EM yubodr@163.com NR 15 TC 2 Z9 2 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2013 VL 111 IS 8 BP 1117 EP 1122 DI 10.1016/j.amjcard.2012.12.036 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 130CK UT WOS:000317890100007 PM 23351458 ER PT J AU Lee, JP Wang, YJ AF Lee, Jennifer Pai Wang, Yi-Jiun TI Testing the predictive ability of the "spinal cord injury equation" in estimating vancomycin clearance SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; RENAL-DISEASE; SERUM CREATININE; DIET; PERFORMANCE; THERAPY AB Purpose. A new method of estimating drug clearance in patients with spinal cord injury (SCI) was tested against other methods through a retrospective analysis of its predictive ability in estimating vancomycin clearance. Methods. A retrospective chart-based investigation was conducted at a hospital with a large SCI population. Using data collected from electronic patient records, 179 cases were reviewed, and 87 cases met the inclusion criteria: a diagnosis of longstanding SCI, administration of vancomycin via i.v. infusion during the 18-month study period, and at least one documented steady-state vancomycin concentration. Using the "spinal cord injury equation" (i.e., CLSCI equation), pharmacokinetic analysis was performed to determine patient-specific clearance values, which were compared to values resulting from five widely used methods of estimating the glomerular filtration rate in spinal cord-injured patients. The primary outcome measures were bias and precision, as indicated by statistical analyses to determine the mean prediction error (ME) and the square root of the mean squared prediction error (RMSE) of each method. Results. Compared with the other evaluated methods, the CLSCI equation was found to be less biased and more precise, with the smallest calculated ME and RMSE values (p < 0.05). The five alternative methods significantly overestimated vancomycin clearance, by 45-92% (p < 0.05). The CLSCI method underestimated vancomycin clearance (by 6%) but not to a significant degree (p = 0.06). Conclusion. The study results suggest that the CLSCI equation for predicting vancomycin clearance was unbiased and may be more precise relative to other frequently used methods in the study population of patients with long-term SCI. Am J Health-Syst Pharm. 2013; 70:669-74 C1 [Lee, Jennifer Pai] Vet Affairs Long Beach Healthcare Syst, Crit Care, Long Beach, CA 90822 USA. [Wang, Yi-Jiun] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Lee, JP (reprint author), Vet Affairs Long Beach Healthcare Syst, 5901 East 7th St, Long Beach, CA 90822 USA. EM jennifer.lee4332a@va.gov NR 23 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD APR 15 PY 2013 VL 70 IS 8 BP 669 EP 674 DI 10.2146/ajhp120329 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 129AU UT WOS:000317811600009 PM 23552044 ER PT J AU Jeong, SM Xiao, CY Finley, LWS Lahusen, T Souza, AL Pierce, K Li, YH Wang, XX Laurent, G German, NJ Xu, XL Li, CL Wang, RH Lee, J Csibi, A Cerione, R Blenis, J Clish, CB Kimmelman, A Deng, CX Haigis, MC AF Jeong, Seung Min Xiao, Cuiying Finley, Lydia W. S. Lahusen, Tyler Souza, Amanda L. Pierce, Kerry Li, Ying-Hua Wang, Xiaoxu Laurent, Gaelle German, Natalie J. Xu, Xiaoling Li, Cuiling Wang, Rui-Hong Lee, Jaewon Csibi, Alfredo Cerione, Richard Blenis, John Clish, Clary B. Kimmelman, Alec Deng, Chu-Xia Haigis, Marcia C. TI SIRT4 Has Tumor-Suppressive Activity and Regulates the Cellular Metabolic Response to DNA Damage by Inhibiting Mitochondrial Glutamine Metabolism SO CANCER CELL LA English DT Article ID FATTY-ACID OXIDATION; GENOMIC INSTABILITY; CALORIE RESTRICTION; INSULIN-SECRETION; CYCLE CHECKPOINT; UREA CYCLE; CANCER; CELLS; SIRTUINS; PROMOTES AB DNA damage elicits a cellular signaling response that initiates cell cycle arrest and DNA repair. Here, we find that DNA damage triggers a critical block in glutamine metabolism, which is required for proper DNA damage responses. This block requires the mitochondrial SIRT4, which is induced by numerous genotoxic agents and represses the metabolism of glutamine into tricarboxylic acid cycle. SIRT4 loss leads to both increased glutamine-dependent proliferation and stress-induced genomic instability, resulting in tumorigenic phenotypes. Moreover, SIRT4 knockout mice spontaneously develop lung tumors. Our data uncover SIRT4 as an important component of the DNA damage response pathway that orchestrates a metabolic block in glutamine metabolism, cell cycle arrest, and tumor suppression. C1 [Jeong, Seung Min; Finley, Lydia W. S.; Laurent, Gaelle; German, Natalie J.; Lee, Jaewon; Csibi, Alfredo; Blenis, John; Haigis, Marcia C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. [Li, Ying-Hua; Wang, Xiaoxu; Kimmelman, Alec] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Xiao, Cuiying; Lahusen, Tyler; Xu, Xiaoling; Li, Cuiling; Wang, Rui-Hong; Deng, Chu-Xia] NIDDKD, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Souza, Amanda L.; Pierce, Kerry; Clish, Clary B.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Cerione, Richard] Cornell Univ, Dept Mol Med, Ithaca, NY 14853 USA. RP Deng, CX (reprint author), NIDDKD, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov; marcia_haigis@hms.harvard.edu RI deng, chuxia/N-6713-2016 FU National Research Foundation of Korea; Korean Government [NRF-2010-357-C00087]; NIH [AG032375]; Glenn Foundation for Medical Research; American Cancer Society; National Cancer Institute [R01 CA157490]; Kimmel Scholar Award; AACR-PanCAN Career Development Award; Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA FX We thank Roderick T. Bronson for analyzing tumors, Moon Hee Yang for help with allograft assays, Annie Lee for technical assistance, and the Nikon Imaging Center at Harvard Medical School. We thank Kevin Haigis for critical reading of the manuscript. S.M.J. was supported in part by a National Research Foundation of Korea grant funded by the Korean Government (NRF-2010-357-C00087). M.C.H. is supported in part by NIH grant AG032375, the Glenn Foundation for Medical Research, and the American Cancer Society New Scholar Award. A.K. is supported by the National Cancer Institute grant R01 CA157490, the Kimmel Scholar Award, and an AACR-PanCAN Career Development Award. This work was also supported in part by the Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA. NR 52 TC 114 Z9 122 U1 2 U2 41 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 APR 15 PY 2013 VL 23 IS 4 BP 450 EP 463 DI 10.1016/j.ccr.2013.02.024 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 130TV UT WOS:000317943900006 PM 23562301 ER PT J AU Xiao, ZX Jiang, Q Willette-Brown, J Xi, SC Zhu, F Burkett, S Back, T Song, NY Datla, M Sun, ZH Goldszmid, R Lin, FC Cohoon, T Pike, K Wu, XL Schrump, DS Wong, KK Young, HA Trinchieri, G Wiltrout, RH Hu, YL AF Xiao, Zuoxiang Jiang, Qun Willette-Brown, Jami Xi, Sichuan Zhu, Feng Burkett, Sandra Back, Timothy Song, Na-Young Datla, Mahesh Sun, Zhonghe Goldszmid, Romina Lin, Fanching Cohoon, Travis Pike, Kristen Wu, Xiaolin Schrump, David S. Wong, Kwok-Kin Young, Howard A. Trinchieri, Giorgio Wiltrout, Robert H. Hu, Yinling TI The Pivotal Role of IKK alpha in the Development of Spontaneous Lung Squamous Cell Carcinomas SO CANCER CELL LA English DT Article ID KAPPA-B-KINASE; NITRIC-OXIDE SYNTHASE; STEM-CELLS; CANCER; MICE; TRANSFORMATION; SUPPRESSOR; SKIN; P63; DIFFERENTIATION AB Here, we report that kinase-dead IKK alpha knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKK alpha downregulation and marked pulmonary inflammation. IKK alpha reduction upregulated the expression of p63, Trim29, and keratin 5 (K5), which serve as diagnostic markers for human lung SCCs. IKK alpha(low)K5(+)p63(hi) cell expansion and SCC formation were accompanied by inflammation-associated deregulation of oncogenes, tumor suppressors, and stem cell regulators. Reintroducing transgenic K5.IKK alpha, depleting macrophages, and reconstituting irradiated mutant animals with wild-type bone marrow (BM) prevented SCC development, suggesting that BM-derived IKKa mutant macrophages promote the transition of I IKK alpha(low)K5(+)p63(hi) to tumor cells. This mouse model resembles human lung SCCs, sheds light on the mechanisms underlying lung malignancy development, and identifies targets for therapy of lung SCCs. C1 [Xiao, Zuoxiang; Jiang, Qun; Willette-Brown, Jami; Zhu, Feng; Back, Timothy; Song, Na-Young; Datla, Mahesh; Goldszmid, Romina; Lin, Fanching; Young, Howard A.; Trinchieri, Giorgio; Wiltrout, Robert H.; Hu, Yinling] NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21701 USA. [Xi, Sichuan; Schrump, David S.] NCI, Ctr Canc Res, Thorac Oncol Sect, Surg Branch, Frederick, MD 21701 USA. [Burkett, Sandra] NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Sun, Zhonghe; Pike, Kristen; Wu, Xiaolin] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Lab Mol Technol, Frederick, MD 21702 USA. [Cohoon, Travis; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wiltrout, RH (reprint author), NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21701 USA. EM wiltrour@mail.nih.gov; huy2@mail.nih.gov RI Jiang, Qun/A-1358-2014; OI wong, kwok kin/0000-0001-6323-235X FU National Cancer Institute [ZIA BC 011212, ZIA BC 011391] FX We thank Teri Plona, Scott Coccodrilli, Arati Raziuddin, Hue Vuong, Vika Grinberg, and Robin Stewart from Laboratory of Molecular Technology, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research for sequencing DDR2, Sox2, and PIK3CA genes in mouse lung SCCs and Dr. Hesed Padilla-Nash and Dr. Thomas Ried from National Institutes of Health for kindly providing a spontaneously transformed lung murine epithelial cell line M2C. This work was supported by the National Cancer Institute (ZIA BC 011212 and ZIA BC 011391 to Y.H.). NR 43 TC 40 Z9 42 U1 0 U2 13 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 APR 15 PY 2013 VL 23 IS 4 BP 527 EP 540 DI 10.1016/j.ccr.2013.03.009 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 130TV UT WOS:000317943900012 PM 23597566 ER PT J AU Clough-Gorr, KM Thwin, SS Bosco, JLF Silliman, RA Buist, DSM Pawloski, PA Quinn, VP Prout, MN AF Clough-Gorr, Kerri M. Thwin, Soe Soe Bosco, Jaclyn L. F. Silliman, Rebecca A. Buist, Diana S. M. Pawloski, Pamala A. Quinn, Virginia P. Prout, Marianne N. TI Incident malignancies among older long-term breast cancer survivors and an age-matched and site-matched nonbreast cancer comparison group over 10 years of follow-up SO CANCER LA English DT Article DE breast cancer; breast cancer survivors; incident malignancies; malignancy; multiple primary malignancies; older women; survivors ID 2ND PRIMARY CANCERS; COLORECTAL-CANCER; CONTRALATERAL BREAST; ADJUVANT RADIOTHERAPY; INCREASED RISK; WOMEN; PREVALENCE; THERAPY AB BACKGROUND: Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged 65 years and are at risk for developing subsequent malignancies. METHODS: Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age 65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk. RESULTS: Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and 73% had a body mass index 30 kg/m2. Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 +/- 2.81 years vs 4.03 +/- 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47). CONCLUSIONS: Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis. Cancer 2013. (c) 2012 American Cancer Society. C1 [Clough-Gorr, Kerri M.] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland. [Clough-Gorr, Kerri M.; Thwin, Soe Soe; Bosco, Jaclyn L. F.; Silliman, Rebecca A.] Boston Univ, Sch Med, Boston Med Ctr, Sect Geriatr, Boston, MA 02118 USA. [Clough-Gorr, Kerri M.] Natl Inst Canc Epidemiol & Registrat, Zurich, Switzerland. [Thwin, Soe Soe] Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Bosco, Jaclyn L. F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Silliman, Rebecca A.; Prout, Marianne N.] Boston Univ, Dept Epidemiol, Sch Publ Heath, Boston, MA 02215 USA. [Buist, Diana S. M.] Grp Hlth Res Inst, Seattle, WA USA. [Pawloski, Pamala A.] HealthPartners Res Fdn, Bloomington, MN USA. [Quinn, Virginia P.] Kaiser Permanente Southern Calif, Res & Evaluat, Pasadena, CA USA. RP Clough-Gorr, KM (reprint author), Boston Med Ctr, 88 East Newton St,Robinson 2, Boston, MA 02118 USA. EM kmclough@bu.edu OI Prout, Marianne/0000-0001-8747-6199 FU Public Health Service grant from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services [R01CA093772-05A2] FX This work was supported by Public Health Service grant R01CA093772-05A2 (Rebecca A. Silliman, principal investigator) from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 28 TC 3 Z9 3 U1 0 U2 6 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 15 PY 2013 VL 119 IS 8 BP 1478 EP 1485 DI 10.1002/cncr.27914 PG 8 WC Oncology SC Oncology GA 126LT UT WOS:000317618700006 PM 23280284 ER PT J AU Landry, JC Feng, Y Cohen, SJ Staley, CA Whittington, R Sigurdson, ER Nimeiri, H Verma, U Prabhu, RS Benson, A AF Landry, Jerome C. Feng, Yang Cohen, Steven J. Staley, Charles A., III Whittington, Richard Sigurdson, Elin Ruth Nimeiri, Halla Verma, Udit Prabhu, Roshan S. Benson, Al Bowen TI Phase 2 study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: ECOG 3204 SO CANCER LA English DT Article DE rectal cancer; colorectal cancer; radiation therapy; chemoradiation; neoadjuvant therapy; combined modality therapy ID METASTATIC COLORECTAL-CANCER; CHEMORADIOTHERAPY; CHEMORADIATION; THERAPY AB BACKGROUND: Recent studies have demonstrated the feasibility of combining oxaliplatin with 5-fluorouracil (5-FU) or capecitibine and radiation therapy. The addition of bevacizumab to chemotherapy improves overall survival for metastatic disease. We initiated a phase 2 trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy followed by surgery and postoperative 5-FU, leucovorin, oxaliplatin (FOLFOX) and bevacizumab for locally advanced rectal cancer. METHODS: Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled. Preoperative treatment was capecitabine (825 mg/m2 twice daily from Monday to Friday), oxaliplatin (50 mg/m2 weekly), bevacizumab (5 mg/kg on days 1, 15, 29), and radiation therapy (50.4 Gy). Surgery was performed by 6 weeks after neoadjuvant therapy. Beginning 8 to 12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles. RESULTS: Fifty-four of 57 enrolled patients were eligible. Forty-nine (91%) patients completed preoperative therapy and underwent surgery. Nine patients (17%; 90% confidence interval, 9%-27%) achieved pathologic complete response. Thirty-two patients (59%) experienced pathologic tumor downstaging, and 53% and 15% of patients experienced worst grade 3 and grade 4 acute toxicity, respectively. Forty-seven percent of patients who underwent surgery experienced a surgical complication. CONCLUSIONS: The primary endpoint of a 30% pathologic complete response rate was not reached; however, the majority of patients experienced pathologic downstaging with this regimen. Increased wound-healing delays and complications may have been related to the addition of bevacizumab, oxaliplatin, or both. Continued observation of these patients will establish the long-term morbidity and efficacy of this combined modality approach. Cancer 2013. (c) 2012 American Cancer Society. C1 [Landry, Jerome C.; Staley, Charles A., III; Prabhu, Roshan S.] Emory Univ, Atlanta, GA 30322 USA. [Landry, Jerome C.; Staley, Charles A., III; Prabhu, Roshan S.] Winship Canc Inst, Atlanta, GA USA. [Feng, Yang] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cohen, Steven J.; Sigurdson, Elin Ruth] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Whittington, Richard] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Nimeiri, Halla; Benson, Al Bowen] Northwestern Univ, Chicago, IL 60611 USA. [Verma, Udit] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Landry, JC (reprint author), Emory Univ, Dept Radiat Oncol, 1365 Clifton Rd NE, Atlanta, GA 30322 USA. EM jland01@emory.edu FU Public Health Service grants [CA23318, CA66636, CA21115, CA27525, CA15488, CA49957, CA17145]; National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services; Genentech FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD) and supported in part by Public Health Service grants CA23318, CA66636, CA21115, CA27525, CA15488, CA49957, and CA17145 and from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services.; All authors have read and approved the manuscript. To the best of our knowledge, no conflict of interest, financial or other, exists except: Steven J Cohen has received honoraria from Genentech; Halla Nimeiri has received honoraria from Genentech; Al Bowen Benson has been a consultant/advisor for Sanofi and Genentech, and has received research funding from Genentech. NR 23 TC 25 Z9 27 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD APR 15 PY 2013 VL 119 IS 8 BP 1521 EP 1527 DI 10.1002/cncr.27890 PG 7 WC Oncology SC Oncology GA 126LT UT WOS:000317618700011 PM 23288663 ER PT J AU Hensley, ML Wathen, JK Maki, RG Araujo, DM Sutton, G Priebat, DA George, S Soslow, RA Baker, LH AF Hensley, Martee L. Wathen, J. Kyle Maki, Robert G. Araujo, Dejka M. Sutton, Gregory Priebat, Dennis A. George, Suzanne Soslow, Robert A. Baker, Laurence H. TI Adjuvant therapy for high-grade, uterus-limited leiomyosarcoma Results of a Phase 2 Trial (SARC 005) SO CANCER LA English DT Article DE adjuvant; chemotherapy; uterine; leiomyosarcoma; survival ID GEMCITABINE PLUS DOCETAXEL; UTERINE SARCOMAS; II TRIAL; PROGNOSTIC-FACTORS; STAGE-I; CHEMOTHERAPY; IFOSFAMIDE; RADIOTHERAPY; ADRIAMYCIN; CISPLATIN AB BACKGROUND: Between 30% and 50% of women who have high-grade uterine leiomyosarcoma (uLMS) limited to the uterus at diagnosis remain progression-free at 2 years. Adjuvant pelvic radiation does not improve outcome. The objective of the current study was to determine the 2-year and 3-year progression-free survival (PFS) among a prospective cohort of women who received adjuvant gemcitabine plus docetaxel followed by doxorubicin. METHODS: Women with uterus-limited, high-grade uLMS and adequate organ function were eligible. Within 12 weeks of complete resection and after confirmation that they had no evidence of disease on computed tomography (CT) images, the patients received 4 cycles of fixed-dose-rate gemcitabine plus docetaxel. Those who were confirmed disease-free on CT scans after cycle 4 received 4 cycles of doxorubicin. CT imaging for recurrence was performed every 3 months for 2 years, then every 6 months for 3 years. RESULTS: In total, 47 women were enrolled (46 evaluable) in 3 years. Characteristics included a median age of 53 years; 1988 International Federation of Gynecology and Obstetrics stage I disease in 81% of patients, stage II disease in 15%, and serosa-only stage IIIA disease in 4%; American Joint Committee on Cancer stage II disease in 13% of patients and stage III disease in 87%; a median tumor size of 8 cm (range, 2.5-30 cm); and a median mitotic rate of 18 mitoses per 10 high-power fields (range, 5-83 mitoses per 10 high-power fields). At a median follow-up of 39.8 months, 21 of 46 patients developed recurrent disease (45.7%). The median time to recurrence was 27.4 months (range, 3-40 months). Seventy-eight percent of patients (95% confidence interval, 67%-91%) were progression-free at 2 years, and 57% (95% confidence interval, 44%-74%) were progression-free at 3 years. The median PFS was not reached and exceeded 36 months. CONCLUSIONS: Among women with high-grade, uterus-limited uLMS who received treatment with adjuvant gemcitabine plus docetaxel followed by doxorubicin, 78% remained progression-free at 2 years, and 57% remained progression-free at 3 years. A randomized trial of adjuvant chemotherapy versus observation to determine whether adjuvant chemotherapy can improve survival in women with uterus-limited uLMS is underway. Cancer 2013. (c) 2013 American Cancer Society. C1 [Hensley, Martee L.] Mem Sloan Kettering Canc Ctr, Dept Med, Gynecol Med Oncol Serv, New York, NY 10065 USA. [Hensley, Martee L.] Weill Cornell Med Coll, New York, NY USA. [Wathen, J. Kyle] Janssen Res & Dev LLC, Titusville, NJ USA. [Maki, Robert G.] Mt Sinai Med Ctr, Pediat Hematol Oncol Div, New York, NY 10029 USA. [Araujo, Dejka M.] Univ Texas MD Anderson Canc Ctr, Sarcoma Med Oncol Div, Houston, TX 77030 USA. [Sutton, Gregory] St Vincents Hosp, Dept Surg, Indianapolis, IN USA. [Priebat, Dennis A.] Washington Canc Inst, Sect Hematol Oncol, Boston, MA USA. [George, Suzanne] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Med Oncol, Boston, MA 02115 USA. [Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Baker, Laurence H.] Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. RP Hensley, ML (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Gynecol Med Oncol Serv, 300 East 66th St,Suite 1355, New York, NY 10065 USA. EM hensleym@mskcc.org OI Soslow, Robert/0000-0002-7269-5898 FU Sarcoma Alliance for Research through Collaboration (SARC) FX Funding for this study was provided by the Sarcoma Alliance for Research through Collaboration (SARC) (clinicaltrials.gov registration NCT00282087). NR 18 TC 49 Z9 51 U1 1 U2 6 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 15 PY 2013 VL 119 IS 8 BP 1555 EP 1561 DI 10.1002/cncr.27942 PG 7 WC Oncology SC Oncology GA 126LT UT WOS:000317618700015 PM 23335221 ER PT J AU Prabhakar, U Maeda, H Jain, RK Sevick-Muraca, EM Zamboni, W Farokhzad, OC Barry, ST Gabizon, A Grodzinski, P Blakey, DC AF Prabhakar, Uma Maeda, Hiroshi Jain, Rakesh K. Sevick-Muraca, Eva M. Zamboni, William Farokhzad, Omid C. Barry, Simon T. Gabizon, Alberto Grodzinski, Piotr Blakey, David C. TI Challenges and Key Considerations of the Enhanced Permeability and Retention Effect for Nanomedicine Drug Delivery in Oncology SO CANCER RESEARCH LA English DT Editorial Material ID SOLID TUMORS; MACROMOLECULAR THERAPEUTICS; CANCER; TRANSLATION; AGENTS AB Enhanced permeability of the tumor vasculature allows macromolecules to enter the tumor interstitial space, whereas the suppressed lymphatic filtration allows them to stay there. This phenomenon, enhanced permeability and retention (EPR), has been the basis of nanotechnology platforms to deliver drugs to tumors. However, progress in developing effective drugs using this approach has been hampered by heterogeneity of EPR effect in different tumors and limited experimental data from patients on effectiveness of this mechanism as related to enhanced drug accumulation. This report summarizes the workshop discussions on key issues of the EPR effect and major gaps that need to be addressed to effectively advance nanoparticle-based drug delivery. Cancer Res; 73(8); 2412-7. (C) 2013 AACR. C1 [Prabhakar, Uma; Grodzinski, Piotr] NCI, Alliance Nanotechnol Canc, Bethesda, MD 20892 USA. [Maeda, Hiroshi] Sojo Univ, Inst DDS Res, Kumamoto, Japan. [Jain, Rakesh K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farokhzad, Omid C.] Harvard Univ, Sch Med, Boston, MA USA. [Farokhzad, Omid C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sevick-Muraca, Eva M.] Univ Texas Hlth Sci Ctr, Brown Fdn Inst Mol Med, Houston, TX USA. [Zamboni, William] Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, UNC Eshelman Sch Pharm, Chapel Hill, NC USA. [Barry, Simon T.; Blakey, David C.] AstraZeneca, Macclesfield, Cheshire, England. [Gabizon, Alberto] Shaare Zedek Med Ctr, Jerusalem, Israel. [Gabizon, Alberto] Hebrew Univ Jerusalem, Sch Med, IL-91010 Jerusalem, Israel. RP Prabhakar, U (reprint author), NCI, Off Canc Nanotechnol Res, Bldg 31 Room 10A52, Bethesda, MD 20892 USA. EM uma.prabhakar@nih.gov; grodzinp@mail.nih.gov RI Maeda, Hiroshi/N-4471-2016; Sevick-Muraca, Eva/A-4152-2017 OI Sevick-Muraca, Eva/0000-0002-8152-4847 FU NCI NIH HHS [P30 CA016086, U54 CA151652] NR 16 TC 362 Z9 364 U1 27 U2 185 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 BP 2412 EP 2417 DI 10.1158/0008-5472.CAN-12-4561 PG 6 WC Oncology SC Oncology GA 126ER UT WOS:000317595800005 PM 23423979 ER PT J AU O'Connor, KW Dejsuphong, D Park, E Nicolae, CM Kimmelman, AC D'Andrea, AD Moldovan, GL AF O'Connor, Kevin W. Dejsuphong, Donniphat Park, Eunmi Nicolae, Claudia M. Kimmelman, Alec C. D'Andrea, Alan D. Moldovan, George-Lucian TI PARI Overexpression Promotes Genomic Instability and Pancreatic Tumorigenesis SO CANCER RESEARCH LA English DT Article ID HOMOLOGOUS RECOMBINATION; FANCONI-ANEMIA; DNA-DAMAGE; REPLICATION FORK; GENE-MUTATIONS; CANCER; REPAIR; BRCA2; CELLS; CARCINOGENESIS AB Treatment options for patients with pancreatic ductal adenocarcinoma (PDAC) remain limited. Therapeutic targets of interest include mutated molecules that predispose to pancreatic cancer such as KRAS and TP53. Here, we show that an element of the homologous recombination pathway of DNA repair, the PARP-binding protein C12orf48/PARI (PARPBP), is overexpressed specifically in pancreatic cancer cells where it is an appealing candidate for targeted therapy. PARI upregulation in pancreatic cancer cells or avian DT40 cells conferred DNA repair deficiency and genomic instability. Significantly, PARI silencing compromised cancer cell proliferation in vitro, leading to cell-cycle alterations associated with S-phase delay, perturbed DNA replication, and activation of the DNA damage response pathway in the absence of DNA damage stimuli. Conversely, PARI overexpression produced tolerance to DNA damage by promoting replication of damaged DNA. In a mouse xenograft model of pancreatic cancer, PARI silencing was sufficient to reduce pancreatic tumor growth in vivo. Taken together, our findings offered a preclinical proof-of-concept for PARI as candidate therapeutic target to treat PDAC. Cancer Res; 73(8); 2529-39. (C) 2013 AACR. C1 [O'Connor, Kevin W.; Dejsuphong, Donniphat; Park, Eunmi; Kimmelman, Alec C.; D'Andrea, Alan D.; Moldovan, George-Lucian] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nicolae, Claudia M.; Moldovan, George-Lucian] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. RP Moldovan, GL (reprint author), Penn State Univ, Coll Med, Dept Biochem & Mol Biol, 500 Univ Dr, Hershey, PA 17033 USA. EM gmoldovan@hmc.psu.edu OI George-Lucian, Moldovan/0000-0003-3825-149X FU NIH [R01DK43889, R37HL52725, P01HL048546, P01CA092584]; Susan G. Komen Breast Cancer Foundation FX This work is supported by NIH grants R01DK43889, R37HL52725, P01HL048546, and P01CA092584 (A.D. D'Andrea) and by Postdoctoral Fellowships from the Susan G. Komen Breast Cancer Foundation (G.-L. Moldovan and E. Park). NR 45 TC 11 Z9 11 U1 2 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 BP 2529 EP 2539 DI 10.1158/0008-5472.CAN-12-3313 PG 11 WC Oncology SC Oncology GA 126ER UT WOS:000317595800016 PM 23436799 ER PT J AU Feng, S Dakhova, O Creighton, CJ Ittmann, M AF Feng, Shu Dakhova, Olga Creighton, Chad J. Ittmann, Michael TI Endocrine Fibroblast Growth Factor FGF19 Promotes Prostate Cancer Progression SO CANCER RESEARCH LA English DT Article ID HEPATOCELLULAR-CARCINOMA; SERUM-CALCIUM; TUMOR-GROWTH; EXPRESSION; FIBROBLAST-GROWTH-FACTOR-19; KLOTHO; METABOLISM; THERAPY; SPECIFICITY; DETERMINES AB Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that fibroblast growth factor (FGF) receptors are important in prostate cancer initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21, and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require alpha-Klotho (KL) and/or beta-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as coreceptors along with classic FGF receptors (FGFR) to mediate potent biologic activity. Here we show that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion, and colony formation of prostate cancer cells at low ligand concentrations. FGF19 silencing in prostate cancer cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in prostate cancer cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biologic effects in prostate cancer. Our findings support the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlight FGF19 as a relevant endocrine FGF in this setting. Cancer Res; 73(8); 2551-62. (C) 2013 AACR. C1 [Feng, Shu; Dakhova, Olga; Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Feng, Shu; Dakhova, Olga; Ittmann, Michael] Baylor Coll Med, Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. [Creighton, Chad J.] Baylor Coll Med, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol & Immunol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU Department of Veterans Affairs Merit Review program; National Cancer Institute [P30 CA125123] FX This work was supported by grants from the Department of Veterans Affairs Merit Review program (MI), the National Cancer Institute to the Dan L. Duncan Cancer (P30 CA125123), and by the use of the facilities of the Michael E. DeBakey VAMC. NR 42 TC 32 Z9 33 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 BP 2551 EP 2562 DI 10.1158/0008-5472.CAN-12-4108 PG 12 WC Oncology SC Oncology GA 126ER UT WOS:000317595800018 PM 23440425 ER PT J AU Liu, QS Xu, CX Kirubakaran, S Zhang, X Hur, W Liu, Y Kwiatkowski, NP Wang, JH Westover, KD Gao, P Ercan, D Niepel, M Thoreen, CC Kang, SA Patricelli, MP Wang, YC Tupper, T Altabef, A Kawamura, H Held, KD Chou, DM Elledge, SJ Janne, PA Wong, KK Sabatini, DM Gray, NS AF Liu, Qingsong Xu, Chunxiao Kirubakaran, Sivapriya Zhang, Xin Hur, Wooyoung Liu, Yan Kwiatkowski, Nicholas P. Wang, Jinhua Westover, Kenneth D. Gao, Peng Ercan, Dalia Niepel, Mario Thoreen, Carson C. Kang, Seong A. Patricelli, Matthew P. Wang, Yuchuan Tupper, Tanya Altabef, Abigail Kawamura, Hidemasa Held, Kathryn D. Chou, Danny M. Elledge, Stephen J. Janne, Pasi A. Wong, Kwok-Kin Sabatini, David M. Gray, Nathanael S. TI Characterization of Torin2, an ATP-Competitive Inhibitor of mTOR, ATM, and ATR SO CANCER RESEARCH LA English DT Article ID MAMMALIAN TARGET; ANTITUMOR-ACTIVITY; RAPAMYCIN MTOR; SIGNALING PATHWAYS; HIGHLY POTENT; CANCER-CELLS; PI3K; MUTATIONS; DISCOVERY; THERAPY AB mTOR is a highly conserved serine/threonine protein kinase that serves as a central regulator of cell growth, survival, and autophagy. Deregulation of the PI3K/Akt/mTOR signaling pathway occurs commonly in cancer and numerous inhibitors targeting the ATP-binding site of these kinases are currently undergoing clinical evaluation. Here, we report the characterization of Torin2, a second-generation ATP-competitive inhibitor that is potent and selective for mTOR with a superior pharmacokinetic profile to previous inhibitors. Torin2 inhibited mTORC1-dependent T389 phosphorylation on S6K (RPS6KB1) with an EC50 of 250 pmol/L with approximately 800-fold selectivity for cellular mTOR versus phosphoinositide 3-kinase (PI3K). Torin2 also exhibited potent biochemical and cellular activity against phosphatidylinositol-3 kinase-like kinase (PIKK) family kinases including ATM(EC50, 28 nmol/L), ATR (EC50, 35 nmol/L), and DNA-PK (EC50, 118 nmol/L; PRKDC), the inhibition of which sensitized cells to Irradiation. Similar to the earlier generation compound Torin1 and in contrast to other reported mTOR inhibitors, Torin2 inhibited mTOR kinase and mTORC1 signaling activities in a sustained manner suggestive of a slow dissociation from the kinase. Cancer cell treatment with Torin2 for 24 hours resulted in a prolonged block in negative feedback and consequent T308 phosphorylation on Akt. These effects were associated with strong growth inhibition in vitro. Single-agent treatment with Torin2 in vivo did not yield significant efficacy against KRAS-driven lung tumors, but the combination of Torin2 with mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor AZD6244 yielded a significant growth inhibition. Taken together, our findings establish Torin2 as a strong candidate for clinical evaluation in a broad number of oncologic settings where mTOR signaling has a pathogenic role. Cancer Res; 73(8); 2574-86. (C) 2013 AACR. C1 [Liu, Qingsong; Kirubakaran, Sivapriya; Zhang, Xin; Hur, Wooyoung; Kwiatkowski, Nicholas P.; Wang, Jinhua; Thoreen, Carson C.; Gray, Nathanael S.] Dana Farber Harvard Canc Ctr, Dept Canc Biol, Ludwig Ctr, Boston, MA USA. [Ercan, Dalia; Janne, Pasi A.] Dana Farber Harvard Canc Ctr, Dept Med Oncol, Ludwig Ctr, Boston, MA USA. [Xu, Chunxiao; Liu, Yan; Gao, Peng; Altabef, Abigail; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Dept Med, Ludwig Ctr, Boston, MA USA. [Xu, Chunxiao; Liu, Yan; Gao, Peng; Altabef, Abigail; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Dept Med Oncol, Ludwig Ctr, Boston, MA USA. [Ercan, Dalia; Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Wang, Yuchuan; Tupper, Tanya] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. [Chou, Danny M.; Elledge, Stephen J.] Howard Hughes Med Inst, Div Genet, Boston, MA 02115 USA. [Ercan, Dalia; Janne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kawamura, Hidemasa; Held, Kathryn D.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Liu, Qingsong; Kirubakaran, Sivapriya; Zhang, Xin; Hur, Wooyoung; Kwiatkowski, Nicholas P.; Wang, Jinhua; Thoreen, Carson C.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Chou, Danny M.; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Niepel, Mario] Harvard Univ, Sch Med, Ctr Cell Decis Proc, Dept Syst Biol, Boston, MA 02115 USA. [Westover, Kenneth D.] Harvard Radiat Oncol Program, Boston, MA USA. [Kang, Seong A.; Sabatini, David M.] MIT, Whitehead Inst Biomed Res, Cambridge, MA USA. [Sabatini, David M.] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA USA. [Kang, Seong A.; Sabatini, David M.] MIT, Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA. [Patricelli, Matthew P.] ActivX Biosci Inc, La Jolla, CA USA. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 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; Wang, Yuchuan/0000-0001-5111-6562; liu, qing song/0000-0002-7829-2547; wong, kwok kin/0000-0001-6323-235X FU NIH [HG006097, RO1 CA122794, CA140594, RO1 AI47389, CA103866, C06 CA059267]; NIH Lung SPORE [P50CA090578]; American Cancer Society FX This study was supported by NIH grant HG006097 (Q. Liu and M. Niepel); C. Xu, Y. Liu, P. Gao, T. Tupper, and K.-K. Wong are supported by NIH RO1 CA122794, CA140594, and NIH Lung SPORE P50CA090578; C.C. Thoreen is supported by Postdoctoral fellowship from the American Cancer Society and S.A. Kang are supported by NIH RO1 AI47389 and CA103866; H. Kawamura, and K.D. Held are supported by NIH C06 CA059267; S.J. Elledge and D.M. Sabatini are Howard Hughes Medical Institute investigators. NR 48 TC 49 Z9 50 U1 4 U2 31 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 BP 2574 EP 2586 DI 10.1158/0008-5472.CAN-12-1702 PG 13 WC Oncology SC Oncology GA 126ER UT WOS:000317595800020 PM 23436801 ER PT J AU Niemi, SM AF Niemi, Steven M. TI Laboratory animals as veterinary patients SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material ID HEART-FAILURE; THERAPY; DISEASE C1 [Niemi, Steven M.] Massachusetts Gen Hosp, Dept Res Management, Boston, MA 02114 USA. [Niemi, Steven M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Niemi, SM (reprint author), Massachusetts Gen Hosp, Dept Res Management, Boston, MA 02114 USA. EM sniemi@partners.org NR 21 TC 3 Z9 3 U1 0 U2 4 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD APR 15 PY 2013 VL 242 IS 8 BP 1063 EP 1065 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 122LJ UT WOS:000317319300010 PM 23547666 ER PT J AU Cerdeira, AS Rajakumar, A Royle, CM Lo, A Husain, Z Thadhani, RI Sukhatme, VP Karumanchi, SA Kopcow, HD AF Cerdeira, Ana Sofia Rajakumar, Augustine Royle, Caroline M. Lo, Agnes Husain, Zaheed Thadhani, Ravi I. Sukhatme, Vikas P. Karumanchi, S. Ananth Kopcow, Hernan D. TI Conversion of Peripheral Blood NK Cells to a Decidual NK-like Phenotype by a Cocktail of Defined Factors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; HYPOXIA-INDUCIBLE FACTOR-1; FETAL-MATERNAL INTERFACE; RECEPTOR EXPRESSION; GESTATIONAL-AGE; DNA METHYLATION; GENE-EXPRESSION; EARLY-PREGNANCY; T-CELLS; GROWTH AB NK cells that populate the decidua are important regulators of normal placentation. In contrast to peripheral blood NK cells, decidual NK (dNK) cells lack cytotoxicity, secrete proangiogenic factors, and regulate trophoblast invasion. In this study we show that exposure to a combination of hypoxia, TGF-beta 1, and a demethylating agent results in NK cells that express killer cell Ig-like receptors, the dNK cell markers CD9 and CD49a, and a dNK pattern of chemokine receptors. These cells secrete vascular endothelial growth factor (a potent proangiogenic molecule), display reduced cytotoxicity, and promote invasion of human trophoblast cell lines. These findings have potential therapeutic applications for placental disorders associated with altered NK cell biology. The Journal of Immunology, 2013, 190: 3939-3948. C1 [Cerdeira, Ana Sofia; Rajakumar, Augustine; Royle, Caroline M.; Lo, Agnes; Husain, Zaheed; Sukhatme, Vikas P.; Karumanchi, S. Ananth; Kopcow, Hernan D.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Cerdeira, Ana Sofia] Gulbenkian Program Adv Med Educ, P-1067001 Lisbon, Portugal. [Cerdeira, Ana Sofia] Univ Porto, Dept Obstet & Gynecol, Ctr Hosp Porto, P-4099001 Oporto, Portugal. [Rajakumar, Augustine; Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Thadhani, Ravi I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Kopcow, Hernan D.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Kopcow, HD (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave,RN359, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu; hkopcow@bidmc.harvard.edu FU Harvard Building Interdisciplinary Research Careers in Women's Health Program [K12 HD051959]; National Institutes of Health; Office of Research in Women's Health; Howard Hughes Medical Institute; Burroughs Welcome Fund; Fundacao Calouste Gulbenkian, Portugal; Fundacao Champalimaud, Portugal; Ministerio da Saude, Portugal; Fundacao para a Ciencia e Tecnologia, Portugal FX This work was supported by the Harvard Building Interdisciplinary Research Careers in Women's Health Program Project K12 HD051959 supported by the National Institutes of Health, the Office of Research in Women's Health (to H.D.K.), the Howard Hughes Medical Institute, and the Burroughs Welcome Fund (to S.A.K.). The Gulbenkian Program for Advanced Medical Education is sponsored by Fundacao Calouste Gulbenkian, Fundacao Champalimaud, Ministerio da Saude e Fundacao para a Ciencia e Tecnologia, Portugal. NR 55 TC 37 Z9 39 U1 0 U2 12 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2013 VL 190 IS 8 BP 3939 EP 3948 DI 10.4049/jimmunol.1202582 PG 10 WC Immunology SC Immunology GA 121WC UT WOS:000317274500013 PM 23487420 ER PT J AU Grimm, MJ Vethanayagam, RR Almyroudis, NG Dennis, CG Khan, ANH D'Auria, AC Singel, KL Davidson, BA Knight, PR Blackwell, TS Hohl, TM Mansour, MK Vyas, JM Rohm, M Urban, CF Kelkka, T Holmdahl, R Segal, BH AF Grimm, Melissa J. Vethanayagam, R. Robert Almyroudis, Nikolaos G. Dennis, Carly G. Khan, A. Nazmul H. D'Auria, Anthony C. Singel, Kelly L. Davidson, Bruce A. Knight, Paul R. Blackwell, Timothy S. Hohl, Tobias M. Mansour, Michael K. Vyas, Jatin M. Rohm, Marc Urban, Constantin F. Kelkka, Tiina Holmdahl, Rikard Segal, Brahm H. TI Monocyte- and Macrophage-Targeted NADPH Oxidase Mediates Antifungal Host Defense and Regulation of Acute Inflammation in Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; ASPERGILLUS-FUMIGATUS CONIDIA; P47(PHOX-/-) MOUSE MODEL; ACUTE LUNG INJURY; ALVEOLAR MACROPHAGES; FUNGAL-INFECTIONS; NEUTROPHILS; CELLS; ACTIVATION; DECTIN-1 AB Chronic granulomatous disease, an inherited disorder of the NADPH oxidase in which phagocytes are defective in the generation of superoxide anion and downstream reactive oxidant species, is characterized by severe bacterial and fungal infections and excessive inflammation. Although NADPH oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where NADPH oxidase has been deemed vital for pathogen killing. In contrast, the function and importance of NADPH oxidase in macrophages are less clear. Therefore, we evaluated susceptibility to pulmonary aspergillosis in globally NADPH oxidase-deficient mice versus transgenic mice with monocyte/macrophage-targeted NADPH oxidase activity. We found that the lethal inoculum was >100-fold greater in transgenic versus globally NADPH oxidase-deficient mice. Consistent with these in vivo results, NADPH oxidase in mouse alveolar macrophages limited germination of phagocytosed Aspergillus fumigatus spores. Finally, globally NADPH oxidase-deficient mice developed exuberant neutrophilic lung inflammation and proinflammatory cytokine responses to zymosan, a fungal cell wall-derived product composed principally of particulate beta-glucans, whereas inflammation in transgenic and wild-type mice was mild and transient. Taken together, our studies identify a central role for monocyte/macrophage NADPH oxidase in controlling fungal infection and in limiting acute lung inflammation. The Journal of Immunology, 2013, 190: 4175-4184. C1 [Grimm, Melissa J.; Vethanayagam, R. Robert; Almyroudis, Nikolaos G.; Dennis, Carly G.; Khan, A. Nazmul H.; D'Auria, Anthony C.; Singel, Kelly L.; Segal, Brahm H.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Almyroudis, Nikolaos G.; Segal, Brahm H.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Med, Buffalo, NY 12414 USA. [Davidson, Bruce A.; Knight, Paul R.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Anesthesiol, Buffalo, NY 12414 USA. [Blackwell, Timothy S.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Hohl, Tobias M.] Fred Hutchinson Canc Res Ctr, Dept Infect Dis, Seattle, WA 98109 USA. [Mansour, Michael K.; Vyas, Jatin M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Rohm, Marc; Urban, Constantin F.] Umea Univ, Dept Clin Microbiol, Lab Mol Infect Med Sweden, S-90185 Umea, Sweden. [Kelkka, Tiina] Turku Univ, Turku Doctoral Program Biomed Sci, MediCity, Turku 20521, Finland. [Kelkka, Tiina; Holmdahl, Rikard] Turku Univ, MediCity, Turku 20521, Finland. [Kelkka, Tiina; Holmdahl, Rikard] Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden. [Segal, Brahm H.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. RP Segal, BH (reprint author), Roswell Pk Canc Inst, Dept Med, Elm & Carlton St, Buffalo, NY 14263 USA. EM brahm.segal@roswellpark.org RI Vyas, Jatin/Q-1627-2016; OI Vyas, Jatin/0000-0002-9985-9565; Hohl, Tobias/0000-0002-9097-5412; Urban, Constantin/0000-0003-1438-1134 FU Chronic Granulomatous Disorder Research Trust; National Institute of Allergy and Infectious Diseases [R01AI079253]; National Cancer Institute Cancer Center Support Grant [CA016056]; Academy of Finland; European Union Grant Masterswitch [HEALTH-F2-2008-223404] FX This work was supported by the Chronic Granulomatous Disorder Research Trust (to B. H. S.), National Institute of Allergy and Infectious Diseases Grant R01AI079253 (to B. H. S.), National Cancer Institute Cancer Center Support Grant CA016056 to Roswell Park Cancer Institute, and by the Academy of Finland and the European Union Grant Masterswitch (HEALTH-F2-2008-223404). NR 65 TC 28 Z9 29 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 15 PY 2013 VL 190 IS 8 BP 4175 EP 4184 DI 10.4049/jimmunol.1202800 PG 10 WC Immunology SC Immunology GA 121WC UT WOS:000317274500035 PM 23509361 ER PT J AU de Schepper, EIT Overdevest, GM Suri, P Peul, WC Oei, EHG Koes, BW Bierma-Zeinstra, SMA Luijsterburg, PAJ AF de Schepper, Evelien I. T. Overdevest, Gijsbert M. Suri, Pradeep Peul, Wilco C. Oei, Edwin H. G. Koes, Bart W. Bierma-Zeinstra, Sita M. A. Luijsterburg, Pim A. J. TI Diagnosis of Lumbar Spinal Stenosis An Updated Systematic Review of the Accuracy of Diagnostic Tests SO SPINE LA English DT Review DE lumbar spinal stenosis; diagnostic accuracy; systematic review ID LOW-BACK-PAIN; COMPUTER-ASSISTED TOMOGRAPHY; CANAL STENOSIS; SUPPORT TOOL; METRIZAMIDE MYELOGRAPHY; FORAMINAL STENOSIS; CLINICAL SCIENCES; DISK HERNIATION; 1984 VOLVO; ULTRASOUND AB Study Design. Systematic review of diagnostic studies. Objective. To update our previous systematic review on the diagnostic accuracy of tests used to diagnose lumbar spinal stenosis. Summary of Background Data. A wide range of clinical, radiological, and electrodiagnostic tests are used to diagnose lumbar spinal stenosis. An accurate diagnosis is vital, because lumbar spinal stenosis may require specific medical advice and treatment. Therefore, it is important to know the accuracy of these diagnostic tests currently available. Methods. A comprehensive literature search was conducted for original diagnostic studies on lumbar spinal stenosis, in which one or more diagnostic tests were evaluated with a reference standard, and diagnostic accuracy was reported or could be calculated. Our previous systematic review included studies up to March 2004; this review is current up to March 2011. Included studies were assessed for their methodological quality using the QUADAS tool. Study characteristics and reported diagnostic accuracy were extracted. Results. Twenty-two additional articles in addition to the 24 included in the previous review met the inclusion criteria. Combined, this resulted in 20 articles concerning imaging tests, 11 articles evaluating electrodiagnostic tests, and 15 articles evaluating clinical tests. Estimates of the diagnostic accuracy of the tests differed considerably. Conclusion. There is a need for a consensus on criteria to define and classify lumbar spinal stenosis. At present, the most promising imaging test for lumbar spinal stenosis is magnetic resonance imaging, avoiding myelography because of its invasiveness and lack of superior accuracy. Electrodiagnostic studies showed no superior accuracy for conventional electrodiagnostic testing compared with magnetic resonance imaging. These tests should be considered in the context of those presenting symptoms with the highest diagnostic value, including radiating leg pain that is exacerbated while standing up, the absence of pain when seated, the improvement of symptoms when bending forward, and a wide-based gait. C1 [de Schepper, Evelien I. T.; Koes, Bart W.; Bierma-Zeinstra, Sita M. A.; Luijsterburg, Pim A. J.] Univ Med Ctr, Erasmus MC, Dept Gen Practice, NL-3000 CA Rotterdam, Netherlands. [Overdevest, Gijsbert M.; Peul, Wilco C.] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. [Suri, Pradeep] VA Boston Healthcare Syst, Dept Div Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Suri, Pradeep] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Oei, Edwin H. G.] Univ Med Ctr, Erasmus MC, Dept Radiol, NL-3000 CA Rotterdam, Netherlands. RP de Schepper, EIT (reprint author), Univ Med Ctr, Erasmus MC, Dept Gen Practice, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM e.deschepper@erasmusmc.nl RI Koes, Bart/K-4614-2016 OI Koes, Bart/0000-0002-0450-9969 NR 61 TC 17 Z9 17 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 15 PY 2013 VL 38 IS 8 BP E469 EP E481 DI 10.1097/BRS.0b013e31828935ac PG 13 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 125TY UT WOS:000317565400005 PM 23385136 ER PT J AU Vaid, M Prasad, R Singh, T Elmets, CA Xu, H Katiyar, SK AF Vaid, Mudit Prasad, Ram Singh, Tripti Elmets, Craig A. Xu, Hui Katiyar, Santosh K. TI Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE DNA repair; Contact hypersensitivity; Cyclobutane pyrimidine dimer; Nucleotide excision repair; Silymarin; Ultraviolet radiation ID UV-INDUCED IMMUNOSUPPRESSION; ANTIGEN-PRESENTING ACTIVITY; CONTACT HYPERSENSITIVITY; SKIN-CANCER; TRANSPLANT RECIPIENTS; PYRIMIDINE DIMERS; IRRADIATED MICE; RISK-FACTOR; IN-VITRO; INDUCTION AB Silymarin inhibits UVB-induced immunosuppression in mouse skin. To identify the molecular mechanisms underlying this effect, we used an adoptive transfer approach in which dendritic cells (DCs) from the draining lymph nodes of donor mice that had been UVB-exposed and sensitized to 2,4,-dinitrofluorobenzene (DNFB) were transferred into naive recipient mice. The contact hypersensitivity (CHS) response of the recipient mice to DNFB was then measured. When DCs were obtained from UVB-exposed donor mice that were not treated with silymarin, the CHS response was suppressed confirming-the role of DCs in the UVB-induced immunosuppression. Silymarin treatment of UVB-exposed donor mice relieved this suppression of the CHS response in the recipients. Silymarin treatment was associated with rapid repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in DCs and silymarin treatment did not prevent UV-induced immunosuppression in XPA-deficient mice which are unable to repair UV-induced DNA damage. The CHS response in mice receiving DCs from silymarin-treated UV-exposed donor mice also was associated with enhanced secretion of Th1-type cytokines and stimulation of T cells. Adoptive transfer of T cells revealed that transfer of either CD8(+) or CD4(+) cells from silymarin-treated, UVB-exposed donors resulted in enhancement of the CHS response. Cell culture study showed enhanced secretion of IL-2 and IFN gamma by CD8(+) T cells, and reduced secretion of Th2 cytokines by CD4(+) T cells, obtained from silymarin-treated UVB-exposed mice. These data suggest that DNA repair-dependent functional activation of DCs, a reduction in CD4(+) regulatory T-cell activity, and stimulation of CD8(+) effector T cells contribute to silymarin-mediated inhibition of UVB-induced immunosuppression. (C) 2013 Elsevier Inc. All rights reserved. C1 [Vaid, Mudit; Prasad, Ram; Singh, Tripti; Elmets, Craig A.; Xu, Hui; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Elmets, Craig A.; Xu, Hui; Katiyar, Santosh K.] Univ Alabama Birmingham, Skin Dis Res Ctr, Birmingham, AL 35294 USA. [Elmets, Craig A.; Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Institutes of Health [CA140197]; DAB Skin Diseases Research Center [AR050948]; Veterans Administration Merit Review Award [5I01BX001059, 1I01BX001410] FX This work was supported by the funds from National Institutes of Health (Grant # CA140197) to S.K.K. and H.X., the DAB Skin Diseases Research Center (AR050948), and the Veterans Administration Merit Review Award (5I01BX001059 and 1I01BX001410) to C.A.E. and S.K.K. We thank Dr. Fiona Hunter for her assistance in editing the manuscript. NR 39 TC 5 Z9 6 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 2013 VL 85 IS 8 BP 1066 EP 1076 DI 10.1016/j.bcp.2013.01.026 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 115XS UT WOS:000316845800005 PM 23395695 ER PT J AU Li, XB Hartwell, KJ Owens, M LeMatty, T Borckardt, JJ Hanlon, CA Brady, KT George, MS AF Li, Xingbao Hartwell, Karren J. Owens, Max LeMatty, Todd Borckardt, Jeffrey J. Hanlon, Colleen A. Brady, Kathleen T. George, Mark S. TI Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Reduces Nicotine Cue Craving SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Craving; dorsolateral prefrontal cortex; nicotine; smoking; tobacco; transcranial magnetic stimulation ID PREDICTING SMOKING-CESSATION; FAGERSTROM TEST; STRIATAL DOPAMINE; RANDOMIZED-TRIAL; TOBACCO SMOKING; MOTOR CORTEX; DEPRESSION; DEPENDENCE; ADDICTION; BRAIN AB Background: Repetitive transcranial magnetic stimulation (rTMS) can noninvasively stimulate the brain and transiently amplify or block behaviors mediated through a region. We hypothesized that a single high-frequency rTMS session over the left dorsolateral prefrontal cortex (DLPFC) would reduce cue craving for cigarettes compared with a sham TMS session. Methods: Sixteen non-treatment-seeking, nicotine-dependent participants were randomized to receive either real high-frequency rTMS (10 Hz, 100% resting motor threshold, 5-sec on, 10-sec off for 15 min; 3000 pulses) or active sham (eSham) TMS over the DLPFC in two visits with 1 week between visits. The participants received cue exposure before and after rTMS and rated their craving after each block of cue presentation. Results: Stimulation of the left DLFPC with real, but not sham, rTMS reduced craving significantly from baseline (64.1 +/- .5.9 vs. 45.7 +/- 6.4, t = 2.69, p = .018). When compared with neutral cue craving, the effect of real TMS on cue craving was significantly greater than the effect of sham TMS (12.5 +/- 10.4 vs. 9.1 +/- 10.4; t = 2.07, p = .049). More decreases in subjective craving induced by TMS correlated positively with higher Fagerstrom Test for Nicotine Dependence score (r = .58, p =.031) and more cigarettes smoked per day (r = .57, p = .035). Conclusions: One session of high-frequency rTMS (10 Hz) of the left DLPFC significantly reduced subjective craving induced by smoking cues in nicotine-dependent participants. Additional studies are needed to explore rTMS as an aid to smoking cessation. C1 [Li, Xingbao; Hartwell, Karren J.; Owens, Max; LeMatty, Todd; Borckardt, Jeffrey J.; Hanlon, Colleen A.; Brady, Kathleen T.; George, Mark S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hartwell, Karren J.; Brady, Kathleen T.; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Li, XB (reprint author), Med Univ South Carolina IOP, Dept Psychiat, Brain Stimulat Lab, 502 N,67 President St, Charleston, SC 29425 USA. EM lixi@musc.edu FU Brain Stimulation Laboratory at the Medical University of South Carolina; National Institute of Health [5R21DA026085]; Cyberonics; Force Protection; GlaxoSmithKline; Jazz Pharmaceuticals; MECTA; Neurospace; Pure Tech Ventures FX The study was funded by a Grant-in-Kind from the Brain Stimulation Laboratory at the Medical University of South Carolina and a grant from National Institute of Health (Grant No. 5R21DA026085 to KTB, MSG); Mark George has served as a paid consultant to or received research support from Cyberonics, Force Protection, GlaxoSmithKline, Jazz Pharmaceuticals, MECTA, Neurospace, and Pure Tech Ventures and as an unpaid consultant to Brainsonix, Brainsway, Cephos, MECTA, NeoSync, and Neuronetics. All other authors report no biomedical financial interests or potential conflicts of interest. NR 68 TC 35 Z9 36 U1 6 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2013 VL 73 IS 8 BP 714 EP 720 DI 10.1016/j.biopsych.2013.01.003 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 120GT UT WOS:000317159500005 PM 23485014 ER PT J AU Mayer, KH Zanoni, BC AF Mayer, Kenneth H. Zanoni, Brian C. TI HIV Chemoprophylaxis for Adolescents: Educable Moment, Not Magic Bullet SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE HIV; prevention; adolescents; preexposure prophylaxis ID UNITED-STATES; PREEXPOSURE PROPHYLAXIS; AFRICAN-AMERICAN; SEXUAL-BEHAVIOR; RISK REDUCTION; PREVENTION; TRIAL; INTERVENTIONS; SURVEILLANCE; TRANSMISSION C1 [Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Mayer, Kenneth H.; Zanoni, Brian C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zanoni, Brian C.] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA USA. [Zanoni, Brian C.] Harvard, Charlestown, MA USA. RP Mayer, KH (reprint author), Fenway Hlth, 1340 Boylston St, Boston, MA 02215 USA. EM kmayer@fenwayhealth.org FU NIAID NIH HHS [T32 AI052074] NR 25 TC 0 Z9 0 U1 0 U2 0 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 15 PY 2013 VL 56 IS 8 BP 1156 EP 1158 DI 10.1093/cid/cis1026 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 113WM UT WOS:000316700100020 PM 23223593 ER PT J AU Chi, W Wu, E Morgan, BA AF Chi, Woo Wu, Eleanor Morgan, Bruce A. TI Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline SO DEVELOPMENT LA English DT Article DE Hair; Dermal papilla; Stem cell niche ID BETA-CATENIN ACTIVITY; STEM-CELLS; REGENERATION; ACTIVATION; EXPRESSION; FOLLICLES; MATRIX; GROWTH; BEHAVIORS; VOLUME AB Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss. C1 [Morgan, Bruce A.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Morgan, BA (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu FU National Institutes of Health, National Institute of Arthritis, Musculoskeletal and Skin Diseases [R01AR055256] FX This work was supported by a grant from the National Institutes of Health, National Institute of Arthritis, Musculoskeletal and Skin Diseases [R01AR055256 to B.A.M.]. Deposited in PMC for release after 12 months. NR 25 TC 53 Z9 55 U1 0 U2 11 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR 15 PY 2013 VL 140 IS 8 BP 1676 EP 1683 DI 10.1242/dev.090662 PG 8 WC Developmental Biology SC Developmental Biology GA 114HH UT WOS:000316731200007 PM 23487317 ER PT J AU Twigg, SRF Babbs, C van den Elzen, MEP Goriely, A Taylor, S McGowan, SJ Giannoulatou, E Lonie, L Ragoussis, J Akha, ES Knight, SJL Zechi-Ceide, RM Hoogeboom, JAM Pober, BR Toriello, HV Wall, SA Passos-Bueno, MR Brunner, HG Mathijssen, IMJ Wilkie, AOM AF Twigg, Stephen R. F. Babbs, Christian van den Elzen, Marijke E. P. Goriely, Anne Taylor, Stephen McGowan, Simon J. Giannoulatou, Eleni Lonie, Lorne Ragoussis, Jiannis Akha, Elham Sadighi Knight, Samantha J. L. Zechi-Ceide, Roseli M. Hoogeboom, Jeannette A. M. Pober, Barbara R. Toriello, Helga V. Wall, Steven A. Rita Passos-Bueno, M. Brunner, Han G. Mathijssen, Irene M. J. Wilkie, Andrew O. M. TI Cellular interference in craniofrontonasal syndrome: males mosaic for mutations in the X-linked EFNB1 gene are more severely affected than true hemizygotes SO HUMAN MOLECULAR GENETICS LA English DT Article ID VARIABLE EXPRESSION; EPHRIN-B1; DYSPLASIA; INHERITANCE; PHENOTYPE; HUMANS; FAMILY AB Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with hypertelorism as the only feature. X-inactivation is proposed to explain the more severe outcome in heterozygous females, as this leads to functional mosaicism for cells with differing expression of EPHRIN-B1, generating abnormal tissue boundariesua process that cannot occur in hemizygous males. Apparently challenging this model, males occasionally present with a more severe female-like CFNS phenotype. We hypothesized that such individuals might be mosaic for EFNB1 mutations and investigated this possibility in multiple tissue samples from six sporadically presenting males. Using denaturing high performance liquid chromatography, massively parallel sequencing and multiplex-ligation-dependent probe amplification (MLPA) to increase sensitivity above standard dideoxy sequencing, we identified mosaic mutations of EFNB1 in all cases, comprising three missense changes, two gene deletions and a novel point mutation within the 5 untranslated region (UTR). Quantification by Pyrosequencing and MLPA demonstrated levels of mutant cells between 15 and 69. The 5 UTR variant mutates the stop codon of a small upstream open reading frame that, using a dual-luciferase reporter construct, was demonstrated to exacerbate interference with translation of the wild-type protein. These results demonstrate a more severe outcome in mosaic than in constitutionally deficient males in an X-linked dominant disorder and provide further support for the cellular interference mechanism, normally related to X-inactivation in females. C1 [Twigg, Stephen R. F.; Babbs, Christian; Goriely, Anne; Giannoulatou, Eleni; Wilkie, Andrew O. M.] Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England. [Taylor, Stephen; McGowan, Simon J.; Giannoulatou, Eleni] Univ Oxford, Weatherall Inst Mol Med, Computat Biol Res Grp, Oxford OX3 9DS, England. [van den Elzen, Marijke E. P.; Mathijssen, Irene M. J.] Univ Med Ctr, Erasmus MC, Dept Plast & Reconstruct Surg, Rotterdam, Netherlands. [Hoogeboom, Jeannette A. M.] Univ Med Ctr, Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Lonie, Lorne; Ragoussis, Jiannis] Univ Oxford, Wellcome Trust Ctr Human Genet, Genom Grp, Oxford OX3 9DS, England. [Akha, Elham Sadighi; Knight, Samantha J. L.] Univ Oxford, Wellcome Trust Ctr Human Genet, NIHR Biomed Res Ctr Oxford, Oxford OX3 9DS, England. [Zechi-Ceide, Roseli M.] Univ Sao Paulo, Dept Clin Genet, Hosp Rehabil & Craniofacial Anomalies, Sao Paulo, Brazil. [Pober, Barbara R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pober, Barbara R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Toriello, Helga V.] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [Wall, Steven A.; Wilkie, Andrew O. M.] Oxford Univ Hosp NHS Trust, Craniofacial Unit, Oxford, England. [Rita Passos-Bueno, M.] Univ Sao Paulo, Inst Biociencias, Ctr Estudos Genoma Humano, Sao Paulo, Brazil. [Brunner, Han G.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. RP Wilkie, AOM (reprint author), Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. EM andrew.wilkie@imm.ox.ac.uk RI Brunner, Han/C-9928-2013; Zechi-Ceide, Roseli /I-8178-2013; Passos-Bueno, Maria Rita/I-6796-2016; OI Zechi-Ceide, Roseli /0000-0002-4526-3336; Passos-Bueno, Maria Rita/0000-0002-9248-3008; Twigg, Stephen/0000-0001-5024-049X; Giannoulatou, Eleni/0000-0002-7084-6736; McGowan, Simon/0000-0001-9720-1914; Goriely, Anne/0000-0001-9229-7216; Wilkie, Andrew/0000-0002-2972-5481 FU Wellcome Trust [090532/Z/09/Z, 075491/Z/04, 078666, 093329]; NIHR Biomedical Research Centre, Oxford; Department of Health's NIHR Biomedical Research Centres funding scheme FX This work was supported by the Wellcome Trust (Award Grant Number 090532/Z/09/Z to S.J.L.K.; 075491/Z/04 to L. L. and J.R.; 078666 to A.O.M.W.; 093329 to S. R. F. T. and A.O.M.W.). S.J.L.K. was supported by the NIHR Biomedical Research Centre, Oxford, with funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. NR 33 TC 17 Z9 17 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2013 VL 22 IS 8 BP 1654 EP 1662 DI 10.1093/hmg/ddt015 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 117PK UT WOS:000316965400015 PM 23335590 ER PT J AU Ganesh, SK Tragante, V Guo, W Guo, YR Lanktree, MB Smith, EN Johnson, T Castillo, BA Barnard, J Baumert, J Chang, YPC Elbers, CC Farrall, M Fischer, ME Franceschini, N Gaunt, TR Gho, JMIH Gieger, C Gong, Y Isaacs, A Kleber, ME Leach, IM McDonough, CW Meijs, MFL Mellander, O Molony, CM Nolte, IM Padmanabhan, S Price, TS Rajagopalan, R Shaffer, J Shah, S Shen, HQ Soranzo, N van der Most, PJ Van Iperen, EPA Van Setten, JA Vonk, JM Zhang, L Beitelshees, AL Berenson, GS Bhatt, DL Boer, JMA Boerwinkle, E Burkley, B Burt, A Chakravarti, A Chen, W Cooper-DeHoff, RM Curtis, SP Dreisbach, A Duggan, D Ehret, GB Fabsitz, RR Fornage, M Fox, E Furlong, CE Gansevoort, RT Hofker, MH Hovingh, GK Kirkland, SA Kottke-Marchant, K Kutlar, A LaCroix, AZ Langaee, TY Li, YR Lin, HH Liu, K Maiwald, S Malik, R Murugesan, G Newton-Cheh, C OConnell, JR Onland-Moret, NC Ouwehand, WH Palmas, W Penninx, BW Pepine, CJ Pettinger, M Polak, JF Ramachandran, VS Ranchalis, J Redline, S Ridker, PM Rose, LM Scharnag, H Schork, NJ Shimbo, D Shuldiner, AR Srinivasan, SR Stolk, RP Taylor, HA Thorand, B Trip, MD van Duijn, CM Verschuren, WM Wijmenga, C Winkelmann, BR Wyatt, S Young, JH Boehm, BO Caulfield, MJ Chasman, DI Davidson, KW Doevendans, PA FitzGerald, GA Gums, JG Hakonarson, H Hillege, HL Illig, T Jarvik, GP Johnson, JA Kastelein, JJP Koenig, W Marz, W Mitchell, BD Murray, SS Oldehinkel, AJ Rader, DJ Reilly, MP Reiner, AP Schadt, EE Silverstein, RL Snieder, H Stanton, AV Uitterlinden, AG van der Harst, P van der Schouw, YT Samani, NJ Johnson, AD Munroe, PB de Bakker, PIW Zhu, XF Levy, D Keating, BJ Asselbergs, FW AF Ganesh, Santhi K. Tragante, Vinicius Guo, Wei Guo, Yiran Lanktree, Matthew B. Smith, Erin N. Johnson, Toby Castillo, Berta Almoguera Barnard, John Baumert, Jens Chang, Yen-Pei Christy Elbers, Clara C. Farrall, Martin Fischer, Mary E. Franceschini, Nora Gaunt, Tom R. Gho, Johannes M. I. H. Gieger, Christian Gong, Yan Isaacs, Aaron Kleber, Marcus E. Leach, Irene Mateo McDonough, Caitrin W. Meijs, Matthijs F. L. Mellander, Olle Molony, Cliona M. Nolte, Ilja M. Padmanabhan, Sandosh Price, Tom S. Rajagopalan, Ramakrishnan Shaffer, Jonathan Shah, Sonia Shen, Haiqing Soranzo, Nicole van der Most, Peter J. Van Iperen, Erik P. A. Van Setten, Jessic A. Vonk, Judith M. Zhang, Li Beitelshees, Amber L. Berenson, Gerald S. Bhatt, Deepak L. Boer, Jolanda M. A. Boerwinkle, Eric Burkley, Ben Burt, Amber Chakravarti, Aravinda Chen, Wei Cooper-DeHoff, Rhonda M. Curtis, Sean P. Dreisbach, Albert Duggan, David Ehret, Georg B. Fabsitz, Richard R. Fornage, Myriam Fox, Ervin Furlong, Clement E. Gansevoort, Ron T. Hofker, Marten H. Hovingh, G. Kees Kirkland, Susan A. Kottke-Marchant, Kandice Kutlar, Abdullah LaCroix, Andrea Z. Langaee, Taimour Y. Li, Yun R. Lin, Honghuang Liu, Kiang Maiwald, Steffi Malik, Rainer Murugesan, Gurunathan Newton-Cheh, Christopher OConnell, Jeffery R. Onland-Moret, N. Charlotte Ouwehand, Willem H. Palmas, Walter Penninx, Brenda W. Pepine, Carl J. Pettinger, Mary Polak, Joseph F. Ramachandran, Vasan S. Ranchalis, Jane Redline, Susan Ridker, Paul M. Rose, Lynda M. Scharnag, Hubert Schork, Nicholas J. Shimbo, Daichi Shuldiner, Alan R. Srinivasan, Sathanur R. Stolk, Ronald P. Taylor, Herman A. Thorand, Barbara Trip, Mieke D. van Duijn, Cornelia M. Verschuren, W. Monique Wijmenga, Cisca Winkelmann, Bernhard R. Wyatt, Sharon Young, J. Hunter Boehm, Bernhard O. Caulfield, Mark J. Chasman, Daniel I. Davidson, Karina W. Doevendans, Pieter A. FitzGerald, Garret A. Gums, John G. Hakonarson, Hakon Hillege, Hans L. Illig, Thomas Jarvik, Gail P. Johnson, Julie A. Kastelein, John J. P. Koenig, Wolfgang Maerz, Winfried Mitchell, Braxton D. Murray, Sarah S. Oldehinkel, Albertine J. Rader, Daniel J. Reilly, Muredach P. Reiner, Alex P. Schadt, Eric E. Silverstein, Roy L. Snieder, Harold Stanton, Alice V. Uitterlinden, Andre G. van der Harst, Pim van der Schouw, Yvonne T. Samani, Nilesh J. Johnson, Andrew D. Munroe, Patricia B. de Bakker, Paul I. W. Zhu, Xiaofeng Levy, Daniel Keating, Brendan J. Asselbergs, Folkert W. CA CARDIOGRAM METASTROKE LifeLines Cohort Study TI Loci influencing blood pressure identified using a cardiovascular gene-centric array SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HISTAMINE-RECEPTOR H-1; CORONARY-HEART-DISEASE; PULSE PRESSURE; EXPRESSION; P53; HYPERTENSION; MDM2; MICE; METAANALYSIS AB Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention. C1 [Ganesh, Santhi K.; Scharnag, Hubert] Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA. [Tragante, Vinicius; Gho, Johannes M. I. H.; Meijs, Matthijs F. L.; Doevendans, Pieter A.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, NL-3508 GA Utrecht, Netherlands. [Tragante, Vinicius; Elbers, Clara C.; Van Setten, Jessic A.; Onland-Moret, N. Charlotte; de Bakker, Paul I. W.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3508 GA Utrecht, Netherlands. [Elbers, Clara C.; Onland-Moret, N. Charlotte; van der Schouw, Yvonne T.; de Bakker, Paul I. W.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands. [Guo, Wei; Zhu, Xiaofeng] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Silverstein, Roy L.] Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Dept Mol Med, Cleveland, OH 44106 USA. [Guo, Yiran; Castillo, Berta Almoguera; Li, Yun R.; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp Philadelphia, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Lanktree, Matthew B.] Univ Western Ontario, Dept Med, Schulich Sch Med & Dent, London, ON, Canada. [Lanktree, Matthew B.] Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, London, ON, Canada. [Smith, Erin N.] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. [Smith, Erin N.] Univ Calif San Diego, Sch Med, Radys Childrens Hosp, La Jolla, CA 92093 USA. [Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, London EC1M 6BQ, England. [Johnson, Toby; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Genome Ctr, William Harvey Res Inst, London EC1M 6BQ, England. [Johnson, Toby; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, London EC1M 6BQ, England. [Barnard, John; Zhang, Li; Beitelshees, Amber L.] Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Silverstein, Roy L.] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44106 USA. [Baumert, Jens; Thorand, Barbara] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Chang, Yen-Pei Christy; Shen, Haiqing] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Chang, Yen-Pei Christy; OConnell, Jeffery R.; Shuldiner, Alan R.; Mitchell, Braxton D.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford OX3 7BN, England. [Fischer, Mary E.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Gaunt, Tom R.] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England. [Gong, Yan; McDonough, Caitrin W.; Burkley, Ben; Cooper-DeHoff, Rhonda M.; Langaee, Taimour Y.; Gums, John G.; Johnson, Julie A.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA. [Gong, Yan; McDonough, Caitrin W.; Burkley, Ben; Cooper-DeHoff, Rhonda M.; Langaee, Taimour Y.; Johnson, Julie A.] Univ Florida, Ctr Pharmacogen, Gainesville, FL USA. [Gums, John G.] Univ Florida, Dept Community Hlth & Family Med, Gainesville, FL USA. [Isaacs, Aaron; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Kleber, Marcus E.] LURIC Study Nonprofit LLC, Freiburg, Germany. [Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Mannheim Med Fac, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, Germany. [Leach, Irene Mateo; Hillege, Hans L.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Nolte, Ilja M.; van der Most, Peter J.; Vonk, Judith M.; Stolk, Ronald P.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Med, Div Nephrol, Groningen, Netherlands. [Hofker, Marten H.] Univ Groningen, Univ Med Ctr Groningen, Med Biol Sect, Dept Pathol & Med Biol, Groningen, Netherlands. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [LifeLines Cohort Study] Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands. [Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands. [Mellander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Mellander, Olle] Skane Univ Hosp, Ctr Emergency Med, Malmo, Sweden. [Molony, Cliona M.] Rosetta Inpharmat, Dept Genet, Seattle, WA USA. [Padmanabhan, Sandosh] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland. [Price, Tom S.] Inst Psychiat, MRC SGDP Ctr, London, England. [Rajagopalan, Ramakrishnan; Burt, Amber; Furlong, Clement E.; Ranchalis, Jane; Jarvik, Gail P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Shaffer, Jonathan; Palmas, Walter; Shimbo, Daichi; Davidson, Karina W.] Columbia Univ, Dept Med, New York, NY USA. [Shah, Sonia] UCL, UCL Genet Inst, Dept Genet Evolut & Environm, London WC1E 6BT, England. [Soranzo, Nicole] Univ Cambridge, Cambridge, England. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Ouwehand, Willem H.] NHS Blood & Transplant, Cambridge, England. [Ouwehand, Willem H.] Wellcome Trust Sanger Inst, Hinxton, England. [Van Iperen, Erik P. A.; Asselbergs, Folkert W.] AMC, Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Van Iperen, Erik P. A.] AMC, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands. [Hovingh, G. Kees; Kastelein, John J. P.] AMC, Dept Vasc Med, Amsterdam, Netherlands. [Trip, Mieke D.] AMC, Dept Cardiol, Amsterdam, Netherlands. [Berenson, Gerald S.; Chen, Wei; Srinivasan, Sathanur R.] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Boer, Jolanda M. A.; Verschuren, W. Monique] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr, Div Epidemiol, Houston, TX USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Chakravarti, Aravinda; Ehret, Georg B.] Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Young, J. Hunter] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Curtis, Sean P.] Merck Res Labs, Rahway, NJ 07065 USA. [Dreisbach, Albert; Fox, Ervin; Taylor, Herman A.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Wyatt, Sharon] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. [Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA. [Fabsitz, Richard R.; Pettinger, Mary] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Kirkland, Susan A.] Dalhousie Univ, Dept Community Hlth & Epidemiol, Halifax, NS B3H 3J5, Canada. [Kottke-Marchant, Kandice; Murugesan, Gurunathan] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA. [Kutlar, Abdullah] Med Coll Georgia, Augusta, GA 30912 USA. [LaCroix, Andrea Z.; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Lin, Honghuang; Ramachandran, Vasan S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Ramachandran, Vasan S.; Johnson, Andrew D.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Maiwald, Steffi] Univ Amsterdam, Dept Vasc Med, Amsterdam, Netherlands. [Malik, Rainer] Univ Munich, Klinikum Grosshadern, Inst Stroke & Dementia Res, D-80539 Munich, Germany. [Malik, Rainer] Univ Munich, Klinikum Grosshadern, Neurol Klin, D-80539 Munich, Germany. [Newton-Cheh, Christopher; de Bakker, Paul I. W.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Dept Psychiat, Amsterdam, Netherlands. [Pepine, Carl J.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA. [Polak, Joseph F.] Tufts Med Ctr, Dept Radiol, Boston, MA USA. [Redline, Susan; Ridker, Paul M.; Rose, Lynda M.; Chasman, Daniel I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Scharnag, Hubert] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Schork, Nicholas J.; Murray, Sarah S.] Scripps Translat Sci Inst, La Jolla, CA USA. [Schork, Nicholas J.] Scripps Res Inst, La Jolla, CA 92037 USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Winkelmann, Bernhard R.] Cardiol Grp, Frankfurt, Germany. [Boehm, Bernhard O.] Univ Ulm, Med Ctr, Div Endocrinol, D-89069 Ulm, Germany. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 1, D-89069 Ulm, Germany. [Davidson, Karina W.] Columbia Univ, Dept Psychiat, New York, NY USA. [FitzGerald, Garret A.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Maerz, Winfried] Synlab Acad, Mannheim, Germany. [Murray, Sarah S.] Scripps Hlth, La Jolla, CA USA. [Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Stanton, Alice V.] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England. [Samani, Nilesh J.] Glenfield Gen Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England. RP Keating, BJ (reprint author), Univ Penn, Dept Pediat, Off 1016 Abramson Bldg,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bkeating@mail.med.upenn.edu; f.w.asselbergs@umcutrecht.nl RI Jarvik, Gail/N-6476-2014; Gaunt, Tom/O-3918-2014; Johnson, Andrew/G-6520-2013; sebastianovitsch, stepan/G-8507-2013; Stanton, Alice/F-4697-2012; de Bakker, Paul/B-8730-2009; Shah, Sonia/N-7547-2013; Wijmenga, Cisca/D-2173-2009; van der Schouw, Yvonne/F-8327-2014; Thorand, Barbara/B-5349-2014; Guo, Yiran/H-4120-2011; Price, Thomas/B-7372-2008; EHRET, Georg/A-9532-2009; Boehm, Bernhard/F-8750-2015; Onland-Moret, N. Charlotte/G-9185-2011; Padmanabhan, Sandosh/S-3963-2016; OI Jarvik, Gail/0000-0002-6710-8708; Gaunt, Tom/0000-0003-0924-3247; de Bakker, Paul/0000-0001-7735-7858; Shah, Sonia/0000-0001-5860-4526; van der Schouw, Yvonne/0000-0002-4605-435X; Thorand, Barbara/0000-0002-8416-6440; Guo, Yiran/0000-0002-6549-8589; Price, Thomas/0000-0001-7356-2109; Gieger, Christian/0000-0001-6986-9554; Wijmenga, Cisca/0000-0002-5635-1614; van Iperen, Erik/0000-0001-7107-3168; Mitchell, Braxton/0000-0003-4920-4744; Ouwehand, Willem/0000-0002-7744-1790; Kleber, Marcus/0000-0003-0663-7275; EHRET, Georg/0000-0002-5730-0675; Lanktree, Matthew/0000-0002-5750-6286; Lin, Honghuang/0000-0003-3043-3942; Stanton, Alice/0000-0002-4961-165X; Johnson, Toby/0000-0002-5998-3270; Padmanabhan, Sandosh/0000-0003-3869-5808; Ramachandran, Vasan/0000-0001-7357-5970; Soranzo, Nicole/0000-0003-1095-3852 FU National Heart, Lung and Blood Institute; Broad Institute [N01-HC-65226] FX We thank the National Heart, Lung and Blood Institute and the research institutions, study investigators and field staff for their support in creating the CARe program for biomedical research. We also thank the study participants, without whom this endeavor would not have been possible. DNA samples were genotyped in part through the Broad Institute (N01-HC-65226). NR 63 TC 61 Z9 61 U1 1 U2 49 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2013 VL 22 IS 8 BP 1663 EP 1678 DI 10.1093/hmg/dds555 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 117PK UT WOS:000316965400016 PM 23303523 ER PT J AU Johnson, NP Chavez, JF Mosley, WJ Flaherty, JD Fox, JM AF Johnson, Nils P. Chavez, Jose F. Mosley, William J., II Flaherty, James D. Fox, Justin M. TI Performance of electrocardiographic criteria to differentiate Takotsubo cardiomyopathy from acute anterior ST elevation myocardial infarction SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Electrocardiogram; Takotsubo cardiomyopathy; ST-segment elevation myocardial infarction; Diagnostic criteria; Diagnostic accuracy ID SEGMENT ELEVATION; TAKO-TSUBO; DIAGNOSIS; ECG AB Background: The initial electrocardiogram (ECG) in Takotsubo cardiomyopathy (TC) can mimic an acute, anterior ST-segment elevation myocardial infarction (STEMI). Given the profound and immediate treatment differences between TC and STEMI, it would be clinically valuable to distinguish them using ECG criteria. Methods: Presenting ECGs for proven cases of TC and acute, anterior STEMI were retrospectively collected. QRS onset and J-point were manually identified using custom software to compute median ST deviation for each lead. Six published ECG criteria were examined for diagnostic accuracy using the clinical diagnosis as the gold standard. Results: 33 TC and 263 acute, anterior STEMI cases were identified. ST-segment deviation differed significantly between groups for all leads except aVR, I, V5, and V6. All six published ECG criteria showed a marked reduction in diagnostic accuracy in our validation cohort, except for a combination of ST-elevation in leads V2<1.75 mm and V3<2.5 mm (sensitivity 79%, specificity 73% for TC). Conclusion: Our study demonstrates the limited diagnostic accuracy of published ECG rules to distinguish TC from acute, anterior STEMI. Given the rarity of TC and the clinical consequences of a "false positive" TC diagnosis based on ECG criteria alone, such rules should not be used in practice. TC remains a diagnosis of exclusion after emergent angiography in patients with an acute coronary syndrome and significant ST-segment elevation. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Johnson, Nils P.; Chavez, Jose F.; Mosley, William J., II; Flaherty, James D.; Fox, Justin M.] Northwestern Univ, Dept Med, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA. [Johnson, Nils P.] Univ Texas Houston, Weatherhead PET Ctr Preventing & Reversing Athero, Div Cardiol, Dept Med,Med Sch, Houston, TX 77030 USA. [Johnson, Nils P.] Mem Hermann Hosp, Houston, TX USA. [Fox, Justin M.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Johnson, NP (reprint author), Univ Texas Houston, Weatherhead PET Ctr Preventing & Reversing Athero, Med Sch Houston, 6431 Fannin St,Room 4-256 MSB, Houston, TX 77030 USA. EM Nils.Johnson@uth.tmc.edu NR 16 TC 12 Z9 12 U1 0 U2 2 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 APR 15 PY 2013 VL 164 IS 3 BP 345 EP 348 DI 10.1016/j.ijcard.2011.07.029 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 112NT UT WOS:000316599700023 PM 21802749 ER PT J AU Gramfort, A Strohmeier, D Haueisen, J Hamalainen, MS Kowalski, M AF Gramfort, A. Strohmeier, D. Haueisen, J. Haemaelaeinen, M. S. Kowalski, M. TI Time-frequency mixed-norm estimates: Sparse M/EEG imaging with non-stationary source activations SO NEUROIMAGE LA English DT Article DE Inverse problem; Magnetoencephalography (MEG); Electroencephalography (EEG); Sparse structured priors; Convex optimization; Time-frequency; Algorithms ID INVERSE PROBLEM; SOURCE RECONSTRUCTION; CORTICAL ACTIVITY; EEG; MEG; LOCALIZATION; PERFORMANCE; SHRINKAGE; ALGORITHM; PURSUIT AB Magnetoencephalography (MEG) and electroencephalography (EEG) allow functional brain imaging with high temporal resolution. While solving the inverse problem independently at every time point can give an image of the active brain at every millisecond, such a procedure does not capitalize on the temporal dynamics of the signal. Linear inverse methods (minimum-norm, dSPM, sLORETA, beamformers) typically assume that the signal is stationary: regularization parameter and data covariance are independent of time and the time varying signal-to-noise ratio (SNR). Other recently proposed non-linear inverse solvers promoting focal activations estimate the sources in both space and time while also assuming stationary sources during a time interval. However such a hypothesis holds only for short time intervals. To overcome this limitation, we propose time-frequency mixed-norm estimates (TF-MxNE), which use time-frequency analysis to regularize the ill-posed inverse problem. This method makes use of structured sparse priors defined in the time-frequency domain, offering more accurate estimates by capturing the non-stationary and transient nature of brain signals. State-of-the-art convex optimization procedures based on proximal operators are employed, allowing the derivation of a fast estimation algorithm. The accuracy of the TF-MxNE is compared with recently proposed inverse solvers with help of simulations and by analyzing publicly available MEG datasets. (c) 2013 Elsevier Inc. All rights reserved. C1 [Gramfort, A.] Telecom ParisTech, Inst Mines Telecom, CNRS LTCI, F-75014 Paris, France. [Gramfort, A.] INRIA, Parietal Team, Saclay, France. [Gramfort, A.] CEA Saclay, F-91191 Gif Sur Yvette, France. [Gramfort, A.; Haemaelaeinen, M. S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gramfort, A.; Haemaelaeinen, M. S.] Harvard Univ, Sch Med, Charlestown, MA USA. [Strohmeier, D.; Haueisen, J.] Ilmenau Univ Technol, Inst Biomed Engn & Informat, Ilmenau, Germany. [Haueisen, J.] Univ Hosp Jena, Dept Neurol, Biomagnet Ctr, Jena, Germany. [Kowalski, M.] Supelec CNRS Univ Paris Sud, Lab Signaux & Syst L2S, F-91192 Gif Sur Yvette, France. RP Gramfort, A (reprint author), Telecom ParisTech, Inst Mines Telecom, CNRS LTCI, 37-39 Rue Dareau, F-75014 Paris, France. EM alexandre.gramfort@telecom-pariste.fr RI Hamalainen, Matti/C-8507-2013; Haueisen, Jens/B-7183-2011 OI Haueisen, Jens/0000-0003-3871-2890 FU National Center for Research Resources [41 RR014075-11]; National Institute of Biomedical Imaging and Bioengineering [5R01EB009048, R01 EB006385]; German Research Foundation [Ha 2899/8-2]; French Agence Nationale de la Recherche (ANR) [ViMAGINEANR-08-BLAN-0250-02] FX This work was supported by the National Center for Research Resources P41 RR014075-11, the National Institute of Biomedical Imaging and Bioengineering grants 5R01EB009048 and R01 EB006385, the German Research Foundation (Ha 2899/8-2), and the French Agence Nationale de la Recherche (ANR) grant ViMAGINEANR-08-BLAN-0250-02. NR 46 TC 49 Z9 50 U1 0 U2 35 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2013 VL 70 BP 410 EP 422 DI 10.1016/j.neuroimage.2012.12.051 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 100LX UT WOS:000315703800040 PM 23291276 ER PT J AU McKenna, JT Yang, C Franciosi, S Winston, S Abarr, KK Rigby, MS Yanagawa, Y McCarley, RW Brown, RE AF McKenna, James T. Yang, Chun Franciosi, Serena Winston, Stuart Abarr, Kathleen K. Rigby, Matthew S. Yanagawa, Yuchio McCarley, Robert W. Brown, Ritchie E. TI Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE green fluorescent protein; glutamic acid decarboxylase; electrical coupling; H-current; parvalbumin ID RETICULAR THALAMIC NUCLEUS; GREEN FLUORESCENT PROTEIN; SLEEP-WAKE STATE; CEREBRAL-CORTEX; VISUAL-CORTEX; CHOLINE-ACETYLTRANSFERASE; PROJECTION NEURONS; DIAGONAL BAND; IN-VITRO; IMMUNOHISTOCHEMICAL LOCALIZATION AB The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium-binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67-GFP knock-in mice) or PV+ neurons (PV-Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67-GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 m) or medium-sized (1520 m) GFP+ neurons. Most medium and large-sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast-firing and spontaneously active in vitro. They exhibited prominent hyperpolarization-activated inward currents and subthreshold spikelets, suggestive of electrical coupling. PV+ neurons recorded in PV-Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep. J. Comp. Neurol., 521:12251250, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [McKenna, James T.; Yang, Chun; Franciosi, Serena; Winston, Stuart; McCarley, Robert W.; Brown, Ritchie E.] VA Boston Healthcare Syst, Neurosci Lab, Brockton, MA 02301 USA. [McKenna, James T.; Yang, Chun; Franciosi, Serena; Winston, Stuart; McCarley, Robert W.; Brown, Ritchie E.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. [Franciosi, Serena] Univ Milan, Sch Med, Inst Human Physiol 2, Milan, Italy. [Abarr, Kathleen K.; Rigby, Matthew S.] Stonehill Coll, Easton, MA 02357 USA. [Yanagawa, Yuchio] Gunma Univ, Grad Sch Med, Dept Genet & Behav Neurosci, Maebashi, Gumma 3718511, Japan. [Yanagawa, Yuchio] JST, CREST, Maebashi, Gumma 3718511, Japan. RP Brown, RE (reprint author), VA Boston Healthcare Syst, Dept Psychiat, In Vitro Neurophysiol Lab, 940 Belmont St, Brockton, MA 02301 USA. EM Ritchie_Brown@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Brown, Ritchie/0000-0002-7164-4132 FU Department of Veterans Affairs Medical Research Service Award; NIMH [R01 MH039683, R21 MH094803]; NHLBI [HL095491]; MEXT, Japan; Takeda Science Foundation FX Grant sponsor: Department of Veterans Affairs Medical Research Service Award (to R.W. McCarley); NIMH; Grant number: R01 MH039683; Grant sponsor: NHLBI; Grant number: HL095491 (to R.W. McCarley); Grant sponsor: NIMH; Grant number: R21 MH094803 (to R.E. Brown); Grant sponsor: Grants-in-Aids for Scientific Research from MEXT, Japan and Takeda Science Foundation (to Y. Yanagawa). NR 87 TC 21 Z9 22 U1 2 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 15 PY 2013 VL 521 IS 6 BP 1225 EP 1250 DI 10.1002/cne.23290 PG 26 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 095IT UT WOS:000315328600003 PM 23254904 ER PT J AU Kopeikina, KJ Polydoro, M Tai, HC Yaeger, E Carlson, GA Pitstick, R Hyman, BT Spires-Jones, TL AF Kopeikina, Katherine J. Polydoro, Manuela Tai, Hwan-Ching Yaeger, Erich Carlson, George A. Pitstick, Rose Hyman, Bradley T. Spires-Jones, Tara L. TI Synaptic alterations in the rTg4510 mouse model of tauopathy SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE Alzheimer's disease; tauopathy; hyperphosphorylated tau; array tomography ID PAIRED HELICAL FILAMENTS; OLIGOMERIC AMYLOID-BETA; WILD-TYPE TAU; ALZHEIMERS-DISEASE; AXONAL-TRANSPORT; TRANSGENIC MICE; NEURONAL LOSS; DENDRITIC SPINES; IN-VIVO; MITOCHONDRIAL DYSFUNCTION AB Synapse loss, rather than the hallmark amyloid- (A) plaques or tau-filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer's disease (AD) brain. The role of A in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau overexpression in a mouse model (rTg4510) will lead to age-dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold-based counting and a manual stereology-based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multiphoton in vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons, suggesting these cells may be particularly vulnerable to tau-induced degeneration. Postmortem, we confirm the presence of tau in dendritic spines of rTg4510-YFP mouse brain by array tomography. These data implicate tau-induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes, thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together, these data show morphological and biochemical synaptic consequences in response to tau overexpression in the rTg4510 mouse model. J. Comp. Neurol., 521:13341353, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Kopeikina, Katherine J.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Kopeikina, Katherine J.; Polydoro, Manuela; Tai, Hwan-Ching; Yaeger, Erich; Hyman, Bradley T.; Spires-Jones, Tara L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Carlson, George A.; Pitstick, Rose] McLaughlin Res Inst, Great Falls, MT 59405 USA. RP Spires-Jones, TL (reprint author), MGH Neurol, 114 16th St, Charlestown, MA 02129 USA. EM tspires@partners.org OI TAI, HWAN-CHING/0000-0003-0668-9163 FU National Institutes of Health [AG08487, T32AG000277, AG026249, R00AG33670]; Alzheimer's Association FX Grant sponsor: National Institutes of Health; Grant numbers: AG08487, T32AG000277, AG026249, R00AG33670; Grant sponsor: Alzheimer's Association Zenith Award. NR 88 TC 26 Z9 26 U1 1 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 15 PY 2013 VL 521 IS 6 BP 1334 EP 1353 DI 10.1002/cne.23234 PG 20 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 095IT UT WOS:000315328600008 PM 23047530 ER PT J AU Ueno, K Hirata, H Hinoda, Y Dahiya, R AF Ueno, Koji Hirata, Hiroshi Hinoda, Yuji Dahiya, Rajvir TI Frizzled homolog proteins, microRNAs and Wnt signaling in cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Review DE FZD; cancer; microRNA; Wnt signaling ID RENAL-CELL CARCINOMA; HUMAN HEPATOCELLULAR-CARCINOMA; WNT/BETA-CATENIN PATHWAY; EPITHELIAL-MESENCHYMAL TRANSITION; POTENTIAL THERAPEUTIC TARGET; HUMAN SYNOVIAL SARCOMA; HUMAN BLADDER-CANCER; BETA-CATENIN; MOLECULAR-CLONING; OVARIAN-CANCER AB Wnt signaling pathways play important roles in tumorigenesis and are initiated by binding of Wnt to various receptors including frizzleds (FZDs). FZDs are one of several families of receptors comprised of FZD/LRP/ROR2/RYK in the Wnt signaling pathway. Expression of some FZD receptors are up regulated, thereby activating the Wnt signaling pathway and is correlated with cancer malignancy and patient outcomes (recurrence and survival) in many cancers. The FZD family contains ten genes in humans and their function has not been completely examined including the regulatory mechanisms of FZD genes in cancer. Knockdown of FZDs may suppress the Wnt signaling pathway resulting in decreased cell growth, invasion, motility and metastasis of cancer cells. Recently a number of microRNAs (miRNAs) have been identified and reported to be important in several cancers. MiRNAs regulate target gene expression at both the transcription and translation levels. The study of miRNA is a newly emerging field and promises to be helpful in understanding the pathogenesis of FZDs in cancer. In addition, miRNAs may be useful in regulating FZDs in cancer cells. Therefore, the aim of this review is to discuss current knowledge of the functional mechanisms of FZDs in cancer, including regulation by miRNAs and the potential for possible use of miRNAs and FZDs in future clinical applications. C1 [Ueno, Koji; Hirata, Hiroshi; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Ueno, Koji; Hirata, Hiroshi; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Hinoda, Yuji] Yamaguchi Univ, Grad Sch Med, Dept Oncol & Lab Med, Yamaguchi, Japan. RP Dahiya, R (reprint author), Vet Affairs Med Ctr, Urol Res Ctr 112F, 4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urology.ucsf.edu FU National Center for Research Resources of the National Institutes of Health [R01CA138642, R01CA130860, R01CA160079]; VA Merit Review; VA Program Project FX Grant sponsors: National Center for Research Resources of the National Institutes of Health; Grant numbers: R01CA138642, R01CA130860, R01CA160079; Grant sponsors: VA Merit Review, VA Program Project NR 158 TC 24 Z9 26 U1 2 U2 93 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2013 VL 132 IS 8 BP 1731 EP 1740 DI 10.1002/ijc.27746 PG 10 WC Oncology SC Oncology GA 090OE UT WOS:000314987800002 PM 22833265 ER PT J AU Ghosh, SK Uchida, M Yoo, B Ross, AW Gendler, SJ Gong, JL Moore, A Medarova, Z AF Ghosh, Subrata K. Uchida, Masashi Yoo, Byunghee Ross, Alana W. Gendler, Sandra J. Gong, Jianlin Moore, Anna Medarova, Zdravka TI Targeted imaging of breast tumor progression and therapeutic response in a human uMUC-1 expressing transgenic mouse model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast cancer; underglycosylated MUC-1 antigen; molecular imaging; target-specific contrast agent; antigen downregulation ID CARCINOMA IN-SITU; CA 15-3; SIRNA DELIVERY; CANCER; MUC1; CELLS; ANTIGEN; IMMUNOTHERAPY; METASTASES; DIAGNOSIS AB The ability to monitor breast cancer initiation and progression on the molecular level would provide an effective tool for early diagnosis and therapy. In the present study, we focused on the underglycosylated MUC-1 tumor antigen (uMUC-1), which is directly linked to tumor progression from pre-malignancy to advanced malignancy in breast cancer and has been identified as the independent predictor of local recurrence and tumor response to chemotherapy. We investigated whether changes in uMUC-1 expression during tumor development and therapeutic intervention could be monitored non-invasively using molecular imaging approach with the uMUC-1-specific contrast agent (MN-EPPT) detectable by magnetic resonance and fluorescence optical imaging. This was done in mice that express human uMUC-1 tumor antigen (MMT mice) and develop spontaneous mammary carcinoma in a stage-wise fashion. After the injection of MN-EPPT there was a significant reduction in average T2 relaxation times of the mammary fat pad between pre-malignancy and cancer. In addition, T2 relaxation times were already altered at pre-malignant state in these mice compared to non-tumor bearing mice. This indicated that targeting uMUC-1 could be useful for detecting pre-malignant transformation in the mammary fat pad. We also probed changes in uMUC-1 expression with MN-EPPT during therapy with doxorubicin (Dox). We observed that tumor delta-T2s were significantly reduced by treatment with Dox indicating lower accumulation of MN-EPPT. This correlated with a lower level of MUC-1 expression in the Dox-treated tumors, as confirmed by immunoblotting. Our study could provide a very sensitive molecular imaging approach for monitoring tumor progression and therapeutic response. C1 [Ghosh, Subrata K.; Uchida, Masashi; Yoo, Byunghee; Ross, Alana W.; Moore, Anna; Medarova, Zdravka] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Mol Imaging Lab, HST Athinoula A Martinos Ctr Biomed Imaging,MGH, Boston, MA USA. [Gendler, Sandra J.] Mayo Clin, Dept Biochem & Mol Biol, Scottsdale, AZ USA. [Gong, Jianlin] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH,Mol Imaging Lab, HMS Athinoula A Martinos Ctr Biomed Imaging,MIT, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu; zmedarova@partners.org FU NIH [1RO1CA135650] FX This study was supported in part by the NIH grant award 1RO1CA135650 to A. M. and Z.M. NR 38 TC 9 Z9 10 U1 0 U2 35 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2013 VL 132 IS 8 BP 1860 EP 1867 DI 10.1002/ijc.27872 PG 8 WC Oncology SC Oncology GA 090OE UT WOS:000314987800015 PM 23015160 ER PT J AU Singh, H Ash, JS Sittig, DF AF Singh, Hardeep Ash, Joan S. Sittig, Dean F. TI Safety Assurance Factors for Electronic Health Record Resilience (SAFER): study protocol SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Electronic health records; Health information technology; Patient safety; Risk assessment; Resilience ID PHYSICIAN ORDER ENTRY; INFORMATION-TECHNOLOGY; PATIENT-SAFETY; MEDICATION ERRORS; CLASSIFICATION; SYSTEMS; CARE; MANAGEMENT AB Background: Implementation and use of electronic health records (EHRs) could lead to potential improvements in quality of care. However, the use of EHRs also introduces unique and often unexpected patient safety risks. Proactive assessment of risks and vulnerabilities can help address potential EHR-related safety hazards before harm occurs; however, current risk assessment methods are underdeveloped. The overall objective of this project is to develop and validate proactive assessment tools to ensure that EHR-enabled clinical work systems are safe and effective. Methods/Design: This work is conceptually grounded in an 8-dimension model of safe and effective health information technology use. Our first aim is to develop self-assessment guides that can be used by health care institutions to evaluate certain high-risk components of their EHR-enabled clinical work systems. We will solicit input from subject matter experts and relevant stakeholders to develop guides focused on 9 specific risk areas and will subsequently pilot test the guides with individuals representative of likely users. The second aim will be to examine the utility of the self-assessment guides by beta testing the guides at selected facilities and conducting on-site evaluations. Our multidisciplinary team will use a variety of methods to assess the content validity and perceived usefulness of the guides, including interviews, naturalistic observations, and document analysis. The anticipated output of this work will be a series of self-administered EHR safety assessment guides with clear, actionable, checklist-type items. Discussion: Proactive assessment of patient safety risks increases the resiliency of health care organizations to unanticipated hazards of EHR use. The resulting products and lessons learned from the development of the assessment guides are expected to be helpful to organizations that are beginning the EHR selection and implementation process as well as those that have already implemented EHRs. Findings from our project, currently underway, will inform future efforts to validate and implement tools that can be used by health care organizations to improve the safety of EHR-enabled clinical work systems. C1 [Singh, Hardeep] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. [Ash, Joan S.] Oregon Hlth & Sci Univ, Sch Med, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Sittig, Dean F.] Univ Texas Houston, Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. RP Singh, H (reprint author), Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.edu FU Westat [HHSP-23320095655WC0095655]; Office of the National Coordinator for Health Information Technology (ONC) [HHSP23337003T]; Houston VA Health Services Research and Development Center of Excellence [HFP90-020] FX The SAFER project is supported through a subcontract from Westat (HHSP-23320095655WC0095655; Anticipating the Unintended Consequences of Health IT) funded by the Office of the National Coordinator for Health Information Technology (ONC) (HHSP23337003T; to Drs. Singh, Ash, and Sittig); and the Houston VA Health Services Research and Development Center of Excellence (HFP90-020) (Dr. Singh). Neither ONC nor its funds were involved in the manuscript writing process. NR 33 TC 9 Z9 9 U1 3 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD APR 12 PY 2013 VL 13 AR 46 DI 10.1186/1472-6947-13-46 PG 8 WC Medical Informatics SC Medical Informatics GA 139FH UT WOS:000318566700001 PM 23587208 ER PT J AU Dolga, AM Netter, MF Perocchi, F Doti, N Meissner, L Tobaben, S Grohm, J Zischka, H Plesnila, N Decher, N Culmsee, C AF Dolga, Amalia M. Netter, Michael F. Perocchi, Fabiana Doti, Nunzianna Meissner, Lilja Tobaben, Svenja Grohm, Julia Zischka, Hans Plesnila, Nikolaus Decher, Niels Culmsee, Carsten TI Mitochondrial Small Conductance SK2 Channels Prevent Glutamate-induced Oxytosis and Mitochondrial Dysfunction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CA2+-ACTIVATED K+ CHANNELS; NEURONAL CELL-DEATH; POTASSIUM CHANNELS; ATP CHANNEL; PROVIDES NEUROPROTECTION; INTEGRATIVE GENOMICS; THERAPEUTIC TARGETS; ALZHEIMERS-DISEASE; CEREBRAL-ISCHEMIA; CALCIUM UNIPORTER AB Small conductance calcium-activated potassium (SK2/K(Ca)2.2) channels are known to be located in the neuronal plasma membrane where they provide feedback control of NMDA receptor activity. Here, we provide evidence that SK2 channels are also located in the inner mitochondrial membrane of neuronal mitochondria. Patch clamp recordings in isolated mitoplasts suggest insertion into the inner mitochondrial membrane with the C and N termini facing the intermembrane space. Activation of SK channels increased mitochondrial K+ currents, whereas channel inhibition attenuated these currents. In a model of glutamate toxicity, activation of SK2 channels attenuated the loss of the mitochondrial transmembrane potential, blocked mitochondrial fission, prevented the release of proapoptotic mitochondrial proteins, and reduced cell death. Neuroprotection was blocked by specific SK2 inhibitory peptides and siRNA targeting SK2 channels. Activation of mitochondrial SK2 channels may therefore represent promising targets for neuroprotective strategies in conditions of mitochondrial dysfunction. C1 [Dolga, Amalia M.; Doti, Nunzianna; Tobaben, Svenja; Grohm, Julia; Culmsee, Carsten] Univ Marburg, Inst Pharmakol & Klin Pharm, Fachbereich Pharm, D-35032 Marburg, Germany. [Netter, Michael F.; Decher, Niels] Univ Marburg, Inst Physiol & Pathophysiol, Fachbereich Med, D-35037 Marburg, Germany. [Perocchi, Fabiana] Harvard Univ, Sch Med, Dept Syst Biol & Med, Boston, MA 02114 USA. [Perocchi, Fabiana] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perocchi, Fabiana] Univ Munich, Gene Ctr, D-81377 Munich, Germany. [Doti, Nunzianna; Plesnila, Nikolaus] Royal Coll Surgeons Ireland, Dept Neurodegenerat, Dublin 2, Ireland. [Doti, Nunzianna] CNR, Inst Biostruct & Bioimaging, I-1680131 Naples, Italy. [Meissner, Lilja; Plesnila, Nikolaus] Univ Munich, Sch Med, Inst Stroke & Dementia Res, D-81377 Munich, Germany. [Zischka, Hans] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Toxicol, D-85764 Neuherberg, Germany. RP Dolga, AM (reprint author), Univ Marburg, Inst Pharmakol & Klin Pharm, Fachbereich Pharm, Karl von Frisch Str 1, D-35032 Marburg, Germany. EM dolga@staff.uni-marburg.de; culmsee@staff.uni-marburg.de FU Alzheimer Forschung Initiative e.V FX This work was supported in part by a grant from Alzheimer Forschung Initiative e.V. NR 51 TC 12 Z9 13 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 12 PY 2013 VL 288 IS 15 BP 10792 EP 10804 DI 10.1074/jbc.M113.453522 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 125TU UT WOS:000317565000057 PM 23430260 ER PT J AU Dell'Italia, LJ Ferrario, CM AF Dell'Italia, Louis J. Ferrario, Carlos M. TI The Never-ending Story of Angiotensin Peptides Beyond Angiotensin I and II SO CIRCULATION RESEARCH LA English DT Editorial Material DE Editorial; alamandine; angiotensin-converting enzyme; renin-angiotensin system ID SYSTEM; RENIN; RECEPTORS; ENZYMES; FAMILY; HEART; MAS C1 [Dell'Italia, Louis J.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Dell'Italia, Louis J.] UAB Comprehens Cardiovasc Ctr, Birmingham, AL USA. [Ferrario, Carlos M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Div Surg Sci, Winston Salem, NC 27103 USA. RP Dell'Italia, LJ (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiol, 434 BMRII,901 19th St S, Birmingham, AL 35294 USA. EM loudell@uab.edu FU NHLBI NIH HHS [P01 HL051952] NR 18 TC 3 Z9 3 U1 0 U2 7 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 APR 12 PY 2013 VL 112 IS 8 BP 1086 EP 1087 DI 10.1161/CIRCRESAHA.113.301246 PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 124QW UT WOS:000317481700002 PM 23580768 ER PT J AU Gorgun, GT Whitehill, G Anderson, JL Hideshima, T Maguire, C Laubach, J Raje, N Munshi, NC Richardson, PG Anderson, KC AF Goerguen, Guellue Topal Whitehill, Gregory Anderson, Jennifer L. Hideshima, Teru Maguire, Craig Laubach, Jacob Raje, Noopur Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. TI Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans SO BLOOD LA English DT Article ID T-REGULATORY CELLS; CANCER-PATIENTS; DENDRITIC CELLS; BONE-MARROW; PERIPHERAL-BLOOD; IDENTIFICATION; PROGRESSION; GROWTH; IMMUNOSUPPRESSION; DIFFERENTIATION AB Myeloid-derived suppressor cells (MDSCs) are a heterogeneous, immature myeloid cell population with the ability to suppress immune responses. MDSCs have been characterized in infections, inflammatory diseases, and solid tumors; however, their presence and role in the tumor-promoting, immune-suppressive microenvironment in hematologic malignancies remains unclear. We assessed the presence, frequency, and functional characteristics of MDSCs in patients with newly diagnosed, relapsed, and relapsed/refractory multiple myeloma (MM) compared with healthy donors. Additionally, we evaluated the immunomodulatory effects of lenalidomide and bortezomib on MDSCs in MM. CD11b(+)CD14-HLA-DR(-/low)CD33(+)CD15(+) MDSCs were significantly increased in both the peripheral blood and the bone marrow of patients with active MM compared with healthy donors. Furthermore, MDSCs induced MM growth while suppressing T-cell-mediated immune responses. Conversely, MM cells induced the development of MDSCs from healthy donor peripheral blood mononuclear cells, confirming a bidirectional interaction between MDSCs and MM cells and immune effector cells. Our results further suggest that MDSCs may be associated with the activity of disease in MM. Importantly, our studies suggest that inhibition of the tumor-promoting and immune-suppressive functions of MDSCs in MM may represent a promising novel immune-based therapeutic strategy. C1 [Goerguen, Guellue Topal; Whitehill, Gregory; Anderson, Jennifer L.; Hideshima, Teru; Maguire, Craig; Laubach, Jacob; Munshi, Nikhil C.; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Whitehill, Gregory] Haverford Coll, Haverford, PA 19041 USA. [Anderson, Jennifer L.] Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. [Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA. RP Gorgun, GT (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM gullu_gorgun@dfci.harvard.edu FU National Institutes of Health National Cancer Institute Specialized Program of Research Excellence in Myeloma [P50 CA100707]; National Institutes of Health National Cancer Institute Host-Tumor Cell Interactions in Myeloma: Therapeutic Applications [P01 CA78378]; National Institutes of Health National Cancer Institute Molecular Sequelae of Myeloma-Bone Marrow Interactions: Therapeutic Applications [R01 CA50947]; Amgen; Celgene; Novartis; AstraZeneca FX This work was supported by the National Institutes of Health National Cancer Institute Specialized Program of Research Excellence in Myeloma (grant P50 CA100707) (K. C. A.); the National Institutes of Health National Cancer Institute Host-Tumor Cell Interactions in Myeloma: Therapeutic Applications (grant P01 CA78378) (K. C. A.); and the National Institutes of Health National Cancer Institute Molecular Sequelae of Myeloma-Bone Marrow Interactions: Therapeutic Applications (grant R01 CA50947) (K.C.A.).; K.C.A. is an honoraria of Celgene, Millennium, Onyx; P. G. R. is an honoraria of Celgene, Millennium, Johnson & Johnson; N.C.M. is an honoraria of Celgene, Millennium, Novartis; and N.R. received research funding from, and is an honoraria of Amgen, Celgene, Novartis, AstraZeneca. The remaining authors declare no competing financial interests. NR 49 TC 93 Z9 97 U1 1 U2 17 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 11 PY 2013 VL 121 IS 15 BP 2975 EP 2987 DI 10.1182/blood-2012-08-448548 PG 13 WC Hematology SC Hematology GA 183OH UT WOS:000321825700022 PM 23321256 ER PT J AU Chen, CM Shanmugasundaram, K Rigby, AC Kung, AL AF Chen, Changmin Shanmugasundaram, Kumaran Rigby, Alan C. Kung, Andrew L. TI Shikonin, a natural product from the root of Lithospermum erythrorhizon, is a cytotoxic DNA-binding agent SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Shikonin; Ewing sarcoma; Cytotoxic chemotherapy; Natural product; Transcription; High throughput screen ID EWINGS-SARCOMA; ALPHASCREEN(TM) TECHNOLOGY; CARCINOMA-CELLS; GROOVE-BINDERS; BREAST-CANCER; INHIBITION; ASSAY; INDUCTION; EXPRESSION; APOPTOSIS AB To search for compounds that disrupt binding of the EWS-FLII fusion protein to its cognate targets, we developed a homogeneous high-throughput proximity assay and screened 5200 small molecule compounds. Many well-known DNA-binding chemotherapeutic agents, such as actinomycin D, cisplatin, doxorubicin, daunorubicin, and epirubicin scored in the assay and not surprising also disrupted the binding of other transcription factors. Unexpectedly, we found that Shikonin, a natural product from the root of Lithospermum erythrorhizon, similarly disrupted protein-DNA interactions. Mechanistic studies demonstrated that Shikonin displaces SYBR green from binding to the minor groove of DNA and is able to inhibit topoisomerase mediated DNA relaxation. In cells, Shikonin blocked the binding of EWS-FLI1 to the NR0B1 promoter, and attenuated gene expression. Shikonin rapidly induced G2/M arrest and apoptosis in Ewing sarcoma cells. These results demonstrate that contrary to other purported mechanisms of action, Shikonin is a DNA-binding cytotoxic agent. (C) 2013 Elsevier B.V. All rights reserved. C1 [Chen, Changmin] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Chen, Changmin] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02215 USA. [Shanmugasundaram, Kumaran; Rigby, Alan C.] Harvard Univ, Sch Med, Div Mol & Vasc Med, Ctr Vasc Biol Res,Dept Med,Beth Israel Deaconess, Boston, MA 02215 USA. [Kung, Andrew L.] Columbia Univ, Med Ctr, Div Pediat Hematol Oncol Stem Cell Transplant, New York, NY 10032 USA. RP Kung, AL (reprint author), Columbia Univ, Med Ctr, 3959 Broadway, New York, NY 10032 USA. EM akung@columbia.edu OI Kung, Andrew/0000-0002-9091-488X NR 47 TC 9 Z9 11 U1 1 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD APR 11 PY 2013 VL 49 IS 1 BP 18 EP 26 DI 10.1016/j.ejps.2013.02.003 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 126SA UT WOS:000317640300003 PM 23422689 ER PT J AU Asch, DA Muller, RW Volpp, KG AF Asch, David A. Muller, Ralph W. Volpp, Kevin G. TI Conflicts and Compromises in Not Hiring Smokers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Asch, David A.; Volpp, Kevin G.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.; Muller, Ralph W.; Volpp, Kevin G.] Univ Penn, Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Muller, Ralph W.] Univ Penn, Univ Penn Hlth Syst, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X NR 5 TC 11 Z9 11 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 11 PY 2013 VL 368 IS 15 BP 1371 EP 1373 DI 10.1056/NEJMp1303632 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 122QT UT WOS:000317333600002 PM 23534547 ER PT J AU Ryan, DP Friedmann, AM Schmitz, MD Ryan, RJH AF Ryan, Daniel P. Friedmann, Alison M. Schmitz, Matthew D. Ryan, Russell J. H. TI Case 11-2013: A 4-Year-Old Boy with Fever and Abdominal Pain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE APPENDICITIS; BURKITTS-LYMPHOMA; CHILDREN; APPENDECTOMY; METAANALYSIS; PHLEGMON; ABSCESS; CELLS; RISK C1 [Ryan, Daniel P.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. [Friedmann, Alison M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Schmitz, Matthew D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ryan, Russell J. H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ryan, Daniel P.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Friedmann, Alison M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Schmitz, Matthew D.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Ryan, Russell J. H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. NR 16 TC 2 Z9 2 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 11 PY 2013 VL 368 IS 15 BP 1435 EP 1444 DI 10.1056/NEJMcpc1209304 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 122QT UT WOS:000317333600013 PM 23574123 ER PT J AU Bhatt, DL AF Bhatt, Deepak L. TI Timely PCI for STEMI - Still the Treatment of Choice SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED-TRIALS; ANGIOPLASTY; THERAPY C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 14 Z9 15 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 APR 11 PY 2013 VL 368 IS 15 BP 1446 EP 1447 DI 10.1056/NEJMe1302670 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 122QT UT WOS:000317333600014 PM 23473397 ER PT J AU Wu, H AF Wu, Hao TI Higher-Order Assemblies in a New Paradigm of Signal Transduction SO CELL LA English DT Article ID CRYSTAL-STRUCTURE; RECEPTOR; COMPLEX; ACTIVATION; APOPTOSIS; MECHANISM; REVEALS; KINASE; TRAF6; FORMS AB Recent studies have revealed that multiple intracellular signaling proteins may assemble into structured, yet sometimes infinite, higher-order signaling machines for transmission of receptor activation information to cellular responses. These studies advance our understanding of cell signaling and implicate new molecular mechanisms in proximity-driven enzyme activation, threshold behavior, signal amplification, reduction of biological noise, and temporal and spatial control of signal transduction. C1 [Wu, Hao] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wu, H (reprint author), Childrens Hosp, Program Cellular & Mol Med, 300 Longwood Ave, Boston, MA 02115 USA. EM hao.wu@childrens.harvard.edu FU National Institutes of Health FX I apologize for incomplete citations due to space limitation and thank my colleagues and lab members for many insightful discussions, in particular Kai Wucherpfennig, Hong Qian, Qi Qiao, Qian Yin, and Neer Asherie. This work is supported by the National Institutes of Health. NR 24 TC 95 Z9 95 U1 5 U2 47 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 11 PY 2013 VL 153 IS 2 BP 287 EP 292 DI 10.1016/j.cell.2013.03.013 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 122WR UT WOS:000317349700009 PM 23582320 ER PT J AU Whyte, WA Orlando, DA Hnisz, D Abraham, BJ Lin, CY Kagey, MH Rahl, PB Lee, TI Young, RA AF Whyte, Warren A. Orlando, David A. Hnisz, Denes Abraham, Brian J. Lin, Charles Y. Kagey, Michael H. Rahl, Peter B. Lee, Tong Ihn Young, Richard A. TI Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes SO CELL LA English DT Article ID EMBRYONIC STEM-CELLS; WNT SIGNALING PATHWAY; HUMAN GENOME; SELF-RENEWAL; RNAI SCREEN; COACTIVATOR COMPLEX; EXPRESSION; PLURIPOTENCY; DIFFERENTIATION; CIRCUITRY AB Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator. Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. Super-enhancers thus play key roles in the control of mammalian cell identity. C1 [Whyte, Warren A.; Orlando, David A.; Hnisz, Denes; Abraham, Brian J.; Lin, Charles Y.; Kagey, Michael H.; Rahl, Peter B.; Lee, Tong Ihn; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lin, Charles Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM young@wi.mit.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU National Institutes of Health [HG002668, CA146445] FX We thank Tom Volkert, Jennifer Love, Sumeet Gupta, and Jeong-Ah Kwon at the Whitehead Genome Technologies Core for Solexa sequencing; Lee M. Lawton, Jessica Reddy, Ana D'Alessio, and Jasmine M. De Cock for experimental assistance; and Alla A. Sigova, Alan C. Mullen, Roshan M. Kumar, and members of the Young lab for helpful discussion. This work was supported by the National Institutes of Health grants HG002668 (R.A.Y.) and CA146445 (R.A.Y. and T.I.L.). R.A.Y. is a founder and D.A.O. and P.B.R. have become employees of Syros Pharmaceuticals. NR 75 TC 614 Z9 620 U1 14 U2 161 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 11 PY 2013 VL 153 IS 2 BP 307 EP 319 DI 10.1016/j.cell.2013.03.035 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 122WR UT WOS:000317349700011 PM 23582322 ER PT J AU Loven, J Hoke, HA Lin, CY Lau, A Orlando, DA Vakoc, CR Bradner, JE Lee, TI Young, RA AF Loven, Jakob Hoke, Heather A. Lin, Charles Y. Lau, Ashley Orlando, David A. Vakoc, Christopher R. Bradner, James E. Lee, Tong Ihn Young, Richard A. TI Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers SO CELL LA English DT Article ID RNA-POLYMERASE-II; BROMODOMAIN PROTEIN BRD4; MULTIPLE-MYELOMA; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; C-MYC; THERAPEUTIC TARGET; CANCER EPIGENETICS; BET BROMODOMAINS; MEDIATOR COMPLEX AB Chromatin regulators have become attractive targets for cancer therapy, but it is unclear why inhibition of these ubiquitous regulators should have gene-specific effects in tumor cells. Here, we investigate how inhibition of the widely expressed transcriptional coactivator BRD4 leads to selective inhibition of the MYC oncogene in multiple myeloma (MM). BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes. They also co-occupied a small set of exceptionally large super-enhancers associated with genes that feature prominently in MM biology, including the MYC oncogene. Treatment of MM tumor cells with the BET-bromodomain inhibitor JQ1 led to preferential loss of BRD4 at super-enhancers and consequent transcription elongation defects that preferentially impacted genes with super-enhancers, including MYC. Super-enhancers were found at key oncogenic drivers in many other tumor cells. These observations have implications for the discovery of cancer therapeutics directed at components of super-enhancers in diverse tumor types. C1 [Loven, Jakob; Hoke, Heather A.; Lin, Charles Y.; Lau, Ashley; Orlando, David A.; Lee, Tong Ihn; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Hoke, Heather A.; Lau, Ashley; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Lin, Charles Y.] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA. [Vakoc, Christopher R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Lin, Charles Y.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM young@wi.mit.edu RI Young, Richard/F-6495-2012; OI Young, Richard/0000-0001-8855-8647; Vakoc, Christopher/0000-0002-1158-7180 FU Swedish Research Council [VR-B0086301]; Damon-Runyon Cancer Research Foundation; Burroughs-Welcome CAMS award; NCI Cancer Center Support Grant Development Fund [CA45508]; National Institutes of Health [HG002668, CA146445] FX We thank Zi Peng Fan for bioinformatics support; Michael R. McKeown for help with cell viability assays; Jun Qi for providing JQ1; Tom Volkert, Jennifer Love, Sumeet Gupta, and Jeong-Ah Kwon at the Whitehead Genome Technologies Core for Solexa sequencing; and members of the Young, Bradner, and Vakoc labs for helpful discussion. This work was supported by a Swedish Research Council Postdoctoral Fellowship VR-B0086301 (J.L.), the Damon-Runyon Cancer Research Foundation (J.E.B.), a Burroughs-Welcome CAMS award and NCI Cancer Center Support Grant Development Fund CA45508 (C.R.V.), and National Institutes of Health grants HG002668 (R.A.Y.) and CA146445 (R.A.Y., T. I. L.). R.A.Y. and J.E.B. are founders, J.L. and D.A.O. have become employees, and C.R.V. is a scientific advisor of Syros Pharmaceuticals. NR 74 TC 471 Z9 476 U1 19 U2 169 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 11 PY 2013 VL 153 IS 2 BP 320 EP 334 DI 10.1016/j.cell.2013.03.036 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 122WR UT WOS:000317349700012 PM 23582323 ER PT J AU Xiong, Y McCormack, M Li, L Hall, Q Xiang, CB Sheen, J AF Xiong, Yan McCormack, Matthew Li, Lei Hall, Qi Xiang, Chengbin Sheen, Jen TI Glucose-TOR signalling reprograms the transcriptome and activates meristems SO NATURE LA English DT Article ID E2F TARGET GENES; ARABIDOPSIS; ROOT; GROWTH; RAPAMYCIN; PROLIFERATION; EXPRESSION; NUTRIENT; ENERGY; DIFFERENTIATION AB Meristems encompass stem/progenitor cells that sustain postembryonic growth of all plant organs. How meristems are activated and sustained by nutrient signalling remains enigmatic in photosynthetic plants. Combining chemical manipulations and chemical genetics at the photoautotrophic transition checkpoint, we reveal that shoot photosynthesis-derived glucose drives target-of-rapamycin (TOR) signalling relays through glycolysis and mitochondrial bioenergetics to control root meristem activation, which is decoupled from direct glucose sensing, growth-hormone signalling and stem-cell maintenance. Surprisingly, glucose-TOR signalling dictates transcriptional reprogramming of remarkable gene sets involved in central and secondary metabolism, cell cycle, transcription, signalling, transport and protein folding. Systems, cellular and genetic analyses uncover TOR phosphorylation of E2Fa transcription factor for an unconventional activation of S-phase genes, and glucose-signalling defects in e2fa root meristems. Our findings establish pivotal roles of glucose-TOR signalling in unprecedented transcriptional networks wiring central metabolism and biosynthesis for energy and biomass production, and integrating localized stem/progenitor-cell proliferation through inter-organ nutrient coordination to control developmental transition and growth. C1 [Xiong, Yan; McCormack, Matthew; Li, Lei; Hall, Qi; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Xiong, Yan; McCormack, Matthew; Li, Lei; Hall, Qi; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xiong, Yan; McCormack, Matthew; Li, Lei; Hall, Qi; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Xiang, Chengbin] Univ Sci & Technol China, Sch Life Sci, Hefei 230023, Peoples R China. RP Xiong, Y (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM xiong@molbio.mgh.harvard.edu; sheen@molbio.mgh.harvard.edu RI Li, Lei/F-9826-2015 FU MGH Tosteson Postdoctoral Fellowship; Chinese Academy of Sciences [KSCX3-YW-N-007]; NSF; NIH; WJC Special Project RDA-Korea [PJ009106] FX We thank N. Dai and J. Avruch for S6K antibodies and advice, J. L. Celenza for stimulating discussion, M. D. Curtis and Y. J. Niu for the oestradiol-inducible binary vector, L. Li and J. Bush for seeds and plants, B. Muller for TCS::GFP, J. Friml for DR5::GFP, N. S. Gray and D. M. Sabatini for torin1, and J. F. Li, H. Lee and M. Ramon for critical reading of the manuscript. Y. X. is supported by the MGH Tosteson Postdoctoral Fellowship. C. X. is supported by Chinese Academy of Sciences (KSCX3-YW-N-007). The Research is supported by the NSF, NIH and WJC Special Project (PJ009106) RDA-Korea to J.S. NR 42 TC 122 Z9 127 U1 12 U2 174 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 11 PY 2013 VL 496 IS 7444 BP 181 EP + DI 10.1038/nature12030 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 122VM UT WOS:000317346300033 PM 23542588 ER PT J AU Tannahill, GM Curtis, AM Adamik, J Palsson-McDermott, EM McGettrick, AF Goel, G Frezza, C Bernard, NJ Kelly, B Foley, NH Zheng, L Gardet, A Tong, Z Jany, SS Corr, SC Haneklaus, M Caffrey, BE Pierce, K Walmsley, S Beasley, FC Cummins, E Nizet, V Whyte, M Taylor, CT Lin, H Masters, SL Gottlieb, E Kelly, VP Clish, C Auron, PE Xavier, RJ O'Neill, LAJ AF Tannahill, G. M. Curtis, A. M. Adamik, J. Palsson-McDermott, E. M. McGettrick, A. F. Goel, G. Frezza, C. Bernard, N. J. Kelly, B. Foley, N. H. Zheng, L. Gardet, A. Tong, Z. Jany, S. S. Corr, S. C. Haneklaus, M. Caffrey, B. E. Pierce, K. Walmsley, S. Beasley, F. C. Cummins, E. Nizet, V. Whyte, M. Taylor, C. T. Lin, H. Masters, S. L. Gottlieb, E. Kelly, V. P. Clish, C. Auron, P. E. Xavier, R. J. O'Neill, L. A. J. TI Succinate is an inflammatory signal that induces IL-1 beta through HIF-1 alpha SO NATURE LA English DT Article ID RECEPTOR GPR91; HYPOXIA; ACTIVATION; PROTEIN; CELLS; GAMMA; LINKS; METABOLISM; INHIBITION; MECHANISM AB Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis(1). Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1 beta but not tumour-necrosis factor-a in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and down-regulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (gamma-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1 alpha, an effect that is inhibited by 2-deoxyglucose, with interleukin-1 beta as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1 beta production during inflammation. C1 [Tannahill, G. M.; Curtis, A. M.; Palsson-McDermott, E. M.; McGettrick, A. F.; Bernard, N. J.; Kelly, B.; Foley, N. H.; Jany, S. S.; Corr, S. C.; Haneklaus, M.; Kelly, V. P.; O'Neill, L. A. J.] Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland. [Adamik, J.; Auron, P. E.] Duquesne Univ, Dept Biol Sci, Pittsburgh, PA 15282 USA. [Goel, G.; Xavier, R. J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Frezza, C.; Zheng, L.; Gottlieb, E.] Beatson Inst Canc Res, Apoptosis & Tumour Physiol Lab, Glasgow G61 1BD, Lanark, Scotland. [Frezza, C.; Xavier, R. J.] Hutchison MRC Res Ctr, Med Res Council Canc Cell Unit, Cambridge CB2 0X2, England. [Gardet, A.; Pierce, K.; Clish, C.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Tong, Z.; Lin, H.] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. [Caffrey, B. E.] Trinity Coll Dublin, Smurfit Inst Genet, Dublin 2, Ireland. [Walmsley, S.; Whyte, M.] Univ Sheffield, Dept Infect & Immun, Acad Unit Resp Med, Sheffield S10 2RX, S Yorkshire, England. [Beasley, F. C.; Nizet, V.] Univ Calif San Diego, Ctr Neural Circuits & Behav, Div Pediat, V Nizet Lab, La Jolla, CA 92093 USA. [Cummins, E.; Taylor, C. T.] Univ Coll Dublin, Conway Inst, Dublin 4, Ireland. [Masters, S. L.] Walter & Eliza Hall Inst Med Res, Inflammat Div, Parkville, Vic 3052, Australia. RP O'Neill, LAJ (reprint author), Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland. EM laoneill@tcd.ie RI Gottlieb, Eyal/G-6450-2010; Masters, Seth/N-2886-2013; OI Gottlieb, Eyal/0000-0002-9770-0956; Masters, Seth/0000-0003-4763-576X; Corr, Sinead/0000-0001-9930-5039; Adamik, Juraj/0000-0002-3604-158X; Bernard, Nicholas/0000-0002-9483-7922 FU European Research Council; Science Foundation Ireland; Health Research Board; European Union FP7 programme 'TIMER'; Wellcome Trust; National Institutes of Health; Helmsley Trust; Nestle Research Centre; VESKI; Duquesne University Hunkele Dreaded Disease Award; Interleukin Foundation; National Health and Medical Research Council FX We thank the European Research Council, Science Foundation Ireland, the Health Research Board, European Union FP7 programme 'TIMER', Wellcome Trust, National Institutes of Health, Helmsley Trust, Nestle Research Centre, VESKI, The Duquesne University Hunkele Dreaded Disease Award, The Interleukin Foundation and the National Health and Medical Research Council for funding. We also thank R. Thompson for assistance with Hif1a-/- mice and M. Murphy for discussions. NR 30 TC 391 Z9 395 U1 14 U2 123 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 11 PY 2013 VL 496 IS 7444 BP 238 EP + DI 10.1038/nature11986 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 122VM UT WOS:000317346300045 PM 23535595 ER PT J AU Goss, PE Ingle, JN Pritchard, KI Ellis, MJ Sledge, GW Budd, GT Rabaglio, M Ansari, RH Johnson, DB Tozer, R D'Souza, DP Chalchal, H Spadafora, S Stearns, V Perez, EA Liedke, PER Lang, I Elliott, C Gelmon, KA Chapman, JAW Shepherd, LE AF Goss, Paul E. Ingle, James N. Pritchard, Kathleen I. Ellis, Matthew J. Sledge, George W. Budd, G. Thomas Rabaglio, Manuela Ansari, Rafat H. Johnson, David B. Tozer, Richard D'Souza, David P. Chalchal, Haji Spadafora, Silvana Stearns, Vered Perez, Edith A. Liedke, Pedro E. R. Lang, Istvan Elliott, Catherine Gelmon, Karen A. Chapman, Judy-Anne W. Shepherd, Lois E. TI Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27-A Randomized Controlled Phase III Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONSTEROIDAL AROMATASE INHIBITORS; ADJUVANT ENDOCRINE THERAPY; TAMOXIFEN; ADHERENCE AB Purpose In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. Patients and Methods We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. Results In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. Conclusion This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA. 27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer. J Clin Oncol 31:1398-1404. (C) 2013 by American Society of Clinical Oncology C1 [Goss, Paul E.; Liedke, Pedro E. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Ellis, Matthew J.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Sledge, George W.] Indiana Univ Hlth, Indianapolis, IN USA. [Ansari, Rafat H.] Northern Indiana Canc Res Consortium, South Bend, IN USA. [Budd, G. Thomas] Cleveland Clin, Cleveland, OH 44106 USA. [Johnson, David B.] Canc Ctr Kansas, Wichita, KS USA. [Stearns, Vered] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Pritchard, Kathleen I.] Univ Toronto, Toronto, ON, Canada. [Tozer, Richard] Juravinski Canc Ctr, Hamilton, ON, Canada. [D'Souza, David P.] London Reg Canc Program, London, England. [Spadafora, Silvana] Algoma Reg Canc Ctr, Sault Ste Marie, ON, Canada. [Elliott, Catherine; Chapman, Judy-Anne W.; Shepherd, Lois E.] NCIC Clin Trials Grp, Kingston, ON, Canada. [Chalchal, Haji] Regina Gen Hosp, Regina, SK, Canada. [Gelmon, Karen A.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Rabaglio, Manuela] Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. [Rabaglio, Manuela] Univ Bern, Inselspital, CH-3010 Bern, Switzerland. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lawrence House,55 Fruit St,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org FU Canadian Cancer Society Research Institute [015469]; National Institutes of Health [2U10CA077202, CA32102]; Pfizer; Avon Foundation, New York, NY; AstraZeneca; Novartis FX Supported by Canadian Cancer Society Research Institute Grant No. 015469, National Institutes of Health Grants No. 2U10CA077202 and CA32102, and Pfizer. P. E. G. and P. E. R. L. are supported by the Avon Foundation, New York, NY.; Research Funding: Matthew J. Ellis, AstraZeneca; Vered Stearns, Novartis, Pfizer NR 29 TC 72 Z9 75 U1 1 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2013 VL 31 IS 11 BP 1398 EP 1404 DI 10.1200/JCO.2012.44.7805 PG 7 WC Oncology SC Oncology GA 120MM UT WOS:000317174400012 PM 23358971 ER PT J AU Argiris, A Ghebremichael, M Gilbert, J Lee, JW Sachidanandam, K Kolesar, JM Burtness, B Forastiere, AA AF Argiris, Athanassios Ghebremichael, Musie Gilbert, Jill Lee, Ju-Whei Sachidanandam, Kamakshi Kolesar, Jill M. Burtness, Barbara Forastiere, Arlene A. TI Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; LUNG-CANCER; SOMATIC MUTATIONS; TYROSINE KINASE; CLINICAL-TRIALS; PLUS CETUXIMAB; COLON-CANCER; OLDER-ADULTS; ERLOTINIB AB Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN. J Clin Oncol 31:1405-1414. (C) 2013 by American Society of Clinical Oncology C1 [Argiris, Athanassios] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gilbert, Jill] Vanderbilt Univ, Nashville, TN USA. [Sachidanandam, Kamakshi; Kolesar, Jill M.] Univ Wisconsin, Madison, WI USA. [Burtness, Barbara] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Forastiere, Arlene A.] Johns Hopkins Univ, Baltimore, MD USA. RP Argiris, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Div Hematol Oncol, 7979 Wurzbach Rd,MC8232,Zeller Bldg,4th Floor,Roo, San Antonio, TX 78229 USA. EM Argiris@uthscsa.edu FU Public Health Service from the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services [CA23318, CA66636, CA21115, CA39229, CA16116]; AstraZeneca; Genentech; sanofi-aventis FX Supported in part by Public Health Service Grants No. CA23318, CA66636, CA21115, CA39229, and CA16116 from the National Cancer Institute, National Institutes of Health, US Department of Health and Human Services.; Athanassios Argiris, AstraZeneca; Jill M. Kolesar, AstraZeneca; Barbara Burtness, Genentech, sanofi-aventis NR 49 TC 60 Z9 60 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2013 VL 31 IS 11 BP 1405 EP 1414 DI 10.1200/JCO.2012.45.4272 PG 10 WC Oncology SC Oncology GA 120MM UT WOS:000317174400013 PM 23460714 ER PT J AU Neuss, MN Malin, JL Chan, S Kadlubek, PJ Adams, JL Jacobson, JO Blayney, DW Simone, JV AF Neuss, Michael N. Malin, Jennifer L. Chan, Stephanie Kadlubek, Pamela J. Adams, John L. Jacobson, Joseph O. Blayney, Douglas W. Simone, Joseph V. TI Measuring the Improving Quality of Outpatient Care in Medical Oncology Practices in the United States SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER CARE; AMERICAN-SOCIETY; PRACTICE GUIDELINES; OF-CARE; CHEMOTHERAPY AB Purpose The American Society of Clinical Oncology Quality Oncology Practice Initiative (QOPI) has provided a method for measuring process-based practice quality since 2006. We sought to determine whether QOPI scores showed improvement in measured quality over time and, if change was demonstrated, which factors in either the measures or participants were associated with improvement. Methods The analysis included 156 practice groups from a larger group of 308 that submitted data from 2006 to 2010. One hundred fifty-two otherwise eligible practices were excluded, most commonly for insufficient data submission. A linear regression model that controlled for varied initial performance was used to estimate the effect of participation over time and evaluate participant and measure characteristics of improvement. Results Participants completed a mean of 5.06 (standard deviation, 1.94) rounds of data collection. Adjusted mean quality scores improved from 0.71 (95% CI, 0.42 to 0.91) to 0.85 (95% CI, 0.60 to 0.95). Overall odds ratio of improvement over time was 1.09 (P < .001). The greatest improvement was seen in measures that assessed newly introduced clinical information, in which the mean scores improved from 0.05 (95% CI, 0.01 to 0.17) to 0.69 (95% CI, 0.33 to 0.91; P < .001). Many measures showed no change over time. Conclusion Many US oncologists have participated in QOPI over the past 6 years. Participation over time was highly correlated with improvement in measured performance. Greater and faster improvement was seen in measures concerning newly introduced clinical information. Some measures showed no change despite opportunity for improvement. J Clin Oncol 31:1471-1477. (C) 2013 by American Society of Clinical Oncology C1 [Neuss, Michael N.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Malin, Jennifer L.] WellPoint, Indianapolis, IN USA. [Chan, Stephanie; Adams, John L.] RAND Corp, Santa Monica, CA USA. [Blayney, Douglas W.] Stanford Med Ctr, Stanford Canc Ctr, Palo Alto, CA USA. [Kadlubek, Pamela J.] Amer Soc Clin Oncol, Alexandria, VA USA. [Jacobson, Joseph O.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Simone, Joseph V.] Simone Consulting, Dunwoody, GA USA. RP Neuss, MN (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, 2220 Pierce Ave,694 Preston Res Bldg, Nashville, TN 37232 USA. EM michael.n.neuss@vanderbilt.edu FU Blue Cross Blue Shield of Michigan FX Douglas W. Blayney, Blue Cross Blue Shield of Michigan NR 27 TC 20 Z9 20 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2013 VL 31 IS 11 BP 1471 EP 1477 DI 10.1200/JCO.2012.43.3300 PG 7 WC Oncology SC Oncology GA 120MM UT WOS:000317174400022 PM 23478057 ER PT J AU Giedt, RJ Koch, PD Weissleder, R AF Giedt, Randy J. Koch, Peter D. Weissleder, Ralph TI Single Cell Analysis of Drug Distribution by Intravital Imaging SO PLOS ONE LA English DT Article ID IN-VIVO; SELECTION METHOD; OPEN-LABEL; SEGMENTATION; INHIBITION; MULTICENTER; OLAPARIB; KINASE; CANCER; TUMORS AB Recent advances in the field of intravital imaging have for the first time allowed us to conduct pharmacokinetic and pharmacodynamic studies at the single cell level in live animal models. Due to these advances, there is now a critical need for automated analysis of pharmacokinetic data. To address this, we began by surveying common thresholding methods to determine which would be most appropriate for identifying fluorescently labeled drugs in intravital imaging. We then developed a segmentation algorithm that allows semi-automated analysis of pharmacokinetic data at the single cell level. Ultimately, we were able to show that drug concentrations can indeed be extracted from serial intravital imaging in an automated fashion. We believe that the application of this algorithm will be of value to the analysis of intravital microscopy imaging particularly when imaging drug action at the single cell level. C1 [Giedt, Randy J.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Koch, Peter D.; Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institutes of Health [R01 CA164448, P01 CA139980, T32 CA079443] FX This work was supported by grants R01 CA164448, P01 CA139980 and T32 CA079443 from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 6 Z9 6 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 APR 10 PY 2013 VL 8 IS 4 AR e60988 DI 10.1371/journal.pone.0060988 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123IQ UT WOS:000317382000035 PM 23593370 ER PT J AU Shanechi, MM Williams, ZM Wornell, GW Hu, RC Powers, M Brown, EN AF Shanechi, Maryam M. Williams, Ziv M. Wornell, Gregory W. Hu, Rollin C. Powers, Marissa Brown, Emery N. TI A Real-Time Brain-Machine Interface Combining Motor Target and Trajectory Intent Using an Optimal Feedback Control Design SO PLOS ONE LA English DT Article ID POSTERIOR PARIETAL CORTEX; GOAL-DIRECTED MOVEMENTS; PREMOTOR CORTEX; CORTICAL-NEURONS; NEURAL PROSTHETICS; COMPUTER INTERFACE; SPIKING ACTIVITY; REACHING TASK; ARM MOVEMENTS; STATE AB Real-time brain-machine interfaces (BMI) have focused on either estimating the continuous movement trajectory or target intent. However, natural movement often incorporates both. Additionally, BMIs can be modeled as a feedback control system in which the subject modulates the neural activity to move the prosthetic device towards a desired target while receiving real-time sensory feedback of the state of the movement. We develop a novel real-time BMI using an optimal feedback control design that jointly estimates the movement target and trajectory of monkeys in two stages. First, the target is decoded from neural spiking activity before movement initiation. Second, the trajectory is decoded by combining the decoded target with the peri-movement spiking activity using an optimal feedback control design. This design exploits a recursive Bayesian decoder that uses an optimal feedback control model of the sensorimotor system to take into account the intended target location and the sensory feedback in its trajectory estimation from spiking activity. The real-time BMI processes the spiking activity directly using point process modeling. We implement the BMI in experiments consisting of an instructed-delay center-out task in which monkeys are presented with a target location on the screen during a delay period and then have to move a cursor to it without touching the incorrect targets. We show that the two-stage BMI performs more accurately than either stage alone. Correct target prediction can compensate for inaccurate trajectory estimation and vice versa. The optimal feedback control design also results in trajectories that are smoother and have lower estimation error. The two-stage decoder also performs better than linear regression approaches in offline cross-validation analyses. Our results demonstrate the advantage of a BMI design that jointly estimates the target and trajectory of movement and more closely mimics the sensorimotor control system. C1 [Shanechi, Maryam M.] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA. [Shanechi, Maryam M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. [Shanechi, Maryam M.; Wornell, Gregory W.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Shanechi, Maryam M.; Williams, Ziv M.; Hu, Rollin C.; Powers, Marissa] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Shanechi, Maryam M.; Williams, Ziv M.; Hu, Rollin C.; Brown, Emery N.] Harvard Univ, Sch Med, Boston, MA USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Shanechi, MM (reprint author), Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA. EM shanechi@cornell.edu FU National Institutes of Health (NIH) [DP1-0D003646-01, R01-EB006385] FX This work was supported by National Institutes of Health (NIH) Grant Nos. DP1-0D003646-01 and R01-EB006385. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 73 TC 22 Z9 22 U1 1 U2 34 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 10 PY 2013 VL 8 IS 4 AR e59049 DI 10.1371/journal.pone.0059049 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123IQ UT WOS:000317382000003 PM 23593130 ER PT J AU Clark, KB Hassert, DL AF Clark, Kevin B. Hassert, Derrick L. TI Undecidability and opacity of metacognition in animals and humans SO FRONTIERS IN PSYCHOLOGY LA English DT Editorial Material ID SELF-AWARENESS; MINDS; CONFIDENCE; CHILDREN C1 [Clark, Kevin B.] Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. [Hassert, Derrick L.] Trinity Christian Coll, Dept Psychol, Palos Hts, IL USA. RP Clark, KB (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. EM kbclarkphd@yahoo.com NR 42 TC 2 Z9 2 U1 2 U2 11 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD APR 9 PY 2013 VL 4 AR 171 DI 10.3389/fpsyg.2013.00171 PG 3 WC Psychology, Multidisciplinary SC Psychology GA AA2PU UT WOS:000330937300001 PM 23576999 ER PT J AU Maeda, A Okazaki, M Baron, DM Dean, T Khatri, A Mahon, M Segawa, H Abou-Samra, AB Juppner, H Bloch, KD Potts, JT Gardella, TJ AF Maeda, Akira Okazaki, Makoto Baron, David M. Dean, Thomas Khatri, Ashok Mahon, Mathew Segawa, Hiroko Abou-Samra, Abdul B. Jueppner, Harald Bloch, Kenneth D. Potts, John T., Jr. Gardella, Thomas J. TI Critical role of parathyroid hormone (PTH) receptor-1 phosphorylation in regulating acute responses to PTH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calcium homeostasis; family B GPCR; phosphate homeostasis; receptor phosphorylation ID (PTH)/PTH-RELATED PROTEIN-RECEPTOR; PLASMA CALCIUM; BETA-ARRESTIN; INTERNALIZATION; HYPERPARATHYROIDISM; CONFORMATIONS; HOMEOSTASIS; SELECTIVITY; INJECTION; BINDING AB Agonist-induced phosphorylation of the parathyroid hormone (PTH) receptor 1 (PTHR1) regulates receptor signaling in vitro, but the role of this phosphorylation in vivo is uncertain. We investigated this role by injecting "knock-in" mice expressing a phosphorylation-deficient (PD) PTHR1 with PTH ligands and assessing acute biologic responses. Following injection with PTH (1-34), or with a unique, long-acting PTH analog, PD mice, compared with WT mice, exhibited enhanced increases in CAMP levels in the blood, as well as enhanced cAMP production and gene expression responses in bone and kidney tissue. Surprisingly, however, the hallmark hypercalcemic and hypophosphatemic responses were markedly absent in the PD mice, such that paradoxical hypocalcemic and hyperphosphatemic responses were observed, quite strikingly with the long-acting PTH analog. Spot urine analyses revealed a marked defect in the capacity of the PD mice to excrete phosphate, as well as CAMP, into the urine in response to PTH injection. This defect in renal excretion was associated with a severe, PTH-induced impairment in glomerular filtration, as assessed by the rate of FITC-inulin clearance from the blood, which, in turn, was explainable by an overly exuberant systemic hypotensive response. The overall findings demonstrate the importance in vivo of PTH-induced phosphorylation of the PTHR1,in regulating acute ligand responses, and they serve to focus attention on mechanisms that underlie the acute calcemic response to PTH and factors, such as blood phosphate levels, that influence it. C1 [Maeda, Akira; Okazaki, Makoto; Dean, Thomas; Khatri, Ashok; Mahon, Mathew; Segawa, Hiroko; Jueppner, Harald; Potts, John T., Jr.; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Maeda, Akira; Okazaki, Makoto; Baron, David M.; Dean, Thomas; Khatri, Ashok; Mahon, Mathew; Segawa, Hiroko; Jueppner, Harald; Bloch, Kenneth D.; Potts, John T., Jr.; Gardella, Thomas J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Baron, David M.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Abou-Samra, Abdul B.] Hamad Med Corp, Doha, Qatar. RP Potts, JT (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM potts.john@mgh.harvard.edu; gardella@helix.mgh.harvard.edu FU National Institutes of Health [DK-11794] FX Monica Reyes assisted with animal breeding. This work was supported by National Institutes of Health Grant DK-11794. NR 33 TC 17 Z9 17 U1 2 U2 38 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 9 PY 2013 VL 110 IS 15 BP 5864 EP 5869 DI 10.1073/pnas.1301674110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125KE UT WOS:000317537900031 PM 23533279 ER PT J AU Wu, CL Schroeder, BE Ma, XJ Cutie, CJ Wu, SL Salunga, R Zhang, Y Kattan, MW Schnabel, CA Erlander, MG McDougal, WS AF Wu, Chin-Lee Schroeder, Brock E. Ma, Xiao-Jun Cutie, Christopher J. Wu, Shulin Salunga, Ranelle Zhang, Yi Kattan, Michael W. Schnabel, Catherine A. Erlander, Mark G. McDougal, W. Scott TI Development and validation of a 32-gene prognostic index for prostate cancer progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; RADICAL PROSTATECTOMY; ADJUVANT RADIOTHERAPY; BIOCHEMICAL FAILURE; POSTOPERATIVE NOMOGRAM; PREOPERATIVE NOMOGRAM; DISEASE RECURRENCE; BREAST-CANCER; RISK; CARCINOMA AB The accurate determination of the risk of cancer recurrence is an important unmet need in the management of prostate cancer. Patients and physicians must weigh the benefits of currently avail: able therapies against the potential morbidity of these treatments. Herein we describe the development of a gene expression-based continuous risk index and a validation of this test in an independent, blinded cohort of post-radical prostatectomy (RP) patients. A gene expression signature, prognostic for prostate-specific antigen (PSA) recurrence, was identified through a bioinformatic analysis of the expression of 1,536 genes in malignant prostate tissue from a training cohort of consecutive patients treated with RP. The assay was transferred to a real-time RT-PCR platform, and a continuous risk index model was constructed based on the expression of 32 genes. This 32-gene risk index model was validated in an independent, blinded cohort of 270 RP patients. In multivariate analyses, the risk index was prognostic for risk of PSA recurrence and had added value over standard prognostic markers such as Gleason score, pathologic tumor stage, surgical margin status, and presurgery PSA (hazard ratio, 4.05; 95% confidence interval, 1.50-10.94; P = 0.0057). Furthermore, RP patients could be stratified based on the risk of PSA recurrence and the development of metastatic disease. The 32-gene signature identified here is a robust prognostic marker for disease recurrence. This assay may aid in postoperative treatment selection and has the potential to impact decision making at the biopsy stage. C1 [Wu, Chin-Lee; Wu, Shulin] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, Chin-Lee; Cutie, Christopher J.; McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wu, Chin-Lee; Cutie, Christopher J.; McDougal, W. Scott] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Schroeder, Brock E.; Ma, Xiao-Jun; Salunga, Ranelle; Zhang, Yi; Schnabel, Catherine A.; Erlander, Mark G.] bioTheranostics Inc, San Diego, CA 92121 USA. [Kattan, Michael W.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM WMCDOUGAL@PARTNERS.ORG FU bioTheranostics, Inc.; John and Claire Bertucci Prostate Cancer Foundation FX The authors thank Hongying Yi, PhD, for statistical support; Jingmei Su, Yen Tran, and J. Todd Tuggle for study assistance; Sandra Kirley, BA, for collection of data and preparation of tissue samples; and Dennis Sgroi, MD, and Donald S. Kaufman, MD, for advice. C.-L.W. received research funding from bioTheranostics, Inc. John and Claire Bertucci Prostate Cancer Foundation provided funding support. NR 34 TC 18 Z9 20 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 9 PY 2013 VL 110 IS 15 BP 6121 EP 6126 DI 10.1073/pnas.1215870110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125KE UT WOS:000317537900075 PM 23533275 ER PT J AU Mandawat, A Curtis, JP Mandawat, A Njike, VY Lampert, R AF Mandawat, Anant Curtis, Jeptha P. Mandawat, Aditya Njike, Valentine Y. Lampert, Rachel TI Safety of Pacemaker Implantation in Nonagenarians An Analysis of the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample SO CIRCULATION LA English DT Article DE biological pacemakers; complications; epidemiology; geriatrics; population ID ELDERLY-PATIENTS; UNITED-STATES; PERMANENT PACEMAKER; COMPLICATIONS; OUTCOMES; SURVIVAL; RISK; AGE; DEFIBRILLATORS; COMORBIDITY AB Background-Data are scarce on outcomes of pacemaker implantation in nonagenarians (age >= 90 years). Methods and Results-We identified patients >70 years of age (n=115 683) who underwent initial pacemaker implantation in the 2004 to 2008 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample. Outcomes included in-hospital mortality, complications, length of stay, and charges. Unadjusted outcomes were compared using chi(2) and Mantel-Haenszel tests. Multivariate hierarchical logistic models and stepwise linear regression models adjusted for case-mix variation and clustering. Eleven percent (12 917) were >90 years of age. Relative to patients aged 70 to 79 years, patients >90 years of age were more likely to have moderate/severe comorbidity (Charlson score >1; 43.2% versus 40.1%) and less likely to be admitted electively (17.5% versus 29.9%), all P<0.001. The unadjusted mortality and complication rates in patients aged 70 to 79 years were 0.60% (confidence interval [CI], 0.53-0.67%) and 5.61% (CI, 5.40-5.82%), respectively, and in patients aged >90 years were 1.87% (CI, 1.63-2.11%) and 6.31% (CI, 5.89-6.72%). Length of stay and charges in patients aged 70 to 79 years were 3.22 days (CI, 3.20-3.24 days) and $38 871 (CI, $38 700-$39 043), and in patients aged >90 years, 4.27 days (CI, 4.25-4.30 days) and $41 373 (CI, $41 190-$41 556). Multivariable analysis revealed severe comorbidity (odds ratio, 5.00; 95% CI, 4.05-6.17) was a greater predictor of mortality than increasing age (odds ratio, 2.81 per decade; CI, 2.35-3.35), all P<0.001. Similarly, severe comorbidity (Charlson score >5) was more strongly associated with complications, length of stay, and charges than age. Conclusions-Although increasing age predicts worsening outcomes in the elderly, the absolute rates are modest, even in nonagenarians, and comorbidity is a stronger predictor. (Circulation. 2013;127:1453-1465.) C1 [Mandawat, Anant; Curtis, Jeptha P.; Lampert, Rachel] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Curtis, Jeptha P.] Yale Univ, Sch Med, Ctr Outcomes Res & Evaluat, New Haven, CT 06520 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. [Njike, Valentine Y.] Yale Univ, Yale Griffin Prevent Res Ctr, Sch Publ Hlth, Derby, CT USA. RP Lampert, R (reprint author), Yale Univ, Sch Med, Sect Cardiovasc Med, 789 Howard Ave,Dana 319, New Haven, CT 06520 USA. EM rachel.lampert@yale.edu FU Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources) [8UL1TR000170-05]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard University; Medtronic; St. Jude Medical; Boston Scientific FX This work was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health.; Dr Curtis reports significant ownership interest in Medtronic. Dr Lampert reports significant research grants from Medtronic, St. Jude Medical, and Boston Scientific and modest honoraria from Medtronic. The other authors report no conflicts. NR 38 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 9 PY 2013 VL 127 IS 14 BP 1453 EP + DI 10.1161/CIRCULATIONAHA.113.001434 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 122VS UT WOS:000317346900012 PM 23513066 ER PT J AU Bonaca, MP Scirica, BM Creager, MA Olin, J Bounameaux, H Dellborg, M Lamp, JM Murphy, SA Braunwald, E Morrow, DA AF Bonaca, Marc P. Scirica, Benjamin M. Creager, Mark A. Olin, Jeffrey Bounameaux, Henri Dellborg, Mikael Lamp, Jessica M. Murphy, Sabina A. Braunwald, Eugene Morrow, David A. TI Vorapaxar in Patients With Peripheral Artery Disease Results From TRA2 degrees P-TIMI 50 SO CIRCULATION LA English DT Article DE ischemia; outcome assessment; peripheral arterial disease; platelet aggregation inhibitors; vorapaxar ID SECONDARY PREVENTION; ATHEROTHROMBOTIC EVENTS; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIALS; CHARISMA TRIAL; ASPIRIN; RISK; METAANALYSIS; CLOPIDOGREL AB Background-Vorapaxar is a novel antagonist of protease-activated receptor-1, the primary receptor for thrombin on human platelets that is also present on vascular endothelium and smooth muscle. Patients with peripheral artery disease are at risk of systemic atherothrombotic events, as well as acute and chronic limb ischemia and the need for peripheral revascularization. Methods and Results-The Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA2 degrees P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26 449 patients with stable atherosclerotic vascular disease (myocardial infarction, stroke, or peripheral artery disease). Patients with qualifying peripheral artery disease (n=3787) had a history of claudication and an ankle-brachial index of <0.85 or prior revascularization for limb ischemia. The primary efficacy end point was cardiovascular death, myocardial infarction, or stroke, and the principal safety end point was Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) bleeding. In the peripheral artery disease cohort, the primary end point did not differ significantly with vorapaxar (11.3% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.78-1.14; P=0.53). However, rates of hospitalization for acute limb ischemia (2.3% versus 3.9%; hazard ratio, 0.58; 95% confidence interval, 0.39-0.86; P=0.006) and peripheral artery revascularization (18.4% versus 22.2%; hazard ratio, 0.84; 95% confidence interval, 0.73-0.97; P=0.017) were significantly lower in patients randomized to vorapaxar. Bleeding occurred more frequently with vorapaxar compared with placebo (7.4% versus 4.5%; hazard ratio, 1.62; 95% confidence interval, 1.21-2.18; P=0.001). Conclusions-Vorapaxar did not reduce the risk of cardiovascular death, myocardial infarction, or stroke in patients with peripheral artery disease; however, vorapaxar significantly reduced acute limb ischemia and peripheral revascularization. The beneficial effects of protease-activated receptor-1 antagonism on limb vascular events were accompanied by an increased risk of bleeding. C1 [Bonaca, Marc P.; Scirica, Benjamin M.; Creager, Mark A.; Lamp, Jessica M.; Murphy, Sabina A.; Braunwald, Eugene; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, Boston, MA 02115 USA. [Bonaca, Marc P.; Scirica, Benjamin M.; Creager, Mark A.; Lamp, Jessica M.; Murphy, Sabina A.; Braunwald, Eugene; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Olin, Jeffrey] Mt Sinai Sch Med, Wiener Cardiovasc Inst, New York, NY USA. [Olin, Jeffrey] Mt Sinai Sch Med, Henry R Kravis Ctr Cardiovasc Hlth, New York, NY USA. [Bounameaux, Henri] Univ Hosp Geneva, Fac Med Geneva, Div Angiol & Hemostasis, Dept Med Specialties, Geneva, Switzerland. [Dellborg, Mikael] Univ Gothenburg, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden. [Dellborg, Mikael] Sahlgrens Univ Hosp, Gothenburg, Sweden. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org FU Merck and Co.; Accumetrics; Amgen; AstraZeneca; Beckman Coulter; Bristol-Myers Squibb; CV Therapeutics; Daiichi Sankyo Co Ltd; Eli Lilly and Co; GlaxoSmithKline; Integrated Therapeutics; Nanosphere; Novartis Pharmaceuticals; Nuvelo; OrthoClinical Diagnostics; Pfizer; Roche Diagnostics; Sanofi-Aventis; Sanofi-Synthelabo; Siemens Medical Solutions; Singulex; National Heart, Lung, and Blood Institute [K12 HL083786]; Lexicon; Arena; Gilead; Eisai; Aastrom Biosciences; Baxter Healthcare; Genzyme; Merck; Plurestem; Swiss National Foundation; Bayer-Schering Pharma; Schering-Plow; Daiichi-Sankyo; Boehringer-Ingelheim; Actelion; Eli Lilly; Amarin Pharmaceuticals; Beckman-Coulter; Critical Diagnostics; Genentech; Instrumentation Laboratory; Novartis; Servier FX The TRA2 degrees P-TIMI 50 Trial was sponsored by Merck and Co.; The TIMI Study Group has received significant research grant support from Accumetrics, Amgen, AstraZeneca, Beckman Coulter, Bristol-Myers Squibb, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Integrated Therapeutics, Merck and Co, Nanosphere, Novartis Pharmaceuticals, Nuvelo, OrthoClinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, Siemens Medical Solutions, and Singulex. Dr Bonaca was supported by a Research Career Development Award (K12 HL083786) from the National Heart, Lung, and Blood Institute. Dr Scirica has received consulting fees from Lexicon, Arena, Gilead, and Eisai. Dr Creager has received consulting fees from Aastrom Biosciences, AstraZeneca, Baxter Healthcare, and Genzyme. Dr Olin has received consulting fees from Merck and Plurestem. Dr Bounameaux has received research support, consulting fees, and/or honoraria for lectures from the Swiss National Foundation, Bayer-Schering Pharma, Schering-Plow, Daiichi-Sankyo, Bristol-Myers-Squibb, GlaxoSmithKline, Pfizer, Boehringer-Ingelheim, and sanofi-aventis. Dr Dellborg has received consulting fees and/or honoraria for lectures from Schering-Plow, Pfizer, Merck, Boehringer-Ingelheim, and Actelion. S.A. Murphy has received consulting fees from Eli Lilly and Amarin Pharmaceuticals. Dr Braunwald has served as a consultant for Merck (no compensation), Amorcyte, Daiichi Sankyo, Medicines Co, Ikaria, CardioRentis, Sanofi-Aventis, and CVRx (no compensation). Dr Morrow has received consulting fees from Beckman-Coulter, Boehringer-Ingelheim, Critical Diagnostics, Genentech, Gilead, Instrumentation Laboratory, Merck, Novartis, Roche Diagnostics, and Servier. J.M. Lamp reports no conflicts. NR 22 TC 70 Z9 72 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 9 PY 2013 VL 127 IS 14 BP 1522 EP + DI 10.1161/CIRCULATIONAHA.112.000679 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 122VS UT WOS:000317346900019 PM 23501976 ER PT J AU Mauer, AC Baron, SJ Yeh, RW Scott, NS AF Mauer, Andreas C. Baron, Suzanne J. Yeh, Robert W. Scott, Nandita S. TI Caesarian Dissection A Case of Chest Pain and Dyspnea During Delivery SO CIRCULATION LA English DT Article DE acute coronary syndrome; coronary artery dissection, spontaneous; heart failure; pregnancy; tomography, optical coherence ID CORONARY-ARTERY DISSECTION; OPTICAL COHERENCE TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; BRAIN NATRIURETIC PEPTIDE; INTRAVASCULAR ULTRASOUND; HEART-DISEASE; PREGNANCY; MANAGEMENT; INTERVENTION; DIAGNOSIS C1 [Mauer, Andreas C.; Baron, Suzanne J.; Yeh, Robert W.; Scott, Nandita S.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mauer, AC (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB8-813, Boston, MA 02114 USA. EM amauer@partners.org NR 25 TC 0 Z9 0 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 APR 9 PY 2013 VL 127 IS 14 BP 1530 EP 1535 DI 10.1161/CIRCULATIONAHA.112.000858 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 122VS UT WOS:000317346900020 PM 23569120 ER PT J AU Januzzi, JL AF Januzzi, James L., Jr. TI Natriuretic Peptides, Ejection Fraction, and Prognosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE heart failure; natriuretic peptides; preserved ejection fraction; prognosis ID EMERGENCY-DEPARTMENT PRIDE; HEART-FAILURE; DYSPNEA; PREDICTION; MORTALITY; PROBNP; TRIAL; CHF C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Yawkey 5984,32 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 9 TC 7 Z9 7 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 APR 9 PY 2013 VL 61 IS 14 BP 1507 EP 1509 DI 10.1016/j.jacc.2013.01.039 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 120SL UT WOS:000317192300007 PM 23500284 ER PT J AU Schonberg, MA Walter, LC AF Schonberg, Mara A. Walter, Louise C. TI Talking About Stopping Cancer Screening-Not So Easy SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID OLDER; WOMEN; CARE C1 [Schonberg, Mara A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gen Med & Primary Care,Dept Med, Boston, MA 02215 USA. [Walter, Louise C.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Schonberg, MA (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, 1309 Beacon,Off 219, Brookline, MA 02446 USA. EM mschonbe@bidmc.harvard.edu FU NCI NIH HHS [R01 CA134425]; NIA NIH HHS [K23AG028584, K24AG041180] NR 10 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR 8 PY 2013 VL 173 IS 7 BP 532 EP 533 DI 10.1001/jamainternmed.2013.3233 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 154NR UT WOS:000319683400011 PM 23479053 ER PT J AU Gross, AL Jones, RN Inouye, SK AF Gross, Alden L. Jones, Richard N. Inouye, Sharon K. TI The Meaning of Delirium reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID DEMENTIA C1 [Gross, Alden L.; Jones, Richard N.; Inouye, Sharon K.] Harvard Univ, Sch Med, Inst Aging Res, Hebrew SeniorLife,Aging Brain Ctr, Boston, MA 02131 USA. [Gross, Alden L.; Jones, Richard N.; Inouye, Sharon K.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02131 USA. [Inouye, Sharon K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02131 USA. [Inouye, Sharon K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02131 USA. RP Gross, AL (reprint author), Harvard Univ, Sch Med, Inst Aging Res, 1200 Ctr St, Boston, MA 02131 USA. EM aldengross@hsl.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD APR 8 PY 2013 VL 173 IS 7 BP 598 EP 599 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 154NR UT WOS:000319683400039 ER PT J AU Singh, T Katiyar, SK AF Singh, Tripti Katiyar, Santosh K. TI Honokiol Inhibits Non-Small Cell Lung Cancer Cell Migration by Targeting PGE(2)-Mediated Activation of beta-Catenin Signaling SO PLOS ONE LA English DT Article ID NATURAL-PRODUCT; NITRIC-OXIDE; GUANYLATE-CYCLASE; COX-2 EXPRESSION; COLON-CANCER; IN-VIVO; CYCLOOXYGENASE-2; APOPTOSIS; CARCINOMA; GROWTH AB Lung cancer remains a leading cause of death due to its metastasis to distant organs. We have examined the effect of honokiol, a bioactive constituent from the Magnolia plant, on human non-small cell lung cancer (NSCLC) cell migration and the molecular mechanisms underlying this effect. Using an in vitro cell migration assay, we found that treatment of A549, H1299, H460 and H226 NSCLC cells with honokiol resulted in inhibition of migration of these cells in a dose-dependent manner, which was associated with a reduction in the levels of cyclooxygenase-2 (COX-2) and prostaglandin E-2 (PGE(2)). Celecoxib, a COX-2 inhibitor, also inhibited cell migration. Honokiol inhibited PGE(2)-enhanced migration of NSCLC cells, inhibited the activation of NF-kappa B/p65, an upstream regulator of COX-2, in A549 and H1299 cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-kappa B, also inhibited migration of NSCLC cells. PGE(2) has been shown to activate beta-catenin signaling, which contributes to cancer cell migration. Therefore, we checked the effect of honokiol on beta-catenin signaling. It was observed that treatment of NSCLC cells with honokiol degraded cytosolic beta-catenin, reduced nuclear accumulation of beta-catenin and down-regulated matrix metalloproteinase (MMP)-2 and MMP-9, which are the down-stream targets of beta-catenin and play a crucial role in cancer cell metastasis. Honokiol enhanced: (i) the levels of casein kinase-1 alpha, glycogen synthase kinase-3 beta, and (ii) phosphorylation of beta-catenin on critical residues Ser(45), Ser(33/37) and Thr(41). These events play important roles in degradation or inactivation of beta-catenin. Treatment of celecoxib also reduced nuclear accumulation of beta-catenin in NSCLC cells. FH535, an inhibitor of Wnt/beta-catenin pathway, inhibited PGE(2)-enhanced cell migration of A549 and H1299 cells. These results indicate that honokiol inhibits non-small cell lung cancer cells migration by targeting PGE(2)-mediated activation of delta-catenin signaling. C1 [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Tripti; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Nutr Obes Res Ctr, Birmingham, AL USA. [Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. EM skatiyar@uab.edu FU Veterans Administration [1I01BX001410-01] FX This research was financially supported by the Veterans Administration Merit Review Award (1I01BX001410-01, S.K.K.). The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 25 Z9 29 U1 3 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 8 PY 2013 VL 8 IS 4 AR e60749 DI 10.1371/journal.pone.0060749 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130FG UT WOS:000317898000059 PM 23580348 ER PT J AU Dearling, JLJ Looby, R Caravan, PD Packard, AB AF Dearling, Jason L. J. Looby, Richard Caravan, Peter D. Packard, Alan B. TI Simple approach to high sensitivity trace metal analysis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Dearling, Jason L. J.; Packard, Alan B.] Boston Childrens Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Looby, Richard; Caravan, Peter D.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Dearling, Jason L. J.; Caravan, Peter D.; Packard, Alan B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. EM alan.packard@childrens.harvard.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 APR 7 PY 2013 VL 245 MA 68-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602666 ER PT J AU Greer, A Kimani, S Ghosh, G Ghogare, A Rudshteyn, B Bartusik, D Hasan, T AF Greer, Alexander Kimani, Stanley Ghosh, Goutam Ghogare, Ashwini Rudshteyn, Benjamin Bartusik, Dorota Hasan, Tayyaba TI Synthesis and characterization of PEGylated chlorin sensitizers for the photodynamic killing of human ovarian cancer cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Greer, Alexander; Kimani, Stanley; Ghosh, Goutam; Ghogare, Ashwini; Rudshteyn, Benjamin; Bartusik, Dorota] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA. [Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hasan, Tayyaba] Harvard Univ, Sch Med, Boston, MA 02114 USA. EM agreer@brooklyn.cuny.edu NR 0 TC 0 Z9 0 U1 1 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 APR 7 PY 2013 VL 245 MA 760-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303603418 ER PT J AU Rai, PR AF Rai, Prakash R. TI Triple combination nanochemoprevention of breast cancer SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Rai, Prakash R.] Univ Massachusetts, Dept Chem Engn, Lowell, MA 01854 USA. [Rai, Prakash R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Engn Med, Boston, MA 02114 USA. EM Prakash_Rai@uml.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 58-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851303714 ER PT J AU Verdine, GL AF Verdine, Gregory L. TI Next-generation therapeutics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Chem Biol Initiat, Boston, MA 02214 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02214 USA. EM gregory_verdine@harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 118-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300720 ER PT J AU Petibon, Y Ouyang, J Zhu, X Huang, C Reese, TG Chun, SY Li, Q El Fakhri, G AF Petibon, Y. Ouyang, J. Zhu, X. Huang, C. Reese, T. G. Chun, S. Y. Li, Q. El Fakhri, G. TI Cardiac motion compensation and resolution modeling in simultaneous PET-MR: a cardiac lesion detection study SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; RESPIRATORY MOTION; IMAGE-RECONSTRUCTION; HUMAN-OBSERVER; GATED PET; 3D PET; REGISTRATION; DISPLACEMENT; FRACTION; PET/MRI AB Cardiac motion and partial volume effects (PVE) are two of the main causes of image degradation in cardiac PET. Motion generates artifacts and blurring while PVE lead to erroneous myocardial activity measurements. Newly available simultaneous PET-MR scanners offer new possibilities in cardiac imaging as MRI can assess wall contractility while collecting PET perfusion data. In this perspective, we develop a list-mode iterative reconstruction framework incorporating both tagged-MR derived non-rigid myocardial wall motion and position dependent detector point spread function (PSF) directly into the PET system matrix. In this manner, our algorithm performs both motion 'deblurring' and PSF deconvolution while reconstructing images with all available PET counts. The proposed methods are evaluated in a beating non-rigid cardiac phantom whose hot myocardial compartment contains small transmural and non-transmural cold defects. In order to accelerate imaging time, we investigate collecting full and half k-space tagged MR data to obtain tagged volumes that are registered using non-rigid B-spline registration to yield wall motion information. Our experimental results show that tagged-MR based motion correction yielded an improvement in defect/myocardium contrast recovery of 34-206% as compared to motion uncorrected studies. Likewise, lesion detectability improved by respectively 115-136% and 62-235% with MR-based motion compensation as compared to gating and no motion correction and made it possible to distinguish non-transmural from transmural defects, which has clinical significance given the inherent limitations of current single modality imaging in identifying the amount of residual ischemia. The incorporation of PSF modeling within the framework of MR-based motion compensation significantly improved defect/myocardium contrast recovery (5.1-8.5%, p < 0.01) and defect detectability (39-56%, p < 0.01). No statistical difference was found in PET contrast and lesion detectability based on motion fields obtained with half and full k-space tagged data. C1 [Petibon, Y.; Ouyang, J.; Zhu, X.; Huang, C.; Reese, T. G.; Chun, S. Y.; Li, Q.; El Fakhri, G.] Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Med Imaging Sci Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Reese, T. G.] Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP El Fakhri, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Med Imaging Sci Nucl Med & Mol Imaging, Boston, MA 02114 USA. EM elfakhri@pet.mgh.harvard.edu RI Chun, Se Young/B-6653-2013; OI Huang, Chuan/0000-0001-6052-0663; Chun, Se Young/0000-0001-8739-8960 FU [NIH-R21-EB012326]; [R01-CA165221] FX This work was supported by NIH-R21-EB012326 and R01-CA165221. The authors would like to thank Grae Arabasz for his help during the point sources and phantom acquisitions. NR 44 TC 25 Z9 25 U1 1 U2 23 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD APR 7 PY 2013 VL 58 IS 7 BP 2085 EP 2102 DI 10.1088/0031-9155/58/7/2085 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 106YJ UT WOS:000316181300008 PM 23470288 ER PT J AU Carabe, A Espana, S Grassberger, C Paganetti, H AF Carabe, Alejandro Espana, Samuel Grassberger, Clemens Paganetti, Harald TI Clinical consequences of relative biological effectiveness variations in proton radiotherapy of the prostate, brain and liver SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID LOW-ENERGY PROTONS; LINEAR-QUADRATIC MODEL; HAMSTER V79 CELLS; BEAM THERAPY; RBE; CANCER; HYPOFRACTIONATION; MICRODOSIMETRY; FRACTIONATION; INACTIVATION AB Proton relative biological effectiveness (RBE) is known to depend on the (alpha/beta)(x) of irradiated tissues, with evidence of similar to 60% variation over (alpha/beta)(x) values from 1-10 Gy. The range of (alpha/beta)(x) values reported for prostate tumors (1.2-5.0 Gy), brain tumors (10-15 Gy) and liver tumors (13-17 Gy) imply that the proton RBE for these tissues could vary significantly compared to the commonly used generic value of 1.1. Our aim is to evaluate the impact of this uncertainty on the proton dose in Gy(RBE) absorbed in normal and tumor tissues. This evaluation was performed for standard and hypofractionated regimens. RBE-weighted total dose (RWTD) distributions for 15 patients (five prostate tumors, five brain tumors and five liver tumors) were calculated using an in-house developed RBE model as a function of dose, dose-averaged linear energy transfer (LETd) and (alpha/beta)(x). Variations of the dose-volume histograms (DVHs) for the gross tumor volume (GTV) and the organs at risk due to changes of (alpha/beta)(x) and fractionation regimen were calculated and the RWTD received by 10% and 90% of the organ volume reported. The goodness of the plan, bearing the uncertainties, was then evaluated compared to the delivered plan, which considers a constant RBE of 1.1. For standard fractionated regimens, the prostate tumors, liver tumors and all critical structures in the brain showed typically larger RBE values than 1.1. However, in hypofractionated regimens lower values of RBE than 1.1 were observed in most cases. Based on DVH analysis we found that the RBE variations were clinically significant in particular for the prostate GTV and the critical structures in the brain. Despite the uncertainties in the biological input parameters when estimating RBE values, the results show that the use of a variable RBE with dose, LETd and (alpha/beta)(x) could help to further optimize the target dose in proton treatment planning. Most importantly, this study shows that the consideration of RBE variations could influence the comparison of proton and photon treatments in clinical trials, in particular in the case of the prostate. C1 [Carabe, Alejandro] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Espana, Samuel] Univ Ghent, Dept Med Imaging & Signal Proc MEDISIP, B-9000 Ghent, Belgium. [Grassberger, Clemens; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grassberger, Clemens; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Carabe, A (reprint author), Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. EM a.carabe@uphs.upenn.edu RI Espana, Samuel/E-9240-2010 OI Espana, Samuel/0000-0001-9092-4597 FU Federal Share of program [C06 CA059267] FX The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. Thanks are extended to Professor Roger G Dale for his useful comments on the BED calculations. NR 37 TC 16 Z9 16 U1 2 U2 12 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD APR 7 PY 2013 VL 58 IS 7 BP 2103 EP 2117 DI 10.1088/0031-9155/58/7/2103 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 106YJ UT WOS:000316181300009 PM 23470339 ER PT J AU Jacobson, CA Freedman, AS AF Jacobson, Caron A. Freedman, Arnold S. TI First-line treatment of indolent lymphoma: axing CHOP? SO LANCET LA English DT Editorial Material ID NON-HODGKINS-LYMPHOMA; LARGE-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; PLUS RITUXIMAB; LOW-GRADE; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; MAINTENANCE; VINCRISTINE; SURVIVAL C1 [Jacobson, Caron A.; Freedman, Arnold S.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM arnold_freedman@dfci.harvard.edu NR 12 TC 3 Z9 3 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 J9 LANCET JI Lancet PD APR 6 PY 2013 VL 381 IS 9873 BP 1163 EP 1165 DI 10.1016/S0140-6736(12)61965-5 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 122WU UT WOS:000317350100006 PM 23433738 ER PT J AU Huo, YL Choy, JS Wischgoll, T Luo, T Teague, SD Bhatt, DL Kassab, GS AF Huo, Yunlong Choy, Jenny Susana Wischgoll, Thomas Luo, Tong Teague, Shawn D. Bhatt, Deepak L. Kassab, Ghassan S. TI Computed tomography-based diagnosis of diffuse compensatory enlargement of coronary arteries using scaling power laws SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE coronary compensatory enlargement; scaling power law; computed tomography ID BLOOD-FLOW; TREE; MORPHOMETRY; DISEASE; ATHEROSCLEROSIS; EXTRACTION AB Glagov's positive remodelling in the early stages of coronary atherosclerosis often results in plaque rupture and acute events. Because positive remodelling is generally diffused along the epicardial coronary arterial tree, it is difficult to diagnose non-invasively. Hence, the objective of the study is to assess the use of scaling power law for the diagnosis of positive remodelling of coronary arteries based on computed tomography (CT) images. Epicardial coronary arterial trees were reconstructed from CT scans of six Ossabaw pigs fed on a high-fat, high-cholesterol, atherogenic diet for eight months as well as the same number of body-weight-matched farm pigs fed on a lean chow (101.9 +/- 16.1 versus 91.5 +/- 13.1 kg). The high-fat diet Ossabaw pig model showed diffuse positive remodelling of epicardial coronary arteries. Good fit of measured coronary data to the length-volume scaling power law (L-c = KLVVc7/9, where L-c and V-c are crown length and volume) were found for both the high-fat and control groups (R-2 = 0.95 +/- 0.04 and 0.99 +/- 0.01, respectively). The coefficient, K-LV, decreased significantly in the high-fat diet group when compared with the control (14.6 +/- 2.6 versus 40.9 +/- 5.6). The flow-length scaling power law, however, was nearly unaffected by the positive remodelling. The length-volume and flow-length scaling power laws were preserved in epicardial coronary arterial trees after positive remodelling. K-LV < 18 in the length-volume scaling relation is a good index of positive remodelling of coronary arteries. These findings provide a clinical rationale for simple, accurate and non-invasive diagnosis of positive remodelling of coronary arteries, using conventional CT scans. C1 [Huo, Yunlong; Choy, Jenny Susana; Luo, Tong; Teague, Shawn D.; Kassab, Ghassan S.] Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA. [Wischgoll, Thomas] Wright State Univ, Dayton, OH 45435 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Huo, Yunlong] Peking Univ, Beijing 100871, Peoples R China. RP Kassab, GS (reprint author), Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA. EM gkassab@iupui.edu RI Huo, Yunlong/N-8155-2013; OI Huo, Yunlong/0000-0003-4121-3224 FU National Institute of Health-National Heart, Lung and Blood Institute [HL-092048]; American Heart Association Scientist Development [0830181N] FX This study is supported in part by the National Institute of Health-National Heart, Lung and Blood Institute grant no. HL-092048 (G.S.K.) and the American Heart Association Scientist Development grant no. 0830181N (Y.H.). NR 24 TC 5 Z9 5 U1 1 U2 8 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD APR 6 PY 2013 VL 10 IS 81 AR 20121015 DI 10.1098/rsif.2012.1015 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093NY UT WOS:000315199800020 PM 23365197 ER PT J AU Browne, RW Kantarci, A LaMonte, MJ Andrews, CA Hovey, KM Falkner, KL Cekici, A Stephens, D Genco, RJ Scannapieco, FA Van Dyke, TE Wactawski-Wende, J AF Browne, Richard W. Kantarci, Alpdogan LaMonte, Michael J. Andrews, Christopher A. Hovey, Kathleen M. Falkner, Karen L. Cekici, Ali Stephens, Danielle Genco, Robert J. Scannapieco, Frank A. Van Dyke, Thomas E. Wactawski-Wende, Jean TI Performance of Multiplex Cytokine Assays in Serum and Saliva among Community-Dwelling Postmenopausal Women SO PLOS ONE LA English DT Article ID INTERNAL QUALITY-CONTROL; BIOLOGICAL VARIATION; ELISA; VALIDATION; RULES; IDENTIFICATION; QUANTITATION; INFLAMMATION; IMMUNOASSAYS; TECHNOLOGY AB Multiplexing arrays increase the throughput and decrease sample requirements for studies employing multiple biomarkers. The goal of this project was to examine the performance of Multiplex arrays for measuring multiple protein biomarkers in saliva and serum. Specimens from the OsteoPerio ancillary study of the Women's Health Initiative Observational Study were used. Participants required the presence of at least 6 teeth and were excluded based on active cancer and certain bone issues but were not selected on any specific condition. Quality control (QC) samples were created from pooled serum and saliva. Twenty protein markers were measured on five multiplexing array panels. Sample pretreatment conditions were optimized for each panel. Recovery, lower limit of quantification (LLOQ) and imprecision were determined for each analyte. Statistical adjustment at the plate level was used to reduce imprecision estimates and increase the number of usable observations. Sample pre-treatment improved recovery estimates for many analytes. The LLOQ for each analyte agreed with manufacturer specifications except for MMP-1 and MMP-2 which were significantly higher than reported. Following batch adjustment, 17 of 20 biomarkers in serum and 9 of 20 biomarkers in saliva demonstrated acceptable precision, defined as <20% coefficient of variation (<25% at LLOQ). The percentage of cohort samples having levels within the reportable range for each analyte varied from 10% to 100%. The ratio of levels in saliva to serum varied from 1:100 to 28:1. Correlations between saliva and serum were of moderate positive magnitude and significant for CRP, MMP-2, insulin, adiponectin, GM-CSF and IL-5. Multiplex arrays exhibit high levels of analytical imprecision, particularly at the batch level. Careful sample pre-treatment can enhance recovery and reduce imprecision. Following statistical adjustments to reduce batch effects, we identified biomarkers that are of acceptable quality in serum and to a lesser degree in saliva using Multiplex arrays. C1 [Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA. [Kantarci, Alpdogan; Cekici, Ali; Stephens, Danielle; Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol, Boston, MA USA. [LaMonte, Michael J.; Hovey, Kathleen M.; Falkner, Karen L.; Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, New York, NY USA. [Andrews, Christopher A.] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. [Genco, Robert J.; Scannapieco, Frank A.] SUNY Buffalo, Dept Oral Biol, New York, NY USA. RP Browne, RW (reprint author), SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA. EM rwbrowne@buffalo.edu OI Scannapieco, Frank/0000-0002-8804-6593 FU NHLBI FX The funder NHLBI had a role in the study design but not in the data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 10 Z9 10 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 5 PY 2013 VL 8 IS 4 AR e59498 DI 10.1371/journal.pone.0059498 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RZ UT WOS:000319109800011 PM 23577067 ER PT J AU Jiang, HB Chen, W Zhu, GC Zhang, LJ Tucker, BR Hao, L Feng, SM Ci, HL Ma, JQ Wang, L Stashenko, P Li, YP AF Jiang, Hongbing Chen, Wei Zhu, Guochun Zhang, Lijie Tucker, Byron Hao, Liang Feng, Shengmei Ci, Hongliang Ma, Junqing Wang, Lin Stashenko, Philip Li, Yi-Ping TI RNAi-Mediated Silencing of Atp6i and Atp6i Haploinsufficiency Prevents Both Bone Loss and Inflammation in a Mouse Model of Periodontal Disease SO PLOS ONE LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; IN-VITRO; T-CELL; OSTEOCLAST DIFFERENTIATION; ALLOGRAFT-REJECTION; PARKINSONS-DISEASE; MEMBRANE-PROTEIN; IMMUNE-RESPONSE; B-LYMPHOCYTE; GENE-THERAPY AB Periodontal disease affects about 80% of adults in America, and is characterized by oral bacterial infection-induced gingival inflammation, oral bone resorption, and tooth loss. Periodontitis is also associated with other diseases such as rheumatoid arthritis, diabetes, and heart disease. Although many efforts have been made to develop effective therapies for this disease, none have been very effective and there is still an urgent need for better treatments and preventative strategies. Herein we explored for the first time the possibility that adeno-associated virus (AAV)-mediated RNAi knockdown could be used to treat periodontal disease with improved efficacy. For this purpose, we used AAV-mediated RNAi knockdown of Atp6i/TIRC7 gene expression to target bone resorption and gingival inflammation simultaneously. Mice were infected with the oral pathogen Porphyromonas gingivalis W50 (P. gingivalis) in the maxillary periodontium to induce periodontitis. We found that Atp6i depletion impaired extracellular acidification and osteoclast-mediated bone resorption. Furthermore, local injection of AAV-shRNA-Atp6i/TIRC7 into the periodontal tissues in vivo protected mice from P. gingivalis infection-stimulated bone resorption by >85% and decreased the T-cell number in periodontal tissues. Notably, AAV-mediated Atp6i/TIRC7 knockdown also reduced the expression of osteoclast marker genes and inflammation-induced cytokine genes. Atp6i(+/-) mice with haploinsufficiency were similarly protected from P. gingivalis infection-stimulated bone loss and gingival inflammation. This suggests that AAV-shRNA-Atp6i/TIRC7 therapeutic treatment may significantly improve the health of millions who suffer from P. gingivalis-mediated periodontal disease. C1 [Jiang, Hongbing; Chen, Wei; Zhu, Guochun; Tucker, Byron; Hao, Liang; Feng, Shengmei; Ci, Hongliang; Ma, Junqing; Li, Yi-Ping] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Jiang, Hongbing; Ma, Junqing; Wang, Lin] Nanjing Med Univ, Coll Stomatol, Nanjing, Jiangsu, Peoples R China. [Tucker, Byron] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Endodont, Boston, MA 02115 USA. [Zhang, Lijie; Stashenko, Philip] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. [Zhang, Lijie] Hebei Med Univ, Hosp 3, Dept Clin Lab, Shijiazhuang, Hebei Province, Peoples R China. RP Chen, W (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM wechen@uab.edu; ypli@uab.edu FU National Institutes of Health [DE-020533-01, R01-AR-055307] FX This work was supported by National Institutes of Health grants DE-020533-01 (Y.P.L.) and R01-AR-055307 (Y.P.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 14 Z9 14 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 5 PY 2013 VL 8 IS 4 AR e58599 DI 10.1371/journal.pone.0058599 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RZ UT WOS:000319109800004 PM 23577057 ER PT J AU Sung, RJ Zhang, M Qi, Y Verdine, GL AF Sung, Rou-Jia Zhang, Michael Qi, Yan Verdine, Gregory L. TI Structural and Biochemical Analysis of DNA Helix Invasion by the Bacterial 8-Oxoguanine DNA Glycosylase MutM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; PROTEIN-STRUCTURE; REPAIR ENZYME; FPG PROTEIN; LESION; 7,8-DIHYDRO-8-OXOGUANINE; SYSTEM; RECOGNITION; VALIDATION; COMPLEXES AB MutM is a bacterial DNA glycosylase that serves as the first line of defense against the highly mutagenic 8-oxoguanine (oxoG) lesion, catalyzing glycosidic bond cleavage of oxoG to initiate base excision DNA repair. Previous work has shown that MutM actively interrogates DNA for the presence of an intrahelical oxoG lesion. This interrogation process involves significant buckling and bending of the DNA to promote extrusion of oxoG from the duplex. Structural snapshots have revealed several different highly conserved residues that are prominently inserted into the duplex in the vicinity of the target oxoG before and after base extrusion has occurred. However, the roles of these helix-invading residues during the lesion recognition and base extrusion process remain unclear. In this study, we set out to probe the function of residues Phe(114) and Met(77) in oxoG recognition and repair. Here we report a detailed biochemical and structural characterization of MutM variants containing either a F114A or M77A mutation, both of which showed significant decreases in the efficiency of oxoG repair. These data reveal that Met77 plays an important role in stabilizing the lesion-extruded conformation of the DNA. Phe(114), on the other hand, appears to destabilize the intrahelical state of the oxoG lesion, primarily by buckling the target base pair. We report the observation of a completely unexpected interaction state, in which the target base pair is ruptured but remains fully intrahelical; this structure vividly illustrates the disruptive influence of MutM on the target base pair. C1 [Sung, Rou-Jia; Verdine, Gregory L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Zhang, Michael; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Sung, Rou-Jia; Verdine, Gregory L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Chem Biol Initiat, Boston, MA 02115 USA. [Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. [Qi, Yan] Harvard Univ, Sch Med, Grad Program Biophys, Boston, MA 02115 USA. RP Verdine, GL (reprint author), 12 Oxford St, Cambridge, MA 02138 USA. EM gregory_verdine@harvard.edu FU National Institutes of Health [GM044853, CA100742]; Harvard College Research Program; National Science Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants GM044853 and CA100742.; Supported by a grant by the Harvard College Research Program.; Supported by a predoctoral fellowship from the National Science Foundation. NR 33 TC 13 Z9 13 U1 0 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 5 PY 2013 VL 288 IS 14 BP 10012 EP 10023 DI 10.1074/jbc.M112.415612 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119RB UT WOS:000317114000040 PM 23404556 ER PT J AU Apps, R Qi, Y Carlson, JM Chen, HY Gao, XJ Thomas, R Yuki, Y Del Prete, GQ Goulder, P Brumme, ZL Brumme, CJ John, M Mallal, S Nelson, G Bosch, R Heckerman, D Stein, JL Soderberg, KA Moody, MA Denny, TN Zeng, X Fang, JY Moffett, A Lifson, JD Goedert, JJ Buchbinder, S Kirk, GD Fellay, J McLaren, P Deeks, SG Pereyra, F Walker, B Michael, NL Weintrob, A Wolinsky, S Liao, W Carrington, M AF Apps, Richard Qi, Ying Carlson, Jonathan M. Chen, Haoyan Gao, Xiaojiang Thomas, Rasmi Yuki, Yuko Del Prete, Greg Q. Goulder, Philip Brumme, Zabrina L. Brumme, Chanson J. John, Mina Mallal, Simon Nelson, George Bosch, Ronald Heckerman, David Stein, Judy L. Soderberg, Kelly A. Moody, M. Anthony Denny, Thomas N. Zeng, Xue Fang, Jingyuan Moffett, Ashley Lifson, Jeffrey D. Goedert, James J. Buchbinder, Susan Kirk, Gregory D. Fellay, Jacques McLaren, Paul Deeks, Steven G. Pereyra, Florencia Walker, Bruce Michael, Nelson L. Weintrob, Amy Wolinsky, Steven Liao, Wilson Carrington, Mary TI Influence of HLA-C Expression Level on HIV Control SO SCIENCE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; T-CELL RESPONSES; DETERMINANTS; ASSOCIATIONS; METAANALYSIS; ALLELES; SYNAPSE; ESCAPE; NUMBER AB A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease. C1 [Apps, Richard; Qi, Ying; Gao, Xiaojiang; Thomas, Rasmi; Yuki, Yuko; Carrington, Mary] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Apps, Richard; Qi, Ying; Gao, Xiaojiang; Yuki, Yuko; Goulder, Philip; Pereyra, Florencia; Walker, Bruce; Carrington, Mary] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. [Apps, Richard; Qi, Ying; Gao, Xiaojiang; Yuki, Yuko; Goulder, Philip; Pereyra, Florencia; Walker, Bruce; Carrington, Mary] Harvard Univ, Boston, MA 02114 USA. [Carlson, Jonathan M.; Heckerman, David; Zeng, Xue] Microsoft Res, ESci Grp, Los Angeles, CA 90024 USA. [Chen, Haoyan; Fang, Jingyuan; Liao, Wilson] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94115 USA. [Chen, Haoyan; Lifson, Jeffrey D.] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Digest Dis, Dept Gastroenterol,Ren Ji Hosp, Shanghai 200001, Peoples R China. [Del Prete, Greg Q.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD 21702 USA. [Goulder, Philip] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Goulder, Philip] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. [Brumme, Zabrina L.; Brumme, Chanson J.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada. [Brumme, Zabrina L.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [John, Mina; Mallal, Simon] Murdoch Univ, Inst Immunol & Infect Dis, Murdoch, WA 6150, Australia. [Nelson, George] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Ctr Canc Res Genet Core, Basic Res Program, Frederick, MD 21702 USA. [Bosch, Ronald] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Stein, Judy L.; Soderberg, Kelly A.; Moody, M. Anthony; Denny, Thomas N.] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Zeng, Xue] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Dermatol, Beijing 100053, Peoples R China. [Moffett, Ashley] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Buchbinder, Susan] San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. [Kirk, Gregory D.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Fellay, Jacques; McLaren, Paul] Univ Lausanne Hosp, Inst Microbiol, CH-1015 Lausanne, Switzerland. [Fellay, Jacques; McLaren, Paul] Ecole Polytech Fed Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94105 USA. [Michael, Nelson L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA. [Weintrob, Amy] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20817 USA. [Wolinsky, Steven] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. RP Carrington, M (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. EM carringm@mail.nih.gov RI Del Prete, Gregory/C-2030-2012; Moffett, Ashley/J-9754-2013; SHCS, int. coll. A/G-4083-2011; Fellay, Jacques/A-6681-2009; SHCS, all/G-4072-2011; OI Fellay, Jacques/0000-0002-8240-939X; Denny, Thomas/0000-0002-7364-8276; Wolinsky, Steven/0000-0002-9625-6697; Moody, Tony/0000-0002-3890-5855; Brumme, Chanson/0000-0003-2722-5288 FU National Institutes of Health (NIH) [HHSN261200800001E, N02-CP-55504, RO1-AI046995, R01-DA04334, R01-DA12568, R01-AI060460]; Bill & Melinda Gates Foundation [38599]; Mark and Lisa Schwartz Foundation; Wellcome Trust; NIH National Institute of Allergy and Infectious Diseases (NIAID) Center for HIV/AIDS Vaccine Immunology [U01-AI-067854]; Australian National Health and Medical Research Council [384702]; National Institutes of Health [K08AR057763, R01-DA-04334, R01-DA-12568]; Creative and Novel Ideas in HIV Research Program [P30 AI027767-24]; Swiss National Science Foundation [33CSC0-108787]; NIAID; National Cancer Institute; National Heart, Lung, and Blood Institute [UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]; [RO1 AI087145]; [K24AI069994]; [P30 AI027763]; [UL1 RR024131]; [P30 MH62246]; [R24 AI067039] FX This study makes use of data generated by the Wellcome Trust Case Control Consortium (WTCCC); a full list of investigators who contributed to the generation of this data is available at www.wtccc.org.uk. The data reported in this paper are tabulated in the main paper and supplementary materials. Data and materials will be shared subject to institutional review board (IRB) provisions regarding patient privacy. Please contact the corresponding author. Those interested in obtaining Center for HIV/AIDS Vaccine Immunology (CHAVI) samples used in this study should contact M. C. and M. A. M. A Simple Letter Agreement for the Transfer of Materials will be executed between the institutions involved, and an IRB approval/exemption should be obtained by the recipient institution when appropriate. Clinical specimens from the Multicenter AIDS Cohort Study (MACS) are subject to the terms and conditions of the MACS Master Material Transfer Agreement for Non-Profit Institutions. The project has been funded in part with federal funds from the National Institutes of Health (NIH) under contracts HHSN261200800001E, N02-CP-55504, RO1-AI046995, R01-DA04334, R01-DA12568, and R01-AI060460. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services or the Department of Defense, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This research was supported in part by grants from the Bill & Melinda Gates Foundation as part of the Collaboration for AIDS Vaccine Discovery and grant ID38599, the Mark and Lisa Schwartz Foundation, the Wellcome Trust, the NIH National Institute of Allergy and Infectious Diseases (NIAID) Center for HIV/AIDS Vaccine Immunology (U01-AI-067854), and the Australian National Health and Medical Research Council (Program Grant 384702). Further funding was from the National Institutes of Health grant K08AR057763 and the Creative and Novel Ideas in HIV Research Program through a supplement to the University of Alabama at the Birmingham Center For AIDS Research funding (P30 AI027767-24), made possible by collaborative efforts of the Office of AIDS Research, NIAID, and the International AIDS Society. We thank M. Trubey and A. Lara for cytometry assistance and all the patients and investigators contributing to samples studied in the WTCCC, CHAVI, Multicenter Hemophilia Cohort Study, San Francisco City Clinic Cohort, Massachusetts General Hospital Controller Cohort, United States Military HIV Natural History Study, DC Gay Cohort Study, British Columbia HOMER cohort, Western Australian HIV Cohort Study, US AIDS Clinical Trials Group, Durban, AIDS Linked to Intravenous Experience (supported by National Institutes of Health grants R01-DA-04334 and R01-DA-12568), Swiss HIV Cohort Study (supported by the Swiss National Science Foundation grant number 33CSC0-108787), Study on the Consequences of Protease Inhibitor Era (supported by grants RO1 AI087145, K24AI069994, P30 AI027763, UL1 RR024131, P30 MH62246, and R24 AI067039), and MACS cohorts (funded by NIAID, with supplemental funding from the National Cancer Institute and the National Heart, Lung, and Blood Institute [grants UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041]. NR 25 TC 117 Z9 118 U1 2 U2 51 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 5 PY 2013 VL 340 IS 6128 BP 87 EP 91 DI 10.1126/science.1232685 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 118XS UT WOS:000317061100052 PM 23559252 ER PT J AU Ding, QR Regan, SN Xia, YL Oostrom, LA Cowan, CA Musunuru, K AF Ding, Qiurong Regan, Stephanie N. Xia, Yulei Oostrom, Leonie A. Cowan, Chad A. Musunuru, Kiran TI Enhanced Efficiency of Human Pluripotent Stem Cell Genome Editing through Replacing TALENs with CRISPRs SO CELL STEM CELL LA English DT Letter C1 [Ding, Qiurong; Regan, Stephanie N.; Xia, Yulei; Oostrom, Leonie A.; Cowan, Chad A.; Musunuru, Kiran] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Ding, Qiurong; Regan, Stephanie N.; Xia, Yulei; Oostrom, Leonie A.; Cowan, Chad A.; Musunuru, Kiran] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Cowan, Chad A.; Musunuru, Kiran] Broad Inst, Cambridge, MA 02142 USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Musunuru, Kiran] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Musunuru, K (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM kiranmusunuru@gmail.com FU NHLBI NIH HHS [R00-HL098364, R00 HL098364, R01 HL118744, R01-HL118744, U01 HL107440]; NIDDK NIH HHS [R01 DK095384, R01 DK097768, R01-DK097768] NR 7 TC 168 Z9 200 U1 3 U2 55 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD APR 4 PY 2013 VL 12 IS 4 BP 393 EP 394 DI 10.1016/j.stem.2013.03.006 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VD UT WOS:000329569500006 PM 23561441 ER PT J AU Beerman, I Bock, C Garrison, BS Smith, ZD Gu, HC Meissner, A Rossi, DJ AF Beerman, Isabel Bock, Christoph Garrison, Brian S. Smith, Zachary D. Gu, Hongcang Meissner, Alexander Rossi, Derrick J. TI Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging SO CELL STEM CELL LA English DT Article ID SELF-RENEWAL CAPACITY; IN-VIVO; AGE; DIFFERENTIATION; TRANSPLANTATION; DAMAGE; TRANSCRIPTION; COMMITMENT; FREQUENCY; EXPANSION AB The functional potential of hematopoietic stem cells (HSCs) declines during aging, and in doing so, significantly contributes to hematopoietic pathophysiology in the elderly. To explore the relationship between age-associated HSC decline and the epigenome, we examined global DNA methylation of HSCs during ontogeny in combination with functional analysis. Although the DNA methylome is generally stable during aging, site-specific alterations of DNA methylation occur at genomic regions associated with hematopoietic lineage potential and selectively target genes expressed in downstream progenitor and effector cells. We found that age-associated HSC decline, replicative limits, and DNA methylation are largely dependent on the proliferative history of HSCs, yet appear to be telomere-length independent. Physiological aging and experimentally enforced proliferation of HSCs both led to DNA hypermethylation of genes regulated by Polycomb Repressive Complex 2. Our results provide evidence that epigenomic alterations of the DNA methylation landscape contribute to the functional decline of HSCs during aging. C1 [Beerman, Isabel; Garrison, Brian S.; Rossi, Derrick J.] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA 02116 USA. [Beerman, Isabel; Garrison, Brian S.; Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Beerman, Isabel; Bock, Christoph; Garrison, Brian S.; Smith, Zachary D.; Meissner, Alexander; Rossi, Derrick J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Bock, Christoph; Smith, Zachary D.; Gu, Hongcang; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Meissner, Alexander; Rossi, Derrick J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Meissner, A (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM alexander_meissner@harvard.edu; derrick.rossi@childrens.harvard.edu RI Bock, Christoph/B-6723-2008 OI Bock, Christoph/0000-0001-6091-3088 FU Harvard Stem Cell Institute; Pew Charitable Trusts FX We would like to thank A. Zguro, R. Gazit, L. Fang, and M. Ziller for technical assistance; P. Mandal for helpful discussions; and E. Beerman for editorial help. This work was supported by a grant from the Harvard Stem Cell Institute. A. M. is supported by the Pew Charitable Trusts. D.J.R. and A. M. are New York Stem Cell Foundation, Robertson Investigators. NR 60 TC 126 Z9 130 U1 4 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD APR 4 PY 2013 VL 12 IS 4 BP 413 EP 425 DI 10.1016/j.stem.2013.01.017 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 287VD UT WOS:000329569500009 PM 23415915 ER PT J AU Huertas-Vazquez, A Nelson, CP Guo, XQ Reinier, K Uy-Evanado, A Teodorescu, C Ayala, J Jerger, K Chugh, H Braund, PS Deloukas, P Hall, AS Balmforth, AJ Jones, M Taylor, KD Pulit, SL Newton-Cheh, C Gunson, K Jui, J Rotter, JI Albert, CM Samani, NJ Chugh, SS AF Huertas-Vazquez, Adriana Nelson, Christopher P. Guo, Xiuqing Reinier, Kyndaron Uy-Evanado, Audrey Teodorescu, Carmen Ayala, Jo Jerger, Katherine Chugh, Harpriya Braund, Peter S. Deloukas, Panos Hall, Alistair S. Balmforth, Anthony J. Jones, Michelle Taylor, Kent D. Pulit, Sara L. Newton-Cheh, Christopher Gunson, Karen Jui, Jonathan Rotter, Jerome I. Albert, Christine M. Samani, Nilesh J. Chugh, Sumeet S. CA WTCCC TI Novel Loci Associated with Increased Risk of Sudden Cardiac Death in the Context of Coronary Artery Disease SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; ACUTE MYOCARDIAL-INFARCTION; COMMON VARIANTS; UNEXPECTED DEATH; SUSCEPTIBILITY LOCI; BINDING PROTEIN; HEART-DISEASE; QRS DURATION; PR INTERVAL; POPULATION AB Background: Recent genome-wide association studies (GWAS) have identified novel loci associated with sudden cardiac death (SCD). Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD). Methods and Findings: Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD) from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC). Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93 x 10(-12), OR = 1.60) and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64 x 10(-8), OR = 2.41). Conclusions: Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility. C1 [Huertas-Vazquez, Adriana; Reinier, Kyndaron; Uy-Evanado, Audrey; Teodorescu, Carmen; Ayala, Jo; Jerger, Katherine; Chugh, Harpriya; Chugh, Sumeet S.] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. [Nelson, Christopher P.; Braund, Peter S.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit Cardiov, Leicester, Leics, England. [Guo, Xiuqing; Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England. [Hall, Alistair S.; Balmforth, Anthony J.] Univ Leeds, Dept Clin Cardiol, Leeds, W Yorkshire, England. [Jones, Michelle] Cedars Sinai Med Ctr, Dept Med, Div Endocrinol & Metab, Los Angeles, CA 90048 USA. [Pulit, Sara L.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Gunson, Karen] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jui, Jonathan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Albert, Christine M.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Div Prevent Med,Ctr Arrhyth, Boston, MA USA. RP Samani, NJ (reprint author), Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. EM njs@le.ac.uk; sumeet.chugh@cshs.org RI Deloukas, Panos/B-2922-2013; Breen, Gerome/A-5540-2010; OI Hattersley, Andrew/0000-0001-5620-473X; Newman, William/0000-0002-6382-4678; Deloukas, Panos/0000-0001-9251-070X; Breen, Gerome/0000-0003-2053-1792; Maller, Julian/0000-0002-1565-9559; Hocking, Lynne J/0000-0002-2414-2826; Wain, Louise/0000-0003-4951-1867; Burren, Oliver/0000-0002-3388-5760; Lango Allen, Hana/0000-0002-7803-8688; Zeggini, Eleftheria/0000-0003-4238-659X; Eyre, Stephen/0000-0002-1251-6974; Ouwehand, Willem/0000-0002-7744-1790 FU British Heart Foundation (BHF); British Cardiovascular Society FX The Oregon Sudden Unexpected Death Study acknowledges the significant contribution of American Medical Response and the Portland/Gresham fire departments. SSC holds the Pauline and Harold Price Chair in Cardiac Electrophysiology at the Cedars-Sinai Heart Institute. Recruitment of the British Heart Foundation Heart Family Heart Study was funded by the British Heart Foundation (BHF) and the PRAMIS Study by the British Cardiovascular Society. NJS holds a Chair funded by the BHF and is a UK National Institute for Health Research (NIHR) Senior Investigator. This work falls under the portfolio of research conducted within the NIHR Leicester Cardiovascular Biomedical Research Unit. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 14 Z9 14 U1 0 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 4 PY 2013 VL 8 IS 4 AR e59905 DI 10.1371/journal.pone.0059905 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RK UT WOS:000319108100011 PM 23593153 ER PT J AU Chekaluk, Y Wu, CL Rosenberg, J Riester, M Dai, QS Lin, S Guo, YA McDougal, WS Kwiatkowski, DJ AF Chekaluk, Yvonne Wu, Chin-Lee Rosenberg, Jonathan Riester, Markus Dai, Qishan Lin, Sharron Guo, Yanan McDougal, W. Scott Kwiatkowski, David J. TI Identification of Nine Genomic Regions of Amplification in Urothelial Carcinoma, Correlation with Stage, and Potential Prognostic and Therapeutic Value SO PLOS ONE LA English DT Article ID COPY NUMBER ALTERATIONS; TRANSITIONAL-CELL CARCINOMA; PAPILLARY BLADDER-CANCER; CHROMOSOMAL-ABERRATIONS; GENETIC ALTERATIONS; HYBRIDIZATION; MUTATIONS; FREQUENT; TUMORS; TARGET AB We performed a genome wide analysis of 164 urothelial carcinoma samples and 27 bladder cancer cell lines to identify copy number changes associated with disease characteristics, and examined the association of amplification events with stage and grade of disease. Multiplex inversion probe (MIP) analysis, a recently developed genomic technique, was used to study 80 urothelial carcinomas to identify mutations and copy number changes. Selected amplification events were then analyzed in a validation cohort of 84 bladder cancers by multiplex ligation-dependent probe assay (MLPA). In the MIP analysis, 44 regions of significant copy number change were identified using GISTIC. Nine gene-containing regions of amplification were selected for validation in the second cohort by MLPA. Amplification events at these 9 genomic regions were found to correlate strongly with stage, being seen in only 2 of 23 (9%) Ta grade 1 or 1-2 cancers, in contrast to 31 of 61 (51%) Ta grade 3 and T2 grade 2 cancers, p<0.001. These observations suggest that analysis of genomic amplification of these 9 regions might help distinguish non-invasive from invasive urothelial carcinoma, although further study is required. Both MIP and MLPA methods perform well on formalin-fixed paraffin-embedded DNA, enhancing their potential clinical use. Furthermore several of the amplified genes identified here (ERBB2, MDM2, CCND1) are potential therapeutic targets. C1 [Chekaluk, Yvonne; Guo, Yanan; Kwiatkowski, David J.] Brigham & Womens Hosp, Div Translat Med, Boston, MA 02115 USA. [Wu, Chin-Lee; Lin, Sharron; Guo, Yanan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rosenberg, Jonathan] Mem Sloan Kettering Canc Ctr, Div Genitourinary Oncol, York, NY USA. [Riester, Markus] Harvard Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Riester, Markus] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. [McDougal, W. Scott] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM WMCDOUGAL@PARTNERS.ORG; dk@rics.bwh.harvard.edu OI Rosenberg, Jonathan/0000-0003-2637-4249; Riester, Markus/0000-0002-4759-8332 FU National Institutes of Health (NIH), National Cancer Institute (NCI) [1P01CA120964] FX This work was supported by National Institutes of Health (NIH), National Cancer Institute (NCI) 1P01CA120964. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 14 Z9 14 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 APR 4 PY 2013 VL 8 IS 4 AR e60927 DI 10.1371/journal.pone.0060927 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RK UT WOS:000319108100069 PM 23593348 ER PT J AU D'Addio, F Ueno, T Clarkson, M Zhu, BG Vergani, A Freeman, GJ Sayegh, MH Ansari, MJI Fiorina, P Habicht, A AF D'Addio, Francesca Ueno, Takuya Clarkson, Michael Zhu, Baogong Vergani, Andrea Freeman, Gordon J. Sayegh, Mohamed H. Ansari, Mohammed Javeed I. Fiorina, Paolo Habicht, Antje TI CD160Ig Fusion Protein Targets a Novel Costimulatory Pathway and Prolongs Allograft Survival SO PLOS ONE LA English DT Article ID CD8(+) T-CELLS; MHC CLASS-I; HERPESVIRUS ENTRY MEDIATOR; CHRONIC VIRAL-INFECTION; CARDIAC ALLOGRAFTS; CUTTING EDGE; NK CELLS; TRANSPLANTATION TOLERANCE; CD28-DEFICIENT MICE; SUPPRESSOR-CELLS AB CD160 is a cell surface molecule expressed by most NK cells and approximately 50% of CD8(+) cytotoxic T lymphocytes. Engagement of CD160 by MHC class-I directly triggers a costimulatory signal to TCR-induced proliferation, cytokine production and cytotoxic effector functions. The role of CD160 in alloimmunity is unknown. Using a newly generated CD160 fusion protein (CD160Ig) we examined the role of the novel costimulatory molecule CD160 in mediating CD4(+) or CD8(+) T cell driven allograft rejection. CD160Ig inhibits alloreactive CD8(+) T cell proliferation and IFN-gamma production in vitro, in particular in the absence of CD28 costimulation. Consequently CD160Ig prolongs fully mismatched cardiac allograft survival in CD4(-/-), C28(-/-) knockout and CTLA4Ig treated WT recipients, but not in WT or CD8(-/-) knockout recipients. The prolonged cardiac allograft survival is associated with reduced alloreactive CD8(+) T cell proliferation, effector/memory responses and alloreactive IFN-gamma production. Thus, CD160 signaling is particularly important in CD28-independent effector/memory CD8(+) alloreactive T cell activation in vivo and therefore may serve as a novel target for prevention of allograft rejection. C1 [D'Addio, Francesca; Ueno, Takuya; Clarkson, Michael; Vergani, Andrea; Sayegh, Mohamed H.; Ansari, Mohammed Javeed I.; Fiorina, Paolo; Habicht, Antje] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal,Transplantat Res Ctr, Boston, MA 02115 USA. [D'Addio, Francesca; Ueno, Takuya; Clarkson, Michael; Vergani, Andrea; Sayegh, Mohamed H.; Ansari, Mohammed Javeed I.; Fiorina, Paolo; Habicht, Antje] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [D'Addio, Francesca; Fiorina, Paolo] Ist Sci San Raffaele, Transplantat & Internal Med Div, I-20132 Milan, Italy. [Clarkson, Michael] Cork Univ Hosp, Dept Renal Med, Cork, Ireland. [Zhu, Baogong; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Habicht, Antje] Univ Hosp, Transplant Ctr Munich LMU, Munich, Germany. RP Habicht, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal,Transplantat Res Ctr, Boston, MA 02115 USA. EM antje.habicht@med.uni-muenchen.de RI D'Addio, Francesca/F-3417-2017 OI D'Addio, Francesca/0000-0002-0345-0694 FU National Kidney Foundation; AST-Wyeth Basic Science Faculty; National Institutes of Health [K08 AI080836-01]; ERA-EDTA; SISQT-Biotest Fellowship; ISSNAF-Fondazione Marche fellowship grant; [AI56299]; [AI1051559] FX AH was supported by a National Kidney Foundation fellowship grant, MJA was supported by an AST-Wyeth Basic Science Faculty development grant and a National Institutes of Health grant K08 AI080836-01. MHS and GJF were supported by AI56299 and AI1051559. FD was supported by the ERA-EDTA and the SISQT-Biotest Fellowship, and she is the recipient of ISSNAF-Fondazione Marche fellowship grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 9 Z9 9 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 4 PY 2013 VL 8 IS 4 AR e60391 DI 10.1371/journal.pone.0060391 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RK UT WOS:000319108100037 PM 23593209 ER PT J AU Elman, I Gurvits, TV Tschibelu, E Spring, JD Lasko, NB Pitman, RK AF Elman, Igor Gurvits, Tamara V. Tschibelu, Evelyne Spring, Justin D. Lasko, Natasha B. Pitman, Roger K. TI Neurological Soft Signs in Individuals with Pathological Gambling SO PLOS ONE LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; IMPULSE CONTROL DISORDERS; AUTONOMIC AROUSAL; COCAINE USE; CARDIOVASCULAR COMPLICATIONS; SCHIZOPHRENIC-PATIENTS; PROBLEM GAMBLERS; DRUG-ABUSE; HEART-RATE AB Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e. g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response. C1 [Elman, Igor] Harvard Univ, Sch Med, Providence VA Med Ctr, Cambridge, MA 02138 USA. [Elman, Igor; Tschibelu, Evelyne] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. [Gurvits, Tamara V.; Spring, Justin D.; Lasko, Natasha B.; Pitman, Roger K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Elman, I (reprint author), Harvard Univ, Sch Med, Providence VA Med Ctr, Cambridge, MA 02138 USA. EM ielman@cha.harvard.edu FU National Institute on Drug Abuse [017959] FX This work was supported by grant DA #017959 (to IE) from the National Institute on Drug Abuse. This study was also supported with resources and the use of facilities at the Providence VA Medical Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 110 TC 3 Z9 3 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 APR 4 PY 2013 VL 8 IS 4 AR UNSP e60885 DI 10.1371/journal.pone.0060885 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RK UT WOS:000319108100067 PM 23593341 ER PT J AU LeBlanc, MA Fairn, GD Russo, SB Czyz, O Zaremberg, V Cowart, LA McMaster, CR AF LeBlanc, Marissa A. Fairn, Gregory D. Russo, Sarah B. Czyz, Ola Zaremberg, Vanina Cowart, L. Ashley McMaster, Christopher R. TI The Yeast Oxysterol Binding Protein Kes1 Maintains Sphingolipid Levels SO PLOS ONE LA English DT Article ID PLASMA-MEMBRANE ATPASE; SACCHAROMYCES-CEREVISIAE; STEROL MOVEMENT; TRAFFICKING; PATHWAYS; CELL; ER; PHOSPHATIDYLINOSITOL; HOMEOSTASIS; METABOLISM AB The oxysterol binding protein family are amphitropic proteins that bind oxysterols, sterols, and possibly phosphoinositides, in a conserved binding pocket. The Saccharomyces cerevisiae oxysterol binding protein family member Kes1 (also known as Osh4) also binds phosphoinositides on a distinct surface of the protein from the conserved binding pocket. In this study, we determine that the oxysterol binding protein family member Kes1 is required to maintain the ratio of complex sphingolipids and levels of ceramide, sphingosine-phosphate and sphingosine. This inability to maintain normal sphingolipid homeostasis resulted in misdistribution of Pma1, a protein that requires normal sphingolipid synthesis to occur to partition into membrane rafts at the Golgi for its trafficking to the plasma membrane. C1 [LeBlanc, Marissa A.] Dalhousie Univ, Dept Pathol, Halifax, NS, Canada. [Fairn, Gregory D.] St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Russo, Sarah B.; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Czyz, Ola; Zaremberg, Vanina] Univ Calgary, Dept Biol, Calgary, AB T2N 1N4, Canada. [Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [McMaster, Christopher R.] Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada. RP McMaster, CR (reprint author), Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada. EM christopher.mcmaster@dal.ca FU CIHR; NIH; VA; NSERC FX This work was supported by CIHR (http://www.cihr-irsc.gc.ca/e/193.html), NIH (http://www.nih.gov/), VA (http://www.research.va.gov/funding/), and NSERC (http://www.nserc-crsng.gc.ca/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 24 TC 4 Z9 5 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 4 PY 2013 VL 8 IS 4 AR e60485 DI 10.1371/journal.pone.0060485 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RK UT WOS:000319108100047 PM 23593226 ER PT J AU Moy, ML Teylan, M Weston, NA Gagnon, DR Garshick, E AF Moy, Marilyn L. Teylan, Merilee Weston, Nicole A. Gagnon, David R. Garshick, Eric TI Daily Step Count Predicts Acute Exacerbations in a US Cohort with COPD SO PLOS ONE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; 6-MINUTE WALK DISTANCE; MINIMAL IMPORTANT DIFFERENCE; PHYSICAL-ACTIVITY; FUNCTIONAL STATUS; HEALTH-STATUS; LUNG-DISEASE; RISK-FACTORS; HOSPITALIZATION; POPULATION AB Background: COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs). Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations. Methods: In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count. We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St. George's Respiratory Questionnaire Activity Score (SGRQ-AS). AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months. Results: Mean daily step count was 5804 +/- 3141 steps. Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3 +/- 1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56 +/- 1.09 per person-year). Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42). There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003). Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations. Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations. Conclusions: Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history. These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies. C1 [Moy, Marilyn L.; Garshick, Eric] Vet Hlth Adm, Rehabil Res & Dev Serv, Dept Veteran Affairs, Washington, DC USA. [Moy, Marilyn L.; Teylan, Merilee; Weston, Nicole A.; Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. [Moy, Marilyn L.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Garshick, Eric] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Moy, Marilyn L.; Garshick, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gagnon, David R.] VA Cooperat Studies, Boston, MA USA. RP Moy, ML (reprint author), Vet Hlth Adm, Rehabil Res & Dev Serv, Dept Veteran Affairs, Washington, DC USA. EM marilyn.moy@va.gov OI Gagnon, David/0000-0002-6367-3179 FU Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research; Development Service through a VA Career Development Award; CIMIT: Center for Integration of Medicine and Innovative Technology; VA Rehabilitation Research and Development Merit Review [B6618R] FX The research reported here was supported by the Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award to Dr. Moy. Supported in part by CIMIT: Center for Integration of Medicine and Innovative Technology (Dr. Moy). Supported in part by VA Rehabilitation Research and Development Merit Review Grant B6618R (Dr. Garshick). This study was initiated by the investigators. The results of the present study do not constitute endorsement of the StepWatch Activity Monitor by the authors. Orthocare Innovations had no involvement in the study design, the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the paper for publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 24 Z9 24 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 APR 4 PY 2013 VL 8 IS 4 AR e60400 DI 10.1371/journal.pone.0060400 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RK UT WOS:000319108100038 PM 23593211 ER PT J AU Yeh, WL Shioda, K Coser, KR Rivizzigno, D McSweeney, KR Shioda, T AF Yeh, Wei-Lan Shioda, Keiko Coser, Kathryn R. Rivizzigno, Danielle McSweeney, Kristen R. Shioda, Toshi TI Fulvestrant-Induced Cell Death and Proteasomal Degradation of Estrogen Receptor alpha Protein in MCF-7 Cells Require the CSK c-Src Tyrosine Kinase SO PLOS ONE LA English DT Article ID BREAST-CANCER CELLS; E-SCREEN ASSAY; ER-ALPHA; ENDOCRINE THERAPY; DYNEIN LIGHT-CHAIN-1; MEDIATED DEGRADATION; POSTMENOPAUSAL WOMEN; STEROID-RECEPTORS; PROSTATE-CANCER; GENE-EXPRESSION AB Fulvestrant is a representative pure antiestrogen and a Selective Estrogen Receptor Down-regulator (SERD). In contrast to the Selective Estrogen Receptor Modulators (SERMs) such as 4-hydroxytamoxifen that bind to estrogen receptor alpha (ER alpha) as antagonists or partial agonists, fulvestrant causes proteasomal degradation of ERa protein, shutting down the estrogen signaling to induce proliferation arrest and apoptosis of estrogen-dependent breast cancer cells. We performed genome-wide RNAi knockdown screenings for protein kinases required for fulvestrant-induced apoptosis of the MCF-7 estrogendependent human breast caner cells and identified the c-Src tyrosine kinase (CSK), a negative regulator of the oncoprotein c-Src and related protein tyrosine kinases, as one of the necessary molecules. Whereas RNAi knockdown of CSK in MCF-7 cells by shRNA-expressing lentiviruses strongly suppressed fulvestrant-induced cell death, CSK knockdown did not affect cytocidal actions of 4-hydroxytamoxifen or paclitaxel, a chemotherapeutic agent. In the absence of CSK, fulvestrant-induced proteasomal degradation of ER alpha protein was suppressed in both MCF-7 and T47D estrogen-dependent breast cancer cells whereas the TP53-mutated T47D cells were resistant to the cytocidal action of fulvestrant in the presence or absence of CSK. MCF-7 cell sensitivities to fulvestrant-induced cell death or ERa protein degradation was not affected by small-molecular-weight inhibitors of the tyrosine kinase activity of c-Src, suggesting possible involvement of other signaling molecules in CSK-dependent MCF-7 cell death induced by fulvestrant. Our observations suggest the importance of CSK in the determination of cellular sensitivity to the cytocidal action of fulvestrant. C1 [Shioda, Toshi] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA USA. EM tshioda@partners.org FU Susan G. Komen for Cure grant [FAS0703860, KG090515]; AstraZeneca [IRUSFULV0066] FX This research was supported by Susan G. Komen for Cure grants FAS0703860 and KG090515, and AstraZeneca Preclinical Study Support IRUSFULV0066, awarded to T. Shioda. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 98 TC 20 Z9 21 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 4 PY 2013 VL 8 IS 4 AR UNSP e60889 DI 10.1371/journal.pone.0060889 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146RK UT WOS:000319108100068 PM 23593342 ER PT J AU Marneros, AG Beck, AE Turner, EH McMillin, MJ Edwards, MJ Field, M Sobreira, NLD Perez, ABA Fortes, JAR Lampe, AK Uzielli, MLG Gordon, CT Plessis, G Le Merrer, M Amiel, J Reichenberger, E Shively, KM Cerrato, F Labow, BI Tabor, HK Smith, JD Shendure, J Nickerson, DA Bamshad, MJ AF Marneros, Alexander G. Beck, Anita E. Turner, Emily H. McMillin, Margaret J. Edwards, Matthew J. Field, Michael Sobreira, Nara Lygia de Macena Perez, Ana Beatriz A. Fortes, Jose A. R. Lampe, Anne K. Uzielli, Maria Luisa Giovannucci Gordon, Christopher T. Plessis, Ghislaine Le Merrer, Martine Amiel, Jeanne Reichenberger, Ernst Shively, Kathryn M. Cerrato, Felecia Labow, Brian I. Tabor, Holly K. Smith, Joshua D. Shendure, Jay Nickerson, Deborah A. Bamshad, Michael J. CA Univ Washington TI Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FINLAY-MARKS-SYNDROME; BTB DOMAIN; ADDITIONAL MANIFESTATIONS; FAMILY AB Scalp-ear-nipple (SEN) syndrome is a rare, autosomal-dominant disorder characterized by cutis aplasia of the scalp; minor anomalies of the external ears, digits, and nails; and malformations of the breast. We used linkage analysis and exome sequencing of a multiplex family affected by SEN syndrome to identify potassium-channel tetramerization-domain-containing 1 (KCTD1) mutations that cause SEN syndrome. Evaluation of a total of ten families affected by SEN syndrome revealed KCTD1 missense mutations in each family tested. All of the mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac, tram track, and broad complex (BTB) domain that is required for transcriptional repressor activity. KCTD1 inhibits the transactivation of the transcription factor AP-2 alpha (TFAP2A) via its BTB domain, and mutations in TFAP2A cause cutis aplasia in individuals with branchiooculofacial syndrome (BOFS), suggesting a potential overlap in the pathogenesis of SEN syndrome and BOFS. The identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB-domain-containing transcriptional repressor during ectodermal development. C1 [Marneros, Alexander G.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Beck, Anita E.; McMillin, Margaret J.; Shively, Kathryn M.; Bamshad, Michael J.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Turner, Emily H.; Smith, Joshua D.; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Edwards, Matthew J.] Univ Western Sydney Macarthur, Sch Med, Campbelltown, NSW 2560, Australia. [Field, Michael] Genet Learning Disabil Serv, Newcastle, NSW 2298, Australia. [Sobreira, Nara Lygia de Macena] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Perez, Ana Beatriz A.] Univ Fed Sao Paulo, Dept Morphol & Genet, Clin Genet Ctr, BR-04021001 Sao Paulo, Brazil. [Fortes, Jose A. R.] Pontificia Univ Catolica Parana, Dept Internal Med, BR-1155 Curitiba, Parana, Brazil. [Lampe, Anne K.] Western Gen Hosp, South East Scotland Clin Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Uzielli, Maria Luisa Giovannucci] Univ Florence, Dept Genet & Mol Med, I-50132 Florence, Italy. [Gordon, Christopher T.] Hop Necker Enfants Malad, Dept Genet, INSERM, U781, F-75015 Paris, France. [Gordon, Christopher T.] Univ Paris Descartes Sorbonne Paris Cite, Inst Imagine, F-75015 Paris, France. [Plessis, Ghislaine; Le Merrer, Martine; Amiel, Jeanne] Hop Cote Nacre, CHU Caen, Serv Genet, F-14033 Caen 9, France. [Reichenberger, Ernst] Univ Connecticut, Ctr Hlth, Dept Reconstruct Sci, Farmington, CT 06030 USA. [Cerrato, Felecia; Labow, Brian I.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA 02115 USA. [Tabor, Holly K.] Treuman Katz Ctr Pediat Bioeth, Seattle Childrens Res Inst, Seattle, WA 98101 USA. RP Bamshad, MJ (reprint author), Univ Washington, Dept Pediat, Seattle, WA 98195 USA. EM mbamshad@uw.edu RI sebastianovitsch, stepan/G-8507-2013; Gordon, Christopher/F-1267-2017; OI Gordon, Christopher/0000-0002-9300-8399; Turner, Emily/0000-0001-9040-9229; Shendure, Jay/0000-0002-1516-1865 FU National Institutes of Health National Human Genome Research Institute [1U54HG006493, 1RC2HG005608, 5RO1HG004316]; Life Sciences Discovery Fund [2065508, 0905001]; Washington Research Foundation FX We thank the families for their participation and support; Tracy Dudding-Byth for clinical assistance; Kati Buckingham and Christa Poel for technical assistance; and Jennifer E. Below for discussion. Our work was supported in part by grants from the National Institutes of Health National Human Genome Research Institute (1U54HG006493 to M.B., D.N., and J.S.; 1RC2HG005608 to M.B., D.N., and J.S.; and 5RO1HG004316 to H.T.), the Life Sciences Discovery Fund (2065508 and 0905001), and the Washington Research Foundation. NR 19 TC 14 Z9 15 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR 4 PY 2013 VL 92 IS 4 BP 621 EP 626 DI 10.1016/j.ajhg.2013.03.002 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 124FR UT WOS:000317449700015 PM 23541344 ER PT J AU Bhatt, DL Stone, GW Mahaffey, KW Gibson, CM Steg, PG Hamm, CW Price, MJ Leonardi, S Gallup, D Bramucci, E Radke, PW Widimsky, P Tousek, F Tauth, J Spriggs, D McLaurin, BT Angiolillo, DJ Genereux, P Liu, TP Prats, J Todd, M Skerjanec, S White, HD Harrington, RA AF Bhatt, Deepak L. Stone, Gregg W. Mahaffey, Kenneth W. Gibson, C. Michael Steg, P. Gabriel Hamm, Christian W. Price, Matthew J. Leonardi, Sergio Gallup, Dianne Bramucci, Ezio Radke, Peter W. Widimsky, Petr Tousek, Frantisek Tauth, Jeffrey Spriggs, Douglas McLaurin, Brent T. Angiolillo, Dominick J. Genereux, Philippe Liu, Tiepu Prats, Jayne Todd, Meredith Skerjanec, Simona White, Harvey D. Harrington, Robert A. CA CHAMPION PHOENIX Investigators TI Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE CORONARY SYNDROMES; ELEVATION MYOCARDIAL-INFARCTION; ACHIEVE OPTIMAL MANAGEMENT; ANTIPLATELET THERAPY; CLOPIDOGREL PRETREATMENT; CARDIOVASCULAR EVENTS; STANDARD THERAPY; CHAMPION TRIALS; INTERVENTION; METAANALYSIS AB BACKGROUND The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects. METHODS In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours. RESULTS The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P = 0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P = 0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P = 0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups. CONCLUSIONS Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.) C1 [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Stone, Gregg W.] Columbia Univ, Med Ctr, New York, NY USA. [Stone, Gregg W.] Cardiovasc Res Fdn, New York, NY USA. [Mahaffey, Kenneth W.; Gallup, Dianne] Duke Clin Res Inst, Durham, NC USA. [Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. [Steg, P. Gabriel] Univ Paris Diderot, INSERM, U698, Paris, France. [Steg, P. Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris, France. [Hamm, Christian W.] Kerckhoff Heart & Thorax Ctr, Bad Nauheim, Germany. [Price, Matthew J.] Scripps Clin, La Jolla, CA 92037 USA. [Price, Matthew J.] Scripps Translat Sci Inst, La Jolla, CA USA. [Leonardi, Sergio; Bramucci, Ezio] Fdn IRCCS Policlin S Matteo, Pavia, Italy. [Radke, Peter W.] Univ Klinikum Schleswig Holstein, D-23538 Lubeck, Germany. [Widimsky, Petr] Fak Nemocnice Kralovske Vinohrady, Prague, Czech Republic. [Tousek, Frantisek] Nemocnice Ceske Budejovice, Ceske Budejovice, Czech Republic. [Tauth, Jeffrey] Natl Pk Med Ctr, Hot Springs, AR USA. [Spriggs, Douglas] Clearwater Cardiovasc & Intervent Consultants, Clearwater, FL USA. [McLaurin, Brent T.] AnMed Hlth, Anderson, SC USA. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Jacksonville, FL USA. [Liu, Tiepu; Prats, Jayne; Todd, Meredith; Skerjanec, Simona] Med Co, Parsippany, NJ USA. [White, Harvey D.] Green Lane Cardiovasc Serv, Auckland, New Zealand. [Harrington, Robert A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu RI Verheugt, F.W.A./H-8105-2014; Vasilieva, Elena/B-2137-2016; Poerner, Tudor/L-1755-2016; Widimsky, Petr/P-8088-2016; OI Poerner, Tudor/0000-0001-9303-6165; Widimsky, Petr/0000-0001-5686-7752; Leonardi, Sergio/0000-0002-4800-6132; Van de Werf, Frans/0000-0001-9479-7767; Brilakis, Emmanouil/0000-0001-9416-9701 FU Medicines Company; CHAMPION PHOENIX FX Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.govnumber, NCT01156571.) NR 33 TC 249 Z9 261 U1 7 U2 39 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 4 PY 2013 VL 368 IS 14 BP 1303 EP 1313 DI 10.1056/NEJMoa1300815 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 117YT UT WOS:000316989900007 PM 23473369 ER PT J AU Hussain, M Tangen, CM Berry, DL Higano, CS Crawford, ED Liu, G Wilding, G Prescott, S Sundaram, SK Small, EJ Dawson, NA Donnelly, BJ Venner, PM Vaishampayan, UN Schellhammer, PF Quinn, DI Raghavan, D Ely, B Moinpour, CM Vogelzang, NJ Thompson, IM AF Hussain, Maha Tangen, Catherine M. Berry, Donna L. Higano, Celestia S. Crawford, E. David Liu, Glenn Wilding, George Prescott, Stephen Sundaram, Subramanian Kanaga Small, Eric Jay Dawson, Nancy Ann Donnelly, Bryan J. Venner, Peter M. Vaishampayan, Ulka N. Schellhammer, Paul F. Quinn, David I. Raghavan, Derek Ely, Benjamin Moinpour, Carol M. Vogelzang, Nicholas J. Thompson, Ian M., Jr. TI Intermittent versus Continuous Androgen Deprivation in Prostate Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID QUALITY-OF-LIFE; CLINICAL-TRIAL; SUPPRESSION; FLUTAMIDE; LEUPROLIDE; CARCINOMA; THERAPY AB Background Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. Methods Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization. Results A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P = 0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events. Conclusions Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.govnumber, NCT00002651.) C1 [Hussain, Maha] Univ Michigan, Ann Arbor, MI 48109 USA. [Tangen, Catherine M.; Ely, Benjamin] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA. [Berry, Donna L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Liu, Glenn; Wilding, George] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [Prescott, Stephen] St James Univ Hosp, Leeds, W Yorkshire, England. [Sundaram, Subramanian Kanaga] Pinderfields Gen Hosp, Mid Yorkshire Hosp, Wakefield, W Yorkshire, England. [Small, Eric Jay] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dawson, Nancy Ann] Georgetown Univ, Hosp Lombardi, Ctr Comprehens Canc, Washington, DC USA. [Donnelly, Bryan J.] Prostate Canc Ctr, Calgary, AB, Canada. [Venner, Peter M.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Vaishampayan, Ulka N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Schellhammer, Paul F.] Urol Virginia, Norfolk, VA USA. [Quinn, David I.] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Raghavan, Derek] Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC USA. [Moinpour, Carol M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Vogelzang, Nicholas J.] US Oncol Res, McKesson Specialty Hlth, The Woodlands, TX USA. [Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA. RP Hussain, M (reprint author), Univ Michigan, Div Hematol Oncol, 1500 E Med Ctr Dr,7314 CC, Ann Arbor, MI 48109 USA. EM mahahuss@umich.edu RI Quinn, David/F-4343-2015 OI Quinn, David/0000-0002-1411-0417 FU National Cancer Institute; National Cancer Institute [CA32102, CA38926, CA14028, CA55582, CA42777, CA35192, CA46441, CA46282, CA27057, CA128567, CA45807, CA20319, CA58416]; AstraZeneca; Fonds Cancer (FOCA) from Belgium; National Cancer Institute. [CA46113, CA04919, CA76132, CA58861, CA58686, CA68183, CA12644, CA35261, CA35431, CA46368, CA22433, CA63848, CA67575, CA76447, CA67663, CA46136, CA86780, CA35281, CA63844, CA45560, CA37981, CA11083, CA35178, CA95860, CA35176, CA21115, CA31949, CA77202, CCSRI 015469] FX Funded by the National Cancer Institute and others; ClinicalTrials.govnumber, NCT00002651.; Supported in part by PHS Cooperative Agreements awarded by the National Cancer Institute (CA32102, CA38926, CA14028, CA55582, CA42777, CA35192, CA46441, CA46282, CA27057, CA128567, CA45807, CA20319, CA58416, CA46113, CA04919, CA76132, CA58861, CA58686, CA68183, CA12644, CA35261, CA35431, CA46368, CA22433, CA63848, CA67575, CA76447, CA67663, CA46136, CA86780, CA35281, CA63844, CA45560, CA37981, CA11083, CA35178, CA95860, CA35176, CA21115, CA31949, CA77202, and CCSRI 015469) and in part by AstraZeneca. The contribution of EORTC to this study was supported by Fonds Cancer (FOCA) from Belgium. NR 26 TC 167 Z9 176 U1 0 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 4 PY 2013 VL 368 IS 14 BP 1314 EP 1325 DI 10.1056/NEJMoa1212299 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 117YT UT WOS:000316989900008 PM 23550669 ER PT J AU Houchens, N Dhaliwal, G Askari, F Kim, B Saint, S AF Houchens, Nathan Dhaliwal, Gurpreet Askari, Frederick Kim, Benjamin Saint, Sanjay TI The Essential Element SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALKALINE-PHOSPHATASE ACTIVITY; FULMINANT HEPATIC-FAILURE; ACUTE LIVER-FAILURE; WILSONS-DISEASE; HEMOLYTIC-ANEMIA; DIAGNOSIS; UPDATE C1 [Houchens, Nathan; Askari, Frederick; Saint, Sanjay] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Saint, Sanjay] Hlth Serv Res & Dev Ctr Excellence, Dept Vet Affairs VA, Ann Arbor, MI USA. [Dhaliwal, Gurpreet; Kim, Benjamin] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. RP Houchens, N (reprint author), Univ Michigan Hlth Syst, 3119 Taubman Ctr,1500 E Med Ctr Dr,SPC 5376, Ann Arbor, MI 48109 USA. EM nathanho@umich.edu FU Doximity FX Dr. Saint reports receiving payment for board membership from and holding stock in Doximity. No other potential conflict of interest relevant to this article was reported. NR 15 TC 0 Z9 0 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 4 PY 2013 VL 368 IS 14 BP 1345 EP 1351 DI 10.1056/NEJMcps1203173 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 117YT UT WOS:000316989900013 PM 23550673 ER PT J AU Ribas, A Hodi, FS Callahan, M Konto, C Wolchok, J AF Ribas, Antoni Hodi, F. Stephen Callahan, Margaret Konto, Cyril Wolchok, Jedd TI Hepatotoxicity with Combination of Vemurafenib and Ipilimumab SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ANTITUMOR-ACTIVITY; IMMUNOTHERAPY; MELANOMA C1 [Ribas, Antoni] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Callahan, Margaret; Wolchok, Jedd] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Konto, Cyril] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. RP Ribas, A (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA. EM wolchokj@mskcc.org FU NCI NIH HHS [P30 CA008748] NR 5 TC 299 Z9 304 U1 3 U2 21 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 4 PY 2013 VL 368 IS 14 BP 1365 EP 1366 DI 10.1056/NEJMc1302338 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 117YT UT WOS:000316989900026 PM 23550685 ER PT J AU Son, J Lyssiotis, CA Ying, H Wang, X Hua, S Ligorio, M Perera, RM Ferrone, CR Mullarky, E Ng, SC Kang, Y Fleming, JB Bardeesy, N Asara, JM Haigis, MC DePinho, RA Cantley, LC Kimmelman, AC AF Son, Jaekyoung Lyssiotis, Costas A. Ying, Haoqiang Wang, Xiaoxu Hua, Sujun Ligorio, Matteo Perera, Rushika M. Ferrone, Cristina R. Mullarky, Edouard Ng Shyh-Chang Kang, Ya'an Fleming, Jason B. Bardeesy, Nabeel Asara, John M. Haigis, Marcia C. DePinho, Ronald A. Cantley, Lewis C. Kimmelman, Alec C. TI Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway SO NATURE LA English DT Article ID MASS-SPECTROMETRY; TRANSFORMED-CELLS; ADDICTION; GLUCOSE AB Cancer cells have metabolic dependencies that distinguish them from their normal counterparts(1). Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes(2). Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into alpha-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours. C1 [Son, Jaekyoung; Wang, Xiaoxu; Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02215 USA. [Lyssiotis, Costas A.; Mullarky, Edouard; Ng Shyh-Chang; Cantley, Lewis C.] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02215 USA. [Lyssiotis, Costas A.; Mullarky, Edouard; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Ying, Haoqiang; Hua, Sujun; DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Ligorio, Matteo; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Perera, Rushika M.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Ng Shyh-Chang] Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Stem Cell Program, Boston, MA 02130 USA. [Ng Shyh-Chang] Dana Farber Canc Inst, Boston, MA 02130 USA. [Kang, Ya'an; Fleming, Jason B.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Asara, John M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Haigis, Marcia C.] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02215 USA. RP Cantley, LC (reprint author), Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02215 USA. EM lec2014@med.cornell.edu; Alec_Kimmelman@DFCI.harvard.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Shyh-Chang, Ng/0000-0003-3138-9525 FU Dana Farber Cancer Institute; National Cancer Institute [R01 CA157490]; Kimmel Scholar Award; AACR-PanCAN Career Development Award; NIH [T32 CA009382-26, P01 CA117969, 5P01CA120964-05]; Dana-Farber/Harvard Cancer Center Support Grant [5P30CA006516-46] FX We would like to thank D. Anastasiou for advice and helpful comments on the manuscript; M. Yuan and S. Breitkopf for technical help with mass spectrometry experiments; J. Erickson, R. Cerione and J. Escobedo for the GLS inhibitors. Grant support derives from the Dana Farber Cancer Institute (A. C. K.), National Cancer Institute Grant R01 CA157490 (A. C. K.), Kimmel Scholar Award (A. C. K.), AACR-PanCAN Career Development Award (A. C. K.), NIH grants T32 CA009382-26 (H.Y.) and P01 CA117969 (L. C. C. and R. A. D.). C. A. L. is the Amgen Fellow of the Damon Runyon Cancer Research Foundation (DRG-2056-10). NIH grants 5P01CA120964-05 and Dana-Farber/Harvard Cancer Center Support Grant 5P30CA006516-46 (J.M.A.). NR 25 TC 332 Z9 345 U1 24 U2 187 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 4 PY 2013 VL 496 IS 7443 BP 101 EP + DI 10.1038/nature12040 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 117ZZ UT WOS:000316993400033 PM 23535601 ER PT J AU Jiang, H Khan, S Wang, Y Charron, G He, B Sebastian, C Du, JT Kim, R Ge, E Mostoslavsky, R Hang, HC Hao, Q Lin, HN AF Jiang, Hong Khan, Saba Wang, Yi Charron, Guillaume He, Bin Sebastian, Carlos Du, Jintang Kim, Ray Ge, Eva Mostoslavsky, Raul Hang, Howard C. Hao, Quan Lin, Hening TI SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine SO NATURE LA English DT Article ID HISTONE DEACETYLASE; MAMMALIAN-CELLS; PROTEIN; PRECURSOR; ACYLATION; SIRTUINS; INSIGHTS; NAD(+); MICE AB The Sir2 family of enzymes or sirtuins are known as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases(1) and have been implicated in the regulation of transcription, genome stability, metabolism and lifespan(2,3). However, four of the seven mammalian sirtuins have very weak deacetylase activity in vitro. Here we show that human SIRT6 efficiently removes long-chain fatty acyl groups, such as myristoyl, from lysine residues. The crystal structure of SIRT6 reveals a large hydrophobic pocket that can accommodate long-chain fatty acyl groups. We demonstrate further that SIRT6 promotes the secretion of tumour necrosis factor-alpha (TNF-alpha) by removing the fatty acyl modification on K19 and K20 of TNF-alpha. Protein lysine fatty acylation has been known to occur in mammalian cells, but the function and regulatory mechanisms of this modification were unknown. Our data indicate that protein lysine fatty acylation is a novel mechanism that regulates protein secretion. The discovery of SIRT6 as an enzyme that controls protein lysine fatty acylation provides new opportunities to investigate the physiological function of a protein post-translational modification that has been little studied until now. C1 [Jiang, Hong; Khan, Saba; He, Bin; Du, Jintang; Kim, Ray; Ge, Eva; Lin, Hening] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. [Wang, Yi; Hao, Quan] Univ Hong Kong, Dept Physiol, Hong Kong, Hong Kong, Peoples R China. [Charron, Guillaume; Hang, Howard C.] Rockefeller Univ, Lab Chem Biol & Microbial Pathogenesis, New York, NY 10065 USA. [Sebastian, Carlos; Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Lin, HN (reprint author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. EM qhao@hku.hk; hl379@cornell.edu RI Hao, Quan/C-4304-2009 FU NIH [R01GM086703, R01GM093072, R01GM087544]; [GRF766510] FX This work was supported in part by NIH R01GM086703 (H. L.), R01GM093072 (R. M.), Hong Kong GRF766510 (Q. H.) and NIH R01GM087544 (H. C. H.). We thank C. Zhang for help with the cloning of SIRT6 WT and H133Y to generate lentiviral particles and the staff at the Shanghai Synchrotron Radiation Facility for assistance during the data collection. NR 29 TC 189 Z9 198 U1 4 U2 77 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 4 PY 2013 VL 496 IS 7443 BP 110 EP + DI 10.1038/nature12038 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 117ZZ UT WOS:000316993400035 PM 23552949 ER PT J AU Targum, SD Nakagawa, A Sato, Y AF Targum, Steven D. Nakagawa, Atsuo Sato, Yuji TI A cross-cultural comparison study of depression assessments conducted in Japan SO ANNALS OF GENERAL PSYCHIATRY LA English DT Article DE Cross-cultural comparison; Depression ratings; Asian culture; MADRS ID MONTGOMERY-ASBERG DEPRESSION AB Background: The advent of global clinical trials has necessitated the use of English-based rating instruments in diverse cultures where English is clearly not the primary language. The cross-cultural applicability of rating instruments developed in one language with only one cultural group is an important issue in both research and clinical settings where these instruments might be used. We examined the cross-cultural applicability of the Montgomery-Asberg Depression Rating Scale (MADRS) in Japan. Methods: As part of a rater-training program for a clinical trial in Japan, we assessed inter-rater agreement using two videotaped MADRS interviews administered in Japanese and produced with English subtitles. We looked for possible interpretational variance that might have been generated by cultural differences between Japanese raters in Japan and English-speaking raters in the USA scoring the same interviews. Results: The US and Japanese raters demonstrated high inter-rater agreement and no significant scoring difference on the total MADRS score. The subtitles in English did not adversely affect the overall scoring. We separately analyzed the 10 individual items from each of the two MADRS interviews used for rater training. Of the 20 items, 18 were concordant between the US and Japanese raters. In one interview, the US raters scored lassitude significantly higher (p = 0.013) and the inability to feel significantly lower (p = 0.037) than the Japanese raters, reflecting a possible interpretational difference on these items. Conclusion: Although developed in Europe, these findings support the general applicability of the MADRS to assess the severity of depressive symptoms in Japan. We did note significant scoring differences on 2 of the 20 individual items, suggesting a possible cultural difference. It is possible that more interviews might have revealed more interpretational differences. These findings highlight the need for cultural familiarity when assessing psychiatric patients. C1 [Targum, Steven D.] Clintara LLC, Boston, MA 02116 USA. [Targum, Steven D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nakagawa, Atsuo] Keio Univ, Sch Med, Translat Med Ctr, Natl Ctr Neurol & Psychiat, Tokyo 1608582, Japan. [Nakagawa, Atsuo] Keio Univ, Sch Med, Dept Neuropsychiat, Tokyo 1608582, Japan. [Sato, Yuji] Keio Univ, Sch Med, Ctr Clin Res, Tokyo 1608582, Japan. RP Targum, SD (reprint author), Clintara LLC, 505 Tremont St,907, Boston, MA 02116 USA. EM sdtargum@yahoo.com FU Clintara LLC. FX The authors thank Tina Oakes (Eli Lilly and Company) and Maurizio Fava (Massachusetts General Hospital). In addition, the staff from Keio University (Tokyo, Japan), Clintara LLC and CTNI-Massachusetts General Hospital who participated in the coordination of this program are also acknowledged. Financial support for this study came from a research grant from Clintara LLC. NR 17 TC 1 Z9 1 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-859X J9 ANN GEN PSYCHIATR JI Ann. Gen. Psychiatr. PD APR 3 PY 2013 VL 12 AR 9 DI 10.1186/1744-859X-12-9 PG 6 WC Psychiatry SC Psychiatry GA 188HD UT WOS:000322182500001 PM 23551964 ER PT J AU Jiang, XJ Castelao, JE Vandenberg, D Carracedo, A Redondo, CM Conti, DV Cotore, JPP Potter, JD Newcomb, PA Passarelli, MN Jenkins, MA Hopper, JL Gallinger, S Le Marchand, L Martinez, ME Ahnen, DJ Baron, JA Lindor, NM Haile, RW Gago-Dominguez, M AF Jiang, Xuejuan Esteban Castelao, J. Vandenberg, David Carracedo, Angel Redondo, Carmen M. Conti, David V. Paredes Cotore, Jesus P. Potter, John D. Newcomb, Polly A. Passarelli, Michael N. Jenkins, Mark A. Hopper, John L. Gallinger, Steven Le Marchand, Loic Martinez, Maria E. Ahnen, Dennis J. Baron, John A. Lindor, Noralane M. Haile, Robert W. Gago-Dominguez, Manuela TI Genetic Variations in SMAD7 Are Associated with Colorectal Cancer Risk in the Colon Cancer Family Registry SO PLOS ONE LA English DT Article ID GENOME-WIDE ASSOCIATION; GROWTH-FACTOR-BETA; TGF-BETA; CANDIDATE GENES; SUSCEPTIBILITY; EXPRESSION; VARIANTS; CELLS; 18Q21; EPIDEMIOLOGY AB Background: Recent genome-wide studies identified a risk locus for colorectal cancer at 18q21, which maps to the SMAD7 gene. Our objective was to confirm the association between SMAD7 SNPs and colorectal cancer risk in the multi-center Colon Cancer Family Registry. Materials and Methods: 23 tagging SNPs in the SMAD7 gene were genotyped among 1,592 population-based and 253 clinic-based families. The SNP-colorectal cancer associations were assessed in multivariable conditional logistic regression. Results: Among the population-based families, both SNPs rs12953717 (odds ratio, 1.29; 95% confidence interval, 1.12-1.49), and rs11874392 (odds ratio, 0.80; 95% confidence interval, 0.70-0.92) were associated with risk of colorectal cancer. These associations were similar among the population-and the clinic-based families, though they were significant only among the former. Marginally significant differences in the SNP-colorectal cancer associations were observed by use of nonsteroidal anti-inflammatory drugs, cigarette smoking, body mass index, and history of polyps. Conclusions: SMAD7 SNPs were associated with colorectal cancer risk in the Colon Cancer Family Registry. There was evidence suggesting that the association between rs12953717 and colorectal cancer risk may be modified by factors such as smoking and use of nonsteroidal anti-inflammatory drugs. C1 [Jiang, Xuejuan; Vandenberg, David; Conti, David V.; Haile, Robert W.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Esteban Castelao, J.; Redondo, Carmen M.] Complejo Hosp Univ Vigo, Oncol & Genet Unit, Serv Galego Saude SERGAS, Vigo, Spain. [Carracedo, Angel; Gago-Dominguez, Manuela] Complejo Hosp Univ Santiago, Genom Med Grp, Galician Fdn Genom Med, Serv Galego Saude SERGAS,Inst Invest Sanitaria Sa, Santiago De Compostela, Spain. [Paredes Cotore, Jesus P.] Univ Hosp Santiago de Compostela, Dept Surg, Santiago De Compostela, Spain. [Potter, John D.; Newcomb, Polly A.; Passarelli, Michael N.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Jenkins, Mark A.; Hopper, John L.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia. [Gallinger, Steven] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Martinez, Maria E.] Univ Calif San Diego, San Diego Moores Canc Ctr, San Diego, CA 92103 USA. [Ahnen, Dennis J.] Denver VA Med Ctr, Denver, CO USA. [Ahnen, Dennis J.] Univ Colorado, Denver, CO 80202 USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. RP Gago-Dominguez, M (reprint author), Complejo Hosp Univ Santiago, Genom Med Grp, Galician Fdn Genom Med, Serv Galego Saude SERGAS,Inst Invest Sanitaria Sa, Santiago De Compostela, Spain. EM manuela.gago.dominguez@sergas.es RI Gallinger, Steven/E-4575-2013; Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Potter, John/0000-0001-5439-1500; Carracedo, Angel/0000-0003-1085-8986 FU National Cancer Institute, National Institutes of Health [5R01CA114472-02, RFA CA-95-011]; Australasian Colorectal Cancer Family Registry [U01 CA097735]; University of Southern California Familial Colorectal Neoplasia Collaborative Group [U01 CA074799]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01 CA074800]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; University of Hawaii Colorectal Cancer Family Registry [U01 CA074806]; University of California, Irvine Informatics Center [U01 CA078296]; Accion Estrategica de Salud del Instituto de Salud Carlos III [FIS PI12/02125]; FIS Intrasalud [PS09/02368]; Botin Foundation FX This work was supported by National Cancer Institute, National Institutes of Health, grant # 5R01CA114472-02 and RFA # CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s: the Australasian Colorectal Cancer Family Registry (U01 CA097735); the University of Southern California Familial Colorectal Neoplasia Collaborative Group (U01 CA074799); the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800); the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); the Seattle Colorectal Cancer Family Registry (U01 CA074794); the University of Hawaii Colorectal Cancer Family Registry (U01 CA074806); the University of California, Irvine Informatics Center (U01 CA078296); FIS PI12/02125 Accion Estrategica de Salud del Instituto de Salud Carlos III; FIS Intrasalud (PS09/02368); and the Botin Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 7 Z9 7 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 3 PY 2013 VL 8 IS 4 AR e60464 DI 10.1371/journal.pone.0060464 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 143BA UT WOS:000318840100075 PM 23560096 ER PT J AU Matsuoka, K Koreth, J Kim, HT Bascug, G McDonough, S Kawano, Y Murase, K Cutler, C Ho, VT Alyea, EP Armand, P Blazar, BR Antin, JH Soiffer, RJ Ritz, J AF Matsuoka, Ken-ichi Koreth, John Kim, Haesook T. Bascug, Gregory McDonough, Sean Kawano, Yutaka Murase, Kazuyuki Cutler, Corey Ho, Vincent T. Alyea, Edwin P. Armand, Philippe Blazar, Bruce R. Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome TI Low-Dose Interleukin-2 Therapy Restores Regulatory T Cell Homeostasis in Patients with Chronic Graft-Versus-Host Disease SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID IN-VIVO; PLASMA-LEVELS; CHRONIC GVHD; IL-2; RECEPTOR; TRANSPLANTATION; EXPANSION; MAINTENANCE; EXPRESSION; MECHANISMS AB CD4(+)Foxp3(+) regulatory T cells (T-regs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation. We recently reported that daily administration of low-dose interleukin-2 (IL-2) induces selective expansion of functional T-regs and clinical improvement of chronic graft-versus-host disease (GVHD). To define the mechanisms of action of IL-2 therapy, we examined the immunologic effects of this treatment on homeostasis of CD4(+) T cell subsets after transplant. We first demonstrated that chronic GVHD is characterized by constitutive phosphorylation of signal transducer and activator of transcription 5 (Stat5) in conventional CD4(+) T cells (T-cons) associated with elevated amounts of IL-7 and IL-15 and relative functional deficiency of IL-2. IL-2 therapy resulted in the selective increase of Stat5 phosphorylation in T-regs and a decrease of phosphorylated Stat5 in T-cons. Over an 8-week period, IL-2 therapy induced a series of changes in T-reg homeostasis, including increased proliferation, increased thymic export, and enhanced resistance to apoptosis. Low-dose IL-2 had minimal effects on T-cons. These findings define the mechanisms whereby low-dose IL-2 therapy restores the homeostasis of CD4(+) T cell subsets and promotes the reestablishment of immune tolerance. C1 [Matsuoka, Ken-ichi; Koreth, John; Bascug, Gregory; McDonough, Sean; Kawano, Yutaka; Murase, Kazuyuki; Cutler, Corey; Ho, Vincent T.; Alyea, Edwin P.; Armand, Philippe; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. [Matsuoka, Ken-ichi; Koreth, John; Kawano, Yutaka; Murase, Kazuyuki; Cutler, Corey; Ho, Vincent T.; Alyea, Edwin P.; Armand, Philippe; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Kim, Haesook T.; Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [Kim, Haesook T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Blazar, Bruce R.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [Ritz, Jerome] Harvard Stem Cell Inst, Boston, MA 02138 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02215 USA. EM Jerome_Ritz@dfci.harvard.edu FU NIH [AI29530, CA142106]; Jock and Bunny Adams Research and Education Endowment; Ted and Eileen Pasquarello Research Fund; Dana-Farber Dunkin' Donuts Rising Star award; American Society of Blood and Marrow Transplantation/Pharmion New Investigator award FX Funding: This work was supported by NIH grants AI29530 and CA142106, the Jock and Bunny Adams Research and Education Endowment, and the Ted and Eileen Pasquarello Research Fund. J.K. is supported in part by a Dana-Farber Dunkin' Donuts Rising Star award and an American Society of Blood and Marrow Transplantation/Pharmion New Investigator award. NR 47 TC 93 Z9 97 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 3 PY 2013 VL 5 IS 179 AR 179ra43 DI 10.1126/scitranslmed.3005265 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 118PF UT WOS:000317037000006 PM 23552371 ER PT J AU Ozkumur, E Shah, AM Ciciliano, JC Emmink, BL Miyamoto, DT Brachtel, E Yu, M Chen, PI Morgan, B Trautwein, J Kimura, A Sengupta, S Stott, SL Karabacak, NM Barber, TA Walsh, JR Smith, K Spuhler, PS Sullivan, JP Lee, RJ Ting, DT Luo, X Shaw, AT Bardia, A Sequist, LV Louis, DN Maheswaran, S Kapur, R Haber, DA Toner, M AF Ozkumur, Emre Shah, Ajay M. Ciciliano, Jordan C. Emmink, Benjamin L. Miyamoto, David T. Brachtel, Elena Yu, Min Chen, Pin-i Morgan, Bailey Trautwein, Julie Kimura, Anya Sengupta, Sudarshana Stott, Shannon L. Karabacak, Nezihi Murat Barber, Thomas A. Walsh, John R. Smith, Kyle Spuhler, Philipp S. Sullivan, James P. Lee, Richard J. Ting, David T. Luo, Xi Shaw, Alice T. Bardia, Aditya Sequist, Lecia V. Louis, David N. Maheswaran, Shyamala Kapur, Ravi Haber, Daniel A. Toner, Mehmet TI Inertial Focusing for Tumor Antigen-Dependent and -Independent Sorting of Rare Circulating Tumor Cells SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CANCER-PATIENTS; PERIPHERAL-BLOOD; SEPARATION; ENRICHMENT; ANTIBODIES; DEPLETION; FLOW AB Circulating tumor cells (CTCs) are shed into the bloodstream from primary and metastatic tumor deposits. Their isolation and analysis hold great promise for the early detection of invasive cancer and the management of advanced disease, but technological hurdles have limited their broad clinical utility. We describe an inertial focusing-enhanced microfluidic CTC capture platform, termed "CTC-iChip," that is capable of sorting rare CTCs from whole blood at 10(7) cells/s. Most importantly, the iChip is capable of isolating CTCs using strategies that are either dependent or independent of tumor membrane epitopes, and thus applicable to virtually all cancers. We specifically demonstrate the use of the iChip in an expanded set of both epithelial and nonepithelial cancers including lung, prostate, pancreas, breast, and melanoma. The sorting of CTCs as unfixed cells in solution allows for the application of high-quality clinically standardized morphological and immunohistochemical analyses, as well as RNA-based single-cell molecular characterization. The combination of an unbiased, broadly applicable, high-throughput, and automatable rare cell sorting technology with generally accepted molecular assays and cytology standards will enable the integration of CTC-based diagnostics into the clinical management of cancer. C1 [Ozkumur, Emre; Shah, Ajay M.; Emmink, Benjamin L.; Chen, Pin-i; Morgan, Bailey; Stott, Shannon L.; Karabacak, Nezihi Murat; Barber, Thomas A.; Walsh, John R.; Smith, Kyle; Spuhler, Philipp S.; Kapur, Ravi; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Ciciliano, Jordan C.; Miyamoto, David T.; Yu, Min; Trautwein, Julie; Kimura, Anya; Sengupta, Sudarshana; Stott, Shannon L.; Sullivan, James P.; Lee, Richard J.; Ting, David T.; Luo, Xi; Shaw, Alice T.; Bardia, Aditya; Sequist, Lecia V.; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Miyamoto, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Brachtel, Elena; Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Yu, Min; Luo, Xi; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Sullivan, James P.; Lee, Richard J.; Ting, David T.; Shaw, Alice T.; Bardia, Aditya; Sequist, Lecia V.; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Maheswaran, Shyamala; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu RI sebastianovitsch, stepan/G-8507-2013; Karabacak, N Murat/D-7227-2013; OI Karabacak, N Murat/0000-0003-2761-5593; Ting, David/0000-0002-3261-2322 FU NIH P41 Biotechnology Resource Center; NIH National Institute of Biomedical Imaging and Bioengineering; Stand Up to Cancer; Howard Hughes Medical Institute; Prostate Cancer Foundation; Charles Evans Foundation; Department of Defense Prostate Cancer Research Program; Mazzone-DF/HCC (Dana-Farber/Harvard Cancer Center); Conquer Cancer Foundation; Johnson Johnson FX Funding: This work was partially supported by NIH P41 Biotechnology Resource Center (M. T.), NIH National Institute of Biomedical Imaging and Bioengineering (M. T. and D. A. H.), Stand Up to Cancer (D. A. H., M. T., and S. M.), Howard Hughes Medical Institute (D. A. H.), Prostate Cancer Foundation and Charles Evans Foundation (D. A. H. and M. T.), Department of Defense Prostate Cancer Research Program (D. T. M. and R.J.L.), Mazzone-DF/HCC (Dana-Farber/Harvard Cancer Center) (D. T. M.), Conquer Cancer Foundation (R.J.L.), Prostate Cancer Foundation (R.J.L.), and Johnson & Johnson (M.T. and S.M.). NR 30 TC 152 Z9 161 U1 24 U2 227 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 3 PY 2013 VL 5 IS 179 AR 179ra47 DI 10.1126/scitranslmed.3005616 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 118PF UT WOS:000317037000008 PM 23552373 ER PT J AU O'Hare, AM AF O'Hare, Ann M. TI Measures to Define Chronic Kidney Disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID MORTALITY RISK; AGE C1 VA Puget Sound Healthcare Syst, Hosp & Specialty Med Serv, Seattle, WA USA. RP O'Hare, AM (reprint author), VA Puget Sound Healthcare Syst, Hosp & Specialty Med Serv, Seattle, WA USA. EM ann.o'hare@va.gov NR 5 TC 4 Z9 4 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 APR 3 PY 2013 VL 309 IS 13 BP 1343 EP 1343 DI 10.1001/jama.2013.1328 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 117EC UT WOS:000316934500010 PM 23549569 ER PT J AU Joynt, KE Orav, EJ Jha, AK AF Joynt, Karen E. Orav, E. John Jha, Ashish K. TI Mortality Rates for Medicare Beneficiaries Admitted to Critical Access and Non-Critical Access Hospitals, 2002-2010 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-CARE; RURAL HOSPITALS; MYOCARDIAL-INFARCTION; 30-DAY MORTALITY; PATIENT OUTCOMES; PERFORMANCE; IMPROVEMENT; COSTS AB Importance Critical access hospitals (CAHs) provide inpatient care to Americans living in rural communities. These hospitals are at high risk of falling behind with respect to quality improvement, owing to their limited resources and vulnerable patient populations. How they have fared on patient outcomes during the past decade is unknown. Objective To evaluate trends in mortality for patients receiving care at CAHs and compare these trends with those for patients receiving care at non-CAHs. Design, Setting, and Patients Retrospective observational study using data from Medicare fee-for-service patients admitted to US acute care hospitals with acute myocardial infarction (1 902 586 admissions), congestive heart failure (4 488 269 admissions), and pneumonia (3 891 074 admissions) between 2002 and 2010. Main Outcome Measures Trends in risk-adjusted 30-day mortality rates for CAHs and other acute care US hospitals. Results Accounting for differences in patient, hospital, and community characteristics, CAHs had mortality rates comparable with those of non-CAHs in 2002 (composite mortality across all 3 conditions, 12.8% vs 13.0%; difference, -0.3% [95% CI, -0.7% to 0.2%]; P=.25). Between 2002 and 2010, mortality rates increased 0.1% per year in CAHs but decreased 0.2% per year in non-CAHs, for an annual difference in change of 0.3% (95% CI, 0.2% to 0.3%; P<.001). Thus, by 2010, CAHs had higher mortality rates compared with non-CAHs (13.3% vs 11.4%; difference, 1.8% [95% CI, 1.4% to 2.2%]; P<.001). The patterns were similar when each individual condition was examined separately. Comparing CAHs with other small, rural hospitals, similar patterns were found. Conclusions and Relevance Among Medicare beneficiaries with acute myocardial infarction, congestive heart failure, or pneumonia, 30-day mortality rates for those admitted to CAHs, compared with those admitted to other acute care hospitals, increased from 2002 to 2010. New efforts may be needed to help CAHs improve. JAMA. 2013;309(13):1379-1387 www.jama.com C1 [Joynt, Karen E.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Orav, E. John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Joynt, Karen E.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Orav, E. John; Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Joynt, Karen E.; Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Joynt, KE (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org FU National Heart, Lung, and Blood Institute, National Institutes of Health [1K23HL109177-01] FX Dr Joynt was supported by grant 1K23HL109177-01 from the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 29 TC 23 Z9 23 U1 0 U2 15 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 APR 3 PY 2013 VL 309 IS 13 BP 1379 EP 1387 DI 10.1001/jama.2013.2366 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 117EC UT WOS:000316934500027 PM 23549583 ER PT J AU Rozental, TD Deschamps, LN Taylor, A Earp, B Zurakowski, D Day, CS Bouxsein, ML AF Rozental, Tamara D. Deschamps, Laura N. Taylor, Alexander Earp, Brandon Zurakowski, David Day, Charles S. Bouxsein, Mary L. TI Premenopausal Women with a Distal Radial Fracture Have Deteriorated Trabecular Bone Density and Morphology Compared with Controls without a Fracture SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID IN-VIVO ASSESSMENT; HR-PQCT IMAGES; OSTEOPOROTIC FRACTURES; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; FOREARM FRACTURES; SKELETAL SITES; HIP FRACTURE; FRAGILITY FRACTURES; BODY-COMPOSITION AB Background: Measurement of bone mineral density by dual x-ray absorptiometry combined with clinical risk factors is currently the gold standard in diagnosing osteoporosis. Advanced imaging has shown that older patients with fragility fractures have poor bone microarchitecture, often independent of low bone mineral density. We hypothesized that premenopausal women with a fracture of the distal end of the radius have similar bone mineral density but altered bone microarchitecture compared with control subjects without a fracture. Methods: Forty premenopausal women with a recent distal radial fracture were prospectively recruited and matched with eighty control subjects without a fracture. Primary outcome variables included trabecular and cortical microarchitecture at the distal end of the radius and tibia by high-resolution peripheral quantitative computed tomography. Bone mineral density at the wrist, hip, and lumbar spine was also measured by dual x-ray absorptiometry. Results: The fracture and control groups did not differ with regard to age, race, or body mass index. Bone mineral density was similar at the femoral neck, lumbar spine, and distal one-third of the radius, but tended to be lower in the fracture group at the hip and ultradistal part of the radius (p = 0.06). Trabecular microarchitecture was deteriorated in the fracture group compared with the control group at both the distal end of the radius and distal end of the tibia. At the distal end of the radius, the fracture group had lower total density and lower trabecular density, number, and thickness compared with the control group (-6% to 14%; p < 0.05 for all). At the distal end of the tibia, total density, trabecular density, trabecular thickness, and cortical thickness were lower in the fracture group than in the control group (-7% to 14%; p < 0.01). Conditional logistic regression showed that trabecular density, thickness, separation, and distribution of trabecular separation remained significantly associated with fracture after adjustment for age and ultradistal radial bone mineral density (adjusted odds ratios [OR]: 2.01 to 2.98; p < 0.05). At the tibia, total density, trabecular density, thickness, cortical area, and cortical thickness remained significantly associated with fracture after adjustment for age and femoral neck bone mineral density (adjusted OR:1.62 to 2.40; p < 0.05). Conclusions: Despite similar bone mineral density values by dual x-ray absorptiometry, premenopausal women with a distal radial fracture have significantly poorer bone microarchitecture at the distal end of the radius and tibia compared with control subjects without a fracture. Early identification of women with poor bone health offers opportunities for interventions aimed at preventing further deterioration and reducing fracture risk. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthopaed Surg, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Endocrine, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesiol, Boston Childrens Hosp, Boston, MA USA. RP Rozental, TD (reprint author), Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, 330 Brookline Ave,Stoneman 10, Boston, MA 02215 USA. NR 64 TC 21 Z9 23 U1 1 U2 4 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 APR 3 PY 2013 VL 95A IS 7 BP 633 EP 642 DI 10.2106/JBJS.L.00588 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AF8MZ UT WOS:000334971600009 PM 23553299 ER PT J AU Pace-Schott, EF AF Pace-Schott, Edward F. TI Dreaming as a story-telling instinct SO FRONTIERS IN PSYCHOLOGY LA English DT Editorial Material ID EYE-MOVEMENT SLEEP; BRAINS DEFAULT NETWORK; HYPOTHALAMIC FUNCTIONAL CONNECTIVITY; SLOW-WAVE SLEEP; REM-SLEEP; COGNITIVE NEUROSCIENCE; MODE NETWORK; STORY COMPREHENSION; WAKING; ACTIVATION C1 [Pace-Schott, Edward F.] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. [Pace-Schott, Edward F.] Massachusetts Gen Hosp, Charlestown, MA USA. RP Pace-Schott, EF (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. EM epace-schott@partners.org FU NIMH NIH HHS [R21 MH090357] NR 75 TC 9 Z9 9 U1 3 U2 9 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD APR 2 PY 2013 VL 4 AR 159 DI 10.3389/fpsyg.2013.00159 PG 4 WC Psychology, Multidisciplinary SC Psychology GA AA1FQ UT WOS:000330842300001 PM 23565105 ER PT J AU Rajakumari, S Wu, J Ishibashi, J Lim, HW Giang, AH Won, KJ Reed, RR Seale, P AF Rajakumari, Sona Wu, Jun Ishibashi, Jeff Lim, Hee-Woong Giang, An-Hoa Won, Kyoung-Jae Reed, Randall R. Seale, Patrick TI EBF2 Determines and Maintains Brown Adipocyte Identity SO CELL METABOLISM LA English DT Article ID DIET-INDUCED THERMOGENESIS; ACTIVATED RECEPTOR-GAMMA; ADIPOSE-TISSUE; PPAR-GAMMA; WHITE FAT; GENE-EXPRESSION; ADULT HUMANS; TRANSCRIPTIONAL COMPLEX; INSULIN-RESISTANCE; TRANSGENIC MICE AB The master transcription factor Ppar gamma regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Ppar gamma also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Ppar gamma binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif was highly enriched within brown adipose-specific Ppar gamma binding sites that we identified by genome-wide ChIP-Seq. Of the Ebf isoforms, Ebf2 was selectively expressed in brown relative to white adipocytes and was bound at brown adipose-specific Ppar gamma target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Ppar gamma to its brown-selective binding sites and reprogrammed cells to a brown fat fate. Brown adipose cells and tissue from Ebf2-deficient mice displayed a loss of brown-specific characteristics and thermogenic capacity. Together, these results identify Ebf2 as a key transcriptional regulator of brown fat cell fate and function. C1 [Rajakumari, Sona; Ishibashi, Jeff; Lim, Hee-Woong; Won, Kyoung-Jae; Seale, Patrick] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Rajakumari, Sona; Ishibashi, Jeff; Seale, Patrick] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Lim, Hee-Woong; Won, Kyoung-Jae] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Wu, Jun; Giang, An-Hoa] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. [Reed, Randall R.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Ctr Sensory Biol,Dept Neurosci, Baltimore, MD 21205 USA. RP Seale, P (reprint author), Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. EM sealep@upenn.edu OI Lim, Hee-Woong/0000-0001-8599-1808 FU NIH [1K01DK094824]; NIDDK/NIH [R00 DK081605]; NIGMS/NIH [DP2OD007288]; Searle Scholars Award FX We thank Drs. Mitch Lazar and Dave Steger for expert guidance with ChIP studies, Dr. Mary Selak for help with oxygen consumption assays, Li Huang for expert technical assistance, and members of the Seale lab for helpful discussions. We are grateful to the Functional Genomics Core of the Penn Diabetes and Endocrinology Research Center (DK19525) for high-throughput sequencing and data analyses. J.W. is supported by an NIH grant (1K01DK094824). This work was supported by NIDDK/NIH award R00 DK081605, NIGMS/NIH award DP2OD007288, and a Searle Scholars Award to P.S. NR 45 TC 84 Z9 88 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD APR 2 PY 2013 VL 17 IS 4 BP 562 EP 574 DI 10.1016/j.cmet.2013.01.015 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 242TR UT WOS:000326265600011 PM 23499423 ER PT J AU Brudner, M Karpel, M Lear, C Chen, L Yantosca, LM Scully, C Sarraju, A Sokolovska, A Zariffard, MR Eisen, DP Mungall, BA Kotton, DN Omari, A Huang, IC Farzan, M Takahashi, K Stuart, L Stahl, GL Ezekowitz, AB Spear, GT Olinger, GG Schmidt, EV Michelow, IC AF Brudner, Matthew Karpel, Marshall Lear, Calli Chen, Li Yantosca, L. Michael Scully, Corinne Sarraju, Ashish Sokolovska, Anna Zariffard, M. Reza Eisen, Damon P. Mungall, Bruce A. Kotton, Darrell N. Omari, Amel Huang, I-Chueh Farzan, Michael Takahashi, Kazue Stuart, Lynda Stahl, Gregory L. Ezekowitz, Alan B. Spear, Gregory T. Olinger, Gene G. Schmidt, Emmett V. Michelow, Ian C. TI Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors SO PLOS ONE LA English DT Article ID MANNOSE-BINDING LECTIN; RP-C4-CYP21-TNX RCCX MODULES; POLYMERASE-CHAIN-REACTION; COPY-NUMBER VARIATIONS; WEST NILE VIRUS; ENVELOPE GLYCOPROTEINS; INFLAMMATORY RESPONSE; SURFACE GLYCOPROTEIN; FALCIPARUM-MALARIA; SERINE PROTEASE-2 AB Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes. C1 [Brudner, Matthew; Karpel, Marshall; Chen, Li; Yantosca, L. Michael; Sarraju, Ashish; Sokolovska, Anna; Takahashi, Kazue; Stuart, Lynda; Ezekowitz, Alan B.; Schmidt, Emmett V.; Michelow, Ian C.] Massachusetts Gen Hosp, Dept Pediat, Programs Dev Immunol, Boston, MA 02114 USA. [Lear, Calli; Scully, Corinne; Olinger, Gene G.] USA, Div Virol, Med Res Inst Infect Dis, Frederick, MD USA. [Zariffard, M. Reza] Rush Univ, Dept Immunol & Microbiol, Med Ctr, Chicago, IL 60612 USA. [Eisen, Damon P.] Royal Melbourne Hosp, Victorian Infect Dis Serv, Parkville, Vic 3050, Australia. [Mungall, Bruce A.] Commonwealth Sci & Ind Res Org CSIRO Livestock In, Australian Anim Hlth Lab, Geelong, Vic, Australia. [Kotton, Darrell N.; Omari, Amel] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Huang, I-Chueh; Farzan, Michael] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Stahl, Gregory L.] Brigham & Womens Hosp, CETRI, Boston, MA 02115 USA. [Huang, I-Chueh; Farzan, Michael; Takahashi, Kazue; Stuart, Lynda; Stahl, Gregory L.; Schmidt, Emmett V.; Michelow, Ian C.] Harvard Univ, Sch Med, Boston, MA USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Dept Pediat, Programs Dev Immunol, Boston, MA 02114 USA. EM eschmidt@partners.org; ian_michelow@brown.edu OI Olinger, Gene/0000-0001-7338-0292; Kotton, Darrell/0000-0002-9604-8476 FU National Institutes of Health [U01 AI070330]; United States Department of Defense, Defense Threat Reduction Agency Biological Therapeutics Program [4.10006, 4.10007] FX This work was supported by National Institutes of Health Grant U01 AI070330 (to EVS) and by United States Department of Defense, Defense Threat Reduction Agency Biological Therapeutics Program Grants 4.10006 and 4.10007 (to GGO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 102 TC 17 Z9 17 U1 1 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 2 PY 2013 VL 8 IS 4 AR e60838 DI 10.1371/journal.pone.0060838 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 127RY UT WOS:000317717300151 PM 23573288 ER PT J AU Raeder, H Vesterhus, M El Ouaamari, A Paulo, JA McAllister, FE Liew, CW Hu, J Kawamori, D Molven, A Gygi, SP Njolstad, PR Kahn, CR Kulkarni, RN AF Raeder, Helge Vesterhus, Mette El Ouaamari, Abdelfattah Paulo, Joao A. McAllister, Fiona E. Liew, Chong Wee Hu, Jiang Kawamori, Dan Molven, Anders Gygi, Steven P. Njolstad, Pal R. Kahn, C. Ronald Kulkarni, Rohit N. TI Absence of Diabetes and Pancreatic Exocrine Dysfunction in a Transgenic Model of Carboxyl-Ester Lipase-MODY (Maturity-Onset Diabetes of the Young) SO PLOS ONE LA English DT Article ID CRE RECOMBINASE; REPORTER STRAIN; GENE-EXPRESSION; KNOCKOUT MICE; MOUSE; MUTATIONS; ABSORPTION; DEFICIENCY; RECEPTOR; CELLS AB Background: CEL-MODY is a monogenic form of diabetes with exocrine pancreatic insufficiency caused by mutations in CARBOXYL-ESTER LIPASE (CEL). The pathogenic processes underlying CEL-MODY are poorly understood, and the global knockout mouse model of the CEL gene (CELKO) did not recapitulate the disease. We therefore aimed to create and phenotype a mouse model specifically over-expressing mutated CEL in the pancreas. Methods: We established a monotransgenic floxed (flanking LOX sequences) mouse line carrying the human CEL mutation c.1686delT and crossed it with an elastase-Cre mouse to derive a bitransgenic mouse line with pancreas-specific overexpression of CEL carrying this disease-associated mutation (TgCEL). Following confirmation of murine pancreatic expression of the human transgene by real-time quantitative PCR, we phenotyped the mouse model fed a normal chow and compared it with mice fed a 60% high fat diet (HFD) as well as the effects of short-term and long-term cerulein exposure. Results: Pancreatic exocrine function was normal in TgCEL mice on normal chow as assessed by serum lipid and lipid-soluble vitamin levels, fecal elastase and fecal fat absorption, and the normoglycemic mice exhibited normal pancreatic morphology. On 60% HFD, the mice gained weight to the same extent as controls, had normal pancreatic exocrine function and comparable glucose tolerance even after resuming normal diet and follow up up to 22 months of age. The cerulein-exposed TgCEL mice gained weight and remained glucose tolerant, and there were no detectable mutation-specific differences in serum amylase, islet hormones or the extent of pancreatic tissue inflammation. Conclusions: In this murine model of human CEL-MODY diabetes, we did not detect mutation-specific endocrine or exocrine pancreatic phenotypes, in response to altered diets or exposure to cerulein. C1 [Raeder, Helge; Vesterhus, Mette; El Ouaamari, Abdelfattah; Liew, Chong Wee; Hu, Jiang; Kawamori, Dan; Molven, Anders; Njolstad, Pal R.; Kahn, C. Ronald; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Raeder, Helge; Vesterhus, Mette; Molven, Anders; Njolstad, Pal R.] Univ Bergen, Dept Clin Med, KG Jebsen Ctr Diabet Res, Bergen, Norway. [Raeder, Helge; Vesterhus, Mette; Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Raeder, Helge] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway. [Paulo, Joao A.; McAllister, Fiona E.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Molven, Anders] Univ Bergen, Gade Inst, Bergen, Norway. [Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway. [Njolstad, Pal R.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Raeder, H (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM helge.rader@uib.no FU National Institutes of Health (NIH) [RO1 DK67536]; Norwegian Research Foundation; Haukeland University Hospital; Innovest; University of Bergen, Norway; ESPE Sabbatical Leave Programme; Fulbright Foundation; Norwegian Research Council; Western Norway Regional Health Authority grant; Norwegian Endocrine Society; National Institutes of Health [DK33201, DK55545]; Joslin Diabetes and Endocrinology Research Center [DK34834] FX The funds to develop some reagents in this study were supported by National Institutes of Health (NIH) Grant RO1 DK67536 (to RNK). This study was supported in part by funds from the Norwegian Research Foundation, Haukeland University Hospital, Innovest, and University of Bergen, Norway, and an ESPE Sabbatical Leave Programme and the Fulbright Foundation (to PRN), a Leiv Eiriksson Mobility Grant from The Norwegian Research Council (to MV and HR), a Western Norway Regional Health Authority grant (to HR), a Norwegian Endocrine Society grant (to HR), a Fulbright Foundation grant (to HR), and by National Institutes of Health Grants DK33201 and DK55545 (to CRK), and the Joslin Diabetes and Endocrinology Research Center Grant DK34834. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 2 Z9 2 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 APR 2 PY 2013 VL 8 IS 4 AR e60229 DI 10.1371/journal.pone.0060229 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 127RY UT WOS:000317717300072 ER PT J AU Junco, SE Wang, RJ Gaipa, JC Taylor, AB Schirf, V Gearhart, MD Bardwell, VJ Demeler, B Hart, PJ Kim, CA AF Junco, Sarah E. Wang, Renjing Gaipa, John C. Taylor, Alexander B. Schirf, Virgil Gearhart, Micah D. Bardwell, Vivian J. Demeler, Borries Hart, P. John Kim, Chongwoo A. TI Structure of the Polycomb Group Protein PCGF1 in Complex with BCOR Reveals Basis for Binding Selectivity of PCGF Homologs SO STRUCTURE LA English DT Article ID SOMATIC MUTATIONS; REPRESSIVE COMPLEX; COREPRESSOR; DOMAIN; PRC1; IDENTIFICATION; LEUKEMIA; SUBTYPE; SYSTEM; RING1B AB Polycomb-group RING finger homologs (PCGF1, PCGF2, PCGF3, PCGF4, PCGF5, and PCGF6) are critical components in the assembly of distinct Polycomb repression complex 1 (PRC1)-related complexes. Here, we identify a protein interaction domain in BCL6 corepressor, BCOR, which binds the RING finger- and WD40-associated ubiquitin-like (RAWUL) domain of PCGF1 (NSPC1) and PCGF3 but not of PCGF2 (MEL18) or PCGF4 (BMW. Because of the selective binding, we have named this domain PCGF Ub-like fold discriminator (PUFD). The structure of BCOR PUFD bound to PCGF1 reveals that (1) PUFD binds to the same surfaces as observed for a different Polycomb group RAWUL domain and (2) the ability of PUFD to discriminate among RAWULs stems from the identity of specific residues within these interaction surfaces. These data show the molecular basis for determining the binding preference for a PCGF homolog, which ultimately helps determine the identity of the larger PRC1-like assembly. C1 [Junco, Sarah E.; Wang, Renjing; Gaipa, John C.; Taylor, Alexander B.; Schirf, Virgil; Demeler, Borries; Hart, P. John; Kim, Chongwoo A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Junco, Sarah E.; Wang, Renjing; Gaipa, John C.; Taylor, Alexander B.; Schirf, Virgil; Demeler, Borries; Hart, P. John; Kim, Chongwoo A.] Univ Texas Hlth Sci Ctr San Antonio, CTRC, San Antonio, TX 78229 USA. [Gearhart, Micah D.; Bardwell, Vivian J.] Univ Minnesota, Dept Genet Cell Biol & Dev, Mason Canc Ctr, Minneapolis, MN 55455 USA. [Gearhart, Micah D.; Bardwell, Vivian J.] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN 55455 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Kim, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, MSC 7760,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chong@biochem.uthscsa.edu FU American Heart Association [0830111N]; American Cancer Society [RSG-08-285-01-GMC]; Department of Defense Breast Cancer Research Program [BC075278]; National Institutes of Health [5R01CA071540]; NIH-NCI [2P30 CA054174-17]; XSEDE [TG-MCB070039]; Welch Foundation [AQ-1399]; UTHSCSA Executive Research Committee; Cancer Therapy Research Center; Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy [DE-AC02-05CH11231]; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; Michigan Economic Development Corporation; Michigan Technology Tr-Corridor [085P1000817] FX This work was supported by the American Heart Association (0830111N to OAK.), the American Cancer Society (RSG-08-285-01-GMC to C.A.K.), the Department of Defense Breast Cancer Research Program (BC075278 to C.A.K.), the National Institutes of Health (5R01CA071540 to V.J.B.), NIH-NCI (2P30 CA054174-17 to B.D. and P.J.H.), XSEDE (TG-MCB070039 to B.D.), and the Welch Foundation (AQ-1399 to P.J.H.). UTHSCSA core facilities are supported by the UTHSCSA Executive Research Committee and the Cancer Therapy Research Center. This work is based upon research at Beamline 4.2.2 of the Molecular Biology Consortium at the Advance Light Source (ALS). ALS is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Advanced Photon Source is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tr-Corridor (Grant 085P1000817). We also thank Dr. Jay Nix (ALS) and Dr. Dmitri Ivanov (APS) for assistance with the data collection. NR 42 TC 24 Z9 28 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD APR 2 PY 2013 VL 21 IS 4 BP 665 EP 671 DI 10.1016/j.str.2013.02.013 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 128WJ UT WOS:000317800100016 PM 23523425 ER PT J AU Lee, JH Park, S Hyun, H Bordo, MW Oketokoun, R Nasr, KA Frangioni, JV Choi, HS AF Lee, Jeong Heon Park, Sunny Hyun, Hoon Bordo, Mark W. Oketokoun, Rafiou Nasr, Khaled A. Frangioni, John V. Choi, Hak Soo TI High-Throughput Screening of Small Molecule Ligands Targeted to Live Bacteria Surface SO ANALYTICAL CHEMISTRY LA English DT Article ID DECONVOLUTION MICROSCOPY; IDENTIFICATION; ASSAYS AB The discovery of small molecule ligands targeted to the surface of live pathogenic bacteria would enable an entirely new class of antibiotics. We report the development and validation of a microarray-based high-throughput screening platform for bacteria that exploits 300 mu m diameter chemical spots in a 1 in. x 3 in. nanolayered glass slide format. Using 24 model compounds and 4 different bacterial strains, we optimized the screening technology, including fluorophore-based optical deconvolution for automated scoring of affinity and cyan-magenta-yellow-key (CMYK) color-coding for scoring of both affinity and specificity. The latter provides a lossless, one-dimensional view of multidimensional data. By linking in silico analysis with cell binding affinity and specificity, we could also begin to identify the physicochemical factors that affect ligand performance. The technology we describe could form the foundation for developing new classes of antibiotics. C1 [Lee, Jeong Heon; Hyun, Hoon; Bordo, Mark W.; Oketokoun, Rafiou; Frangioni, John V.; Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Robot Chem Grp, Ctr Mol Imaging, Boston, MA 02215 USA. [Lee, Jeong Heon; Hyun, Hoon; Bordo, Mark W.; Oketokoun, Rafiou; Frangioni, John V.; Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Frangioni, John V.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Park, Sunny] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Nasr, Khaled A.] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA. RP Choi, HS (reprint author), BIDMC, Room SL-436A,330 Brookline Ave, Boston, MA 02215 USA. EM jfrangio@bidmc.harvard.edu; hchoi@bidmc.harvard.edu RI Choi, Hak Soo/C-9954-2011 FU Nehemias Gorin Foundation; National Institutes of Health; NCI BRP [R01-CA-115296]; NIBIB [R01-EB-010022, R01-EB-011523]; Dana Foundation Program in Brain and Immuno-Imaging FX We thank Alex Allardyce (ChemAxon, Budapest, Hungary), Marsha Paul (Caliper LS, Hopkinton, MA), Brian Stall (Bruker Daltonics, Billerica, MA), Rene Schena (ArrayIt Corp., Sunnyvale, CA), Colin Johnson (LAE Technologies, Barrie, Canada), and Yangsun Kim (HST, Newark, NJ) for technical support and many helpful discussions. We thank David Burrington, Jr. for editing and Eugenia Trabucchi for administrative assistance. This study was supported by a grant from the Nehemias Gorin Foundation and the following grants from the National Institutes of Health, NCI BRP grant #R01-CA-115296 (JVF), NIBIB grant #R01-EB-010022 (J.V.F. and H.S.C.), and NIBIB grant #R01-EB-011523 (H.S.C. and J.V.F.), and the Dana Foundation Program in Brain and Immuno-Imaging (H.S.C.). NR 22 TC 8 Z9 8 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 2 PY 2013 VL 85 IS 7 BP 3508 EP 3514 DI 10.1021/ac303199x PG 7 WC Chemistry, Analytical SC Chemistry GA 120MA UT WOS:000317173200010 PM 23461528 ER PT J AU Kullgren, JT Troxel, AB Loewenstein, G Asch, DA Norton, LA Wesby, L Tao, YY Zhu, JS Volpp, KG AF Kullgren, Jeffrey T. Troxel, Andrea B. Loewenstein, George Asch, David A. Norton, Laurie A. Wesby, Lisa Tao, Yuanyuan Zhu, Jingsan Volpp, Kevin G. TI Individual- Versus Group-Based Financial Incentives for Weight Loss A Randomized, Controlled Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID LOSS PROGRAM; EATING QUESTIONNAIRE-R18; MONETARY INCENTIVES; FOOD PROVISION; OBESITY; HEALTH; PREDICTORS; OVERWEIGHT; ATTRITION; REGRET AB Background: Data on the effectiveness of employer-sponsored financial incentives for employee weight loss are limited. Objective: To test the effectiveness of 2 financial incentive designs for promoting weight loss among obese employees. Design: Randomized, controlled trial. (ClinicalTrials.gov: NCT01208350) Setting: Children's Hospital of Philadelphia. Participants: 105 employees with a body mass index between 30 and 40 kg/m(2). Intervention: 24 weeks of monthly weigh-ins (control group; n = 35); individual incentive, designed as $100 per person per month for meeting or exceeding weight-loss goals (n = 35); and group incentive, designed as $500 per month split among participants within groups of 5 who met or exceeded weight-loss goals (n = 35). Measurements: Weight loss after 24 weeks (primary outcome) and 36 weeks and changes in behavioral mediators of weight loss (secondary outcomes). Results: Group-incentive participants lost more weight than control participants (mean between-group difference, 4.4 kg [95% CI, 2.0 to 6.7 kg]; P < 0.001) and individual-incentive participants (mean between-group difference, 3.2 kg [CI, 0.9 to 5.5 kg]; P = 0.008). Twelve weeks after incentives ended and after adjustment for 3-group comparisons, group-incentive participants maintained greater weight loss than control group participants (mean between-group difference, 2.9 kg [CI, 0.5 to 5.3 kg]; P = 0.016) but not greater than individual-incentive participants (mean between-group difference, 2.7 kg [CI, 0.4 to 5.0 kg]; P = 0.024). Limitation: Single employer and short follow-up. Conclusion: A group-based financial incentive was more effective than an individual incentive and monthly weigh-ins at promoting weight loss among obese employees at 24 weeks. C1 Univ Michigan, Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. Univ Penn, Perelman Sch Med,Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, Penn CMU Roybal Ctr Behav Econ & Hlth, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. RP Kullgren, JT (reprint author), Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Clin Management Res, POB 130170, Ann Arbor, MI 48113 USA. EM jkullgre@med.umich.edu OI Asch, David/0000-0002-7970-286X; Troxel, Andrea/0000-0002-1393-3075 FU National Institute on Aging [RC2103282621]; Department of Veterans Affairs; Robert Wood Johnson Foundation FX National Institute on Aging.; By grant RC2103282621 (National Institute on Aging). Support was also provided by the Department of Veterans Affairs and the Robert Wood Johnson Foundation. NR 52 TC 57 Z9 57 U1 2 U2 29 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 APR 2 PY 2013 VL 158 IS 7 BP 505 EP + DI 10.7326/0003-4819-158-7-201304020-00002 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 123VM UT WOS:000317419400001 PM 23546562 ER PT J AU Caverzagie, KJ Iobst, WF Aagaard, EM Hood, S Chick, DA Kane, GC Brigham, TP Swing, SR Meade, LB Bazari, H Bush, RW Kirk, LM Green, ML Hinchey, KT Smith, CD AF Caverzagie, Kelly J. Iobst, William F. Aagaard, Eva M. Hood, Sarah Chick, Davoren A. Kane, Gregory C. Brigham, Timothy P. Swing, Susan R. Meade, Lauren B. Bazari, Hasan Bush, Roger W. Kirk, Lynne M. Green, Michael L. Hinchey, Kevin T. Smith, Cynthia D. TI The Internal Medicine Reporting Milestones and the Next Accreditation System SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 Univ Nebraska Med Ctr, Omaha, NE 68198 USA. Thomas Jefferson Univ, Jefferson Med Coll, Amer Board Internal Med, Philadelphia, PA 19107 USA. Amer Coll Physicians, Philadelphia, PA USA. Univ Colorado, Sch Med, Aurora, CO USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Accreditat Council Grad Med Educ, Chicago, IL 60654 USA. Baystate Med Ctr, Springfield, MA 01199 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Yale Univ, Sch Med, New Haven, CT USA. RP Caverzagie, KJ (reprint author), Univ Nebraska Med Ctr, Dept Internal Med, 985185 Nebraska Med Ctr, Omaha, NE 68198 USA. EM kelly.caverzagie@unmc.edu RI sebastianovitsch, stepan/G-8507-2013 NR 8 TC 35 Z9 35 U1 1 U2 5 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 APR 2 PY 2013 VL 158 IS 7 BP 557 EP + DI 10.7326/0003-4819-158-7-201304020-00593 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 123VM UT WOS:000317419400007 PM 23358671 ER PT J AU Rose, JJ Newby, LK Broderick, S Chiswell, K Van de Werf, F Armstrong, PW Mahaffey, KW Harrington, RA Ohman, EM Giugliano, RP Goodman, SG White, HD Califf, RM Granger, CB Lopes, RD AF Rose, Jason J. Newby, L. Kristin Broderick, Samuel Chiswell, Karen Van de Werf, Frans Armstrong, Paul W. Mahaffey, Kenneth W. Harrington, Robert A. Ohman, E. Magnus Giugliano, Robert P. Goodman, Shaun G. White, Harvey D. Califf, Robert M. Granger, Christopher B. Lopes, Renato D. TI Left Bundle Branch Block in Non-ST-Segment Elevation Acute Coronary Syndromes Incidence, Angiographic Characteristics, and Clinical Outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID ACUTE MYOCARDIAL-INFARCTION C1 [Rose, Jason J.; Newby, L. Kristin; Broderick, Samuel; Chiswell, Karen; Harrington, Robert A.; Ohman, E. Magnus; Giugliano, Robert P.; Califf, Robert M.; Granger, Christopher B.; Lopes, Renato D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Van de Werf, Frans] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Van de Werf, Frans] Leuven Coordinating Ctr, Louvain, Belgium. [Armstrong, Paul W.] Univ Alberta, Div Cardiol, Edmonton, AB, Canada. [Giugliano, Robert P.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA. [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Terrence Donnelly Heart Ctr, Div Cardiol, Toronto, ON M5B 1W8, Canada. [White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. RP Lopes, RD (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Box 3850 2400 Pratt St Room 0311,Terrace Level, Durham, NC 27705 USA. EM renato.lopes@duke.edu RI Granger, Christopher/D-3458-2014; OI Granger, Christopher/0000-0002-0045-3291; Van de Werf, Frans/0000-0001-9479-7767 NR 5 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 APR 2 PY 2013 VL 61 IS 13 BP 1461 EP 1463 DI 10.1016/j.jacc.2012.12.032 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 120SB UT WOS:000317191200017 PM 23500249 ER PT J AU Efstathiou, JA Gray, PJ Zietman, AL AF Efstathiou, J. A. Gray, P. J. Zietman, A. L. TI Proton beam therapy and localised prostate cancer: current status and controversies SO BRITISH JOURNAL OF CANCER LA English DT Review DE proton beam; radiation; prostate cancer; quality of life; cost; evidence ID INTENSITY-MODULATED RADIOTHERAPY; CONFORMAL RADIATION-THERAPY; RANDOMIZED CONTROLLED-TRIAL; DOSE-ESCALATION; PHASE-II; RISK; TOXICITY; IMRT; ADENOCARCINOMA; REDUCTION AB Proton therapy is a promising, but costly, treatment for prostate cancer. Theoretical physical advantages exist; yet to date, it has been shown only to be comparably safe and effective when compared with the alternatives and not necessarily superior. If clinically meaningful benefits do exist for patients, more rigorous study will be needed to detect them and society will require this to justify the investment of time and money. New technical advances in proton beam delivery coupled with shortened overall treatment times and declining device costs have the potential to make this a more cost-effective therapy in the years ahead. C1 [Efstathiou, J. A.; Gray, P. J.; Zietman, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Efstathiou, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. EM jefstathiou@partners.org NR 49 TC 18 Z9 18 U1 0 U2 13 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 APR 2 PY 2013 VL 108 IS 6 BP 1225 EP 1230 DI 10.1038/bjc.2013.100 PG 6 WC Oncology SC Oncology GA 118PX UT WOS:000317038800001 PM 23481182 ER PT J AU Lesnock, JL Darcy, KM Tian, C DeLoia, JA Thrall, MM Zahn, C Armstrong, DK Birrer, MJ Krivak, TC AF Lesnock, J. L. Darcy, K. M. Tian, C. DeLoia, J. A. Thrall, M. M. Zahn, C. Armstrong, D. K. Birrer, M. J. Krivak, T. C. TI BRCA1 expression and improved survival in ovarian cancer patients treated with intraperitoneal cisplatin and paclitaxel: a Gynecologic Oncology Group Study SO BRITISH JOURNAL OF CANCER LA English DT Article DE ovarian cancer; intraperitoneal chemotherapy; BRCA1 immunohistochemistry ID SPORADIC OVARIAN; DNA-REPAIR; PROTEIN EXPRESSION; MESSENGER-RNA; CHEMOTHERAPY; MUTATIONS; CARCINOMA; RESISTANCE; BRCANESS; BREAST AB Background: Breast cancer 1, early onset (BRCA1) is a tumour-suppressor gene associated with familial epithelial ovarian cancer (EOC). Reduced BRCA1 expression is associated with enhanced sensitivity to platinum-based chemotherapy. We sought to examine the prognostic relevance of BRCA1 expression in EOC patients treated with intraperitoneal platinum/taxane. Methods: The GOG-172 was a phase III, multi-institutional randomised trial of intravenous paclitaxel and cisplatin (IV therapy) vs intravenous paclitaxel, intraperitoneal cisplatin plus paclitaxel (IP therapy) in patients with optimally resected stage III EOC. The BRCA1 expression was assessed with immunohistochemistry (IHC) staining blinded to clinical outcome in archival tumour specimens. Slides with <= 10% staining were defined as aberrant and >10% as normal. Correlations between BRCA1 expression and progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier method and Cox regression analysis. Results: Of the 393 patients, 189 tumours had aberrant expression, and 204 had normal BRCA1 expression. There was an interaction between BRCA1 expression and route of administration on OS (P = 0.014) but not PFS (P = 0.054). In tumours with normal BRCA1 expression, the median OS was 58 months for IP group vs 50 months for IV group (P = 0.818). In tumours with aberrant BRCA1 expression, the median OS was 84 vs 47 months in the IP vs IV group, respectively (P = 0.0002). Aberrant BRCA1 expression was an independent prognostic factor for better survival in women randomised to IP therapy (hazard ratio (HR) = 0.67, 95% confidence interval (CI) = 0.47-0.97, P = 0.032). Similar survival was observed in the IV and IP patients with normal BRCA1 expression. Multivariate but not univariate modelling demonstrated that IV patients with aberrant vs normal BRCA1 expression had worse survival. Conclusion: Decreased BRCA1 expression is associated with a 36-month survival improvement in patients with EOC treated with IP chemotherapy. Although these results merit validation in future studies, the results suggest that decreased BRCA1 expression predicts for improved response to cisplatin-based IP chemotherapy with cisplatin and paclitaxel. C1 [Lesnock, J. L.; Krivak, T. C.] UPMC, Magee Womens Hosp, Div Gynecol Oncol, Pittsburgh, PA 15213 USA. [Darcy, K. M.; Tian, C.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA. [DeLoia, J. A.] Georgetown Univ, Med Ctr, Washington, DC 20057 USA. [Thrall, M. M.] Univ Washington, Seattle, WA 98195 USA. [Zahn, C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Armstrong, D. K.] Johns Hopkins Sch Med, Kimmel Canc Ctr, Baltimore, MD 21231 USA. [Birrer, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Krivak, TC (reprint author), UPMC, Magee Womens Hosp, Div Gynecol Oncol, Pittsburgh, PA 15213 USA. EM Tkrivak@mail.magee.edu FU National Cancer Institute [CA 27469, CA 37517]; Gynecologic Oncology Group/Ovarian Cancer Research Fund New Investigator Award FX This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and the GOG Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517) as well as a grant from the Gynecologic Oncology Group/Ovarian Cancer Research Fund New Investigator Award (to TCK). NR 37 TC 32 Z9 35 U1 0 U2 11 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 APR 2 PY 2013 VL 108 IS 6 BP 1231 EP 1237 DI 10.1038/bjc.2013.70 PG 7 WC Oncology SC Oncology GA 118PX UT WOS:000317038800002 PM 23462720 ER PT J AU Kumar, RS Douglas, PS Peterson, ED Anstrom, KJ Dai, D Brennan, JM Hui, PYM Booth, ME Messenger, JC Shaw, RE AF Kumar, Robert S. Douglas, Pamela S. Peterson, Eric D. Anstrom, Kevin J. Dai, David Brennan, J. Matthew Hui, Peter Y. M. Booth, Michael E. Messenger, John C. Shaw, Richard E. TI Effect of Race and Ethnicity on Outcomes With Drug-Eluting and Bare Metal Stents Results in 423 965 Patients in the Linked National Cardiovascular Data Registry and Centers for Medicare & Medicaid Services Payer Databases SO CIRCULATION LA English DT Article DE continental population groups; coronary artery disease; drug-eluting stents; ethnic groups; outcome assessment; percutaneous coronary intervention ID PERCUTANEOUS CORONARY INTERVENTION; RACIAL-DIFFERENCES; DYNAMIC REGISTRY; ARTERY-DISEASE; HEART-DISEASE; REVASCULARIZATION; VETERANS; SURVIVAL; RISK AB Background-Black, Hispanic, and Asian patients have been underrepresented in percutaneous coronary intervention clinical trials; therefore, there are limited data available on outcomes for these race/ethnicity groups. Methods and Results-We examined outcomes in 423 965 patients in the National Cardiovascular Data Registry CathPCI Registry database linked to Medicare claims for follow-up. Within each race/ethnicity group, we examined trends in drug-eluting stent (DES) use, 30-month outcomes, and relative outcomes of DES versus bare metal stents. Overall, 390 351 white, 20 191 black, 9342 Hispanic, and 4171 Asian patients >65 years of age underwent stent implantation from 2004 through 2008 at 940 National Cardiovascular Data Registry participating sites. Trends in adoption of DES were similar across all groups. Relative to whites, black and Hispanic patients undergoing percutaneous coronary intervention had higher long-term risks of death and myocardial infarction (blacks: hazard ratio, 1.28; 95% confidence interval, 1.24-1.32; Hispanics: hazard ratio, 1.15; 95% confidence interval, 1.10-1.21). Long-term outcomes were similar in Asians and whites (hazard ratio, 0.99; 95% confidence interval, 0.92-1.08). Use of DES was associated with better 30-month survival and lower myocardial infarction rates compared with the use of bare metal stents among all race/ethnicity groups except Hispanics, who had similar outcomes with DES or bare metal stents. Conclusions-Black and Hispanic patients undergoing percutaneous coronary intervention had worse long-term outcomes relative to white and Asian patients. Compared with bare metal stent use, DES use was generally associated with superior long-term outcomes in all racial and ethnic groups, although these differences were not statistically significant in Hispanic patients. (Circulation. 2013;127:1395-1403.) C1 [Kumar, Robert S.] Lenox Hill Hosp, New York, NY 10021 USA. [Douglas, Pamela S.; Peterson, Eric D.; Anstrom, Kevin J.; Dai, David; Brennan, J. Matthew; Booth, Michael E.] Duke Clin Res Inst, Durham, NC USA. [Hui, Peter Y. M.; Shaw, Richard E.] Calif Pacific Med Ctr, San Francisco, CA USA. [Messenger, John C.] Denver VA Med Ctr, Denver, CO USA. RP Kumar, RS (reprint author), Virginia Hart, Lenox Hill Intervent Cardiac & Vasc Serv, 130 E 77th St,9th Floor Black Hall, New York, NY 10075 USA. EM robertskumar@gmail.com FU Agency for Healthcare Research and Quality, US Department of Health and Human Services, Rockville, MD, as part of the Cardiovascular Consortium; Developing Evidence to Inform Decisions About Effectiveness (DEcIDE) program [24-EHC-1, HHSAA290-2005-0032-TO4-WA2]; Eli Lilly; Johnson Johnson; AstraZeneca; Eli Lilly Co; Medtronic; Proctor and Gamble FX This project was sponsored by the Agency for Healthcare Research and Quality, US Department of Health and Human Services, Rockville, MD, as part of the Cardiovascular Consortium and funded under project identification 24-EHC-1 and work assignment number HHSAA290-2005-0032-TO4-WA2 as part of the Developing Evidence to Inform Decisions About Effectiveness (DEcIDE) program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Service.; Dr Peterson reports research support from Eli Lilly and Johnson & Johnson. Dr. Anstrom has received research support from AstraZeneca, Eli Lilly & Co, Medtronic, and Proctor and Gamble; has served as a consultant for Abbott Vascular, AstraZeneca, Bristol Meyer Squibb, and Ikaria; and has served on Data Monitoring committees for Pfizer and Vertex. The other authors report no conflicts. NR 27 TC 15 Z9 16 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 2 PY 2013 VL 127 IS 13 BP 1395 EP + DI 10.1161/CIRCULATIONAHA.113.001437 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 117JG UT WOS:000316948900015 PM 23547179 ER PT J AU Ganzfried, BF Riester, M Haibe-Kains, B Risch, T Tyekucheva, S Jazic, I Wang, XV Ahmadifar, M Birrer, MJ Parmigiani, G Huttenhower, C Waldron, L AF Ganzfried, Benjamin Frederick Riester, Markus Haibe-Kains, Benjamin Risch, Thomas Tyekucheva, Svitlana Jazic, Ina Wang, Xin Victoria Ahmadifar, Mahnaz Birrer, Michael J. Parmigiani, Giovanni Huttenhower, Curtis Waldron, Levi TI curatedOvarianData: clinically annotated data for the ovarian cancer transcriptome SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article ID GENE-EXPRESSION PROFILE; SURVIVAL; CARCINOMA; BIOCONDUCTOR; SIGNATURE; R/BIOCONDUCTOR; BIOINFORMATICS; PROGNOSIS; NETWORK; PACKAGE AB This article introduces a manually curated data collection for gene expression meta-analysis of patients with ovarian cancer and software for reproducible preparation of similar databases. This resource provides uniformly prepared microarray data for 2970 patients from 23 studies with curated and documented clinical metadata. It allows users to efficiently identify studies and patient subgroups of interest for analysis and to perform meta-analysis immediately without the challenges posed by harmonizing heterogeneous microarray technologies, study designs, expression data processing methods and clinical data formats. We confirm that the recently proposed biomarker CXCL12 is associated with patient survival, independently of stage and optimal surgical debulking, which was possible only through meta-analysis owing to insufficient sample sizes of the individual studies. The database is implemented as the curatedOvarianData Bioconductor package for the R statistical computing language, providing a comprehensive and flexible resource for clinically oriented investigation of the ovarian cancer transcriptome. The package and pipeline for producing it are available from http://bcb.dfci.harvard.edu/ovariancancer. C1 [Ganzfried, Benjamin Frederick; Riester, Markus; Risch, Thomas; Tyekucheva, Svitlana; Jazic, Ina; Wang, Xin Victoria; Ahmadifar, Mahnaz; Parmigiani, Giovanni; Waldron, Levi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ganzfried, Benjamin Frederick; Riester, Markus; Tyekucheva, Svitlana; Wang, Xin Victoria; Parmigiani, Giovanni; Huttenhower, Curtis; Waldron, Levi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Haibe-Kains, Benjamin] Inst Rech Clin Montreal, Bioinformat & Computat Genom Lab, Montreal, PQ H2W 1R7, Canada. [Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Waldron, L (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM levi@jimmy.harvard.edu RI Haibe-Kains, Benjamin/D-3702-2011; OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Riester, Markus/0000-0002-4759-8332; Waldron, Levi/0000-0003-2725-0694; Huttenhower, Curtis/0000-0002-1110-0096 FU National Cancer Institute at the National Institutes of Health [1RC4CA156551-01]; National Science Foundation [CAREER DBI-1053486]; National Cancer Institute [U54CA143798] FX National Cancer Institute at the National Institutes of Health [1RC4CA156551-01 to G. P. and M. B.]; the National Science Foundation [CAREER DBI-1053486 to C. H.]. M. R. acknowledges support from the National Cancer Institute initiative to found Physical Science Oncology Centers [U54CA143798]. Funding for open access charge: National Science Foundation [CAREER DBI-1053486 to C. H.]. NR 46 TC 33 Z9 33 U1 0 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PD APR 2 PY 2013 AR bat013 DI 10.1093/database/bat013 PG 10 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 117DH UT WOS:000316931800001 ER PT J AU Stone, JH AF Stone, John H. TI Aortitis, retroperitoneal fibrosis, and IgG4-related disease SO PRESSE MEDICALE LA English DT Article; Proceedings Paper CT 16th International Vasculitis and ANCA Workshop CY APR 14-17, 2013 CL Inst Cordeliers, Paris, FRANCE HO Inst Cordeliers ID LYMPHOPLASMACYTIC AORTITIS; SYSTEMIC-DISEASE; ANEURYSM; PANCREATITIS; PATHOLOGY C1 [Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Rheumatol Unit, Boston, MA USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55,Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 26 TC 1 Z9 3 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 622 EP 625 DI 10.1016/j.lpm.2013.01.042 PN 2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500048 PM 23465296 ER PT J AU Pendergraft, W Mcgrath, M Murphy, A Murphy, P Laliberte, K Niles, J AF Pendergraft, W. Mcgrath, M. Murphy, A. Murphy, P. Laliberte, K. Niles, J. TI Characterization of drug-induced ANCA vasculitis at Massachusetts's general hospital (MGH): 1989-2012 SO PRESSE MEDICALE LA English DT Meeting Abstract C1 [Pendergraft, W.; Murphy, A.; Murphy, P.; Laliberte, K.; Niles, J.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Mcgrath, M.] Brigham & Womens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 654 EP 655 DI 10.1016/j.lpm.2013.02.011 PN 2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500065 ER PT J AU Roth, A Ooi, J Hess, J Van Timmeren, M Berg, E Poulton, C Mcgregor, J Burkart, M Hogan, S Hu, Y Winnik, W Nachman, P Stegeman, C Niles, J Heeringa, P Free, M Kitching, R Holdsworth, S Jennette, C Preston, G Falk, R AF Roth, A. Ooi, J. Hess, J. Van Timmeren, M. Berg, E. Poulton, C. Mcgregor, J. Burkart, M. Hogan, S. Hu, Y. Winnik, W. Nachman, P. Stegeman, C. Niles, J. Heeringa, P. Free, M. Kitching, R. Holdsworth, S. Jennette, C. Preston, G. Falk, R. TI ANCA epitope specificity determines pathogenicity, detectability and clinical predictive value SO PRESSE MEDICALE LA English DT Meeting Abstract C1 [Roth, A.; Hess, J.; Berg, E.; Poulton, C.; Mcgregor, J.; Burkart, M.; Hogan, S.; Hu, Y.; Nachman, P.; Free, M.; Jennette, C.; Preston, G.; Falk, R.] Univ N Carolina, Chapel Hill, NC USA. [Ooi, J.; Kitching, R.; Holdsworth, S.] Monash Univ, Clayton, Vic, Australia. [Van Timmeren, M.; Stegeman, C.; Heeringa, P.] Univ Groningen, Groningen, Netherlands. [Winnik, W.] US EPA, Res Triangle Pk, NC 27711 USA. [Niles, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 664 EP 664 DI 10.1016/j.lpm.2013.02.033 PN 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500087 ER PT J AU Xie, G Roschandel, D Sherva, R Monach, P Lu, Y Kung, T Carrington, K Carette, S Dellaripa, P Edberg, J Hoffman, G Khalidi, N Langford, C Mahr, A St Clair, EW Seo, P Specks, U Spiera, R Stone, J Ytterberg, S Raychaudhuri, S De Bakker, P Farrer, L Amos, C Merkel, P Siminovitch, K AF Xie, G. Roschandel, D. Sherva, R. Monach, P. Lu, Y. Kung, T. Carrington, K. Carette, S. Dellaripa, P. Edberg, J. Hoffman, G. Khalidi, N. Langford, C. Mahr, A. St Clair, E. W. Seo, P. Specks, U. Spiera, R. Stone, J. Ytterberg, S. Raychaudhuri, S. De Bakker, P. Farrer, L. Amos, C. Merkel, P. Siminovitch, K. TI Granulomatosis with polyangiitis (Wegener's) is associated with HLA-DPB1*04 and EMA6A gene variants. Evidence from a genome-wide analysis SO PRESSE MEDICALE LA English DT Meeting Abstract C1 [Xie, G.; Roschandel, D.; Kung, T.; Carrington, K.; Carette, S.; Siminovitch, K.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Sherva, R.; Monach, P.; Farrer, L.] Boston Univ, Boston, MA 02215 USA. [Lu, Y.; Dellaripa, P.; Raychaudhuri, S.; De Bakker, P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Edberg, J.] Univ Alabama Birmingham, Birmingham, AL USA. [Hoffman, G.; Langford, C.] Cleveland Clin, Cleveland, OH 44106 USA. [Khalidi, N.] McMaster Univ, Toronto, ON, Canada. [Mahr, A.; St Clair, E. W.] Univ Paris, F-75252 Paris, France. [Seo, P.] Johns Hopkins Univ, Baltimore, MD USA. [Specks, U.; Ytterberg, S.] Mayo Clin, Rochester, MN USA. [Spiera, R.] Hosp Special Surg, New York, NY 10021 USA. [Stone, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Amos, C.] Dartmouth Coll, Hanover, NH USA. [Merkel, P.] Univ Penn, Philadelphia, PA 19104 USA. RI de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 668 EP 668 DI 10.1016/j.lpm.2013.02.042 PN 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500096 ER PT J AU Clain, J Specks, U Stone, J AF Clain, J. Specks, U. Stone, J. TI The association of IgM ANCA with alveolar hemorrhage revisited SO PRESSE MEDICALE LA English DT Meeting Abstract C1 [Clain, J.; Specks, U.] Mayo Clin, Rochester, MN USA. [Stone, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 685 EP 685 DI 10.1016/j.lpm.2013.02.080 PN 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500133 ER PT J AU Unizony, S Keroack, B Stone, JH AF Unizony, S. Keroack, B. Stone, J. H. TI Tocilizumab for the treatment of giant cell arteritis: Extended follow-up SO PRESSE MEDICALE LA English DT Meeting Abstract C1 [Unizony, S.; Stone, J. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Keroack, B.] Tufts Univ, Sch Med, Maine Med Ctr, Portland, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 727 EP 727 DI 10.1016/j.lpm.2013.02.178 PN 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500231 ER PT J AU Tomasson, G Davis, JC Hoffman, GS Mccune, WJ Specks, U Spiera, R St Clair, EW Stone, JH Merkel, PA AF Tomasson, G. Davis, J. C. Hoffman, G. S. Mccune, W. J. Specks, U. Spiera, R. St Clair, E. W. Stone, J. H. Merkel, P. A. TI The value of a patient global assessment for disease activity in granulomatosis with polyangiitis SO PRESSE MEDICALE LA English DT Meeting Abstract C1 [Tomasson, G.] Univ Iceland, Reykjavik, Iceland. [Davis, J. C.] Genentech Inc, San Francisco, CA 94080 USA. [Hoffman, G. S.] Cleveland Clin, Cleveland, OH 44106 USA. [Mccune, W. J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Specks, U.] Mayo Clin, Rochester, MN USA. [Spiera, R.] Hosp Special Surg, New York, NY 10021 USA. [St Clair, E. W.] Duke Univ, Durham, NC 27706 USA. [Stone, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merkel, P. A.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 749 EP 749 DI 10.1016/j.lpm.2013.02.229 PN 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500282 ER PT J AU Pendergraft, W Cortazar, F Wenger, J Murphy, A Laliberte, K Niles, J AF Pendergraft, W. Cortazar, F. Wenger, J. Murphy, A. Laliberte, K. Niles, J. TI Maintenance therapy using rituximab-induced continuous B cell depletion for ANCA vasculitis SO PRESSE MEDICALE LA English DT Meeting Abstract C1 [Pendergraft, W.; Cortazar, F.; Wenger, J.; Murphy, A.; Laliberte, K.; Niles, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 774 EP 775 DI 10.1016/j.lpm.2013.02.292 PN 2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500344 ER PT J AU Pendergraft, W Mcgrath, M Murphy, A Murphy, P Laliberte, K Niles, J AF Pendergraft, W. Mcgrath, M. Murphy, A. Murphy, P. Laliberte, K. Niles, J. TI Gestational rituximab exposure in women with vasculitis SO PRESSE MEDICALE LA English DT Meeting Abstract C1 [Pendergraft, W.; Murphy, A.; Murphy, P.; Laliberte, K.; Niles, J.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Mcgrath, M.] Brigham & Womens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 776 EP 777 DI 10.1016/j.lpm.2013.02.296 PN 2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500348 ER PT J AU Miloslavsky, E Specks, U Merkel, P Seo, P Spiera, R Langford, C Hoffman, G Kallenberg, C St Clair, W Tchao, N Ding, L Ikle, D Jepson, B Brunetta, P Stone, J AF Miloslavsky, E. Specks, U. Merkel, P. Seo, P. Spiera, R. Langford, C. Hoffman, G. Kallenberg, C. St Clair, W. Tchao, N. Ding, L. Ikle, D. Jepson, B. Brunetta, P. Stone, J. TI Retreatment with Rituximab in the RAVE Trial SO PRESSE MEDICALE LA English DT Meeting Abstract ID MAINTENANCE C1 [Miloslavsky, E.; Stone, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Specks, U.] Mayo Clin, Rochester, MN USA. [Merkel, P.] Univ Penn, Philadelphia, PA 19104 USA. [Seo, P.] Johns Hopkins Univ, Baltimore, MD USA. [Spiera, R.] Hosp Special Surg, New York, NY 10021 USA. [Langford, C.; Hoffman, G.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kallenberg, C.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, W.] Duke Univ, Durham, NC 27706 USA. [Tchao, N.] Immune Tolerance Network, Bethesda, MD USA. [Ding, L.] NIAID, Bethesda, MD 20892 USA. [Ikle, D.; Jepson, B.] Rho, Chapel Hill, NC USA. [Brunetta, P.] Genentech Inc, San Francisco, CA 94080 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 778 EP 778 DI 10.1016/j.lpm.2013.02.300 PN 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500352 ER PT J AU Miloslavsky, E Specks, U Merkel, P Seo, P Spiera, R Langford, C Hoffman, G Kallenberg, C St Clair, W Tchao, N Ding, L Ikle, D Jepson, B Brunetta, P Stone, J AF Miloslavsky, E. Specks, U. Merkel, P. Seo, P. Spiera, R. Langford, C. Hoffman, G. Kallenberg, C. St Clair, W. Tchao, N. Ding, L. Ikle, D. Jepson, B. Brunetta, P. Stone, J. TI Safety of remission induction with rituximab versus cyclophosphamide in patients 65 and older with severe ANCA-associated vasculitis SO PRESSE MEDICALE LA English DT Meeting Abstract ID POLYARTERITIS-NODOSA C1 [Miloslavsky, E.; Stone, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Specks, U.] Mayo Clin, Rochester, MN USA. [Merkel, P.] Univ Penn, Philadelphia, PA 19104 USA. [Seo, P.] Johns Hopkins Univ, Baltimore, MD USA. [Spiera, R.] Hosp Special Surg, New York, NY 10021 USA. [Langford, C.; Hoffman, G.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kallenberg, C.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, W.] Duke Univ, Durham, NC 27706 USA. [Tchao, N.] Immune Tolerance Network, Bethesda, MD USA. [Ding, L.] NIAID, Bethesda, MD 20892 USA. [Ikle, D.; Jepson, B.] Rho, Chapel Hill, NC USA. [Brunetta, P.] Genentech Inc, San Francisco, CA 94080 USA. NR 3 TC 1 Z9 1 U1 1 U2 4 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0755-4982 EI 2213-0276 J9 PRESSE MED JI Presse Med. PD APR PY 2013 VL 42 IS 4 BP 779 EP 780 DI 10.1016/j.lpm.2013.02.302 PN 2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AA3FO UT WOS:000330978500354 ER PT J AU Ibrahim, SA Franklin, PD AF Ibrahim, Said A. Franklin, Patricia D. TI Race and Elective Joint Replacement: Where a Disparity Meets Patient Preference SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Ibrahim, Said A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Franklin, Patricia D.] Univ Massachusetts, Med Ctr, Dept Orthoped & Phys Rehabil, Worcester, MA USA. RP Ibrahim, SA (reprint author), Philadelphia VA Med Ctr ANNEX, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM said.ibrahim2@va.gov OI Franklin, Patricia D/0000-0002-4441-0533 FU AHRQ HHS [P50 HS018910-01, P50 HS018910]; NIAMS NIH HHS [K24 AR055259, 1K24AR055259-01] NR 6 TC 6 Z9 6 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2013 VL 103 IS 4 BP 583 EP 584 DI 10.2105/AJPH.2012.301077 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA0DU UT WOS:000330766100019 PM 23409914 ER PT J AU Edmondson, D Gamboa, C Cohen, A Anderson, AH Kutner, N Kronish, I Mills, MA Muntner, P AF Edmondson, Donald Gamboa, Christopher Cohen, Andrew Anderson, Amanda H. Kutner, Nancy Kronish, Ian Mills, Mary A. Muntner, Paul TI Association of Posttraumatic Stress Disorder and Depression With All-Cause and Cardiovascular Disease Mortality and Hospitalization Among Hurricane Katrina Survivors With End-Stage Renal Disease SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ACUTE CORONARY SYNDROME; ACUTE MYOCARDIAL-INFARCTION; NATIONAL COMORBIDITY SURVEY; ADVERSE CARDIAC EVENTS; HEMODIALYSIS-PATIENTS; HEART-DISEASE; MAJOR DEPRESSION; MENTAL-ILLNESS; SYMPTOMS; PTSD AB Objectives. We determined the association of psychiatric symptoms in the year after Hurricane Katrina with subsequent hospitalization and mortality in end-stage renal disease (ESRD) patients. Methods. A prospective cohort of ESRD patients (n = 391) treated at 9 hemodialysis centers in the New Orleans, Louisiana, area in the weeks before Hurricane Katrina were assessed for posttraumatic stress disorder (PTSD) and depression symptoms via telephone interview 9 to 15 months later. Two combined outcomes through August 2009 (maximum 3.5-year follow-up) were analyzed: (1) all-cause and (2) cardiovascular-related hospitalization and mortality. Results. Twenty-four percent of participants screened positive for PTSD and 46% for depression; 158 participants died (79 cardiovascular deaths), and 280 participants were hospitalized (167 for cardiovascular-related causes). Positive depression screening was associated with 33% higher risk of all-cause (hazard ratio [HR] = 1.33; 95% confidence interval [CI] = 1.06, 1.66) and cardiovascular-related hospitalization and mortality (HR = 1.33; 95% CI = 1.01, 1.76). PTSD was not significantly associated with either outcome. Conclusions. Depression in the year after Hurricane Katrina was associated with increased risk of hospitalization and mortality in ESRD patients, underscoring the long-term consequences of natural disasters for vulnerable populations. C1 [Edmondson, Donald; Kronish, Ian] Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, New York, NY USA. [Gamboa, Christopher; Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Cohen, Andrew] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Anderson, Amanda H.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kutner, Nancy] Emory Univ, US Renal Data Syst, Atlanta, GA 30322 USA. [Mills, Mary A.] Boston VA Healthcare Syst, Boston, MA USA. RP Muntner, P (reprint author), Univ Alabama Birmingham, Dept Epidemiol, 1665 Univ Blvd,Suite 230J, Birmingham, AL 35294 USA. EM pmuntner@uab.edu RI Edmondson, Donald/G-7486-2016; OI Kronish, Ian/0000-0003-0945-2380 FU Columbia University's Clinical and Translational Science Awards from the National Center for Advancing Translational Science-National Center for Research Resources/National Institutes of Health [UL1 RR024156]; National Institutes of Health [KM1 CA-156709, HL-088117, K01 DK092353, N01-DK-1-2471, HHSN267200715004C,, N01-DK-7-5004] FX This study was supported in part by Columbia University's Clinical and Translational Science Awards from the National Center for Advancing Translational Science-National Center for Research Resources/National Institutes of Health (grant UL1 RR024156). D. Edmondson is supported by the National Institutes of Health (grants KM1 CA-156709 and HL-088117). A. H. Anderson is supported by the National Institutes of Health (grant K01 DK092353). This study was supported by a subcontract to Tulane University from the National Institutes of Health (contract N01-DK-1-2471) and by the National Institutes of Health (contract HHSN267200715004C, ADB No. N01-DK-7-5004). NR 47 TC 3 Z9 3 U1 5 U2 8 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2013 VL 103 IS 4 BP E130 EP E137 DI 10.2105/AJPH.2012.301146 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA0DU UT WOS:000330766100017 PM 23409901 ER PT J AU Wakeman, SE AF Wakeman, Sarah E. TI LANGUAGE AND ADDICTION: CHOOSING WORDS WISELY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID CARE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wakeman, SE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM swakeman@partners.org NR 8 TC 4 Z9 4 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2013 VL 103 IS 4 BP E1 EP E2 DI 10.2105/AJPH.2012.301191 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA0DU UT WOS:000330766100001 PM 23409913 ER PT J AU Gupta, S Vemulakonda, GA Suhler, EB Yeh, S Albini, TA Mandelcorn, E Flaxel, CJ AF Gupta, Seema Vemulakonda, G. A. Suhler, Eric B. Yeh, Steven Albini, Thomas A. Mandelcorn, Efrem Flaxel, Christina J. TI Cytomegalovirus retinitis in the absence of AIDS SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article ID IMMUNOCOMPETENT PATIENT; TRIAMCINOLONE; INFECTION; ADULT AB Objective: The purpose of this study was to evaluate systemic and ophthalmic features associated with Cytomegalovirus (CMV) retinitis in immunocompetent patients. Design: Retrospective chart review. Participants: Nine patients with CMV retinitis who were clinically immunocompetent at the time of diagnosis. Methods: Retrospective chart review of patients evaluated at the Casey Eye Institute, University of Washington, Bascom Palmer Eye Institute and University of Toronto. IRB approval was obtained. Retrospective chart review of patients evaluated at the Casey Eye Institute, University of Washington, Bascom Palmer Eye Institute and University of Toronto. IRB approval was obtained. Results: Seven of the nine patients in our series were 60 years of age or above. Three patients had intravitreal steroid and VEGF inhibitor injections in the preceding year in the affected eye. Five of the nine patients were initially misdiagnosed to have acute retinal necrosis (ARN) for which they were on Valacyclovir for a variable period of time. Seven patients had anterior chamber and eight had vitreous inflammation. Six of the nine patients exhibited vascular attenuation or obliteration. All patients showed improvement in retinitis within weeks following therapy with intravitreal foscarnet and/or ganciclovir and systemic valganciclovir. C1 [Gupta, Seema; Suhler, Eric B.; Flaxel, Christina J.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. [Vemulakonda, G. A.] Univ Washington, Seattle, WA 98195 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Yeh, Steven] Emory Eye Ctr, Decatur, GA USA. [Albini, Thomas A.] Bascom Palmer Eye Inst, Miami, FL USA. [Mandelcorn, Efrem] Univ Toronto, Toronto, ON, Canada. RP Flaxel, CJ (reprint author), OHSU, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM flaxelc@ohsu.edu OI Albini, Thomas/0000-0003-2199-9047 NR 10 TC 8 Z9 8 U1 0 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD APR PY 2013 VL 48 IS 2 BP 126 EP 129 DI 10.1016/j.jcjo.2012.12.002 PG 4 WC Ophthalmology SC Ophthalmology GA AA5NX UT WOS:000331147800026 PM 23561607 ER PT J AU Leng, J Ho, HP Yu, XG Chang, E Lichterfeld, M AF Leng, Jin Ho, Hsin-Pin Yu, Xu G. Chang, Emmanuel Lichterfeld, Mathias TI Cell-intrinsic mechanisms of HIV-1 immune defense in elite controllers SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 14th Annual International Meeting of the Institute-of-Human-Virology CY OCT 14-17, 2012 CL Univ Maryland Sch Med, Baltimore, MD SP Inst Human Virol HO Univ Maryland Sch Med C1 [Leng, Jin; Ho, Hsin-Pin; Yu, Xu G.; Chang, Emmanuel; Lichterfeld, Mathias] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2013 VL 62 SU 1 BP 43 EP 43 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 300IQ UT WOS:000330458000026 ER PT J AU Reinherz, EL AF Reinherz, Ellis L. TI The cardinal rule of antibody- and CTL-eliciting vaccine design: specificity in a biological context SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 14th Annual International Meeting of the Institute-of-Human-Virology CY OCT 14-17, 2012 CL Univ Maryland Sch Med, Baltimore, MD SP Inst Human Virol HO Univ Maryland Sch Med C1 [Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR PY 2013 VL 62 SU 1 BP 46 EP 46 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 300IQ UT WOS:000330458000033 ER PT J AU Moye, J Sabatino, CP Brendel, RW AF Moye, Jennifer Sabatino, Charles P. Brendel, Rebecca Weintraub TI Evaluation of the Capacity to Appoint a Healthcare Proxy SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Advance directives; capacity; competency; healthcare power of attorney; healthcare proxy; informed consent ID DECISION-MAKING CAPACITY; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; PATIENTS COMPETENCE; ADVANCE DIRECTIVES; BIPOLAR DISORDER; INFORMED-CONSENT; OLDER-ADULTS; DEMENTIA; PARTICIPATION AB The appointment of a healthcare proxy is the most common way through which patients appoint a surrogate decision maker in anticipation of a future time in which they may lack the ability to make medical decisions themselves. In some situations, when a patient has not previously appointed a surrogate decision maker through an advance directive, the healthcare team may ask whether the patient, although lacking the capacity to make a healthcare decision, might still have the capacity to appoint a healthcare proxy. In this article the authors summarize the existing, albeit limited, legal and empirical basis for this capacity and propose a model for assessing capacity to appoint a healthcare proxy that incorporates clinical factors in the context of the risks and benefits specific to surrogate appointment under the law. In particular, it is important to weigh patients' understanding and choice within the context of the risks and benefits of the medical and interpersonal factors. Questions to guide capacity assessment are provided for clinical use and refinement through future research. C1 [Moye, Jennifer] VA Boston Healthcare Syst, Brockton Div, Brockton, MA 02301 USA. [Moye, Jennifer; Brendel, Rebecca Weintraub] Harvard Univ, Sch Med, Boston, MA USA. [Sabatino, Charles P.] Amer Bar Assoc, Chicago, IL 60611 USA. [Brendel, Rebecca Weintraub] Massachusetts Gen Hosp, Ctr Law Brain & Behav, Boston, MA 02114 USA. RP Moye, J (reprint author), VA Boston Healthcare Syst, Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM Jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Intramural VA [VA999999]; NIMH NIH HHS [R29 MH057104] NR 40 TC 6 Z9 6 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD APR PY 2013 VL 21 IS 4 BP 326 EP 336 DI 10.1016/j.jagp.2012.09.001 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 298WS UT WOS:000330355800003 PM 23498379 ER PT J AU Wayangankar, SA Abu-Fadel, MS Aronow, HD Kennedy, KF Gupta, R Yeh, RW Gray, WA Rosenfield, K Hennebry, TA AF Wayangankar, Siddharth A. Abu-Fadel, Mazen S. Aronow, Herbert D. Kennedy, Kevin F. Gupta, Raghav Yeh, Robert W. Gray, William A. Rosenfield, Kenneth Hennebry, Thomas A. TI Hemorrhagic and Ischemic Outcomes After Bivalirudin Versus Unfractionated Heparin During Carotid Artery Stenting A Propensity Score Analysis From the NCDR SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE bivalirudin; bleeding; carotid artery stenting; heparin ID PERCUTANEOUS CORONARY INTERVENTION; ELEVATION MYOCARDIAL-INFARCTION; ACADEMIC RESEARCH CONSORTIUM; ENDARTERECTOMY; REGISTRY; NEUROPROTECTION; ANTICOAGULANT; ASSOCIATION; AGE AB Background-The direct thrombin inhibitor, bivalirudin, is associated with similar efficacy and superior safety in patients undergoing percutaneous coronary intervention. However, the role of direct thrombin inhibitors in carotid artery stenting is not well defined. The objective of this study was to compare the safety and effectiveness of bivalirudin and unfractionated heparin (UFH) for carotid artery stenting. We hypothesized that bivalirudin would be associated with less in-hospital postprocedure bleeding than UFH but similar rates of in-hospital and 30-day ischemic outcomes. Methods and Results-We compared the incidence of in-hospital hemorrhagic and in-hospital/30-day ischemic outcomes among patients in the CARE Registry who underwent carotid artery stenting between May 2005 and March 2012 using bivalirudin or UFH. Propensity score matching was used to obtain a balanced cohort of 3555 patients in each treatment group. Patients treated with bivalirudin had a significantly lower incidence of bleeding or hematoma requiring red blood cell transfusions (0.9% versus 1.5%; odds ratio, 0.57 [0.36-0.89]; P=0.01) when compared with UFH-treated patients. The incidence of in-hospital and 30-day ischemic outcomes, including death, myocardial infarction, stroke, transient ischemic attack, and the composite outcome, death/myocardial infarction/stroke, did not differ significantly between groups. Conclusions-Bivalirudin was associated with lower rates of hemorrhagic outcomes compared with UFH during the index hospitalization for carotid artery stenting. In-hospital and 30-day ischemic events were similar between the 2 groups. Randomized comparisons of these agents are needed to confirm these findings. C1 [Wayangankar, Siddharth A.; Abu-Fadel, Mazen S.; Gupta, Raghav] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Aronow, Herbert D.] Michigan Heart & Vasc Inst, Ann Arbor, MI USA. [Kennedy, Kevin F.] St Lukes Hosp, Mid Amer Heart & Vasc Inst, Kansas City, MO USA. [Gray, William A.] Columbia Univ, Med Ctr, New York, NY USA. [Yeh, Robert W.; Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hennebry, Thomas A.] Oklahoma Heart Hosp, Oklahoma City, OK USA. RP Wayangankar, SA (reprint author), OUHSC, Dept Med, Cardiovasc Dis Sect, 920 Stanton L Young Blvd,POB 26901,WP3010, Oklahoma City, OK 73104 USA. EM siddharth-wayangankar@ouhsc.edu FU National Cardiovascular Data Registry of the American College of Cardiology Foundation FX This research was supported by the National Cardiovascular Data Registry of the American College of Cardiology Foundation. The views expressed in this article represent those of the author(s) and do not necessarily represent the official views of the National Cardiovascular Data Registry or its associated professional societies identified at www.ncdr.com. NR 22 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD APR PY 2013 VL 6 IS 2 BP 131 EP 138 DI 10.1161/CIRCINTERVENTIONS.112.974857 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 298YT UT WOS:000330361600011 PM 23532554 ER PT J AU Myat, A Redwood, SR Qureshi, AC Thackray, S Cleland, JGF Bhatt, DL Williams, B Gersh, BJ AF Myat, Aung Redwood, Simon R. Qureshi, Ayesha C. Thackray, Simon Cleland, John G. F. Bhatt, Deepak L. Williams, Bryan Gersh, Bernard J. TI Renal Sympathetic Denervation Therapy for Resistant Hypertension A Contemporary Synopsis and Future Implications SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Review DE apparent resistant hypertension; radiofrequency ablation; renal denervation; sympathetic nervous system; true resistant hypertension ID LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED CONTROLLED-TRIAL; SYMPLICITY HTN-2 TRIAL; HIGH-BLOOD-PRESSURE; HIGH-RISK; ARTERIAL-HYPERTENSION; ATRIAL-FIBRILLATION; NERVOUS-SYSTEM; UNITED-STATES; SLEEP-APNEA C1 [Myat, Aung; Redwood, Simon R.] Kings Coll London, BHF Ctr Res Excellence, London WC2R 2LS, England. [Qureshi, Ayesha C.] Univ London, London, England. [Thackray, Simon; Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Williams, Bryan] UCL, London, England. [Williams, Bryan] NIHR UCL Hosp Biomed Res Ctr, London, England. [Gersh, Bernard J.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. RP Gersh, BJ (reprint author), Mayo Clin, Dept Med, Div Cardiovasc Dis, Rochester, MN 55905 USA. EM Gersh.Bernard@mayo.edu OI Cleland, John/0000-0002-1471-7016 FU British Heart Foundation [FS/11/70/28917]; Department of Health NR 96 TC 14 Z9 18 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD APR PY 2013 VL 6 IS 2 BP 184 EP 197 DI 10.1161/CIRCINTERVENTIONS.112.000037 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 298YT UT WOS:000330361600018 PM 23591420 ER PT J AU Greeson, J Douglas, H Hoge, EA Chesney, MA AF Greeson, Jeffrey Douglas, Haley Hoge, Elizabeth A. Chesney, Margaret A. TI THE IMPACT OF MINDFULNESS-BASED INTERVENTIONS ON MECHANISMS OF STRESS REACTIVITY & RECOVERY SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-Psychosomatic-Society CY MAR 13-16, 2013 CL Miami, FL SP Amer Psychosomat Soc C1 [Greeson, Jeffrey] Duke Univ, Med Ctr, Durham, NC USA. [Douglas, Haley] Univ Washington, Seattle, WA 98195 USA. [Hoge, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chesney, Margaret A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Greeson, Jeffrey/A-9272-2009 OI Greeson, Jeffrey/0000-0003-4871-1197 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 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2013 VL 75 IS 3 BP A2 EP A2 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 300MG UT WOS:000330467400002 ER PT J AU Hoge, EA Metcalf, CA Morris, LK Simon, NM AF Hoge, Elizabeth A. Metcalf, Christina A. Morris, Laura K. Simon, Naomi M. TI MINDFULNESS MEDITATION FOR GENERALIZED ANXIETY DISORDER: EFFECTS ON RESILIENCE, ANXIETY, AND HYPOTHALAMIC PITUITARY ADRENAL (HPA) AXIS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-Psychosomatic-Society CY MAR 13-16, 2013 CL Miami, FL SP Amer Psychosomat Soc C1 [Hoge, Elizabeth A.; Metcalf, Christina A.; Morris, Laura K.; Simon, Naomi M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2013 VL 75 IS 3 BP A2 EP A2 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 300MG UT WOS:000330467400004 ER PT J AU Huffman, JC Celano, CM Suarez, L Mastromauro, CA Januzzi, JL AF Huffman, Jeff C. Celano, Christopher M. Suarez, Laura Mastromauro, Carol A. Januzzi, James L. TI FEASIBILITY AND UTILITY OF SCREENING FOR DEPRESSION AND ANXIETY DISORDERS IN PATIENTS WITH CARDIOVASCULAR DISEASE SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-Psychosomatic-Society CY MAR 13-16, 2013 CL Miami, FL SP Amer Psychosomat Soc C1 [Huffman, Jeff C.; Celano, Christopher M.; Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Suarez, Laura; Mastromauro, Carol A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2013 VL 75 IS 3 BP A146 EP A146 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 300MG UT WOS:000330467400464 ER PT J AU Russell, DC Smith, TL Krahn, DD Graskamp, P Singh, D Kolden, GG Sigmund, H Zhang, ZJ AF Russell, Douglas C. Smith, Tracey L. Krahn, Dean D. Graskamp, Peter Singh, Dalip Kolden, Gregory G. Sigmund, Heidi Zhang, Zhengjun TI HEMODYNAMIC EFFECTS OF COGNITIVE BEHAVORAL STRESS MANAGEMENT IN RECIPIENTS OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS: A RANDOMIZED CLINICAL TRIAL SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract CT 71st Annual Scientific Meeting of the American-Psychosomatic-Society CY MAR 13-16, 2013 CL Miami, FL SP Amer Psychosomat Soc C1 [Russell, Douglas C.; Smith, Tracey L.; Krahn, Dean D.; Sigmund, Heidi] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Graskamp, Peter; Singh, Dalip] Med Coll Wisconsin, Zablocki Vet Adm Med Ctr, Milwaukee, WI 53226 USA. [Kolden, Gregory G.; Zhang, Zhengjun] Univ Wisconsin, Madison, WI USA. RI Smith, Tracey/J-2030-2014 OI Smith, Tracey/0000-0001-5338-9142 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD APR PY 2013 VL 75 IS 3 BP A50 EP A51 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 300MG UT WOS:000330467400163 ER PT J AU Carroll, L AF Carroll, L. TI The effect of intensive care unit work environment on nurse perceptions of family presence during resuscitation and invasive procedures SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING LA English DT Meeting Abstract C1 [Carroll, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1474-5151 EI 1873-1953 J9 EUR J CARDIOVASC NUR JI Eur. J. Cardiovasc. Nurs. PD APR PY 2013 VL 12 SU 1 MA P210 BP S80 EP S80 PG 1 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 276FW UT WOS:000328735000156 ER PT J AU Potter, MP Buxton, D Bostic, JQ AF Potter, Mona Patel Buxton, David Bostic, Jeff Q. TI Coping Strategies for Child Bully-Victims SO PEDIATRIC ANNALS LA English DT Article ID SCHOOL-STUDENTS; PARENTAL MALTREATMENT; MIDDLE SCHOOL; VICTIMIZATION; ASSOCIATIONS; RISK; INTERVENTION; ADOLESCENCE; EXPERIENCES; DEPRESSION C1 [Potter, Mona Patel; Bostic, Jeff Q.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Buxton, David] Massachusetts Gen Hosp, McLean Hosp, Boston, MA 02114 USA. [Bostic, Jeff Q.] Massachusetts Gen Hosp, Dept Psychiat, Sch Psychiat, Boston, MA 02114 USA. RP Bostic, JQ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA. EM jbostic@partners.org NR 31 TC 0 Z9 0 U1 1 U2 10 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 EI 1938-2359 J9 PEDIATR ANN JI Pediatr. Annu. PD APR PY 2013 VL 42 IS 4 BP 57 EP 61 DI 10.3928/00904481-20130326-08 PG 5 WC Pediatrics SC Pediatrics GA 273RB UT WOS:000328552900001 ER PT J AU Buxton, D Clancy, S O'Malley, P AF Buxton, David Clancy, Sandra O'Malley, Patricia TI Working with Families Perceived as Difficult SO PEDIATRIC ANNALS LA English DT Article ID CARE; CHILDREN C1 [Buxton, David] Massachusetts Gen Hosp, McLean Hosp, Boston, MA 02114 USA. [Clancy, Sandra; O'Malley, Patricia] Massachusetts Gen Hosp, Pediat Palliat Care Serv, Boston, MA 02114 USA. [Clancy, Sandra] Massachusetts Gen Hosp Children, Family Advisory Council, Boston, MA USA. [O'Malley, Patricia] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Buxton, D (reprint author), 151 Tremont St,Apt 18U, Boston, MA 02111 USA. EM dbuxton80@yahoo.com NR 6 TC 1 Z9 1 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 EI 1938-2359 J9 PEDIATR ANN JI Pediatr. Annu. PD APR PY 2013 VL 42 IS 4 BP 167 EP 171 DI 10.3928/00904481-20130326-13 PG 5 WC Pediatrics SC Pediatrics GA 273RB UT WOS:000328552900018 PM 23556530 ER PT J AU Nguyen, T Edmonds, S Solimeo, S Wolinsky, F Roblin, D Saag, K Cram, P AF Thuy Nguyen Edmonds, Stephanie Solimeo, Samantha Wolinsky, Fredric Roblin, Douglas Saag, Kenneth Cram, Peter TI SEX AND RACIAL DIFFERENCES OF OSTEO POROSIS KNOWLEDGE AMONG PATIENTS PRESENTING FOR DXA SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT Interdisciplinary Symposium on Osteoporosis - Patient-Centered Care - Developing Successful Bone Health Teams CY APR 18-21, 2013 CL Chicago, IL SP Natl Osteoporosis Fdn C1 [Thuy Nguyen; Edmonds, Stephanie; Wolinsky, Fredric; Cram, Peter] Univ Iowa, Iowa City, IA USA. [Solimeo, Samantha] US Dept Vet Affairs, Iowa City, IA USA. [Roblin, Douglas] Kaiser Permanente, Atlanta, GA USA. [Saag, Kenneth] Univ Alabama Birmingham, Birmingham, AL USA. RI Cram, Peter/K-4472-2014 OI Cram, Peter/0000-0002-1910-346X NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD APR PY 2013 VL 24 SU 2 MA P25 BP S436 EP S437 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 270WN UT WOS:000328350000025 ER PT J AU Cucciare, MA Simpson, T Hoggatt, KJ Gifford, E Timko, C AF Cucciare, Michael A. Simpson, Tracy Hoggatt, Katherine J. Gifford, Elizabeth Timko, Christine TI SUBSTANCE USE AMONG WOMEN VETERANS: EPIDEMIOLOGY TO EVIDENCE-BASED TREATMENT SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE Substance misuse; women Veterans; alcohol; drugs; screening; evidence-based treatment ID BRIEF ALCOHOL INTERVENTION; BEHAVIORAL-COUNSELING INTERVENTIONS; RANDOMIZED CONTROLLED-TRIAL; DRUG-DEPENDENT WOMEN; AFFAIRS HEALTH-CARE; USE DISORDERS; FEMALE VETERANS; GENDER-DIFFERENCES; PREGNANT-WOMEN; CLINICAL-TRIAL AB An increasing percentage of women are U.S. Military Veterans. We review the substance misuse rates and comorbidities and the risk factors for and consequences of substance use among women Veterans. Women Veterans may have higher rates of substance misuse and comorbid psychiatric and medical disorders than male Veterans and women who are not Veterans. Studies support the AUDIT-C as a scaled marker of alcohol-related risk among female Veterans, but validated drug screening instruments are needed. We discuss evidence-based approaches in terms of treating women Veterans' substance misuse in primary and specialty care settings, along with knowledge gaps and potential research priorities to improve care in this special population. C1 [Cucciare, Michael A.; Gifford, Elizabeth; Timko, Christine] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Simpson, Tracy] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Simpson, Tracy] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Hoggatt, Katherine J.] Vet Affairs Greater Los Angeles Hlth Care Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Gifford, Elizabeth] Vet Affairs Palo Alto Hlth Care Syst, Program Evaluat Resource Ctr, Menlo Pk, CA 94025 USA. [Timko, Christine] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. RP Cucciare, MA (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd 152, Menlo Pk, CA 94025 USA. EM michael.cucciare@va.gov NR 98 TC 14 Z9 14 U1 4 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0887 EI 1545-0848 J9 J ADDICT DIS JI J. Addict. Dis. PD APR 1 PY 2013 VL 32 IS 2 BP 119 EP 139 DI 10.1080/10550887.2013.795465 PG 21 WC Substance Abuse SC Substance Abuse GA 262SD UT WOS:000327757000001 PM 23815420 ER PT J AU Kalapatapu, RK Lewis, DF Vinogradov, S Batki, SL Winhusen, T AF Kalapatapu, Raj K. Lewis, Daniel F. Vinogradov, Sophia Batki, Steven L. Winhusen, Theresa TI RELATIONSHIP OF AGE TO IMPULSIVITY AND DECISION MAKING: A BASELINE SECONDARY ANALYSIS OF A BEHAVIORAL TREATMENT STUDY IN STIMULANT USE DISORDERS SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE Cocaine; methamphetamine; aging; addiction; neurocognitive ID RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE DISORDERS; COCAINE-DEPENDENT INDIVIDUALS; IOWA GAMBLING TASK; BORDERLINE PERSONALITY-DISORDER; DRUG-ABUSE; OLDER-ADULTS; COGNITIVE REHABILITATION; METHAMPHETAMINE USE; EXECUTIVE FUNCTIONS AB Because stimulant use disorders remain prevalent across the lifespan, cognition is an important area of clinical care and research focus among aging adults with stimulant use disorders. This secondary analysis of a National Institute on Drug Abuse Clinical Trials Network study suggests that decision making, verbal learning/memory, executive function, and set shifting are important cognitive domains to screen clinically and treat in aging adults with stimulant use disorders. Some suggestions are made on how clinical treatment providers can practically use these results. An important direction for future research is the development of cognitively remediating treatments for impaired cognitive domains in aging adults with stimulant use disorders. C1 [Kalapatapu, Raj K.; Vinogradov, Sophia; Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Kalapatapu, Raj K.; Vinogradov, Sophia; Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Lewis, Daniel F.; Winhusen, Theresa] Univ Cincinnati, Coll Med, Cincinnati Addict Res Ctr, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. RP Kalapatapu, RK (reprint author), San Francisco VA Med Ctr, Bldg 8 Mental Hlth,Room 4C,4150 Clement St, San Francisco, CA 94121 USA. EM kalapatapu.raj.k@gmail.com OI Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [T32 DA007294, U10DA013732, K23 DA034883, K23DA 034883, U10 DA013732] NR 94 TC 2 Z9 2 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0887 EI 1545-0848 J9 J ADDICT DIS JI J. Addict. Dis. PD APR 1 PY 2013 VL 32 IS 2 BP 206 EP 216 DI 10.1080/10550887.2013.795471 PG 11 WC Substance Abuse SC Substance Abuse GA 262SD UT WOS:000327757000007 PM 23815427 ER PT J AU Berman, NC Calkins, AW Abramowitz, JS AF Berman, Noah C. Calkins, Amanda W. Abramowitz, Jonathan S. TI Longer-term effects of inducing harm related intrusions: Implications for research on obsessional phenomena SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Thought Action Fusion; In Vivo; OCD; Experimental Paradigm ID THOUGHT-ACTION FUSION; COMPULSIVE DISORDER; COGNITIVE THEORY; NEUTRALIZATION; QUESTIONNAIRE; VALIDATION; INVENTORY; BELIEFS AB Although numerous researchers use in vivo thought induction paradigms to study obsessional phenomena, institutional review boards (IRBs) frequently raise questions about the potential harm that these studies might cause non-treatment seeking participants and clinical psychologists have argued that these paradigms might violate the APA ethics code. Thus, the current study examined longer-term psychological effects of inducing harm-related intrusive thoughts in non-treatment seeking undergraduates. Participants were asked to think about a close relative or friend getting into a car collision and then rated their level of distress and thought action fusion-like (TAF) beliefs. One week later, participants completed an online survey that assessed their current level of distress, TAF beliefs, and their interpretation of intrusions. We found significant decreases in vivo ratings of: anxiety, likelihood TAF, moral TAF, and the urge to neutralize the effects of thinking the thought. Additionally, participants considered their intrusive thoughts to be less significant and dangerous after a week's time. Our data suggest that thought induction paradigms are not associated with longer-term psychological risk and provide a safe and non-intrusive way of studying OCD phenomena in a laboratory setting. (C) 2013 Elsevier Inc. All rights reserved. C1 [Berman, Noah C.; Abramowitz, Jonathan S.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Calkins, Amanda W.] Boston Univ, Ctr Anxiety Related Disorders, Boston, MA 02215 USA. RP Berman, NC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,ACC 815, Boston, MA 02114 USA. EM berman.noah@gmail.com OI Baker, Amanda/0000-0002-0103-5411 NR 25 TC 0 Z9 0 U1 2 U2 8 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 2013 VL 2 IS 2 BP 109 EP 113 DI 10.1016/j.jocrd.2013.01.006 PG 5 WC Psychiatry SC Psychiatry GA 257VB UT WOS:000327414800006 ER PT J AU Goetter, EM Herbert, JD Forman, EM Yuen, EK Gershkovich, M Glassman, LH Rabin, SJ Goldstein, SP AF Goetter, Elizabeth M. Herbert, James D. Forman, Evan M. Yuen, Erica K. Gershkovich, Marina Glassman, Lisa H. Rabin, Stephanie J. Goldstein, Stephanie P. TI Delivering exposure and ritual prevention for obsessive-compulsive disorder via videoconference: Clinical considerations and recommendations SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Obsessive-compulsive disorder; Exposure and ritual prevention; Telehealth; Videoconference-mediated exposure therapy ID COGNITIVE-BEHAVIORAL THERAPY; QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; WORKING ALLIANCE INVENTORY; BECK DEPRESSION INVENTORY; RESPONSE PREVENTION; CONTROLLED-TRIAL; COMORBIDITY; PSYCHOTHERAPY; VALIDATION AB Exposure and ritual prevention (ERP) has been shown to be effective for treating obsessive-compulsive disorder (OCD), but many people with OCD are not able to access this specialized, evidence-based mental health treatment. Internet-mediated technologies, e.g., videoconferencing, represent a way to increase the availability of evidence-based treatments such as ERP, but given that OCD is a complex disorder requiring a nuanced treatment approach, clinicians attempting to implement ERP remotely should appreciate not only the advantages but also the challenges associated with treating OCD from a distance. Using a case example, we describe this treatment method and discuss relevant clinical considerations. (C) 2013 Elsevier Inc. All rights reserved. C1 [Goetter, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goetter, Elizabeth M.; Herbert, James D.; Forman, Evan M.; Gershkovich, Marina; Glassman, Lisa H.; Rabin, Stephanie J.; Goldstein, Stephanie P.] Drexel Univ, Philadelphia, PA 19104 USA. [Yuen, Erica K.] Med Univ S Carolina, Charleston, SC 29425 USA. [Yuen, Erica K.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. [Rabin, Stephanie J.] Minneapolis VA Hlth Care Syst, Minneapolis, MN 55417 USA. RP Goetter, EM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM egoetter@partners.org RI Forman, Evan/I-1042-2012; OI Rabin, Stephanie/0000-0002-8282-0867 NR 70 TC 6 Z9 6 U1 4 U2 9 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 2013 VL 2 IS 2 BP 137 EP U108 DI 10.1016/j.jocrd.2013.01.003 PG 9 WC Psychiatry SC Psychiatry GA 257VB UT WOS:000327414800010 ER PT J AU Rasmussen, JL Brown, TA Steketee, GS Barlow, DH AF Rasmussen, Jessica L. Brown, Timothy A. Steketee, Gail S. Barlow, David H. TI Impulsivity in hoarding SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Article DE Hoarding; Acquisition; Impulsivity ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RISK-TASK BART; DECISION-MAKING; COMMUNITY SAMPLE; SYMPTOM; MODEL; AGE; INHIBITION; COMORBIDITY AB Acquisition in hoarding appears to have impulsive features likely to be evident in behavioral impulsivity and response inhibition. This study used a multi-dimensional model of impulsivity to examine this construct in participants with hoarding (n=32) and anxiety disorders (n=32) who received a diagnostic assessment and completed self-report forms and neuropsychological tasks measuring impulsivity. A diagnosis of hoarding predicted higher levels of self-reported urgency, as well as greater difficulties with response inhibition and lowered adaptive and maladaptive risk taking, independent of social phobia, generalized anxiety disorder and major depressive disorder. However, when age was controlled, hoarding ceased to predict these outcomes independent of other psychiatric diagnoses. Although specific symptoms of hoarding appeared significantly related to some aspects of impulsivity, analyses indicated that age accounted for these findings. In the present study, as in other studies, hoarding participants averaged approximately 25 years older than those with anxiety disorders, rendering examination of response inhibition and risk taking in hoarding versus anxiety disorders more difficult. Further research on other aspects of impulsivity (e.g., reward delay, planning/foresight) in hoarding and other psychiatric conditions with age matched comparison samples can advance understanding of these disorders and potentially lead to innovative treatments. Published by Elsevier Inc. C1 [Rasmussen, Jessica L.; Brown, Timothy A.; Barlow, David H.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Steketee, Gail S.] Boston Univ, Sch Social Work, Boston, MA 02215 USA. RP Rasmussen, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St,2nd Floor, Boston, MA 02215 USA. EM jrasmuss@bu.edu FU university dissertation award FX Funding for this study was provided by a university dissertation award. The grantees of the award had no role in the study design, collection, analysis or interpretation of data, writing the manuscript or the decision to submit the manuscript for publication. NR 50 TC 6 Z9 6 U1 6 U2 10 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 2013 VL 2 IS 2 BP 183 EP 191 DI 10.1016/j.jocrd.2013.02.004 PG 9 WC Psychiatry SC Psychiatry GA 257VB UT WOS:000327414800016 ER PT J AU Sampaio, AS Hounie, AG Petribu, K Cappi, C Morais, IA Quarantini, LC Filho, HPV do Rosario, MD Stewart, SE Fargeness, J Matthews, C Arnold, P Richter, M Kennedy, J Hanna, GL Pauls, DL Miguel, EC AF Sampaio, A. S. Hounie, A. G. Petribu, K. Cappi, C. Morais, I. A. Quarantini, L. C. Filho, H. P. V. da Conceicao do Rosario, M. Stewart, S. E. Fargeness, J. Matthews, C. Arnold, P. Richter, M. Kennedy, J. Hanna, G. L. Pauls, D. L. Miguel Filho, E. C. TI Association between MAO-A and Obsessive-Compulsive Disorder related phenotypes SO JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS LA English DT Meeting Abstract DE Obsessive-Compulsive Disorder; Catechol-O-Methyltransferase; Monoamine Oxidase; Genetic Association Study C1 [Sampaio, A. S.; Hounie, A. G.; Cappi, C.; Morais, I. A.; Filho, H. P. V.; Miguel Filho, E. C.] Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, Sao Paulo, Brazil. [Sampaio, A. S.; Quarantini, L. C.] Univ Fed Bahia, UFBA Fed Univ Bahia, Fac Med, Salvador, BA, Brazil. [Petribu, K.] Univ Pernambuco, UPE, Fac Ciencias Med, Recife, PE, Brazil. [da Conceicao do Rosario, M.] Univ Fed Sao Paulo, UNIFESP, Sao Paulo, Brazil. [Stewart, S. E.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Stewart, S. E.; Fargeness, J.; Pauls, D. L.] Massachusetts Gen Hosp, PNGU, Boston, MA 02114 USA. [Matthews, C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Arnold, P.; Richter, M.; Kennedy, J.] Univ Toronto, Toronto, ON, Canada. [Hanna, G. L.] Univ Michigan, Ann Arbor, MI 48109 USA. RI Stewart, Evelyn/K-6961-2014; OI Stewart, S. Evelyn/0000-0002-0994-6383 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 2211-3649 J9 J OBSESS-COMPULS REL JI J. Obsessive-Compuls. Relat. Disord. PD APR PY 2013 VL 2 IS 2 BP 228 EP 228 PG 1 WC Psychiatry SC Psychiatry GA 257VB UT WOS:000327414800038 ER PT J AU Zivin, K AF Zivin, Kara TI How Are Prescribing Decisions Made? SO PSYCHIATRIC SERVICES LA English DT Editorial Material C1 [Zivin, Kara] US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI USA. [Zivin, Kara] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Zivin, K (reprint author), US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2013 VL 64 IS 4 BP 295 EP 295 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255VL UT WOS:000327268100007 PM 23543162 ER PT J AU Rosen, MI Afshartous, DR Nwosu, S Scott, MC Jackson, JC Marx, BP Murdoch, M Sinnott, PL Speroff, T AF Rosen, Marc I. Afshartous, David R. Nwosu, Samuel Scott, Melanie C. Jackson, James C. Marx, Brian P. Murdoch, Maureen Sinnott, Patricia L. Speroff, Theodore TI Racial Differences in Veterans' Satisfaction With Examination of Disability From Posttraumatic Stress Disorder SO PSYCHIATRIC SERVICES LA English DT Article ID PATIENT SATISFACTION; ATTITUDES; CARE; CLINICIAN; DISPARITIES; BENEFITS; SCALE AB Objective: The examination that determines if a veteran has service-connected posttraumatic stress disorder (PTSD) affects veterans' lives for years. This study examined factors potentially associated with veterans' perception of their examination's quality. Methods: Veterans (N=384) being evaluated for an initial PTSD service-connection claim were randomly assigned to receive either a semistructured interview or the examiner's usual interview. Immediately after the interview, veterans completed confidential ratings of the examinations' quality and of their examiners' interpersonal qualities and competence. Extensive data characterizing the veterans, the 33 participating examiners, and the examinations themselves were collected. Results: Forty-seven percent of Caucasian veterans and 34% of African-American veterans rated their examination quality as excellent. African Americans were less likely than Caucasians to assign a higher quality rating (odds ratio=.61, 95% confidence interval=.38-.99, p=.047). Compared with Caucasians, African Americans rated their examiners as having significantly worse interpersonal qualities but not lower competence. Ratings were not significantly related to the veterans' age, gender, marital status, eventual diagnosis of PTSD, Global Assessment of Functioning score, the examiner's perception of the prevalence of malingering, or the presence of a third party during the examination. Conclusions: Ratings of disability examinations were generally high, although ratings were less favorable among African-American veterans than among Caucasian veterans. C1 [Rosen, Marc I.] Vet Affairs VA Connecticut Healthcare Syst, Dept Psychiat, West Haven, CT 06516 USA. [Scott, Melanie C.] Vet Affairs VA Connecticut Healthcare Syst, Dept Psychol, West Haven, CT 06516 USA. [Rosen, Marc I.; Scott, Melanie C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Afshartous, David R.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Nwosu, Samuel; Jackson, James C.; Speroff, Theodore] VA Tennessee Valley Healthcare Syst, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Nwosu, Samuel; Jackson, James C.; Speroff, Theodore] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Speroff, Theodore] VA Boston Healthcare Syst, Dept Biostat, Boston, MA USA. [Jackson, James C.] VA Boston Healthcare Syst, Dept Medicine, Boston, MA USA. [Marx, Brian P.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Murdoch, Maureen] Univ Minnesota, Sch Med, Gen Internal Med Sect, Ctr Chron Dis Outcomes Res,Minneapolis VA Hlth Ca, Minneapolis, MN 55455 USA. [Murdoch, Maureen] Univ Minnesota, Sch Med, Dept Internal Med, Minneapolis, MN 55455 USA. [Sinnott, Patricia L.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Palo Alto, CA USA. [Sinnott, Patricia L.] Stanford Univ, Ctr Hlth Policy, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. RP Rosen, MI (reprint author), Vet Affairs VA Connecticut Healthcare Syst, Dept Psychiat, 116A, West Haven, CT 06516 USA. EM marc.rosen@yale.edu FU Veterans Affairs (VA) Health Services Research and Development Quality Enhancement Research Initiative Program [SDR 06-331]; Veterans Integrated Service Network 1 Mental Illness Research, Education and Clinical Center; Raytheon BBN Technologies; Charles River Analytics FX This project was supported by the Veterans Affairs (VA) Health Services Research and Development Quality Enhancement Research Initiative Program (SDR 06-331) and by the Veterans Integrated Service Network 1 Mental Illness Research, Education and Clinical Center. The authors thank the E3-PTSD collaborative investigators for their work in this study, including Heather Davis-Underwood, Elliot Fielstein, Elise Ratchford, Katherine Strickland, Dorothy Scanlan, Karin E. Thompson, Sheila Corrigan, Janet C'deBaca, Mitzi Dearborn, Michelle Sharp, Christina M. Klauber, Elizabeth Jones, Erin Olgren, Eli Reich, Rachel Coleman, Yordanka Koleva, and Lisa Fenton; the Veterans Benefits Administration Systematic Technical Accuracy Review program; and the VA medical centers that participated in this project.; Dr. Marx receives support from Raytheon BBN Technologies and Charles River Analytics. The other authors report no competing interests. NR 32 TC 1 Z9 1 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2013 VL 64 IS 4 BP 354 EP 359 DI 10.1176/appi.ps.201100526 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255VL UT WOS:000327268100017 PM 23318842 ER PT J AU Marx, BP Pollack, S AF Marx, Brian P. Pollack, Stacey TI A False Dilemma and an Unfair Characterization of Veterans SO PSYCHIATRIC SERVICES LA English DT Letter ID POSTTRAUMATIC-STRESS-DISORDER; THERAPY C1 [Marx, Brian P.] VA Boston Healthcare Syst, VA Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Marx, Brian P.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Pollack, Stacey] US Dept Vet Affairs, Washington, DC USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst, VA Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2013 VL 64 IS 4 BP 392 EP 392 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255VL UT WOS:000327268100026 PM 23543170 ER PT J AU Yang, S AF Yang, Suzanne TI The Routledge Handbook of Deviant Behavior SO PSYCHIATRIC SERVICES LA English DT Book Review C1 [Yang, Suzanne] Vet Affairs Pittsburgh Healthcare Syst, Vet Integrated Serv Network 4, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Yang, S (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Vet Integrated Serv Network 4, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD APR PY 2013 VL 64 IS 4 BP E4 EP E4 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 255VL UT WOS:000327268100004 ER PT J AU Alonso, A Krijthe, BP Aspelund, T Stepas, KA Pencina, MJ Moser, CB Sinner, MF Sotoodehnia, N Fontes, JD Janssens, ACJW Kronmal, RA Magnani, JW Witteman, JC Chamberlain, AM Lubitz, SA Schnabel, RB Agarwal, SK McManus, DD Ellinor, PT Larson, MG Burke, GL Launer, LJ Hofman, A Levy, D Gottdiener, JS Kaab, S Couper, D Harris, TB Soliman, EZ Stricker, BHC Gudnason, V Heckbert, SR Benjamin, EJ AF Alonso, Alvaro Krijthe, Bouwe P. Aspelund, Thor Stepas, Katherine A. Pencina, Michael J. Moser, Carlee B. Sinner, Moritz F. Sotoodehnia, Nona Fontes, Joao D. Janssens, A. Cecile J. W. Kronmal, Richard A. Magnani, Jared W. Witteman, Jacqueline C. Chamberlain, Alanna M. Lubitz, Steven A. Schnabel, Renate B. Agarwal, Sunil K. McManus, David D. Ellinor, Patrick T. Larson, Martin G. Burke, Gregory L. Launer, Lenore J. Hofman, Albert Levy, Daniel Gottdiener, John S. Kaeaeb, Stefan Couper, David Harris, Tamara B. Soliman, Elsayed Z. Stricker, Bruno H. C. Gudnason, Vilmundur Heckbert, Susan R. Benjamin, Emelia J. TI Simple Risk Model Predicts Incidence of Atrial Fibrillation in a Racially and Geographically Diverse Population: the CHARGE-AF Consortium SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE atrial fibrillation; epidemiology; risk factors ID ATHEROSCLEROSIS RISK; AFRICAN-AMERICANS; SURVIVAL ANALYSIS; HEART-FAILURE; COMMUNITIES; FLUTTER; DESIGN; STROKE; PREVALENCE; WHITES AB Background-Tools for the prediction of atrial fibrillation (AF) may identify high-risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors. Methods and Results-Individual-level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19% African Americans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C-statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C-statistic, 0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, -0.0032; 95% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C-statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C-statistic, 0.705; 95% CI, 0.664 to 0.747) and calibration was adequate. Conclusion-A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe. C1 [Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Krijthe, Bouwe P.; Janssens, A. Cecile J. W.; Witteman, Jacqueline C.; Hofman, Albert; Stricker, Bruno H. C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Stricker, Bruno H. C.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Stricker, Bruno H. C.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Stepas, Katherine A.; Pencina, Michael J.; Moser, Carlee B.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Sotoodehnia, Nona] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA. [Sotoodehnia, Nona] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Sinner, Moritz F.; Fontes, Joao D.; Magnani, Jared W.; McManus, David D.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Sinner, Moritz F.; Fontes, Joao D.; Magnani, Jared W.; McManus, David D.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Chamberlain, Alanna M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Sinner, Moritz F.; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Schnabel, Renate B.] Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Eppendorf, Germany. [Agarwal, Sunil K.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Couper, David] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC USA. [Burke, Gregory L.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Gottdiener, John S.] Univ Maryland, Med Ctr, Div Cardiol, Baltimore, MD 21201 USA. [Sinner, Moritz F.; Kaeaeb, Stefan] Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany. [Soliman, Elsayed Z.] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC 27109 USA. [Stricker, Bruno H. C.] Inspectorate Hlth Care, The Hague, Netherlands. [Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany. [McManus, David D.] Univ Massachusetts, Dept Med, Worcester, MA 01605 USA. [McManus, David D.] Univ Massachusetts, Dept Quantitat Hlth Sci, Worcester, MA 01605 USA. [McManus, David D.] Worcester Polytech Inst, Dept Biomed Engn, Worcester, MA 01609 USA. RP Alonso, A (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM alonso@umn.edu; emelia@bu.edu RI Schnabel, Renate/F-6527-2014; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015; Alonso, Alvaro/A-4917-2010; OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084; Alonso, Alvaro/0000-0002-2225-8323; Larson, Martin/0000-0002-9631-1254; Janssens, A Cecile/0000-0002-6153-4976; Benjamin, Emelia/0000-0003-4076-2336 FU NIH [N01-AG-12100]; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; NHLBI [RC1HL099452, RC1HL101056, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, R01HL088456]; American Heart Association [09SDG2280087, 09FTF2190028]; NIA [AG-023629, AG-15928, AG-20098, AG-027058]; German Heart Foundation; Erasmus Medical Center; Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam FX AGES: The Age, Gene/Environment Susceptibility Reykjavik Study has been funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This work was additionally funded by grants RC1HL099452 and RC1HL101056 from NHLBI and 09SDG2280087 from the American Heart Association. CHS: The Cardiovascular Health Study was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grants HL080295 and R01HL088456, with additional contribution from NINDS. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the NIA. See also http://www.chs-nhlbi.org/pi.htm. FHS: 6R01-NS 17950, N01-HC 25195, 1R01HL092577 (to Drs. Ellinor and Benjamin), 1RC1HL101056 (to Drs. Alonso and Benjamin), 1R01HL102214 (to Drs. Heckbert and Benjamin), 1R01AG028321 (to Dr. Benjamin), American Heart Association award 09FTF2190028 (to Dr. Magnani) and 1R21HL106092 (to Dr. Magnani). Dr. Sinner was supported by the German Heart Foundation. RS: The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. NR 40 TC 115 Z9 116 U1 2 U2 22 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 2013 VL 2 IS 2 AR UNSP e000102 DI 10.1161/JAHA.112.000102 PG 20 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243ST UT WOS:000326338400002 PM 23537808 ER PT J AU Schwamm, LH AF Schwamm, Lee H. TI When in Rome, Do Like the Romans: Certifying Stroke Centers With the Rod of Aesculapius or the Medical Caduceus of Hermes? SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Editorial Material ID BRAIN ATTACK COALITION; ACUTE ISCHEMIC-STROKE; RECOMMENDATIONS; ESTABLISHMENT; ASSOCIATION; STATEMENT C1 [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, C Miller Fisher Endowed Chair, Dept Neurol ACC 720, MGH,55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 21 TC 2 Z9 2 U1 2 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 2013 VL 2 IS 2 AR UNSP e000120 DI 10.1161/JAHA.113.000120 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243ST UT WOS:000326338400001 PM 23557752 ER PT J AU Carl, JR Soskin, DP Kerns, C Barlow, DH AF Carl, Jenna R. Soskin, David P. Kerns, Caroline Barlow, David H. TI Positive emotion regulation in emotional disorders: A theoretical review SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE Emotion regulation; Positive emotion; Anxiety; Depression; Bipolar ID MAJOR DEPRESSIVE DISORDER; GENERALIZED ANXIETY DISORDER; LOVING-KINDNESS MEDITATION; DSM-IV ANXIETY; AFFECTIVE STARTLE MODULATION; APPROACH SYSTEM BAS; BIPOLAR DISORDER; ATTENTIONAL BIAS; BEHAVIORAL ACTIVATION; NEGATIVE AFFECT AB Conceptualizations of emotion regulation have led to the identification of cognitive and behavioral regulatory abnormalities that contribute to the development and maintenance of emotional disorders. However, existing research on emotion regulation in anxiety and mood disorders has primarily focused on the regulation of negative emotions rather than positive emotions. Recent findings indicate that disturbances in positive emotion regulation occur across emotional disorders, and may be a generative target for treatment research. The aims of this paper are to: 1. Present a transdiagnostic model of positive emotion disturbances in emotional disorders; 2. Review evidence for disturbances in positive emotion regulation in emotional disorders across categories of emotion regulation; and 3. Propose treatment strategies that may address these disturbances. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Carl, Jenna R.; Kerns, Caroline; Barlow, David H.] Boston Univ, Ctr Anxiety & Related Disorders, Dept Psychol, Boston, MA 02215 USA. [Soskin, David P.] Harvard Univ, Sch Med, Ctr Treatment Resistant Depress, Depress Clin & Res Program,Massachusetts Gen Hosp, Boston, MA USA. RP Carl, JR (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM jcarl@bu.edu NR 189 TC 43 Z9 48 U1 17 U2 95 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 EI 1873-7811 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD APR PY 2013 VL 33 IS 3 BP 343 EP 360 DI 10.1016/j.cpr.2013.01.003 PG 18 WC Psychology, Clinical SC Psychology GA 229DI UT WOS:000325241600002 PM 23399829 ER PT J AU Tofthagen, C Visovsky, CM Hopgood, R AF Tofthagen, Cindy Visovsky, Constance M. Hopgood, Rachelle TI Chemotherapy-Induced Peripheral Neuropathy: An Algorithm to Guide Nursing Management SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID PHARMACOLOGICAL MANAGEMENT; PAIN; RECOMMENDATIONS; STRENGTH; CANCER; GO AB Oncology nurses play a critical role in the assessment and management of chemotherapy-induced peripheral neuropathy (CIPN). Baseline and ongoing evaluation of physical function is a critical but often overlooked aspect of assessment of CIPN. The diversity of symptoms and the complexity associated with neuromuscular assessment lead to challenges in evaluation and management of CIPN. To meet this challenge, the authors devised a feasible algorithm to guide oncology nurses in the assessment and management of CIPN using techniques that can easily be implemented in a variety of clinical settings. Managing pain, maintaining safety, and maximizing physical function are the primary goals for nursing management of CIPN. C1 [Tofthagen, Cindy; Visovsky, Constance M.; Hopgood, Rachelle] Univ S Florida, Coll Nursing, Tampa, FL 33620 USA. [Tofthagen, Cindy] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA USA. [Tofthagen, Cindy] Univ Massachusetts Boston, Boston, MA USA. RP Tofthagen, C (reprint author), Univ S Florida, Coll Nursing, Tampa, FL 33620 USA. EM ctofthag@health.usf.edu FU NCI NIH HHS [U54 CA156732, U54 CA156734] NR 36 TC 6 Z9 7 U1 2 U2 9 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD APR PY 2013 VL 17 IS 2 BP 138 EP 144 DI 10.1188/13.CJON.138-144 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 220EC UT WOS:000324563800008 PM 23538249 ER PT J AU Spiegel, BMR AF Spiegel, Brennan M. R. TI Patient-Reported Outcomes in Gastroenterology: Clinical and Research Applications SO JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE Gastroenterology; Patient-reported outcomes; Quality of life ID QUALITY-OF-LIFE; GASTROESOPHAGEAL-REFLUX DISEASE; IRRITABLE-BOWEL-SYNDROME; TREATMENT SATISFACTION QUESTIONNAIRE; UPPER GASTROINTESTINAL DISORDERS; LAPAROSCOPIC NISSEN FUNDOPLICATION; FECAL INCONTINENCE QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIAL; INFORMATION-SYSTEM PROMIS; NEPEAN DYSPEPSIA INDEX AB Patient-generated reports, also known as Patient-Reported Outcomes (PROs), capture the patients' illness experience in a structured format and may help bridge the gap between patients and providers. PROs measure any aspect of patient-reported health (e. g., physical, emotional or social symptoms) and can help to direct care and improve clinical outcomes. When clinicians systematically collect patient-reported data in the right place at the right time, PRO measurement can effectively aid in detection and management of conditions, improve satisfaction with care and enhance the patient-provider relationship. This review article summarizes the latest approaches to PRO measuring for clinical trials and clinical practice, with a focus on use of PROs in gastroenterology. C1 [Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu NR 139 TC 9 Z9 9 U1 2 U2 6 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 J9 J NEUROGASTROENTEROL JI J. Neurogastroenterol. Motil. PD APR PY 2013 VL 19 IS 2 BP 137 EP 148 DI 10.5056/jnm.2013.19.2.137 PG 12 WC Gastroenterology & Hepatology; Clinical Neurology SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 225ZV UT WOS:000325004700004 PM 23667745 ER PT J AU Lin, PC Giannopoulou, EG Park, K Mosquera, JM Sboner, A Tewari, AK Garraway, LA Beltran, H Rubin, MA Elemento, O AF Lin, Pei-Chun Giannopoulou, Eugenia G. Park, Kyung Mosquera, Juan Miguel Sboner, Andrea Tewari, Ashutosh K. Garraway, Levi A. Beltran, Himisha Rubin, Mark A. Elemento, Olivier TI Epigenomic Alterations in Localized and Advanced Prostate Cancer SO NEOPLASIA LA English DT Article ID CANDIDATE TUMOR-SUPPRESSOR; DNA METHYLATION; DOWN-REGULATION; MASS-SPECTROMETRY; GENOME; GENE; HYPERMETHYLATION; CELLS; IDENTIFICATION; PROTEINS AB Although prostate cancer (PCa) is the second leading cause of cancer death among men worldwide, not all men diagnosed with PCa will die from the disease. A critical challenge, therefore, is to distinguish indolent PCa from more advanced forms to guide appropriate treatment decisions. We used Enhanced Reduced Representation Bisulfite Sequencing, a genome-wide high-coverage single-base resolution DNA methylation method to profile seven localized PCa samples, seven matched benign prostate tissues, and six aggressive castration-resistant prostate cancer (CRPC) samples. We integrated these data with RNA-seq and whole-genome DNA-seq data to comprehensively characterize the PCa methylome, detect changes associated with disease progression, and identify novel candidate prognostic biomarkers. Our analyses revealed the correlation of cytosine guanine dinucleotide island (CGI)-specific hypermethylation with disease severity and association of certain breakpoints (deletion, tandem duplications, and interchromosomal translocations) with DNA methylation. Furthermore, integrative analysis of methylation and single-nucleotide polymorphisms (SNPs) uncovered widespread allele-specific methylation (ASM) for the first time in PCa. We found that most DNA methylation changes occurred in the context of ASM, suggesting that variations in tumor epigenetic landscape of individuals are partly mediated by genetic differences, which may affect PCa disease progression. We further selected a panel of 13 CGIs demonstrating increased DNA methylation with disease progression and validated this panel in an independent cohort of 20 benign prostate tissues, 16 PCa, and 8 aggressive CRPCs. These results warrant clinical evaluation in larger cohorts to help distinguish indolent PCa from advanced disease. C1 [Lin, Pei-Chun; Park, Kyung; Mosquera, Juan Miguel; Sboner, Andrea; Rubin, Mark A.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. [Lin, Pei-Chun; Rubin, Mark A.] Weill Cornell Med Coll, Grad Sch Med Sci, Grad Program Biochem & Struct Biol Cell & Dev Bio, New York, NY 10065 USA. [Giannopoulou, Eugenia G.; Elemento, Olivier] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA. [Giannopoulou, Eugenia G.; Sboner, Andrea; Elemento, Olivier] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA. [Tewari, Ashutosh K.] Weill Cornell Med Coll, Dept Urol, New York, NY 10065 USA. [Tewari, Ashutosh K.] Weill Cornell Med Coll, LeFrak Ctr Robot Surg, New York, NY 10065 USA. [Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beltran, Himisha] Weill Cornell Med Coll, Dept Med, Div Hematol Oncol, New York, NY 10065 USA. RP Elemento, O (reprint author), Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, Dept Physiol & Biophys, 1305 York Ave, New York, NY 10065 USA. EM rubinma@med.cornell.edu; ole2001@med.cornell.edu RI Sboner, Andrea/C-6487-2008; OI Sboner, Andrea/0000-0001-6915-3070; Rubin, Mark/0000-0002-8321-9950 FU Early Detection Research Network [U01 CA 11275-07]; Prostate Cancer Foundation Young Investigator Award; National Science Foundation CAREER grant FX This study was funded by the Early Detection Research Network grant U01 CA 11275-07 (M.A.R.), the Prostate Cancer Foundation Young Investigator Award (H.B.), and the National Science Foundation CAREER grant (O.E.). NR 48 TC 25 Z9 26 U1 2 U2 6 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD APR PY 2013 VL 15 IS 4 BP 373 EP + DI 10.1593/neo.122146 PG 15 WC Oncology SC Oncology GA 219DO UT WOS:000324486000003 PM 23555183 ER PT J AU Salazar, G Yeddula, K Wicky, S Oklu, R Ganguli, S Waltman, AC Walker, TG Kalva, SP AF Salazar, Gloria Yeddula, Kalpana Wicky, Stephan Oklu, Ramhi Ganguli, Suvranu Waltman, Arthur C. Walker, Thomas G. Kalva, Sanjeeva P. TI Image-guided placement of port catheters: Is there an increased risk of infection if the port is immediately accessed and used? SO JOURNAL OF VASCULAR ACCESS LA English DT Article DE Catheter-related infection; Central venous catheterization; Chemotherapy; Interventional radiology; Ports; Vascular access ID CENTRAL VENOUS ACCESS AB Purpose: To compare complication rates in patients who have port-a-catheters inserted and left accessed for immediate use and those who have ports inserted but not accessed. Methods: In this retrospective, IRB-approved study, medical records of patients who received a port catheter between 9/2009 and 2/2010 were reviewed. The data collected included patient demographics, diagnosis, procedure and complications. The patients were categorized into two groups: accessed (patients in whom the port was accessed with a Huber needle for immediate intravenous use and the patient left the procedure area with needle indwelling) and control (patients in whom the ports were not accessed). Complications were classified according to Society of Interventional Radiology guidelines. Results are given as mean +/- SD. Statistical analysis was performed with student t test and statistical significance was considered at P<.05. Results: A total of 467 ports were placed in 465 patients (Men: 206); 10.7% in the accessed group (n=50, age: 60 +/- 13.9) and 89.3% in the control group (n=417, age: 59 +/- 13.5). There were no statistically significant differences in patient demographics between the groups. The overall complication rate was 0.6% (n=3). Two complications (hematoma causing skin necrosis and thrombosis of the port) occurred in the control group and one (infection) in the accessed group. Infection rates after procedures were 2% (1/50) in the accessed group and 0% (0/417) in the control group. There was no statistically significant difference in overall complication (P=.1) and infection (P=.1) rates among the groups. Conclusions: Leaving the port accessed immediately after placement does not increase the risk of infection or other complications. C1 [Salazar, Gloria; Yeddula, Kalpana; Wicky, Stephan; Oklu, Ramhi; Ganguli, Suvranu; Waltman, Arthur C.; Walker, Thomas G.; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Salazar, G (reprint author), Massachusetts Gen Hosp, 55 Fruit St GRB 293, Boston, MA 02114 USA. EM gmsalazar@partners.org NR 10 TC 0 Z9 0 U1 0 U2 2 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1129-7298 J9 J VASC ACCESS JI J. Vasc. Access PD APR-JUN PY 2013 VL 14 IS 2 BP 170 EP 174 DI 10.5301/jva.5000110 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 210UQ UT WOS:000323860600013 PM 23080333 ER PT J AU Walter, J Tirosh, I Frugoni, F Lee, YN Lo, M Notarangelo, LD Dunham, J Pillai, S Luning-Prak, N AF Walter, Jolan Tirosh, Irit Frugoni, Francesco Lee, Yu Nee Lo, Mindy Notarangelo, Luigi D. Dunham, Jonathan Pillai, Shiv Luning-Prak, Nina TI LUPUS PATIENT WITH IMPAIRED RECEPTOR EDITING HAS HETEROZYGOUS RAG2 MUTATION SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 [Walter, Jolan] MassGen Hosp Children, Dept Pediat, Div Allergy Immunol, Boston, MA USA. [Walter, Jolan; Tirosh, Irit; Frugoni, Francesco; Lee, Yu Nee; Lo, Mindy] Boston Childrens Hosp, Boston, MA USA. [Notarangelo, Luigi D.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Dunham, Jonathan; Luning-Prak, Nina] Univ Penn, Philadelphia, PA 19104 USA. [Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2013 VL 33 IS 3 BP 682 EP 682 PG 1 WC Immunology SC Immunology GA 201EO UT WOS:000323123700047 ER PT J AU Walker, MA Slate, N Lax, T Alejos, A Volpi, S Sweetser, DA Sims, KB Walter, J AF Walker, Melissa A. Slate, Nancy Lax, Timothy Alejos, Alexandra Volpi, Stefano Sweetser, David A. Sims, Katherine B. Walter, Jolan TI PREDISPOSITION TO INFECTION AND SIRS IN OXIDATIVE PHOSPHORYLATION DISORDERS: 8 YEARS' EXPERIENCE IN A NEW ENGLAND COHORT FOLLOWED AT MASSACHUSETTS GENERAL HOSPITAL AND PARTNERS AFFLIATES SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 [Walker, Melissa A.; Slate, Nancy; Sweetser, David A.] MassGen Hosp Children, Boston, MA USA. [Lax, Timothy] Masschusetts Gen Hosp, Boston, MA USA. [Alejos, Alexandra] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Volpi, Stefano] Childrens Hosp, Boston, MA 02115 USA. [Sims, Katherine B.] MassGen Hosp Children, Div Neurol, Dept Pediat, Boston, MA USA. [Walter, Jolan] MassGen Hosp Children, Div Allergy Immunol, Dept Pediat, Boston, MA USA. RI Volpi, Stefano/O-3717-2014 OI Volpi, Stefano/0000-0002-7129-868X NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2013 VL 33 IS 3 BP 683 EP 683 PG 1 WC Immunology SC Immunology GA 201EO UT WOS:000323123700049 ER PT J AU Farough, S Walker, MA Canapari, CA Van Cleave, J Slate, N Verbsky, JW Sweetser, DA Sims, KB Walter, J AF Farough, Samira Walker, Melissa A. Canapari, Craig A. Van Cleave, Jeanne Slate, Nancy Verbsky, James W. Sweetser, David A. Sims, Katherine B. Walter, Jolan TI IMMUNE DYSFUNCTION WITH COENZYME Q10 DEFICIENCY IMPROVES AFTER COENZYME Q10 REPLACEMENT IN A FOUR YEAR-OLD CHILD WITH RECURRENT INFECTIONS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 [Farough, Samira; Canapari, Craig A.; Walter, Jolan] MassGen Hosp Children, Dept Pediat, Div Pulm Allergy Immunol, Boston, MA USA. [Walker, Melissa A.; Van Cleave, Jeanne; Slate, Nancy; Sweetser, David A.] MassGen Hosp Children, Boston, MA USA. [Verbsky, James W.] Med Coll Wisconsin, Dept Pediat, Div Rheumatol, Milwaukee, WI 53226 USA. [Sims, Katherine B.] MassGen Hosp Children, Div Neurol, Dept Pediat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2013 VL 33 IS 3 BP 684 EP 685 PG 2 WC Immunology SC Immunology GA 201EO UT WOS:000323123700053 ER PT J AU Lax, T Torgerson, TR Schneider, L Sims, KB Shah, U Friedmann, A Walter, J AF Lax, Timothy Torgerson, Troy R. Schneider, Lynda Sims, Katherine B. Shah, Uzma Friedmann, Alison Walter, Jolan TI IMMUNE DYSREGULATION, TELOMERE SHORTENING, AND LIVER DISEASE IN A PEDIATRIC PATIENT: A THERAPEUTIC DILEMMA SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 [Lax, Timothy] Masschusetts Gen Hosp, Boston, MA USA. [Torgerson, Troy R.] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA. [Schneider, Lynda] Boston Childrens Hosp, Dept Pediat, Div Allergy Immunol, Boston, MA USA. [Sims, Katherine B.] MassGen Hosp Children, Dept Pediat, Div Neurol, Boston, MA USA. [Shah, Uzma] MassGen Hosp Children, PediatricDept Pediat, Div Gastroenterol & Nutr, Boston, MA USA. [Friedmann, Alison] MassGen Hosp Children, Dept Pediat, Boston, MA USA. [Walter, Jolan] MassGen Hosp Children, Dept Pediat, Div Pulm Allergy Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD APR PY 2013 VL 33 IS 3 BP 685 EP 685 PG 1 WC Immunology SC Immunology GA 201EO UT WOS:000323123700055 ER PT J AU Basu, P Siriki, R Shah, NJ Farhat, S Mittimani, K Atluri, S Rahaman, M Brown, RS AF Basu, P. Siriki, R. Shah, N. J. Farhat, S. Mittimani, K. Atluri, S. Rahaman, M. Brown, R. S., Jr. TI EFFECT OF N ACETYLCYSTEINE (NAC) IN HYPOXIA INDUCED LIVER INJURY (HILI) - A RANDOMIZED PLACEBO CONTROL CLINICAL TRIAL SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT International Liver Congress / 48th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 24-28, 2013 CL Amsterdam, NETHERLANDS SP European Assoc Study Liver (EASL) C1 [Basu, P.; Farhat, S.; Brown, R. S., Jr.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Basu, P.; Siriki, R.; Mittimani, K.; Atluri, S.; Rahaman, M.] Forest Hills Hosp, Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, N. J.] Mt Sinai Sch Med, James J Peters VA Med Ctr, New York, NY USA. EM ravisiriki@gmail.com 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 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2013 VL 58 SU 1 MA 358 BP S148 EP S148 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199GQ UT WOS:000322983000359 ER PT J AU Basu, PP Siriki, R Shah, NJ Farhat, S Mittimani, K Atluri, S Rahaman, M Brown, RS AF Basu, P. P. Siriki, R. Shah, N. J. Farhat, S. Mittimani, K. Atluri, S. Rahaman, M. Brown, R. S., Jr. TI ROMIPLOSTIM'S EFFECT TO OPTIMIZE SVR WITH TELAPRAVIR, RIBAVIRIN, AND PEG INTERFERON-alfa 2a IN THROMBOCYTOPENIC CIRRHOTICS WITH CHRONIC HEPATITIS C. RESTRAINT C- PLACEBO RCT SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT International Liver Congress / 48th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 24-28, 2013 CL Amsterdam, NETHERLANDS SP European Assoc Study Liver (EASL) C1 [Basu, P. P.; Farhat, S.; Brown, R. S., Jr.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Basu, P. P.; Siriki, R.; Mittimani, K.; Atluri, S.; Rahaman, M.] Forest Hills Hosp, Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, N. J.] James J Peters VA Med Ctr, Mt Sinai Sch Med, New York, NY USA. EM ravisiriki@gmail.com 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 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2013 VL 58 SU 1 MA 906 BP S373 EP S374 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199GQ UT WOS:000322983001168 ER PT J AU Basu, PP Siriki, R Shah, NJ Farhat, S Mittimani, K Atluri, S Rahaman, M Brown, RS AF Basu, P. P. Siriki, R. Shah, N. J. Farhat, S. Mittimani, K. Atluri, S. Rahaman, M. Brown, R. S., Jr. TI TELAPREVIR WITH ADJUSTED DOSE OF RIBAVIRIN IN NAIVE CHC-G1: EFFICACY AND TREATMENT IN CHC IN HEMODIALYSIS POPULATION. TARGET C (RCT) SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT International Liver Congress / 48th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 24-28, 2013 CL Amsterdam, NETHERLANDS SP European Assoc Study Liver (EASL) C1 [Basu, P. P.; Farhat, S.; Brown, R. S., Jr.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Basu, P. P.; Siriki, R.; Mittimani, K.; Atluri, S.; Rahaman, M.] Forest Hills Hosp, Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, N. J.] Mt Sinai Sch Med, James J Peters VA Med Ctr, New York, NY USA. EM basu.patrick@gmail.com NR 0 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2013 VL 58 SU 1 MA 67 BP S30 EP S31 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199GQ UT WOS:000322983000068 ER PT J AU Jon, AF Khan, AN Cheema, AR Karellas, A Malik, Z Khosa, F Welty, FK Clouse, ME AF Jon, A. F. Khan, A. N. Cheema, A. R. Karellas, A. Malik, Z. Khosa, F. Welty, F. K. Clouse, M. E. TI QUANTIFICATION OF LIVER FAT USING NON-CONTRAST CT: COMPARISON OF LIVER/SPLEEN RATIO (CTL/S), LIVER-SPLEEN DIFFERENCE (CTL-T) WITH LIVER FAT PERCENTAGE (CTLFP) SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT International Liver Congress / 48th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 24-28, 2013 CL Amsterdam, NETHERLANDS SP European Assoc Study Liver (EASL) C1 [Jon, A. F.] Harvard Univ, Beth Israel Deaconness Med Ctr, Boston, MA 02115 USA. [Khan, A. N.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. [Cheema, A. R.; Malik, Z.; Welty, F. K.; Clouse, M. E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Karellas, A.] Univ Massacheusetts, Med Ctr, Worcester, MA USA. [Khosa, F.] Emory Univ, Med Ctr, Atlanta, GA 30322 USA. EM mclouse@bidmc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2013 VL 58 SU 1 MA 1324 BP S534 EP S534 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199GQ UT WOS:000322983001583 ER PT J AU Mohanty, A Erqou, S Butt, AA AF Mohanty, A. Erqou, S. Butt, A. A. TI ERYTHROPOIETIN USE FOR THERAPY ASSOCIATED ANEMIA IN HEPATITIS C VIRUS INFECTION AND RISK OF MORTALITY SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT International Liver Congress / 48th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY APR 24-28, 2013 CL Amsterdam, NETHERLANDS SP European Assoc Study Liver (EASL) C1 [Mohanty, A.; Erqou, S.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Butt, A. A.] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA USA. [Butt, A. A.] VA Pittsburgh Healthcare Syst, Div Infect Dis, Internal Med, Pittsburgh, PA USA. [Butt, A. A.] Sheikh Khalifa Med City, Internal Med, Abu Dhabi, U Arab Emirates. EM mohantya@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2013 VL 58 SU 1 MA 478 BP S196 EP S196 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 199GQ UT WOS:000322983000479 ER PT J AU Alvarez-Breckenridge, CA Yu, JH Caligiuri, MA Chiocca, EA AF Alvarez-Breckenridge, Christopher A. Yu, Jianhua Caligiuri, Michael A. Chiocca, E. Antonio TI Uncovering a novel mechanism whereby NK cells interfere with glioblastoma virotherapy SO ONCOIMMUNOLOGY LA English DT Article DE brain tumor; cancer; glioblastoma; innate immunity; oncolytic virus ID VESICULAR STOMATITIS-VIRUS; GLIOMA VIROTHERAPY; SUPPRESSION; RESPONSES; INNATE; POTENCY AB Despite initial promising results, the success of clinical trials testing oncolytic viruses in glioblastoma patients has been limited. Innate immunity appears to be one among several barriers against successful viral oncolysis. Recent findings suggest a mechanism by which natural killer cells limit the efficacy of oncolytic viruses via natural cytotoxicity receptors. C1 [Alvarez-Breckenridge, Christopher A.] Ohio State Univ, Med Ctr, Med Scientist Training Program, Columbus, OH 43210 USA. [Alvarez-Breckenridge, Christopher A.; Chiocca, E. Antonio] Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, Columbus, OH 43210 USA. [Yu, Jianhua; Caligiuri, Michael A.; Chiocca, E. Antonio] Ohio State Univ, Med Ctr, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Chiocca, E. Antonio] Harvard Univ, Brigham & Womens Hosp, Dept Neurosurg, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, Columbus, OH 43210 USA. EM eachiocca@partners.org FU NCI NIH HHS [R01 CA155521] NR 10 TC 6 Z9 6 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 J9 ONCOIMMUNOLOGY JI OncoImmunology PD APR 1 PY 2013 VL 2 IS 4 AR e23658 DI 10.4161/onci.23658 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 193NJ UT WOS:000322566200016 PM 23734319 ER PT J AU Waldron, TJ Quatromoni, JG Karakasheva, TA Singhal, S Rustgi, AK AF Waldron, Todd J. Quatromoni, Jon G. Karakasheva, Tatiana A. Singhal, Sunil Rustgi, Anil K. TI Myeloid derived suppressor cells: Targets for therapy SO ONCOIMMUNOLOGY LA English DT Article DE Myeloid derived suppressor cells; docetaxol; RNA aptamer; CpG oligodeoxynucleotides (ODN); cyclophosphamide; gemcitabine; curcumin ID TUMOR-BEARING HOST; NITRIC-OXIDE SYNTHASE; CD8(+) T-CELLS; CANCER-PATIENTS; IMMUNOSUPPRESSIVE ACTIVITY; ESTABLISHED TUMORS; ANTITUMOR IMMUNITY; EQUILIBRIUM STATE; POOR SURVIVAL; OCCULT CANCER AB The goal of achieving measurable response with cancer immunotherapy requires counteracting the immunosuppressive characteristics of tumors. One of the mechanisms that tumors utilize to escape immunosurveillance is the activation of myeloid derived suppressor cells (MDSCs). Upon activation by tumor-derived signals, MDSCs inhibit the ability of the host to mount an anti-tumor immune response via their capacity to suppress both the innate and adaptive immune systems. Despite their relatively recent discovery and characterization, anti-MDSC agents have been identified, which may improve immunotherapy efficacy. C1 [Waldron, Todd J.; Karakasheva, Tatiana A.; Rustgi, Anil K.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Waldron, Todd J.; Karakasheva, Tatiana A.; Rustgi, Anil K.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Quatromoni, Jon G.; Singhal, Sunil] Hosp Univ Penn, Dept Surg, Div Thorac Surg, Sch Med, Philadelphia, PA 19104 USA. [Singhal, Sunil] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. [Rustgi, Anil K.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Rustgi, AK (reprint author), Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. EM anil2@mail.med.upenn.edu FU National Institutes of Health/NCI [P01-CA098101, U01-CA14305603]; National Institutes of Health/NIDDK [T32-DK007066]; National Institutes of Health [F32-CA162719]; National Institutes of Health/NIDDK Center for Molecular Studies in Digestive and Liver Diseases [P30-DK050306]; American Cancer Society [RP-10-033-01-CCE] FX This work was supported by the National Institutes of Health/NCI grant P01-CA098101 (AKR, TW), National Institutes of Health/NCI grant U01-CA14305603 (AKR), National Institutes of Health/NIDDK (T32-DK007066) (TW), National Institutes of Health (F32-CA162719) (TW), National Institutes of Health/NIDDK Center for Molecular Studies in Digestive and Liver Diseases (P30-DK050306), and American Cancer Society (RP-10-033-01-CCE). We are grateful for members of the Rustgi and Singhal labs for discussions. NR 89 TC 24 Z9 24 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 J9 ONCOIMMUNOLOGY JI OncoImmunology PD APR 1 PY 2013 VL 2 IS 4 AR e24117 DI 10.4161/onci.24117 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA 193NJ UT WOS:000322566200024 PM 23734336 ER PT J AU McKee, AC AF McKee, Ann C. TI Interneuronal spreading of tau pathology in chronic traumatic encephalopathy SO PRION LA English DT Meeting Abstract DE chronic traumatic encephalopathy; tau protein; traumatic brain injury ID PROPAGATION; DISEASE C1 [McKee, Ann C.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. NR 8 TC 0 Z9 0 U1 1 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD APR-MAY PY 2013 VL 7 SU S BP 9 EP 9 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202LL UT WOS:000323217500022 ER PT J AU Silva, TB Mauad, EC Carvalho, AL Jacobs, LA Shulman, LN AF Silva, T. B. Mauad, E. C. Carvalho, A. L. Jacobs, L. A. Shulman, L. N. TI Difficulties in implementing an organized screening program for breast cancer in Brazil with emphasis on diagnostic methods SO RURAL AND REMOTE HEALTH LA English DT Article DE Brazil; breast cancer; community health systems; diagnosis; screening; symptoms ID SERVICES TASK-FORCE; RANDOMIZED-TRIAL; UNITED-STATES; HEALTH-CARE; MAMMOGRAPHY; WOMEN; KNOWLEDGE; COUNTRIES; PERFORMANCE; PREDICTORS AB Introduction: Breast cancer is the most common type of cancer among women, and the leading cause of cancer deaths worldwide. Among early detection methods, screening by mammography has been used in most developed countries as gold standard. The goal of this study was to evaluate the difficulties and opportunities in implementing breast cancer screening in Brazil, with an emphasis on the diagnostic methods used according to stage distribution. Methods: Between 2007 and 2009, 248 women were diagnosed with breast cancer in the Barretos region. Most of these were interviewed in their homes using a questionnaire with sociodemographic and preventive breast cancer screening questions. All other data were obtained from Barretos Cancer Hospital (BCH) medical records. Results: The screening program conducted by BCH was responsible for 46.1% of diagnosed cases, with 30.1% of these referred from the private system and 23.8% from the public system. Among asymptomatic women screened by the BCH Screening Program 70.8% had clinical stage 0-I disease, compared with 58.1% in the private and 50% in the public systems. Monthly breast self-examination was reported by 48.5% of the women. Clinical breast examinations were regularly performed by 88.9% of gynecologists in the private and 40.7% in the public health systems. Only 5.6% of the women reported difficulty in accessing mammography and this was most frequently due to fear of the disease or lack of knowledge about mammography in asymptomatic women. Conclusion: This breast cancer screening program resulted in a substantial number of patients presenting with clinical stage (CS) 0-I disease. The success of this program was due to intensive community interventions, free mammography, and the availability of health care and mammography close to patients' homes. C1 [Silva, T. B.; Mauad, E. C.; Carvalho, A. L.] Barretos Canc Hosp, Dept Prevencao, Sao Paulo, Brazil. [Jacobs, L. A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Shulman, L. N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shulman, L. N.] Harvard Univ, Sch Med, Boston, MA USA. RP Silva, TB (reprint author), Barretos Canc Hosp, Dept Prevencao, Sao Paulo, Brazil. RI Carvalho, Andre/C-1185-2011; Carvalho, Andre/S-7053-2016 OI Carvalho, Andre/0000-0001-7214-6402; Carvalho, Andre/0000-0001-7214-6402 NR 45 TC 5 Z9 5 U1 1 U2 9 PU AUSTRALIAN RURAL HEALTH EDUC NETWORK PI DEAKIN WEST PA PO BOX 242, DEAKIN WEST, ACT 2600, AUSTRALIA SN 1445-6354 J9 RURAL REMOTE HEALTH JI Rural Remote Health PD APR-JUN PY 2013 VL 13 IS 2 AR 2321 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 190UF UT WOS:000322365600017 PM 23597169 ER PT J AU Shimizu, M Zaninotto, G Nagata, K Graham, DY Lauwers, GY AF Shimizu, Michio Zaninotto, Giovanni Nagata, Koji Graham, David Y. Lauwers, Gregory Y. TI Esophageal squamous cell carcinoma with special reference to its early stage SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE Early esophageal squamous cell carcinoma; Squamous intraepithelial neoplasia; Endoscopic mucosal resection (EMR); Endoscopic submucosal dissection (ESD); Chromoendoscopy; Narrow band imaging (NBI); Esophagectomy ID ENDOSCOPIC SUBMUCOSAL DISSECTION; LYMPH-NODE DISSECTION; BARRETTS-ESOPHAGUS; INTRAEPITHELIAL NEOPLASIA; MUCOSAL RESECTION; CLINICAL-OUTCOMES; CANCER; RISK; ADENOCARCINOMA; DYSPLASIA AB The term 'early squamous cell carcinoma of the oesophagus', which was previously restricted to superficial carcinoma with no lymph node metastasis, now encompasses intramucosal carcinoma regardless of the nodal status. Such lesions are rare in Western countries, where the experience is limited. In recent years, the development and greater use of chromoendoscopy and narrow band imaging (NBI), both of which facilitate the evaluation of mucosal morphology, have played an important role in the detection of early esophageal squamous cell carcinoma. In addition, the techniques and indications of endoscopic resection (mucosal resection [EMR] and mucosal dissection [ESD]) are still being refined. In the present article, we will discuss the clinical and pathologic features of esophageal early squamous cell carcinoma, as well as the epidemiology and aetiology of esophageal cancer in general. In addition, we will provide a therapeutic decision tree taking into account endoscopic and surgical modalities as they apply to early esophageal squamous cell carcinoma. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Shimizu, Michio; Nagata, Koji] Saitama Med Univ, Saitama Int Med Ctr, Dept Pathol, Hidaka City, Saitama 3501298, Japan. [Zaninotto, Giovanni] Univ Padua, Sch Med, Dept Surg Gastroenterol & Oncol, Padua, Italy. [Graham, David Y.] Michael E DeBakey VA Med Ctr, Dept Med, Houston, TX USA. [Graham, David Y.] Baylor Coll Med, Houston, TX 77030 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Div Surg Pathol, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. RP Shimizu, M (reprint author), Saitama Med Univ, Saitama Int Med Ctr, Dept Pathol, 1397-1 Yamane, Hidaka City, Saitama 3501298, Japan. EM shimizu@saitama-med.ac.jp NR 77 TC 13 Z9 19 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6918 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD APR PY 2013 VL 27 IS 2 BP 171 EP 186 DI 10.1016/j.bpg.2013.03.010 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187DC UT WOS:000322096100003 PM 23809239 ER PT J AU Jokhi, V Ashley, J Nunnari, J Noma, A Ito, N Wakabayashi-Ito, N Moore, MJ Budnik, V AF Jokhi, Vahbiz Ashley, James Nunnari, John Noma, Akiko Ito, Naoto Wakabayashi-Ito, Noriko Moore, Melissa J. Budnik, Vivian TI Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope SO CELL REPORTS LA English DT Article ID PROTEIN COMPLEXES; SYNAPSE FORMATION; WNT; PLASTICITY; MECHANISM; WINGLESS; ATPASES; COMMON; EXPORT; APKC AB A previously unrecognized mechanism through which large ribonucleoprotein (megaRNP) granules exit the nucleus is by budding through the nuclear envelope (NE). This mechanism is akin to the nuclear egress of herpes-type viruses and is essential for proper synapse development. However, the molecular machinery required to remodel the NE during this process is unknown. Here, we identify Torsin, an AAA-ATPase that in humans is linked to dystonia, as a major mediator of primary megaRNP envelopment during NE budding. In torsin mutants, megaRNPs accumulate within the perinuclear space, and the messenger RNAs contained within fail to reach synaptic sites, preventing normal synaptic protein synthesis and thus proper synaptic bouton development. These studies begin to establish the cellular machinery underlying the exit of megaRNPs via budding, offer an explanation for the "nuclear blebbing" phenotype found in dystonia models, and provide an important link between Torsin and the synaptic phenotypes observed in dystonia. C1 [Jokhi, Vahbiz; Ashley, James; Nunnari, John; Budnik, Vivian] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Worcester, MA 01605 USA. [Noma, Akiko; Moore, Melissa J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Dept Biochem & Mol Pharmacol,RNA Inst, Worcester, MA 01605 USA. [Noma, Akiko; Moore, Melissa J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Dept Biochem & Mol Pharmacol,Neuro Therapeut Inst, Worcester, MA 01605 USA. [Ito, Naoto; Wakabayashi-Ito, Noriko] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol & Radiol, Sch Med, Boston, MA 02114 USA. [Ito, Naoto; Wakabayashi-Ito, Noriko] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. RP Budnik, V (reprint author), Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Worcester, MA 01605 USA. EM vivian.budnik@umassmed.edu FU University of Massachusetts Medical School Electron Microscopy Facility; National Institutes of Health [R01 NS063228] FX We thank Drs. Xandra Breakefield, Mary Munson, Reid Gilmore, Emiliano Ricci, and members of the Budnik lab for helpful comments on the manuscript and discussions. We would like to thank the University of Massachusetts Medical School Electron Microscopy Facility for support in our ultrastructural studies and the Vienna Drosophila RNAi facility for providing the Torsin-RNAi line. We also thank Drs. Pamela Gayer, Yosef Gruenbaum, Georg Krohne, and Gertrud Schupbach for the generous gift of antibodies. This work was supported by National Institutes of Health grant R01 NS063228 (to V.B.). M.J.M. is a Howard Hughes Medical Institute investigator. V.J. carried out most of the experiments and contributed intellectually to the project. J.A. carried out some of the ultrastructural studies and contributed intellectually to the project and manuscript writing. J.N. carried out most the ultrastructural experiments. A.N. performed supporting FISH in wild-type and mutant larvae. N.I. and N.W.-I. provided the unpublished TorsinDelta E fly strain and contributed to discussions. M.J.M. provided critical intellectual input and helped write the manuscript. V.B. directed the project and wrote the manuscript. NR 29 TC 51 Z9 51 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD APR PY 2013 VL 3 IS 4 BP 988 EP 995 DI 10.1016/j.celrep.2013.03.015 PG 8 WC Cell Biology SC Cell Biology GA 184NH UT WOS:000321897100003 PM 23583177 ER PT J AU Barker, CF Markmann, JF AF Barker, Clyde F. Markmann, James F. TI Historical Overview of Transplantation SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID DONOR BONE-MARROW; SKIN HOMOGRAFTS; HUMAN-KIDNEY; RENAL HOMOTRANSPLANTATION; IMMUNOLOGICAL-TOLERANCE; CYCLOSPORIN-A; CLINICAL TRANSPLANTATION; ANTILYMPHOCYTIC-SERUM; IDENTICAL-TWINS; THORACIC-DUCT AB Except for legends and claims of miracles, most histories of transplantation cover only the last 60 years because there were no earlier successes. However, the story of even this era has been documented in such rich detail that a full account would fill several volumes. Thus, this brief summary must be limited to highly selected "landmarks." Some landmarks had an immediate impact, but the importance of others went unrecognized for decades. Some findings that deserved landmark status were overlooked or forgotten, whereas others of no biological significance had major impact. Placing these events in perspective is challenging. Several of transplantation's pioneers are still alive, and most of the others are within living memory. Virtually all of them have produced their own accounts. For the most part, they agree on what the "landmarks" are, but their differences in emphasis and perspective make an interesting story. C1 [Barker, Clyde F.] Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Barker, Clyde F.; Markmann, James F.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. [Barker, Clyde F.; Markmann, James F.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. RP Barker, CF (reprint author), Hosp Univ Penn, Dept Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. EM clyde.barker@uphs.upenn.edu FU NIAID NIH HHS [R01 AI057851] NR 119 TC 2 Z9 2 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD APR PY 2013 VL 3 IS 4 AR a014977 DI 10.1101/cshperspect.a014977 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 187ZK UT WOS:000322160300001 PM 23545575 ER PT J AU Bauman, J Langer, C Quon, H Algazy, K Lin, A Desai, A Mutale, F Weiss, J AF Bauman, Jessica Langer, Corey Quon, Harry Algazy, Kenneth Lin, Alexander Desai, Arati Mutale, Faith Weiss, Jared TI Induction chemotherapy with cetuximab, carboplatin and paclitaxel for the treatment of locally advanced squamous cell carcinoma of the head and neck SO EXPERIMENTAL AND THERAPEUTIC MEDICINE LA English DT Article DE locally advanced squamous cell carcinoma of the head and neck; head and neck cancer; induction chemotherapy; chemoradiotherapy ID HUMAN-PAPILLOMAVIRUS; PLUS CETUXIMAB; CANCER; SURVIVAL; FLUOROURACIL; RADIOTHERAPY; CISPLATIN; DOCETAXEL; CHEMORADIOTHERAPY; RADIATION AB Although controversy exists in the management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), clinicians often use induction chemotherapy for treatment of the most advanced cases. One promising regimen combines weekly cetuximab (400 mg/m(2) loading dose followed by 250 mg/m(2)) with carboplatin (AUC of 2) and paclitaxel (90 mg/m(2)). We retrospectively evaluated patients treated with this regimen prior to definitive chemoradiation or surgery between May 2008 and December 2011. The primary endpoint used for this retrospective analysis was feasibility. Thirty consecutive, unselected patients were included. Median follow-up was 13.7 months (range, 5.0-38.7 months). All but one patient had stage IV SCCHN. Dose intensity was high for carboplatin (92%), paclitaxel (93%) and cetuximab (85%). Grade 3-4 toxicities occurred in <7% of the study population and were limited to rash, neutropenia and infusion reactions. Response rate (RR) to induction chemotherapy was 97% (30% complete response, 67% partial response). All patients completed subsequent chemoradiotherapy or surgery. Nineteen patients (63%) demonstrated a complete response and 11 patients (37%) demonstrated a partial response. Median overall survival and progression-free survival data are not yet mature. The RR to therapy in our off-protocol experience is at least comparable to that observed in the two phase II studies of this regimen and appears superior to that observed with docetaxel, cisplatin and fluorouracil (TPF). C1 [Bauman, Jessica] Dana Farber Canc Inst, Div Hematol & Oncol, Boston, MA 02115 USA. [Langer, Corey; Algazy, Kenneth; Desai, Arati; Mutale, Faith] Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA. [Quon, Harry] Johns Hopkins Univ, Dept Radiat Oncol, Baltimore, MD 21205 USA. [Lin, Alexander] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Weiss, Jared] Univ N Carolina, Div Hematol & Oncol, Chapel Hill, NC 27599 USA. RP Weiss, J (reprint author), Univ N Carolina, 170 Manning Dr,Campus Box 7305, Chapel Hill, NC 27599 USA. EM jared_weiss@med.unc.edu FU Celgene; GSK; Astellas FX Dr Corey Langer is currently a member of the Advisory Boards of BMS, Imclone and Lilly, and a former member of their Speaker's Bureaus. Dr Jared Weiss has received research funding from Celgene, GSK and Astellas. NR 24 TC 5 Z9 6 U1 1 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-0981 J9 EXP THER MED JI Exp. Ther. Med. PD APR PY 2013 VL 5 IS 4 BP 1247 EP 1253 DI 10.3892/etm.2013.948 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 185AK UT WOS:000321937400053 PM 23599744 ER PT J AU Sykes, SM Scadden, DT AF Sykes, Stephen M. Scadden, David T. TI Modeling Human Hematopoietic Stem Cell Biology in the Mouse SO SEMINARS IN HEMATOLOGY LA English DT Article ID BONE-MARROW MICROENVIRONMENT; PROGENITOR CELLS; ENDOTHELIAL-CELLS; DEFINITIVE HEMATOPOIESIS; MYELODYSPLASTIC SYNDROME; DYSKERATOSIS-CONGENITA; COMMON PRECURSOR; DEFICIENT MICE; YOLK-SAC; IN-VIVO AB Hematopoietic stem cells (HSCs) have the immense task of supplying an organism with enough blood to sustain a lifespan. Much of what is known about how this scant population of cells can meet the varying demand of producing more than 10(11) cells per day comes from studies conducted in an animal that is a fraction of our size and lives roughly 1/30th of our lifespan. The differences in longevity can be expected to impose different demands on a cell essential for existence. It is therefore unsurprising that while the mouse has proven invaluable in defining the organizing principals of how hematopoiesis is governed, mediators of cell localization as well as a range of experimental methods, the differences in cell cycling, DNA repair and specific molecular features of HSCs in humans are evident and important. Here, the utility and drawbacks of the mouse as an experimental model for human HSC biology are discussed. Semin Hematol 50:92-100. (C) 2013 Published by Elsevier Inc. C1 [Sykes, Stephen M.] Fox Chase Canc Ctr, Res Inst, Philadelphia, PA 19111 USA. [Scadden, David T.] Harvard Univ, Ctr Regenerat Med, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst,Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Sykes, SM (reprint author), Fox Chase Canc Ctr, Res Inst, Immune Cell Dev & Host Def, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Stephen_Sykes@fccc.edu; David_Scadden@harvard.edu FU NCI NIH HHS [R00 CA158461]; NHLBI NIH HHS [R01 HL044851, U01 HL100402]; NIBIB NIH HHS [R01 EB014703]; NIDDK NIH HHS [R01 DK050234] NR 80 TC 4 Z9 4 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2013 VL 50 IS 2 BP 92 EP 100 DI 10.1053/j.seminhematol.2013.03.029 PG 9 WC Hematology SC Hematology GA 174NZ UT WOS:000321164000003 PM 24216169 ER PT J AU Arnstein, P Herr, K AF Arnstein, Paul Herr, Keela TI Risk Evaluation and Mitigation Strategies for Older Adults with Persistent Pain SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NONMALIGNANT PAIN; AMERICAN SOCIETY; OPIOID THERAPY; MEDICATION USE; POPULATION; MANAGEMENT; STATEMENT; OVERDOSE; BRAIN AB The U.S. Food and Drug Administration issued Risk Evaluation and Mitigation Strategies for certain analgesic agents, but all medicines for older adults warrant risk-reduction considerations. Although not all older adults have pain, a higher prevalence of persistent pain exists in this population. Nursing actions are needed to minimize the negative impact persistent pain, analgesic agents, or both have on physical, mental, and social functioning. Practices vary considerably, ranging from failing to use analgesic agents for older adults with considerable pain to exposing them to potentially life-threatening toxicities, overdoses, or drug interactions. Older adults tend to be more vulnerable to side effects and drug interactions due to differences in drug distribution, metabolism, and elimination; thus, vigilant assessment and monitoring is needed to mitigate risks whenever analgesic agents are used. This review delineates these vulnerabilities while informing clinicians of the strategies needed to promote safe, effective use of medications when treating pain in older adults. C1 [Arnstein, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herr, Keela] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. RP Arnstein, P (reprint author), Massachusetts Gen Hosp GRB 1034, 55 Fruit St, Boston, MA 02114 USA. EM pmarnstein@partners.org FU Connell Nursing Research Scholars Program at Massachusetts General Hospital FX The authors have disclosed no conflicts of interest, financial or otherwise. Dr. Arnstein acknowledges that this project was sponsored in part with support from the Connell Nursing Research Scholars Program at Massachusetts General Hospital. NR 44 TC 1 Z9 1 U1 1 U2 6 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD APR PY 2013 VL 39 IS 4 BP 56 EP + DI 10.3928/00989134-20130221-01 PG 11 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 164XG UT WOS:000320444800008 PM 23445186 ER PT J AU Ofman, P Khawaja, O Rahilly-Tierney, CR Peralta, A Hoffmeister, P Reynolds, MR Gaziano, JM Djousse, L AF Ofman, Peter Khawaja, Owais Rahilly-Tierney, Catherine R. Peralta, Adelqui Hoffmeister, Peter Reynolds, Mathew R. Gaziano, J. Michael Djousse, Luc TI Regular Physical Activity and Risk of Atrial Fibrillation A Systematic Review and Meta-analysis SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; epidemiology; physical exercise; risk factors ID ENDURANCE SPORT PRACTICE; CARDIOVASCULAR-DISEASE; TASK-FORCE; FOLLOW-UP; FLUTTER; MEN; PREVENTION; MANAGEMENT; EXERCISE; ADULTS AB Background-Although previous studies have suggested that competitive athletes have a higher risk of atrial fibrillation than the general population, limited and inconsistent data are available on the association between regular physical activity and the risk of atrial fibrillation. Methods and Results-A systematic, comprehensive literature search was performed using MEDLINE, EMBASE, and COCHRANE until 2011. Extracted data from the eligible studies were meta-analyzed using fixed effects model. Four studies, which included 95 526 subjects, were eligible for meta-analysis. For all of the studies included, the extreme groups (ie, maximum versus minimal amount of physical activity) were used for the current analyses. The total number of participants belonging to the extreme groups was 43 672. The pooled odds ratio (95% confidence interval) for atrial fibrillation among regular exercisers was 1.08 (0.97-1.21). Conclusions-Our data do not support a statistically significant association between regular physical activity and increased incidence of atrial fibrillation. C1 [Ofman, Peter; Peralta, Adelqui; Hoffmeister, Peter; Reynolds, Mathew R.; Gaziano, J. Michael] Harvard Univ, Sch Med, Div Cardiol, VA Boston Healthcare Syst, Boston, MA USA. [Ofman, Peter; Rahilly-Tierney, Catherine R.; Gaziano, J. Michael; Djousse, Luc] Harvard Univ, Sch Med, Div Aging, Dept Med, Boston, MA 02115 USA. [Rahilly-Tierney, Catherine R.; Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Ofman, Peter; Rahilly-Tierney, Catherine R.; Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA. [Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA USA. [Khawaja, Owais] Dartmouth Hitchcock Med Ctr, Sect Crit Care, Lebanon, NH 03766 USA. RP Ofman, P (reprint author), VA Boston Healthcare Syst, Dept Cardiol, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Peter.Ofman@VA.gov RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 NR 21 TC 40 Z9 40 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD APR PY 2013 VL 6 IS 2 BP 252 EP 256 DI 10.1161/CIRCEP.113.000147 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167XB UT WOS:000320667700011 PM 23515264 ER PT J AU Stengel, A Rivier, J Tache, Y AF Stengel, Andreas Rivier, Jean Tache, Yvette TI Modulation of the adaptive response to stress by brain activation of selective somatostatin receptor subtypes SO PEPTIDES LA English DT Review DE ACTH; Anxiety; Autonomic nervous system; Catecholamines; CRF; Food intake; Gastrointestinal motility; Octreotide; ODT8-SST; Stress ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; COLONIC MOTOR FUNCTION; GROWTH-HORMONE SECRETION; FOOD-INTAKE; INDUCED INHIBITION; MESSENGER-RNA; NEUROPEPTIDE-Y; CENTRAL CRF; C-FOS AB Somatostatin-14 was discovered in 1973 in the hypothalamus as a peptide inhibiting growth hormone release. Somatostatin interacts with five receptor subtypes (sst(1-5)) which are widely distributed in the brain with a distinct, but overlapping, expression pattern. During the last few years, the development of highly selective peptide agonists and antagonists provided new insight to characterize the role of somatostatin receptor subtypes in the pleiotropic actions of somatostatin. Recent evidence in rodents indicates that the activation of selective somatostatin receptor subtypes in the brain blunts stress-corticotropin-releasing factor (CRF) related ACTH release (sst(2/5)), sympathetic-adrenal activaton (sst(5)), stimulation of colonic motility (sst(1)), delayed gastric emptying (sst(5)), suppression of food intake (sst(2)) and the anxiogenic-like (sst(2)) response. These findings suggest that brain somatostatin signaling pathways may play an important role in dampening CRF-mediated endocrine, sympathetic, behavioral and visceral responses to stress. Published by Elsevier Inc. C1 [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90095 USA. [Stengel, Andreas; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Stengel, Andreas] Charite Med Ctr, Dept Med, Div Psychosomat Med, Berlin, Germany. [Stengel, Andreas] Charite Med Ctr, Dept Med, Obes Ctr Berlin, Berlin, Germany. [Stengel, Andreas] Univ Berlin, Berlin, Germany. [Rivier, Jean] Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU German Research Foundation [STE 1765/3-1]; Charite university [89441 176]; Sonnenfeld foundation; VA Research Career Scientist Award; VA Merit Award; NIH R01 [DK 33061, DK57238] FX A.S. received funding from the German Research Foundation (STE 1765/3-1) Charite university funding (89441 176) and an equipment grant of the Sonnenfeld foundation. Y.T. is in receipt of the VA Research Career Scientist Award, VA Merit Award and NIH R01grants DK 33061 and DK57238. J.R. is the Dr. Frederik Paulsen Chair in Neurosciences Professor. NR 109 TC 9 Z9 9 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD APR PY 2013 VL 42 BP 70 EP 77 DI 10.1016/j.peptides.2012.12.022 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 165OI UT WOS:000320492800010 PM 23287111 ER PT J AU Bacallado, S Favaro, S Trippa, L AF Bacallado, Sergio Favaro, Stefano Trippa, Lorenzo TI BAYESIAN NONPARAMETRIC ANALYSIS OF REVERSIBLE MARKOV CHAINS SO ANNALS OF STATISTICS LA English DT Article DE Reversibility; mixtures of Markov chains; reinforced random walks; Bayesian nonparametrics; species sampling; two-parameter Hoppe urn; molecular dynamics ID REINFORCED RANDOM-WALK AB We introduce a three-parameter random walk with reinforcement, called the (theta, alpha, beta) scheme, which generalizes the linearly edge reinforced random walk to uncountable spaces. The parameter beta smoothly tunes the (theta, alpha, beta) scheme between this edge reinforced random walk and the classical exchangeable two-parameter Hoppe urn scheme, while the parameters a and theta modulate how many states are typically visited. Resorting to de Finetti's theorem for Markov chains, we use the (theta, alpha, beta) scheme to define a nonparametric prior for Bayesian analysis of reversible Markov chains. The prior is applied in Bayesian nonparametric inference for species sampling problems with data generated from a reversible Markov chain with an unknown transition kernel. As a real example, we analyze data from molecular dynamics simulations of protein folding. C1 [Bacallado, Sergio] Stanford Univ, Dept Stat, Clark Ctr, Stanford, CA 94305 USA. [Favaro, Stefano] Univ Turin, Dept Econ & Stat, I-10134 Turin, Italy. Coll Carlo Alberto, Moncalieri, Italy. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Trippa, Lorenzo] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Bacallado, S (reprint author), Stanford Univ, Dept Stat, Clark Ctr, S296, Stanford, CA 94305 USA. EM sergiob@stanford.edu; stefano.favaro@unito.it; ltrippa@jimmy.harvard.edu FU NSF [DMS-09-00700]; European Research Council (ERC) through StG "N-BNP" [306406]; [NIH-R01-GM062868] FX Supported by Grant NIH-R01-GM062868 and NSF Grant DMS-09-00700.; Supported by the European Research Council (ERC) through StG "N-BNP" 306406. NR 28 TC 2 Z9 2 U1 0 U2 4 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0090-5364 J9 ANN STAT JI Ann. Stat. PD APR PY 2013 VL 41 IS 2 BP 870 EP 896 DI 10.1214/13-AOS1102 PG 27 WC Statistics & Probability SC Mathematics GA 165MO UT WOS:000320488200017 ER PT J AU Downes, J Dewhirst, FE Tanner, ACR Wade, WG AF Downes, Julia Dewhirst, Floyd E. Tanner, Anne C. R. Wade, William G. TI Description of Alloprevotella rava gen. nov., sp nov., isolated from the human oral cavity, and reclassification of Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov. SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID ACIDS AB Five strains of anaerobic, Gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group. Phylogenetic analysis of full-length 16S rRNA gene sequences showed that these strains represented a novel group within the family Prevotellaceae, and the most closely related species was Prevotella tannerae. P. tannerae and the novel taxon are deeply branched from the genus Prevotella, with sequence identities to the type strain of the type species of Prevotella, Prevotella melaninogenica, of 82.2 and 85.6%, respectively. The novel genus Alloprevotella gen. nov. is proposed to accommodate the novel species Alloprevotella rava gen. nov., sp. nov. and the previously named Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov. The type species is Alloprevotella tannerae. The type strain of Alloprevotella rava is 81/4-12(T) (=DSM 22548(T) =CCUG 58091(T)) and the type strain of Alloprevotella tannerae is ATCC 51259(T) =CCUG 34292(T) =CIP 104476(T) =NCTC 13073(T). Alloprevotella rava is weakly to moderately saccharolytic and produces moderate amounts of acetic acid and major amounts of succinic acid as end products of fermentation. Strains are sensitive to 20% bile and hydrolyse gelatin. The principal cellular long-chain fatty acids are anteiso-C-15:0, iso-C-15:0, C-16:0, iso-C-17:0 and iso-C-17:0 3-OH. The G+C content of the DNA of the type strain is 47 mol%. C1 [Downes, Julia; Wade, William G.] Kings Coll London, Inst Dent, London SE1 9RT, England. [Dewhirst, Floyd E.; Tanner, Anne C. R.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Wade, WG (reprint author), Kings Coll London, Inst Dent, Guys Campus, London SE1 9RT, England. EM william.wade@kcl.ac.uk OI Wade, William/0000-0003-2685-826X FU Guy's and St Thomas' Charity [R050724]; UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre; King's College London; National Institute for Dental Research [DE016937] FX This research was supported by a grant from the Guy's and St Thomas' Charity (ref. R050724). The authors acknowledge financial support from the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London. Investigators F. E. D., A. C. R. T. and W. G. W. were supported in part by National Institute for Dental Research grant DE016937. NR 15 TC 17 Z9 17 U1 0 U2 6 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD APR PY 2013 VL 63 BP 1214 EP 1218 DI 10.1099/ijs.0.041376-0 PN 4 PG 5 WC Microbiology SC Microbiology GA 155YF UT WOS:000319785700001 PM 22753527 ER PT J AU Wolfgang, WJ Passaretti, TV Jose, R Cole, J Coorevits, A Carpenter, AN Jose, S Van Landschoot, A Izard, J Kohlerschmidt, DJ Vandamme, P Dewhirst, FE Fisher, MA Musser, KA AF Wolfgang, William J. Passaretti, Teresa V. Jose, Reashma Cole, Jocelyn Coorevits, An Carpenter, Andrea N. Jose, Sherly Van Landschoot, Anita Izard, Jacques Kohlerschmidt, Donna J. Vandamme, Peter Dewhirst, Floyd E. Fisher, Mark A. Musser, Kimberlee A. TI Neisseria oralis sp nov., isolated from healthy gingival plaque and clinical samples SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID MICROBIOME; STRAINS; HYBRIDIZATION; LIKELIHOOD; DIVERSITY; ALGORITHM; SPECIMENS; SEQUENCES; ACCURATE; SKIN AB A polyphasic analysis was undertaken of seven independent isolates of Gram-negative cocci collected from pathological clinical samples from New York, Louisiana, Florida and Illinois and healthy subgingival plaque from a patient in Virginia, USA. The 16S rRNA gene sequence similarity among these isolates was 99.7-100%, and the closest species with a validly published name was Neisseria lactamica (96.9% similarity to the type strain). DNA-DNA hybridization confirmed that these isolates are of the same species and are distinct from their nearest phylogenetic neighbour, N. lactamica. Phylogenetic analysis of 16S and 23S rRNA gene sequences indicated that the novel species belongs in the genus Neisseria. The predominant cellular fatty acids were C-16:0, summed feature 3 (C-16:1 omega 7c and/or iso-C-15:0 2-OH) and C-18:1 omega 7c. The cellular fatty acid profile, together with other phenotypic characters, further supports the inclusion of the novel species in the genus Neisseria. The name Neisseria oralis sp. nov. (type strain 6332(T) =DSM 25276(T) =LMG 26725(T)) is proposed. C1 [Wolfgang, William J.; Passaretti, Teresa V.; Jose, Reashma; Cole, Jocelyn; Carpenter, Andrea N.; Jose, Sherly; Kohlerschmidt, Donna J.; Musser, Kimberlee A.] New York State Dept Hlth, Wadsworth Ctr, Bacteriol Lab, Albany, NY 12201 USA. [Wolfgang, William J.; Musser, Kimberlee A.] SUNY Albany, Dept Biomed Sci, Albany, NY 12201 USA. [Coorevits, An; Van Landschoot, Anita] Univ Coll Ghent, Dept Appl Engn Sci, Lab Biochem & Brewing, B-9000 Ghent, Belgium. [Coorevits, An; Van Landschoot, Anita; Vandamme, Peter] Univ Ghent, Dept Biochem & Microbiol, Lab Microbiol LM UGent, B-9000 Ghent, Belgium. [Izard, Jacques; Dewhirst, Floyd E.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Izard, Jacques; Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Fisher, Mark A.] Inst Clin & Expt Pathol, Salt Lake City, UT USA. [Fisher, Mark A.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. RP Wolfgang, WJ (reprint author), New York State Dept Hlth, Wadsworth Ctr, Bacteriol Lab, POB 22002, Albany, NY 12201 USA. EM wwolfgan@wadsworth.org RI Vandamme, Peter/B-7967-2009; OI Izard, Jacques/0000-0002-5904-5436; Wolfgang, William/0000-0003-1769-0215; Vandamme, Peter/0000-0002-5581-7937 FU University College Ghent; NIDCR [DE016937] FX The authors wish to thank the Wadsworth Center Applied Genomic Technologies Core and the Broad Institute of MIT and Harvard for sequencing, the Wadsworth Center Orphan Bacterium Collection for curation of the novel strains described in this study, Margo Cnockaert for assistance with the DNA hybridization studies and Dr Andrea Habura for helpful discussions relating to the phylogenetic analysis of the novel species. A. C. received a grant from the research fund of University College Ghent. F. E. D. and J. I. were supported by NIDCR grant DE016937. NR 26 TC 9 Z9 9 U1 0 U2 12 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD APR PY 2013 VL 63 BP 1323 EP 1328 DI 10.1099/ijs.0.041731-0 PN 4 PG 6 WC Microbiology SC Microbiology GA 155YF UT WOS:000319785700018 PM 22798652 ER PT J AU Lu, L Hannoush, RN Goess, BC Varadarajan, S Shair, MD Kirchhausen, T AF Lu, Lei Hannoush, Rami N. Goess, Brian C. Varadarajan, Shankar Shair, Matthew D. Kirchhausen, Tom TI The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TRANS-GOLGI NETWORK; MEMBRANE-PROTEIN; ER CISTERNAE; TUBULES; CELLS; APPARATUS; LOCALIZATION; MICROTUBULES; ORGANIZATION; MECHANISMS AB The mammalian endoplasmic reticulum (ER) is an organelle that maintains a complex, compartmentalized organization of interconnected cisternae and tubules while supporting a continuous flow of newly synthesized proteins and lipids to the Golgi apparatus. Using a phenotypic screen, we identify a small molecule, dispergo, that induces reversible loss of the ER cisternae and extensive ER tubulation, including formation of ER patches comprising densely packed tubules. Dispergo also prevents export from the ER to the Golgi apparatus, and this traffic block results in breakdown of the Golgi apparatus, primarily due to maintenance of the constitutive retrograde transport of its components to the ER. The effects of dispergo are reversible, since its removal allows recovery of the ER cisternae at the expense of the densely packed tubular ER patches. This recovery occurs together with reactivation of ER-to-Golgi traffic and regeneration of a functional Golgi with correct morphology. Because dispergo is the first small molecule that reversibly tubulates the ER and inhibits its export function, it will be useful in studying these complex processes. C1 [Lu, Lei; Hannoush, Rami N.; Kirchhausen, Tom] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Lu, Lei; Hannoush, Rami N.; Kirchhausen, Tom] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Lu, Lei] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. [Hannoush, Rami N.; Goess, Brian C.; Shair, Matthew D.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Hannoush, Rami N.] Genentech Inc, Dept Early Discovery Biochem, San Francisco, CA 94080 USA. [Goess, Brian C.] Furman Univ, Dept Chem, Greenville, SC 29613 USA. [Varadarajan, Shankar] Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM Kirchhausen@crystal.harvard.edu RI Lu, Lei/A-2225-2011 OI Lu, Lei/0000-0002-8192-1471 FU Canadian Institutes of Health Research; National Sciences and Engineering Research Council of Canada; U.S. Department of Defense (National Defense Science and Engineering Graduate Fellowship); National Institutes of Health [GM-075252]; New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility, Boston, MA [U54 AI057159]; SBS SUG [P01 GM62556, M58080013] FX We thank M. Ericsson for help with electron microscopy and E. Marino for maintaining the imaging resources in the Kirchhausen laboratory, and Yoshiki Tanaka for assistance with the nuclear magnetic resonance, infrared, and high-resolution mass spectrometry characterization of dispergo. R.H. was a recipient of postdoctoral fellowships from the Canadian Institutes of Health Research and National Sciences and Engineering Research Council of Canada. B.G. was a recipient of a doctoral fellowship from the U.S. Department of Defense (National Defense Science and Engineering Graduate Fellowship). This work was supported in part by National Institutes of Health Grant GM-075252 (to T.K.) and U54 AI057159 (New England Regional Center of Excellence in Biodefense and Emerging Infectious Disease, Core Imaging Facility, Boston, MA), as well as P01 GM62556 (to T.K. and M.S.) and SBS SUG M58080013 (to L.L.). NR 36 TC 5 Z9 5 U1 1 U2 23 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR 1 PY 2013 VL 24 IS 7 BP 1020 EP 1029 DI 10.1091/mbc.E12-08-0575 PG 10 WC Cell Biology SC Cell Biology GA 173YY UT WOS:000321120900013 PM 23389632 ER PT J AU Katz, NP Birnbaum, H Brennan, MJ Freedman, JD Gilmore, GP Jay, D Kenna, GA Madras, BK McElhaney, L Weiss, RD White, AG AF Katz, Nathaniel P. Birnbaum, Howard Brennan, Michael J. Freedman, John D. Gilmore, Gary P. Jay, Dennis Kenna, George A. Madras, Bertha K. McElhaney, Lisa Weiss, Roger D. White, Alan G. TI Prescription Opioid Abuse: Challenges and Opportunities for Payers SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CHRONIC PAIN PATIENTS; SUBSTANCE USE DISORDERS; CHRONIC NONCANCER PAIN; NEW-YORK-STATE; UNITED-STATES; PRIMARY-CARE; UNIVERSAL PRECAUTIONS; BENZODIAZEPINE USE; MEDICAID-PATIENTS; ILLICIT DRUG AB Objectives: Prescription opioid abuse and addiction are serious problems with growing societal and medical costs, resulting in billions of dollars of excess costs to private and governmental health insurers annually. Although difficult to accurately assess, prescription opioid abuse also leads to increased insurance costs in the form of property and liability claims, and costs to state and local governments for judicial, emergency, and social services. This manuscript's objective is to provide payers with strategies to control these costs, while supporting safe use of prescription opioid medications for patients with chronic pain. Method: A Tufts Health Care Institute Program on Opioid Risk Management meeting was convened in June 2010 with private and public payer representatives, public health and law enforcement officials, pain specialists, and other stakeholders to present research and develop recommendations on solutions that payers might implement to combat this problem. Results: While protecting access to prescription opioids for patients with pain, private and public payers can implement strategies to mitigate financial risks associated with opioid abuse, using internal strategies such as formulary controls, claims data surveillance, and claims matching; and external policies and procedures that support and educate physicians on reducing opioid risks among patients with chronic pain. Conclusions: Reimbursement policies, incentives, and health technology systems that encourage physicians to use universal precautions, to consult prescription monitoring program (PMP) data, and to implement Screening, Brief Intervention, and Referral to Treatment protocols have a high potential to reduce insurer risks while addressing a serious public health problem. C1 [Katz, Nathaniel P.] Tufts Univ, Sch Med, Tufts Hlth Care Inst, Program Opioid Risk Management, Boston, MA 02111 USA. [Birnbaum, Howard; White, Alan G.] Anal Grp Inc, Boston, MA USA. [Brennan, Michael J.] Bridgeport Hosp, Bridgeport, CT USA. [Freedman, John D.] Freedman Healthcare LLC, Newton, MA USA. [Gilmore, Gary P.] MassHlth, Boston, MA USA. [Gilmore, Gary P.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA. [Jay, Dennis] Coalit Insurance Fraud, Washington, DC USA. [Kenna, George A.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Madras, Bertha K.] Harvard Univ, Sch Med, NEPRC, Southborough, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [McElhaney, Lisa] Natl Assoc Drug Divers Investigators, Lutherville Timonium, MD USA. [Weiss, Roger D.] Harvard Univ, Sch Med, Boston, MA USA. [Weiss, Roger D.] McLean Hosp, Belmont, MA 02178 USA. RP Katz, NP (reprint author), Analges Solut, 232 Pond St, Natick, MA 01760 USA. EM nkatz@analgesicsolutions.com FU Tufts Health Care Institute Program on Opioid Risk Management; National Institutes of Health [RR00168, OD0111303]; National Institute on Drug Abuse [U10 DA 15831, K24 DA022288] FX Funding for this manuscript is provided by the Tufts Health Care Institute Program on Opioid Risk Management. Dr Madras is supported by the National Institutes of Health (RR00168, OD0111303). Dr Weiss reports that his work is supported by grants U10 DA 15831 and K24 DA022288 from the National Institute on Drug Abuse. NR 79 TC 23 Z9 23 U1 6 U2 20 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2013 VL 19 IS 4 BP 295 EP 302 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 155WX UT WOS:000319782200004 PM 23725361 ER PT J AU Mroz, P Parwani, AV Kulesza, P AF Mroz, Pawel Parwani, Anil V. Kulesza, Piotr TI Central Pathology Review for Phase III Clinical Trials SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID COOPERATIVE ONCOLOGY GROUP; ANATOMIC PATHOLOGY; SURGICAL PATHOLOGY; QUALITY ASSURANCE; DIAGNOSIS; EXPERIENCE; FUTURE; GLIOMA AB Context.-Central pathology review (CPR) was initially designed as a quality control measure. The potential of CPR in clinical trials was recognized as early as in the 1960s and quickly became embedded as an integral part of many clinical trials since. Objective.-To review the current experience with CPR in clinical trials, to summarize current developments in virtual microscopy, and to discuss the potential advantages and disadvantages of this technology in the context of CPR. Data Sources.-A PubMed (US National Library of Medicine) search for published studies was conducted, and the relevant articles were reviewed, accompanied by the authors' experience at their practicing institution. Conclusions.-The review of the available literature strongly suggests the growing importance of CPR both in the clinical trial setting as well as in second opinion cases. However, the currently applied approach significantly impedes efficient transfer of slides and patient data. Recent advances in imaging, digital microscopy, and Internet technologies suggest that the CPR process may be dramatically streamlined in the foreseeable future to allow for better diagnosis and quality assurance than ever before. In particular, whole slide imaging may play an important role in this process and result in a substantial reduction of the overall turnaround time required for slide review at the central location. Above all, this new approach may benefit the large clinical trials organized by oncology cooperative groups, since most of those trials involve complicated logistics owing to enrollment of large number of patients at several remotely located participating institutions. C1 [Mroz, Pawel; Kulesza, Piotr] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. [Mroz, Pawel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Parwani, Anil V.] Univ Pittsburgh, Sch Med, Dept Pathol, Shadyside Hosp, Pittsburgh, PA USA. RP Kulesza, P (reprint author), Northwestern Univ, ECOG ACRIN PCO RL, Pathol Core Facil, 251 E Huron St,Galter Pavil 7-132E, Chicago, IL 60611 USA. EM p-kulesza@northwestern.edu NR 29 TC 4 Z9 5 U1 0 U2 3 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2013 VL 137 IS 4 BP 492 EP 495 DI 10.5858/arpa.2012-0093-RA PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 155VT UT WOS:000319777200007 PM 23544938 ER PT J AU Ahmad, R Alam, M Rajabi, H Kufe, DW AF Ahmad, Rehan Alam, Maroof Rajabi, Hasan Kufe, Donald W. TI MUC1-C ACTIVATES C/EBP beta-MEDIATED INDUCTION OF ALDEHYDE DEHYDROGENASE EXPRESSION IN BREAST CANCER CELLS SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Ahmad, Rehan] King Saud Univ, Coll Med, Riyadh 11461, Saudi Arabia. [Alam, Maroof; Rajabi, Hasan; Kufe, Donald W.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA lb99 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883503333 ER PT J AU Amendt, BA Zhang, ZC Gutierrez, D Li, X Bidlack, F Cao, HJ Wang, JB Margolis, HC AF Amendt, Brad A. Zhang, Zichao Gutierrez, Diana Li, Xiao Bidlack, Felicitas Cao, Huojun Wang, Jianbo Margolis, Henry C. TI The LIM Homeodomain Transcription Factor Lhx6: A Transcriptional Repressor that Interacts with Pituitary Homeobox 2 (PITX2) to Regulate Odontogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Amendt, Brad A.; Zhang, Zichao; Gutierrez, Diana; Li, Xiao; Cao, Huojun; Wang, Jianbo] Univ Iowa, Iowa City, IA USA. [Bidlack, Felicitas; Margolis, Henry C.] Forsyth Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 522.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883500157 ER PT J AU Bar-Peled, L Chantranupong, L Cherniack, A Chen, W Ottina, K Grabiner, B Spear, E Carter, S Meyerson, M Sabatini, DM AF Bar-Peled, Liron Chantranupong, Lynne Cherniack, Andrew Chen, Walter Ottina, Kathleen Grabiner, Brian Spear, Eric Carter, Scott Meyerson, Matthew Sabatini, David M. TI A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Bar-Peled, Liron; Chantranupong, Lynne; Chen, Walter; Ottina, Kathleen; Grabiner, Brian; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Cherniack, Andrew; Carter, Scott] Broad Inst Harvard & MIT, Cambridge, MA USA. [Spear, Eric] Johns Hopkins Sch Med, Baltimore, MD USA. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sabatini, David M.] Howard Hughes Med Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 832.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883500335 ER PT J AU Bautista, PA Yagi, Y AF Bautista, Pinky Abarca Yagi, Yukako TI Improved color visualization of histological structures through multispectral image fusion SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Bautista, Pinky Abarca] Massachusetts Gen, Pathol, Boston, MA USA. [Yagi, Yukako] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 52.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883502179 ER PT J AU Bechard, LJ Feldman, HA Gura, K Venick, R Guinan, EC Gordon, C Duggan, C AF Bechard, Lori J. Feldman, Henry A. Gura, Kathleen Venick, Robert Guinan, Eva C. Gordon, Catherine Duggan, Christopher TI Bone loss during hematopoietic cell transplantation (HCT) in children SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Bechard, Lori J.; Duggan, Christopher] Childrens Hosp, Ctr Nutr, Boston, MA 02115 USA. [Feldman, Henry A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Gura, Kathleen] Childrens Hosp, Dept Pharm, Boston, MA 02115 USA. [Venick, Robert] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. [Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gordon, Catherine] Hasbro Childrens Hosp, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 372.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883502167 ER PT J AU Beloiartsev, A Ventocilla, C Winkler, JD Bloch, KD Zapol, WM AF Beloiartsev, Arkadi Ventocilla, Christian Winkler, Jeffrey D. Bloch, Kenneth D. Zapol, Warren M. TI Inhibition of Soluble Epoxide Hydrolase Augments Hypoxic Pulmonary Vasoconstriction and Improves Gas Exchange in Mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Beloiartsev, Arkadi; Bloch, Kenneth D.; Zapol, Warren M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Ventocilla, Christian; Winkler, Jeffrey D.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 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 2013 VL 27 MA 1140.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860505386 ER PT J AU Bird, SS Gregory, KE Gross, VS Marur, VR Lazarev, AV Walker, WA Kristal, BS AF Bird, Susan S. Gregory, Katherine E. Gross, Vera S. Marur, Vasant R. Lazarev, Alexander V. Walker, W. Allen Kristal, Bruce S. TI Fecal Lipidomics Analysis using Liquid Chromatography- Mass Spectrometry SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Bird, Susan S.; Marur, Vasant R.; Kristal, Bruce S.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Gregory, Katherine E.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Gross, Vera S.; Lazarev, Alexander V.] Pressure BioSci Inc, South Easton, MA USA. [Walker, W. Allen] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 3 U2 8 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 2013 VL 27 MA 815.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501019 ER PT J AU Camarata, T Vasilyev, A Arnaout, A AF Camarata, Troy Vasilyev, Aleksandr Arnaout, Amin TI Role of Sca-1 after ischemia/reperfusion injury in adult mouse kidney SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Camarata, Troy; Vasilyev, Aleksandr; Arnaout, Amin] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 750.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501330 ER PT J AU Cho, EY Nan, HM Giovannucci, EL Wu, KN Selhub, J Paul, L Rosner, B Fuchs, C AF Cho, Eunyoung Nan, Hongmei Giovannucci, Edward L. Wu, Kana Selhub, Jacob Paul, Ligi Rosner, Bernard Fuchs, Charles TI Pre-diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Cho, Eunyoung; Nan, Hongmei; Giovannucci, Edward L.; Rosner, Bernard] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cho, Eunyoung; Nan, Hongmei; Giovannucci, Edward L.; Rosner, Bernard] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Kana] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Selhub, Jacob; Paul, Ligi] Tufts Univ, Boston, MA 02111 USA. [Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 120.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883503369 ER PT J AU Christensen, HL Damkier, HH Brown, D Praetorius, J AF Christensen, Henriette Lajgaard Damkier, Helle Hasager Brown, Dennis Praetorius, Jeppe TI The choroid plexus regulation of cerebrospinal fluid pH SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Christensen, Henriette Lajgaard; Damkier, Helle Hasager; Praetorius, Jeppe] Aarhus Univ, Dept Biomed, Aarhus C, Denmark. [Brown, Dennis] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 730.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501277 ER PT J AU Coon, S Schwartz, J Singh, S AF Coon, Steven Schwartz, John Singh, Satish TI GIP Regulates Pept1 via Akt and EPAC Signaling Pathways in Intestinal Epithelial Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Coon, Steven; Schwartz, John; Singh, Satish] Boston Univ, Dept Med, Boston, MA 02215 USA. [Coon, Steven] Boston Univ Clin Transit Sci Inst, Boston, MA USA. [Singh, Satish] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1162.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501458 ER PT J AU Cowart, LA AF Cowart, L. Ashley TI Dietary Fat Composition Modifies Cell Sphingolipid Biosynthesis to Mediate the consequences of obesity. SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Cowart, L. Ashley] Med Univ S Carolina, Charleston, SC 29425 USA. [Cowart, L. Ashley] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 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 2013 VL 27 MA 453.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883500557 ER PT J AU Crivello, N Spires-Jones, T Shukitt-Hale, B Carey, A Roe, A Smith, D Blusztajn, JK Hyman, B Rosenberg, I AF Crivello, Natalia Spires-Jones, Tara Shukitt-Hale, Barbara Carey, Amanda Roe, Annie Smith, Donald Blusztajn, Jan Krzysztof Hyman, Bradley Rosenberg, Irwin TI Folate deficiency accelerates Alzheimer's disease related pathology in APP/PS1 mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Crivello, Natalia; Shukitt-Hale, Barbara; Carey, Amanda; Roe, Annie; Rosenberg, Irwin] Tufts Univ, Aging & Neurosci Lab, JM USDA HNRCA, Boston, MA 02111 USA. [Smith, Donald] Tufts Univ, JM USDA HNRCA, Comparat Biol Unit, Boston, MA 02111 USA. [Spires-Jones, Tara; Hyman, Bradley] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Blusztajn, Jan Krzysztof] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1077.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883503354 ER PT J AU Desai, R Savechenkov, P Ge, R Bruzik, K Raines, D Miller, K AF Desai, Rooma Savechenkov, Pavel Ge, Rile Bruzik, Karol Raines, Douglas Miller, Keith TI R- and S-mTFD-MPPB, an Anesthetic and a Convulsant, Have Opposing Effect on gamma-Aminobutyric acid (GABA) type A Receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Desai, Rooma; Ge, Rile; Raines, Douglas; Miller, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Savechenkov, Pavel; Bruzik, Karol] Univ Illinois, Chicago, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA lb556 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860500355 ER PT J AU Donnelly, BF Needham, PG Snyder, AC Roy, A Khadem, S Brodsky, JL Subramanya, AR AF Donnelly, Bridget F. Needham, Patrick G. Snyder, Avin C. Roy, Ankita Khadem, Shaheen Brodsky, Jeffrey L. Subramanya, Arohan R. TI Cytoplasmic Hsp70 and Hsp90 regulate functionally distinct ER quality control checkpoints during thiazide-sensitive NaCl cotransporter biogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Donnelly, Bridget F.; Snyder, Avin C.; Roy, Ankita; Khadem, Shaheen; Subramanya, Arohan R.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Needham, Patrick G.; Brodsky, Jeffrey L.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. [Khadem, Shaheen; Subramanya, Arohan R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1210.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860505287 ER PT J AU Doslikova, B Garfield, A Shaw, J Evans, M Burdakov, D Billups, B Heisler, L AF Doslikova, Barbora Garfield, Alastair Shaw, Jill Evans, Mark Burdakov, Denis Billups, Brian Heisler, Lora TI 5-HT2C Receptor agonist anorectic efficacy potentiated by 5-HT1B Receptor agonist co-application; an effect mediated via augmented pro-opiomelanocortin neuron activation SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Doslikova, Barbora; Shaw, Jill; Billups, Brian; Heisler, Lora] Univ Cambridge, Cambridge, England. [Evans, Mark] Univ Cambridge, IMS, Cambridge, England. [Garfield, Alastair] BIDMC, Boston, MA USA. [Burdakov, Denis] MRC NIMR, London, England. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA lb521 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504450 ER PT J AU Eguchi, T Calderwood, S AF Eguchi, Takanori Calderwood, Stuart TI Cooperative role of MMP-3 and HP1 in heat shock protein transcription SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Eguchi, Takanori; Calderwood, Stuart] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 977.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883500373 ER PT J AU Fasler-Kan, E Barteneva, N Meyer, P AF Fasler-Kan, Elizaveta Barteneva, Natasha Meyer, Peter TI Exploring phospho-signaling pathways in patients with agerelated macular degeneration (AMD), human pigment epithelial cell line ARPE-19 and porcine ocular tissue SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Fasler-Kan, Elizaveta] Inst Chem & Bioanalyt, Muttenz, Switzerland. [Barteneva, Natasha] Immune Dis Inst, Flow Cytometry Core, Boston, MA USA. [Meyer, Peter] Univ Basel, Ophtalmol Dept, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 645.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504379 ER PT J AU Gao, AQ Kantarci, A Gao, HW Van Dyke, T AF Gao, Anqi Kantarci, Alpdogan Gao, Hongwei Van Dyke, Thomas TI Novel role of Suppressor of Cytokine Signaling 3 in regulating LPS-induced Matrix Metalloproteinase 13 gene expression in osteoblasts SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Gao, Anqi; Kantarci, Alpdogan; Van Dyke, Thomas] Forsyth Inst, Cambridge, MA USA. [Gao, Hongwei] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 132.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501189 ER PT J AU Gosselin, K Bechard, LJ Feldman, HA Kellogg, M Gura, K Sonis, A Venick, R Gordon, CM Guinan, EC Duggan, C AF Gosselin, Kerri Bechard, Lori J. Feldman, Henry A. Kellogg, Mark Gura, Kathleen Sonis, Andrew Venick, Robert Gordon, Catherine M. Guinan, Eva C. Duggan, Christopher TI Changes in serum citrulline during hematopoietic cell transplantation (HCT) in children SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Gosselin, Kerri; Bechard, Lori J.; Feldman, Henry A.; Kellogg, Mark; Gura, Kathleen; Sonis, Andrew; Duggan, Christopher] Boston Childrens Hosp, Boston, MA USA. [Venick, Robert] UCLA Mattel Childrens Hosp, Los Angeles, CA USA. [Gordon, Catherine M.] Brown Univ, Providence, RI 02912 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 846.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501298 ER PT J AU Grigoryeva, L Hill, E Da Silva, N AF Grigoryeva, Lubov Hill, Eric Da Silva, Nicolas TI Postnatal development of mononuclear phagocytes in the mouse epididymis SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 734.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860503355 ER PT J AU Gruionu, G Bazou, D Song, J AF Gruionu, Gabriel Bazou, Despina Song, Johnatan TI Untangling Tumor Vasculature SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 Massachusetss Gen Hosp, Charlestown, MA USA. Massachusetss Gen Hosp, Edwin I Steele Lab Tumor Biol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 685.13 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860505300 ER PT J AU Gruionu, G Gruionu, L Munn, LL AF Gruionu, Gabriel Gruionu, Lucian Munn, Lance L. TI Flow-Induced Structural Adaptation of Tumor Vasculature by Selective Micro-Laser Ablation SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Gruionu, Gabriel; Munn, Lance L.] Massachusetss Gen Hosp, Charlestown, MA USA. [Gruionu, Gabriel; Munn, Lance L.] Harvard Univ, Sch Med, Charlestown, MA USA. [Gruionu, Gabriel; Gruionu, Lucian] Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol, Craiova, Romania. [Gruionu, Lucian] Univ Craiova, Craiova, Romania. RI Gruionu, Lucian/F-6121-2011; Munn, Lance/L-3950-2016 OI Gruionu, Lucian/0000-0002-4526-0864; Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 898.16 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504431 ER PT J AU Hashimoto, N Tanaka, T Snuderl, M Yagi, Y AF Hashimoto, Noriaki Tanaka, Toru Snuderl, Matija Yagi, Yukako TI Development of a viewing system for a whole tissue from multiple tissue blocks SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Hashimoto, Noriaki; Tanaka, Toru; Snuderl, Matija; Yagi, Yukako] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hashimoto, Noriaki; Snuderl, Matija; Yagi, Yukako] Harvard Univ, Sch Med, Boston, MA USA. [Tanaka, Toru] Chiba Univ, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 52.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501566 ER PT J AU Herter-Sprie, GS Wong, KK AF Herter-Sprie, Grit Sophie Wong, Kwok-Kin TI Mouse models of cancer - how to optimize their predictive value in cancer drug development SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Herter-Sprie, Grit Sophie; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Herter-Sprie, Grit Sophie; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1088.17 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504409 ER PT J AU Hotta, R Carreon-Rodriguez, A Belkind-Gerson, J Goldstein, AM AF Hotta, Ryo Carreon-Rodriguez, Alfonso Belkind-Gerson, Jaime Goldstein, Allan M. TI Isolation and Characterization of Enteric Nervous System Stem Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Hotta, Ryo; Carreon-Rodriguez, Alfonso; Belkind-Gerson, Jaime; Goldstein, Allan M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carreon-Rodriguez, Alfonso] Inst Nacl Salud Publ, Ctr Invest Salud Poblac, Cuernavaca, Morelos, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 752.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501643 ER PT J AU Hruby, A O'Donnell, CJ Jacques, PF Meigs, JB Wood, RJ McKeown, NM AF Hruby, Adela O'Donnell, Christopher J. Jacques, Paul F. Meigs, James B. Wood, Richard J. McKeown, Nicola M. TI Associations of magnesium intake with coronary artery calcification in the Framingham Heart Study SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Hruby, Adela; Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wood, Richard J.] Univ Massachusetts, Dept Nutr, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 622.6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883502472 ER PT J AU Hung, DT AF Hung, Deborah T. TI Small molecules, toxins and cell death pathways SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Hung, Deborah T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Broad Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 213.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501188 ER PT J AU Iacovelli, J Arany, Z Saint-Geniez, M AF Iacovelli, Jared Arany, Zoltan Saint-Geniez, Magali TI PGC-1 isoforms modulate the antioxidant response of photoreceptors to photo-oxidative stress SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Iacovelli, Jared; Saint-Geniez, Magali] Mass Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA USA. [Iacovelli, Jared; Arany, Zoltan; Saint-Geniez, Magali] Harvard Univ, Sch Med, Boston, MA USA. [Arany, Zoltan] Beth Israel Deaconess Med Ctr, Cadiovasc Inst, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 2013 VL 27 MA 1086.10 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504579 ER PT J AU Ingram, KH Thalacker-Mercer, A Garvey, WT AF Ingram, Katherine Heimburger Thalacker-Mercer, Anna Garvey, W. Timothy TI Individual amino acids and insulin sensitivity: relationships determined by race and gender SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Ingram, Katherine Heimburger] Kennesaw State Univ, Kennesaw, GA USA. [Thalacker-Mercer, Anna] Cornell Univ, Ithaca, NY USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Birmingham, AL USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 631.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504260 ER PT J AU Irie, T Sips, P Tokuda, K Ichinose, F AF Irie, Tomoya Sips, Patrick Tokuda, Kentaro Ichinose, Fumito TI Protein S-nitrosylation regulates Ca2+handling and myofilament Ca2+sensitivity in beta-adrenergic signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Irie, Tomoya; Sips, Patrick; Tokuda, Kentaro; Ichinose, Fumito] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 921.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502032 ER PT J AU Jacques, PF Cassidy, A Rogers, G Meigs, JB Dwyer, JT AF Jacques, Paul F. Cassidy, Aedin Rogers, Gail Meigs, James B. Dwyer, Johanna T. TI Intakes of Dietary Flavonoid Sub-classes and Incidence of Type 2 Diabetes SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Jacques, Paul F.; Rogers, Gail; Dwyer, Johanna T.] Tufts Univ, USDA, Human Nutr Res Ctr, Boston, MA 02111 USA. [Cassidy, Aedin] Univ E Anglia, Norwich Med Sch, Norwich NR4 7TJ, Norfolk, England. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Dwyer, Johanna T.] Tufts Med Ctr, Frances Stern Nutr Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 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 2013 VL 27 MA 106.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505460 ER PT J AU Jung, S Je, Y Giovannucci, E Willet, WC Rosner, B Ogino, S Cho, E AF Jung, Seungyoun Je, Youjin Giovannucci, Edward Willet, Walter C. Rosner, Bernard Ogino, Shuji Cho, Eunyoung TI Development of dietary methyl score using plasma homocysteine level in the large two US cohort study SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Jung, Seungyoun; Giovannucci, Edward; Willet, Walter C.; Rosner, Bernard; Cho, Eunyoung] Channing Div Network Med, Dept Med, Boston, MA USA. [Je, Youjin] Kyung Hee Univ, Seoul, South Korea. [Giovannucci, Edward; Willet, Walter C.; Rosner, Bernard; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 2013 VL 27 MA 622.10 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883506048 ER PT J AU Karastergiou, K Bredella, MA Smith, SR Miller, KK Fried, SK AF Karastergiou, Kalypso Bredella, Miriam A. Smith, Steven R. Miller, Karen K. Fried, Susan K. TI Growth Hormone Receptor In Human Subcutaneous Adipose Tissue: Gluteal Versus Abdominal Depots SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Karastergiou, Kalypso; Fried, Susan K.] Boston Univ, Boston, MA 02215 USA. [Bredella, Miriam A.; Miller, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Steven R.] Florida Hosp, Sanford Burnham Inst, Orlando, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 630.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505349 ER PT J AU Kashambwa, R Chiuve, S Meyerhardt, J Sato, K Hu, F Fung, T AF Kashambwa, Rutendo Chiuve, Stephanie Meyerhardt, Jeffrey Sato, Kaori Hu, Frank Fung, Teresa TI Post diagnosis diet quality and colorectal cancer survival SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Kashambwa, Rutendo; Chiuve, Stephanie; Hu, Frank; Fung, Teresa] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Meyerhardt, Jeffrey; Sato, Kaori] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fung, Teresa] Simmons Coll, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 372.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504501 ER PT J AU Kellogg, DL Zhao, J Wu, YB Roman, L Johnson, JM AF Kellogg, Dean Lundt Zhao, Joan Wu, Yubo Roman, Linda Johnson, John Marshall TI Evidence that chronic inhibition of the mammalian Target of Rapamycin (mTOR) reduces skin blood flow in humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Kellogg, Dean Lundt] South Texas Vet Hlth Care Syst, Geriatr Educ & Clin Ctr, San Antonio, TX USA. [Kellogg, Dean Lundt; Zhao, Joan; Wu, Yubo; Roman, Linda; Johnson, John Marshall] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 1 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 2013 VL 27 MA lb668 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860506258 ER PT J AU Kim, B Da Silva, N Roy, J Shum, W Breton, S AF Kim, Bongki Da Silva, Nicolas Roy, Jeremy Shum, Winnie Breton, Sylvie TI Luminal testicular factors are essential for the luminalreaching property of basal cells in the mouse epididymis SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Kim, Bongki; Da Silva, Nicolas; Roy, Jeremy; Shum, Winnie; Breton, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Ctr Syst Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 734.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860503126 ER PT J AU Kingston, RE Armache, KJ Simon, MD West, J Grau, D Garlick, J Davis, C AF Kingston, Robert E. Armache, Karim-Jean Simon, Matthew D. West, Jason Grau, Daniel Garlick, Joseph Davis, Chris TI Epigenetic mechanism: silent nucleosomal structures and non-coding RNAs. SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Kingston, Robert E.; Armache, Karim-Jean; Simon, Matthew D.; West, Jason; Grau, Daniel; Garlick, Joseph; Davis, Chris] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kingston, Robert E.; Armache, Karim-Jean; Simon, Matthew D.; West, Jason; Grau, Daniel; Garlick, Joseph] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Davis, Chris] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 456.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883500146 ER PT J AU Koh, HJ Toyoda, T Jung, MM Lee, MY Hirshman, MF Goodyear, LJ AF Koh, Ho-Jin Toyoda, Taro Jung, Michelle M. Lee, Min-Young Hirshman, Michael F. Goodyear, Laurie J. TI The Role of Skeletal Muscle Tribbles 3 (TRB3) on Endoplasmic Reticulum (ER) stress- and high fat diet-induced insulin resistance SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Koh, Ho-Jin; Toyoda, Taro; Jung, Michelle M.; Lee, Min-Young; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1154.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504485 ER PT J AU Kunert, C Padera, TP Munn, LL AF Kunert, Christian Padera, Timothy P. Munn, Lance L. TI Dynamics of Nitric Oxide Activity are Sufficient and Optimal to Drive Lymphatic Pumping SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Kunert, Christian; Padera, Timothy P.; Munn, Lance L.] Harvard Univ, Sch Med, Mass Gen Hosp, Boston, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 681.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504390 ER PT J AU Leone, VA Huang, E Wang, YW Devkota, S Zale, E Dalal, S Chang, EB AF Leone, Vanessa A. Huang, Edmond Wang, Yunwei Devkota, Suzanne Zale, Elizabeth Dalal, Sushila Chang, Eugene B. TI Antibiotic-Induced Gut Microbiota Alters Period-2 Circadian Gene Expression in Liver SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Leone, Vanessa A.; Huang, Edmond; Wang, Yunwei; Zale, Elizabeth; Dalal, Sushila; Chang, Eugene B.] Univ Chicago, Chicago, IL 60637 USA. [Devkota, Suzanne] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1205.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501509 ER PT J AU Lezcano, C Kleffel, S Laga, AC Zhan, Q DoRosario, A Frank, MH Wang, LD Murphy, GF Schatton, T AF Lezcano, Cecilia Kleffel, Sonja Laga, Alvaro C. Zhan, Qian DoRosario, Andrew Frank, Markus H. Wang, Linda Murphy, George F. Schatton, Tobias TI Expression of MDR-transporter, ABCB5, in Merkel cell carcinoma SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Lezcano, Cecilia; Kleffel, Sonja; Laga, Alvaro C.; Zhan, Qian; Frank, Markus H.; Murphy, George F.; Schatton, Tobias] Brigham & Womens Hosp, Boston, MA 02115 USA. [DoRosario, Andrew] Dana Farber Canc Inst, Ctr Cutaneous Oncol, Boston, MA 02115 USA. [Frank, Markus H.; Schatton, Tobias] Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [Wang, Linda] St Johns Mercy Med Ctr, Inst Canc Care, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1087.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501406 ER PT J AU Li, Y Friedman, AA Yu, ZS Tamez, H Wenger, J Thadhani, R Watkins, BA AF Li, Yong Friedman, Allon A. Yu, Zhangsheng Tamez, Hector Wenger, Julia Thadhani, Ravi Watkins, Bruce A. TI Phospholipid PUFA: a better indicator for assessing health risks SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Li, Yong; Watkins, Bruce A.] Univ Connecticut, Diet & Hlth Initiat, Storrs, CT USA. [Friedman, Allon A.; Yu, Zhangsheng] Indiana Univ Sch Med, Indianapolis, IN USA. [Tamez, Hector; Wenger, Julia; Thadhani, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1072.16 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504571 ER PT J AU Ma, JT Sloan, M Fox, CS Hoffmann, U Jacques, PF McKeown, NM AF Ma, Jiantao Sloan, Matthew Fox, Caroline S. Hoffmann, Udo Jacques, Paul F. McKeown, Nicola M. TI Sugar-sweetened beverage consumption is associated with relative distribution of abdominal adipose tissue in the Framingham Heart Study SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Ma, Jiantao] Tufts Univ, Jean Mayer USDA HNRCA, Boston, MA 02111 USA. [Sloan, Matthew] Univ Massachusetts, Sch Med, Worcester, MA USA. [Fox, Caroline S.] NHLBI, Framingham, MA USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Jacques, Paul F.; McKeown, Nicola M.] Tutfs Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 126.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860500120 ER PT J AU Marshansky, V Hosokawa, H Zhuang, ZJ Randazzo, PA Gruber, G Ausiello, DA AF Marshansky, Vladimir Hosokawa, Hiroyuki Zhuang, Zhenjie Randazzo, Paul A. Grueber, Gerhard Ausiello, Dennis A. TI Novel role of cytohesin-2 in regulation of macropinocytosis pathway and cell proliferation SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Marshansky, Vladimir; Hosokawa, Hiroyuki; Zhuang, Zhenjie; Ausiello, Dennis A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Ctr Syst Biol, Boston, MA USA. [Randazzo, Paul A.] NCI, Lab Cel Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA. [Grueber, Gerhard] Nanyang Technol Univ, Sch Biol Sci, Div Struct Biol Biochem, Singapore, Singapore. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 591.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883500220 ER PT J AU Meng, SS Zhang, XH Giovannucci, EL Ma, J Fuchs, C Cho, EY AF Meng, Shasha Zhang, Xuehong Giovannucci, Edward L. Ma, Jing Fuchs, Charles Cho, Eunyoung TI No association between garlic intake and risk of colorectal cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Meng, Shasha; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Zhang, Xuehong; Giovannucci, Edward L.; Ma, Jing; Cho, Eunyoung] Brigham & Womens Hosp, Boston, MA 02115 USA. [Zhang, Xuehong; Giovannucci, Edward L.; Ma, Jing; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA. [Fuchs, Charles] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 847.20 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505447 ER PT J AU Meyerson, M AF Meyerson, Matthew TI Somatic genome alterations in triple-negative breast cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 328.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860500500 ER PT J AU Mougios, V Huh, JY Panagiotou, G Kabasakalis, A Mantzoros, C AF Mougios, Vasileios Huh, Joo Young Panagiotou, Grigorios Kabasakalis, Athanasios Mantzoros, Christos TI Responses of circulating irisin to different exercises in humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Mougios, Vasileios; Kabasakalis, Athanasios] Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. [Huh, Joo Young; Panagiotou, Grigorios; Mantzoros, Christos] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Huh, Joo Young; Panagiotou, Grigorios; Mantzoros, Christos] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 712.17 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502499 ER PT J AU Mudge, D Bielenberg, DR Serhan, K Hwang, SH Hammock, BD Kieran, MW Panigrahy, D AF Mudge, Dayna Bielenberg, Diane R. Serhan, Karolina Hwang, Sung Hee Hammock, Bruce D. Kieran, Mark W. Panigrahy, Dipak TI Epoxyeicosanoid regulation of tumor lymphangiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Mudge, Dayna; Bielenberg, Diane R.; Serhan, Karolina; Kieran, Mark W.; Panigrahy, Dipak] Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA. [Mudge, Dayna; Serhan, Karolina; Kieran, Mark W.; Panigrahy, Dipak] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. [Hwang, Sung Hee; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Hwang, Sung Hee; Hammock, Bruce D.] Univ Calif Davis, Canc Res Ctr, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA lb457 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883502570 ER PT J AU Murshid, A Chou, SD Eguchi, T Calderwood, S AF Murshid, Ayesha Chou, Shiuh Dih Eguchi, Takanori Calderwood, Stuart TI Role of HSF1 and FoxO3 in proteotoxic stress induced Macroautophagy SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Murshid, Ayesha; Chou, Shiuh Dih; Eguchi, Takanori; Calderwood, Stuart] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 994.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502055 ER PT J AU Nagy, N Akbareian, S Steiger, C Molnar, D Barad, C Goldstein, AM AF Nagy, Nandor Akbareian, Sophie Steiger, Casey Molnar, David Barad, Csilla Goldstein, Allan M. TI Expression and function of tenascin-C during colorectal enteric nervous system development SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Nagy, Nandor; Molnar, David; Barad, Csilla] Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1085 Budapest, Hungary. [Nagy, Nandor; Akbareian, Sophie; Steiger, Casey; Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 965.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501059 ER PT J AU Nanthakumar, NN Meng, D Newburg, DS AF Nanthakumar, Nanda N. Meng, Di Newburg, David S. TI Microbiota and glucocorticoids regulate postnatal developmental of intestinal Fut2 gene expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Nanthakumar, Nanda N.; Newburg, David S.] Boston Coll, Chestnut Hill, MA 02167 USA. [Meng, Di] Harvard Univ, Sch Med, Charlestown, MA USA. [Meng, Di] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 951.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502053 ER PT J AU Nichols, JM Maiellaro, I Abi-Jaoude, J Curci, S Hofer, AM AF Nichols, Jonathan Michael Maiellaro, Isabella Abi-Jaoude, Joanne Curci, Silvana Hofer, Aldebaran M. TI Involvement of Store-operated cAMP signaling in the regulation of colonic secretory function SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Nichols, Jonathan Michael; Maiellaro, Isabella; Abi-Jaoude, Joanne; Curci, Silvana; Hofer, Aldebaran M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, West Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1163.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860500073 ER PT J AU Noel, S Manjourides, J Scott, TM Spiro, A Tucker, KL AF Noel, Sabrina Manjourides, Justin Scott, Tammy M. Spiro, Avron, III Tucker, Katherine L. TI Coffee intake and cognitive functioning in men SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Noel, Sabrina; Manjourides, Justin; Tucker, Katherine L.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Scott, Tammy M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 840.15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860505551 ER PT J AU Nunes, P Ernandez, T Roth, I Qiao, XM Feraille, E Brown, D Hasler, U AF Nunes, Paula Ernandez, Thomas Roth, Isabelle Qiao, Xiaomu Feraille, Eric Brown, Dennis Hasler, Udo TI Autophagy is induced by hypertonic stress and is associated with microtubule-dependent pericentrosomsal clustering of autolysosomes SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Nunes, Paula; Ernandez, Thomas; Roth, Isabelle; Qiao, Xiaomu; Feraille, Eric; Hasler, Udo] Univ Geneva, Dept Cellular Physiol & Metab, Geneva, Switzerland. [Nunes, Paula; Brown, Dennis; Hasler, Udo] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [Nunes, Paula; Brown, Dennis; Hasler, Udo] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 728.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501576 ER PT J AU Park, CY Burger, S Frykenberg, M Tambe, D Zhou, EH Krishnan, R Marinkovic, A Tschumperlin, D Butler, J Lavoie, T Dowell, M Chen, BH Gardel, M Green, G Solway, J Fredberg, J AF Park, Chan Young Burger, Stephanie Frykenberg, Matthew Tambe, Dhananjay Zhou, Enhua Krishnan, Ramaswamy Marinkovic, Aleksander Tschumperlin, Daniel Butler, James Lavoie, Tera Dowell, Maria Chen, Bohao Gardel, Margaret Green, Geoffrey Solway, Julian Fredberg, Jeffrey TI HIGH-THROUGHPUT SCREENING BY TRACTION MICROSCOPY SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Park, Chan Young; Tambe, Dhananjay; Zhou, Enhua; Marinkovic, Aleksander; Tschumperlin, Daniel; Butler, James; Fredberg, Jeffrey] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Burger, Stephanie; Frykenberg, Matthew] Northeastern Univ, Boston, MA 02115 USA. [Krishnan, Ramaswamy] BIDMC, Boston, MA USA. [Lavoie, Tera; Dowell, Maria; Chen, Bohao; Gardel, Margaret; Green, Geoffrey; Solway, Julian] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 894.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502287 ER PT J AU Park, E D'Andrea, AD AF Park, Eunmi D'Andrea, Alan D. TI The Fanconi Anemia Pathway Induces Senescence and Suppresses Tumorigenesis in Vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Park, Eunmi; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 2013 VL 27 MA lb400 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860505498 ER PT J AU Patel, SR Sheth, S Mian, M Bourne, S Flaherty, A Eskandar, E AF Patel, Shaun R. Sheth, Sameer Mian, Matt Bourne, Sarah Flaherty, Alice Eskandar, Emad TI Correlation and Causation: Systems Level Understanding of Decision-Making Signals at the Single-Neuronal Level in the Human Brain SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Patel, Shaun R.; Sheth, Sameer; Mian, Matt; Bourne, Sarah; Flaherty, Alice; Eskandar, Emad] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1124.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883503177 ER PT J AU Paunescu, TG Huynh, C Lechner, L Goetze, B Stern, L Breton, S Brown, D AF Paunescu, Teodor G. Huynh, Chuong Lechner, Lorenz Goetze, Bernhard Stern, Lewis Breton, Sylvie Brown, Dennis TI Helium ion microscopy of the rodent kidney and male reproductive tract SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Paunescu, Teodor G.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Breton, Sylvie; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Huynh, Chuong; Lechner, Lorenz; Goetze, Bernhard; Stern, Lewis] Carl Zeiss Microscopy LLC, Peabody, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 683.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860503093 ER PT J AU Pazos, MA Hurley, BP AF Pazos, Michael A. Hurley, Bryan P. TI Hepoxilin A(3) is a key driver of neutrophil migration in a model of acute P. aeruginosa infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Pazos, Michael A.; Hurley, Bryan P.] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. [Pazos, Michael A.; Hurley, Bryan P.] Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1215.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501496 ER PT J AU Picard, N Hennings, JC Huebner, A Stauber, T Maier, H Brown, D Jentsch, T Vargas-Poussou, R Eladari, D Huebner, C AF Picard, Nicolas Hennings, Jean-Christopher Huebner, Antje Stauber, Tobias Maier, Hannes Brown, Dennis Jentsch, Thomas Vargas-Poussou, Rosa Eladari, Dominique Huebner, Christian TI Vacuolar proton pump a4 subunit is critical for inner ear development and renal function SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Picard, Nicolas; Eladari, Dominique] INSERM, Paris, France. [Hennings, Jean-Christopher; Huebner, Antje; Huebner, Christian] Inst Human Genet & Anthropol, Jena, Germany. [Stauber, Tobias; Jentsch, Thomas] Max Delbruck Ctr Mol Med, Berlin, Germany. [Maier, Hannes] Hannover Med Sch, D-30623 Hannover, Germany. [Brown, Dennis] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Vargas-Poussou, Rosa] Hop Georges Pompidou, Paris, France. RI Stauber, Tobias/E-4005-2010; Hannes, Maier/A-9457-2012; Picard, Nicolas/B-6677-2012 OI Stauber, Tobias/0000-0003-0727-6109; Hannes, Maier/0000-0001-8457-5327; Picard, Nicolas/0000-0002-1695-3389 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1115.24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501428 ER PT J AU Priolo, C Pyne, S McDunn, J Rose, J Ravasz, E Zadra, G Photopoulos, C Scaglia, N DeMarzo, A Loda, M AF Priolo, Carmen Pyne, Saumyadipta McDunn, Jonathan Rose, Joshua Ravasz, Erzsebet Zadra, Giorgia Photopoulos, Cornelia Scaglia, Natalia DeMarzo, Angelo Loda, Massimo TI The Metabolic Fingerprints of Prostate Cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Priolo, Carmen; Pyne, Saumyadipta; Rose, Joshua; Zadra, Giorgia; Photopoulos, Cornelia; Scaglia, Natalia; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [McDunn, Jonathan] Metabolon Inc, Durham, NC USA. [Ravasz, Erzsebet] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [DeMarzo, Angelo] Johns Hopkins Univ, Baltimore, MD USA. [Loda, Massimo] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 471.9 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883503389 ER PT J AU Reddy, AT Lakshmi, SP Dornadula, S Pinni, S Rampa, DR Reddy, RC AF Reddy, Aravind T. Lakshmi, Sowmya P. Dornadula, Sireesh Pinni, Sudheer Rampa, Dileep R. Reddy, Raju C. TI Suppressing Allergic Airway Disease with Nitrated Fatty Acids SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1216.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860500483 ER PT J AU Ross, JS Hu, W Rosen, B Snider, AJ Obeid, LM Cowart, LA AF Ross, Jessica Shavonne Hu, Wei Rosen, Bess Snider, Ashley J. Obeid, Lina M. Cowart, L. Ashley TI Sphingosine Kinase 1 is regulated by PPAR alpha in response to free fatty acids and mediates skeletal muscle IL-6 production and signaling in diet-induced obesity SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Ross, Jessica Shavonne; Hu, Wei; Snider, Ashley J.; Cowart, L. Ashley] Med Univ S Carolina, Charleston, SC 29425 USA. [Ross, Jessica Shavonne] Med Univ S Carolina, Mol & Cellular Biol & Pathobiol Program, Charleston, SC 29425 USA. [Rosen, Bess] Boston Univ, Sch Med, Boston, MA 02118 USA. [Snider, Ashley J.; Cowart, L. Ashley] Ralph H Johnson VA Ctr, Charleston, SC USA. [Obeid, Lina M.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Obeid, Lina M.] Northport VA Ctr, Northport, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 813.18 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505050 ER PT J AU Roy, J Ruan, YC Hill, E Visconti, P Krapf, D Vinegoni, C Breton, S AF Roy, Jeremy Ruan, Ye Chun Hill, Eric Visconti, Pablo Krapf, Dario Vinegoni, Claudio Breton, Sylvie TI Regulation of basal cell plasticity by epidermal growth factor (EGF) and c-Src in vivo in the mouse epididymis SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Roy, Jeremy; Ruan, Ye Chun; Hill, Eric; Breton, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Ctr Syst Biol, Boston, MA USA. [Vinegoni, Claudio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Visconti, Pablo; Krapf, Dario] Univ Massachusetts, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 734.12 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502252 ER PT J AU Russo, SB Tidhar, R Futerman, A Cowart, LA AF Russo, Sarah Brice Tidhar, Rotem Futerman, Anthony Cowart, L. Ashley TI Myristate-derived d16:o-sphingolipids constitute an abundant cardiac sphingolipid pool with distinct synthetic routes and functional properties SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Russo, Sarah Brice; Cowart, L. Ashley] Med Univ S Carolina, Charleston, SC 29425 USA. [Tidhar, Rotem; Futerman, Anthony] Weizmann Inst Sci, IL-76100 Rehovot, Israel. [Cowart, L. Ashley] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 813.15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504450 ER PT J AU Shirozu, K Tokuda, K Marutani, E Lefer, D Wang, R Ichinose, F AF Shirozu, Kazuhiro Tokuda, Kentaro Marutani, Eizo Lefer, David Wang, Rui Ichinose, Fumito TI Cystathione-gamma-lyase deficiency protects mice from galactosamine/LPS-induced acute liver failure SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Shirozu, Kazuhiro; Tokuda, Kentaro; Marutani, Eizo; Ichinose, Fumito] Massachusetts Gen Hosp, Charlestown, MA USA. [Shirozu, Kazuhiro; Tokuda, Kentaro; Marutani, Eizo; Ichinose, Fumito] Harvard Univ, Sch Med, Charlestown, MA USA. [Lefer, David] Emory Univ, Sch Med, Atlanta, GA USA. [Wang, Rui] Lakehead Univ, Thunder Bay, ON P7B 5E1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1161.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502139 ER PT J AU Sholl, LM Garcia, E Jia, YH MacConaill, L Lindeman, N AF Sholl, Lynette Marie Garcia, Elizabeth Jia, Yonghui MacConaill, Laura Lindeman, Neal TI High throughput mutation profiling of lung adenocarcinoma SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Sholl, Lynette Marie; Lindeman, Neal] Brigham & Womens Hosp, Boston, MA 02115 USA. [Garcia, Elizabeth; Jia, Yonghui; MacConaill, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 58.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883500209 ER PT J AU Sips, PY Zou, L Irie, T Nguyen, R Chao, W Kaneki, M Ichinose, F AF Sips, Patrick Yves Zou, Lin Irie, Tomoya Rebecca Nguyen Chao, Wei Kaneki, Masao Ichinose, Fumito TI Septic cardiomyopathy is improved by enhancing cardiomyocyte denitrosylation capacity SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Sips, Patrick Yves; Zou, Lin; Irie, Tomoya; Rebecca Nguyen; Chao, Wei; Kaneki, Masao; Ichinose, Fumito] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 921.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860503395 ER PT J AU Song, JW Bazou, D Munn, LL AF Song, Jonathan W. Bazou, Despina Munn, Lance L. TI Flow-mediated Vessel Guidance SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 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 2013 VL 27 MA 688.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860501248 ER PT J AU Thalacker-Mercer, A Ingram, KH Garvey, WT AF Thalacker-Mercer, Anna Ingram, Katherine Heimburger Garvey, W. Timothy TI Fat utilization impacts the negative relationship between insulin sensitivity and Leucine SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Thalacker-Mercer, Anna] Cornell Univ, Ithaca, NY USA. [Ingram, Katherine Heimburger] Kennesaw State Univ, Kennesaw, GA USA. [Garvey, W. Timothy] Univ Alabama Birmingham, Birmingham, AL USA. [Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 226.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504131 ER PT J AU Unger, ER Panicker, G Wong, J Wallstrom, G Haddad, R D'Souza, G Posner, M Anderson, KS AF Unger, Elizabeth R. Panicker, Gitika Wong, Jessica Wallstrom, Garrick Haddad, Robert D'Souza, Gypsyamber Posner, Marshall Anderson, Karen S. TI Differential antibody responses to HPV16 in cervical and oropharyngeal cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Unger, Elizabeth R.; Panicker, Gitika] Ctr Dis Control & Prevent, Atlanta, GA USA. [Wong, Jessica; Haddad, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wallstrom, Garrick; Anderson, Karen S.] Arizona State Univ, Tempe, AZ USA. [D'Souza, Gypsyamber] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Posner, Marshall] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1087.10 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504008 ER PT J AU Wakiyama, A Black, KM Pacak, CA Ericsson, M Barnett, RJ Drumm, C Seth, P Bloch, DB Levitsky, S Cowan, DB McCully, JD AF Wakiyama, Akihiro Black, Kendra M. Pacak, Christina A. Ericsson, Maria Barnett, Reanne J. Drumm, Ciara Seth, Pankaj Bloch, Donald B. Levitsky, Sidney Cowan, Douglas B. McCully, James D. TI Transplantation of Autologously-Derived Mitochondria Protects the Heart from Ischemia-Reperfusion Injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Wakiyama, Akihiro; Black, Kendra M.; Barnett, Reanne J.; Drumm, Ciara; Levitsky, Sidney; McCully, James D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Seth, Pankaj] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. [Pacak, Christina A.; Cowan, Douglas B.] Bosto Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Ericsson, Maria; Seth, Pankaj; Bloch, Donald B.; Levitsky, Sidney; Cowan, Douglas B.; McCully, James D.] Harvard Univ, Sch Med, Boston, MA USA. [Bloch, Donald B.] Massachusetts Gen Hosp, Rheumatol Allergy & Immunol 5Div, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1209.7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502171 ER PT J AU Wang, JM Iacovelli, J Spencer, C Saint-Geniez, M AF Wang, Jinmei Iacovelli, Jared Spencer, Carrie Saint-Geniez, Magali TI New insights on sodium iodate-induced retinal degeneration SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Wang, Jinmei; Iacovelli, Jared; Spencer, Carrie; Saint-Geniez, Magali] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 873.15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505060 ER PT J AU White, J Ruas, J Rao, R Kleiner, S Wu, J Spiegelman, B AF White, James Ruas, Jorge Rao, Rajesh Kleiner, Sandra Wu, Jun Spiegelman, Bruce TI A novel PGC-1a isoform induced by resistance training regulates skeletal muscle hypertrophy SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [White, James; Ruas, Jorge; Rao, Rajesh; Kleiner, Sandra; Wu, Jun; Spiegelman, Bruce] Harvard Univ, Sch Med, DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 2013 VL 27 MA 940.18 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504158 ER PT J AU Wilkinson, CW Colasurdo, EA Pagulayan, KF Shofer, JB Peskind, ER AF Wilkinson, Charles W. Colasurdo, Elizabeth A. Pagulayan, Kathleen F. Shofer, Jane B. Peskind, Elaine R. TI Prevalence of chronic hypopituitarism after blast concussion SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Wilkinson, Charles W.; Colasurdo, Elizabeth A.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Pagulayan, Kathleen F.; Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, Educ & Clin Ctr, VA Northwest Network Mental Illness Res, Seattle, WA USA. [Wilkinson, Charles W.; Pagulayan, Kathleen F.; Shofer, Jane B.; Peskind, Elaine R.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 935.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860500321 ER PT J AU Yagi, Y Bautista, PA Klepeis, V Mino-Kenudson, M AF Yagi, Yukako Bautista, Pinky Abarca Klepeis, Veronica Mino-Kenudson, Mari TI 3D-based approach for efficient analysis of immunostained histology images in evaluating downstream pathway activation in malignant tumors with molecular targets SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Yagi, Yukako; Bautista, Pinky Abarca; Klepeis, Veronica; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 52.5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883503215 ER PT J AU Yang, JL Zahr, A Alcaide, P Jones, A Gregory-Ksander, M Luscinskas, FW Ksander, B Argueso, P D'Amore, PA AF Yang, Jinling Zahr, Alisar Alcaide, Pilar Jones, Alexander Gregory-Ksander, Meredith Luscinskas, Francis W. Ksander, Bruce Argueso, Pablo D'Amore, Patricia A. TI A role for endomucin-1 in maintaining a non-inflammatory endothelial surface and in the regulation of leukocyte-endothelial cell interactions SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Yang, Jinling; Zahr, Alisar; Jones, Alexander; Gregory-Ksander, Meredith; Ksander, Bruce; Argueso, Pablo; D'Amore, Patricia A.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Yang, Jinling; Zahr, Alisar; Gregory-Ksander, Meredith; Ksander, Bruce; Argueso, Pablo; D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Alcaide, Pilar] Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA USA. [Luscinskas, Francis W.] Harvard Univ, Brigham & Womens Hosp, Div Vasc Res, Sch Med, Boston, MA 02115 USA. [Luscinskas, Francis W.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 57.4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860504241 ER PT J AU Yu, BL Lei, C Shahid, M Beloiartsev, A Bloch, KD Zapol, WM AF Yu, Binglan Lei, Chong Shahid, Mohd Beloiartsev, Arkadi Bloch, Kenneth D. Zapol, Warren M. TI Inhaled nitric oxide attenuates the adverse effects of transfusing stored red blood cells in mice with endothelial dysfunction after hemorrhagic shock SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Yu, Binglan; Lei, Chong; Shahid, Mohd; Beloiartsev, Arkadi; Bloch, Kenneth D.; Zapol, Warren M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 920.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860503394 ER PT J AU Zamarioli, A Morse, L Battaglino, R Maranho, D Volpon, JB Paula, FA Shimano, AC AF Zamarioli, Ariane Morse, Leslie Battaglino, Ricardo Maranho, Daniel Volpon, Jose B. Paula, Francisco A. Shimano, Antonio C. TI Morphological, mechanical and biochemical changes in long bones following spinal cord injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Zamarioli, Ariane; Maranho, Daniel; Volpon, Jose B.; Paula, Francisco A.; Shimano, Antonio C.] Univ Sao Paulo, BR-14049 Ribeirao Preto, Brazil. [Morse, Leslie] Spaulding Rehabil, Boston, MA USA. [Battaglino, Ricardo] Forsyth Inst, Cambridge, MA USA. RI Zamarioli, Ariane/K-7001-2012; Volpon, Jose /D-3041-2012; Maranho, Daniel Augusto/C-1337-2013; Shimano, Antonio/E-1455-2014 OI Zamarioli, Ariane/0000-0002-7939-0528; Volpon, Jose /0000-0002-2120-0138; Maranho, Daniel Augusto/0000-0002-3893-0292; NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 521.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501236 ER EF